Viral and parasitic dermatoses Gabriella Emri, Éva Remenyik Herpes simplex • primary herpes: erythematous plaque followed soon by grouped vesicles, secondary pustules, erosions, ulceration, fever, lymph node enlargement, maybe aseptic meningitis • recurrences: less severe, maybe lymph node enlargement • Precipitating factors: common cold, stress, menstruation, sunlight, fever, immunodeficiency, psychic influences, stomach upsets, trauma • Transmission: skin/skin, skin/mucosa, mucosa/skin contact • Diagnosis: clinical suspicion confirmed by Tzanck smear (multinucleated giant keratinocytes), culture, PCR, serology, histology (reticular epidermal degeneration, multilocular vesicles, intranuclear inclusion bodies) eczema herpeticum (Kaposi’s varicelliform eruption): atopic dermatitis, Darier disease, thermal burns, pemphigus vulgaris, ichthyosis, mycosis fungoides, not grouped, confluent erosions, on face, neck, trunk • Differential diagnosis: – aphthous stomatitis, hand-foot-and-mouth disease, herpangina, erythema multiforme maior – fixed drug eruption • Treatment: – acute (first 3 days!) • acyclovir 5x 200mg 5 days, • famcyclovir 3x 250 mg 5 days – recurrence (>6x per year) • acyclovir 3-2x 200mg 6 months • famcyclovir 2x 250 mg 5 days • topical: acyclovir, antibiotics Varicella-zoster virus Pathogenesis I. drop infection or direct contact infection and replication within resp. tract epithelial cells – primary viremia reticuloendothelial system - secondary viremia – exanthem and enanthem Varicella (chickenpox) vasculitis, eosinophil inclusion body (endothel, fibroblast, lymphatic endothel) balloon degeneration (epidermal cells) •macules, papules, vesicles surrounded by hyperemic halo, pustules, crusts simultaneously, vesicles on palate •begins on face and scalp, spreading inferiorly to trunk and extremities • Differential diagnosis: other viral infections, HSV, zoster, eczema herpeticum, impetigo, prurigo simplex subacuta, vasculitis, insect bite • 30% asymptomatic • Complications: aseptic meningitis/ meningoencephalitis (cerebellitis), pneumonia, polyradiculoneuritis (Guillain-Barre type), Reyesyndroma • In pregnancy: w13-20 fetal varicella syndroma, abortus, perinatal varicella • Therapy: ZnO-lotion, antiseptics, acyclovir, VZVimmunoglobulin • Vaccine: attenuated live virus Pathogenesis II. Sensory nerves – sensory ganglia – latent infection Sensory ganglia – viral replication – sensory nerve – exanthema Herpes zoster dermatomal pain, grouped vesicles on hyperemic edematous base Herpes zoster • Differential diagnosis: cardial, pleural disease, acute abdomen, vertebral disease, herpes simplex (viral culture), contact dermatitis, localized bacterial infection • 5 % headache, malaise, fever, lymphadenopathy • >50% throcacic, 10-20% trigeminal, 10-20% lumbosacral and cervical • Immunosuppressed: multidermatomal, recurrent, hemorrhagicnecrotic-gangraenous • Sensory and motor nerve changes: – Ramsay-Hunt syndrome: facial and auditory nerves involvement • Ophthalmic zoster: conjunctivitis, keratitis, scleritis, iritis • Postherpetic neuralgia 9% (4 ws-10 ys) • Dissemination in elderly or immunosuppr.(encephalitis 0,20,5%, pneumonia 1%) • Treatment: – antiviral (first 3 days!) • acyclovir 5x 800mg 7 days per os or 3x 510 mg/kg/d iv, • famcyclovir 3x500 mg 7 days – antibiotics – vitamin B – prednisone? (postherpetic neuralgia) – pain reliever (capsaicin) – topical: acyclovir, antibiotics, antiseptics Human papilloma viruses HPV-1 and HPV-4 HPV-6 and HPV-11 HPV-16 skin and plantar warts condylomata acuminata cervix carcinoma (E6→p53, E7→Rb) -Verruca vulgaris: hyperkeratotic, clefted surface, with reddishbrown dots -Verruca plana juvenile (Flat warts) -Condyloma acuminata (moist warts): HPV 16, 18, 31, 33; risk for SCC; subclinical: 5% acetic acid for 5 min Treatment of warts Exfoliative agents • salicylic acid+lactic acid in collodion • 40% salicylic acid, then collodion or liquid N2 • retinoic acid Condyloma: podophyllin 10-25% <0,5 ml per session 1-4 h 2x/w, podophyllotoxin Immunomodifiers alpha interferon, imiquimode Surgical: • Liquid nitrogen • Electrosurgery • Curettage • Laser Molluscum contagiosum (Molluscum contagiosum virus- poxvirus (DNA)): umbilicated, pearly-white papules; Treatment: Liquid nitrogen, Curettage Milker’s nodule and human Orf • Parapoxviruses • Nodular lesions on exposed sites – animals (cattle, sheep, goats, yaks, etc.), spontaneous resolution within 4-6 ws • Differential diagnosis: furunculosis, cat-scratch disease, cellulitis, erysipelas, erysipeloid, insect bite, swimming pool granuloma, leishmaniasis, pyogenic granuloma, bacillary angiomatosis • Therapy: symptomatic Virus induced (infectious) exanthems • Adenoviruses, CMV, enteroviruses (Coxsackie viruses, echovirus), EBV, flavivirus (dengue), HBV, HHV-6 (exanthem subitum, roseola infantum), HIV, orbivirus (Colorado tick fever), paramyxovirus (morbilli), parvovirus B19 (erythema infectiosum), reoviruses, respiratory syncytial virus, rhinovirus, rotaviruses, rubella virus • Erythematous macules, papules, perhaps vesicles, petechiae, usually head, neck, trunk, proximal extremities – Differential diagnosis: drug eruption, infectious mononucleosis with ampicillin or amoxicillin • Gianotti-Crosti sy.: Papular acrodermatitis of childhood Measles (morbilli): •Measles virus (paramyxovirus) •erythematous macules, papules, confluent on face, neck, shoulders, tiny bluishwhite papules with eryth. areola on buccal mucosa (Koplik’s spot), •initially on the forehead (4. febrile day), •exanthem fades in 4-6 ds with scaling Rubella (German measles): •Rubella virus •Pink macules, papules, confluent on trunk, petechiae on soft palate •1. day: Initially on the forehead, spreading inferiorly to face, trunk, and extremities, •2. day: faxial exanthem fades, •3. day: exanthem fades completely Erythema infectiosum (slapped-cheeks sy.): •Parvovirus B19 •Duration : 1 week •Other symptoms: joint pain, low grade fever Scabies • Sarcoptes scabiei (female mite) • Scabies incognito, Norwegian (crusted) scabies, nodular scabies • Distribution: lower abdomen, genital area, webs of the fingers, wrists • Transmission: skin to skin contact, clothing, bedding (might be nosocomial) • Incubation: 1 month • Dg.: clinical sign, microscopic examination • Diff. dg.: pyoderma, pediculosis, neurotic itching • Treatment: permethrin 5% cream, for 8-12 hs, treatment of close family, cleaning, antihistamins, steroid, benzyl benzoate Generalized intense, nocturnal pruritus, burrows, vesicles, nodules, secondary urticarial papules, eczematous plaques, excoriations, crust Pediculosis • Louse, Pediculus humanus capitis, P. h. corporis, Phthirus pubis • Lesions: lice bite, secondary due to itching (excoriations, pyogen superinfection, id reaction) • Transmission: skin to skin contact, clothing, bedding • Dg.: clinical signs • Diff. dg.: pyoderma, seborrheic dermatitis, scabies, neurotic itching • Treatment: permethrin, cleaning, antihistamins Cutaneous larva migrans: erythematous, serpiginous, papular or vesicular linear lesions, Ancylostoma brasiliense, A. caninum, Uncinaria stenocephala, Bunostomum phlebotomum, A. duodenale, Necator americanus; self-limited (4-6 ws); th.: thiabendazole, liquid N2 Leishmaniasis: single or multiple cutaneous papules at the site of a sandfly bite (face, arms and legs), often evolving into nodules and ulcers, heal spontaneously with depressed scar; diagnosis: clinical suspicion and histology AIDS Primary HIV infection (seroconversion) Group I Primary HIV >10 years Group II Asymptomatic phase Group III Generalized lymphadenopathy AIDS Death Group IV Symptomatic/AIDS Viral load CD4 lymphocyte levels 0 12 weeks 10 years Symptomatic phase of HIV-infection - AIDS Group IVA HIV wasting syndrome (AIDS) and constitutional disease Group IVB HIV encephalopathy (AIDS) and neurological disease Group IVC1 Major opportunistic infections specified as AIDS defining Group IVC2 Minor opportunistic infections Group IVD Cancers specified as AIDS defining Group IVE Other conditions Constitutional symptoms in HIV infection x Weight loss > 10% baseline x Fever lasting at least 1 month x Diarrhoea lasting at least 1 month AIDS-defining diseases: HIV-positivity+ • Protozoon-diseases: Toxoplasma-encephalitis, Cryptosporidium-enteritis, Pneumocystis carinii (jiroveci)-pneumonia • Mycotic diseases: Candida-oesophagitis, -tracheitis, -bronchitis, -pneumonia, Cryptococcus-meningitis, other extrapulmonary Cryptococcus-infection, Aspergillus infection (pneumonia, meningitis), disseminated or extrapulmonary Histoplasmosis, chronic intestinal Isosporidiosis • Bacterial diseases: recidiv Salmonella-sepsis, Tbc, recurrent septicaemia, pneumonia, meningitis, osteomyelitis, arthritis, internal organ abscesses (Haemophilus, Streptococcus, Staphylococcus aureus), disseminated or extrapulmonary atypical Mycobacterium (avium, kansasii) • Viral diseases: CMV (not liver-, kidney-, lgl. inv.), HSV-1, -2 (>1 month, ulcerated skin, mucosal inv., bronchitis, pneumonia, oesophagitis), progressiv multifocal leukencephalopathy, Papovavirus HIV-encephalopathy • Tumors: non-Hodgkin lymphoma, Kaposi-sarcoma, invasive cervix ca., HIVwasting sy. • <200 CD4+ T-lymphocyte/μl (US) Skin diseases in AIDS • Suspicious skin symptoms: – seborrheic dermatitis, molluscum contagiosum with exaggerated presentation; – sudden acute exacerbation of psoriasis; treatment failure e.g. against dermatophytosis • Marker skin symptoms: – seborrheic dermatitis, oral hairy leukoplakia >500 CD4+ cells/ μl; – giant mollusca, large non-healing perirectal ulcers (HSV) <50 CD4+ cells/μl • HIV-related skin disorders: – infectious diseases (opportunistic, mixed), – non-infectious diseases, – neoplastic diseases, – adverse drug reactions Infectious HIV-related cutaneous disorders • Viral infections – Exanthem of primary HIV infection (acute retroviral syndrome) – HSV – VZV – Poxvirus – HPV – CMV – EBV Infectious HIV-related cutaneous disorders • Bacterial infections – S. aureus: Bullous impetigo, ecthyma, folliculitis, abscesses; botryomycosis (chronic suppuration, atypical plaquelike lesions); pyomyositis – Pseudomonas (bacteremia, hot tube folliculitis) – H. influenzae (head and neck infections) – Mycoplasma salivarium, Bacteroides fragilis, Fusobacterium varium, F. necrophorum, Enterobacter cloacae – periodontal infections – Bacillary angiomatosis – Mycobacteria – Syphilis Infectiosus HIV-kapcsolt bőrbetegségek • Fungal infections – Candidiasis – Dermatophytoses – Systemic fungal infections – Pneumocystis jiroveci – Other Opportunistic systemic mycoses • Candidiasis (Candida albicans, Candida spp.) • Aspergillosis (Aspergillus fumigatus 90%, Aspergillus spp.) • Mucormycosis (Mucor spp., Rhizopus spp., Absidia spp., Cunighamella spp.) Primary systemic mycoses • Cryptococcosis – molluscum contagiosum-like, also in asymptomatic patients • Coccidioidomycosis – hemorrhagic nonspecific, in severely illed patients • Histoplasmosis – hemorrhagic, papular, ulceronecrotic • Primary infection: lung • Dg.: suspicious lesion → prompt biopsy → histology and culture; chemiluminescent DNA species-specific probes (rapid) – C. neoformans, C. immitis, H. capsulatum • Th.: amphotericin B, flucytosine, fluconazole, itraconazole Non-infectious HIV-related cutaneous disorders • Papulosquamous disorders – Seborrheic dermatitis – Psoriasis – Granuloma annulare – Reiter’s disease – Papular pruritic disorders – Eosinophilic folliculitis – Other: xerosis, ichthyosis, atopic dermatitis, pityriasis rubra pilaris Non-infectious HIV-related cutaneous disorders • • • • Hair and nail disorders Vitiligo Vasculitis Photosensitivity reactions – UV light hypersensitivity – PCT – CAD • Metabolic changes – Lipodystrophy (th-associated) – Malnutrition Neoplastic HIV-related cutaneous disorders • Cervical neoplasia – HPV-associated – Multifocal, quickly progressive, frequently recure in patients • Anal squamous epithelial cancer – HPV and immunosuppression • Non-Hodgkin’s lymphoma • Kaposi’s sarcoma • Other cancers: more agressive clinical outcome, predominant skin cancer is BCC • Chemotherapy: more drug-drug interactions, more severe neutropenia, more need for GM-CSF HAART • Highly active anti-retroviral therapy – 2 nucleoside or nucleotide RT inhibitors (NRTI) + PR inhibitor (PI) or non-nucleoside RT inhibitor (NNRTI) – AIDS or <200/μl CD4+: indicated, otherwise individual NRTI – zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, enofovir, emtricitabine, combivir, trizivir, truvada, epzicom NNRTI – nevirapine, delavirdine, efavirenz PI – saquinavir, indinavir, ritonavir, nelfinavir, amprenavir, lopinavir/ritonavir, atazanavir, fosamprenavir, tipranavir, darunavir • There is no proofreading function of RT, there is recombination among the RNA chains (diploid RNA genom) • 14% of new infections in USA, 10% in Europe show resistance to at least one inhibitor – New: fusion inhibitor enfuvirtide, integrase inhibitor raltregavir
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