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  1. Viral DiseasesPart 1 Michael Hohnadel KCOM 11/25/03

  2. Herpesvirus Group • Double stranded DNA virus which replicates in the nucleus. • Produces latent, lifelong infection. • Includes:VZV, HSV, CMV, EBV, Human Herpes virus – 6, -7, -8. Animal Virus.

  3. Herpes Simplex • One of most prevalent infections worldwide. • 85% of adults are seropositive for HSV-1. • 20% adults seropositive for HSV-2. • More are infected than symptomatic disease would indicate. • 50% HSV-1 infected individuals asymptomatic. • 20% HSV-2 individuals asymptomatic. • 60% of others do not recognize symptoms as those of HSV-2.

  4. Herpes Simplex • Diagnosis • Tzanck Smear: • 60-90% accurate, 3-13 % false + • Nonspecific (HSV and VZV) • Used on acute vesicular lesions • Multinucleated giant cells jig saw nucleus. • D. I. F. • More accurate • Identifies virus type. • Viral culture • PCR • Biopsy with immunoperoxidase

  5. Tzanck Smear Multinucleated giant cell

  6. Herpes Simplex • Serologic testing • Not used to determine if skin lesion is HSV. • Only indicates infection, not cause of lesion. • High background positive. • Used if need to know if previously infected • Treatment: • Acyclovir, Valacyclovir. • Action : Acyclic nucleoside analog of guanosine which inhibits HSV DNA polymerase.

  7. Orolabial Herpes • 95 % HSV –1 • Presentation: Grouped vesicles on an erythematous base. • May occur anywhere inoculated. • Often prodrome of tingling or itching. • Variable severity of recurrent lesions. • Mild flu like symptoms may be present. • UVB exposure frequent trigger. • Herpetic Gingivostomatitis • 1 % of infections • Erosions , ulcers in mouth with white base associated with fever, lymphadenopathy and malaise.

  8. Orolabial Herpes

  9. Orolabial Herpes • Treatment: • Prevention with sun block and UVB avoidance. • Acyclovir 200mg bid. • Acyclovir 200mg 5x / day • Prophylaxis for dermabrasion, chemical peels, laser resurfacing.

  10. Herpetic Infections • Herpetic Sycosis • blade shaving after facial herpes induces a slowly spreading folliculitis of the beard with few isolated vesicles. • Herpes Gladiatorum • Herpetic whitlow • Herpetic infection of the fingers. • Healthcare workers, children (thumb sucking) • Adults: 2/3 cases HSV-2, Children nearly 100% HSV-1

  11. Herpetic Infections

  12. Herpetic Whitlow

  13. Herpetic Infections • Herpetic Keratoconjunctivitis • Punctate keratitis or as dendritic ulcers. • Common cause of vision impairment in the U.S. • Topical Corticosteroids may cause corneal ulceration. • Recurrences are common.

  14. Herpetic Keratoconjunctivitis

  15. Herpetic Infections • Recurrent Erythema Multiforme Minor • H.A.E.M. caused by HSV-1 in most cases. • Presentation: Papules some of which become classic E.M. target lesions of palms, elbows, knees and oral mucosa. • Atypical lesions: 3% multiple or solitary large red painful plaques, subcutaneous nodules or asymmetric targets. • Chronic Acyclovir to prevent.

  16. Erythema Multiforme Minor

  17. Genital Herpes • Infection of HSV-2 in 85% of cases. • Spread by Skin to Skin contact • Active lesions are infective • Asymptomatic shedding accounts for the majority of transmission. • Prior HSV-1 infection does not protect from HSV-2 infection but may lessen severity of first outbreak. • Primary infection: • Grouped vesicles which appear for 7-14 days. • Fever, Flu like symptoms, inguinal lymphadenopathy, proctitis if rectal involvement.

  18. Genital Herpes

  19. Genital Herpes • Recurrent lesions with typical prodrome of burning/itching followed by the formation of grouped vesicles which form erosions and heal without scarring over 7 days. • HSV-2 facts: • 20% truly asymptomatic, 20% recognize their lesions, 60% have lesion but don’t recognize them as HSV or don’t notice them at all. • Recurrences are common (6 / year).

  20. Genital Herpes - Treatment Primary Lesions Acyclovir 200-400 mg five times/ day. Also, Valacyclovir 1000 mg bid. Recurrent lesions ( >6 lesions/ year) • Acute lesions • Acyclovir 200mg 5 times daily. Also, Valacyclovir 500 mg bid. • Suppressive therapy • Acyclovir 400 mg bid or tid suppresses 85 % of recurrences. 20 % recurrence free during TX. • Also Valacyclovir 500 mg QD (1000 mg QD if > 10 recurrences / year.) • After 10 years of suppressive TX, many pts can stop medication and retain a reduction in number of lesions.

  21. Intrauterine and Neonatal Herpes • Prevalence 1500 – 2000 cases / year. • 70 % HSV-2 acquired at time of delivery. • Intrauterine infection (rare) • Primary lesions of mother • May cause fetal anomalies: skin lesions, scars, microcephally, microphthalamos, encephalitis, calcifications. • Almost always permanent sequelae. • HSV-1 acquired through postnatally by contact with orolabial disease.

  22. Intrauterine and Neonatal Herpes • Extent of initial involvement predicts outcome: • Localized: rarely fatal. 10% with long term sequelae • Disseminated disease fatal 15-20%. If brain dissemination, 50% with long term sequelae. • Presentations in newborns • 70% present with skin vesicles. Incubation of 3 wks, vesicles may appear after discharge. • Disseminated herpes with CNS involvement may occur without skin involvement. • 20% of cases never have vesicles. • TX: Acyclovir 250 mg/(m)^2 q8 hours x7 days

  23. Neonatal Herpes

  24. Neonatal Herpes

  25. Intrauterine and Neonatal Herpes • Prevention and management: • 70% of mothers of HSV infected infants are asymptomatic at delivery and have no HX of infection. • Primary vs secondary infection at time of delivery as well as active lesions important. • Active recurrent lesion 2-5% risk of HSV infection. • Active primary lesion 33-50% risk of HSV infection. • If active lesions at time of delivery then C-section. • Pregnancy with HSV infection controversial: • Routine cultures not recommended. • Avoid scalp electrodes. • HSV-1 more frequently transmitted. • If primary lesion during pregnancy – Acyclovir during 3rd trimester.

  26. Disseminated HS infection • Newborns, premature, malnourished, Immnosup. and children to age 3 years are at risk. • Presentation: Severe herpetic gingivostomatitis followed by dissemination to viscera esp. the liver, lungs and GI and brain. • Death possible • TX Acyclovir

  27. Eczema Herpeticum • Also called Kaposi’s Varicelliform eruption. • Herpes infection in pt with atopic dermatitis results in infection throughout the eczematous areas with hundreds of vesicles. • Also occurs in: Dariers, pemphigus, pemphigoid, Wiskott-Aldridge or burns. • Self limited in healthy individuals. • TX: IV or oral acyclovir in all cases

  28. Eczema Herpeticum

  29. Eczema Herpeticum

  30. Herpes Simplex in theImmunocompromised • Any erosive mucocutaneous lesion should raise suspicion of herpes simples. • Often less vesicular and more erosive with crusting • Hallmarks: 1.) Pain 2.) active vesicular border 3.) scalloped periphery. • Extensive involvement. • Tzanck smears less valuable (erosions) • DIF is specific and rapid if needed. • TX: Acyclovir. Consider suppressive therapy • Acyclovir resistance cases: foscarnet

  31. Immunocompromised

  32. Immunocompromised

  33. Varicella • Infection with Varicella Zoster • Transmission by contact or respiratory route. • Initially virus seeds the internal organs at 4-6 days. At 11-20 days the skin eruption occurs. • Individuals are infectious 4 days before and 5 days after exanthem appears. • In adults 30.9 / 100,000 death rate.

  34. Varicella • Presentation: Faint erythematous macules develop into teardrop vesicles in 24 hours. Fresh crops of vesicles appear for several days on trunk, face or oral mucosa. Vesicles become pustular, umbilicated and crusted. Number of lesions averages about 300. • Secondary bacterial infection may result in scarring. • Other complications: • Pneumonia: neonates and adults (1/400) • Reyes syndrome: encephalitis, hepatitis with aspirin use. • Thrombocytopenia • Purpura Fulminans: DIC with low proteins C and S

  35. Varicella

  36. Varicella

  37. Varicella

  38. Varicella • Treatment: • Acyclovir for severe cases, high risk individuals and adults (>13 years). • No Aspirin!!! • Topical Antipruritics • Isolate from immunocompromised.

  39. Varicella Prevention: • Varicella Vaccine • Live attenuated virus • 95% effective • Those who do contract varicella have mild case. • At present immunity appears to be lasting. • Modified Varicella-like syndrome (MLSV) • 15 days after exposure to varicella virus. • 35-50 macules and papules, few vesicles. • Mild, afebrile course lasting 5 days

  40. Varicella in Pregnancy • Increased risk of spontaneous abortion (3% by 20 wks), congenital varicella syndrome and fetal death. Possible increase in pre-term labor. • Mother at increased risk for varicella pneumonia. • Congenital Varicella Syndrome • Hypoplastic limbs, scars, ocular and CNS disease. • F > M • 1-2% risk, highest between weeks 13 and 20.

  41. Congenital Varicella Syndrome

  42. Varicella in Pregnancy • Fetal infection may result in Herpes Zoster early in life (<2 yrs). • Occurs in 1% of VZ complicated pregnancies with highest risk at wks 25-36 wks gestation. • Prevention: VZIG for non-immune pregnant mothers within the first 72-96 hours of exposure. • Use only with proven seronegativity. Only 20% of those who relate neg. HX of VAR infection earlier in life are seronegative.

  43. Varicella in Pregnancy Neonatal Risk • Mother who develops varicella 5 days before to 2 days after childbirth places newborn at risk for severe varicella. • Virus acquired transplacentally before mother has produced antibodies. Newborns immune system is very vulnerable. • Treatment: VZIG and Acyclovir • No treatment mortality 30%

  44. Varicella in the Immunocompromised • May result severe and protracted infections. • Consider in cancer, AIDS and for those on systemic steroids or other immunosuppressive meds. • More numerous lesions, more necrotic lesions, Large lesions. • Prior infection is not protective • Non dermatome distribution may indicate reactivation. • Before TX available, 1/3 of children with cancer developed complications of varicella and 7% died.

  45. Varicella in the Immunocompromised • Treatment and Prevention • VZIG • Given within 96 hours after high risk exposure • Household contact with VZ, face to face/5 min contact, Indoors with VZ for 1 hour. • Reduces severity of infection, not frequency. • No proven value once clinical disease develops. • Varicella vaccination before anticipated immunosuppression is helpful • Acyclovir • IV acyclovir given until two days after new vesicles stop appearing. In HIV cases, until vesicles have healed. • Also: Valacyclovir, Famciclovir. • Crucial to give for adequate time in adequate dose to prevent resistance.

  46. Herpes Zoster • Reactivation of latent herpes zoster infection from the dorsal root ganglia • Over 1-5 days new lesions develop. These become pustular and crust. • Typically along a dermatome with some overflow to adjacent dermatomes. • Preceded by pain, itching several days • Duration of the lesion is dependent on: • Age. Young = 2-3wks, Older = 5-6wks • Severity of lesions • Immunosuppression • Incidence of H.Z. increases with age (esp>50 yrs) and immunosuppression.

  47. Herpes Zoster

  48. Herpes Zoster • Heals without scaring in young. Increased incidence of scaring in elderly and severe eruptions. • Subtypes of Herpes Zoster Disseminated Zoster • Defined as >20 vesicles outside dermatome. • Chiefly elderly or Immunocompromised • Hemorrhagic/gangrenous lesions with outlying vesicles or bullae. • Systemic symptoms include fever, H.A., meningeal irritation. Rarely, encephalitis.

  49. Disseminated Herpes Zoster

  50. Herpes Zoster Zoster Subtypes (Continued) Ophthalmic Zoster • Involvement of fifth cranial nerve, ophthalmic branch • Lesion location verses eye involvement: • If tip/side of nose ‘Hutchinson’s sign’, eyeball affected 76 % vs 34 % if not involved. • If lid margin affected virtually 100 % involvement. • Ocular complications: • Uveitis 92 % • Keratitis 50 % • Less common: glaucoma, optic neuritis, retinal necrosis • Other: encephalitis • Lesions tend to reoccur (as long as ten years). • Ophthalmology consult.