Viral HHV Presentation PDF

DR Hanna Haydar  INTRODUCTION Viruses consist of only one type of nucleic acid, either DNA or RNA.  CLASSIFICATION DNA viruses include:- Herpes viruses Parvovirus Papovaviruses (human papovaviruses) Poxviruses (molluscum contagiosum virus) Parapoxvi...

DR Hanna Haydar  INTRODUCTION Viruses consist of only one type of nucleic acid, either DNA or RNA.  CLASSIFICATION DNA viruses include:- Herpes viruses Parvovirus Papovaviruses (human papovaviruses) Poxviruses (molluscum contagiosum virus) Parapoxviruses (Milker’s nodule virus) RNA viruses include:  Paramyxovirus (measles virus)  Rubivirus (rubella virus)  Picornaviruses (Caxsackie virus A16 and enterovirus 71)  Retroviruses (HIV)  HERPES VIRUSES Classification of human herps viruses(HHVs) HSV-1 cause herpes labialis HSV-2 cause gential herps HHV-3 varicella-zoster virus(vzv) cause chickenpox(varicella) and shingles(herpes zoster) HHV-4 Epstein-Barr virus(Infectious Mononucleosis andOral Hairy leukoplakia etc) HHV-5 cytomegalovirus(congenital deafness ,blindness due to retinitis in AIDS patient HHV-6 roseola infantum HHV-7 roseola infantum and pitrysis rosea HHV-8 KAPOSI SARCOMA  HERPES SIMPLEX  Etiology  It is caused by herpes simplex virus (HSV) (herpesvirus hominis). It comprises two antigenic types.  1. HSV-1 is usually associated with facial infections and occurs mainly in infants and young children.  2. HSV-2 is classically found in genital infections and occurs mainly after puberty and often transmitted sexually.  The sites infected by the two HSV types are not mutually exclusive and show considerable overlap in the sites of involvement.  Route of Transmission May be through skin or mucosa by: By direct contact or droplets of infection: It is usually seen in children. By sexual contact: It is usually seen in adults. Herpes simplex virus (HSV) infections are best described to have three stages. 1. Primary infection: IP (3-7) days its effect children(2-5)YERS Inital Hsv infection in indivduals without pre existing antibody to Hsv1 or HSV 2 Fever malaise burning before the onset of the lesions painful vesicels on erythamtous base no tendensy to grouping with enlarged tender regoinal LNs crusting of the lesions and spontaneous resolution occurs within 2-6 weeks 2. Latent infection:  After reaching sensory ganglion, HSV gene expression is severely restricted and produces no viral proteins. Therefore, remains undetected by host defense mechanisms.  3. Recurrent infection: In this last stage, due to certain risk factors like old age and cellular immune dysfunction, the latent virus starts replicating and via antegrade axonal transport reaches peripheral site where it causes recurrent disease.  It occurs due to reactivation of HSV-1 in trigeminal  ganglion and HSV-2 in sacral ganglion.  Triggering factors: Minor trauma, emotional stress, premenstrual period, UVetc.  Sites of predilection: Outer third of lower lip and perioral areas (herpes labialis).  Clinical varieties 1 herps labialis (facilas) comenst sitevermilliom border and perioral areas 2 Herpetic gingivostomatitis high grade fever and painful oral ulcer 3 ECZEMA HERPTICUM (Kaposi’s varicellform eruption) 4 Herpetic whitlow:Infection 0f the digits in dental and medical personnel who don’t routinely use glove 5 keratoconjunctivits 6 herpatic folliculitis mainly at the beard region in males 7herptic pneumonia (fatal)  te 8 HS encephalitis manifest as sezizures lethargy irritability tremors poor feeding temperature instability abulging fontanelle and pyramidal tract signs 9 HERPS gladiatorum in wrestlers and involving extra mucosal sites (face neck arms ) 10 Disseminated HS in compromised host Ne0natal herps 70% due to HSV-2 Clinical Spectrum: localized infection (Skin, Eyes and mouth..) CNS disease  severe disseminated disease (sepsis, encephalitis, hepatitis, pneumonia, and coagulopathy ; fatality = up to 50%) Incubation period up to 3/52. So, often diagnosed after hospital discharge. 70% of mothers are asymptomatic or have no reported h/o herpes infection. Treatment= IV acyclovir 250mg/m2 every 8 hours for 7 day  Genital herps; genital herps; ○ 1° infection often asymptomatic, but can → painful/tender erosions on external genitalia, vagina, cervix, buttocks, and perineum (women) +/− lymphadenopathy/dysuria (women mainly) 1° worse in women – ↑% extragenital involvement, urinary retention, and aseptic meningitis (10%) ○ Recurrent – mildly symptomatic with few vesicles lasting about 1 week; frequency of outbreaks usually decreases over time  Eczema herpeticum (Kaposi’s varicelliform eruption): − Etiology: It results from widespread infection of damaged skin due to HSV-1 Occur with atopic dermatitis Seborrheic Dermatitis Scabies Darier’s Disease Hailey-Hailey Diseas. it should be considered in child with infected eczema who is more ill and toxic than expectation  Investigations FOR HSV1 AND HSV2  Tzanck Smear (giant multinucleated epithelial cells)  Nonspecific  Accuracy?? 60-90%  Direct Florescence Antibody test  Results available in hours!! Virus specific; more accurate;  Biopsy with immuno-peroxidase staining  PCR  Viral Culture  Results available in 48-72 hours  Serology  Does not give information about the current lesion. Helpful if partner diagnosed, to determine if prophylaxis needed. Also good for epidemiological studies.  Management of HSV Infections Mild uncomplicated eruptions: − Need no systemic antiviral treatment − Keep the lesions clean and dry is all that is required − Topical antibacterial agents may be used to treat secondary bacterial infection. For severe primary infection, antiviral therapy should be started. Systemic antiviral agents  Antiviral Therapy Primary herpes genitalis: Acyclovir cream and ointments (applied 4 to 5 times) are beneficial. Recurrent herpes genitalis:  − Topical imiquimod has some beneficial effect. − Topical acyclovir in not beneficial. Acyclovir resistance First line drug; IV Foscarnet Second line, or failure / intolerance of first line; Cidofovir  Varicella (Chickenpox) Epidemiology Prevalence: Very common Age: Often during childhood Season: Common in cooler months while it drops off in summer months  Varicella (Chickenpox)  Infection with VZV (HHV-3)  More severe symptoms with age and immune suppression  Lifelong immunity to natural infection  Prodromal symptomsFever, malaise, headache and anorexia often precedes the rash by 2–3 days  Skin eruption: “dewdrop on rose petal” vesicles are smaller in size and are surrounded erythema Lesions in different stages of development Begins on the face and spreads down to trunk. Lesions are most profuse on trunk and least on the peripheral parts of limbs (centripetal distribution).  Varicella (Chickenpox)  Incubation; 10-21 days (organs seeded at around 6 days)  Transmission; Direct contact and respiratory droplet  Contagious; 4+ days before lesions, until crusted  Scarring; If lesions large, picked, or secondarily infected.  Pneumonia rare in kids, more common in adults  Encephalitis and ataxia most common neurologic effects  Complications; osteomyelitis, septicemia, myocarditis, DIC and purpura fulminans,Reye’s Syndrome= Hepatitis, Acute encephalopathy  Treatment: Acyclovir 20mg/kg – up to 800mg qid x 5/7 Transportation During varicella, VZV travels from skin and is transported centripetally up along the sensory fibers to the sensory ganglia. The virus establishes there as a latent infection and persists for life Recurrence Under the influence of certain risk factors (older age, immunosuppression, local trauma, irradiation of spinal column, tumor involvements, etc.) the virus gets reactivated and multiplies in the ganglia. Virus then spreads down and is released around the sensory nerve endings where it produces vesicles in cluster. Such clusters in a dermatome manifest as herpes zoster.  Varicella in Pregnant Women and Neonates  Congenital Varicella Syndrome  Maternal infection with VZV during first 20 weeks of gestation (fetal)  Severe illness in mother (varicella pneumonia in many)  Risk of spontaneous abortion (3%) and preterm labor  Risk of fetal anomalies; LBW, Hypoplastic ribs/limb anomalies (limb paresis, hypoplasia), scars, ocular and CNS disease (Dev’t delays, microphthalmia, cataracts, nystagmus, chorioretinitis, hydrocephalus) Neonatal; Maternal primary infection 7 days before, to 2 days after delivery. Presents at 0- 14 days Vesicles on erythematous base, generalized distribution Severe neonatal varicella. Rx with VZIG and IV Acyclovir  Treatment In normal children A benign and self-limiting condition. Treat symptomatically with oral antihistamines, antipyretics and topical soothing agents like calamine lotion. Routine aciclovir treatment is not required Normal adolescents (beyond 13 years) and adults Treat with oral aciclovir (800 mg 5 times a day for 7 days) routinely as soon as possible (due to risk of developing life threatening pneumonia).  Immunosuppressed patients with Varicella Lesions same but more numerous, necrotic, larger If patient has no prior history of disease or vaccination, + high risk contact give VZIG within 96h  Herpes Zoster (Shingles) Etiology Causative agent: VZV During chickenpox virus settles in sensory root ganglion and lies dormant for variable period (usually in years). - Reactivation of virus causes herpes zoster Predisposing factors for reactivation are: − Older age: A strong risk factor − Underlying HIV infection − Immunosuppression: Due to lymphoreticular malignancies,  e.g., Hodgkin’s disease and leukemia.  Herpetic rash and pain: − Pain:   Almost always present   Characteristically of burning type   Varies from mild to very severe excruciating intolerable pain  Zoster sine herpete – pain without skin lesions  − Morphology: Typically consist of closely grouped vesicles on an erythematous base unlike random distribution of varicella ,vesicles in zoster dermatomel.  Most distinctly, the rash is localized and distributed Unilaterally  It is generally limited to a single dermatome innervated by a single sensory ganglion. − Mucous membranes of the affected dermatome may also show involvement. Thoracic (55%) Cranial (20%) Lumbar (15%) Sacral (5%) Course Herpes zoster lesions evolve more slowly than varicella In older patients: The eruption is most severe and lasts longer (3–4 weeks). Scarring more common with age In children and young adults: It is least severe with shorter duration (2–3 weeks).  Complications Secondary bacterial infection Generalized disseminated eruption (disseminated zoster): More than 20 lesions outside the affected dermatome Rule out lymphoreticular malignancies, e.g., Hodgkin’s disease, leukemia and HIV infection. Involvement of eye: It is indicated by presence of avesicles on the tip or side of nose (Hutchinson’s sign) which are innervated by nasociliary (branch of trigeminal nerve) nerve which also innervates eye. Swelling of eyelids: It is very common in patients with herpes zoster opthalmicus. Swelling may even extend to other side also  Ramsay Hunt syndrome: It is due to involvement of both facial and auditory nerves. It consists of triad of:− - Facial palsy - Herpes zoster of external ear - Ear pain with or without tinnitus, vertigo, and deafness.  Postherpetic neuralgia (PHN): − It refers to the persistent neuralgic pain left in the affected dermatome after the healing of herpetic lesions. − Most common, most troublesome and intractable complication. − It is unusual in children, but incidence and severity increases with age.. Risk of PHN is more in patients of ophthalmic zoster and in those having severe pain during acute phase. Pain may be of continuous or spasmodic type. Allodynia is a disabling component of the disease and patient suffers pain after the slightest touch of affected skin by wind or clothing. It may disturb sleep and daily routines of life. PHN usually subsides spontaneously over several months. Recurrence: There is a unique tendency in HIV-infected patients to have multiple recurrences or to involve multiple dermatomes simultaneously  Diagnosis Important features for diagnosis: Severe burning pain Unilateral and dermatomal distribution Grouped vesicular eruption on an erythematous base  Treatment Mild cases Require symptomatic treatment Topical therapy: Topically applied calamine lotion may alleviate the pain and speed up the drying of vesicles. Topical antiviral agents are not effective. Oral analgesics Severe cases 1. Parenteral analgesics − When pain disturbs sleep at night then combination of pentazocine and pheniramine maleate may be injected IM for few days. 2. Reassure the patient that: − Your problem has been correctly diagnosed by the doctor.. 4. Antiviral therapy − It should be started within 72 hours of rash onset. − Systemic antiviral drugs will help in limiting the extent, duration and severity of pain and rash of acute phase. − It will decrease the incidence of PHN. Indications Patients older than 50 years of age Ophthalmic zoster Immunocompromised or HIV infected patients Severe involvement (disseminated or hemorrhagic or multidermatomal lesions) Drugs All the following three drugs are pregnancy category B drugs. Give one of them orally. Aciclovir 800 mg 5 times a day for 7 -10 days Valaciclovir 1 gm TDS for 7 days Famciclovir 250 or 500 mg TDS for 7 days  Indications of IV antiviral therapy Severely compromised: Treat with IV aciclovir. Advanced AIDS patients or aciclovir resistant patients: Treat with foscarnet 40 mg/kg IV 8 hourly until healing. Management of postherpetic neuralgia  10% of patients have pain 1 month after onset of zoster  10% - 25% of those still have pain at 1 year  Treatment options:  Capsaicin  topical anesthetics  Topical aspirin  Nerve blocks  Tricyclic antidepressants (1st line systemic Rx) (amitriptyline)25mg daily for 3-6 month  Gabapentin (Neurontin) – if pain is not controlled by TCA  Zostavax Live attenuated vaccine, one dose FDA approved for those >age 60 OK for nursing moms, and HIV pts if CD4 % >15%; NOT OK if pregnant Same strain of virus used in Varivax but 14x the potency Significantly reduced cases of zoster (by 51%) and PHN (66%)  Epstein-Barr Virus / HHV-4 Gamma herpesvirus Infects mucosal epithelial cells, B lymphocytes By age 20, 95% popn. latently infected Spread via oral secretions Causes Infectious Mononucleosis ( glandular fever) characterized by: Fever Adenopathy Splenomegaly Atypical Lymphocytosis Present in 3% - 16% of patients Edema of eyelids Macular or morbilliform rash Treatment with Ampicillin results in itchy morbilliform exanthem Pinhead-sized petechiae in mucous membranes Painful genital ulcerations may precede other symptoms Labs show abnormal lymphocytes (Downey cells), elevated LFTs  Oral Hairy leukoplakia Not a reactivation but a repeated direct infection Does not scrape off with tongue blade No tx needed (or use podophyllin monthly) This diagnosis should prompt testing for HIV  CMV / HHV-5 Beta - herpesvirus 90% exposed infants are asymptomatic Others can get jaundice, HSM, cerebral calcifications, chorioretinitis, microcephaly, MR, deafness In AIDS ( CD4 counts