Viral Skin Infections ICM I Summer 2009 Rich Callahan MSPA, PA-C Overview • • • • • Viral Warts Molluscum Contagiosum Herpes Simplex Varicella Herpes Zoster Viral Warts • Caused by Human Papilloma Virus (HPV) • Wide variety of presentations from subclinical infection to benign epithelial tumors of skin and mucosa • 150+ subtypes of HPV identified • Several subtypes associated with cancer pathogenesis – Squamous Cell Carcinoma (SCC) of skin, mucosa, cervix, etc Viral Warts - Pathogenesis • Virus ubiquitous in the environment – it is around us all the time • Spread by skin-to-skin contact or by contaminated surfaces. • Virus needs break in skin surface to enter and infect epidermis. • Virus occupies skin cells in an intracellular fashion, making immune recognition and response more difficult. • Compromised immune status (HIV, organ transplant) generally results in more widespread, significant infection. Genital Warts (Condyloma Acuminata) • Generally an STD, but not always • When seen in children, may or may not indicate sexual abuse • When seen around orifices (anus;vagina) important to investigate further as infection in rectum/vagina more likely to lead to squamous dysplasia and SCC Treatment of Warts • Most cases resolve spontaneously in 1-3 years. • Patient expectations prior to treatment extremely important – cutting, burning and freezing of warts does not guarantee a cure – visible warts can disappear and reappear as infection becomes subclinical • I never treat warts without discussing appropriate expectations first – warts can be one of the most stubborn diseases to treat! Treatment of Warts • Destructive treatment: Aim is to destroy skin cells occupied by virus in hopes of stimulation an immune response: • Liquid nitrogen cryotherapy • Electrodessication • Surgical removal • Canthacur/Podophyllin/Topical retinoids Treatment of Warts • Topical Chemotherapy: • 5-FU (5-Fluorouracil) – compound more rapidly absorbed by abnormally dividing infected keratinocytes causing premature cell death and clearance of warts • Treatment generally used for AK (precancers) but occasionally used on viral warts Treatment of Warts • Topical Immunotherapy: Geared towards stimulating a more pronounced immune response • Aldara (imiquimod) • DNCB and SADBE: Induce allergic reaction in skin (type IV delayed hypersensitivity) which summons lymphocytes to treated area in hopes of stimulation immune recognition and response Molluscum Contagiosum • Pox Virus • Red, pink or flesh-colored papules or nodules with characteristic central umbilication • Can be transmitted by direct skin-to-skin contact, fomites or autoinoculation • Adults/children who pick at them can literally spread hundreds around the body Molluscum Contagiosum • Generally seen in children or as sexually transmitted disease in adults • Ranges from classic presentation to mimicry of other diseases – can look a lot like acne if on the face. • Black dot sign: When lightly frozen by cryotherapy, lesions of molluscum exhibit characteristic black dot on superior aspect Molluscum Contagiosum Treatment • Physical Destruction – Electrocautery, curettage, cryotherapy, manipulation • Chemical destruction – cantharadin, topical retinoids • Immunotherapy – Aldara (imiquimod) • Unlike warts, treatment of molluscum stimulates brisk immune response with spontaneous resolution of all lesions in 4-6 weeks. In really stubborn/widespread cases must suspect immune compromise such as HIV disease • In rare cased, Cidofovir IV. Herpes Simplex Virus (HSV) • Where does the name come from? • Herpes – “creeping” or snake-like eruption • Simplex – uncomplicated compared to other blistering eruptions as generally confined to and recurrent in one area of body. • Two Strains of HSV: HSV 1 and HSV 2 • HSV 1 generally face/lips and HSV 2 generally genitals/anal area. • Virus doesn’t follow any rules: HSV 1 can appear on genital and HSV 2 can appear on face Herpes Simplex Virus (HSV) • On lips, also known as herpes labialis, cold sore or “fever blister” • On fingers, called herpetic whitlow • On wrestlers and other athletes, called herpes gladiatorum • Inside mouth, called herpes gingivostomatitis • Ocular HSV/Herpes facial paralysis • Remember, can occur anywhere! Herpes Simplex Virus (HSV) • HSV is a recurrent disease, which after initial exposure and infection, ascends peripheral sensory nerves to the nerve ganglion, where it then resides in a latent fashion • Virus contagious skin-to-skin contact or exposure to fluid from active blisters. Initial infection generally subclinical; asymptomatic • Virus then tracks down cutaneous nerves innervating affected area and becomes latent in nerve roots for indeterminate period of time, waiting for right set of circumstances (immune compromise) to reactivate HSV – Clinical Presentation • Great majority of HSV cases are recurrent, and present with symptoms localized to affected area. • In the rare case of a true symptomatic primary infection: Patient will have vesicles at inoculation site, with regional lymphadenopathy. • +/- malaise, fever, fatigue, myalgias, headache HSV – Clinical Presentation • Symptomatic infection starts with burning/tingling sensation in affected area • 12-24 hours later, erythematous macules/patches appear, soon followed by rapid development of painful, yellow, fluid-filled vesicles • Vesicles rupture 24-48 hours later leaving painful, crusted ulcerations and erosions. • Eruption usually clears in 7-10 days and re-enters period of asymptomatic latency. In some cases, can take up to 4 weeks for it to clear entirely HSV – Clinical Presentation • Most contagious in active phase when blister fluid present. • Small number of individuals asymptomatically shed virus from normal appearing skin in small quantities • Be careful about playing blame game: First clinical eruption can be preceded by 10+ years of subclinical infection, as is rare for primary infection to be symptomatic • Some studies of general population have shown that up to 75% of us carry antibodies to HSV! HSV – Clinical Presentation • Wide range in severity of eruption – not always classic, full-blown vesicular eruption • Can present as pruritic red macules and patches, or red papules mimicking acne vulgaris. • Majority of patients with HSV are asymptomatic carriers • Trigger factors for eruption: Physical/emotional stress, sunburn, trauma, concurrent skin disease, fever, menstruation HSV – Clinical Presentation • Remember: Location of clinical eruption doesn’t always correspond to that of primary infection. • For example: 1st symptomatic episode on buttocks – could be preceded by primary anogenital infection, as any skin innervated by a lumbrosacral ganglion is fair game. HSV - Diagnosis • Often a clinical diagnosis • Viral Culture for HSV 1/HSV 2 • Tzanck Smear (not used in my community that often) • Dermatopathology • Serology (takes 2 to 6 weeks to seroconvert HSV antibodies after primary infection) • Antigen detection/PCR: Expensive, but has just replaced Viral Cx at our institution as goldstandard diagnostic test. HSV – Treatment • Topicals: Acyclovir 5% ointment, Penciclovir 1% cream • Oral meds: Acyclovir, valcyclovir (valtrex), famciclovir (famvir) • For severe, disseminated infections: IV acyclovir, foscarnet HSV – Viral Shedding • Active HSV lesions shed virus into environment – highest viral counts in vesicle fluid • Areas of skin infected by HSV continue to shed virus even after infection clinically resolved HSV – Viral Shedding • Viral shedding rates highest in: • First year after acquisition of HSV and patients with frequent outbreaks • Duration of shedding longer in primary episode as compared with recurrences • Primary infection: ~12 days • Recurrence: ~2-5 days HSV – Viral Shedding • Treatment with oral antivirals greatly reduces amount/duration of viral shedding both after symptomatic episode and in patients prone to frequent outbreaks who shed more virus • It’s called daily suppressive therapy: • Valacyclovir (Valtrex) 500/1000mg daily • Famciclovir (Famvir) 250mg daily Varicella – “Chicken Pox” • VZV – Varicella Zoster Virus, What is it? • Common herpes virus infecting ~98% of human populations by adulthood • As primary infection resolves (chicken pox,) virus retreats to sensory nerve ganglia and enters period of latency. • VZV immunity declines with age, concurrent disease/malignancy, immune compromise – this allows VZV to re-activate as localized dermatomal infection called “shingles” or herpes zoster Varicella – “Chicken Pox” • ~90% of cases occur in children 10 y/o or younger. • Unusual in adults • Transmitted by respiratory contact with airborne droplets and direct skin-to-skin contact – highly contagious! • Incubation period 10-23 days • Epidemics in schools usually winter/spring VSV – Clinical Presentation • Presents as evolving rash composed of successive crops of papules and wheals which quickly evolve into yellow vesicles on an erythematous base – the so-called “dew drop on a rose petal.” • Lesions then evolve into pustules and crusts 12-24 later. • Crusts resolve in 1-3 weeks, can leave scars. VSV – Clinical Presentation • Distribution: Rash usually starts on face/scalp, then progress downwards to trunk/extremities. • Often affects mucous membranes • Often accompanied by mild fever and malaise • Infection can be more severe in adults, with potential severe prodrome and complication by Varicella pneumonia • Extremely pruritic = scratching = secondary bacterial infection • Greater age of patient = greater severity of primary infection VSV – Treatment • VSV vaccine: ~80% effective. Should be used in VSV negative adults, patients with immune compromise, childhood cancers. • In healthy children, symptomatic treatment with antipruritics and rest appropriate • In select cases: Oral/IV antivirals • Occasionally VSV secondarily infected with bacteria – treat accordingly Herpes Zoster • Commonly known as “shingles” • Reactivation of latent VSV in dorsal root or cranial nerve ganglion cells • ~66% of patients are > 40 years old • Lesions appear over several days, usually resolve in 2-4 weeks • Disease more severe/longer duration in immunocompromised patients Herpes Zoster • Severe HZ can be first sign of HIV of underlying malignancy (often Hodgkin’s disease) • Average adult has one episode over lifetime • Patients with multiple episodes over a short period of time indicate further investigation HZ - Presentation • Lesions often preceded by pruritis, tenderness and pain and/or neurologic changes such as hyperesthesia, dysesthesia and hypoesthesia • This pain often confused with Sciatica, renal/urinary stones, cholecystitis (gallbladder disease,) and pleural/cardiac disease • Neurologic symptoms can precede the eruption by 3-10 days HZ - Presentation • Lesions appear posteriorly, the progress in anterior direction, then to peripheral locations • Presents as grouped papules, vesicles, pustules and crusts on erythematous base • Lesions spontaneously heal in 1-2 weeks HZ - Presentation • 50% of cases involve thoracic nerves • 15-20% cervical or lumbar nerves • Remainder involve sacral and cranial nerve roots HZ - Presentation • Be wary of lesions presenting on nasal tip as this defines involvement of nasociliary branch of ophthalmic division of trigeminal nerve (CN V1) • ~33% of cases of ophthalmic zoster involve CN V1 • Ophthalmic Zoster can be extremely destructive to eyeball apparatus • Zoster with nasal tip involvement indicates immediate referral to ophthalmology for further investigation! • May need IV antivirals – let ophthalmology make that call! HZ - Diagnosis • Usually a clinical diagnosis based on characteristic prodromal symptoms and appearance • When it’s Zoster it usually looks/acts like zoster…..but when in doubt…. • Usually do viral culture for VSV • Can also do skin biopsy for histopathology, Tzanck smear, Antibody studies, etc. HZ - Treatment • Immunization ~80% effective (Zostavax) • Symptomatic treatment with lotions and antihistamines • Oral/IV antiviral treatments – the sooner initiated in course of illness the more effective they are! • Treatment of full-blown HZ rash won’t alter course that much • May occassionally need to treat secondary bacterial infection with oral/topical antibiotics PHN – Post Herpetic Neuralgia • Syndrome defined by pain and/or other neurologic symptoms within affected dermatome persisting beyond 4 of onset of skin lesions of HZ • Can last months to years beyond the illness itself • Severe pain during prodrome/onset of skin lesions highly predictive for PHN