Atlas of Lower Extremity Skin Disease 2022

Atlas of Lower Extremity Skin Disease Tracey C. Vlahovic Stephen M. Schleicher Atlas of Lower Extremity Skin Disease AL Grawany Tracey C. Vlahovic • Stephen M. Schleicher Atlas of Lower Extremity Skin Disease Tracey C. Vlahovic Podiatric Medicine Temple University Philadelphia, PA, USA Stephen M. Schleicher DermDox Dermatology Centers Sugarloaf, PA, USA ISBN 978-3-031-07949-8 ISBN 978-3-031-07950-4 https://doi.org/10.1007/978-3-031-07950-4 (eBook) © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland AL Grawany To my parents, Edward and Lou Ann, for their never-ending support and love. To my students, current and former, for always inspiring me to do more. To my patients for being my greatest teachers. Tracey C. Vlahovic To my loyal patients and wonderful staff. And to the pets and wildlife that have enriched my life and the lives of others. Stephen M. Schleicher Preface Lower extremity skin disorders are often overlooked by clinicians. Ailments such as eczema, psoriasis, and tinea at times prove difficult to distinguish clinically and misdiagnosis can lead to inappropriate therapy. Many practitioners are mystified when confronted with an abnormal appearing nail. Delay in recognizing skin cancer may adversely impact morbidity and mortality. New therapies have revolutionized the management of both psoriasis and eczema. Topics featured include nail pathology, fungal and bacterial infections, xerotic and hyperkeratotic disorders, autoimmune diseases and vasculopathies, benign and malignant lesions, systemic diseases, and ulcerations. The concluding chapters present a review of biopsy techniques as well as an overview of current dermatological therapies. This work is a collaboration between a dermatologist and a podiatric physician gathering years of clinical experience in these related fields. The two of us created the first joint dermatology/podiatry fellowship in the USA. Our atlas is a valuable, concise, and practical guide for medical professionals and students who deal with the lower extremities and will enhance both diagnostic and treatment acumen. Philadelphia, PA, USA Sugarloaf, PA, USA Tracey C. Vlahovic Stephen M. Schleicher vii AL Grawany Acknowledgments We would like to thank our patients for the privilege of being their physicians and for entrusting us in their care. We would also like to thank the staff at Springer, Kristopher Spring and Lee Klein, for their support and guidance during the writing and editorial process. ix Contents 1 Nail Disorders of the Lower Extremity�� 1 1.1Nail Plate Changes�� 1 1.1.1Beau’s Lines�� 1 1.1.2Onychomadesis �� 1 1.1.3Onychorrhexis�� 2 1.1.4Trachyonychia (Twenty Nail Dystrophy) �� 2 1.2Nail Shape and Size Changes �� 3 1.2.1Anonychia �� 3 1.2.2Koilonychia (Spoon Nails)�� 3 1.2.3Pincer Nails�� 4 1.2.4Clubbing�� 4 1.2.5Onychogryphosis�� 5 1.3Nail Color Changes�� 5 1.3.1Leukonychia�� 5 1.3.2Longitudinal Melanonychia�� 5 1.3.3Green Nails/Chloronychia�� 6 1.3.4Yellow Nail Syndrome�� 6 1.4Nail Plate–Nail Bed Adhesion Issues �� 7 1.4.1Onycholysis�� 7 1.4.2Disappearing Nail Bed�� 7 1.5Unique Toenail Issues �� 8 1.5.1Subungual Hematoma�� 8 1.5.2Ingrown Toenails�� 8 1.5.3Congenital Malalignment of the Great Toenail�� 8 1.5.4Retronychia �� 9 1.6Dermatologic Disease Related Nail Disorders �� 9 1.6.1Nail Psoriasis�� 9 1.6.2Nail Lichen Planus�� 9 1.7Infections of the Nail Unit�� 10 1.7.1Herpes Simplex (Herpetic Whitlow)�� 10 1.7.2Periungual Viral Warts�� 10 1.7.3Onychomycosis�� 11 1.8Tumors of the Nails�� 11 1.8.1Pyogenic Granuloma�� 11 1.8.2Fibroma/Fibrokeratoma�� 12 1.8.3Myxoid Cyst (Mucoid Cyst) �� 12 1.8.4Subungual Exostosis �� 13 1.8.5Nail Matrix Nevi �� 13 1.8.6Bowen’s Disease and Squamous Cell Carcinoma�� 13 1.8.7Subungual Melanoma �� 14 References�� 14 xi AL Grawany xii 2 Superficial Fungal Infections of the Lower Extremity �� 17 2.1Interdigital Tinea Pedis �� 17 2.2Moccasin Tinea Pedis �� 18 2.3Vesicular or Vesiculobullous Tinea Pedis �� 18 2.4Tinea Incognito �� 18 2.5Majocchi’s Granuloma�� 19 2.6Tinea Nigra �� 19 2.7Laboratory Tests�� 20 2.8Treatment�� 20 References�� 20 3 Infections and Infestations of the Lower Extremity �� 21 3.1Bacterial Infections �� 21 3.1.1Abscess �� 21 3.1.2Cellulitis�� 21 3.1.3Erythrasma�� 22 3.1.4Folliculitis �� 22 3.1.5Impetigo�� 22 3.1.6Pitted Keratolysis�� 23 3.2Viral Infections�� 23 3.2.1Hand, Foot, and Mouth Disease�� 23 3.2.2Herpes Zoster�� 23 3.2.3Molluscum Contagiosum�� 24 3.2.4Plantar Verruca�� 24 3.3Infestations�� 25 3.3.1Bed Bugs�� 25 3.3.2Fleas�� 25 3.3.3Scabies�� 26 3.3.4Ticks/Lyme Disease�� 26 References�� 27 4 Xerotic and Hyperkeratotic Disorders of the Lower Extremity�� 29 4.1Xerosis�� 29 4.2Corns and Calluses�� 29 4.3Asteatotic Eczema (Erythema Craquele)�� 30 4.4Keratoderma Climactericum (Haxthausen’s Disease)�� 30 4.5Ichthyosis�� 31 4.6Palmoplantar Keratoderma �� 31 4.7Porokeratosis�� 32 4.8Topical Therapies for Xerotic Conditions�� 32 References�� 32 5 Papulosquamous Disorders of the Lower Extremity�� 35 5.1Psoriasis�� 35 5.2Lichen Planus�� 36 5.3Lichen Striatus�� 37 References�� 38 6 Contact, Irritant, Atopic, and Stasis Dermatitis of the Lower Extremity�� 39 6.1Contact and Irritant Dermatitis �� 39 6.2Atopic Dermatitis�� 40 6.3Stasis Dermatitis �� 40 References�� 42 Contents Contents xiii 7 Concerns of the Lower Extremity in Skin of Color�� 43 7.1Pigmentation Disorders and Inflammatory Conditions�� 43 7.1.1Erythema �� 43 7.1.2Post-inflammatory Hyperpigmentation�� 43 7.1.3Post-inflammatory Hypopigmentation�� 44 7.1.4Vitiligo�� 44 7.1.5Melanonychia�� 45 7.2Scars�� 46 References�� 47 8 Autoimmune Diseases and Vasculopathies of the Lower Extremity �� 49 8.1Chilblains�� 49 8.2COVID Toes�� 49 8.3Systemic Lupus Erythematosus�� 50 8.4Systemic Sclerosis�� 50 8.5Vitiligo�� 51 References�� 51 9 Benign and Malignant Lesions of the Lower Extremity�� 53 9.1Benign Lesions�� 53 9.1.1Acral Nevus�� 53 9.1.2Actinic Keratoses�� 53 9.1.3Angiokeratoma�� 54 9.1.4Dermatofibroma�� 54 9.1.5Lipoma�� 55 9.1.6Neurofibroma�� 55 9.1.7Poroma�� 55 9.1.8Pyogenic Granuloma�� 56 9.1.9Seborrheic Keratosis �� 56 9.1.10Stucco Keratoses �� 57 9.2Malignant Lesions�� 57 9.2.1Basal Cell Carcinoma �� 57 9.2.2Kaposi’s Sarcoma�� 57 9.2.3Keratoacanthoma�� 58 9.2.4Melanoma �� 59 9.2.5Squamous Cell Carcinoma�� 59 9.2.6Mycosis Fungoides (Cutaneous T-Cell Lymphoma)�� 59 References�� 60 10 Blistering Eruptions of the Lower Extremity�� 63 10.1Bullous Pemphigoid�� 63 10.2Dermatitis Herpetiformis�� 63 10.3Epidermolysis Bullosa Acquisita�� 63 10.4Acropustulosis of Infancy �� 64 References�� 65 11 Self-Induced and Psychogenic Skin Conditions of the Lower Extremity �� 67 11.1Erythema Ab Igne �� 67 11.2Prurigo Nodularis�� 67 11.3Tanorexia�� 67 11.4Delusions of Parasitosis�� 68 References�� 69 AL Grawany xiv 12 Skin Signs of Systemic Disease and Reactive Disorders of the Lower Extremity�� 71 12.1Diabetic Dermopathy�� 71 12.2Erythema Multiforme�� 71 12.3Erythema Nodosum�� 72 12.4Granuloma Annulare�� 72 12.5Idiopathic Guttate Hypomelanosis�� 72 12.6Leukocytoclastic Vasculitis �� 73 12.7Lipodermatosclerosis�� 73 12.8Necrobiosis Lipoidica �� 74 12.9Perforating Folliculitis�� 74 12.10Porokeratosis�� 75 12.11Pretibial Myxedema�� 75 References�� 76 13 Ulcerations of the Lower Extremity �� 77 13.1Diagnosis�� 77 13.1.1Shape�� 77 13.1.2Base�� 77 13.1.3Peri-wound Skin�� 77 13.1.4Location�� 77 13.2Arterial Ulcers�� 77 13.3Diabetic Ulcers�� 78 13.4Venous Ulcers �� 78 13.5Pyoderma Gangrenosum�� 79 13.6Sickle Cell Ulcer �� 79 13.7Calciphylaxis�� 79 13.8Pressure Ulcers�� 80 References�� 80 14 Drug Eruptions of the Lower Extremity�� 81 14.1Morbilliform Drug Eruptions�� 81 14.2Fixed Drug Eruption �� 81 14.3Acute Generalized Exanthematous Pustulosis�� 82 References�� 82 15 Biopsy Techniques of the Lower Extremity�� 83 15.1Shave Biopsy�� 83 15.2Punch Biopsy�� 84 15.3Excisional and Incisional Biopsies �� 85 15.4Curettage and Electrodesiccation�� 86 15.5Nail Biopsy �� 87 References�� 88 16 Dermatologic Therapies of the Lower Extremity: Topical and Systemic �� 89 References�� 91 Index�� 93 Contents 1 Nail Disorders of the Lower Extremity The nail is an appendage of the skin that provides a protective barrier to the underlying distal phalanx and soft tissue structures from trauma. Nail appearance and discomfort are the motivators for patients to schedule a consultation. Onychodystrophy is any alteration of nail morphology and is caused by either exogenous or endogenous factors. One of the most common types of toenail onychodystrophy is onychomycosis which represents about half of nail pathologies; other conditions that may mimic dermatophyte infection of the nail unit include psoriasis, lichen planus, and trauma. This chapter will explore a range of disorders that affect the nail. 1.1Nail Plate Changes 1.1.1Beau’s Lines Beau’s lines are transverse depressions in the nail plate that originate within the matrix and progress distally as the nail grows. They occur after a stressful event that temporarily interrupts nail formation or mitotic function of the proximal matrix. Beau’s lines are the most common and least specific nail change in systemic diseases. The margin is parallel to the lunula when the cause is internal and is more apparent on thumb and great toenails. The time of stress can be calculated after measuring the distance from the cuticle to the lines. Multiple transverse lines indicate a repetitive or recurrent stressor. The depth of the depression represents the extent of damage. If there is complete inhibition of nail growth for around 2 weeks, Beau’s line will reach maximum depth resulting in onychomadesis [1]. Diseases associated with Beau’s lines include: cardiovascular (myocardial infarction, myocarditis, peripheral vascular disease); endocrine (diabetes mellitus, hypoparathyroidism, thyrotoxicosis); hematologic (Hodgkin’s lymphoma); infec- Fig. 1.1 Beau’s lines in the presence of onychomycosis on the great toenail tious (hand, foot, and mouth disease, Kawasaki disease, measles, syphilis, mumps, sepsis); pulmonary (hypoxemia, pneumonia, pulmonary embolism); renal (chronic renal failure); use of cytostatic drugs, high fever, exposure to extreme cold, psychological stress, and poor nutritional status. Idiopathic and inherited forms may also occur (Fig. 1.1). 1.1.2Onychomadesis Onychomadesis results from an insult to the matrix and can present with shedding of the nail or a proximal sulcus that splits the nail plate into two parts. This condition is an extreme expression of Beau’s lines, and the causes are the same [1, 2]. In the toenails, trauma is often an inducing factor. The condition is best managed conservatively with treatment of any underlying cause and avoidance of trauma (Fig. 1.2). © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_1 AL Grawany 1 2 1 Nail Disorders of the Lower Extremity Fig. 1.2 Onychomadesis of the great toenail Fig. 1.3 Onychorrhexis as viewed through a dermatoscope 1.1.3Onychorrhexis Onychorrhexis refers to the longitudinal lines or depressions of the nail plate. Onychorrhexis manifests as nail plate splitting, longitudinal thickening, or multiple splits leading to triangular fragments at the nails’ free edge. Nail matrix involvement leads to abnormalities in epithelial growth and keratinization [3]. Among the various factors causing onychorrhexis are disorders of vascularization and oxygenation (such as anemia or arteriosclerosis), as well as systemic and dermatologic diseases (disorders of cornification and inflammatory diseases). Onychorrhexis may also be caused by microtrauma to the proximal nail fold. Raynaud disease, lichen striatus, and trachyonychia can lead to longitudinal splits. Filing of the nail and application of nail hardeners may smooth and fill in the gaps (Fig. 1.3) [3]. 1.1.4Trachyonychia (Twenty Nail Dystrophy) Trachyonychia is a descriptive term referring to rough nail changes [4]. Trachyonychia can affect all nails, referred to as twenty nail dystrophy. It is characterized by brittle, thin nails, with excessive ridging. The excessive ridging causes a rough, opaque appearance in the nails. The nails appear as if they have been sandpapered. The cuticle is also hyperkeratotic and ragged. Twenty nail dystrophy may present as an idiopathic disorder of the nails or it can be associated with a Fig. 1.4 Trachyonychia of toenails 1–5 variety of other disorders such as including vitiligo, atopic dermatitis, lichen planus, psoriasis, and alopecia areata. 1.2 Nail Shape and Size Changes 3 Trachyonychia is a disease of the nail matrix, and a pathological diagnosis requires a nail matrix punch or a longitudinal nail biopsy. The disease is benign, and the diagnosis is made clinically. There is no universally accepted treatment for this chronic disorder. Treatments such as topical or oral steroid treatments are for cosmetic purposes. Treatment options include topical and intralesional steroids. Twenty nail dystrophy may be present as an idiopathic disorder of the nails or it can be associated with a variety of other disorders such as vitiligo, atopic dermatitis, lichen planus, psoriasis, and alopecia areata (Fig. 1.4). 1.2Nail Shape and Size Changes 1.2.1Anonychia Anonychia is defined as the absence of all, one, or several nails. It can be congenital or acquired and may be associated with trauma, ichthyosis, lichen planus, infection, and contact dermatitis. It may also be self-induced or iatrogenic (surgically induced). Aplastic anonychia is a congenital disorder marked by absence of nails at birth. In acquired nail atrophy, the damage to nail unit progresses and no recognizable nail remains. Hypoplasia of the nail occurs as complete absence of the nail unit as seen on the thumb, index fingers, and toes of patients with nail and patella absence syndrome, an autosomal dominant syndrome presenting at birth. Patients later develop crippling degenerative joint disease and renal failure [5]. Diagnosis is confirmed by genetic testing. Camouflage with an artificial nail or nail bed tattoo art improves cosmesis (Fig. 1.5). Fig. 1.5 Iatrogenic anonychia of toes 1, 2, and 4 1.2.2Koilonychia (Spoon Nails) Koilonychia, also known as spoon nails, presents as a longitudinally and/or transversely concave nail plate with everted lateral edges. The nail may be thinned and brittle. The features are most prominent in the thumb or great toe, especially in children. Spoon nails are flattened or concave in the middle with laterally everted edges. Trachyonychia or onychomycosis may accompany koilonychia. Spoon nails are often seen in the setting of inflammatory skin disease, onychomycosis, or secondary to anemia. Associated diseases include lichen planus, psoriasis, iron storage diseases such as hemochromatosis, and iron deficiencies such as Plummer-Vinson syndrome. Other conditions Fig. 1.6 Pincer nail on second toenail include endocrine disorders such as hyper- and hypothyroidism, diabetes. Chronic renal failure, upper gastrointestinal carcinomas, and repetitive trauma can also induce koilonychia. Diagnosis is based on clinical appearance. Topical or injectable steroids, may improve the condition when secondary to psoriasis or lichen planus. When caused by iron related disorders, the focus of treatment is on iron supplementation [6]. In children the deformity may spontaneously regress (Fig. 1.6). AL Grawany 4 1 Nail Disorders of the Lower Extremity 1.2.3Pincer Nails Also known as a trumpet nail, pincer nails are the result of transverse overcurvature of the nail plate that increases distally along the longitudinal axis. It most commonly affects the great toenail and can arise secondary to nail psoriasis, underlying tumor, illfitting shoes, and other biomechanical issues. Some cases are hereditary. This condition is not the same as an ingrown nail. It can be hereditary or acquired and may be painful. Pincer nails are presumed caused by either lack of ground reaction force on the digit or an increase in the automatic curvature force. Lack of ground reaction force could result in mismatched ventral and dorsal nail matrix growth resulting in an inward curvature of the distal nail. A pincer nail is a result of transverse overcurvature of the Fig. 1.7 Clubbing of all digits on foot nail plate that increases distally along the longitudinal axis. It often affects the great toenail but can affect any nail. It may appear as a result of nail psoriasis, underlying tumor, illfitting shoes, and other biomechanical issues of the foot. It is hypothesized that pincer nails may either be caused by the lack of ground reaction force on the digit or by an increase in the automatic curvature force. If there is a lack of ground reaction force, it is plausible that the ventral and dorsal nail matrix grow in a mismatched state resulting in an inward curvature of the distal nail. Pincer nails may be painful. Recurrence is high with conservative therapies (trimming, debridement, bracing) if the underlying issues are not addressed [7]. Surgical procedures such as the ZigZag or Inverted T may be required to correct an associated boney osteophyte and flatten out the nail bed (Fig. 1.6). 1.2.4Clubbing Clubbing is an increase of both the longitudinal and transverse nail plate curvature with soft digital tissue hypertrophy. Usually, all 20 digits are involved. The condition is caused by proliferation of the connective tissue between the nail matrix and the distal phalanx. The angle made by the proximal nail fold and the nail plate (Lovibond angle) is greater than 180°, creating the “Schamroth sign,” which is an obliteration of the normally diamond-shaped space formed when dorsal sides of the distal phalanges of the corresponding right and left digits are opposed [8]. Clubbing is classified into three major categories: idiopathic, hereditary, and acquired. The latter form is associated with a multitude of conditions including heart and lung disease. Lung cancer is the most cause of clubbing. Successful treatment of any underlying condition will reverse clubbing. Clubbing has been reported with Crohn’s disease, ulcerative colitis, hepatic cirrhosis, primary hypertrophic osteoar- Fig. 1.8 Onychogryphosis of all nails thropathy, cystic fibrosis, esophageal cancer, lung cancer, bronchiectasis, lung abscess, pulmonary fibrosis, celiac sprue, cyanotic congenital heart disease, bacterial endocarditis, congestive heart failure, myxoid tumor, and mesothelioma. It can also be hereditary. Treatment of the underlying disorder may decrease or, if caught early enough, reverse the nail pathology (Fig. 1.7). 1.3 Nail Color Changes 1.2.5Onychogryphosis Onychogryphosis (also known as ram’s horn nails) is gross thickening and hardening of a nail, which becomes elongated, curved, and deformed. Onychogryphotic nails are characterized by hypertrophic, hyperkeratotic nail plate thickening with increased discoloration, and a loss of translucency. The terms oyster-like, claw, or ram’s horn nails have been used to describe this deformity. The thickened nails are often marked with transverse striations. These nails can be painful and can lift off or ulcerate the nail bed [9]. Onychogryphosis may result from lack of proper nail care, poor blood supply, injury to the matrix by repeated minor trauma, onychomycosis, diabetes, and/or malnutrition. Onychogryphotic nails are also associated with pachyonychia congenita which is an autosomal dominant keratin disorder that affects infants and children. Treatment involves debridement of the thickened nail plate (Fig. 1.8). 1.3Nail Color Changes 1.3.1Leukonychia Leukonychia refers to the white discoloration of nail. It is traditionally classified into several subtypes. True leukonychia, where the pathology originates in the matrix, can be total, subtotal (proximal two-thirds white and distal part pink), or partial (transverse, punctate, or longitudinal). It may be inherited or acquired. The acquired form may be associated with trauma, chemotherapeutic agents, hypocalcaemia, zinc deficiency, heavy metal poisoning, and systemic diseases [10]. Mees’ lines are true leukonychia classically due to arsenic or thallium intoxication. The condition presents as single or multiple, transverse, narrow, non-blanching whitish lines that run parallel to the lunula across the entire nail bed. Other conditions associated with Mees’ lines include Hodgkin’s disease, leprosy, tuberculosis, malaria, herpes zoster, chemotherapeutic drugs, carbon monoxide and antimony poisoning, renal and cardiac failure, pneumonia, carcinoid tumors, childbirth and systemic lupus erythematosus [11]. Apparent leukonychia, where the pathology is in the nail bed, is referred to as Muehrcke’s lines, half and half (Lindsay’s) nails, and Terry’s nails. Muehrcke’s lines are double white transverse lines caused by vascular congestion in the nail bed. The findings disappear with digital compression and do not migrate with the growth of the nail. Muehrcke’s lines can result from chronic hypoalbuminemia, liver disease, chronic renal failure, malnutrition, and cytostatic drugs. Muehrcke’s bands may be confused with Mees’ lines, the difference is that they resolve with normalization of the serum albumin and do not grow out distally [12]. 5 Transverse Leukonychia is also known as leukonychia striata. Transverse leukonychia is a true leukonychia defined by white bands in the nail plate that traverse the width of the nail and run parallel to the lunula. These are found on both the fingers and toes. The most common cause of transverse leukonychia is repetitive microtrauma. The nail disorder is also associated with ulcerative colitis, chemotherapy, acute arsenic poisoning, nutritional deficiencies, and renal failure [13]. Muehrcke’s lines are double white transverse lines caused by vascular congestion in the nail bed. They disappear with digital compression and do not migrate with the growth of the nail. They can result from chronic hypoalbuminemia, liver disease, chronic renal failure, malnutrition, and cytostatic drugs. Muehrcke’s bands may be confused with Mees’ lines, the difference is that they resolve with normalization of the serum albumin and do not grow out distally [13]. Half and half nails are also called Lindsay’s nails and present as a discoloration of the nail with a half proximal white portion and a distal half reddish pink to brown. The discoloration remains fixed with nail pressure and remains stationary with nail growth, indicating that the pathology begins within the nail bed although the underlying mechanism is not well understood. This nail condition is found in patients with chronic renal failure. Terry’s nails are leukonychia of the entire nail except for a thin 1–2 mm pink to brownish band at the distal free edge. They are mainly associated with hepatic cirrhosis, but can appear in congestive cardiac failure, diabetes mellitus, peripheral vascular disease, chronic renal failure, leprosy, malnutrition, tuberculosis, and HIV patients [12]. Diagnosis is made through clinical presentation and applying digital compression. Lines that do not fade or blanch after compression indicate nail matrix pathology. Serial photographs of the nails can document whether the striations grow out with the nail. Since most transverse leukonychia are caused by repetitive microtrauma, treatment is usually not required as the lines will grow out with the nail. When caused by a disease, toxin, or nutritional deficiency correction of the underlying etiology will improve striations and discoloration (Fig. 1.9). 1.3.2Longitudinal Melanonychia Longitudinal melanonychia, also known as melanonychia striata, is a pigmented brown to black band within the nail plate which results from deposition of melanin by nail matrix melanocytes. Pigment extends to the distal edge of the nail plate. Dependent on cause, longitudinal melanonychia can involve single or multiple nails [14]. It is common in darkly pigmented individuals with nearly all African-Americans developing one or more bands by the age of 50. However, a AL Grawany 6 1 Nail Disorders of the Lower Extremity Fig. 1.9 Leukonychia of great toenail and second nail similar solitary pigmented streak presenting in an individual of Caucasian decent should raise suspicion of melanoma. Extension of pigment into periungual area is referred to as Hutchinson’s sign and may also be an important indicator of malignancy. Longitudinal melanonychia may result from either melanocytic activation or melanocytic proliferation. Activated melanocytes within the nail matrix can increase melanin production without an increase in number of cells. Common causes of longitudinal melanonychia due to melanocytic activation include racial melanonychia, pregnancy, trauma, inflammatory states (lichen planus and psoriasis), iatrogenic (medication), and systemic diseases (Addison’s disease). Syndrome associated melanonychia (Laugier-Hunziker, Peutz-Jeghers, and Touraine syndromes) also presents with mucosal hyperpigmentation. Melanocytic proliferation also leads to increased melanin production. Examples are nail nevi which can be acquired or congenital and melanoma. Extension of pigment into the periungual area is referred to as Hutchinson’s sign. Most cases of melanonychia are benign. Management of underlying systemic disease or discontinuation of the offending substance may decrease nail hyperpigmentation. In the case of suspected subungual melanoma, a biopsy should be performed [15]. Once malignancy is established, a local excision or amputation may be required. Subungual melanoma is commonly misdiagnosed, resulting in a treatment delay (Fig. 1.10). Fig. 1.10 Longitudinal melanonychia as viewed with a dermatoscope 1.3.3Green Nails/Chloronychia An Infection of the nail plate caused by Pseudomonas aeruginosa results in a green discoloration of the nail plate. Chloronychia is characterized by green pigmentation of the nail plate, proximal onychocryptosis, and distal onycholysis. The green discoloration is caused by pigments secreted by P. aeruginosa, namely pyoverdine and pyocyanin [16]. It can also be caused by staining from a dye in clothing or products. The condition is usually asymptomatic. Diagnosis may be confirmed by bacterial culture of nail scrapings. Chloronychia may prove difficult to treat. Therapeutic options include application of topical silver sulfadiazine, gentamicin, polymyxin B, bacitracin, and oral quinolones (ciprofloxacin) [17]. Brushing the nail bed daily with 2% sodium hypochlorite solution may promote clearing. No serious sequelae have been reported (Fig. 1.11) [18]. 1.3.4Yellow Nail Syndrome Yellow nail syndrome is characterized by a triad of thickened yellow nails, primary lymphedema, and respiratory manifestations. Yellowish to green discolored nails are the main clinical manifestation. The discoloration represents a subset 1.4 Nail Plate–Nail Bed Adhesion Issues 7 Fig. 1.11 Green nails resulting from soaking in isopropyl alcohol with wintergreen of chromonychia and xanthonychia [19]. Features may include thickening of the nail plate with an enhanced transverse curvature, hardened/difficult-to-trim nail (scleronychia), and disappearance of the cuticle [20]. Usually opaque and visible, the lunula “disappears” because of nail hyperkeratosis. Onycholysis may occur with possible proximal spreading, leading to complete nail shedding [21]. The nail changes may spontaneously improve. Fig. 1.12 Onycholysis of great toenail 1.4Nail Plate–Nail Bed Adhesion Issues 1.4.1Onycholysis Onycholysis of the nail is the spontaneous separation of the nail plate from the nail bed. Separation begins at the distal free margin of the nail and advances proximally to the nail matrix and lateral borders. The dethatched portion of nail will appear yellow white in color. Onycholysis of the nail is associated with psoriasis, candida infection, onychomycosis, yellow nail syndrome, contact dermatitis, medications, endocrine disorders, environmental causes, connective tissue disorders, and phototoxicity. Culture is recommended to rule out dermatophytosis. Patients should be advised to keep nails short to avoid mechanical trauma (Fig. 1.12). 1.4.2Disappearing Nail Bed Disappearing nail bed (DNB) is characterized by irreversible epithelialization of the nail bed following longstanding onycholysis [22]. This phenomenon can affect both fingernails and toenails. Factors that predispose to development of DNB in toenails include increasing age, history of trauma, surgery, onychomycosis, psoriasis, and onychogryphosis. DNB can Fig. 1.13 Disappearing nail bed of bilateral hallux nails facilitate the growth of dermatophytes and is unsightly. It may induce painful conditions such as distal ingrown toenails. Both conservative and surgical treatments have been described for the management of DNB. The conservative options include taping of the distal skin of the digit, wearing shoes with a wide toe box to accommodate the deformity and prevent further trauma, and camouflaging with a cosmetic resin. As DNB progresses, the distal pulp of the toe enlarges and deforms. This creates a physical barrier for the nail to grow forward and predisposes the digit to the development of distal paronychia. One conservative method that has been attempted is taping of the skin distal to the nail plate to stretch the skin away from the plate and reduce the size of the distal pulp (Fig. 1.13). AL Grawany 8 1.5Unique Toenail Issues 1.5.1Subungual Hematoma Subungual hematoma is a collection of blood between the nail plate and nail bed usually caused by trauma. Bleeding occurs in the space between the nail plate and underlying nail bed and matrix. Since the nail is stationary, blood collects beneath the nail plate and forms a hematoma. Increase in pressure leads to swelling and pain [23]. Extensive hematomas may suggest injury to the nail bed and matrix and even fracture the distal phalanx. Nail trephination is the standard treatment for relieving pressure and pain. Radiographs may be recommended as 20–25% of subungual hematomas are associated with phalangeal fracture [23]. Drainage may be achieved using an 18-gauge needle, #11 scalpel, heated paper clip, or cauterization if the hematoma involves less than 25% of the nail plate. If greater than 25% of the nail plate is involved, removal of the nail for direct visualization and inspection of the nail bed is recommended. Antibiotic therapy and tetanus prophylaxis should also be considered. Complications of nail trephination may include temporary or permanent nail deformity, scarring of the nail bed epithelium, infection, and inadequate evacuation (Fig. 1.14). 1.5.2Ingrown Toenails Onychocryptosis is an ingrowing of the lateral toenail edge. Like pincer nails, ingrown toenails contain a distal incurvated nail edge. Contributing factors include improper nail trimming and physical forces from ill-fitting shoes. Paronychia of the Fig. 1.14 Subungual hematoma on hallux nail 1 Nail Disorders of the Lower Extremity great toenail, or inflammation/infection of the lateral and proximal nail folds usually accompanies the incurvated lateral nail plate. Purulence due to a bacterial infection is generally seen in this condition on the feet, whereas candida infection is more common in chronic thumb-suckers. Treatments may entail topical antibiotic and anti-inflammatory medications, oral antibiotic therapy, taping of the offending nail border to pull the inflamed skin away from the nail, education on proper nail trimming, incision and drainage of the abscess, and surgical removal of the onychocryptotic nail plate (partial nail avulsion or total nail avulsion) (Figs. 1.15 and 1.16) [24]. 1.5.3Congenital Malalignment of the Great Toenail The hallmark of this congenital nail condition is a lateral deviation of the nail plate with respect to the distal phalanx’s longitudinal axis [25]. The nail is discolored presenting with varying degrees of yellow, green, gray, black, or brown. Greenish hue may indicate Pseudomonas colonization, and brown or black discoloration may indicate a subungual hemorrhage or fungal infection. Wave-like transverse ridging (Beau’s line-like) across the nail plate gives the nail an oyster shell-like appearance. The free end of the nail may appear pointed or triangular. The condition usually occurs bilaterally with only hallux involvement and may overlap with hallux valgus. The nail becomes onycholytic and thickened as it progresses and is accompanied by a distal wall of skin which further prevents the nail from growing forward longitudinally. Onychocryptosis and paronychia may develop as the nail continues its curvilinear path toward the second digit. Nails spontaneously regress in less than 50 percent of cases [25]. From a Fig. 1.15 Onychocryptosis of lateral border of hallux nail 1.6 Dermatologic Disease Related Nail Disorders 9 Fig. 1.18 Retronychia of proximal nail fold Fig. 1.16 Paronychia of bilateral nail borders of great toenail such as wearing poorly fitting shoes or activities like hiking [26]. It presents with a paronychia or granulation tissue at the proximal nail fold and nail plate onycholysis. Females are predominately affected and the big toe is usually involved. Treatment consists of totally avulsing the nail plate and avoidance of possible triggers to prevent future trauma (Fig. 1.18). 1.6Dermatologic Disease Related Nail Disorders 1.6.1Nail Psoriasis Fig. 1.17 Congenital malalignment of great toe surgical perspective, the optimal time to correct this deformity is before the age of two. The traditional surgical approach is a crescent-shaped resection proximal to the nail bed and matrix with rotation of the entire nail unit allowing the nail plate to grow in parallel to the distal phalanx (Fig. 1.17) [25]. 1.5.4Retronychia Retronychia describes ingrowth of the proximal nail plate into the proximal nail fold. The condition usually follows trauma Nail psoriasis may appear as pitting of the nail plate, leukonychia, red spots in the nail bed (salmon patches or oil drop), onycholysis, splinter hemorrhages, and nail bed hyperkeratosis [27]. The clinical differentiation between nail psoriasis and other conditions such as onychomycosis is at times challenging and both disorders may coexist. Nail psoriasis often accompanies psoriatic arthritis. Nail psoriasis may respond to topical or intralesional corticosteroids and topical vitamin D3 analogues. Other topical treatments include tacrolimus, fluorouracil, and tazarotene. Oral systemic therapies (acitretin, methotrexate, cyclosporine and apremilast) and biologics (including inhibitors of tumor necrosis factor alpha, IL17 and IL23 are used to treat moderate to severe disease (Fig. 1.19) [28]. 1.6.2Nail Lichen Planus The inflammatory skin condition lichen planus (LP) involves the nail in about 10% of patients. Fingernails are most affected. Early disease is characterized by thinning of the nail plate and longitudinal ridging. Pterygium results from adhesion of the eponychium and the matrix, leading to splitting the nail. Complete loss of the nail plate may follow [29]. AL Grawany 10 Dermatoscopy can aid in recognition with diagnosis confirmed histopathologically. First line treatment is injection of triamcinolone acetonide [30]. Additional therapies include intramuscular steroids and oral retinoids. Intralesional and intramuscular corticosteroids are first line therapy. Additional therapeutic options include tacrolimus, pimecrolimus, cyclosporine, and retinoids (Fig. 1.20) [30]. 1 Nail Disorders of the Lower Extremity 1.7Infections of the Nail Unit 1.7.1Herpes Simplex (Herpetic Whitlow) Herpetic whitlow is a blistering infection of a digit caused by the herpes simplex virus [31]. It most commonly occurs in children and has been reported in ungloved health care workers and contact sport athletes. The condition manifests as painful vesicles swelling, and erythema of the distal phalangeal area. This may be preceded by burning, pruritis, and/or tingling in the affected finger. Vesicles may coalesce and lead to a superficial ulceration. The diagnosis is usually made clinically and can be confirmed by culture, PCR testing, or Tzanck smear [32]. Herpetic whitlow usually involves a finger, but involvement of a toe has been reported [32]. The condition is self- limiting with resolution of symptoms occurring in 7–10 days. Antiviral therapy may shorten the duration of symptoms. Recurrence may be precipitated by fever, sun exposure, or stress (Fig. 1.21). 1.7.2Periungual Viral Warts Fig. 1.19 Nail psoriasis showing nail dystrophy and periungual erythema Fig. 1.20 Nail lichen planus with pterygium formation on great toenail Viral warts, or verrucae, are caused by human papillomavirus (HPV), a double-stranded DNA virus that infects the epidermis. When presenting in and/or around the nail unit, it is referred to as a periungual wart. A periungual wart may be present underneath the nail plate in the nail bed or on the lateral or proximal nail folds. Lack of skin lines, hyperkeratosis, and small pinpoint black dots Fig. 1.21 Herpetic whitlow of the hallux 1.8 Tumors of the Nails 11 Fig. 1.22 Periungual verruca on second digit following cauterization (thrombosed capillaries) are seen throughout the lesion (Fig. 1.22) [33]. Fig. 1.23 Distal subungual onychomycosis of bilateral great toenails 3. Candidal onychomycosis: Onychomycosis caused by Candida occurs most frequently in patients with chronic mucocutaneous candidiasis. The nail can present with Onychomycosis is a dermatophyte or superficial fungal infeconycholysis and paronychia. tion of the nail unit. The condition represents about half of toe- 4. Superficial white onychomycosis: The white powdery nail pathologies [34]. Onychomycosis or tinea unguium is material that accompanies this type of onychomycosis caused by invasion of the nail unit by dermatophytes, non- is present on the dorsal aspect of the nail plate. The dermatophyte molds, and/or Candida albicans. Infected nails condition occurs in tropical climates and it is typically are described as onycholytic, discolored, and hyperkeratotic caused by Trichophyton mentagrophytes or non-dermawith subungual debris. Clinicians may encounter concomitant tophyte molds. Clinicians may mistakenly identify tinea pedis or tinea cruris in patients with onychomycosis. proximal subungual onychomycosis as superficial Onychomycosis is more common in toenails. Fingernail onywhite onychomycosis in very young children due to chomycosis is much less frequent than toenail onychomycosis. their thin nail plates. Several subtypes of onychomycosis have been described: Oral or topical antifungal medications are used to treat 1. Distal (or distal lateral) subungual onychomycosis: This onychomycosis. Consideration should be given to environis the most common type in adults and children. It pres- mental factors such as socks, shoe gear, and living quarters ents as onycholysis with discoloration, subungual debris, (Fig. 1.23). and hyperkeratosis. Concurrent tinea pedis is often seen interdigitally or plantarly on the foot. Trichophyton rubrum is the most common pathogen. 1.8Tumors of the Nails 2. Proximal subungual onychomycosis: This most commonly presents in immunocompromised patients as a 1.8.1Pyogenic Granuloma leukonychia or white discoloration of the proximal nail plate. Distal subungual debris is lacking. Trichophyton Pyogenic granuloma is a benign vascular tumor commonly rubrum and non-dermatophyte molds are the common found within the lateral nail sulcus of the nail bed of the pathogens. great toe and fingers. Lesions typically present as a pain- 1.7.3Onychomycosis AL Grawany 12 1 Nail Disorders of the Lower Extremity Fig. 1.24 Pyogenic granulomas are friable skin lesions that frequently bleed Fig. 1.26 Myxoid cyst creating pressure on nail matrix of second nail and leaving a depression subtypes include dermatofibromas, acquired periungual fibrokeratomas, and Koenen tumors [36–38]. Dermatofibromas are pea-shaped growths that may develop spontaneously or after trauma. Acquired periungual fibrokeratomas are small, asymptomatic fleshy growths with a keratotic distal tip that usually arise following local trauma. Koenen tumors (periungual fibromas) arise in 50% of patients with tuberous sclerosis during childhood or adolescence and occur more commonly on the toenails. Koenen tumors may present as multiple digitated growths that can produce a longitudinal groove in the nail plate due to matrix compression (Fig. 1.25). 1.8.3Myxoid Cyst (Mucoid Cyst) Fig. 1.25 Periungual fibroma on top of hallux nail plate less erythematous mass [35]. The name is a misnomer as lesions are not associated with purulence or granulomatous changes. Lesions may be induced by trauma and less frequently by hormonal changes associated with pregnancy or medications including oral retinoids. Surgical excision, curettage with cautery, and ablative lasers are therapeutic options (Fig. 1.24). 1.8.2Fibroma/Fibrokeratoma These are benign tumors of connective tissue that can originate in the nail matrix or within the nail bed and folds. True fibromas develop as painless slow growing benign nodular tumors that are firm or elastic in consistency. Nail fibroma A mucoid cyst is a benign growth in which the synovium herniates through the joint capsule. The lesion presents as a solitary, non-moveable, smooth-surfaced papule, or nodule localized to the lateral or dorsal aspects of the distal interphalangeal joint. Viscous, jelly-like fluid flows when punctured. It commonly involves the middle or index fingers of the dominant hand and can affect the toes. A traumatic event may trigger it, and the condition is often found in association with osteoarthritis of the underlying joint. Histologically they appear like ganglia with a stalk leading from the joint capsule but they lack a true epithelial lining, making them a pseudocyst. The cyst is fixed to the skin, grows slowly, and contains a viscous yellowish fluid. Some cysts resolve spontaneously [39]. Treatment options include surgery, needling and drainage, sclerosant or steroid injection, and cryotherapy. Recurrence rates are variable (Fig. 1.26) [40]. 1.8 Tumors of the Nails 13 Fig. 1.28 Nail matrix nevi in a child as viewed with a dermatoscope Fig. 1.27 Exostosis of distal phalanx after hallux toenail removed in OR 1.8.4Subungual Exostosis Subungual exostosis is an uncommon benign osseocartilaginous tumor affecting the distal phalanx of the fingers and toes that most commonly affects the hallux. It is characterized by a cartilaginous cap composed of fibrocartilage and bone [41]. Lesions most commonly affect persons under the age of 18 with an equal male-to-female ratio and are associated with a history of pain, erythema, and deformity of the nail bed progressing over several months [42]. Diagnosis is made by radiographically. Precipitating factors include infection, trauma, tumor, hereditary abnormality, and activation of a cartilaginous cyst. Marginal surgical excision with minimal trauma to the nail bed is the treatment of choice (Fig. 1.27) [43]. 1.8.5Nail Matrix Nevi Nail matrix nevi presents as a pigmented longitudinal streak within the nail plate. Nail matrix nevi, a benign manifestation of longitudinal melanonychia, occurs more commonly in dark-skinned individuals and can occur in individuals of all ages, with no sex predilection [44]. Dermoscopy may aid in recognition although a punch biopsy is required to definitively differentiate between benign nail matrix nevus from subungual melanoma. Pigmentation occurs when melanin is deposited in the nail matrix by melanocytes. As the nail continues to grow and melanocytes continue to deposit melanin, a longitudinal streak occurs in the nail plate [15]. Melanin deposition in a benign nevus occurs by melanocytic hyperplasia, which is an increase in the number of melanocytes within the nail matrix itself, rather than an increase in amount of melanin produced by the melanocytes. True nevi are not typically caused by trauma, fungal infection, or systemic disease. Nail matrix nevi are considered benign, and no further treatment is necessary once a definitive diagnosis is made (Fig. 1.28). 1.8.6Bowen’s Disease and Squamous Cell Carcinoma Subungual squamous cell carcinoma (SCC) is a malignancy that can occur in any digit but is more common in fingers than in toes. Subungual SCC is a rare entity but is the most common malignancy of the nail bed. The neoplasm can arise from the nail matrix, the nail bed, the nail groove, or the lateral nail folds. The great toe is most frequently affected. Growth of the neoplasm is usually slow, and clinical presentation is not usually specific. Appearance can present as paronychia, onycholysis, hematoma, ulceration, or a nodule. Age of appearance can vary greatly, but subungual SCC most frequently appears in middle-aged Caucasian males [45]. Bowen’s disease is a very early form of SCC and is commonly referred to as SCC in situ. Biopsy is the gold standard for diagnosis of subungual SCC. Treatment involves excision of the lesion (Fig. 1.29). AL Grawany 14 1 Nail Disorders of the Lower Extremity Fig. 1.29 SCC of great toenail bed 1.8.7Subungual Melanoma Subungual melanoma is a neoplasm derived from malignant melanocytes that originate in the nail matrix. Classic presentation is a dark pigmented band grown longitudinally through the nail unit and usually occurs on the great toe, thumb, or index finger. Subungual melanoma is proportionately the most common form of melanoma in dark-skinned individuals [46]. It initially presents as a longitudinal brown or black band through the nail unit. It is often misdiagnosed as a benign nail matrix nevus. As the melanoma evolves over weeks to months, the neoplasm can undergo changes such as larger width, irregular pigmentation, extension to the nail fold (Hutchinson’s sign), ulceration, formation of a nodule, and resultant nail destruction and dystrophy. In some cases, subungual melanoma is amelanotic and not pigmented [47]. Subungual melanoma is not thought to be influenced by UVA or UVB exposure. Exact pathogenesis is unknown, but it can be associated with nail bed trauma, weakened immune system, and familial history of melanoma or other malignancies [48]. Treatment includes removal of affected nail and wide excision of the nail unit with adequate margins. Amputation may be necessary. Prognosis can be good but depends on depth and extent of invasion (Fig. 1.30). Fig. 1.30 Subungual melanoma of hallux that was misdiagnosed as a paronychia and pyogenic granuloma References 1. Braswell MA, Daniel CR 3rd, Brodell RT. Beau lines, onychomadesis, and retronychia: a unifying hypothesis. J Am Acad Dermatol. 2015;73(5):849–55. 2. Damevska K, Gocev G, Pollozahani N, Nikolovska S, Neloska L. Onychomadesis following cutaneous vasculitis. Acta Dermatovenerol Croat. 2015;25(1):77–9. 3. Baran R. The nail in dermatological disease. In: Baran & Dawber’s diseases of the nails and their management. Oxford, UK: Blackwell Publishing Ltd.; 2012. p. 257–314. 4. Gordon K, Vega J, Tosti A. Trachyonychia: a comprehensive review. Indian J Dermatol Venereol Leprol. 2011;77(6):640–5. 5. Bodman MA. Nail dystrophies. Clin Podiatr Med Surg. 2004;21(4):663–87, viii 6. Taguchi Y, Takashima S, Tanaka K. Koilonychia in a patient with subacute iron-deficiency anemia. Intern Med. 2013;52(20):2379. 7. Baran R, Haneke E, Richert B. Pincer nails: definition and surgical treatment. Dermatol Surg. 2001;27(3):261. References 8. Fawcett RS, Linford S, Stulberg DL. Nail abnormalities: clues to systemic disease. Am Fam Physician. 2004;69(6):1417–24. 9. Maddy T. Hair and nail diseases in the mature patient. Clin Dermatol. 2018;36(2):159–66. 10. Canavan T, Tosti A, Mallory H, McKay K, Cantrell W, Elewski B. An idiopathic leukonychia totalis and leukonychia partialis case report and review of the literature. Skin Append Disord. 2015;1(1):38–42. 11. Sharma S, Gupta A, Deshmukh A, Puri V. Arsenic poisoning and Mees’ lines. QJM. 2016;109(8):565–6. 12. Chávez-López MA, Arce-Martínez FJ, Tello-Esparza A. Muehrcke lines associated to active rheumatoid arthritis. J Clin Rheumatol. 2013;19(1):30–1. 13. Maino KL, Stashower ME. Traumatic transverse leukonychia. Skinmed. 2004;3(1):53–5. 14. Salem A, Gamil H, Hamed M, Galal S. Nail changes in patients with liver disease. J Eur Acad Dermatol Venereol. 2010;24(6): 649–54. 15. Jefferson J, Rich P. Melanonychia. Dermatol Res Pract. 2012;2012:952186. https://doi.org/10.1155/2012/952186. 16. Metzner MJ, Billington AR, Payne WG. Melanonychia. Eplasty. 2015;15:ic48. 17. Chiriac A, Brzezinski P, Foia L, Marincu I. Chloronychia: Green Nail Syndrome Caused by Pseudomonas aeruginosa in elderly persons. Clin Interv Aging. 2015;10:265–7. 18. Rallis E, Paparizos V, Flemetakis A, Katsambas A. Pseudomonas fingernail infection successfully treated with topical nadifloxacin in HIV-positive patients: report of two cases. AIDS. 2010;24(7):1087–8. 19. Matsuura H, Senoo A, Saito M, Hamanaka Y. Green nail syndrome. QJM An Intl J Med. 2017;110(9):609. 20. Baran R. Pigmentations of the nails (chromonychia). J Dermatol Surg Oncol. 1978;4:250–4. 21. Stosiek N, Peters KP, Hiller D, Riedl B, Hornstein OP. Yellow nail syndrome in a patient with mycosis fungoides. J Am Acad Dermatol. 1993;28:792–4. 22. Venencie PY, Dicken CH. Yellow nail syndrome: report of five cases. J Am Acad Dermatol. 1984;10:187–92. 23. Daniel R, Meir B, Avner S. An update on the disappearing nail bed. Skin Append Disord. 2017;3(1):15–7. https://doi. org/10.1159/000455013. 24. Malay S. Trauma to the nail bed and associated structures. Podiat Inst. 1993;1993:133. 25. Haneke E. Controversies in the treatment of ingrown nails. Dermatol Res Pract. 2012;2012:783924. 26. Domínguez-Cherit J, Lima-Galindo AA. Congenital malalignment of the great toenail: conservative and definitive treatment. Pediatr Dermatol. 2021;38(3):555–60. https://doi.org/10.1111/pde.14548. 27. Mello CDBF, et al. Ret onychia. An Bras Dermatol. 2018;93(5):707– 11. https://doi.org/10.1590/abd1806-4841.20187908. 28. Thomas L, Azad J, Takwale A. Management of nail psoriasis. Clin Exp Dermatol. 2021;46(1):3–8. https://doi.org/10.1111/ced.14314. 29. Wechsuruk P, Bunyaratavej S, Kiratiwongwan R, Suphatsathienkul P, Wongdama S, Leeyaphan C. Clinical features and treatment outcomes of nail lichen planus: a retrospective study. JAAD Case Rep. 2021;22(17):43–8. https://doi.org/10.1016/j.jdcr.2021.09.015. 15 30. Iorizzo M, Tosti A, Starace M, Baran R, Daniel CR 3rd, Di Chiacchio N, Goettmann S, Grover C, Haneke E, Lipner SR, Rich P, Richert B, Rigopoulos D, Rubin AI, Zaiac M, Piraccini BM. Isolated nail lichen planus: an expert consensus on treatment of the classical form. J Am Acad Dermatol. 2020;83(6):1717–23. https://doi.org/10.1016/j.jaad.2020.02.056. 31. Betz D, Fane K. Herpetic whitlow. [Updated 2021 Aug 6]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK482379/ 32. Collier E, Parikh P, Martin-Blais R, Chen J, Anand V. Herpetic whitlow of the toe presenting with severe viral cellulitis. Pediatr Dermatol. 2019;36(3):406–7. https://doi.org/10.1111/pde.13795. 33. Bae JM, Kang H, Kim HO, Park YM. Differential diagnosis of plantar wart from corn, callus and healed wart with the aid of dermoscopy. Br J Dermatol. 2009;160(1):220–2. 34. Lipner SR, Scher RK. Part I: onychomycosis: clinical overview and diagnosis. J Am Acad Dermatol. 2018;80(4):835–51. 35. Richert B, Lecerf P, Caucanas M, André J. Nail tumors. Clin Dermatol. 2013;31(5):602–17. 36. Abimelec P, Dumontier C. Basic and advanced nail surgery (Part 2: indications and complications). In: Scher RK, Daniel III RC, editors. Nails: diagnosis, therapy, and surgery. Elsevier Saunders; 2005. p. 291. 37. Baran R, Perrin C, Baudet J, Requena L. Clinical and histological patterns of dermatofibromas of the nail apparatus. Clin Exp Dermatol. 1994;l19(1):31–5. 38. Kojima T, Nagano T, Uchida M. Periungual fibroma. J Hand Surg Am. 1987;12(3):465–70. 39. Hernández-Lugo A, Domínguez-Cherit J, Vega-Memije M. Digital mucoid cyst: the ganglion type. Int J Dermatol. 1999;38(7):533–5. 40. Balakirski GM, Loeser C, Baron J, Dippel E, Schmitt L. Effectiveness and safety of surgical excision in the treatment of digital mucoid cysts. Dermatol Surg. 2017;43(7):928–33. 41. DaCambra MP, Gupta SK, Ferri-de-Barros F. Subungual exostosis of the toes: a systematic review. Clin Orthop Relat Res. 2018;472(4):1251–9. 42. Davis DA, Cohen PR. Subungual exostosis: case report and review of the literature. Pediatr Dermatol. 1996;13(3):212–8. 43. Letts M, Davidson D, Nizalik E. Subungual exostosis: diagnosis and treatment in children. J Trauma. 1998;44(2):346–9. 44. Lee JH, Lim Y, Park JH, Lee JH, Jang KT, Kwon EJ, Lee DY. Clinicopathologic features of 28 cases of nail matrix nevi (NMNs) in Asians: comparison between children and adults. J Am Acad Dermatol. 2018;78(3):479–89. 45. Sousa Padilha CB, Almeida Balassiano LK, Pinto JC, Souza FCS, Kac BK, Treu CM. Subungual squamous cell carcinoma. An Bras Dermatol. 2016;91(6):817–9. 46. Lee JH, Park J-H, Lee JH, Lee D-Y. Early detection of subungual melanoma in situ: proposal of ABCD strategy in clinical practice based on case series. Ann Dermatol. 2018;30(1):36–40. 47. Chamberlain A, Ng J. Cutaneous melanoma--atypical variants and presentations. Aust Fam Physician. 2009;38:476–82. 48. Singal A, Pandhi D, Gogoi P, Grover C. Subungual melanoma is not so rare: report of four cases from India. Indian Dermatol Online J. 2017;8(6):471–4. AL Grawany 2 Superficial Fungal Infections of the Lower Extremity Superficial fungal infections of the lower extremity may be caused by dermatophytes, yeast, and molds and may become secondarily infected with bacteria. Dermatophytes that prefer skin, hair, and nails are Trichophyton sp, Microsporum sp, and Epidermophyton sp. The most common pedal pathogen is Trichophyton rubrum. Dermatophytes are contagious and may be transferred from soil, animals, fomites, and from other humans. Wearing shoes, sneakers, and boots contributes to a warm and moist environment, an optimal milieu for fungi to thrive. These pedal infections, known as tinea pedis or athlete’s foot, generally occur in the interdigital areas where prolonged moisture causes maceration, and on the plantar surface of the foot leading to dry, scaly, and itchy skin. Populations at risk include those who use communal facilities (pools, dorm showers, gyms); those who wear rubber or non-breathable shoes at work; and persons who are obese, diabetic, immunocompromised, vascularly compromised and are unable to perform regular foot hygiene [1]. KOH examination is useful to determine if a dry, scaly plantar rash is tinea pedis or xerosis. Tinea pedis is positive for the presence of fungal hyphae (Figs. 2.1 and 2.2). Tinea pedis can serve as a nidus of infection resulting in spread to other body sites. Common types of dermatophytosis are tinea corporis (body), tinea cruris (groin), tinea manuum (hands), tinea capitis (scalp), and onychomycosis (nails). Tinea pedis can resemble other conditions including eczema, plaque and pustular psoriasis, allergic contact dermatitis, irritant contact dermatitis, dyshidrosis, xerosis, secondary syphilis, erythrasma, pitted keratolysis, and soft corn (heloma molle). Fig. 2.1 Plantar xerosis has scale within the skin lines and is KOH negative 2.1Interdigital Tinea Pedis Interdigital tinea pedis is the most common form and is often located within the fourth interspace (between the fourth and fifth toes) although all interspaces can be Fig. 2.2 Severe plantar xerosis © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_2 17 18 2 Superficial Fungal Infections of the Lower Extremity affected with spread plantarly to the toe sulcus. The condition can present as a dry, pruritic, and scaly rash or as inflamed, macerated tissue deep in the interspace which can fissure, ulcerate, and become secondarily infected with bacteria such as Corynebacterium or Pseudomonas, resulting in localized cellulitis or lymphangitis (Figs. 2.3, 2.4, and 2.5). Fig. 2.3 Dry interdigital tinea pedis Fig. 2.6 Moccasin tinea pedis 2.2Moccasin Tinea Pedis T. rubrum is the most common cause of this chronic form of tinea pedis that affects the plantar and lateral aspects of the foot in a moccasin shoe-type distribution [1]. Usually bilateral, it presents as serpiginous circular scale which may be erythematous and pruritic. Associated findings can include fissures and onychomycosis (Fig. 2.6). Fig. 2.4 Macerated tissue in interdigital tinea pedis 2.3Vesicular or Vesiculobullous Tinea Pedis This condition presents as vesicles on a background of erythema localized to the dorsum of the foot and is possibly secondary to an autosensitization dermatitis triggered by dermatophytes. Lesions may be painful or pruritic. Differential diagnosis includes pustular psoriasis and bacterial infection (Fig. 2.7) [1]. 2.4Tinea Incognito Fig. 2.5 Superinfected tinea pedis with inflammation dorsally Tinea incognito results from a dermatophyte infection that has been inappropriately treated with topical steroids [2]. The condition may have initially been diagnosed as eczema AL Grawany 2.6 Tinea Nigra 19 Fig. 2.7 Vesicular tinea pedis Fig. 2.9 Majocchi’s granuloma on the leg Fig. 2.8 Tinea incognito resulting from Class I topical steroid use on a tinea pedis infection or psoriasis. Pruritus, scaling, and erythema improve at onset but over time the infection extends. A nondescript macular rash evolves into a circinate patch with raised borders and at times scattered vesicles. KOH (potassium hydroxide) preparation reveals numerous fungal elements. Treatment entails discontinuation of topical steroids and institution of antifungal therapy (Fig. 2.8). 2.5Majocchi’s Granuloma Majocchi’s granuloma, also referred to as granuloma trichophyticum, is a suppurative and granulomatous folliculitis caused by a fungal infection. In most cases the causal agent is Trichophyton rubrum [3]. The condition often occurs in association with tinea unguium and tinea pedis. In women, Majocchi’s granuloma may be precipitated by shaving and waxing. Cases have been related to both topical steroid use and immunosuppression. When associated with the latter common findings include indurated plaques with erythematous subcutaneous nodules [4]. Confirmation of Majocchi’s granuloma is best achieved by fungal culture and/or biopsy. Because the infection is deep-seated within hair follicles topical antifungals are ineffectual. Therapeutic options include terbinafine and itraconazole (Fig. 2.9) [4]. 2.6Tinea Nigra Tinea nigra is a superficial fungal infection caused by Hortaea werneckii. Predominantly found in tropical and subtropical locales, it can be seen in persons returning from endemic areas [5]. The disorder presents as a well-defined, asymptomatic, brown-black hyperpigmented macule or patch without scale on the hands and feet and may be misdiagnosed as an acral nevus or melanoma. KOH and fungal culture are positive and the condition responds well to topical antifungals (Fig. 2.10). 20 2 Superficial Fungal Infections of the Lower Extremity areas. Patients can also use ultraviolet shoe sanitizers to decrease the bioburden in daily shoe gear. Often the patient will self-treat with over-the-counter preparations that consist of medicated foot powders, sprays, and creams such as Castellani’s paint, gentian violet, undecylenic acid, miconazole, clotrimazole, tolnaftate, butenafine, and terbinafine. Prescription antifungal topical preparations include the following: • • • • • • • Fig. 2.10 Tinea nigra on the nail unit that was misdiagnosed as acral melanoma 2.7Laboratory Tests A superficial fungal infection is often suspected based on history and examination. Various laboratory tests may be used to confirm the diagnosis such as KOH examination, fungal culture, periodic acid Schiff (PAS) stain, and polymerase chain reaction (PCR). A punch biopsy may be useful to differentiate tinea from an inflammatory skin disorder like psoriasis. When sampling a dermatitis for KOH or culture, scraping of the leading edge with a No. 15 blade provides the highest yield. Cultures should be observed for up to 4 weeks due to the slow growth of dermatophytes. 2.8Treatment Ciclopirox Econazole Ketoconazole Luliconazole Naftifine Oxiconazole Sertaconazole Longstanding or severe infections may warrant an oral antifungal. Approved medications are griseofulvin, terbinafine, itraconazole, and fluconazole. In addition to a topical antifungal, the clinician may add a keratolytic to descale the plantar skin and decrease transepidermal water loss. Lactic acid, salicylic acid, and urea preparations may facilitate efficacy of the antifungal. Bacterial superinfection may require topical and/or oral antibiotics for adequate control. Topical preparations that decrease sweating such as aluminum chloride solution and powders, as well as botulinum toxin injection, may help prevent recurrence. References 1. Nigam PK, Saleh D. Tinea Pedis. [2021 Jun 7]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. 2. Nowowiejska J, Baran A, Flisiak I. Tinea incognito: a great physician pitfall. J Fungi (Basel). 2022;8(3):312. https://doi.org/10.3390/ jof8030312. 3. Boral H, Durdu M, Ilkit M. Majocchi’s granuloma: current perspectives. Infect Drug Resist. 2018;11:751–60. https://doi.org/10.2147/ IDR.S145027. 4. Castellanos J, Guillén-Flórez A, Valencia-Herrera A, et al. Unusual inflammatory tinea infections: Majocchi’s granuloma and d eep/systemic dermatophytosis. J Fungi (Basel). 2021;7(11):929. https://doi. org/10.3390/jof7110929. 5. Eksomtramage T, Aiempanakit K. Tinea nigra mimicking acral melanocytic nevi. IDCases. 2019;18:e00654. https://doi. org/10.1016/j.idcr.2019.e00654. Patients should be educated on foot hygiene: drying between toes, changing socks and shoes daily, disinfecting family showering areas, and wearing shower shoes in communal AL Grawany 3 Infections and Infestations of the Lower Extremity Bacteria, viruses, and insects can all wreak havoc on our skin. To follow are the most common conditions encountered on the lower extremities that may result from these noxious agents. 3.1Bacterial Infections 3.1.1Abscess Skin abscesses are localized soft tissue swellings usually caused by bacteria and accompanied with erythema and pain. Staphylococcus aureus is the most frequently isolated pathogen from skin abscesses and the incidence of methicillin- resistant (MRSA) strains is significant and a major global health concern [1]. Diagnosis is usually based on history and clinical findings although ultrasound may aid in differentiation from other soft tissue infections such as cellulitis [2]. The absence of purulent drainage does not rule abscess formation. Abscesses in otherwise healthy individuals are best treated with incision and drainage [3]. The use of oral antibiotics to treat uncomplicated cases is somewhat controversial and is often guided by severity of the infection, results of culture if performed, and incidence of local community- associated MRSA (Fig. 3.1). 3.1.2Cellulitis Cellulitis is a frequently encountered bacterial infection that has a propensity to affect the lower legs. Common pathogens are group A streptococcus and staphylococcus aureus; however, the majority of cases are nonculturable and the underlying pathogen is unidentified [4]. The diagnosis is usually based on history and physical examination which reveals localized erythema and swelling associated with warmth and tenderness. More severe cases may be associated with fever. Fig. 3.1 Painful ankle abscess that required drainage and systemic antibiotics Predisposing factors are obesity, diabetes, tinea pedis, and advancing age [5]. The condition may result from incidental trauma such as a superficial abrasion. Empiric treatment of cellulitis often includes a 5-to-7-day course of oral antibiotics active against both streptococci and staphylococci [6]. To prevent recurrence, underlying factors such as lymphedema and tinea pedis should be addressed as well (Fig. 3.2). © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_3 21 22 3 Infections and Infestations of the Lower Extremity Fig. 3.3 Erythrasma is a bacterial condition that fluoresces under a Wood’s light Fig. 3.2 The lower legs are the most common site of cellulitis 3.1.3Erythrasma Erythrasma is a superficial infection of the intertriginous areas. On the foot the condition is localized to the digital interspaces. Erythrasma presents as a scaly rash that may be asymptomatic or macerated, pruritic, and malodorous. It is most commonly associated with Corynebacterium minutissimum which is a member of the normal skin flora capable of invading the stratum corneum given a warm, moist environment [7]. Corynebacterium produces porphyrins that fluoresce coral-red under the Wood’s lamp in contrast to Pseudomonas, which fluoresces green. This procedure is best performed in a darkened room. Differential diagnoses include interdigital tinea pedis, candida infection, and contact dermatitis. Treatment typically consists of topical erythromycin, clindamycin, or Whitfield’s ointment (Fig. 3.3). 3.1.4Folliculitis Folliculitis is an inflammatory reaction that involves hair follicles. The result is either a pustule or an erythematous papule. Friction, occlusion, and perspiration are contributing factors and the thighs and buttocks are commonly involved Fig. 3.4 Folliculitis is an inflammation of hair follicles sites. Most cases are caused by Staphylococcus aureus including both methicillin-sensitive and methicillin-resistant strains [8]. Hot tub folliculitis is due to pseudomonas colonization of hair follicles. The eruption associated with this disorder typically develops within 48 h of exposure to a contaminated water source. Pityrosporum or malassezia folliculitis is a yeast infection that uncommonly occurs on the lower extremities [9]. Folliculitis is usually self-limiting and resolves without therapy although recurrence is not uncommon and may be minimized by use of antibacterial soaps. Severe or persistent cases may warrant topical and/or oral therapies directed at the causative agent (Fig. 3.4). 3.1.5Impetigo Impetigo is a common skin disorder in children but may occur at any age [10]. The condition is highly contagious and predominately affects the lower legs and face. The majority AL Grawany 3.2 Viral Infections of cases are caused by Streptococcus pyogenes or Staphylococcus aureus and cuts and abrasions are common bacterial entrance points. Contact sports such as wrestling and football predispose to transmission. Impetigo is classified as either nonbullous or bullous. Nonbullous impetigo begins as an erythematous macule that quickly vesiculates and ruptures. Dried serous fluid contributes to the honey-combed, crusted appearance. Rubbing and scratching lead to spread of lesions. Bullous impetigo presents with superficial, fragile bullae varying in size. Onset is rapid and spontaneous drainage produces a collarette of scale and crusts. The diagnosis of impetigo is usually made clinically. Lesions should be lightly cleansed to remove superficial crusting. Topical mupirocin is used to treat isolated lesions [11]. Oral antibiotics that cover both S aureus and S pyogenes may be instituted to decrease duration and extent of disease (Fig. 3.5) [12]. 3.1.6Pitted Keratolysis Pitted keratolysis is a superficial bacterial skin infection characterized by malodor and crateriform pitting that affects the pressure-bearing areas of the soles [13]. The condition occurs worldwide but is most prevalent in tropical countries. Those at highest risk are athletes, military personnel, and industrial workers and the disorder is most common in male adolescents and young adults. Causative agents include Kytococcus sedentarius, Dermatophilus congolensis, and Corynebacterium [14]. These organisms produce proteases that dissolve the stratum corneum and result in pits. Secreted sulfur compounds contribute to the malodor. Most lesions are asymptomatic and itching, burning, and pain on ambulation are infrequently noted. 23 Fig. 3.6 Pitted keratolysis manifests as pits of the soles accompanied by malodor Diagnosis of pitted keratolysis is based on the clinical appearance and accompanying odor. Preventative measures include the use of cotton socks, frequent sock changes, cleaning and drying of the feet after exercise or bathing, and minimizing use of occlusive shoes. Successful treatment is usually achieved with topical antibiotic therapies such as clindamycin, erythromycin, fusidic acid, and mupirocin [15]. Nightly application of a drying agent such as aluminum chloride hexahydrate may help prevent recurrence (Fig. 3.6). 3.2Viral Infections 3.2.1Hand, Foot, and Mouth Disease Hand, foot, and mouth disease is a contagious disorder that primarily affects infants and children under the age of 10. The condition is caused by enteroviruses and coxsackieviruses and is transmitted by fecal-oral, oral-oral, and respiratory droplet contact [16]. The incubation period is up to 6 days. A prodrome of fever and malaise is followed in short order by macules and vesicles arising on the hands and feet. Shallow ulcers appear on the buccal mucosa and tongue and these may be painful. Diagnosis is usually made clinically. Hand, foot, and mouth disease is self-limiting with complete resolution within 10 days. Rare complications include aseptic meningitis and myocarditis (Fig. 3.7) [17]. 3.2.2Herpes Zoster Fig. 3.5 Impetigo is a bacterial infection that presents as oozing, crusted patches Herpes zoster, commonly known as shingles, is an acute, painful, blistering eruption. The condition is caused by reactivation of the varicella zoster virus acquired as a sequela of chicken pox infection. The virus remains latent in the sen- 24 3 Infections and Infestations of the Lower Extremity Fig. 3.7 Hand foot and mouth disease is a self-limited viral infection (Courtesy of Lawrence Schiffman, DO) sory ganglia until triggered by a defect in immune surveillance [18]. Precipitating factors include immunosuppressant medications and malignancy. Incidence of herpes zoster is highest in the elderly. Herpes zoster presents as a painful skin rash in a dermatomal distribution. Shortly thereafter grouped vesicles arise and these gradually resolve over the course of two to 3 weeks. Pain that persists greater than 30 days is referred to as postherpetic neuralgia and this dreaded sequela may be intense and incapacitating. The adjuvanted, recombinant varicella zoster virus (VZV) vaccine (Shingrix) has demonstrated high efficacy as a preventative of shingles and is recommended for adults aged 50 and above (Fig. 3.8) [19]. 3.2.3Molluscum Contagiosum Molluscum contagiosum is a common skin disorder caused by a poxvirus [20]. Close contact transmits the virus and autoinoculation results in spread. Preschool and elementary school children are predominately affected [21]. Characteristic lesions are dome shaped, flesh to pink colored papules with umbilicated centers. In healthy patients, infection is generally self-limited and resolves within several months. Spontaneous resolution may be accompanied by an Fig. 3.8 Herpes zoster presents as painful blisters on an erythematous base (Courtesy of Alan Weisman, DPM) inflammatory, eczematoid reaction termed the BOTE sign (short for, beginning of the end) [22]. Treatment with curettage or liquid nitrogen hastens resolution but ablative therapies may be somewhat traumatic to a child and can result in hyperpigmentation (Fig. 3.9). 3.2.4Plantar Verruca Plantar verrucae are caused by the human papillomavirus (HPV). The virus can be found on floors, socks, and sporting equipment and enters the skin through minor trauma. Upon entrance into the epidermis HPV inoculates keratinocytes and continues to replicate [23]. Lesions present as well- defined papillomatous growths with overlying hyperkeratosis. Mosaic warts refer to groups of verrucae clustered together. Pinpoint bleeding upon debridement and disruption of normal skin lines differentiate warts from a plantar callus. Further, lateral compression on a wart induces pain, whereas a callus is most painful with direct pressure. Preventative measures include avoidance of walking barefoot in public areas such as swimming pools, locker AL Grawany 3.3 Infestations 25 Fig. 3.9 Dome-shaped papules are classic for molluscum contagiosum 3.3Infestations 3.3.1Bed Bugs Fig. 3.10 Plantar verruca are persistent and often require multiple treatment sessions rooms, gymnasiums, and public showers. Treatment may prove challenging. Most lesions will eventually resolve spontaneously but patients often seek treatment due to discomfort or cosmesis [24]. Home remedies include wart solutions containing salicylic acid and duct tape. Variable results have been reported with topical agents including cantharidin, imiquimod, and 5-fluorouracil. Liquid nitrogen cryosurgery and laser ablation are office based destructive therapies that usually require multiple sessions (Fig. 3.10). Bed bugs are bloodsucking ectoparasites that are members of the Cimicidae family [25]. The insects feed throughout the night targeting exposed areas of skin such as the arms and legs. Once feeding has ended, bed bugs will relocate to the crevices of a bed or couch. Unengorged insects have flat, reddish-brown oval shaped bodies. Skin lesions manifest as erythematous papules and are extremely pruritic. Bites are often grouped in a linear array of three, the pattern descriptively termed “breakfast, lunch, and dinner” [26]. Individual bites respond to topical steroids and typically resolve within several days. Steam cleaning or treatment with insecticides is usually necessary for complete eradication (Fig. 3.11). 3.3.2Fleas Fleas (Siphonaptera) are bloodsucking ectoparasites and over 2500 species are found worldwide [27]. Domestic cats and dogs are the primary intermediaries to humans. The body of fleas is studded with pointed bristles that facilitate movement within fur. Fleas cannot fly but are impressive 26 Fig. 3.11 Bed bug bites in groups of threes, referred to as breakfast, lunch, and dinner 3 Infections and Infestations of the Lower Extremity Fig. 3.13 Scabies is a contagious skin condition caused by the mite Sarcoptes scabiei 3.3.3Scabies Fig. 3.12 Fleas are often transmitted to humans by their pets jumpers with hind legs allowing them to leap up to 150 times their body length. Flea-bite dermatitis is an allergic reaction caused by substances in their saliva [28]. Cat fleas have a predilection for biting ankles. Bites present as erythematous papules that are often excoriated. Fleas can transmit a number of illnesses including bubonic plague, spotted fever rickettsiosis, and murine typhus. Ridding a home of fleas entails treating pets, washing bedding, and vacuuming carpets (Fig. 3.12). Scabies is an intensely pruritic skin infestation caused by the host-specific mite Sarcoptes scabiei var hominis. The condition is most commonly encountered in institutions such as nursing homes and prisons [29]. The most prominent clinical feature is intense itching especially worse at night. The pruritus is the result of a delayed type-IV hypersensitivity reaction to the mite, feces, and eggs [30]. Classic findings are burrows and small erythematous papules replete with excoriations and hemorrhagic crusts. A dark triangular structure can be visualized on dermoscopy. The most common sites of involvement are the finger and toe webs, wrists, buttocks, genitals, and the breasts in women. Norwegian scabies is a clinical variant that manifests thick crusts that are most prominent on the hands and feet. Immunocompromised and debilitated, elderly individuals are at greatest risk. Successful treatment requires eradication of the mites and may be accomplished with topical or oral anti-scabetic agents [31]. Close contacts should be treated simultaneously (Fig. 3.13). 3.3.4Ticks/Lyme Disease Lyme disease is a tick-borne illness caused by Borrelia burgdorferi, a spirochetal bacterium. Cases are primarily located in northeastern and mid-Atlantic states and are most frequent between the months of May and September [32]. History usually includes recent outdoor activity in a wooded area with development of a rash following a tick bite. The annular AL Grawany References Fig. 3.14 The characteristic rash of Lyme disease, erythema migrans, resembles a “bull’s eye” erythematous patch with central clearing, termed erythema migrans, occurs at the site of the bite and is found in approximately 80% of cases. At least 24 h of attachment is required for disease transmission [33] and the incubation period ranges from 3 to 20 days. Diagnosis of early Lyme disease is facilitated by recognition of the classic rash and history of tick bite in endemic areas, with confirmation established by serologic testing. First line treatment for early disease is doxycycline. Untreated, the condition may lead to arthritis, carditis, and neuropathy (Fig. 3.14). References 1. Hassoun A, Linden PK, Friedman B. Incidence, prevalence, and management of MRSA bacteremia across patient populationsa review of recent developments in MRSA management and treatment. Crit Care. 2017;21(1):211. https://doi.org/10.1186/ s13054-017-1801-3. 2. Subramaniam S, Bober J, Chao J, Zehtabchi S. Point-of-care ultrasound for diagnosis of abscess in skin and soft tissue infections. Acad Emerg Med. 2016;23(11):1298–306. https://doi.org/10.1111/ acem.13049. 3. Hammond SP, Baden LR. Management of skin and soft-tissue infection — polling results. N Engl J Med. 2008;359:e20. 4. Raff AB, Kroshinsky D. Cellulitis: a review. JAMA. 2016;316(3):325–37. https://doi.org/10.1001/jama.2016.8825. 5. Cranendonk DR, Lavrijsen APM, Prins JM, Wiersinga WJ. Cellulitis: current insights into pathophysiology and clinical management. Neth J Med. 2017;75(9):366–78. 6. Sullivan T, de Barra E. Diagnosis and management of cellulitis. Clin Med (Lond). 2018;18(2):160–3. https://doi.org/10.7861/ clinmedicine.18-2-160. 7. Groves JB, Nassereddin A, Freeman AM. Erythrasma. [2021 Aug 11]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. 27 8. Winters RD, Mitchell M. Folliculitis. [2021 Aug 11]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. 9. Berger RS, Seifert MR. Whirlpool folliculitis: a review of its cause, treatment, and prevention. Cutis. 1990;45(2):97–8. 10. Rubenstein RM, Malerich SA. Malassezia (pityrosporum) folliculitis. J Clin Aesthet Dermatol. 2014;7(3):37–41. 11. Hartman-Adams H, Banvard C, Juckett G. Impetigo: diagnosis and treatment. Am Fam Physician. 2014;90(4):229–35. 12. Koning S, van der Sande R, Verhagen AP, van Suijlekom-Smit LW, Morris AD, Butler CC, Berger M, van der Wouden JC. Interventions for impetigo. Cochrane Database Syst Rev. 2012;1(1):CD003261. https://doi.org/10.1002/14651858.CD003261.pub3. 13. Nardi NM, Schaefer TJ. Impetigo. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK430974/. 14. Bristow IR, Lee YL. Pitted keratolysis: a clinical review. J Am Podiatr Med Assoc. 2014;104(2):177–82. 15. Fernández-Crehuet P, Ruiz-Villaverde R. Pitted keratolysis: an infective cause of foot odour. CMAJ. 2015;187(7):519. https://doi. org/10.1503/cmaj.140809. 16. de Almeida HL Jr, Siqueira RN, Meireles Rda S, Rampon G, de Castro LA, Silva RM. Pitted keratolysis. An Bras Dermatol. 2016;91(1):106–8. https://doi.org/10.1590/ abd1806-4841.20164096. 17. Saguil A, Kane SF, Lauters R, Mercado MG. Hand-foot-and- mouth disease: rapid evidence review. Am Fam Physician. 2019;100(7):408–14. 18. Guerra AM, Orille E, Waseem M. Hand foot and mouth disease. [Updated 2021 Sep 20]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Available from: https://www.ncbi. nlm.nih.gov/books/NBK431082/ 19. Nair PA, Patel BC. Herpes zoster. [Updated 2021 Sep 9]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK441824/ 20. Shingrix – an adjuvanted, recombinant herpes zoster vaccine. Med Lett Drugs Ther. 2017:59:195. 21. Trčko K, Hošnjak L, Kušar B, et al. Clinical, histopathological, and virological evaluation of 203 patients with a clinical diagnosis of molluscum contagiosum. Open Forum Infect Dis. 2018;5(11):ofy298. https://doi.org/10.1093/ofid/ofy298. 22. Laxmisha C, Thappa DM, Jaisankar TJ. Clinical profile of molluscum contagiosum in children versus adults. Dermatol Online J. 2003;9(5):1. 23. Niraj B, Siegfried E, Weissler A. Molluscum BOTE sign: a predictor of imminent resolution. Pediatrics. 2013;131(5):e1650–3. https://doi.org/10.1542/peds.2012-2933. 24. Vlahovic TC, Khan MT. The human papillomavirus and its role in plantar warts: a comprehensive review of diagnosis and management. Clin Podiatr Med Surg. 2016;33(3):337–53. https://doi. org/10.1016/j.cpm.2016.02.003. 25. Witchey DJ, Witchey NB, Roth-Kauffman MM, Kauffman MK. Plantar warts: epidemiology, pathophysiology, and clinical management. J Am Osteopath Assoc. 2018;118(2):92–105. https:// doi.org/10.7556/jaoa.2018.024. 26. Akhoundi M, Sereno D, Durand R, et al. Bed bugs (Hemiptera, Cimicidae): overview of classification, evolution and dispersion. Int J Environ Res Public Health. 2020;17(12):4576. https://doi. org/10.3390/ijerph17124576. 27. Peres G, Yugar LBT, Haddad Junior V. Breakfast, lunch, and dinner sign: a hallmark of flea and bedbug bites. An Bras Dermatol. 2018;93(5):759–60. https://doi.org/10.1590/ abd1806-4841.20187384. 28 28. Iannino F, Sulli N, Maitino A, Pascucci I, Pampiglione G, Salucci S. Fleas of dog and cat: species, biology and flea-borne diseases. Vet Ital. 2017;53(4):277–88. https://doi.org/10.12834/VetIt.109.303.3. 29. Lee SE, Johnstone IP, Lee RP, Opdebeeck JP. Putative salivary allergens of the cat flea, Ctenocephalides felis felis. Vet Immunol Immunopathol. 1999;69:229–37. 30. Chandler DJ, Fuller LC. A review of scabies: an infestation more than skin deep. Dermatology. 2019;235(2):79–90. https://doi. org/10.1159/000495290. 3 Infections and Infestations of the Lower Extremity 31. Sunderkötter C, Wohlrab J, Hamm H. Scabies: epidemiology, diagnosis, and treatment. Dtsch Arztebl Int. 2021;118(41):695–704. https://doi.org/10.3238/arztebl.m2021.0296. 32. Med Lett Drugs Ther. 2021;63(1624):73–5. 33. Eisen L. Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks. Ticks Tick Borne Dis. 2018 Mar;9(3):535–42. AL Grawany 4 Xerotic and Hyperkeratotic Disorders of the Lower Extremity Skin barrier function is dependent on the integrity of the stratum corneum. Xerotic and hyperkeratotic disorders are the result of barrier dysfunction. Hydration and free fatty acids contribute to skin integrity. Increased transepidermal water loss causes dehydration of the stratum corneum. Loss of free fatty acids accompanies the aging process and is accentuated by frequent bathing and harsh detergents. Decreased free fatty acids and dehydration lead to cell contracture. Corneocytes curl upwards creating the clinical appearance of scale. 4.1Xerosis Xerotic or dry skin may be classified as mild, moderate, or severe in presentation [1]. On the foot, xerosis can be present within the skin lines of the plantar surface or may be localized to scaling patches such as those seen in moccasin tinea pedis. The condition most commonly occurs in the aging population. Xerosis may be induced by environmental factors such as low humidity and may accompany medical conditions such as thyroid disease, diabetes, and kidney failure. Pruritus is frequently an associated finding. Emollients and keratolytics are the mainstays of therapy (Figs. 4.1 and 4.2). 4.2Corns and Calluses Corns and calluses (also referred to as clavi, heloma, tyloma, and keratoma) are hyperkeratotic lesions that arise in areas of mechanical stress [2]. Corns refer to lesions on the dorsum of the foot, whereas calluses describe plantar foot lesions. Intractable plantar keratosis (IPK) refers to a focal hyperkeratotic plantar lesion that is a conical thickening of the stratum corneum. The cone points deep into the foot. Both mechanical trauma and genetic predisposition may play roles in causality [3]. Fig. 4.1 Mild xerosis with scale visible within skin lines Treatment of dorsal and hyperkeratotic lesions of the foot includes sharp debridement, padding of the area to reduce pressure, insole/orthotic devices, appropriate fitting shoe gear, keratolytic topical agents, and surgical correction of any underlying bony deformity contributing to the corn/callus formation [3] (Fig. 4.3). © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_4 29 30 4 Xerotic and Hyperkeratotic Disorders of the Lower Extremity Fig. 4.2 Severe plantar xerosis Fig. 4.4 Asteatotic eczema on the medial aspect of the leg eczema craquelé due to a similar appearance to the fine lines seen in porcelain [4] and winter itch due to its increased severity in the winter months. Asteatotic eczema commonly presents on the anterior aspect of the leg as pruritic, annular, scaling patches that can resemble tinea infection. It may also appear as fissures mimicking a dry riverbed. Treatment consists of decreasing bathing frequency and application of moisturizing emollients after bathing. More severe cases may warrant topical corticosteroid steroid therapy (Fig. 4.4). 4.4Keratoderma Climactericum (Haxthausen’s Disease) Fig. 4.3 Punctate keratoses on the plantar foot 4.3Asteatotic Eczema (Erythema Craquele) Asteatotic or xerotic eczema is a common form of dry skin encountered on the lower extremities. It is also termed Keratoderma climactericum presents as cracking and fissuring of the plantar heel which may progress distally along the sides of the foot. Post-menopausal females may also develop cracking and fissuring of the heels plantarly [5]. The palms of the hands may also be involved. The condition has a strong correlation to obesity. Patients will often complain of pain with ambulation especially in the presence of heel fissures. Treatment consists of application of a keratolytic and an emollient to decrease the thickness of the skin and improve the epidermal skin barrier (Fig. 4.5). AL Grawany 4.6 Palmoplantar Keratoderma 31 Fig. 4.5 Keratoderma climactericum of the heel 4.5Ichthyosis Ichthyosis is a group of cutaneous disorders characterized by skin that is dry, thickened, and scaly. The condition may be either hereditary or acquired. The most common form is ichthyosis vulgaris which is an autosomal dominant inherited disorder that is estimated to affect 1 in 250 individuals [6]. The disorder typically presents early in childhood and tends to improve with age. It is often seen in association with atopic dermatitis. The classic fish-skin stigmata of ichthyosis vulgaris is the result of dysregulated keratinization in the skin. This abnormal keratinization is associated with mutations in over 50 genes that encode for proteins and enzymes involved in multiple cellular functions including skin barrier homeostasis [7]. Epidermal hyperplasia results in the formation of excess stratum corneum and the characteristic scaly skin. Individuals with ichthyosis have diminished or absent profilaggrin which is synthesized in the granular layer of the epidermis and is a major component of keratohyalin granules [8]. Diagnosis of ichthyosis vulgaris is based on the physical findings and family history. The disorder is chronic and often requires continuous therapy. Topical alpha-hydroxy acids, such as ammonium lactate, are a mainstay of treatment. These agents work by decreasing corneocyte adhesion in the outer stratum corneum. Acquired ichthyosis is rare, usually appears in adulthood, and may be a marker of systemic disease including malignancy [9] (Fig. 4.6). Fig. 4.6 Ichthyosis of the leg 4.6Palmoplantar Keratoderma Palmoplantar keratoderma (PPK) is defined as a persistent thickening of the epidermis of palms and soles and includes genetic and acquired types [10]. Hereditary PPKs are rare and may be inherited either as an autosomal dominant or autosomal recessive manner. Inherited PPKs are caused by mutations that result in abnormalities of keratin. Some forms may be associated with dental abnormalities and hearing loss. Diagnosis of the various hereditary PPKs is based on personal and family history, histopathological findings, and genetic testing to identify subtypes. PPKs are subdivided into diffuse, focal, striate (palms), and punctate forms. Diffuse PPKs, which are the most common, involve the entire palm or sole with or without a strict demarcation. Focal PPKs are associated with painful calluses that often involve the heels, whereas punctate PPKs have small punctate keratosis that can be pitted or project extra-dermally. Acquired palmoplantar keratodermas may be focal or diffuse in nature and may be associated with internal disease, medications, and malignancy. Findings associated with underlying conditions merit additional workup. 32 4 Xerotic and Hyperkeratotic Disorders of the Lower Extremity Fig. 4.7 Diffuse plantar keratoderma Topical treatment with keratolytics such as urea, salicylic acid, and lactic acid, along with debridement, may provide relief. Some cases improve with oral retinoids (Fig. 4.7). 4.7Porokeratosis Porokeratoses are disorders of keratinization that have a defining histologic feature, the cornoid lamellae. This is defined as columns of parakeratosis (retention of nuclei in keratinocytes within the stratum corneum) “resting on a depression where the granular layer is reduced or absent” [10]. There are several types of porokeratoses: porokeratosis of Mibelli, disseminated superficial porokeratosis, porokeratosis palmaris et plantaris disseminata, and the linear and punctate types [11]. Squamous cell carcinomas may uncommonly develop within porokeratosis and lesions should be monitored periodically for change [12]. Porokeratosis plantar discreta is a separate entity that has similar clinical features to porokeratosis of Mibelli [13, 14] but differs from a true porokeratosis histologically [15]. These focal and isolated lesions are more aptly referred to as plantar keratosis or punctate keratosis. A more appropriate term to describe a focal and isolated plantar keratotic lesion is plantar keratosis or punctate keratosis (Fig. 4.8). 4.8Topical Therapies for Xerotic Conditions Topical dermatologic agents are utilized to decrease scale and transepidermal water loss enhancing the epidermal skin barrier. Keratolytics Urea, salicylic acid, and lactic acid creams and lotions help remove excessive scale and soften keratin. They Fig. 4.8 Disseminated superficial actinic porokeratosis of the leg may enhance the penetration of topical steroids when used in combination. Urea is used for debridement and normalization of hyperkeratotic surface lesions associated with xerosis and ichthyosis. Urea gently dissolves the intracellular matrix, loosens the horny layer of skin, and sheds scaly skin at regular intervals, softening hyperkeratotic areas. Salicylic acid is an exfoliant and lactic acid is most appropriate for mild to moderate xerosis. Moisturizers Over-the-counter emollients can be used to restore the function of the epidermal barrier, decrease transepidermal water loss (TEWL), and soothe the skin. Products are best applied within a few minutes of toweling off after bathing. Emollients, when combined with topical steroids may prolong remission and reduce flares. References 1. Baalham P, Birch I, Young M, Beale C. Xerosis of the feet: a comparative study on the effectiveness of two moisturizers. Br J Community Nurs. 2011;16(12):591–2, 594–7. https://doi. org/10.12968/bjcn.2011.16.12.591. 2. Mukhopadhyay AK. Foot that hurts: a brief note on the history of corns and calluses. Indian J Dermatol Venereol Leprol. 2021;87:885–9. 3. Mercier MP, Blanchette V, Cantin V, Brousseau-Foley M. Effectiveness of saline water and lidocaine injection treatment of intractable plantar keratoma: a randomised feasibility AL Grawany References 4. 5. 6. 7. 8. study. J Foot Ankle Res. 2021;14(1):30. https://doi.org/10.1186/ s13047-021-00467-7. Specht S, Persaud Y. Asteatotic Eczema. [2021 Jul 26]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Deschamps P, Leroy D, Pedailles S, Mandard JC. Keratoderma climactericum (Haxthausen’s disease): clinical signs, laboratory findings and etretinate treatment in 10 patients. Dermatologica. 1986;172(5):258–62. https://doi.org/10.1159/000249351. Rare diseases database: ichthyosis vulgaris. National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/ ichthyosis-vulgaris. Oji V, Tadini G, Akiyama M, Blanchet Bardon C, et al. Revised nomenclature and classification of inherited ichthyoses: results of the first ichthyosis consensus conference in Sorèze 2009. J Am Acad Dermatol. 2010;63(4):607–41. Vahlquist A, Fischer J, Törmä H. Inherited nonsyndromic ichthyoses: an update on pathophysiology, diagnosis and treatment. Am J Clin Dermatol. 2018;19(1):51–66. 33 9. Patel N, Spencer LA, English JC 3rd, Zirwas MJ. Acquired ichthyosis. J Am Acad Dermatol. 2006;55(4):647–56. https://doi. org/10.1016/j.jaad.2006.04.047. 10. Guerra L, Castori M, Didona B, Castiglia D, Zambruno G. Hereditary palmoplantar keratodermas. Part I. non-syndromic palmoplantar keratodermas: classification, clinical and genetic features. J Eur Acad Dermatol Venereol. 2018;32(5):704–19. 11. Porokeratosis. Medscape. https://emedicine.medscape.com/ article/1059123-overview. 12. Kanitakis J. Porokeratoses: an update of clinical, aetiopathogenic and therapeutic features. Eur J Dermatol. 2014;24(5):533–44. 13. Taub J, Steinberg MD. Porokeratosis plantaris discreta, a previously unrecognized dermatopathological entity. Int J Dermatol. 1970;9(2):83–90. 14. Lemont H. What’s your diagnosis? Porokeratosis plantaris discreta (Steinberg’s lesion). J Am Podiatr Med Assoc. 2008;98(4):337–8. 15. Yanklowitz B, Harkless L. Porokeratosis plantaris discreta. A misnomer. J Am Podiatr Med Assoc. 1990;80(7):381–4. 5 Papulosquamous Disorders of the Lower Extremity Papulosquamous eruptions are a heterogeneous group of disorders characterized by papules, patches, or plaques associated with varying degrees of scaling. Lesions are usually marginated and, in acute stages, manifest erythema which at the extreme is bright red in appearance. Scale is a manifestation of thickened stratum corneum and papules and plaques result from acanthosis (thickening of the epidermis) or underlying dermal infiltration [1]. Papulosquamoid eruptions that are commonly encountered on the lower extremity include psoriasis, lichen planus, and lichen striatus. Some skin conditions, such as tinea corporis and mycosis fungoides, may be papulosquamoid in appearance. 5.1Psoriasis Psoriasis is a chronic immune-mediated inflammatory disorder that afflicts 3% of the US population [2]. Although skin lesions are the most prominent feature of psoriasis, the condition is a complex, multisystem disease associated with joint involvement, cardiovascular comorbidities, and decreased quality of life [3]. Individuals with psoriasis have an enhanced incidence of anxiety and depression. Up to 90% of patients with psoriasis have the plaque subtype which is characterized by sharply demarcated plaques with an adherent scale. Nails may manifest pitting, onycholysis, and oil-drop discoloration. Psoriatic arthritis is a spondyloarthropathy that often presents as an asymmetrical oligoarthritis which over time can result in significant joint destruction. Associated findings include enthesitis and dactylitis. Guttate, inverse, pustular, and erythrodermic psoriasis are less frequently encountered variants. Guttate psoriasis manifests as small, scattered, erythematous, well-defined scaly lesions predominantly on the trunk. The condition may arise in children or adolescents following a streptococcal infection. Inverse psoriasis appears in the flexural creases on areas such as the groin, axillae, and under the breasts. This form presents as shiny, red, well-demarcated patches without scale. Multiple sterile pustules are the hallmark of pustular psoriasis, which can be generalized or localized to the hands and soles of the feet (palmoplantar psoriasis). Erythrodermic psoriasis is characterized by widespread inflammation and exfoliation, often over a large body surface area. When extensive, this disorder requires prompt diagnosis and treatment to prevent hospitalization. Topical corticosteroids are first line treatment for mild to moderate psoriasis and are available in a variety of strengths and formulations including creams, ointments, gels, solutions, and foams [4]. Topical corticosteroids have anti- inflammatory and vasoconstrictive properties. Vitamin D analogues and vitamin A derivatives are also used topically to treat psoriasis. Salicylic acid and coal tar formulations are available over the counter but lack the efficacy of prescription topical agents. Acitretin, cyclosporine, and methotrexate are oral systemic medications used to treat moderate to severe psoriasis. All require some degree of laboratory monitoring and efficacy is variable [5]. Acitretin is teratogenic and can raise serum triglyceride levels. Cyclosporine, especially if continued long-term, can impair renal function. Methotrexate also is teratogenic and may induce leukopenia, pulmonary fibrosis, elevation of liver enzymes, and, on rare occasions, cirrhosis. Apremilast, a phosphodiesterase inhibitor, is the most recently approved oral agent for the management of psoriasis and psoriatic arthritis. Laboratory monitoring is not required, but gastrointestinal side effects such as nausea and diarrhea may be encountered. The introduction of biologic therapies has revolutionized the treatment of psoriasis [6]. Tumor necrosis factor-alpha (TNF-α) and interleukin (IL) inhibitors are biologic agents that selectively inhibit cytokines involved in the pathogenesis of this disorder. The majority are administered subcutaneously, and dosing schedules range from weekly to quarterly depending on the agent. Tuberculosis testing is required and all of the agents carry warnings of increased risk for infection (Figs. 5.1, 5.2, 5.3, 5.4, and 5.5). © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_5 AL Grawany 35 36 5 Papulosquamous Disorders of the Lower Extremity Fig. 5.3 Palmoplantar pustular psoriasis is a chronic pustular dermatitis that affects the palms and soles Fig. 5.1 Silvery, adherent scales are the hallmark of psoriasis Fig. 5.4 Guttate psoriasis often has a sudden onset and manifests as scaling, erythematous papules, and patches 5.2Lichen Planus Fig. 5.2 Knees, elbows, and scalp are the most common locations involved with plaque psoriasis Lichen planus is a chronic inflammatory autoimmune disorder believed to be mediated by cytotoxic CD8+ T-cells [7]. The condition can affect the skin, nails, and oral mucosa. Classic skin findings are flat-topped, polygonal, erythema- 5.3 Lichen Striatus 37 Fig. 5.5 Onycholysis, discoloration, subungual debris, and pitting are all associated with nail psoriasis tous to violaceous papules. The wrists and ankles are the most common sites of involvement and affected individuals experience itching of variable intensity. Hypertrophic lichen planus is a variant characterized by hyperpigmented plaques. This form is most prevalent in blacks and invariably involves the lower legs. Mucosal lichen planus often presents as a white lacey pattern termed Wickham striae. Ulcerations are the hallmark of erosive oral lichen planus. Disease of the nails may manifest with thinning of the nail plate, splitting, and pterygium formation. Most cases of lichen planus are idiopathic although some are induced by medications and possibly by hepatitis C viral infection [8]. Skin lesions typically clear spontaneously within a 2 year period. First line therapies include potent topical steroids and, for more severe cases, oral or intramuscular steroids. Hypertrophic lichen planus may respond to intralesional steroids although post-inflammatory hyperpigmentation is a common sequela (Figs. 5.6 and 5.7). Fig. 5.6 Lichen planus is a papulosquamous eruption that presents with flat-topped violaceous papules affecting primarily the wrists and ankles 5.3Lichen Striatus Lichen striatus is a unilateral, self-limited eruption that follows the so-called lines of Blaschko [9]. The etiology is unknown but a significant percentage of affected individuals relate a family history of atopic dermatitis. The condition most commonly occurs in preteen and adolescent females and may involve either the trunk or extremities. The onset is heralded by the appearance of red to flesh-colored papules with scale that rapidly extend in a band-like pattern. Nail involvement has been reported but is rare [10]. In most individuals lichen striatus is asymptomatic and of cosmetic concern only; however, some experience intense pruritus. The eruption spontaneously involutes within 1 to 3 years. Potent topical steroids and tacrolimus may relieve the pruritus and hasten resolution (Fig. 5.8). Fig. 5.7 Hypertrophic lichen planus evolves into thickened plaques and is most common on the legs AL Grawany 38 5 Papulosquamous Disorders of the Lower Extremity 3. Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: implications for management. J Am Acad Dermatol. 2017;76(3):393–403. https://doi.org/10.1016/j.jaad.2016.07.065. 4. Elmets CA, Korman NJ, Prater EF, Wong EB, Rupani RN, Kivelevitch D, Armstrong AW, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. J Am Acad Dermatol. 2021;84(2):432–70. https://doi. org/10.1016/j.jaad.2020.07.087. 5. Menter A, Gelfand JM, Connor C, Armstrong AW, Cordoro KM, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. J Am Acad Dermatol. 2020 Jun;82(6):1445–86. https://doi.org/10.1016/j.jaad.2020.02.044. 6. Kamata M, Tada Y. Efficacy and safety of biologics for psoriasis and psoriatic arthritis and their impact on comorbidities: a literature review. Int J Mol Sci. 2020;21(5):1690. https://doi.org/10.3390/ ijms21051690. 7. Boch K, Langan EA, Kridin K, Zillikens D, Ludwig RJ, Bieber K. Lichen planus. Front Med (Lausanne). 2021;8:737813. https:// doi.org/10.3389/fmed.2021.737813. 8. Arnold DL, Krishnamurthy K. Lichen planus. [Updated 2021 Sep 13]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK526126/. 9. Keegan BR, Kamino H, Fangman W, Shin HT, Orlow SJ, Schaffer JV. “Pediatric blaschkitis”: expanding the spectrum of childhood acquired Blaschko-linear dermatoses. Pediatr Dermatol. 2007;24(6):621–7. 10. Iorizzo M, Rubin AI, Starace M. Nail lichen striatus: is dermoscopy useful for the diagnosis? Pediatr Dermatol. 2019;36(6):859–63. https://doi.org/10.1111/pde.13916. Fig. 5.8 Lichen striatus presents as elevated papules in bands that follow the lines of Blaschko References 1. Fox BJ, Odom RB. Papulosquamous diseases: a review. J Am Acad Dermatol. 1985;12(4):597–624. https://doi.org/10.1016/ s0190-9622(85)70084-9. 2. Armstrong AW, Mehta MD, Schupp CW, Gondo GC, Bell SJ, Griffiths CEM. Psoriasis prevalence in adults in the United States. JAMA Dermatol. 2021;157(8):940–6. https://doi.org/10.1001/ jamadermatol.2021.2007. 6 Contact, Irritant, Atopic, and Stasis Dermatitis of the Lower Extremity “Dermatitis” often serves as a catchall phrase for “a rash.” Associated findings usually include itching, redness, and, on biopsy, an inflammatory cell infiltrate [1]. Depending on external cause or underlying disease, dermatitis may be either localized or diffuse in nature. History and examination play a huge role in determining etiology and treatment plan. Four of the most common causes of dermatitis are contact, irritant, atopic, and stasis dermatitis. 6.1Contact and Irritant Dermatitis Contact dermatitis is a delayed hypersensitivity reaction caused by an allergy to an external substance that contacts the skin [2]. This allergic disorder needs to be differentiated from an irritant dermatitis in which the inciting agent causes physical damage to the epidermis. For example, rubbing an abrasive cleanser against the skin will induce an irritant dermatitis. Common causes of contact dermatitis include poison ivy, nickel, fragrances, and topical antibiotics. Acute reactions manifest erythema and itch. When severe, the reaction triggers vesicles and bullae. The cause is often apparent based on history and clinical appearance although at times patch testing is required to pinpoint the inciting chemicals. Skin rashes often encountered by podiatrists include shoe dermatitis and adhesive reactions [3]. Shoe dermatitis may result from mechanical irritation and/or a hypersensitivity reaction. Potential allergens include rubber derivatives, leather, dyes, and metals. Moisture aids in leaching chemicals and the combination of heat, pressure, and friction can result in a concomitant irritant reaction. Common involved sites are the dorsum of the great toes and sides of the feet. Reactions induced by bandages are most likely to be irritant in nature as opposed to allergic although both may coexist when the dressing occludes a topical antibiotic [4]. Fig. 6.1 Irritant dermatitis secondary to chaffing Treatment of an irritant reaction entails protecting the skin from further trauma. Management of allergic reactions requires avoidance of the sensitizing agent. Severe allergic dermatitis merits therapy with topical, and at times, systemic corticosteroids (Figs. 6.1, 6.2, and 6.3). © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_6 AL Grawany 39 40 6 Contact, Irritant, Atopic, and Stasis Dermatitis of the Lower Extremity Fig. 6.2 Poison ivy contains urushiol, a potent sensitizer Fig. 6.4 Eczema is an intensely itchy inflammatory disorder Fig. 6.3 Contact dermatitis to bacitracin (Courtesy of Lawrence Schiffman, DO) 6.2Atopic Dermatitis Atopic dermatitis, commonly referred to as eczema, is an inflammatory condition that afflicts a high percentage of children and often persists into adulthood [5]. The disorder is the product of immune dysregulation in conjunction with an impaired skin barrier functionality [6]. Abnormal filaggrin proteins and defective ceramide production play a substantial role as does the release of pro-inflammatory cytokines including interleukin (IL)-4, IL-13, and IL-31. Hallmarks of the disease include pruritus, xerosis, and erythema. More severe cases may manifest thickened skin (lichenification), oozing, crusting, and excoriations. In children, atopic dermatitis may be widespread with the legs frequently involved [7]. With increasing age eczema tends to be more localized commonly involving the popliteal flexures, lower legs, and feet. Coin-like patches are referred to as nummular eczema. The intensity of pruritus correlates with severity of the disease [8]. Scratching results in mechanical damage to the skin triggering an inflammatory response that heightens itching and leads to new lesions. Eczema has been referred to as the “itch that rashes,” this is the consequence of a self- perpetuating “itch-scratch” cycle [9]. Itch is aggravated by extremes of temperature, wool clothing, and stress. Management of atopic dermatitis is accomplished by improving barrier function and reducing inflammation. Adequate moisturization helps to maintain skin integrity and prevent flare of disease. Topical corticosteroids are considered first line treatment for atopic dermatitis [10]. Additional prescription topical agents include calcineurin inhibitors (tacrolimus and pimecrolimus), crisaborole, a phosphodiesterase inhibitor, and ruxolitinib, a JAK inhibitor. Some cases improve with sunlight or ultraviolet light therapy. Refractory disease may require systemic therapy with immunosuppressants such as glucocorticosteroids and cyclosporine. The targeted biologic dupilumab (an IL-4 and IL-13 inhibitor) provides a revolutionary approach to the management of moderate to severe atopic dermatitis as does the recently approved oral JAK inhibitors abrocitinib and upadacitinib (Figs. 6.4, 6.5, and 6.6). 6.3Stasis Dermatitis Stasis dermatitis affects the lower legs and is a consequence of venous hypertension and insufficiency resulting from retrograde blood flow secondary to incompetent or damaged valves [11]. Prevalence increases with advancing age and 6.3 Stasis Dermatitis 41 discolorations. Chronic cases are frequently accompanied by superficial ulcerations and at times by lipodermatosclerosis [12]. Cellulitis and allergic contact dermatitis may coexist with stasis dermatitis or contribute to misdiagnosis [13]. Leg elevation and compression are mainstays of therapy. Topical steroids are frequently used to manage pruritus and erythema (Figs. 6.7 and 6.8). Fig. 6.7 Stasis dermatitis is bilateral and characterized by edema, erythema, and scale Fig. 6.5 A hallmark of eczema is lichenification Fig. 6.6 Nummular eczema manifests as coin-shaped lesions predisposing factors include varicosities, obesity, sedentary lifestyle, high blood pressure, and congestive heart failure. The medial ankle is most frequently involved with progression to the calves and feet common. Bilateral edema is accompanied by itching, scaling, and erythematous, poorly demarcated patches and plaques. Extravasation of blood vessels leads to hemosiderin deposition and reddish-brown Fig. 6.8 Stasis dermatitis may be accompanied by skin tears and superficial ulcerations AL Grawany 42 6 Contact, Irritant, Atopic, and Stasis Dermatitis of the Lower Extremity References 1. Nedorost ST. Generalized dermatitis in clinical practice. Springer; 2012. p. 1–14. ISBN 9781447128977 2. Usatine RP, Riojas M. Diagnosis and management of contact dermatitis. Am Fam Physician. 2010;82(3):249–55. 3. Adeniran V, Cherian A, Cho JO, Febrian C, Kim ET, Siwy T, Vlahovic TC. Shoe dermatitis. Clin Podiatr Med Surg. 2021;38(4):561–8. https://doi.org/10.1016/j.cpm.2021.06.008. 4. Widman TJ, Oostman H, Storrs FJ. Allergic contact dermatitis from medical adhesive bandages in patients who report having a reaction to medical bandages. Dermatitis. 2008;19(1):32–7. 5. Laughter MR, Maymone MBC, Mashayekhi S, Arents BWM, Karimkhani C, Langan SM, Dellavalle RP, Flohr C. The global burden of atopic dermatitis: lessons from the Global Burden of Disease Study 1990–2017. Br J Dermatol. 2021;184(2):304–9. https://doi. org/10.1111/bjd.19580. 6. David Boothe W, Tarbox JA, Tarbox MB. Atopic dermatitis: pathophysiology. Adv Exp Med Biol. 2017;1027:21–37. https://doi. org/10.1007/978-3-319-64804-0_3. 7. Yew YW, Thyssen JP, Silverberg JI. A systematic review and meta-analysis of the regional and age-related differences in 8. 9. 10. 11. 12. 13. atopic dermatitis clinical characteristics. J Am Acad Dermatol. 2019;80(2):390–401. https://doi.org/10.1016/j.jaad.2018.09.035. Huet F, Faffa MS, Poizeau F, Merhand S, Misery L, Brenaut E. Characteristics of pruritus in relation to self-assessed severity of atopic dermatitis. Acta Derm Venereol. 2019;99(3):279–83. https:// doi.org/10.2340/00015555-3053. Wahlgren CF. Itch and atopic dermatitis: an overview. J Dermatol. 1999;26(11):770–9. https://doi.org/10.1111/j.1346-8138.1999. tb02090.x. Frazier W, Bhardwaj N. Atopic dermatitis: diagnosis and treatment. Am Fam Physician. 2020;101(10):590–8. Sundaresan S, Migden MR, Silapunt S. Stasis dermatitis: pathophysiology, evaluation, and management. Am J Clin Dermatol. 2017;18(3):383–90. https://doi.org/10.1007/s40257-016-0250-0. Patel SK, Surowiec SM. Venous insufficiency. [Updated 2021 Dec 26]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK430975/ Weng QY, Raff AB, Cohen JM, et al. Costs and consequences associated with misdiagnosed lower extremity cellulitis. JAMA Dermatol. 2017;153(2):141–6. https://doi.org/10.1001/ jamadermatol.2016.3816. 7 Concerns of the Lower Extremity in Skin of Color The term “skin of color” describes patients with pigmented skin: African American, Hispanic, Asian (East, Southeast, and South), and non-white ethnic groups such as First Nations/American Indian/Alaskan Native/Native Hawaiian. The U.S. Census has projected that half of the population will be composed of people with skin of color by 2050 [1]. It is important first to recognize the structural and biological differences between black and white skin. Skin color is determined by the distribution of melanin, and there is no difference in the number of melanocytes among groups. The melanocytes, which reside in the basal layer of the epidermis, contain melanosomes filled with tyrosinase that is involved in melanin synthesis. The amount of tyrosinase is generally equal in black and white skin however, the distribution of melanosomes within melanocytes and keratinocytes is different. Besides the distribution of melanosomes contributing to skin color, tyrosinase levels are ten times higher in black skin and produce ten times more melanin than melanocytes in white skin [2]. Injury and inflammation may stimulate melanocytes resulting in untoward pigmentation in persons of color [3]. Epidermal thickness is equivalent in black and white skin, but there are more epidermal lipids in black skin [4]. Transepidermal water loss is lower in black skin, showing statistical significance on the legs in Warrier et al.’s study [4]. Fibroblasts in the dermis of black skin are larger and more numerous and active, factors that may explain the prevalence of keloids and hypertrophic scars in this patient population [5]. 7.1Pigmentation Disorders and Inflammatory Conditions 7.1.1Erythema Recognizing erythema in darker skin types can pose a diagnostic challenge. The fiery red color associated with cellulitis or the erythema accompanying psoriasis and other inflammatory disorders often appears more muted and even violaceous in skin of color patients. A comprehensive skin examination including comparison of a contralateral limb may prove useful in the identification of erythema in darker complected individuals (Figs. 7.1 and 7.2). 7.1.2Post-inflammatory Hyperpigmentation When exposed to inflammation or an injury, melanocytes in individuals with darker skin respond in an exaggerated manner. The emotional and psychological impact of the dyschromia can have a negative impact on the quality of life for the patient [3]. Dyschromia following an inflammatory condition such as acne, eczema, and psoriasis is known as postinflammatory hyperpigmentation (PIH) and results from either an increase in melanin production or uneven distribution of melanin. This excess pigment can reside in the epidermis, dermis, or both [3]. Hyperpigmentation after an injury might result from an influence of inflammatory mediators and reactive oxygen species [3]. The resulting pigmentation may take years to resolve. Treatment of any underlying inflammatory condition is necessary to prevent further pigmentation. Once resolved, PIH may respond to topical hydroquinone. This compound is not a true “bleaching” agent, but rather a tyrosinase blocker that inhibits production of melanin. Long-term hydroquinone use may induce exogenous ochronosis characterized by blue–black macules. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_7 AL Grawany 43 44 Fig. 7.1 Erythema and mild edema at medial hallux nail fold of the left foot 7 Concerns of the Lower Extremity in Skin of Color Fig. 7.2 Non-affected right foot of same patient Other topical products used to treat PIH are topical steroids, tretinoin, licorice extract, niacinamide, and kojic acid. Cosmetic treatments such as chemical peels, microdermabrasion, and laser produce variable results and risk worsening the condition (Figs. 7.3 and 7.4). 7.1.3Post-inflammatory Hypopigmentation Post-inflammatory hypopigmentation, or excessive depigmentation, can result from an inflammatory condition or from a therapeutic intervention, such as long-term topical steroid use. Loss of melanin may be either localized or widespread [6]. The presence of a feathered edge may assist in differentiation from vitiligo. Treatment or removal of the underlying cause may hasten resolution. One form of hypopigmentation frequently encountered by podiatric practitioners is idiopathic guttate hypomelanosis. This condition manifests as discrete hypopigmented macules on the anterior aspect of the legs and is most prominent in darker skinned individuals. The cause is unknown although some cases have been linked to sun exposure. Multiple modalities have been used to treat this disorder including cryotherapy, topical retinoids, and lasers (Fig. 7.5). Fig. 7.3 Dyschromia of the lower leg 7.1.4Vitiligo Vitiligo is a common skin disorder that affects up to 2% of the world population [7, 8]. The condition has an equal prevalence in males and females and almost half of the patients develop the condition before age 20. Vitiligo manifests as well-demarcated depigmented macules. Based on distribution, vitiligo may be classified into three subtypes: generalized, segmental, and localized [9]. The condition is most 7.1 Pigmentation Disorders and Inflammatory Conditions 45 Fig. 7.4 Post-inflammatory hyperpigmentation at the dorsum of the toes Fig. 7.6 Vitiligo of both anterior tibia Sunscreen use is key to preventing further damage to the keratinocytes in the amelanotic patches. Corrective cosmetics can be used as camouflage (Fig. 7.6). 7.1.5Melanonychia Fig. 7.5 Idiopathic guttate hypomelanosis apparent in darker skinned individuals and may negatively impact quality of life. Vitiligo is an autoimmune disease believed to be caused by cytotoxic CD8+ T-cells that suppress melanocytes [10]. Prognosis depends to some degree on age of onset and extent of disease. Therapeutic options include ultraviolet light as well as topical steroids and calcineurin inhibitors although pigmentation is often difficult to achieve and maintain. PUVA phototherapy (psoralen plus UVA light) and narrowband UVB have also been used with some success to repigment, but have limited success in the lower extremity. PUVA works by restimulating the melanocytes still present in the lower portion of the hair follicle to migrate and repigment surrounding skin [11]. Recently JAK inhibitors have demonstrated efficacy and offer a promising therapeutic option [12]. Longitudinal melanonychia describes the linear pigmented brown to black streak seen in the toe and fingernails. Melanonychia seen in patients with skin of color results from activation of melanocytes in the nail matrix and extend to the tip of the nail plate [13]. The condition may appear as a single line or encompass the entire nail plate and is a common occurrence in the African American population with 100% of the nails being affected by the age of 50 [13]. In the Japanese population nail pigmentation can be seen in 10–20% of adults [13]. It is important to distinguish melanonychia commonly seen in patients with skin of color from pigmentation due to other causes including melanoma, hematoma, drugs, fungus, and friction from shoes. Drugs such as antiretrovirals, antimalarials, metals, and psoralen (used in PUVA therapy) may cause darkening of one or more nails. Pigmentation may fade once the offending agent is discontinued. Trichophyton rubrum and many molds may generate melanin-like compounds that pigment the nails. Friction from shoe gear may cause the melanocytes in the nail matrix of the fourth and AL Grawany 46 fifth digits to become activated and result in “frictional” brown-colored longitudinal melanonychia [13]. When determining the etiology of pigmented streaks examine all nails. Streaks on multiple nails favor a diagnosis of longitudinal melanonychia. Guidelines favoring diagnosis of subungual melanoma have been proposed by Levit et al. (Fig. 7.7) [14]: A is for age with the peak during the fifth to seventh decades of life and African-Americans, Asians, and native Americans accounting for one-third of all melanoma cases. B is for breadth of 3 mm or more and variegated borders at the edge of the streak. C is for change in the nail band or lack of change in the nail plate with standard of care treatments. D is for the digit most involved which is the (1) index finger, (2) hallux, and (3) thumb. E is for extension of the pigmentation into the proximal and/ or lateral nail fold (known as Hutchinson’s sign). F is for family or personal history of melanoma. Fig. 7.7 Longitudinal melanonychia 7 Concerns of the Lower Extremity in Skin of Color 7.2Scars Keloids, or scars that extend beyond the original area of injury or trauma, occur more often in the African American and Asian patients than Caucasian with a ratio range of 5:1 to 16:1 [15]. Keloids present a therapeutic challenge to the clinician due to their non-responsiveness to treatments and a psychological challenge to the patient from a cosmetic and at times, painful viewpoint. Hypertrophic scars, unlike keloids, stay within the boundaries of the original trauma and may regress in a few years. Both types of abnormal scar healing are poorly understood as to why they occur and how to prevent them. When choosing a treatment for a keloid or hypertrophic scar, both the clinician and patient must have realistic expectations. The goal is to flatten, depigment, and/or soften the scar because the goal of having no visible scar is unrealistic. Intralesional injection of triamcinolone 10 mg/mL both deep into the dermis and at the area of the dermo-epidermal junction is often a first line treatment. It is helpful to either locally block the area or use a topical anesthetic agent to achieve that deep injection. Laser therapy has been shown, in conjunction with intralesional steroid injection, to be useful in treating keloids [16]. It is important to take caution with the laser’s fluence (J/cm2) and pulse width in Fitzpatrick skin types IV–VI to not burn the skin or cause further pigmentation changes. In addition to the modalities described, topical treatments for keloids include topical corticosteroids, imiquimod, and silicone gel sheeting. If the topical methods fail, surgical excision is an option, but has a high recurrence rate (Fig. 7.8) [15]. Fig. 7.8 Keloids after hammertoe surgery References References 1. Nijhawan RI, Alexis AF Practical approaches to medical and cosmetic dermatology in skin of color patients. Expert Rev Dermatol. 2011. http://www.medscape.org/viewarticle/739758. 2. Iozumi K, Hoganson GE, Pennella R, et al. Role of tyrosinase as the determinant of pigmentation in cultured human melanocytes. J Investigat Dermatol. 1993;100:806–11. 3. Grimes PE. Management of hyperpigmentation in darker racial ethnic groups. Semin Cutan Med Surg. 2009;28:77–85. 4. Warrier AG, Kligman AM, Harper RA, et al. A comparison of black and white skin using noninvasive methods. J Soc Cosmet Chem. 1996;47:229–40. 5. Montagna W, Carlisle K. The architecture of black and white facial skin. JAAD. 1991;24(6):929–37. 6. Ruiz-Maldonado R, de la Luz Orozco-Covarrubias M. Postinflammatory hypopigmentation and hyperpigmentation. Semi Cutan Med Surg. 1997;16(1):36–43. 7. Bergqvist C, Ezzedine K. Vitiligo: a review. Dermatology. 2020;236(6):571–92. 8. Taïeb A, Picardo M, VETF Members. The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force. Pigment Cell Res. 2007;20(1):27–35. https://doi. org/10.1111/j.1600-0749.2006.00355.x. 47 9. Ahmed jan N, Masood S. Vitiligo. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK559149/. 10. Frisoli ML, Essien K, Harris JE. Vitiligo: mechanisms of pathogenesis and treatment. Annu Rev Immunol. 2020;26(38):621–48. https://doi.org/10.1146/annurev-immunol-100919-023531. 11. Falabella R. Treatment of localized vitiligo by autologous minigrafting. Arch Dermatol. 1988;124:1649–55. 12. Komnitski M, Komnitski A, Komnitski Junior A, Silva de Castro CC. Partial repigmentation of vitiligo with tofacitinib, without exposure to ultraviolet radiation. An Bras Dermatol. 2020;95(4):473–6. https://doi.org/10.1016/j.abd.2019.08.032. 13. Tosti A, Piraccini BM, Cadore de Farias D. Dealing with melanonychia. Semin Cutan Med Surg. 2009;28:49–54. 14. Levit EK, Kagen MH, Scher RK, et al. The ABC rule for clinical detection of subungual melanoma. JAAD. 2000;42(2 Pt 1):269–74. 15. Kelly AP. Update on the management of keloids. Semin Cutan Med Surg. 2009;28:71–6. 16. Connell PG, Harland CC. Treatment of keloid scars with pulsed dye laser and intralesional steroid. J Cutan Laser Ther. 2000;2(3):147–50. AL Grawany 8 Autoimmune Diseases and Vasculopathies of the Lower Extremity Autoimmune diseases affect over 24 million individuals in the USA and the incidence is increasing [1]. More than 80 distinct disorders have been identified and research has contributed greatly to our understanding of underlying pathogenesis. Both genetic and environmental factors play a role in the development of disease. All have in common immune dysregulation, the specifics of which help to define each disease. Vasculopathies are a varied group of conditions marked by inflammation of blood vessels. Although many cases are idiopathic, some are directly linked to antibody–antigen complexes. 8.1Chilblains Chilblains, otherwise known as perniosis, is a benign vasospastic acrally located cutaneous disorder. Chilblains occur after exposure to cold temperatures and dampness and are subdivided into primary and secondary forms. The primary form is idiopathic and is not associated with underlying disease. Secondary forms of pernio accompany underlying connective tissue disorder or other pathologic processes such as cryoglobulinemia and monoclonal gammopathy [2]. Chilblains manifest as painful, red-to-purple edematous papules and patches located on the acral surfaces of the fingers and toes. Symptoms usually begin in early winter and often resolve by spring. Patients may develop recurrences during subsequent winters or cold exposure. Although benign and self-limiting, chilblains can resemble other vascular diseases such as thromboemboli and vasculitis leading to an extensive and unproductive workup [3]. Females with a low body mass index are predominantly affected. Transient vasospasm is believed to play a role in pathogenesis [4]. Chilblains are best prevented by avoidance of cold exposure. Calcium channel blockers such as nifedipine are used to prevent recurrence and help promote faster healing (Fig. 8.1). Fig. 8.1 Chilblains is a vascular reactive disorder triggered by exposure to cold and dampness 8.2COVID Toes COVID toes, also referred to as COVID infection-induced chilblains, is a vascular acro-syndrome associated with the SARS-CoV-2 novel coronavirus (COVID-19). This condition is defined as the presence of acute, self-healing, acro- ischemic lesions distinct from those related to acrocyanosis, perniosis, and Schonlein-Henoch vasculitis in the absence of meningococcal sepsis and protein C deficiency [5]. Lesions present as erythematous to violaceous discolorations, papules, or plaques of the distal foot and less frequently the fingers. Bullae and crusting are uncommon. The majority of cases occur in younger patients and may be the only identifiable symptom of viral infection. The condition is associated with mild disease. Lesions last 10 to 14 days and resolve spontaneously. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_8 49 50 8 Autoimmune Diseases and Vasculopathies of the Lower Extremity Fig. 8.3 Subacute cutaneous lupus presenting with scaling, erythematous patches (Courtesy of Lawrence Schiffman, DO) Fig. 8.2 COVID toes is a self-limited condition associated with coronavirus infection COVID toes are associated with an interferon response to the virus which limits viral replication and triggers a chilblain lupus erythematosus-like response through microangiopathic changes [6]. There is no direct link as to causality [7]. Other cutaneous manifestations associated with COVID are urticarial and erythema multiforme-like eruptions [8] as well as nail changes including Beau’s lines (Fig. 8.2) [9]. 8.3Systemic Lupus Erythematosus Systemic lupus erythematosus is an autoimmune disease that may involve multiple organ systems including the skin, joints, heart, lungs, and kidneys. There are three main subtypes of cutaneous lupus: acute cutaneous lupus, discoid lupus, and subacute cutaneous lupus [10]. Acute lupus is associated with positive antinuclear antibodies (ANA) and a distinct malar or “butterfly” rash. The condition most commonly arises in females of childbearing age. Lupus-related Raynaud’s disease occurs in up to one-third of individuals with lupus. Discoid lupus is characterized by scarring and pigmentary changes. The condition may involve the face, scalp, neck, and arms and is most prevalent in African-Americans. Subacute cutaneous lupus erythematosus is a photosensitive dermatosis that has two morphologic variants, annular, and papulosquamous [11]. The annular form is characterized by scaly, circular erythematous plaques which over time coalesce in a polycyclic pattern. The papulosquamous variant resembles eczema with discrete, erythematous scaling patches. Sun avoidance and protection are of paramount importance in the management of cutaneous lupus. Therapeutic modalities range the gamut from topical steroids to immunosuppressants (Fig. 8.3). 8.4Systemic Sclerosis Systemic sclerosis is divided into two distinct entities: scleroderma and morphea [12]. Scleroderma is a systemic disease characterized by cutaneous sclerosis and internal disease involvement, whereas morphea is usually confined to the skin. A subset of systemic sclerosis is a limited cutaneous form that manifests calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias, referred to as CREST syndrome. The cause of systemic sclerosis is unknown. Vascular anomalies, excess fibrosis, and autoimmune dysregulation are factors involved in disease pathogenesis [13]. Skin lesions are often bilateral and symmetrical and are first noted on the fingers and toes. Digits may take on a sausage-like appearance. Nail fold capillaroscopy shows vascular anomalies and digital ischemia can eventuate in auto-amputation. Systemic findings may include interstitial lung involvement, gastroesophageal reflux disease, heart failure, and renal crisis. Morphea, or localized scleroderma, begins as erythematous and indurated inflammatory lesions that progress to atrophic, bound-down plaques. Several subsets are recognized including circumscribed, linear, generalized, and pansclerotic. All are marked by overproduction of collagen. Early stages of morphea may respond to ultrapotent topical steroids. Scleroderma is a systemic disease that is best managed by multi-specialties (Fig. 8.4). AL Grawany References 51 References Fig. 8.4 Fibrotic, bound-down, hyperpigmented patches and plaques characterize morphea 8.5Vitiligo Vitiligo is a common skin disorder that affects up to 2% of the world population [14, 15]. The condition has an equal prevalence in males and females and almost half of the patients develop the condition before age 20. Vitiligo manifests as well-demarcated depigmented macules. Based on distribution, vitiligo may be classified into three subtypes: generalized, segmental, and localized [16]. The condition is most apparent in darker skinned individuals and may negatively impact quality of life. Vitiligo is an autoimmune disease believed to be caused by cytotoxic CD8+ T-cells that suppress melanocytes [17]. Prognosis depends to some degree on age of onset and extent of disease. Therapeutic options include ultraviolet light as well as topical steroids and calcineurin inhibitors although pigmentation is often difficult to achieve and maintain. Recently JAK inhibitors have demonstrated efficacy and offer a promising therapeutic option (see Fig. 7.6) [18]. 1. National Institute of Environmental Health Sciences. Autoimmune diseases. https://www.niehs.nih.gov/health/topics/conditions/autoimmune/index.cfm. 2. Gordon R, Arikian A, Pakula A. Chilblains in Southern California: two case reports and a review of the literature. J Med Case Rep. 2014;8:381. 3. Prakash S, Weisman M. Idiopathic chilblains. Am J Med. 2009;122(12):1152–5. 4. Shahi V, Wetter DA, Cappel JA, MDP D, Spittell PC. Vasospasm is a consistent finding in pernio (chilblains) and a possible clue to pathogenesis. Dermatology. 2015;231:274–9. 5. Mazzotta F, Troccoli T. Acute acro-ischemia in the child at the time of COVID-19. The International Federation of Podiatrists. 2020. https://img.beteve.cat/wp-content/uploads/2020/04/acroischemia- ENG.pdf. 6. Hubiche T, Cardot-Leccia N, Le Duff F, et al. Clinical, laboratory, and interferon-alpha response characteristics of patients with chilblain-like lesions during the COVID-19 pandemic. JAMA Dermatol. 2021;157:202–6. 7. Pilkington S, Watson R. Should we look beyond the interferon signature in chilblain-like lesions associated with COVID-19? Br J Dermatol. 2021; https://doi.org/10.1111/bjd.20784. 8. Daneshgaran G, Dubin DP, Gould DJ. Cutaneous manifestations of COVID-19: an evidence-based review. Am J Clin Dermatol. 2020;21(5):627–39. https://doi.org/10.1007/s40257-020-00558-4. 9. Wollina U, Kanitakis J, Baran R. Nails and COVID-19 - a comprehensive review of clinical findings and treatment. Dermatol Ther. 2021;34(5):e15100. https://doi.org/10.1111/dth.15100. 10. Maidhof W, Hilas O. Lupus: an overview of the disease and management options. P T. 2012;37(4):240–9. 11. Okon LG, Werth VP. Cutaneous lupus erythematosus: diagnosis and treatment. Best Pract Res Clin Rheumatol. 2013;27(3):391– 404. https://doi.org/10.1016/j.berh.2013.07.008. 12. Careta MF, Romiti R. Localized scleroderma: clinical spectrum and therapeutic update. An Bras Dermatol. 2015;90(1):62–73. https:// doi.org/10.1590/abd1806-4841.20152890. 13. Odonwodo A, Badri T, Hariz A. Scleroderma. [Updated 2021 Aug 9]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK537335/. 14. Bergqvist C, Ezzedine K. Vitiligo: a review. Dermatology. 2020;236(6):571–92. 15. Taïeb A, Picardo M, VETF Members. The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force. Pigment Cell Res. 2007;20(1):27–35. https://doi. org/10.1111/j.1600-0749.2006.00355.x. 16. Ahmed jan N, Masood S. Vitiligo. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK559149/. 17. Frisoli ML, Essien K, Harris JE. Vitiligo: mechanisms of pathogenesis and treatment. Annu Rev Immunol. 2020;38:621–48. https:// doi.org/10.1146/annurev-immunol-100919-023531. 18. Komnitski M, Komnitski A, Komnitski Junior A, Silva de Castro CC. Partial repigmentation of vitiligo with tofacitinib, without exposure to ultraviolet radiation. An Bras Dermatol. 2020;95(4):473–6. https://doi.org/10.1016/j.abd.2019.08.032. 9 Benign and Malignant Lesions of the Lower Extremity Differentiation of a benign lesion from a malignant one is usually made clinically. Many of the former do not require treatment unless symptomatic or cosmetically unacceptable. For example, angiolipomas and dermatofibromas may be painful, especially with application of light pressure. Pyogenic granulomas frequently bleed. Seborrheic and stucco keratoses, which are often multiple and hyperpigmented, hyperkeratotic, and elevated, tend to be quite obvious and negatively impact appearance. Indeed, due to their unsightly appearance, seborrheic keratoses have been termed “the barnacles of life.” Fortunately, the majority of benign lesions are amenable to simple office procedures. A bleeding pyogenic granuloma can be removed by shave excision, although recurrences are not uncommon. Seborrheic keratoses may respond to liquid nitrogen cryosurgery or curettage followed by electrodessication. When contemplating treatment of a benign lesion take into account an end result that may not be ideal; postinflammatory hyperpigmentation and exaggerated scar formation. Some cutaneous lesions have malignant potential. A prime example is the actinic keratosis which is a precursor to squamous cell carcinoma. As such, actinic keratoses merit treatment. Some individuals may have dozens of lesions, and given that healing of the lower extremity is often impaired, prioritization of treatment to advanced lesions is often a prudent course of action. Over two million skin cancers are diagnosed each year in the USA. Basal cell carcinoma is the most common subtype and fortunately this neoplasm has miniscule potential to metastasize. However, basal cell carcinoma is locally destructive and will gradually enlarge over time. Squamous cell carcinoma is the second leading cause of skin cancer and most cases are directly linked to either sun exposure or indoor tanning. Suspect squamous cell carcinoma when confronted with a non-healing lesion in any fair-skinned middle aged to elderly individual with a history of actinic keratoses or chronic exposure to ultraviolet light. Squamous cell carcinomas can metastasize. The deadliest form of skin cancer is melanoma; left untreated this skin cancer will metastasize. Melanomas can either arise from preexisting moles or de novo. The majority are pigmented and clinicians should be familiar with the ABCDEs of melanoma recognition as well as the ugly duckling sign. Early recognition and treatment are of paramount importance. 9.1Benign Lesions 9.1.1Acral Nevus Acral nevus refers to a melanocytic lesion of the volar surfaces of the hands and feet. These nevi are frequently encountered in children and adolescents [1]. In adults, acral nevi are most common in patients with darker Fitzpatrick skin types [2]. The majority manifest as well circumscribed, pigmented macules ranging in color from brown to black. Over time some will involute and disappear. Clinical differentiation of acral nevi from more serious pathology such as acral lentiginous melanoma and atypical Spitz nevi may be challenging. Dermoscopy is of great value revealing a parallel furrow pattern, lattice-like pattern, or fibrillar pattern [3]. The majority of acral nevi do not require biopsy or full excision; however, periodic observation and monitoring for change are prudent (Fig. 9.1). 9.1.2Actinic Keratoses Actinic keratoses are localized cutaneous sites of atypical squamous transformation. The lesions present as erythematous, hyperkeratotic papules, patches, or plaques. Several subtypes based on histology have been identified including acantholytic, atrophic, bowenoid, hypertrophic, lichenoid, © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_9 AL Grawany 53 54 9 Benign and Malignant Lesions of the Lower Extremity Fig. 9.3 Angiokeratomas present as wart-like papules varying in coloration from red to black 9.1.3Angiokeratoma Fig. 9.1 Acral nevus of the big toe. Dermoscopy revealed a parallel furrow pattern Angiokeratoma is a benign cutaneous lesion of blood vessels that appears most commonly in elderly individuals [6]. Lesions present as reddened to dark blue or black papules which over time acquire variable degrees of scale that may resemble verrucae. Hyperkeratosis leads to a “pebbled” surface texture. Angiokeratomas are most commonly found on the legs and do not compress with application of pressure. Trauma often leads to bleeding. Biopsy may be necessary to rule out melanoma. Histology reveals multiple ectatic thin- walled blood vessels within the papillary dermis underneath a slightly hyperkeratotic epidermis (Fig. 9.3). 9.1.4Dermatofibroma Dermatofibromas are commonly encountered benign neoplasms that occur most frequently on the lower extremities. Their highest prevalence is in females with onset in middle Fig. 9.2 Actinic keratoses are premalignant lesions that may evolve age [7]. Lesions may result from trauma such as an insect into squamous cell carcinomas bite or minor abrasion. Dermatofibromas slowly increase in size and are usually asymptomatic although tenderness may be elicited with pressure. Lateral compression may induce a and pigmented [4]. Lesions occur almost exclusively on sun- dimple-like depression. Lesions are firm with coloration exposed areas such as the face, hands, and arms with a ranging from light brown to a reddish hue. Eruptive dermasmaller percentage arising on the lower legs. Actinic kerato- tofibromas may arise during pregnancy or as a consequence ses are considered premalignancies with a potential to evolve of immunosuppression and HIV [8]. into frank squamous cell carcinomas. A number of histopathological variants have been reported Actinic keratoses most commonly arise on fair-skinned with the majority classified as fibrous histiocytomas. These individuals for whom photoprotection is mandatory to pre- present as non-capsulated lesions that can extend into supervent lesion formation. Treatment modalities include liquid ficial adipose tissue. Interlacing fascicles of spindled cells nitrogen, curettage and electrodessication, photodynamic are surrounded by a collagenous stroma containing therapy as well as topical imiquimod and fluorouracil fibroblasts, macrophages, and blood vessels. Excision with (Fig. 9.2) [5]. narrow margins is curative (Fig. 9.4). 9.1 Benign Lesions 55 Fig. 9.5 Lipomas are benign tumors composed of adipose tissue. They are compressible and moveable Fig. 9.4 Dermatofibromas present as firm nodules. They are most common in women and have a predilection for the lower extremities 9.1.5Lipoma Lipoma is a tumor composed of adipose tissue that arises within the subcutaneous layer of skin. Lesions may appear anywhere on the body and usually manifest between the ages of 40 and 60 [9]. Lipomas are slow growing and asymptomatic in a majority of patients. They may achieve sizes that exceed 10 cm. Variants include pleomorphic lipoma and angiolipoma, the latter may elicit pain when palpated. Excision is curative. Diagnosis is usually made based on clinical appearance. Lipomas are benign with no potential for malignant transformation. Multiple lipomas may be associated with disorders such as hereditary lipomatosis, Gardner Syndrome, adiposis dolorosa, and Madelung disease (Fig. 9.5) [10]. 9.1.6Neurofibroma Neurofibromas are commonly encountered peripheral nerve sheath tumors. Characteristic lesions are soft, minimally compressible to firm, flesh-colored papules or nodules that are asymptomatic. Isolated tumors are most common on the trunk and head but have been reported on the palms and soles [11]. Bothersome lesions are best removed by excision. Neurofibromatosis is a group of genetic disorders characterized by an abundance of cosmetically disfiguring nerve Fig. 9.6 A neurofibroma is a tumor composed of nerve tissue. Multiple lesions characterize the genetic disorder neurofibromatosis tissue tumors. The most common presentation of neurofibromatosis is neurofibromatosis type 1, or Von Recklinghausen’s Disease [12]. Transmission is autosomal dominant in nature although many cases arise by spontaneous mutation. Accompanying findings include café au lait spots and hamartomas within the eye (Fig. 9.6). 9.1.7Poroma Poroma is a benign adnexal neoplasm that arises from a sweat gland duct. First described over 50 years ago, poromas were believed to be exclusively of eccrine gland origin [13]. AL Grawany 56 9 Benign and Malignant Lesions of the Lower Extremity Fig. 9.7 A poroma is an adnexal tumor that may arise from eccrine or apocrine glands A case of apocrine poroma was first described in 1988 and several additional cases have been documented [14]. Poromas present as slow growing, solitary, dome-shaped papules or nodules that range in hue from flesh-toned to reddish blue. The most common location is on the hands and feet. Definitive diagnosis is made by biopsy. Full excision is recommended as transformation into malignant porocarcinoma may transpire in a significant percentage of lesions (Fig. 9.7) [15]. 9.1.8Pyogenic Granuloma Pyogenic granuloma, also referred to as lobular capillary hemangioma, is an acquired vascular tumor of the skin and mucous membranes [16]. These benign neoplasms are fast growing and characteristically bleed with minor trauma. They are among the most frequently encountered growths in children and are also associated with pregnancy. Pyogenic granulomas are often precipitated by trauma and have been linked to several classes of medications including isotretinoin [17]. Patients usually seek treatment due to episodic bleeding episodes and ulceration. Shave excision, CO2 laser ablation, and curettage with electrodessication are commonly used destructive modalities although recurrence is not uncommon. Both oral and topical beta blockers are effective nonsurgical therapies (Fig. 9.8) [18]. Fig. 9.8 A pyogenic granuloma is a vascular tumor found on the skin and mucous membranes. Lesions grow rapidly and bleed 9.1.9Seborrheic Keratosis Seborrheic keratoses are commonly encountered benign lesions often seen in Caucasian patients aged 50 and above [19]. They occur with equal prevalence in males and females. Ultraviolet light exposure is thought to be a contributing factor although lesions may occur at sites that have received minimal or no prior sunlight. Seborrheic keratoses may be found on any skin surface with the exception of the palms and soles. Most lesions are hyperpigmented, have a rough surface, and appear “stuck on.” They present as round to ovoid, well-demarcated plaques with coloration ranging from light tan to black. Size may exceed 3 cm in diameter. Early lesions may be flesh-colored, smooth, and have a waxy consistency. The majority of lesions are asymptomatic; pruritus and inflammation are not uncommon especially when lesions are irritated by clothing. Histology reveals hyperkeratosis, acanthosis, and papillomatosis. Dermatoscopic findings include comedo-like openings and milia-like cysts [20]. Cryosurgery and curettage are commonly utilized therapies for removal (Fig. 9.9). 9.2 Malignant Lesions Fig. 9.9 Seborrheic keratoses most commonly manifest as hyperkeratotic, hyperpigmented plaques 9.1.10Stucco Keratoses Stucco keratoses are an uncommon subtype of seborrheic keratoses that are localized to the calves and ankles of the lower legs [21]. Incidence is highest in elderly males. Lesions present as gray-white to brownish papules and plaques. Similar to seborrheic keratoses, they appear to be “stuck on,” hence the name. Histology reveals hyperpigmentation and often horn cysts [22]. Stucco keratoses may be cosmetically unacceptable. Early lesions are often scratched off; liquid nitrogen cryosurgery and curettage are simple office procedures for removal (Fig. 9.10). 57 Fig. 9.10 Stucco keratoses are small, flat to raised lesions aptly named because of their “stuck on” appearance include pigmented, superficial, and morpheaform [25]. BCCs of the lower extremity are uncommon. The majority occur on the anterior lower leg and histologically are of the superficial subtype [26]. BCCs slowly enlarge in size and rarely metastasize. Treatment modalities include surgery, cryotherapy, photodynamic therapy, radiotherapy, and the topical therapies fluorouracil and imiquimod (Fig. 9.11) [27]. 9.2.2Kaposi’s Sarcoma Kaposi’s sarcoma is a vascular neoplasm caused by the human herpesvirus 8 (HHV-8) [28]. Dependent on stage, Kaposi’s sarcoma may present as violaceous to e rythematous macules, plaques, or nodules. Diagnosis is confirmed by his9.2Malignant Lesions tology which reveals spindle cell proliferation, vascular channels, and extravasated red blood cells. Mitotic figures 9.2.1Basal Cell Carcinoma increase as the disease progresses. Several clinical forms of this malignancy have been idenBasal cell carcinomas (BCCs) are the most common form of tified including a subset associated with poorly controlled skin cancer with two million cases diagnosed annually in the HIV and one that arises in middle-aged to elderly adults, USA [23]. The neoplasm is usually associated with fair- termed classic Kaposi’s sarcoma [29]. The decreased inciskinned individuals who have a history of ample sun expo- dence of the former is a tribute to the effectiveness of antiretsure. Over 80% of lesions are located on sun-exposed areas roviral therapy. The classic form occurs on the lower and hereditary predisposition is a major contributing factor extremities of individuals of Mediterranean and Eastern to incidence which steadily increases with age [24]. The European descent. Males greater than 50 years of age are majority of BCCs are classified as nodular; other variants predominantly affected. Classic disease usually has a more AL Grawany 58 a 9 Benign and Malignant Lesions of the Lower Extremity b Fig. 9.11 (a) Basal cell carcinomas are the most common form of malignancy. The majority occur on sun-exposed areas such as the head and neck. (b) Superficial basal cell carcinomas present as well circumscribed, erythematous patches or plaques Fig. 9.13 Keratoacanthomas are rapidly growing nodules with a central keratin plug Fig. 9.12 Kaposi’s sarcoma evolves from cells that line lymph or blood vessels. The malignancy is caused by human herpesvirus 8 (Courtesy of Lawrence Schiffman, DO) indolent course. For localized lesions full resolution has been achieved with radiotherapy, intralesional chemotherapy, and topical imiquimod (Fig. 9.12) [30]. 9.2.3Keratoacanthoma Keratoacanthoma is a neoplasm that originates from the pilosebaceous unit. The lesion grows rapidly and presents as a dome shape, skin colored nodule with a central debris-laden core. Keratoacanthomas have been linked to ultraviolet light exposure and trauma as well as to BRAF kinase inhibitors used to treat melanoma [31, 32]. Diagnosis of KA is confirmed by biopsy which reveals well-differentiated squamous epithelium exhibiting a mild degree of pleomorphism and often evidence of the keratin plug. Differentiation from squamous cell carcinoma is often challenging. Although tumors may spontaneously involute within several months, metastatic spread has been reported, and full excision is considered the treatment of choice although this approach has been recently challenged (Fig. 9.13) [33]. 9.2 Malignant Lesions 59 9.2.4Melanoma Malignant melanoma is a potentially deadly form of skin cancer that develops from melanocytes within the epidermis and dermis. Subtypes include superficial spreading melanoma, lentigo maligna melanoma, acral lentiginous melanoma, and nodular melanoma. The majority of melanomas are linked to ultraviolet light exposure. Risk factors include fair skin, red hair, freckles, severe sunburn as a child, indoor tanning, and a family history of this malignancy [34]. The most common sites are the back in men and the legs in women. The ABCDEs of melanoma recognition are as follows: • • • • • Asymmetry Borders (irregular with notching) Color (variegated) Diameter (greater than 6 mm) Evolving or Elevated A valuable screening tool is the “ugly duckling” sign; nevi in the same individual tend to resemble each other, whereas a melanoma looks different from the other pigmented lesions. Acral lentiginous melanoma is the most common variant found in blacks [35]. It has a worse prognosis than other forms of melanoma. Subungual melanoma is an uncommon form of acral melanoma that typically presents as a pigmented horizontal band under the nail plate. Spread of pigment into the surrounding skin is termed Hutchinson’s sign. Recognition of melanoma may be facilitated by dermoscopy. Characteristic findings include an atypical pigment network, irregular dots and globules, and a gray-blue veil [36]. Genetic expression profiling (GEP) is a noninvasive tissue sampling technique that shows promise in early diagnosis of melanoma (Fig. 9.14) [37]. 9.2.5Squamous Cell Carcinoma Squamous cell carcinoma (SCC) is a malignant neoplasm of keratinocytes that represents the second most common form of skin cancer; approximately one million new SCCs are diagnosed each year in the USA [38]. SCC may arise de novo or from a precursor lesion such as an actinic keratosis. Risk factors include advanced age, fair skin, chronic sun exposure, tobacco use, and immunosuppression [39]. More recently a link to indoor tanning has been documented [40]. Advanced tumors characteristically present as hyperkeratotic plaques and nodules. Metastases are uncommon and overall mortality is approximately 2%. High risk tumors Fig. 9.14 Keratoacanthomas are rapidly growing nodules with a central keratotic plug include those that exceed 2 cm in diameter and have ill- defined margins. Lower extremity SCCs usually present as erythematous patches and plaques with variable degrees of crusting. Surgical excision is the treatment of choice (Fig. 9.15). 9.2.6Mycosis Fungoides (Cutaneous T-Cell Lymphoma) Mycosis fungoides is the most common cutaneous T-cell lymphoma [41]. The disorder usually progresses in severity from patches to plaques and ultimately to tumors. The patch stage is characterized by the appearance of nondescript macules that may possess a fine scale. Color changes are often minimal although some cases demonstrate striking hypo- or hyperpigmentation. Differential diagnosis includes common conditions such as eczema, psoriasis, and tinea. Psoriasis- like lesions characterize the plaque stage. Over time the disease evolves into ulcerated or fungating tumors. Early mycosis fungoides are difficult to diagnose both clinically and histopathologically given the similarity to less serious skin disorders. The course is variable. Some patients succumb within a few years of diagnosis, whereas others may live for decades without development of cutaneous tumors. Treatment varies by stage and early disease often responds to potent topical steroids or nitrogen mustard (Fig. 9.16). AL Grawany 60 a 9 Benign and Malignant Lesions of the Lower Extremity c b Fig. 9.15 (a) Melanoma characterized by asymmetry, irregular borders, and variegated coloration. (b) Melanoma is the deadliest form of skin cancer. Early recognition enhances survival. (c) Melanoma of the nail unit manifesting as longitudinal melanonychia (Courtesy of John Turrisi, DPM) References Fig. 9.16 Mycosis fungoides is a T-cell lymphoma that may clinically resemble more common skin conditions such as eczema and psoriasis 1. Savas Erdogan S, Falay Gur T, Turgut Erdemir AV, Dogan B. Dermoscopic characteristics of acral melanocytic nevi in children and adolescents. Pediatr Dermatol. 2020;37(4):597–603. https://doi.org/10.1111/pde.14136. 2. Madankumar R, Gumaste PV, et al. Acral melanocytic lesions in the United States: prevalence, awareness, and dermoscopic patterns in skin-of-color and non-Hispanic white patients. J Am Acad Dermatol. 2016;74(4):724–30.e1. https://doi.org/10.1016/j. jaad.2015.11.035. 3. Watanabe S, Sawada M, Ishizaki S, Kobayashi K, Tanaka M. Comparison of dermatoscopic images of acral lentiginous melanoma and acral melanocytic nevus occurring on body weight- bearing areas. Dermatol Pract Concept. 2014;4(4):47–50. https:// doi.org/10.5826/dpc.0404a08. 4. Schmitt JV, Miot HA. Actinic keratosis: a clinical and epidemiological revision. An Bras Dermatol. 2012;87:425–34. 5. Hashim PW, Chen T, Rigel D, Bhatia N, Kircik LH. Actinic keratosis: current therapies and insights into new treatments. J Drugs Dermatol. 2019;18(5):s161–6. 6. American Osteopathic College of Dermatology (AOCD). Angiokeratoma. Available at https://www.aocd.org/page/ Angiokeratoma. 7. Han TY, Chang HS, Lee JH, Lee WM, Son SJ. A clinical and histopathological study of 122 cases of dermatofibroma (benign fibrous histiocytoma). Ann Dermatol. 2011;23(2):185–92. 8. Zaccaria E, Rebora A, Rongioletti F. Multiple eruptive dermatofibromas and immunosuppression: report of two cases and review of the literature. Int J Dermatol. 2008;47:723–7. 9. Salam GA. Lipoma excision. Am Fam Physician. 2002;65(5):901–4. References 10. Charifa A, Azmat CE, Badri T. Lipoma Pathology. [2021 Dec 12]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. 11. Lee YB, Lee JI, Park HJ, Cho BK. Solitary neurofibromas: does an uncommon site exist? Ann Dermatol. 2012;24(1):101–2. https:// doi.org/10.5021/ad.2012.24.1.101. 12. Tonsgard J. Clincal manifestations and management of neurofibromatosis type 1. Semin Pediatr Neurol. 2006;13(1):2–7. 13. Pinkus H, Rogin JR, Goldman P. Eccrine poroma: tumors exhibiting features of the epidermal sweat duct unit. Arch Dermatol. 1956;74:511–21. 14. Kamiya H, Oyama Z, Kitajima Y. “Apocrine” poroma: review of the literature and case report. J Cutan Pathol. 2001;28:101–4. 15. Robson A, Greene J, Ansari N, et al. Eccrine porocarcinoma (malignant eccrine poroma): a clinicopathologic study of 69 cases. Am J Surg Pathol. 2001;25:710–20. 16. Wollina U, Langner D, França K, Gianfaldoni S, Lotti T, Tchernev G. Pyogenic granuloma - a common benign vascular tumor with variable clinical presentation: new findings and treatment options. Open Access Maced J Med Sci. 2017;5(4):423–6. 17. Benedetto C, Crasto D, Ettefagh L, Nami N. Development of periungual pyogenic granuloma with associated paronychia following isotretinoin therapy: a case report and a review of the literature. J Clin Aesthet Dermatol. 2019;12(4):32–6. 18. Dany M. Beta-blockers for pyogenic granuloma: a systematic review of case reports, case series, and clinical trials. J Drugs Dermatol. 2019;18(10):1006–10. 19. Del Rosso JQ. A closer look at seborrheic keratoses: patient perspectives, clinical relevance, medical necessity, and implications for management. J Clin Aesthet Dermatol. 2017;10(3):16–25. 20. Minagawa A. Dermoscopy-pathology relationship in seborrheic keratosis. J Dermatol. 2017;44(5):518–24. 21. Shall L, Marks R. Stucco keratoses. A clinico-pathological study. Acta Derm Venereol. 1991;71(3):258–61. 22. Alapatt GF, Sukumar D, Bhat MR. A clinicopathological and dermoscopic correlation of seborrheic keratosis. Indian J Dermatol. 2016;61(6):622–7. https://doi.org/10.4103/0019-5154.193667. 23. Asgari MM, Moffet HH, Ray T, et al. Trends in basal cell carcinoma incidence and identification of high-risk subgroups, 1998– 2012. JAMA Dermatol. 2015:E1–6. 24. Kasumagic-Halilovic E, Hasic M, Ovcina-Kurtovic N. A clinical study of basal cell carcinoma. Med Arch. 2019;73(6):394–8. 25. Scrivener Y, Grosshans E, Cribier B. Variations of basal cell carcinomas according to gender, age, location and histopathological subtype. Br J Dermatol. 2002;147(1):41–7. 26. Carlson KC, Connolly SM, Winkelmann RK. Basal cell carcinoma on the lower extremity. J Dermatol Surg Oncol. 1994;20(4):258–9. https://doi.org/10.1111/j.1524-4725.1994.tb01621.x. 27. Fukumoto T, et al. Comparing treatments for basal cell carcinoma in terms of long-term treatment-failure: a network meta-analysis. J Eur Acad Dermatol Venereol. 2019;33(11):2050–7. https://doi. org/10.1111/jdv.15796. 28. Dupin N. Update on oncogenesis and therapy for Kaposi sarcoma. Curr Opin Oncol. 2020 Mar;32(2):122–8. https://doi.org/10.1097/ CCO.0000000000000601. 61 29. Bishop BN, Lynch DT. Kaposi sarcoma. [Updated 2021 Aug 7]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK534839/. 30. Lebbe C, Garbe C, et al. European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation for Research and Treatment of Cancer (EORTC). Diagnosis and treatment of Kaposi’s sarcoma: European consensus-based interdisciplinary guideline (EDF/ EADO/EORTC). Eur J Cancer. 2019;114:117–27. https://doi. org/10.1016/j.ejca.2018.12.036. 31. Kwiek B, Schwartz RA. Keratoacanthoma (KA): an update and review. J Am Acad Dermatol. 2016;74(6):1220–33. https://doi. org/10.1016/j.jaad.2015.11.033. 32. Lacouture M, Sibaud V. Toxic side effects of targeted therapies and immunotherapies affecting the skin, oral mucosa, hair, and nails. Am J Clin Dermatol. 2018;19(Suppl 1):31–9. https://doi. org/10.1007/s40257-018-0384-3. 33. Tisack A, Fotouhi A, Fidai C, Friedman BJ, Ozog D, Veenstra J. A clinical and biological review of keratoacanthoma. Br J Dermatol. 2021;185(3):487–98. https://doi.org/10.1111/bjd.20389. 34. Heistein JB, Acharya U. Malignant melanoma. [Updated 2021 Nov 21]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK470409/. 35. Wu XC, Eide MJ, King J, Saraiya M, Huang Y, Wiggins C, Barnholtz-Sloan JS, Martin N, Cokkinides V, Miller J, Patel P, Ekwueme DU, Kim J. Racial and ethnic variations in incidence and survival of cutaneous melanoma in the United States, 1999- 2006. J Am Acad Dermatol. 2011;65(5 Suppl 1):S26–37. https:// doi.org/10.1016/j.jaad.2011.05.034. 36. Marghoob NG, Liopyris K, Jaimes N. Dermoscopy: a review of the structures that facilitate melanoma detection. J Am Osteopath Assoc. 2019;119(6):380–90. https://doi.org/10.7556/jaoa.2019.067. 37. Skelsey M, Brouha B, Rock J, et al. Non-invasive detection of genomic atypia increases real-world npv and ppv of the melanoma diagnostic pathway and reduces biopsy burden. SKIN J Cutan Med. 2021;5(5):512–23. https://doi.org/10.25251/skin.5.5.9. 38. Waldman A, Schmults C. Cutaneous squamous cell carcinoma. Hematol Oncol Clin North Am. 2019;33(1):1–12. 39. Thompson AK, Kelley BF, Prokop LJ, Murad MH, Baum CL. Risk factors for cutaneous squamous cell carcinoma recurrence, metastasis, and disease-specific death: a systematic review and meta- analysis. JAMA Dermatol. 2016;152:419–28. 40. Lergenmuller S, et al. Association of lifetime indoor tanning and subsequent risk of cutaneous squamous cell carcinoma. JAMA Dermatol. 2019 Oct;2:1–9. 41. Vaidya T, Badri T. Mycosis fungoides. [Updated 2021 Aug 4]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.statpearls.com/articlelibrary/ viewarticle/25428/. AL Grawany Blistering Eruptions of the Lower Extremity Blistering eruptions range the gamut from an acute, self- limiting dermatitis such as poison ivy to the chronic, life- altering disorder epidermolysis bullosa. Some blistering ailments are discussed elsewhere including bullous impetigo, herpes zoster, and erythema multiforme. Blistering disorders are characterized by thin-walled, fluid-filled skin lesions. A small blister is referred to as a vesicle, whereas larger lesions (generally greater than 5 mm) are termed bullae. 10.1Bullous Pemphigoid Bullous pemphigoid is an autoimmune disease seen most frequently in elderly populations [1]. Males and females are affected equally with no racial predilection. Bullae present as tense, oval, or round lesions containing serous or hemorrhagic fluid arising on normal, urticarial, or erythematous skin. Itching is variable and may be severe. Diagnosis is confirmed via histology and immunofluorescence which demonstrate subepidermal blistering, an eosinophilic predominance of inflammatory infiltrate, and IgG circulating autoantibodies to components of the basement membrane zone. Most cases are idiopathic but the condition has recently been linked to drugs including PD-1 inhibitors [2] and dipeptidyl peptidase 4 (DPP-4) inhibitors [3]. Without treatment the disease can persist for several months to years. High potency topical steroids and oral doxycycline may control limited disease. When this is impractical or ineffectual, oral prednisone is the mainstay of therapy. Mycophenolate mofetil, omalizumab, and rituximab have proven of value for control of refractory disease (Fig. 10.1). 10 10.2Dermatitis Herpetiformis Dermatitis herpetiformis is an uncommon blistering disease characterized by papulovesicles symmetrically distributed on extensor surfaces of the extremities and buttocks. Pruritis is near universal and ranges from moderate to severe [4]. The condition peaks in midlife, is most prevalent in individuals of Irish and Scandinavian decent, and is associated with HLA-DQ2 and HLA-DQ8 haplotypes [5]. Immunological stimulation of intestinal mucosa by ingested gluten is a key factor in pathogenesis and deposition of IgA in the dermal papillae is a hallmark of the disease. The diagnosis of dermatitis herpetiformis is based on clinical presentation along with serology, histology, and immunofluorescence. Autoantibodies against transglutaminase are frequently detected in serum. Dapsone is a cornerstone of therapy when strict dietary avoidance of gluten cannot be achieved (Fig. 10.2). 10.3Epidermolysis Bullosa Acquisita Epidermolysis bullosa acquisita (EBA) is a rare blistering condition which worsens during adulthood. It is a subepithelial disorder with tense, fragile bullae accompanied by milia and scarring. EBA can be divided into two subtypes: mechanobullous (classic EBA) and inflammatory EBA [6]. The mechanobullous non-inflammatory subtype presents in trauma prone areas such as the hands, feet, elbows, and knees. Tense, non-inflamed vesicles rupture leaving erosions. Inflammatory EBA presents similar to bullous pemphigoid and other subepithelial autoimmune blistering diseases. EBA is caused by autoantibodies against type VII collagen which helps maintain attachment of the epidermis to the dermis. After the autoantibodies bind, activation of complement leads to deposition of C3a and C5a which recruit leukocytes and mast cells. The result is disruption of the © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_10 63 64 10 Blistering Eruptions of the Lower Extremity a Fig. 10.2 Dermatitis herpetiformis is a chronic skin condition triggered by an immune response to gluten b Fig. 10.1 (a) Bullous pemphigoid may present with urticarial patches and excoriated papules. (b) Tense fluid-filled bullae are a hallmark of disease anchoring fibrils in the basement membrane zones of the skin and mucosa [7]. The condition is chronic and management entails avoidance of trauma and proper wound care (Fig. 10.3). 10.4Acropustulosis of Infancy Acropustulosis of infancy is a disorder most often seen in the first year of life [8]. The etiology is unknown although some cases follow infestation with scabies and a hypersen- Fig. 10.3 Epidermolysis bullosa acquisita in an adult who has endured years of traumatically induced bullae and skin erosions sitivity reaction has been postulated [9]. The condition manifests as recurrent crops of intensely pruritic vesicles and pustules on the palms, soles, wrists, and ankles. The initial eruption lasts for 1 to 2 weeks and can subsequently reappear several weeks later. Spontaneous remission occurs within several months. Diagnosis is usually based on clinical findings. Bacterial and viral cultures are negative and histopathology reveals an intraepidermal pustule containing polymorphonuclear neutrophils and eosinophils. When symptomatic, short-term treatment with mid to high potency topical steroids may promote resolution (Fig. 10.4). AL Grawany References 65 References Fig. 10.4 Acropustulosis of infancy occurs on the hands and feet of infants. Vesicles rapidly progress to sterile pustules 1. Miyamoto D, Santi CG, Aoki V, Maruta CW. Bullous pemphigoid. An Bras Dermatol. 2019;94(2):133–46. https://doi.org/10.1590/ abd1806-4841.20199007. 2. Lopez AT, Khanna T, Antonov N, Audrey-Bayan C, Geskin L. A review of bullous pemphigoid associated with PD-1 and PD-L1 inhibitors. Int J Dermatol. 2018;57(6):664–9. ISSN: 1365-4632 3. Lee SG, Lee HJ, Yoon MS, Kim DH. Association of dipeptidyl peptidase 4 inhibitor use with risk of bullous pemphigoid in patients with diabetes. JAMA Dermatol. 2019;155(2):172–7. https://doi. org/10.1001/jamadermatol.2018.4556. 4. Nguyen CN, Kim SJ. Dermatitis herpetiformis: an update on diagnosis, disease monitoring, and management. Medicina (Kaunas). 2021;57(8):843. https://doi.org/10.3390/medicina57080843. 5. Bolotin D, Petronic-Rosic V. Dermatitis herpetiformis. Part I. epidemiology, pathogenesis, and clinical presentation. J Am Acad Dermatol. 2011;64:1017–24. 6. Ludwig RJ. Clinical presentation, pathogenesis, diagnosis, and treatment of epidermolysis bullosa acquisita. ISRN Dermatol. 2013;2013:812029. https://doi.org/10.1155/2013/812029. 7. Hashimoto T, Ishii N, Ohata C, Furumura M. Pathogenesis of epidermolysis bullosa acquisita, an autoimmune subepidermal bullous disease. J Pathol. 2012 Sep;228(1):1–7. https://doi.org/10.1002/ path.4062. 8. American Osteopathic College of Dermatology (AOCD). Acropustulosis of infancy. Available at https://www.aocd.org/page/ AcropustulosisInfanc. 9. Infantile acropustulosis--how often is it a sequela of scabies? Pediatr Dermatol. 1995;12(3):275–6. Self-Induced and Psychogenic Skin Conditions of the Lower Extremity 11 Some skin conditions are self-induced, albeit unwittingly. A classic example is erythema ab igne which results from prolonged contact with a heat generating device held against the skin. Other skin conditions may have psychogenic undertones such as prurigo nodularis. Tanorexia is a compulsive disorder and delusions of parasitosis is a manifestation of psychosis. 11.1Erythema Ab Igne Erythema ab igne (EAI) is an area of localized reticulated erythema and hyperpigmentation that occurs on parts of the body exposed to prolonged infrared radiation. Chronic exposure injures the epidermis and superficial vascular plexus. Initially erythematous, exposed areas subsequently become mottled and acquire brown, blue, or purple colorations. The most common cause is heating pads and the condition predominately affects females afflicted with longstanding pain [1]. Most cases are asymptomatic and gradual resolution is anticipated once contact with the inciting agent has been discontinued. Squamous cell carcinomas may rarely arise within affected sites (Fig. 11.1) [2]. Fig. 11.1 Erythema ab igne secondary to prolonged use of a heating pad (Courtesy of Ron Hidalgo, DO) 11.2Prurigo Nodularis 11.3Tanorexia Prurigo nodularis is a chronic disorder of the skin characterized by firm nodules that range in color from pink to brown. Common locations include the arms, legs, and upper back. The condition occurs primarily in older adults with men and women equally affected. The pathogenesis involves a chronic itch-scratch cycle believed to be a cutaneous inflammatory neurogenic response mediated by a variety of peptides [3]. A significant percentage of patients admit to anxiety, depres- Tanorexia is a “compulsive need or desire to have and maintain a very dark tan beyond what is typically considered normal” [5]. Chronic excess tanning is now widely considered to be a substance abuse disorder and a true behavioral addiction [6]. Ultraviolet light stimulates production of opioid- related endorphins in the skin which may factor into pathogenesis. Tanning dependence contributes to premature aging and skin cancer. Of particular risk is indoor tanning sion, and suicidal ideation [4]. Therapeutic options include topical and systemic steroids, antihistamines, gabapentin, ultraviolet light, and IL 13 and IL 31 inhibitors (Fig. 11.2). © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_11 AL Grawany 67 68 11 Self-Induced and Psychogenic Skin Conditions of the Lower Extremity Fig. 11.2 Prurigo nodularis is also referred to as pickers nodules Fig. 11.3 Tanorexia is a compulsive need to spend time exposed to sun or an ultraviolet light source for maintenance of a tan which delivers a concentrated dose of ultraviolet light and is believed to cause nearly 400,000 cases of skin cancer in the USA each year (Fig. 11.3) [7]. 11.4Delusions of Parasitosis Delusions of parasitosis is a disorder in which affected individuals have an unwavering and erroneous belief that they are infected with bugs, be they parasites, worms, mites, or other living organisms. A related condition, Morgellons disease, substitutes fibers for insects. As “proof” patients often transport inanimate objects to the office in plastic containers or baggies (“ Ziploc bag sign”) [8]. In keeping with delusional ideation, reasoning or logical discourse is unpersuasive and ineffectual. The oral agent pimozide is the treatment of choice and often induces remission (Fig. 11.4) [9]. Fig. 11.4 Magnified view of a “bug and eggs” brought to the office by a patient suffering from delusions References 69 References 1. Kettelhut EA, Traylor J, Roach JP. Erythema ab igne. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK538250/. 2. Sigmon JR, Cantrell J, Teague D, Sangueza O, Sheehan DJ. Poorly differentiated carcinoma arising in the setting of erythema ab igne. Am J Dermatopathol. 2013;35:676–8. 3. Mullins TB, Sharma P, Riley CA, Sonthalia S. Prurigo Nodularis. 2021. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. 4. Brenaut E, Halvorsen JA, Dalgard FJ, Lien L, Balieva F, Sampogna F, et al. The self-assessed psychological comorbidities of prurigo in European patients: a multicentre study in 13 countries. J Eur Acad 5. 6. 7. 8. 9. Dermatol Venereol. 2019;33(1):157–62. https://doi.org/10.1111/ jdv.15145. https://www.merriam-webster.com/dictionary/tanorexia. Petit A, Lejoyeux M, Reynaud M, Karila L. Excessive indoor tanning as a behavioral addiction: a literature review. Curr Pharm Des. 2014;20(25):4070–5. https://doi.org/10.2174/13816128113199990 615. Wehner MR, Chren MM, Nameth D, et al. International prevalence of indoor tanning: a systematic review and meta-analysis. JAMA Dermatol. 2014;150(4):390–400. Reich A, et al. Delusions of parasitosis: an update. Dermatol Ther. 2019;9(4):631–8. https://doi.org/10.1007/s13555-019-00324-3. Brownstone N, Hakimi M, Koo J. Best practices for management of delusions of parasitosis. SKIN J Cutan Med. 2021;5(5):448–52. https://doi.org/10.25251/skin.5.5.1. AL Grawany Skin Signs of Systemic Disease and Reactive Disorders of the Lower Extremity 12 A skin condition is on occasion the first sign of internal disease. Recognizing a disorder that is caused by, or associated with, an internal malady can result in earlier diagnosis and a more favorable clinical outcome. An example is erythema nodosum; recommended work-up may uncover tuberculosis infection or sarcoid. Some reactive processes are uniquely associated with an underlying condition. A prime example is diabetic dermopathy. Other reactive processes may or may not be found in association with underlying illness. Perforating folliculitis can arise in the context of impaired kidney function although most cases are not linked to internal disease. 12.1Diabetic Dermopathy Diabetic dermopathy, also referred to as “shin spots,” is the most common cutaneous finding in diabetes, occurring in a significant number of longstanding diabetic patients older than 50 years [1]. The condition presents as smooth, well- defined, round to oval atrophic hyperpigmented macules located on the pretibial areas of the lower legs. Lesions are usually bilateral and are distributed in an asymmetric pattern. The condition is asymptomatic. The cause of diabetic dermopathy is unknown although some cases have been linked to minor trauma. Progression is variable and not related to glycemic control [2]. To date no treatment modality has proven of uniform success and lesions may persist indefinitely or spontaneously improve (Fig. 12.1). 12.2Erythema Multiforme Erythema multiforme is a hypersensitivity reaction that can involve both skin and mucous membranes. The condition may be triggered by herpes simplex viral infections and Mycoplasma pneumonia as well as medications that include Fig. 12.1 Diabetic dermopathy presents with hyperpigmented macules nonsteroidal anti-inflammatory drugs, antiepileptics, and antibiotics [3]. The disorder is believed to be triggered by a cell-mediated immune reaction. Patients with cutaneous manifestations of erythema multiforme present with target lesions containing a central blister surrounded by peripheral erythema. These are located in an acral distribution on the palms, back of hands, feet, and extensor surfaces. Lesions are often painless but some patients experience burning sensations. Lesions of the mucosa are also common and may progress to painful erosions. Patients may report fever, malaise, arthralgia, and joint swelling [4]. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_12 71 72 12 Skin Signs of Systemic Disease and Reactive Disorders of the Lower Extremity Fig. 12.2 Bullous lesions associated with erythema multiforme (Courtesy of Lawrence Schiffman, DO) Treatment depends on the severity of the rash as well as the underlying cause if identified. Lesion resolution may be hastened by use of topical steroids and emollients. Healing occurs spontaneously in 2 to 4 weeks. Recurrence is common when linked to herpes infection (Fig. 12.2). 12.3Erythema Nodosum Erythema nodosum (EN) is a cutaneous inflammatory reactive process that most commonly manifests on the lower legs. Characteristic lesions are tender, erythematous to hyperpigmented nodules that are warm to touch and often bilateral. Lesions do not ulcerate and heal without scarring. The condition is most common in women between the ages of 25 and 40 [5]. Diagnosis of EN is usually made clinically. Histopathology of EN reveals a septal panniculitis with varying degrees of superficial and deep perivascular inflammatory lymphocytic infiltration [6]. Although many cases of EN are idiopathic, the disorder may be triggered by contagious disorders including streptococcal infection, tuberculosis, and leprosy [7]. EN has also been associated with inflammatory bowel disease, sarcoid, and malignancies as well as with oral contraceptives. EN is usually self-limited but requires work-up for identifiable causality (Fig. 12.3). 12.4Granuloma Annulare Granuloma annulare (GA) is a benign, noninfectious, self- limited disorder. The condition is most common in women and middle-aged to older individuals [8]. There are several forms of GA including localized, generalized, and subcutaneous [9]. The localized subtype usually presents on the dorsal or lateral surfaces of the hands and feet. The classic appearance is that of an annular flesh colored to erythematous patch or plaque with a slightly elevated border. Generalized GA usually affects adult females and manifests Fig. 12.3 Painful leg nodules indicative of erythema nodosum as multiple erythematous to light brown papules and patches. The trunk and upper thighs are primarily involved. Subcutaneous or deep GA usually occurs in children and is characterized by firm asymptomatic nodules. Most cases of GA are diagnosed clinically. Biopsy reveals palisading granulomatous inflammation accompanied by dermal collagen degeneration admixed with macrophages, neutrophils, and multinucleated giant cells. GA may be triggered by trauma and has been associated with a number of systemic abnormalities including thyroid disease, malignancy, diabetes, and HIV infection [10]. Treatment options for localized disease include topical and intralesional steroids and cryosurgery. Many cases resolve spontaneously within 2 years of onset (Fig. 12.4). 12.5Idiopathic Guttate Hypomelanosis Idiopathic guttate hypomelanosis is an acquired benign leukoderma that presents as discrete annular hypopigmented macules ranging in size from 2 to 6 mm [11]. The condition most commonly arises in elderly, fair-skinned persons with equal distribution in males and females. Relation to sun exposure as well as to hereditary predisposition has been proposed but not universally accepted. The majority of cases AL Grawany 12.7 Lipodermatosclerosis 73 Fig. 12.4 A discolored plaque with raised borders characterizes granuloma annulare Fig. 12.5 Idiopathic guttate hypomelanosis presents with hypopigmented macules are diagnosed clinically. Histopathology reveals a diminished number of melanocytes unlike vitiligo where melanocytes are absent. A number of modalities have been utilized for treatment including cryosurgery, lasers, microdermabrasion, microneedling, and topical retinoids and calcineurin inhibitors. All should be used cautiously to avoid worsening of the leukoderma or inducement of postinflammatory hyperpigmentation (Fig. 12.5). Direct immunofluorescence is often positive [13]. Baseline work-up includes complete blood count, urinalysis, sedimentation rate, and measurement of liver and kidney status. Most cases of leukocytoclastic vasculitis are self-limited. Supportive therapy includes leg elevation and bed rest. If drug induced, removal of the offending medication results in clearance. Symptomatic or persistent cases may respond to colchicine or dapsone [14]. High dose corticosteroids may be required for adequate control (Fig. 12.6). 12.6Leukocytoclastic Vasculitis 12.7Lipodermatosclerosis Leukocytoclastic vasculitis is a small vessel inflammatory process targeting venules and capillaries. Approximately 50% of cases are idiopathic; identifiable causes include medications, infections, autoimmune disease, and underlying malignancy [12]. The condition involves the lower legs and is usually asymptomatic. Palpable purpura is the classic presentation. Lesions are erythematous to violaceous in hue, bilaterally distributed, and often appear in crops. Diagnosis is made by biopsy which reveals neutrophil infiltration within small vessel walls accompanied by fibrinoid necrosis. Lipodermatosclerosis is an inflammatory skin condition of the lower extremities that usually occurs in the setting of venous insufficiency. Unlike stasis dermatitis in which inflammatory changes are more superficial, lipodermatosclerosis is a panniculitis with involvement of subcutaneous fat [15]. The disorder is painful in the acute phase and may resemble cellulitis or erythema nodosum. The prevalence is highest in middle-aged to elderly women [16]. Clinically, lipodermatosclerosis is characterized by the appearance of firm, indurated plaques. Pigmentation may be 74 12 Skin Signs of Systemic Disease and Reactive Disorders of the Lower Extremity Fig. 12.6 The hallmark of leukocytoclastic vasculitis is palpable purpura marked and increases over time. The pattern on the legs has been likened to an “inverted champagne bottle.” Therapies that may prove of value include compression stockings and intralesional triamcinolone (Fig. 12.7) [17]. Fig. 12.7 Inverted champagne bottle appearance of lipodermatosclerosis 12.8Necrobiosis Lipoidica Necrobiosis lipoidica is an inflammatory granulomatous disorder of the skin that most commonly presents on the shins of type 1 diabetics (referred to as necrobiosis lipoidica diabeticorum) [18]. The lesions appear as yellow-red plaques associated with central atrophy, telangiectasias, and raised violaceous borders. The condition predominates in female patients typically between 30 and 40 years of age. Lesions are asymptomatic but can become ulcerated, especially after trauma. The etiology is unknown; autoimmune complex deposition has been postulated to induce vascular changes that lead to collagen degeneration. Altered collagen and microangiopathy are noted on histology [19]. Therapeutic options are many but none has uniform success. Topical and intralesional steroids are often implemented as first line treatment. Topical calcineurin inhibitors, topical retinoids, laser therapy, immunomodulators, biologics, and antimalarials have all been reported to improve this condition. Some cases spontaneously involute (Fig. 12.8). Fig. 12.8 Necrobiosis lipoidica manifests as shiny, atrophic plaques 12.9Perforating Folliculitis Perforating folliculitis is classified as a reactive perforating collagenosis which also includes elastosis perforans serpiginosa and Kyrle disease [20]. Perforating disorders are characterized histologically by the presence of collagen and AL Grawany 12.11 Pretibial Myxedema elastin fibers that penetrate into the follicular spaces of hair follicles. Many cases are linked to systemic diseases such as chronic renal failure, diabetes, and human immunodeficiency virus. Other associations include vitamin A deficiency and growth factor receptor inhibitors. Perforating folliculitis presents with scattered, firm follicular papules distributed on the extremities and buttocks. Papules have varying degrees of erythema and contain central keratotic plugs. Some cases may respond to topical tretinoin or oral therapy with isotretinoin (Fig. 12.9) [21]. 75 12.10Porokeratosis Porokeratosis results from an abnormal clonal focal expansion of keratinocytes [22]. Porokeratosis of Mibelli is a variant that most commonly occurs on the lower legs and manifests as an erythematous patch or plaque with an atrophic center. The lesion is surrounded by a keratotic wall termed a coronoid lamella. Males predominate and the condition may arise at any age. Lesions are slow growing and remain asymptomatic. Some cases appear transmitted in autosomal dominant manner, whereas others may be triggered by extrinsic factors such as ultraviolet light exposure, trauma, and certain medications [23]. Basal and squamous cell carcinomas may uncommonly develop within porokeratosis. Various treatment modalities have been utilized with inconsistent results including imiquimod, topical vitamin D analogues, retinoids, and cryosurgery (Fig. 12.10) [24]. 12.11Pretibial Myxedema Fig. 12.9 Perforating folliculitis presenting with multiple follicular papules a Pretibial myxedema is a reactive process most commonly associated with thyroid disease. The condition results from deposition of hyaluronic acid and other mucopolysaccharides within the dermis and is believed to be a consequence b Fig. 12.10 (a) Porokeratosis is a disorder of keratinization marked histologically by a coronoid lamella. (b) Eruptive porokeratosis is a rare variant presenting with multiple lesions 76 12 Skin Signs of Systemic Disease and Reactive Disorders of the Lower Extremity Fig. 12.11 Pretibial myxedema results from accumulation of glycosaminoglycans of an aberrant immune response [25]. Several subtypes have been identified including nonpitting edema, plaque, nodular, and elephantiasic variants [26]. The condition most commonly manifests in the pretibial areas but may also occur elsewhere including on the dorsal surface of the feet. Pretibial myxedema is asymptomatic but may be of cosmetic concern. The clinical course is variable and some cases improve over time. Both topical steroids and compression may be of value in hastening resolution (Fig. 12.11). References 1. Morgan AJ, Schwartz RA. Diabetic dermopathy: a subtle sign with grave implications. J Am Acad Dermatol. 2008;58(3):447–51. https://doi.org/10.1016/j.jaad.2007.11.013. 2. Mendes AL, Miot HA, Haddad V Jr. Diabetes mellitus and the skin. An Bras Dermatol. 2017;92(1):8–20. https://doi.org/10.1590/ abd1806-4841.20175514. 3. Trayes KP, Love G, Studdiford JS. Erythema multiforme: recognition and management. Am Fam Physician. 2019;100(2):82–8. 4. Hafsi W, Badri T. Erythema multiforme. [2021 Aug 7] In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. 5. Hafsi W, Haseer Koya H. Erythema, Nodosum. StatPearls Publishing. Updated 12 December 2017. Available at: https://www. ncbi.nlm.nih.gov/books/NBK470369. 6. Wilk M, Zelger BG, Hayani K, Zelger B. Erythema nodosum, early stage-a subcutaneous variant of leukocytoclastic vasculitis? Clinicopathological correlation in a series of 13 patients. Am J Dermatopathol. 2020;42(5):329–36. 7. Schwartz RA, Nervi SJ. Erythema nodosum: a sign of systemic disease. Am Fam Physician. 2007;75(5):695–700. 8. Barbieri JS, Rodriguez O, Rosenbach M, Margolis D. Incidence and prevalence of granuloma annulare in the United States. JAMA Dermatol. 2021;157(7):824–30. https://doi.org/10.1001/ jamadermatol.2021.1847. 9. Piette EW, Rosenbach M. Granuloma annulare: clinical and histologic variants, epidemiology, and genetics. J Am Acad Dermatol. 2016;75(3):457–65. https://doi.org/10.1016/j.jaad.2015.03.054. 10. Wang J, Khachemoune A. Granuloma annulare: a focused review of therapeutic options. Am J Clin Dermatol. 2018;19(3):333–44. https://doi.org/10.1007/s40257-017-0334-5. 11. Brown F, Crane JS. Idiopathic Guttate hypomelanosis. [Updated 2021 Sep 20]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm. nih.gov/books/NBK482182/. 12. Takatu CM, Heringer APR, Aoki V, et al. Clinicopathologic correlation of 282 leukocytoclastic vasculitis cases in a tertiary hospital: a focus on direct immunofluorescence findings at the blood vessel wall. Immunol Res. 2017;65(1):395–401. https://doi.org/10.1007/ s12026-016-8850-6. 13. Baigrie D, Bansal P, Goyal A, et al. Leukocytoclastic vasculitis. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Available from: https://www.ncbi. nlm.nih.gov/books/NBK482159/. 14. Fraticelli P, Benfaremo D, Gabrielli A. Diagnosis and management of leukocytoclastic vasculitis. Intern Emerg Med. 2021;16(4):831– 41. https://doi.org/10.1007/s11739-021-02688-x. 15. Kirsner RS, Pardes JB, Eaglstein WH, Falanga V. The clinical spectrum of lipodermatosclerosis. J Am Acad Dermatol. 1993;28(4):623–7. https://doi.org/10.1016/0190-9622(93)70085-8. 16. Bruce AJ, Bennett DD, Lohse CM, Rooke TW, Davis MD. Lipodermatosclerosis: review of cases evaluated at Mayo Clinic. J Am Acad Dermatol. 2002;46(2):187–92. https://doi. org/10.1067/mjd.2002.119101. 17. Campbell LB, Miller OF 3rd. Intralesional triamcinolone in the management of lipodermatosclerosis. J Am Acad Dermatol. 2006;55:166–8. https://doi.org/10.1016/j.jaad.2005.09.043. 18. Lepe K, Riley CA, Salazar FJ. Necrobiosis lipoidica. [Updated 2021 Aug 26]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm. nih.gov/books/NBK459318/. 19. https://emedicine.medscape.com/article/1103467-workup#c7. 20. Mullins TB, Sickinger M, Zito PM. Reactive perforating collagenosis. [Updated 2021 Nov 15]. In: StatPearls [Internet]. Treasure Island, FL): StatPearls Publishing; 2022. Available from: https:// www.ncbi.nlm.nih.gov/books/NBK459214/. 21. https://emedicine.medscape.com/article/1071033-treatment. 22. Vargas-Mora P, Morgado-Carrasco D, Fustà-Novell X. Porokeratosis: a review of its pathophysiology, clinical manifestations, diagnosis, and treatment. Actas Dermosifiliogr (Engl Ed). 2020;111(7):545–60. English, Spanish. https://doi.org/10.1016/j. ad.2020.03.005. 23. Ferreira FR, Santos LD, Tagliarini FA, Lira ML. Porokeratosis of Mibelli--literature review and a case report. An Bras Dermatol. 2013;88(6 Suppl 1):179–82. https://doi.org/10.1590/ abd1806-4841.20132721. 24. Weidner T, Illing T, Miguel D, Elsner P. Treatment of porokeratosis: a systematic review. Am J Clin Dermatol. 2017;18(4):435–49. https://doi.org/10.1007/s40257-017-0271-3. 25. Georgala S, Katoulis AC, Georgala C, et al. Pretibial myxedema as the initial manifestation of Graves’ disease. J Eur Acad Dermatol Venereol. 2002;16(4):380–3. 26. Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. Dermopathy of Graves’ disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab. 2002;87(2):438–46. AL Grawany Ulcerations of the Lower Extremity Ulcers of the lower extremity may be caused by a number of factors. Shape, location, size, appearance, and underlying systemic and/or skin disease aid in diagnosis. Chronic lower extremity wounds may be of diabetic, neuropathic, pressure, or vascular origin [1, 2]. Less common causes are those that arise from inflammation, infection, trauma, physical agents such as radiation or chemicals, tumors, vasculitides, poor nutrition, underlying internal disease, and connective tissue diseases such as rheumatoid arthritis [3]. 13.1Diagnosis Proper diagnosis requires a thorough patient history including the wound’s onset, progression, pain level and other symptoms, underling illnesses, duration, and previous or ongoing treatments. Examination entails evaluation of a number of factors including shape of the ulcer, size, base, coloration, appearance of surrounding tissue, location, and associated skin lesions if present. 13.1.1Shape Ulcer shape and border should be noted. Ulcers may be sloping, scooped out, or punched out and round, oval, stellate, or polyangular in configuration. 13.1.2Base The ulcer base may be dry, soft, moist, granular, or fibrotic. The appearance of the ulcer base not only aids in diagnosing the type of wound but also helps monitor the state of healing. Some wound care clinics have adopted a simple visual classification system based on color; black, yellow, red, or pink. Black wounds are necrotic or ischemic and usually warrant debridement and at times revascularization. 13 Yellow wounds are covered with a collection of necrotic cellular debris. A yellowish membrane is common in arterial ulcers and in the presence of some infections [4]. These wounds require cleansing, surgical, or autolytic debridement. A reddened base is indicative of granulation. Protection and occlusion will hasten the healing process. Granulation tissue is composed of thousands of capillary loops that resemble small granules in the wound bed. Pink wounds are a sign of early epithelization and require protection so that the epithelium can thicken, mature, and allow collagen to re-organize. 13.1.3Peri-wound Skin Peri-wound skin may be characterized as scaling, oozing, keratotic, erythematous, inflamed, purpuric, hyper- or hypopigmented, edematous, or indurated. 13.1.4Location The location of an ulcer often helps to define causation. Venous ulcers usually occur on the lower legs on the area just above the medial malleoli [4]. Arterial ulcers have a predilection for the toes and distal forefoot [4]. Diabetic ulcers are commonly found on the plantar surface of the foot [5]. 13.2Arterial Ulcers Atherosclerosis is the main cause of arterial or ischemic ulcers [4]. Risk factors include smoking and diabetes. Patients may experience intermittent claudication in their calves and/or rest pain. Distal pedal pulses are diminished and/or absent, and capillary refill is delayed. Arterial ulcers are often found on the toes and bony prominences sur- © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_13 77 78 Fig. 13.1 Arterial ulcer on second toe 13 Fig. 13.2 Diabetic foot ulcer rounded by shiny, taut skin. The ulcers are “punched out” in appearance with a round circumference and smooth edges (Fig. 13.1). 13.3Diabetic Ulcers Diabetics have a 20% lifetime risk of developing a foot ulcer [5]. Contributing factors include diabetes-associated peripheral neuropathy and vascular disease. The ulcers are characteristically painless even when infected. The most common location is on the plantar foot. The borders are punched out, with a hyperkeratotic rim. Over 80% of lower extremity amputations are attributed to complications from diabetic ulcerations. Treatment includes debridement of devitalized tissue, off-loading to reduce pressure, and appropriate wound dressings to maintain a moist healing environment (Fig. 13.2). 13.4Venous Ulcers Venous or stasis ulcers are the most common type of leg ulceration [4]. They develop secondary to sustained venous hypertension. Lesions are usually shallow with a ruddy- colored base and irregular wound margin. Edema, varicosities, and altered pigmentation with thickened skin termed lipodermatosclerosis are often present. Discomfort is variable. Venous ulcers are most frequently encountered above Fig. 13.3 Venous stasis ulcer the ankle and below the proximal calf (Figs. 13.3 and 13.4). AL Grawany Ulcerations of the Lower Extremity 13.7 Calciphylaxis 79 Fig. 13.5 Pyoderma gangrenosum Fig. 13.4 Lipodermatosclerosis on the leg 13.5Pyoderma Gangrenosum Pyoderma gangrenosum presents as an ulceration with violaceous peri-wound skin [6]. The disorder occurs most commonly on the lower extremity. The condition can be precipitated or worsened by minor trauma, referred to as “pathergy.” Ulcers expand rapidly and are very painful. Most cases are idiopathic but lesions can be associated with chronic inflammatory bowel disease, arthritis, and autoimmune disorders. Diagnosis is one of the exclusions as there are no confirmatory laboratory tests and biopsy is nonspecific, performed primarily to rule out other pathologies. Lesions are often misdiagnosed as venous stasis ulcers when they occur on the medial aspect of the leg. No single specific therapy has proven universally successful and treatment options include intralesional steroids, oral corticosteroids, cyclosporine, infusion of infliximab, and surgical intervention (skin grafts) (Fig. 13.5). 13.6Sickle Cell Ulcer The most common cutaneous presentation of sickle cell disease is a leg ulcer which is more frequent in sickle cell anemia than in the trait [7]. These ulcers are extremely painful, Fig. 13.6 Sickle cell ulcer on the lateral malleolus may have a punched-out appearance, and occur most commonly over the medial and lateral malleoli. Networks of sickled red cells obstructing the microcirculation to the skin, anemia, and in situ thrombosis factor into pathogenesis. Local trauma to the area may also precipitate ulcer formation. Ulcers tend to be chronic and recurrent and treatment is challenging. Standard local wound care and pain management are mainstays of therapy (Fig. 13.6). 13.7Calciphylaxis Calciphylaxis is a rare, life-threatening disorder of intra- and extravascular calcification that most commonly arises in individuals afflicted with end-stage renal disease. Narrowing and occlusion of subcutaneous microvessels result in necrotic skin lesions that are exquisitely painful. Early lesions are often found on the legs and begin as reticulated, indurated, 80 13 Ulcerations of the Lower Extremity Fig. 13.8 Pressure ulcer on the posterior heel Fig. 13.7 Calciphylaxis ulcerated plaques, and nodules which progress to ulcerations [8]. The prognosis is poor with most patients dying within 1 year of diagnosis [9]. Management involves a multi-disciplinary approach ideally including nephrology, dermatology, wound care, and pain management. Sodium thiosulfate, a chelator of calcium, has been used intravenously and intralesionally to induce remission (Fig. 13.7). 13.8Pressure Ulcers Pressure ulcers, also known as decubitus ulcers and bedsores, are a result of constant and prolonged pressure on a bony prominence [10]. The heel and lateral/medial malleoli are commonly affected sites in patients who are bedridden and are not able to make postural changes regularly. Treatment involves reducing pressure exerted on the area, minimizing the ulcer’s contact with a hard surface, decreasing moisture, and decreasing bioburden to prevent sepsis [10]. The most widely used classification system for pressure ulcers is the NPUAP (national pressure ulcer advisory panel) system [10] (Fig. 13.8). References 1. Eaglstein WH, Falanga V. Chronic wounds. Surg Clin North Am. 1997;77:689–700. 2. Gist S, Tio-Matos I, Falzgraf S, Cameron S, Beebe M. Wound care in the geriatric client. Clin Interv Aging. 2009;4:269–87. 3. Labropoulos N, Manalo D, Patel NP, Tiongson J, Pryor L, Giannoukas AD. Uncommon leg ulcers in the lower extremity. J Vasc Surg. 2007;45(3):568–73. 4. Grey JE, Harding KG, Enoch S. Venous and arterial leg ulcers. BMJ. 2006;332(7537):347–50. 5. Edmonds ME, Foster AV. Diabetic foot ulcers. BMJ. 2006;332(7538):407–10. 6. Barbe M, Batra A, Golding S, Hammond O, Higgins JC, O'Connor A, Vlahovic TC. Pyoderma gangrenosum: a literature review. Clin Podiatr Med Surg. 2021;38(4):577–88. https://doi.org/10.1016/j. cpm.2021.06.002. 7. Sahu T, Verma HK, Ganguly S, Sinha M, Sinha R. Common, but neglected: a comprehensive review of leg ulcers in sickle cell disease. Adv Skin Wound Care. 2021;34(8):423–31. https://doi. org/10.1097/01.ASW.0000755924.12513.40. 8. Ghosh T, Winchester DS, Davis MDP, El-Azhary R, Comfere NI. Early clinical presentations and progression of calciphylaxis. Int J Dermatol. 2017;56(8):856–61. https://doi.org/10.1111/ijd.13622. 9. Nigwekar SU, Thadhani R, Brandenburg VM. Calciphylaxis. N Engl J Med. 2018;378(18):1704–14. https://doi.org/10.1056/ NEJMra1505292. 10. Zaidi SRH, Sharma S. Pressure ulcer. [2022 Feb 9]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. AL Grawany Drug Eruptions of the Lower Extremity 14 A drug eruption is an adverse cutaneous reaction to a medication. Such untoward events are usually mild and promptly resolve upon discontinuation of the inciting drug. Other adverse events such as toxic epidermal necrolysis are associated with systemic involvement and may be life-threatening. Often the offending drug is readily ascertained by history of recent exposure. Sometimes the cause is not as obvious, especially when a patient is on multiple medications or when the reaction resembles other skin disorders. Note as well that drug eruptions can be triggered by over-the-counter, nonprescription medications often overlooked when history is obtained. Several types of drug reactions have been described and include the following: 14.1Morbilliform Drug Eruptions The majority of drug eruptions present as morbilliform rashes. Antibiotics account for over 30% of these reactions with amoxicillin-clavulanic acid, cephalexin, and ciprofloxacin common offenders [1]. Other drug classes include antihypertensives, nonsteroidal anti-inflammatory drugs, and anticonvulsants. Morbilliform eruptions result from a delayed T-cell mediated immune response. The initial rash may occur within 1–2 days following prior exposure or may be delayed up to 8 weeks after first time dosing. Morbilliform drug eruptions commence as erythematous papules and patches that coalesce a few days after onset. Sites of involvement are usually the trunk and extremities; involvement of the face is uncommon. Differentiation from a viral exanthem may be difficult clinically. Discontinuation of the causative drug along with antihistamines and topical steroids usually results in prompt clearance (Fig. 14.1). Fig. 14.1 Morbilliform eruption is the most common manifestation of a drug hypersensitivity reaction 14.2Fixed Drug Eruption Fixed drug eruption is an adverse event to a drug that is marked by the development of well-demarcated macules on the skin or mucosal surfaces. Classic is the appearance of the rash at the same location following ingestion of the causative drug [2]. Lesions are often dusky red in hue and circular to ovoid in appearance. Lesions may increase in severity with © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_14 81 82 14 Drug Eruptions of the Lower Extremity Fig. 14.2 Fixed drug eruption manifests as a well-defined patch that recurs at the same site following re-exposure to a drug subsequent exposures leaving residual hyperpigmentation. The most commonly involved agents include nonsteroidal anti-inflammatory drugs, antibiotics, anticonvulsants, and antimalarials. The underlying pathogenesis involves activation of intraepidermal CD8+ T-cells (Fig. 14.2) [3]. 14.3Acute Generalized Exanthematous Pustulosis Acute generalized exanthematous pustulosis (AGEP) is an uncommon skin rash induced by medication. The rash presents as sterile pustules and papules arising on an erythematous background [4]. Patients may present with fever, pruritus, and elevated white count. Agents that have been implicated include aminopenicillins, quinolones, terbinafine, ketoconazole, and fluconazole. The rash usually arises within 48 h after exposure to the medication. The dermatitis presents on the trunk and intertriginous areas and infrequently involves the mucous membranes. Differential diagnosis includes pustular psoriasis and folliculitis. Symptoms improve within days following discontinuation of the causative drug (Fig. 14.3). Fig. 14.3 Acute generalized exanthematous pustulosis is a drug reaction characterized by the onset of papules and pustules on an erythematous base References 1. Krispinsky AJ, Shedlofsky LB, Kaffenberger BH. The frequency of low-risk morbilliform drug eruptions observed in patients treated with different classes of antibiotics. Int J Dermatol. 2020;59(6):647– 55. https://doi.org/10.1111/ijd.14703. 2. Flowers H, Brodell R, Brents M, et al. Fixed drug eruptions: presentation, diagnosis, and management. South Med J. 2014;107:724–7. 3. Shiohara T. Fixed drug eruption: pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol. 2009;9(4):316–21. 4. Szatkowski J, Schwartz RA. Acute generalized exanthematous pustulosis (AGEP): a review and update. J Am Acad Dermatol. 2015;73(5):843–8. https://doi.org/10.1016/j.jaad.2015.07.017. AL Grawany Biopsy Techniques of the Lower Extremity A skin biopsy is the gold-standard in the histopathologic diagnosis of dermatological conditions. Often, skin biopsies are performed on suspicious pigmented lesions to rule out skin cancer. However, skin neoplasms and inflammatory skin conditions may appear similar and are difficult to distinguish from one another clinically [1]. In these cases, a biopsy not only facilitates a histopathologic diagnosis but may direct the treatment plan. In addition, a biopsy can be curative or possibly lifesaving when one excises the lesion in toto or when the biopsy identifies a treatable malignant diagnosis. Ultimately, a biopsy both can complement and confirm the diagnosis [2]. On the lower extremity, skin biopsies are generally performed on the following: suspicious neoplasms, inflammatory skin conditions, and blistering rashes [2]. Providers should obtain informed consent and forewarn the patient about the possible need for further surgery post-biopsy. For example, after the initial biopsy, another surgical procedure may be necessary for a malignant lesion to be excised in toto. One should also counsel the patient about the possibility of a painful or thickened scar, especially when involving the plantar foot. The techniques covered in this chapter are shave, punch, excisional/incisional, curettage, and nail. Choosing which type of biopsy to use in various clinical scenarios is paramount to facilitate the diagnosis (Table 15.1). 15.1Shave Biopsy The shave biopsy is the most superficial of all the skin biopsies as the specimen encompasses only epidermis and superficial dermis. It is useful for pedunculated or exophytic lesions and is not recommended for the identification of inflammatory skin conditions. Lightly shaving scale from a superficial fungal infection edge for mycological testing is not considered a shave biopsy. Two methods for the shave are the classically described technique with the device cut- 15 Table 15.1 Type of biopsy to use in various clinical scenarios Biopsy method Clinical scenario Shave Skin tags, exophytic lesions, nevi Punch Skin rashes, non-melanoma skin cancer (BCC, SCC), vasculitis, blistering rash (edge of blister for HE stain, perilesional for DIF), ulcers Incisional/ Melanoma, panniculitis excisional ellipse Curettage Verruca, superficial non-melanoma skin cancer (BCC, SCC) that has been diagnosed Nail Longitudinal melanonychia, longitudinal erythronychia, glomus tumor, diagnosis of inflammatory nail disorders (psoriasis, lichen planus, etc.) BCC basal cell carcinoma, SCC squamous cell carcinoma, HE hematoxylin and eosin, DIF direct immunofluorescence ting parallel to the skin or saucerization which creates a slightly deeper specimen. Either of these versions may be performed with one of the following: #10 or #15 surgical blades, an autoclaved razor blade that is bent slightly in a half circle, or a BioBlade (Miltex®) which has a flexible blade. After the surgical site has been prepared, the provider performs either an intradermal injection or a local block of choice, such as a digital block or a “V” block. To perform an intradermal injection, the authors use a 1 cc syringe of lidocaine with a 30-gauge or 27-gauge, ½ inch needle and slowly infiltrate the fluid under the lesion. When using lidocaine with epinephrine, there is a blanching effect which may make visualization of the lesion difficult. No matter which local anesthetic is used, the intradermal injection technique offers immediate anesthesia allowing one to perform the biopsy without delay. Applying the preferred instrument to the skin, a “shaving” motion is used to remove the lesion either parallel to the skin lesion or “saucerized” with a slightly deeper central section. Hemostasis is then obtained by either using a Hyfrecator or applying a topical agent like aluminum chloride. Drawbacks © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_15 83 84 15 Biopsy Techniques of the Lower Extremity of this technique include a pigmented or cosmetically displeasing scar due to secondary wound closure and a lacking histological picture due to the absence of a full thickness specimen (Figs. 15.1, 15.2, 15.3, 15.4, 15.5, and 15.6). 15.2Punch Biopsy In contrast to the shave, the punch biopsy offers a full thickness specimen. A punch biopsy encompasses the epidermis, dermis, and superficial subcutaneous tissue. Therefore, physicians should reserve the punch biopsy for neoplasms, blistering disorders, and inflammatory skin conditions. A punch biopsy may be considered excisional if the lesion is completely encompassed in the diameter of the tool. It may be Fig. 15.3 Using a #10 blade, the shave biopsy is performed Fig. 15.1 Pigmented lesion on the lateral aspect of the ankle Fig. 15.4 A Hyfrecator is used to achieve hemostasis Fig. 15.2 Injection of local anesthesia utilizing the intradermal technique also used as an incisional biopsy if sampling a small area from a larger lesion. Prior to infiltration of local anesthetic, the provider may pinch the skin to find the relaxed skin tension lines [2]. By making the incision parallel to these skin lines, one can use these as a guide to give the best scar outcome. Post- preparation of the site, an intradermal injection of local anesthetic of the surgeon’s choice is infiltrated under the lesion. After a small wheal has been raised, the area is ready to be biopsied. Once local anesthesia has been obtained, the provider applies an appropriately sized disposable punch instrument AL Grawany 85 15.3 Excisional and Incisional Biopsies Fig. 15.5 Utilizing an autoclaved razor blade to perform the shave Fig. 15.7 Injection of local anesthesia prior to punch procedure The depth of applying a punch biopsy into the tissue must be considered carefully due to the unique anatomical surfaces and varying skin thicknesses of the lower extremity. For example, when applying a punch tool to the dorsum of the foot, the provider should be careful in controlling the depth of the biopsy to avoid important structures deep to the lesion such as vascular structures, tendons/ligaments, and bone. In contrast, the entire blade of the punch may be applied on the plantar foot skin. Once the punch has been performed, gently lift the circular button of skin and subcutaneous tissue upwards. Using an iris scissor, cut the fatty attachment as deeply as possible to give the full thickness specimen to pathology. For most skin lesions, the specimen can be sent in formalin. However, if you are sending the specimen for direct immunofluorescence (DIF) staining, you should consult the pathology lab for the best medium for transport (i.e., Michel’s Fixative) since formalin can negatively affect proteins needed for the study [2]. Proceed to suture the defect or use steri-strips to cover the wound. The patient may return in 10 to 14 days for both suture removal and histopathologic diagnosis review (Figs. 15.7, 15.8, and 15.9). 15.3Excisional and Incisional Biopsies Fig. 15.6 The specimen after the shave procedure to the skin. This may range from 2 to 6 mm (diameter), but most providers utilize a 3 or 4 mm punch tool for lower extremity lesions [1]. Use the dominant hand to hold the punch instrument, while the other hand places a gentle perpendicular force to the relaxed skin tension lines away from the lesion. This enables the provider to avoid “dog ears” when closing the defect with suture. Excisional and incisional biopsies both provide a full thickness specimen. When a lesion can be extirpated with a small margin of unaffected skin, an excisional elliptical biopsy is warranted [1]. In circumstances where a small area of a large lesion is sampled, an incisional elliptical biopsy is the procedure of choice. Like the punch biopsy, it is important to consider relaxed skin tension lines. The elliptical incision axis ideally should be parallel to the relaxed skin tension lines for optimal scar outcome. Once you have obtained consent and prepared the 86 15 Biopsy Techniques of the Lower Extremity Fig. 15.8 Application of the punch tool Fig. 15.10 Elliptical incision being performed Fig. 15.9 Excision of the punch specimen Fig. 15.11 Removal of lesion surgical site, use the local anesthetic technique of your choice. With this biopsy technique, the clinician draws an ellipse or fusiform shape with a 3:1 length to width ratio, a 30-degree angle at both corners of the incision, and a 2 mm border around the lesion [3]. After the first pass of the #15 blade to outline the incision, deepen the incision to include the subcutaneous tissue. Proceed to dissect the ellipse of skin carefully in one plane and send the specimen in formalin (or another media if sending for DIF). One may employ simple interrupted or running nylon sutures to close the defect. The technique for incisional biopsy is the same as the excisional biopsy. The only difference is an incisional biopsy does not remove the lesion completely (Figs. 15.10 and 15.11). 15.4Curettage and Electrodesiccation Clinicians use curettage and electrodesiccation when treating verruca or a previously biopsied non-melanoma skin cancer such as superficial basal cell carcinoma. Curettage has limited utilization and provides a fragmented specimen to the pathologist. It does not aid in diagnosing inflammatory skin disorders, neoplasms, and other diseases [2]. Post skin preparation and infiltration of local anesthesia, the provider should apply the curette with firm strokes over the lesion. Only the tissue sample from the first pass with the curette is sent to pathology and in formalin. The curetted material following electrodesiccation will not aid in the diagnosis. Following curettage, topical hemostasis is applied AL Grawany 15.5 Nail Biopsy 87 with a handheld electrocautery device. After the initial curettage and cauterization, the clinician performs curettage and electrodessication twice more on the surgical site to complete the procedure. Like the shave biopsy, this biopsy site will heal by secondary intention and leave a minimal scar. 15.5Nail Biopsy The most common techniques to use for a nail biopsy are the punch and the incisional/excisional methods. These are used to further investigate pigmented lesions of the nail and nail unit tumors. When a patient presents with a dark brown to black longitudinal line on the nail plate, i.e., longitudinal melanonychia, the provider must determine whether to do a nail biopsy [4]. When planning a punch biopsy of that lesion, the physician should involve the most proximal part of pigmented area due to the melanocyte presence in the matrix of the nail unit. Therefore, one should dissect the proximal nail fold back carefully to expose the nail matrix to have appropriate exposure for the procedure. Due to the possible disturbance of the matrix during this procedure, it is imperative to discuss with the patient during the informed consent process that permanent nail dystrophy may occur as the nail grows distally. Direct a 4 mm punch (or smaller/larger depending on the size of the lesion) to the most proximal part of the pigmented area. Using a gentle motion, apply the punch tool to the nail plate and continue to twist the tool through the nail bed [4]. There is minimal to no subcutaneous tissue deep to the nail bed. The punch instrument will most likely touch the distal phalanx. When the clinician feels the periosteum of the distal phalanx, they should carefully pull the punch tool out of the nail unit, cut the lesion as deeply as possible, and place the specimen in formalin. One can fill the circular defect remaining in the nail plate with gel foam or another hemostatic agent and repair the proximal nail fold with suture or steri-strips. If a patient presents with a nail bed neoplasm, one may perform an incisional or excisional biopsy depending on the size of the lesion. Surgical planning involves first removing the nail plate to gain access to the nail bed [4]. Compared to a biopsy of the nail matrix, excising a nail bed lesion is unlikely to cause permanent nail dystrophy. Once the lesion has been removed, it is placed in formalin and sent for histopathologic processing (Figs. 15.12, 15.13, and 15.14). Fig. 15.12 Longitudinal melanonychia on great toenail Fig. 15.13 Application of punch tool to nail 88 15 Biopsy Techniques of the Lower Extremity References 1. Wark KJ, Smith SD, Sebaratnam DF. How to perform a skin biopsy. Med J Aust. 2020;212(4):156–8.e1. https://doi.org/10.5694/ mja2.50473. 2. Sina B, Kao GF, Deng AC, Gaspari AA. Skin biopsy for inflammatory and common neoplastic skin diseases: optimum time, best location and preferred techniques. A critical review. J Cutan Pathol. 2009;36(5):505–10. https://doi. org/10.1111/j.1600-0560.2008.01175.x. 3. Zuber TJ. Fusiform excision. Am Fam Physician. 2003;67(7):1539– 44, 1547–8, 1550 4. Rich P. Nail surgery. In: Bolognia JL, Rapini RP, et al., editors. Dermatology. 1st ed. London: Mosby; 2003. p. 2321–230. Fig. 15.14 Removal of nail specimen AL Grawany Dermatologic Therapies of the Lower Extremity: Topical and Systemic Dermatological formulations provide topical treatment for skin conditions and as a rule have a better safety profile compared to systemic agents. The vehicle houses and supports active ingredients and may enhance penetration beyond the stratum corneum. An ideal vehicle is odorless, easy to apply, inexpensive, non-irritating, and stable. Ointments Ointments are often petrolatum-based and form an occlusive barrier. Ointments have a greasy consistency that aid in hydration of the stratum corneum and enhance potency of the active ingredient. Ointments are well suited for xerotic skin in non-hair bearing areas. 16 Tapes Tapes are strips of an occlusive adhesive impregnated with an active ingredient. Many are formulated to release the active ingredient in a time-controlled manner. Lacquers Lacquers are organic materials with an evaporable solvent that leaves a film. Lacquers are ideally suited for use on nails. Powders Powders contain ground up or pulverized ingredients. Powders have a drying effect and may be used to minimize excess moisture. Vehicle choice is an important consideration when treatCreams Creams are emulsions that can either be oil-in- ing disorders of the lower extremities. Ease of spread water or water-in-oil formulations that impart a slight resi- enhances compliance when dealing with a large, hair-bearing due to the skin. Creams are readily rinsed off and are more surface area such as the lower leg. Depending on the thickcosmetically elegant than ointments. ness of hair, gels, lotions, sprays, and foams might be preferred over creams or ointments from both cosmetic and Lotions Lotions are in essence one liquid (oil) surrounded penetration standpoints. by another liquid (water) which together create an emulsion When dealing with thick plantar skin penetration is an or topical suspension. Lotions are typically less moisturizing important consideration. In comparison to the forearm, the than creams. They are easy to spread on wide body surfaces plantar foot has ten times less absorption than the axilla [1]. and impart a cooling sensation to the skin. An ointment is ideally suited for this locale but may be difficult to keep in contact with the skin. To avoid the greasy Gels Gels are either alcohol-based or water-based. Alcohol- residue of an ointment in a sock or shoe patients can opt for based gels tend to sting more than water-based gels. Both pro- a cream, emulsion, or topical suspension. vide for rapid drying and enhanced penetration. Gels are excellent A topical medication is only effective if utilized as prevehicles for hair bearing areas and, when tolerated, work well in scribed. Vehicles play a significant role in patient adherence. moist intertriginous locations such as interdigital spaces. Tolerability, spread-ability, durability, ease of use, cosmetic elegance, and the need for special storage are just some of Sprays Sprays are metered (pre-measured) pumps of emul- the many factors affecting patient acceptance. sion that dry quickly and can be readily spread over large An interesting study measured vehicle preference in psosurface areas. Of concern is the potential for inhalation, riasis patients [2]. Each subject applied a cream, solution, especially when used on a chronic basis. gel, ointment, foam, and emollient to forearm skin. Assessed quality-of-life factors included time needed for application, Foams Foams are a dispersion of gas in small amounts of smell, feel on skin and hair-bearing sites, clothing stains, liquid. Foam formulations are cosmetically elegant and easy messiness, and method of application. Overall, the preferred to apply. vehicles were solutions and foams. Gender and age may play © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, S. M. Schleicher, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4_16 89 90 16 Dermatologic Therapies of the Lower Extremity: Topical and Systemic a role in vehicle preference as well with women more tolerant of moisturizing bases and a younger audience more attuned to sprays and foams. The following tables offer a guide to some common dermatological treatments for lower extremity skin conditions (Tables 16.1, 16.2, 16.3, 16.4, 16.5, 16.6, 16.7, 16.8, 16.9, 16.10 and 16.11) [3]. Table 16.1 (continued) Class VII Lowest potency Hydrocortisone 2.5% cream, ointment, solution Hydrocortisone 2% lotion Hydrocortisone 1% cream, gel, lotion, ointment, solution, spray Hydrocortisone 0.5% cream, ointment Table 16.2 Non-steroidal topical preparations for eczema Table 16.1 Prescription topical corticosteroid preparations for inflammatory skin conditions Class I Super high potency Betamethasone dipropionate 0.05% gel, lotion, ointment Clobetasol propionate 0.05% cream, emollient cream, gel, lotion, ointment, shampoo, spray, solution Fluocinonide 0.1% cream Flurandrenolide 4 mcg/cm2 tape Halobetasol propionate 0.05% cream, foam, lotion, ointment Class II High potency Amcinonide 0.1% ointment Betamethasone dipropionate augmented formulation (AF) 0.05% cream Clobetasol propionate 0.025% cream Desoximetasone cream, ointment, spray 0.25%, gel 0.05% Diflorasone diacetate 0.05% cream, ointment Fluocinonide 0.05% cream, gel, ointment, solution Halcinonide 0.1% cream, ointment, solution Halobetasol propionate 0.01% lotion Class III High potency Amcinonide 0.1% cream, lotion Betamethasone valerate 0.12% foam, 0.1% ointment Fluocinonide 0.05% emollient cream Fluticasone propionate 0.005% ointment Mometasone furoate 0.1% ointment Triamcinolone acetonide 0.5% cream, ointment Class IV Mid-potency Betamethasone dipropionate 0.05% spray Clocortolone pivalate 0.1% cream Fluocinolone acetonide 0.025% ointment Flurandrenolide 0.05% ointment Fluticasone propionate 0.05% cream Hydrocortisone valerate 0.2% ointment Mometasone furoate 0.1% cream, lotion, solution Triamcinolone acetonide 0.1% cream, ointment, 0.05% ointment, 0.2 mg/s spray Class V Mid-potency Desonide 0.05% gel, ointment Fluocinolone acetonide 0.025% cream Hydrocortisone butyrate 0.1% cream, lotion, ointment, solution Hydrocortisone probutate 0.1% cream Hydrocortisone valerate 0.2% cream Prednicarbate 0.1% emollient cream, ointment Triamcinolone acetonide 0.1% lotion, 0.025% ointment Class VI Low potency Alclometasone dipropionate 0.05% cream, ointment Desonide 0.05% cream, foam, lotion Triamcinolone acetonide 0.025% cream, lotion Prescription Calcineurin inhibitor: Pimecrolimus 1% cream Tacrolimus 0.03% and 0.01% ointment JAK inhibitor: Ruxolitinib 1.5% cream Phosphodiesterase 4 inhibitor: Crisaborole 2% ointment Over-the-counter Benadryl® Itch Stopping Cream (Johnson & Johnson) Calamine Lotion Sarna® Original and Sensitive Anti-Itch Lotion (Crown Laboratories, Inc) Tricalm® Steroid-Free Hydrogel (Life Wear Technologies, LLC) Table 16.3 Prescription topical therapies for plantar verruca The following drugs are not FDA approved for plantar verruca, but their use has been supported by clinical studies Imiquimod 5% cream Sinecatechins 15% ointment Fluorouracil 5% cream Adapalene 0.1% gel Cantharidin 1% liquid Table 16.4 Over-the-counter keratolytics and emollients Urea 40% cream Keralyt® Salicylic acid 5% cream, gel, shampoo (Summers Laboratories Inc) AmLactin® (15% lactic acid) Foot Repair Cream Therapy (Advantice Health, LLC) Aveeno® Skin Relief cream, lotion (Johnson & Johnson) CeraVe® cream (L’Oreal) Curel® Itch Defense® (Kao USA, Inc) Cutemol® Emollient Cream (Summers Laboratories Inc) Dermeleve® Soothing Cream (Advanced Derm Solutions, LLC) Eucerin® original healing cream (Beiersdorf) Gold Bond Ultimate® Eczema Relief Cream and Lotion (Sanofi Consumer Healthcare) Lubriderm® lotion (Johnson & Johnson) Table 16.5 Prescription topical antifungals Ciclopirox olamine 0.77% cream, gel, lotion Ketoconazole cream and shampoo, 2% Luliconazole cream 1% Naftifine HCl 1% and 2% cream and 1% and 2% gel Oxiconazole nitrate cream 1% Sertaconazole nitrate cream 2% AL Grawany 91 References Table 16.6 Over-the-counter topical antifungals Terbinafine hydrochloride cream, gel, spray Butenafine hydrochloride cream Clotrimazole cream Miconazole nitrate powder and spray Table 16.7 Prescription oral antifungals Terbinafine hydrochloride tablets Itraconazole capsules Griseofulvin ultramicrosize tablets Fluconazole tablets Table 16.8 Laundry detergents for sensitive skin All® Free Clear (Henkel Corporation) Arm and Hammer Sensitive Skin (Church & Dwight Co) Dreft® (Procter and Gamble) Tide® Free and Gentle (Procter and Gamble) Table 16.10 (continued) Agent Psoriatic Arthritis (PsA) or Psoriasis (PsO) Biologics TNF-α inhibitors Etanercept PsA, PsO Adalimumab PsA, PsO Infliximab PsA, PsO Certolizumab pegol PsA, PsO Golimumab PsA Interleukin 12 and 23 inhibitor Ustekinumab PsA, PsO Interleukin 17 inhibitors: Secukinumab PsA, PsO Brodalumab PsO Ixekizumab PsA, PsO Interleukin 23 inhibitors: Tildrakizumab-asmn PsO Risankizumab-rzaa PsA, PsO Guselkumab PsA, PsO Table 16.9 Topical nail therapies: prescription (Rx) and over-the- Table 16.11 Topical non-steroidal preparations for psoriasis counter (OTC) topicals Vitamin D Analog For nail dystrophy calcipotriene 0.005% cream and ointment calcitriol ointment 3mcg/g DermaNail® Nail Conditioner (Summers Laboratories) OTC Aryl hydrocarbon receptor agonist Genadur® hydrosoluble nail lacquer (Medimetriks Pharmaceuticals) Rx tapinarof cream, 1% Kerasal® Fungal Nail Renewal Treatment, Advantice Health) OTC Phosphodiesterase 4 inhibitor For onychomycosis (all Rx) roflumilast cream 0.3% Ciclopirox 8% nail solution Tavaborole topical solution 5% Jublia® (Efinaconazole topical solution 10%, Ortho Dermatologics) References Table 16.10 Systemic medications for psoriatic arthritis and psoriasis Agent Oral medications Cyclosporine Methotrexate Acitretin Apremilast Psoriatic Arthritis (PsA) or Psoriasis (PsO) PsO PsA/PsO PsO PsA, PsO 1. Feldman RJ, Maibach HI. Regional variation in percutaneous penetration of 14C cortisol in man. J Invest Dermatol. 1967;48:181–3. 2. Housman TS, Mellen BG, Rapp SR, Fleisher AB, Feldman SR. Patients with psoriasis prefer solution and foam vehicles: a quantitative assessment of vehicle preference. Cutis. 2002;70(6):327–32. 3. UpToDate. Comparison of representative topical corticosteroid preparations (classified according to the United States system). https://www.uptodate.com/contents/image/print?imageKey=DER M%2F62402 Index A Abscess, 21 Acral nevus, 53 Acropustulosis, 64, 65 Actinic keratoses, 53 Acute generalized exanthematous pustulosis (AGEP), 82 Angiokeratoma, 54 Antifungal, 19 Antinuclear antibodies (ANA), 50 Arterial ulcers, 77 Asteatotic eczema, 30 Atherosclerosis, 77 Athlete’s foot, 17 Atopic dermatitis, 40 B Bacterial infections abscess, 21 cellulitis, 21 erythrasma, 22 folliculitis, 22 impetigo, 23 pitted keratolysis, 23 Basal cell carcinomas (BCCs), 53, 57 Bed bugs, 25 Bullous pemphigoid, 63 C Calcineurin inhibitor, 90 Calciphylaxis, 79 Cellulitis, 21 Chilblains, 49 Ciclopirox, 20 Contact dermatitis, 39, 40 Corns and calluses, 29 Coronoid lamella, 75 Corynebacterium, 23 COVID toes, 49 Creams, 89 Curettage, 86 D Delusions, 67 Delusions of parasitosis, 68 Dermatitis herpetiformis, 63, 64 Dermatofibroma, 53, 54 Dermatophilus congolensis, 23 Dermatophyes, 17 Diabetic dermopathy, 71 Diabetic ulcers, 78 Disappearing nail bed (DNB), 7 Drug vehicle, 89 E Econazole, 20 Eczema, 40 Electrodesiccation, 86 Emollients, 90 Epidermolysis bullosa acquisita (EBA), 63 Erythema, 44 Erythema abigne (EAI), 67 Erythema multiforme, 71, 72 Erythema nodosum, 71, 72 Erythrasma, 22 Excisional biopsies, 85 Exostosis, 13 F Fibroma/Fibrokeratoma, 12 Fixed drug eruption, 81 Fleas, 25 Foams, 89 Folliculitis, 22 G Gels, 89 Granuloma annulare (GA), 72 Green nails, 7 H Hand foot and mouth disease, 23, 24 Herpes simplex, 10 Herpes zoster, 23 Horteae werneckii, 19 Hyfrecator, 84 I Ichthyosis, 31 Idiopathic guttate hypomelanosis, 72 Impetigo, 22 Ingrown toenails, 8 Interdigital tinea pedis, 17 Intractable plantar keratosis (IPK), 29 Irritant dermatitis, 39 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 T. C. Vlahovic, DPM, S. M. Schleicher, MD, Atlas of Lower Extremity Skin Disease, https://doi.org/10.1007/978-3-031-07950-4 AL Grawany 93 94 J JAK inhibitor, 90 K Kaposi’s sarcoma, 57, 58 Keloids, 46 Keratoacanthoma, 58 Keratoderma climactericum, 30, 31 Keratolytics, 32, 90 Ketoconazole, 20 Koilonychia, 3 Kytococcus sedentarius, 23 L Lacquers, 89 Leukocytoclastic vasculitis, 73, 74 Leukonychia, 5 Lichen planus, 36, 37 Lichen striatus, 37, 38 Lipodermatosclerosis, 73 Lipoma, 55 Longitudinal melanonychia, 5, 87 Lotions, 89 Luliconazole, 20 Lyme disease, 26 M Majocchi’s granuloma, 19 Melanoma, 53, 59 Melanonychia, 45 Moccasin tinea pedis, 18 Moisturizers, 32 Molluscum contagiosum, 24 Morbilliform drug eruptions, 81 Morgellons disease, 68 Morphea, 50 Mycosis fungoides, 59, 60 Myxoid cyst, 12 N Naftitine, 20 Nail biopsy, 87 Nail color changes green nails, 6 leukonychia, 5 longitudinal melanonychia, 5, 6 Yellow nail syndrome, 7 Nail lichen planus, 9 Nail matrix nevi, 13 Nail plate changes Beau’s lines, 1 onychomadesis, 1 onychorrhexis, 2 trachyonychia, 3 Nail psoriasis, 9 Nail shape and size changes anonychia, 3 clubbing, 4 koilonychia, 3 pincer nails, 4 Index Necrobiosis lipoidica, 74 Neurofibromas, 55 Neurofibromatosis, 55 O Ointments, 89 Onychogryphosis, 5 Onycholysis, 6, 7 Onychomadesis, 1 Onychomycosis, 11 Onychorrhexis, 2 Oral antifungals, 91 Oxiconazole, 20 P Palmoplantar keratoderma (PPK), 31 Palpable purpura, 73 Papulosquamous, 35 Perforating folliculitis, 74 Periodic acid Schiff (PAS), 20 Periungual viral warts, 10 Pigmentation disorders post-inflammatory hyperpigmentation, 43 Pitted keratolysis, 23 Plantar verruca, 90 Plantar verrucae, 24 Porokeratoses, 32 Porokeratosis, 75 Poroma, 55 Post-inflammatory hypopigmentation, 44 Powders, 89 Pressure ulcer, 80 Pretibial myxedema, 75, 76 Prurigo nodularis, 67 Psoriasis, 2, 3, 35, 91 Psoriatic arthritis, 91 Punch biopsy, 84, 85 Pyoderma gangrenosum, 79 Pyogenic granuloma, 11, 56 R Retronychia, 9 S Scabies, 26 Scale, 29 Scars, 46 Seborrheic keratoses, 56 Sertaconazole, 20 Shave biopsy, 83 Sickle cell ulcer, 79 Skin of color, 43, 45 Sprays, 89 Squamous cell carcinoma (SCC), 59 Staphylococcus aureus, 21 Stasis dermatitis, 40, 41 Stucco keratoses, 57 Subungual exostosis, 13 Subungual hematoma, 8 Subungual melanoma, 14 Index Subungual squamous cell carcinoma (SCC), 13 Superficial fungal infections dermatophytes, 17 interdigital tinea pedis, 18 laboratory tests, 20 majocchi’s granuloma, 19 moccasin tinea pedis, 18 molds, 17 tinea incognito, 19 treatment, 20 vesiculobullous tinea pedis, 18 yeast, 17 Systemic lupus erythematosus, 50 Systemic sclerosis, 50 T Tanorexia, 67 Tapes, 89 Tinea incognito, 18 Tinea nigra, 19 Tinea pedis, 17 Topical corticosteroid, 90 Topical nail therapies, 91 Trachyonychia, 2 Trans-epidermal water loss (TEWL), 32 95 Trichophyton rubrum, 17 U Ulcers arterial, 77 calciphylaxis, 80 diabetic, 78 diagnosis, 77 pressure, 80 pyoderma gangrenosum, 79 sickle cell ulcer, 79 venous, 78 V Venous stasis ulcer, 78 Venous ulcers, 78 Vesiculobullous tinea pedis, 18 Vitiligo, 44, 45, 51 X Xerosis, 29 Y Yellow nail syndrome, 6 AL Grawany

Atlas of Lower Extremity Skin Disease 2022

Related documents

Add this document to collection(s)

Add this document to saved

Suggest us how to improve StudyLib