Superficial fungal infection 15 October 2011 Dr. Cheng Tin-sik 鄭天錫醫生 Specialist in Dermatology & Venereology (Social Hygiene Service, CHP, DH) Clinical Assistant Professor (Hon.), CUHK 1 Superficial fungal infections 2 Prevalence: ~ 29.4 million cases Annual economic burden USD$1,953,000,000 in expenses USD$450,000,000 in indirect costs Ranked 4th among 22 skin disease groups evaluated in terms of direct costs USD$1.7 billion with 74% of costs attributable to prescription drugs an estimated average of 4,124,038 ± 202,977 annual visits during the study period (N.B. 2010: 308 million) • Dermatophyte infection • Superficial candidosis • one of the most common human infectious diseases in the world 3 genera: Trichophyton, Microsporum, Epidermophyton Involving the skin, nails, and mucous membranes of the mouth & vagina Candida albicans 80-90% Pityriasis versicolor Superficial fungal infection: Dermatophytosis 4 Practical tips for management (Dermatophyte infection) 5 Clinical features asymmetrical active margin with central clearing fungal infection elsewhere Investigation skin scraping nail clipping microscopy, culture or histology Direct examination 6 microscopy of skin, nail and hair specimens with 10% KOH simplest cheapest immediate identification of spores and hyphae e.g. confirms the dx of tinea capitis Differentiates btw endothrix or ectothrix infection Drawbacks of KOH microscopy Sensitivity: tinea capitis: 67 to 91% tinea pedis 73.3% (95% CI: 66.3 to 79.5%) Onychomycosis: 80% Low specificity: 42.5% (36.6 to 48.6%); 72% (onychomycosis) Unable to differentiate between dermatophytic / Nondermatophytic infections Direct examination - Stains 7 Staining increases sensitivity of direct examination by facilitating the visualization of fungal structures Stains that can be associated to clearing agents Chlorazol black E (CBE) stains only the fungal structures & excludes many artefacts KOH–CBE as sensitive as histopathologic analysis using PAS stain 94.3% vs. 98.8%, NS Blue–Black Ink permanent (Parker Quink) stains fungal elements in deep blue Congo red binds to polysaccharides of the fungal cell wall, particularly beta-D-glucans Fluorochromes Calcofluor white Most convenient binds to chitin may be used in KOH Fungal elements appear blue or green sensitivity significantly higher with calcofluor than with KOH fluorescence microscope 88% and 72%, respectively, P = 0.0116 (Abdelrahman et al) Tinea capitis 8 occurs predominantly in prepubertal children Source: infected puppies & kittens close contact with infected children Usually caused by Trichophyton tonsurans, Microsporum canis, Microsporum audouinii The causative agent varies in different geographical areas. In the USA and in some cities in the UK, T. tonsurans is the most common cause In Hong Kong, tinea capitis is usually caused by M. canis Pet exposure: associated with M. canis Tinea capitis 9 Three patterns of invasion: Ectothrix Arthroconidia found around the hair shaft Endothrix Arthroconidia within the hair shaft Favus Hyphae and air spaces found within the hair shafts caused by T. schoenleinii infection results in a honeycomb destruction of the hair shaft fluorescence under Wood’s light presence of pteridine Many species producing a small spore ectothrix pattern T. schoenleinii Tinea capitis 10 Clinical features: Itch Scalp scaling Irregular, patchy hair loss Lymphadenopathy More severe inflammatory responses: Erythema Pustules / Pustular boggy masses Crusting Scarring alopecia Id reaction: itchy papules around the outer helix of the ear Tinea capitis 11 Seborrhoeic pattern dandruff-like scaling on the scalp Prepubertal children p/w suspected seborrhoeic dermatitis on the scalp: presumed to have tinea capitis until proven otherwise Black dot pattern patchy alopecia with black stumps of broken hair shaft: due to breakage of hair near the scalp Kerion boggy masses covered with pustular folliculitis scarring may ensue afterwards Favus most frequently caused by T. schoenleinii yellow saucer-shaped adherent crusts made up of hyphae and spores occur around the hairs Tinea capitis 12 DDx Seborrhoeic dermatitis scaling of the scalp without significant hair loss Alopecia areata usually complete alopecia in the affected areas (vs patchy alopecia in T. capitis) little or no scaling or inflammation Exclamation mark hair Psoriasis usually more scaling is present. Traction alopecia stress on the hair & hair shaft by tight braiding Trichotillomania obsessive compulsive disorder of pulling one's own hair hair of various lengths & no scalp involvement Tinea capitis - Ix 13 scrape affected areas with a blunt scalpel blade to collect affected hairs, broken-off hair stubs, and scalp scale also pluck hairs from affected areas if possible not suitable for detecting carriers No abnormal areas to take scrapings Store at room temperature. No need to refrigerate If not possible / in an asymptomatic carrier brush with an unused toothbrush or cytobrush passing the brush through the hair ten times in the affected area in suspected carriers: different areas of the scalp send the brush for culture Tinea faciei 14 Asymmetric erythematous eruption Affecting the glabrous skin of the face the redness & the scaling border usu. less pronounced typical annular pattern frequently absent +/- pustules Clue: the presence of red borders which are well demarcated and are often serpiginous. Usually caused by T. rubrum or T. mentagrophytes var. mentagrophytes. Tinea faciei: DDX 15 Seborrhoeic dermatitis usually symmetrical and the lesions are not well demarcated. Photodermatitis usually symmetrical sparing areas that are relatively protected from the sun Perioral and contact dermatitis Rosacea Lupus erythematosus Acne vulgaris Psoriasis Tinea manuum 16 Diffuse hyperkeratosis of the palms and digits Involvement of palmar creases Usually affecting only one hand usually in a patient with tinea pedis resulting in ‘two feet and one hand syndrome’. +/- Tinea unguium of the involved hand Dermatophytes involved: the same as those for tinea pedis and tinea cruris T. rubrum, T. mentagrophytes, and E. floccosum Tinea manuum 17 Conditions confused with tinea manuum xerosis, eczema & chronic irritant contact dermatitis chronic scaling of the palms both palms usually involved & the border not well demarcated Psoriasis affecting the palms presence of well demarcated scaling plaques occurring bilaterally plaques more elevated & erythematous +/- lesions of psoriasis in other parts of the body Tinea corporis 18 dermatophyte infection of the glabrous skin of the trunk and extremities T. rubrum and T. mentagrophytes Pink-to-red annular or arciform patches and plaques scaly or vesicular borders expanding peripherally with a tendency for central clearing Inflammatory follicular papules may be present at the active border 19 Majocchi’s granuloma follicular epithelium grossly involved resulting in folliculitis in the setting of immunosuppression localized (e.g. a potent topical steroid) systemic immunosuppression Mainly caused by T. rubrum C/F: inflammatory papular, pustular or nodular lesions mainly on the limbs or face Tinea gladiatorum transmission of a dermatophyte infection from close skin-to-skin contact of athletes Tinea incognito Topical steroids modify the presentations of fungal infections the inflammatory response decreased well defined margins or scaling absent diffuse erythema +/- scales papules and pustules may be found T. corporis: 20 DDx Nummular eczema the coin-shaped lesions usually multiple & located on the extremities usually no central clearing Pityriasis rosea The herald patch is frequently mistaken for tinea Usu. followed by a generalized eruption within a few weeks Annular psoriasis usually thicker and more scaling than those of fungal infections Erythema annuulare centrifugum the scale is inside the elevated border Granuloma annulare no scaling and the border is more indurated Tinea cruris Flexural tinea usu. occurs in the groin N.B. 3 major causes of a groin rash: tinea cruris, candidiasis, intertrigo Rare in axillae or submammary folds Rare to extend onto the scrotum Infection from patient’s own feet Well defined patch with leading scaly edge Asymmetrical May extend to gluteal fold & buttocks 21 T. cruris: DDx Candidiasis Erythrasma Intertrigo Flexural psoriasis Seborrhoeic dermatitis Contact dermatitis Pseudoacanthosis nigricans Hailey-Hailey disease Extramammary Paget’s disease Langerhan’s cell histiocytosis 22 Tinea pedis 23 Interdigital type: erythema, scaling and maceration with fissures found in the web spaces Esp.between the 4th and 5th toes Moccasin type: diffuse scaling on the soles extending to the sides of the feet Ulcerative type: begins in the 2 lateral interdigital spaces extends to the lateral dorsum and the plantar surface of the arch The lesions of the toe webs are usually macerated and have scaling borders Vesiculobullous type vesicular eruptions on the arch or side of the feet are found Pompholyx like lesions on the hands are the classic dermatophytid reaction Tinea pedis 24 Dyshidrotic eczema & contact dermatitis frequently confused with the vesiculopustular type of tinea pedis the vesicles are usually smaller and rarely progress to pustules Other differential diagnoses eczema, soft corn juvenile plantar dermatosis Erythrasma bacterial infections e.g. pseudomonas Psoriasis/pustular psoriasis secondary syphilis Tinea unguium 25 dermatophytes & non-dermatophytes can cause onychomycosis yeasts or non-dermatophyte moulds: <10% Dermatophytes: ~90% of cases Toenail >fingernail infections usually tinea pedis +ve Tinea unguium Clinical presentations: 26 Distal and lateral subungual onychomycosis (DLSO): Discolouration, subungual hyperkeratosis, distal onycholysis start at the hyponychium spreading proximally Proximal subungual onychomycosis (PSO): Invasion of the nail unit under the proximal nail fold and spread distally usually associated with immunosuppressed conditions, e.g. HIV infection Superficial white onychomycosis (SWO): Invasion of the superficial layers of the nail plate but do not penetrate it leading to a white, crumbly nail surface Total dystrophic onychomycosis complete dystrophy of the nail plate Tinea unguium: specimen collection 27 Wipe with 70% alcohol before sampling. Superficial infection: scrape the surface of the nail with scalpel Nail clipping: sample the full thickness of the nail as proximal as possible Include the scrapings of s/u debris Put the samples into folded dark paper squares and store at room temperature Tinea unguium: investigations 28 Nail clippings / scrapings x fungal microscopy and culture Positive results: Dermatophytes: if either microscopy or culture is positive. Candida species: if both microscopy and culture are positive. Non-dermatophytes: if both microscopy and culture are positive on at least two samples taken at different times. Non-dermatophyte moulds: microscopy of nail specimens with 10% KOH rare causes of nail infection usually colonize nails as a secondary infection following trauma or an underlying dermatophyte infection. Sensitivity: 80%; Specificity: 72% Unable to differentiate between dermatophytic / Nondermatophytic infections Culture a few weeks for definite identification Sensitivity: 59%; Specificity: 82% false negative common culture identification complicated High false-negative rates Based on macroscopic & microscopic morphology and pigmentation dermatophyte isolates from patients on antifungal treatment generally do not show characteristic morphology on culture A negative test cannot definitively exclude fungal nail infection. Repeat if clinical suspicion high Periodic acid schiff (PAS) stain for the presence of dermatophytes higher sensitivity (vs. KOH preparations) Karimzadegan-Nia et al, 2007; Lawry et al, 2000; Weinberg et al, 2005 Non-dermatophyte moulds 29 comprise a large group of heterogeneous filamentous fungi usually considered saprophytic under suitable conditions, some of these species may cause true infections Nail invasion by NDM considered uncommon prevalence rates: ranging from 1.45% to 17.6% only a few species of moulds are regularly identified as causing onychomycosis Acremonium sp, Aspergillus sp, Fusarium sp, Onychocola canadiensis, Scytalidium sp and Scopulariopsis brevicaulis NDM: sensitive to cycloheximide use the Sabouraud’s dextrose agar without cycloheximide The criteria for establishing a diagnosis of NDM nail infection: 1) repeated isolation of the fungus on direct examination of well-sampled specimens 2) repeated positive culture of a species of fungus consistent with the finding on direct microscopic examination 3) failure to isolate dermatophytes in the culture Management of superficial fungal infection: Gerneral 30 principles General advice: e.g avoid sharing of towels and clothing; keep the affected areas cool and dry; frequent washing of clothes, linen; etc. Topical antifungals Advantages of topical antifungals vs oral antifungals Less risk of adverse effects Fewer drug interactions Laboratory tests not needed to monitor treatment Prolonged use of a steroid-antifungal cream may not cure the infection May cause striae Systemic treatment Tinea captitis & tinea unguium severe or extensive disease Failed topical treatment topical treatment may be tried in most other superficial fungal infections. Topical preparations for fungal infections 31 applied to the affected area for 2-4 weeks including a margin of several centimetres of normal skin Continue for 1 or 2 weeks after the last visible rash has cleared Azoles Bifonazole Clotrimazole (Canesten, Lotremin) Econazole Ketoconazole Miconazole (Daktarin) Sulconazole Tioconazole (Trosyd) Allylamine Terbinafine Naftifine Ciclopiroxolamine Polyenes Nystatin Thiocarbamates Tolnaftate Tolciclate Others Whitfield's ointment Undecylenic alkanolamide Tinea capitis: treatment 32 A +ve microscopy / +ve culture of skin scrapings recommended before starting treatment Griseofulvin 500 mg once daily or 250 mg BD; 10-25 mg/kg/d x 8–10/52; standard treatment in the pediatric population Terbinafine 250 mg once daily x 4/52 not licensed for tinea capitis in the UK FDA approved for children > 4 yr ( < 25 kg: 125 mg/d; 25-35 kg: 187.5mg/d; > 35kg: 250mg/d) Adjunctive treatment topical antifungal treatment 2x/week ketoconazole shampoo, selenium sulphide shampoo, or topical terbinafine cream during the first 2 weeks of treatment to reduce transmission. oral antibiotic e.g. flucloxacillin & an antifungal cream active against Gram (+) organisms (e.g. miconazole, clotrimazole, econazole) For secondary infection 33 Seven studies, 2163 subjects Subgroup analysis terbinafine was more efficacious than griseofulvin in treating Trichophyton species (1.616; 95% CI = 1.274- 2.051; P < 0.001) griseofulvin was more efficacious than terbinafine in treating Microsporum species (0.408; 95% CI = 0.254-0.656; P < 0.001) Both griseofulvin and terbinafine demonstrated good safety profiles in the studies. J Am Acad Dermatol 2011;64:663-70 Tinea capitis: Management of contacts 34 Contacts screened for clinically silent fungal carriage on the scalp: household members people closely associated with the infected person screening in schools is not necessary Asymptomatic carriers should be detected and treated Take samples for microscopy and culture Management: treat with selenium sulphide ketoconazole shampoo povidone iodine shampoo (shown to be more efficacious) people with a heavy growth / high spore count on brush culture may require oral antifungal treatment Tinea corporis / cruris 35 topical terbinafine (moderate evidence) & topical imidazoles (weak evidence) Efficacious in the treatment of fungal infections of the groin and body Insufficient trial evidence: superiority of one preparation over another imidazoles currently the most commonly used topical treatments for fungal infections of the skin For inflamed lesions topical antifungal combined with a mildly potent corticosteroid: <= 1 wk Do not give a corticosteroid preparation alone Combination preparation: beware of the increased risk of adverse effects with topical corticosteroids in occluded areas e.g. groins Tinea pedis: treatment 36 Allylamines, azoles, butenafine, ciclopiroxolamine, tolciclate & tolnaftate all efficacious relative to placebo in the treatment of tinea pedis Allylamines greater effectiveness when used for longer The effectiveness of azoles improved over time No difference in treatment failure rates between any of the individual azoles allylamines more efficacious than azoles The meta analysis of 8 trials and outcomes from 962 participants supports the finding that allylamines are more effective than azoles when applied for between 4 to 6 weeks 37 Terbinafine and itraconazole Terbinafine (two weeks treatment) more effective than itraconazole (two weeks treatment) Terbinafine more effective than no treatment (placebo) more effective than griseofulvin No significant difference in effectiveness found between: two weeks of terbinafine vs four weeks of itraconazole fluconazole vs either itraconazole or ketoconazole griseofulvin and ketoconazole different doses of fluconazole Recommendation: to treat initially with topical azoles and use topical allylamines for azole treatment failures Tinea unguium: treatment 38 Confirm the diagnosis before treatment positive microscopy or culture Mild and superficial TU: Superficial onychomycosis Mild distal onychomycosis Lateral onychomycosis topical tx with amorolfine 5% nail lacquer 6 /12 (fingernail) 9–12 /12 (toenail) Amorolfine 5% nail lacquer 1x/wk not approved in the USA 6% treatment failure rates found after 1 month of treatment data collected on a very small sample of people these high rates of success might be unreliable. Tinea unguium: treatment Ciclopiroxolamine 8% nail lacquer: QD Combining data from 2 trials of ciclopiroxolamine versus placebo: Treatment failure rates: 61% & 64% for ciclopiroxolamine These outcomes followed long treatment times (48 weeks) ciclopiroxolamine -> a poor choice for nail infections Butenafine 2%: treatment failure rate: 20% Used in combination with oral treatment: increase cure rates No good evidence from randomized controlled trials on other topical treatments for dermatophyte nail infections: Topical tioconazole / salicylic acid/ undecenoates. Topical treatments for fungal infections of the skin and nails of the foot. (Review) 22 Copyright © 2009 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Tinea unguium: treatment 40 Oral terbinafine 250 mg daily: 6/52 for F/N, 12/52 x T/N oral terbinafine may be more effective than oral itraconazole (weak evidence from RCTs) A meta-analysis of 18 studies: a mycological cure rate of 76%. fewer drug interactions vs. azole antifungals CYP2D6 inhibitor: inc. effect of TCA; Beta blockers & antipsychotics (possible) adverse effects: usually mild and transient Oral itraconazole 200 mg bd x 1 wk per pulse, 2 to 3 pulses oral itraconazole may be less effective than oral terbinafine (weak evidence from RCTs) A meta-analysis of 6 studies on pulse itraconazole: mycological cure rate of 63% Pulsed therapy recommended: no good evidence that it is less effective than continuous therapy; risks of adverse effects may be reduced N.B. this dosing regimen is not licensed Take with fatty meal/ acidic beverage Pityriasis versicolor 41 Commensal yeast: Malassezia species occurs most frequently in hot and humid tropical climates also prevalent in temperate climates Malassezia has an oil requirement for growth increased incidence in adolescents predilection for sebum-rich areas of the skin use of bath oils and skin lubricants may enhance disease development Pityriasis versicolor occurs when the budding yeast form transforms to the mycelial form Various factors implicated: e.g. hot and humid environment, oily skin and excessive sweating. 42 Multiple white, pink to brown, oval to round coalescing macules and patches mild and fine scaling mainly found on the seborrhoeic areas especially the upper trunk and shoulders also found on the face, scalp, antecubital fossae, submammary regions and groins often confluent and quite extensive Flexural areas: sometimes referred to as ‘inverse’ pityriasis versicolor Associated scale may be shown by scratching of the skin surface Produce chemicals that reduce the pigment in the skin, causing whitish patches azelaic acid, pityriacitrin and malassezin ability of the fungus to filter sunlight and the screening effect of tryptophan-dependent metabolites absence of pigmentation in exposed areas 43 Wood's light: a yellow-green fluorescence may be observed in affected areas due to pityrialactone Skin scrapings x microscopy (KOH): clusters of yeast cells and long hyphae like "spaghetti and meatballs“ Malassezia species: difficult to grow in the laboratory scrapings may be reported as "culture negative“ grows best if a lipid such as olive oil added to Littman agar culture medium Malassezia species 44 Pityriasis versicolor not considered to be contagious Infection not due to poor hygiene Inhabit the skin of about 90% of adults without causing harm suppresses the expected immune response to it in some: allowing it to proliferate & cause a skin disorder often without any inflammatory response. Malassezia 45 Members of the genus Malassezia formerly classified as Pityrosporum species P. ovale (oval cells) and P. orbiculare (round cells) Malassezia is the correct name for this genus Identification of isolates from pityriasis versicolor (PV) using the new nomenclature: the causal species more likely to be M. globosa or M. sympodialis Malassezia furfur believed to be the causal organism of PV prior to the description of the new species in 1996 Malassezia furfur Malassezia sympodialis Malassezia globosa Malassezia restricta Malassezia obtusa Malassezia slooffiae Malassezia pachydermatis Malassezia yamatoensis Malassezia dermatis Malassezia nana Malassezia japonica Treatment 46 Treat with shampoo Ketoconazole 2% shampoo once-daily to affected areas for 5/7 Selenium sulphide 2.5% shampoo once-daily to the affected areas for 7 days. off-label indication may cause skin dryness and irritation Smell: unpleasant Lather and leave it on for 10’ then rinse off For small affected areas: Imidazole creams 2–3 weeks Lather and leave it on for 5’ then rinse off e.g. clotrimazole, econazole, ketoconazole, or miconazole Systemic Treatment: itraconazole 200 mg once daily for 7 days fluconazole 50 mg once daily for 2–4 weeks (licensed) or a 300 mg dose once weekly for 4 weeks (off-label). consider prophylactic treatment e.g. prior to exposure warm humid environments or sunshine ketoconazole 2% shampoo once daily x a maximum of 3 days prior to sun exposure limited evidence that weekly or monthly doses of oral antifungals are effective in preventing recurrence, but optimal regimens have not been established Candidiasis Cutaneous candidosis less common than dermatophytosis Candida species capable of producing skin and mucous membrane infections ~200 species ~20 of them associated with human or animal infections e.g. C. albicans, C. tropicalis, C. glabrata, C. parapsilosis, C. krusei, C. guilliermondii C. albicans accounting for most of the infections found among the commensal flora of the diseased skin, mouth, vaginal tract, and gastrointestinal tract 48 Become a pathogen in predisposed conditions e.g. infancy, pregnancy, occluded sites, diabetes, Cushing’s syndrome, immunosuppression, imbalance in the normal microbial flora, etc Predisposing factors: Large skin folds retain heat & moisture: environment suited for yeast infection E.g. older women with pendulous breasts, obese patients with overhanging skinfolds Hot, humid weather; tight or abrasive underclothing; DM, poor hygiene. Inflammatory diseases in skinfolds e.g. psoriasis and the use of topical steroids favour yeast growth within fold areas 49 Rash: red, macerated and well demarcated surrounded by satellite papules and pustules A fringe of moist scale might be found at the border In the skin, pustules are formed dissect under the stratum corneum peeling it away resulting in a red, denuded/macerated, glistening surface with a long, cigarette paper-like, scaling and advancing border Pustules rupture to form a superficial collarette of scale Rash: sore rather than itchy. Usually found in the intertriginous skin folds and other moist, occluded sites genital area / area covered by diaper flexures, e.g. the groin, axillae, finger & toe webs In diaper dermatitis caused by Candida bright red plaques in the inguinal and gluteal folds and satellite pustules may be found Candidal infection is a frequent cause of chronic paronychia manifesting as painful periungual erythema and swelling associated with secondary nail thickening, ridging and discoloration. Oropharyngeal candidiasis 50 white plaques and pustules on oral mucosal surface leaving a raw, bleeding base when removed mechanically Candida balanitis more commonly found in the uncircumcised usually presents with red patches, swelling and tiny pustules Candida vulvovaginitis usually causing itchiness and soreness, a curd-like discharge, pustules, erythema and oedema of the vagina and vulva are found Perianal candidiasis: Pruritus ani & maceration usually found Chronic mucocutaneous candidiasis associated with a hetererogeneous group of autoimmune, immunologic and endocrinologic diseases characterized by recurrent or persistent superficial candidal infections due to an impaired cell-mediated immunity against Candida species 51 DDX of cutaneous candidiasis includes tinea, intertrigo, erythrasma, seborrhoeic dermatitis, psoriasis, etc. Investigations Microscopy: pseudohyphae and yeast forms Isolation of the fungus in culture & its identification In patients with recurrent candidiasis Test for diabetes mellitus & other conditions producing immunosuppression Candidiasis: management General: drying, weight reduction, air-conditioning Nystatin cream or topical imidazole cream BD If perianal skin involved: + Nystatin 100,000 units QID for 5/7 oral fluconazole treatment 50 mg daily for 2 weeks Useful in resisitant cases and for extensive or severe candidiasis 52 THE53END THANK YOU