Viral infections

Viral and parasitic
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
• Precipitating factors: common cold, stress,
menstruation, sunlight, fever, immunodeficiency,
psychic influences, stomach upsets, trauma
• Transmission: skin/skin, skin/mucosa, mucosa/skin
• 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
• 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
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
• Immunosuppressed: multidermatomal, recurrent, hemorrhagicnecrotic-gangraenous
• Sensory and motor nerve changes:
– Ramsay-Hunt syndrome: facial and auditory nerves
• 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
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
• 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
– Differential diagnosis: drug eruption, infectious
mononucleosis with ampicillin or amoxicillin
• Gianotti-Crosti sy.: Papular acrodermatitis of
Measles (morbilli):
•Measles virus
•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
Erythema infectiosum
(slapped-cheeks sy.):
•Parvovirus B19
•Duration : 1 week
•Other symptoms: joint
pain, low grade fever
• 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
• 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
Primary HIV infection (seroconversion)
Group I
Primary HIV
>10 years
Group II
Asymptomatic phase
Group III
Generalized lymphadenopathy
Group IV
Viral load
CD4 lymphocyte levels
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
– sudden acute exacerbation of psoriasis; treatment failure e.g. against
• 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
– Poxvirus
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
– 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
Non-infectious HIV-related cutaneous disorders
Hair and nail disorders
Photosensitivity reactions
– UV light hypersensitivity
• 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
• 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