Hhv

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  • Pityrasis rosea – caused by HHV 6 and HHV 7
  • Small pox
  • Hhv

    1. 1. Viral Infections of SKIN AND MUCOSA I AAU-MF Dept. of Dermato-venereology
    2. 2. HUMAN HERPESVIRUSES • Human herpesviruses (HHVs) (family Herpesviridae) are defined by the architecture of the virion,which has: Core containing a linear double-strand DNA • Icosahedral capsid 100–110 nm in diameter composed of 162 capsomers Envelope containing viral glycoprotein spikes on the surface. • Worldwide, 60–90% of the population is infected with one or more HHVs.
    3. 3. Eight HHVs have been identified: ▪ Herpes simplex virus (HSV)-1 (HHV-1) ▪ HSV-2 (HHV-2) ▪ Varicella-zoster virus (VZ V, or HHV-3) ▪ Epstein-Barr virus (EBV, or HHV-4) ▪ Cytomegalovirus (CMV, or HHV-5) ▪ HHV-6 ▪ HHV-7 ▪ HHV-8 (Kaposi sarcoma–associated virus). • Primary HHV infections are usually asymptomatic with the exception of VZV, which nearly always presents with symptomatic varicella.
    4. 4. After primary infection, HHVs remain latent in neural or lymphoid cells and reactivate if an adequate immune response does not exist. HHVs are categorized into three groups: Alpha, beta, and gamma Herpesviridae ▪ Alpha Herpesviridae : HSV-1, HSV-2, VZV are characterized by a variable host range, relatively short reproductive cycle, rapid spread in culture, rapid destruction of infected cells, and latent infection primarily, but not exclusively, of sensory ganglia.
    5. 5. Beta Herpesviridae : CMV has a restricted host range and spreads slowly in cultures. Gamma Herpesviridae : EBV, HHV-6, HHV-7, HHV-8, and herpes virus saimiri are lymphotropic, specific for either T or B lymphocytes. The HHV-8 DNA sequences are closely homologous to minor capsid and tegument protein genes of gamma herpesviridae EBV and herpesvirus Saimiri.
    6. 6. HERPES SIMPLEX VIRUS (HSV) INFECTION • Whether first-symptomatic or recurrent, may “typically” present clinically with grouped vesicles arising on an erythematous base on keratinized skin or mucous membrane. • Most HSV infections are “atypical,” with patch(es) of erythema, small erosions, fissures, or subclinical lesions that shed HSV. • Once an individual is infected, HSV persists in sensory ganglia for the life of the patient, recurring with lessening in immunity.
    7. 7. • Age of Onset Most commonly young adults; • range, infancy to senescence. • Etiology HSV-1, HSV-2. • Labialis: HSV-1 (80–90%), HSV-2 (10–20%). • Urogenital: HSV-2 (70–90%), HSV-1 (10–30%). • Herpetic whitlow: <20 years of age usually HSV-1; >20 years of age, usually HSV-2. • Neonatal: HSV-2 (70%), HSV-1 (30%).
    8. 8. Transmission • Most transmission occurs when persons shed virus but lack lesions. • Usually skin-skin, skin-mucosa, mucosa-skin contact. Herpes gladiatorum transmitted by skin to-skin contact in wrestlers. • Increased HSV-1 transmission associated with crowded living conditions and lower socioeconomic status
    9. 9. Immunocompromising Factors Predisposing to HSV Reactivation • HIV/AIDS infection, • Malignancy (leukemia/lymphoma), • Transplantation (bone marrow, solid organ), • Chemotherapy, • systemic glucocorticoids, • other immunosuppressive drugs, • Radiotherapy
    10. 10. PATHOGENESIS • Primary HSV infection occurs through close contact with a person shedding virus at a peripheral site, mucosal surface, or secretion. • HSV is inactivated promptly at room temperature; aerosol or fomitic spread unlikely. • Infection occurs via inoculation onto susceptible mucosal surface or break in skin. • After exposure to HSV, the virus replicates in epithelial cells, causing lysis of infected cells, vesicle formation, and local inflammation.
    11. 11. After primary infection at inoculation site, HSV ascends peripheral sensory nerves and enters sensory or autonomic nerve root (vagal) ganglia, where latency is established. • Retrograde transport of HSV among nerves and establishment of latency are not dependent on viral réplication in skin or neurons; neurons can be infected in the absence of symptoms
    12. 12. • Latency can occur after both symptomatic and asymptomatic primary infection. Periodically, HSV may reactivate from its latent state and virus particles then travel along sensory neurons to skin and mucosal sites to cause recurrent disease episodes. • Recurrent mucocutaneous shedding can be associated with or without (asymptomatic shedding) lesions; virus can be transmitted to a new host when shedding occurs.
    13. 13. LABORATORY EXAMINATIONS • Direct Microscopy Tzanck Smear • Optimally, fluid from intact vesicle is smeared thinly on a microscope slide, dried, and stained with either Wright or Giemsa stain. Positive, if acantholytic keratinocytes or multinucleated giant acantholytic keratinocytes are detected. • Positive in 75% of early cases, either primary or recurrent.
    14. 14. Antigen Detection DFA Monoclonal antibodies, specific for HSV-1 and HSV-2 antigens, detect and differentiate HSV antigens on smear from lesion. Cultures: Positive HSV cultures from involved mucocutaneous site or tissue biopsy specimens. Serology • Antibodies to glycoprotein (g)G1 and (g)G2 detect and differentiate past HSV-1 and HSV-2 infections.
    15. 15. • Primary HSV infection can be documented by demonstration of seroconversion. • Recurring herpes can be ruled out if seronegative for HSV antibodies. Polymerase Chain Reaction: To determine HSV-DNA sequences in tissue, smears, or secretion.
    16. 16. DIAGNOSIS:- Clinical suspicion confirmed by viral culture or antigen detection. Cultures used for diagnosing first-episode infections since antibodies to (g)H1 or (g)G2 may take 2–6 weeks to develop.
    17. 17. MANAGEMENT • Prevention:- Skin-to-skin contact should be avoided during outbreak of cutaneous HSV infection. • Topical Antiviral Therapy:- • Approved for herpes labialis; minimal efficacy. • Acyclovir 5% ointment Apply q3h, 6 times daily for 7 days. Approved for initial genital herpes and limited mucocutaneous HSV infections in immunocompromised individuals. • Penciclovir 1% cream Apply q2h while awake for recurrent orolabial infection in immunocompetent individuals.
    18. 18. Oral Antiviral Therapy • Drugs for oral HSV therapy include acyclovir, valacyclovir, and famciclovir. Valacyclovir, the prodrug of acyclovir, has a better bioavailability and is nearly 85% absorbed after oral administration. Famciclovir is equally effective for cutaneous HSV infections. Antiviral agents more effective in treating primary infections than recurrences
    19. 19. Acyclovir 400 mg 3 times daily or 200 mg 5 times daily for 7–10 days Valacyclovir 1 g twice daily for 7–10 days Famciclovir 250 mg 3 times daily for 5–10 days Recurrences Most episodes of recurrent herpes do not benefit from pulse therapy with oral acyclovir. In severe recurrent disease, patients who start therapy at the beginning of the prodrome or within 2 days after onset of lesions may benefit from therapy by shortening and reducing severity of eruption; however, recurrences cannot be prevented.
    20. 20. Chronic suppression:- Decreases frequency of symptomatic recurrences and asymptomatic HSV shedding. After 1 year of continuous daily suppressive therapy, acyclovir should be discontinued to determine the recurrence rate. Acyclovir 400 mg twice daily Valacyclovir 500–1000 mg per day Famciclovir 250 mg twice daily
    21. 21. Mucocutaneous disease in immunocompromised:- Patients with herpes who do not respond to the individuals recommended dose of acyclovir may require a higher oral dose of acyclovir, IV acyclovir, or be infected with an acyclovir- resistant HSV strain, requiring IV foscarnet. Acyclovir 5 mg/kg IV q8h for 7–14 days, or 400 mg 5 times daily for 7–14 days Neonatal:- Acyclovir 20 mg/kg IV q8h for 14–21 days
    22. 22. Herpes simplex virus: positive Tzanck smear
    23. 23. Herpes simplex virus infection: herpetic whitlow
    24. 24. Herpes simplex virus infection: eczema herpeticum on eyelids
    25. 25. VARICELLA ZOSTER VIRUS INFECTIONS • Varicella zoster virus (VZV) is a human herpesvirus that infects 98% of adult populations. • Primary VZV infection (varicella or chickenpox) is nearly always symptomatic and characterized by disseminated pruritic vesicles. • During primary infection, VZV establishes lifelong infection in sensory ganglia.
    26. 26. When immunity to VZV declines, VZV reactivates within the nerve cell, traveling down the neuron to the skin, where it erupts in a dermatomal pattern, i.e., herpes zoster (HZ), or shingles. In the immunocompromised host, primary and reactivated VZV infection is often more severe, associated with higher morbidity rates and some mortality. VZV vaccine has reduced the incidence of varicella and herpes zoster.
    27. 27. Age of Onset • Without immunization, 90% of cases occur in children <10 years, <5% in persons older than 15 years. • With immunization (Varivax), the incidence is markedly reduced. Etiology • VZV, a herpesvirus. • Structurally similar to other herpesviruses: Lipid envelope surrounding nucleocapsid with icosahedral symmetry. Centrally located double-strand DNA with a molecular weight of 80 million
    28. 28. Transmission • Airborne droplets as well as direct contact • Indirect contact uncommon • Patients are contagious several days before varicella exanthem appears and until last crop of vesicles • Crusts are not infectious. • VZV can be aerosolized from skin of individuals with herpes zoster, which is about one-third as contagious as varicella, causing varicella in susceptible contacts.
    29. 29. PATHOGENESIS • In varicella, VZV is thought to enter through mucosa of upper respiratory tract and oropharynx. • Followed by local replication and primary viremia. • VZV then replicates in cells of reticuloendothelial system with subsequent secondary viremia and dissemination to skin and mucous membranes. • Localization of VZV in the basal cell layer is followed by virus replication, ballooning degeneration of epithelial cells, and accumulation of edema fluid. • Second episodes of varicella have been documented but are rare.
    30. 30. LABORATORY EXAMINATIONS • VZV Antigen Detection DFA Smear of vesicle fluid or scraping from ulcer base/margin: Direct • fluorescent antibody (DFA) test detects VZV specific antigens. • Viral Cultures: Isolation of virus on viral culture (human fibroblast monolayers) from vesicular skin lesions, biopsy specimens, corneal scraping, and CSF is possible but more difficult than for HSV.
    31. 31. Tzanck Smear Cytology of fluid or scraping from base of vesicle or pustule shows both giant and multinucleated acantholytic epidermal cells (as does that of HSV infections) Serology Seroconversion documents primary VZV infection.
    32. 32. CLINICAL MANIFESTATION Incubation Period 14 days (range, 10–23 days). Prodrome • Characteristically absent or mild. • Uncommon in children, more common in adults: headache, general aches and pains, severe backache, malaise. • Exanthem appears within 2–3 days. Skin Symptoms Exanthem usually quite pruritic. Skin Lesions In most children, illness begins with appearance of exanthem: • Vesicular lesions evident in successive crops.
    33. 33. • Often single, discrete lesions or scanty in number in children and much more dense in adults. • Initial lesions are papules (often not observed) that may appear as wheals and quickly evolve to vesicles and initially appear as small “drops of water” or “dewdrops on a rose petal”, superficial and thin-walled with surrounding erythema. • Vesicles become umbilicated and rapidly evolve to pustules and crusts over an 8- to 12-h period.
    34. 34. • With subsequent crops, all stages of evolution may be noted simultaneously, i.e., papules, vesicles, pustules, crusts, i.e., polymorphic. • Crusts fall off in 1–3 weeks, leaving a pink, somewhat depressed base. • Characteristic punched-out permanent scars may persist. • Uncommonly, hemorrhage into pustular lesion occurs in otherwise healthy children, i.e., hemorrhagic varicella
    35. 35. Distribution First lesions begin on face and scalp, spreading inferiorly to trunk and extremities. • Most profuse in areas least exposed to pressure, i.e., back between shoulder blades, flanks, axillae, popliteal and anticubital fossae • Density highest on trunk and face, less on extremities • Palms and soles usually spared Mucous Membranes Vesicles (not often observed) and subsequent shallow erosions (2–3 mm) • Most common on palate • Mucosa of nose, conjunctivae, pharynx, larynx, trachea, GI tract, urinary tract, vagina
    36. 36. • Complications Super infection by methicillin-sensitive S . aureus (MSSA), methicillin-resistant S . aureus (MRSA), or GAS Impetigo, furuncles, cellulitis, and gangrene In children 5– 11 years of age, the most common complications are varicella encephalitis and Reye syndrome. • In adults, prodromal symptoms are common and may be severe; Exanthem may last for a week or more, with prolonged period of recovery. • The mortality rate in adults was 15 per 50,000 cases (U.S.); 25% of varicella associated deaths did occur in adults.
    37. 37. Primary varicella pneumonia, which presents 1–6 days after appearance of rash, is relatively common in adults: 16% of adults show x-ray evidence of pneumonitis, but only 4% have clinical signs of pneumonitis. Women have a 10% risk of severe VZV pneumonitis. VZV encephalitis may also complicate varicella in adults. • Less common complications of varicella include viral arthritis, uveitis, conjunctivitis, carditis, inappropriate antidiuretic hormone syndrome, nephritis, and orchitis. • Maternal varicella during the first trimester of pregnancy:
    38. 38. Fetus: Fetal varicella syndrome (limb hypoplasia, eye and brain damage, skin lesions) in 2% of exposed fetuses. Neonatal varicella has higher associated incidence of pneumonitis and encephalitis than occurs in older children. • Immunocompromised or glucocorticoid treated patients with varicella may manifest dissemination, hepatitis, encephalitis, and hemorrhagic complications. • If varicella occurs at an early age when maternal antibody is still present, an individual can have a second episode of varicella.
    39. 39. DIAGNOSIS Usually made on clinical findings alone. MANAGEMENT Prevention Immunization VZV immunization is now available (Varivax) and is 80% effective in preventing symptomatic primary VZV infection. Those at high risk for varicella, who should be immunized, include: normal VZV-negative adults, children with leukemia, and immunocompromised individuals (immunosuppressive treatment, HIV infection, cancer).
    40. 40. Symptomatic therapy Lotions Directed at reducing pruritus. Oral antihistamines Application gives short-term relief of pruritus. Caution re antipyretic agents Antipyretic administration is of concern because of a possible link between aspirin and Reye syndrome in children with varicella. Antiviral agents Otherwise healthy patients If begun within 24 h after onset of varicella, decreases the severity of varicella and reduces secondary cases. Acyclovir∗ 20 mg/kg (800 maximum) four times daily for 5 days Valacyclovir Effective but not an approved use; dosing same as for herpes zoster.

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