Viruses Flashcards

1
Q

Cytomegalovirus infections (CMV)

A

Double-stranded DNA virus; member of the Herpesviridae family
Symptomatic CMV disease in immunocompromised individuals affects almost every organ of the body
CMV is transmitted from person to person via close contact

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2
Q

CMV pneumonia

A

0-6% adults with mononucleosis syndrome develop pneumonia
CMV pneumonia is found on CXR; no clinical significance, rapidly resolving with resolution of primary infection
Life-threatening CMV pneumonia occurs immunocompromised patients (lung transplant recipients have a 50% risk of developing CMV illness)

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3
Q

Cytomegalovirus hepatitis

A

Elevated bilirubin and/or liver enzymes w/ CMV detected
Most common with primary CMV infection & mononucleosis
Mild & transient LFT elevation, rarely hyperbilirubinemia

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4
Q

Cytomegalovirus gastritis and colitis

A

CMV may infect the GI tract from the oral cavity through the colon
Typical manifestation of disease is ulcerative lesions (oral lesions indistinguishable from HSV or aphthous ulcers)
Gastritis may present as pain or hematemesis
Colitis usually presents as diarrhea

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5
Q

Cytomegalovirus retinitis

A

Common opportunistic infection in persons with AIDS, typically those with CD4+lymphocyte counts below 50 cells/µL
Cases have decreased with the use of HAART
Immune reconstitution syndrome (IRIS) is reported in 16%-63% of HIV-infected patients with CMV retinitis following the initiation of HAART (median onset 43 weeks after starting HAART)
CMV IRIS manifest as painless floaters, blurred vision, photopia, decreased visual acuity, or ocular pain

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6
Q

Cytomegalovirus nephritis

A

CMV viremia has been associated with acute glomerular injury
Detecting CMV in the urine of a patient with renal failure does not meet diagnostic criteria for CMV nephritis (clinically inconsequential viruria)

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7
Q

Cytomegalovirus CNS disease

A
Association between CMV and Guillain-Barré Syndrome 
Younger patients (typically < 35 y) present with sensory defects and facial palsy, antiganglioside (GM2) IgM response, and mild long-term sequelae
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8
Q

CMV workup

A

IgM level is elevated in patients with recent CMV infection, or there is a 4-fold increase in IgG titers
False-positive CMV IgM results may be seen in patients with EBV or HHV-6 infections, RF
Anti-CMV immediate early antigen monoclonal antibody test, reacts with an early protein; can detect CMV infection 3 hours into the infection
Detection of the CMV pp65 antigen in leukocytes, expressed only during viral replication, immunofluorescence assay or mRNA amplification
Cytopathology

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9
Q

CMV treatment

A
Best options for treatment and prevention of cytomegalovirus (CMV) disease remain ganciclovir and valganciclovir
2nd line (foscarnet or cidofovir) or are used off-label (leflunomide)
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10
Q

Epstein-Barr Virus

A

EBV is transmitted via intimate contact with body secretions, primarily oropharyngeal secretions
EBV infects the B cells in the oropharyngeal epithelium

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11
Q

Symptomatic EBV

A

Fatigue may be profound initially following 1-2 month incubation
Gradually resolves with in 3 months
Some have initial recovery then prolonged fatigue without the features of infectious mononucleosis
Airway obstruction and central nervous system (CNS) mononucleosis are also responsible for increased morbidity

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12
Q

Presentation of EBV

A

triad of fever, pharyngitis, and lymphadenopathy

Hoaglund sign - bilateral upper-lid edema, last only a few days

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13
Q

EBV workup

A

Heterophile antibody test
Peak levels 2-6 weeks after primary EBV infection; may remain positive up to a year
Latex agglutination assay (using horse RBCs) has sensitivity is 85%; specificity is 100%
Heterophile antibody test (e.g. Monospot test) often negative early; increasing during 1st 6 weeks, if remains negative considered ‘heterophile-negative infectious mononucleosis’

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14
Q

EBV Treatment

A

Short courses of corticosteroids (7-10 days) are indicated for EBV infectious mononucleosis with hemolytic anemia, thrombocytopenia, CNS involvement, or obstructive adenoid/tonsillar enlargement
Patients with EBV infectious mononucleosis who have positive throat cultures for group A streptococci should not be treated because this represents colonization (~30%) rather than infection
Amoxicillin treatment of group A streptococcal oropharyngeal colonization with EBV infectious mononucleosis may result in a maculopapular rash
Fatigue may take some time to resolve, and some patients may develop a state of chronic fatigue that is induced, but not caused by, EBV infectious mononucleosis

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15
Q

Erythema Infectiosum – 5th disease

A

Usually a benign childhood condition characterized by a classic slapped-cheek and subsequent lacy exanthem
Caused by human parvovirus (HPV) B19
Incubation period is usually 7-10 days

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16
Q

3 Phases of Erythema Infectiosum

A

Phase 1: A bright red, raised, slapped-cheek rash with circumoral pallor develops, sparing of nasolabial folds
Phase 2: Occurs 1-4 days later; erythematous maculopapular rash on proximal extremities (usually arms and extensor surfaces) and trunk, which fades into a classic lace-like reticular pattern; palms and soles usually spared
Phase 3: Recurrences of lacy rash for weeks or months (especially with exercise, irritation, or overheating of skin from bathing or sunlight)
Do not, diagnose in phase 1

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17
Q

Fetal hydops - 5th Disease

A

Fetal transmission with severe anemia and resultant congestive heart failure
Occurs <10% of primary maternal infections
½ of women of childbearing age are seropositive (immune and at no risk for the fetus)

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18
Q

Erythema infectiosum Prevention/Isolation

A

Children with erythema infectiosum are not infectious; may attend childcare or school
Routine exclusion of pregnant women from the workplace where erythema infectiosum is occurring is not recommended (due to high prevalence of human parvovirus B19 infection and low incidence of fetal effects)
Exposed pregnant women should consult their OB/GYN regarding immune status and f/u

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19
Q

Herpes Simplex Virus

A

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)
HSV-1 is traditionally associated with orofacial disease
HSV-2 is traditionally associated with genital disease;
Lesion location is not necessarily indicative of viral type
Up to 80% of herpes simplex infections are asymptomatic

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20
Q

HSV - Gingivostomatitis

A

Acute herpetic gingivostomatitis
Primary HSV-1 infection in children 6 mo to 5 yr
Adults may have acute gingivostomatitis (less severe; more symptomatic as a posterior pharyngitis)
Infected saliva from an adult or another child is the mode of infection
Incubation period is 3-6 days

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21
Q

Clinical Features of HSV - Gingivostomatitis

A

Abrupt onset
High temperature (102-104°F)
Anorexia and listlessness
Gingivitis(most striking feature, with markedly swollen, erythematous, friable gums)
Vesicular lesions (develop on the oral mucosa, tongue, and lips and later rupture and coalesce

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22
Q

HSV Workup

A

Herpes simplex virus (HSV) infection is best confirmed by isolation of the virus in tissue culture
PCR has been used to detect HSV-2 as the cause of recurrent meningitis

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23
Q

HSV - Complications

A

Bacterial and fungal superinfections balanitiscan occur in an uncircumcised male due to bacterial infection of the herpetic ulcers
Candidalvaginitisin as many as 10% of women with primary genital herpes, particularly in women with diabetes, mucosal herpetic lesions can be confused withyeast infection
Ocular infections is not uncommon in children as a result of autoinoculation during acute herpetic gingivostomatosis or asymptomatic oropharyngeal HSV infection

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24
Q

HSV Treatment

A

Penciclovir (Denavir) - Inhibitor of DNA polymerase in HSV-1 and HSV-2 strains, inhibiting viral replication
Acyclovir (Zovirax) - Synthetic purine nucleoside analogue with activity against a number of herpesviruses,

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25
HIV
Human immunodeficiency virus (HIV) is a blood-borne, sexually transmissible virus Typically transmitted via Sexual intercourse Shared intravenous drug paraphernalia Mother-to-child transmission (MTCT), which can occur during the birth process or during breastfeeding
26
Where the 2 types of HIV come from?
HIV-1 probably originated from one or more cross-species transfers from chimpanzees in central Africa HIV-2 is closely related to viruses that infect sooty mangabeys in western Africa
27
HIV risk Factors
Unprotected sexual intercourse, especially receptive anal intercourse (8-fold higher risk of transmission) Large number of sexual partners Prior or current STDs Gonorrhea and chlamydia infections increase the HIV transmission risk 3-fold Syphilis raises the transmission risk 7-fold Herpes genitalis raises the transmission risk up to 25-fold during an outbreak Sharing of intravenous drug paraphernalia Receipt of blood products (before 1985 in the US) Mucosal contact with infected blood or needle-stick injuries Maternal HIV infection
28
HIV Presentation
Acute seroconversion manifests as a flulike illness, consisting of fever, malaise, and a generalized rash Asymptomatic phase is generally benign (aka asymptomatic) Generalized lymphadenopathy is common ; may be a presenting symptom Weight loss
29
HIV Workup
high-sensitivity enzyme-linked immunoabsorbent assay (ELISA) should be used for screening CD4 T-cell count is a reliable indicator of the current risk of acquiring opportunistic infections
30
Newly diagnosed HIV infection workup to include the following?
Cytomegalovirus (CMV) testing Syphilis testing Rapid amplification testing for gonococcal and chlamydial infection Hepatitis A, B, and C serology Anti-Toxoplasma antibody Ophthalmologic examination A purified protein derivative skin test (PPD) to evaluate for tuberculosis infection Chest radiography should be performed in patients with a positive PPD test result
31
HIV Staging
Category A - asymptomatic HIV infection without a history of symptoms or AIDS-defining conditions Category B - HIV infection with symptoms that are directly attributable to HIV infection Category C - HIV infection with AIDS-defining opportunistic infections (previous slide with opportunistic infections 3 categories are further subdivided based on the CD4+ T-cell count Categories A1, B1, and C1 - CD4+ T-cell counts > 500/µL Categories A2, B2, and C2 - CD4+ T-cell counts 200/µL - 400/µL A3, B3 and C3 - CD4+ T-cell counts < 200/µL
32
HIV Treatment
Efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) Ritonavir-boosted atazanavir + tenofovir/emtricitabine (ATV/r + TDF/FTC) Ritonavir-boosted darunavir + tenofovir/emtricitabine (DRV/r + TDF/FTC) Raltegravir + tenofovir/emtricitabine
33
Antiretroviral regimen selection is individualized, on the basis of the following:
``` Virologic efficacy Toxicity Pill burden Dosing frequency Drug-drug interaction potential Drug resistance testing results Comorbid conditions ```
34
HIV Prognosis
Untreated HIV infection - overall mortality rate > 90% Average time from infection to death is 8-10 years, although individual variability ranges from less than 1 year to long-term nonprogression Variables implicated in HIV's rate of progression, including CCR5-delta32 heterozygosity, mental health, concomitant drug or alcohol abuse, superinfection with another HIV strain, nutrition, age; also primary risk factor for initial infection
35
Prevention of HIV
Sexual transmission Prevention measures include the following: Abstinence when possible Reduction in number of sexual partners Using barrier contraception Treatment of concurrent sexually transmitted diseases (STDs) Testing of self and partner for HIV infection and other STDs Vertical transmission Prevention measures include the following: Maternal testing Effective control of maternal infection Prenatal antiviral therapy and treatment of mother and infant during labor, delivery, and the neonatal period Cesarean delivery Avoidance of breastfeeding (unless local conditions make this unsafe or unfeasible) Postexposure prophylaxis
36
HPV
``` Human papillomavirus (HPV) produces epithelial tumors of the skin and mucous membranes More than 100 HPV types are known HPV types 6 and 11 - low risk oncogenic potential; formation of condylomata and low-grade precancerous lesions HPV types 16 and 18 - high-risk types of HPV; responsible for most high-grade intraepithelial lesions that may progress to carcinomas ```
37
HPV Incidence
Anogenital HPV is the most common sexually transmitted infection in the US Condylomata acuminata are clinically apparent in 1% of the sexually active population (molecular studies - 10-20% of men/women aged 15-49 yo HPV exposed) Prevalence of 4-13% has been reported by sexually transmitted disease (STD) clinics Common among adolescents and young adults Estimated 80% of sexually active women will have been infected by age 50
38
Laryngeal Papillomatosis
An incubation period (latency period) is 3 months, but periods as long as 20 months Age of onset usually 2-4 yo, but as late as juvenile onset documented, younger age worse prognosis Symptoms include hoarseness, voice changes, croupy cough, stridor Diagnosis by direct laryngoscopy Prevention by HPV vaccine Treatment by direct surgical resection (recurrences are the rule), tracheostomy occasionally required
39
Workup of HPV
Most diagnoses are made clinically Exam of genital lesions with acetic acid helpful Colposcopy & biopsy to determine extent of intraepithelial neoplasia PAP Smear
40
HPV Treatment
No single curative treatment for condylomata acuminata Treatment of most HPV infections involves agents that directly ablate the lesions Medications used in treating HPV disease: Immune response modifiers – imiquimod and interferon alfa and are primarily used in treatment of external anogenital warts or condylomata acuminata Cytotoxic agents - antiproliferative drugs podofilox, podophyllin,
41
Influenza
Highly contagious airborne disease that causes an acute febrile illness (ranging from mild to respiratory failure/death) Most significant immunologic surface proteins include hemagglutinin (H) and neuraminidase (N), which determine virulence
42
Influenza Presentation
Abrupt onset of illness is common (may be able to report the time when the illness began) Fever may vary widely, 100-104°F; feeling feverish /chills Sore throat may be severe and may last 3-5 days (often reason for office visit) Frontal/retro-orbital headache is common; usually severe. (ocular symptoms photophobia, burning sensations, and/or pain upon motion Ptosis is common
43
Complications of Influenza
Pneumonia in highest risk groups: women in the third trimester of pregnancy, elderly individuals, especially nursing home patients; those with cardiovascular disease usually constitute the highest risk group Secondary bacterial pneumonia Staphylococus aureus (most severe with cavitary infiltrates) Haemophilus pneumonia Steptococcus pneumoniae (S pneumoniae and H flu ususally develop Methicillin-susceptible S aureus (MSSA) and methicillin-resistant S aureus (MRSA) pneumonias, often severe & difficult to treat, fatal within 24 hours occasionally
44
Workup of Influenza
Viral culture of nasopharyngeal samples and/or throat samples Rapid diagnostic tests are available, but because of cost, availability, and sensitivity issues, most flu is diagnosed clinically PCR Serologic Testing
45
Influenza Treatment
4 prescription antiviral drugs: oseltamivir, zanamivir, amantadine, rimantadine
46
Measles
one of the most contagious infectious diseases, at least a 90% secondary infection rate in susceptible domestic contacts Measles is marked by prodromal fever, (3-Cs) cough, coryza, conjunctivitis Transmitted via respiratory droplets, which can remain active and contagious, either airborne or on surfaces, for up to 2 hours
47
Measles Prognosis
``` Morbidity and mortality increased Immune deficiency disorders Malnutrition Vitamin A deficiency Inadequate vaccination (60-fold increase in risk of disease due to exposure to imported measles cases) ```
48
Measles Presentation
Incubation period 10-12 days 1st sign usually a high fever often >104 lasting 4-7 days Prodromal phase associated with malaise, fever, anorexia, classic triad (the ‘3-Cs’): Conjunctivitis Cough (may be the final symptom to appear though) Coryza
49
Measles Complications
otitis media, interstitial pneumonitis, bronchopneumonia, laryngotracheobronchitis (ie, croup), exacerbation of tuberculosis acute encephalitis
50
Measles Workup
Serologic testing for IgG (4 fold increase acute-convalescent serum) and IgM (positive by 3rd day of rash for 30-60 days) Isolation of the virus Reverse-transcriptase polymerase chain reaction (RT-PCR) CBC may reveal leukopenia with a relative lymphocytosis and thrombocytopenia LFTs results may reveal elevated transaminase levels in patients with measles hepatitis CXR if pneumonia suspected
51
Measles Treatment
Supportive, IV hydration Vitamin A – reduces severity & duration 50% Postexposure prophylaxis should be considered in unvaccinated contacts Antibiotic treatment of 2nd infections, e.g. pneumonia & otitis media Ribavirin (IV or aerosolized) - treat severely affected and immunocompromised adults with SSPE, no controlled studies MMR - preventive if administered within 3 days of exposure, contraindicated in HIV with CD4 count < 15% Human Ig within 6 days of exposure
52
Molluscum contagiosum
MC virus causes a benign viral infection almost exclusively limited to humans Papules are umbilicated and contain a caseous plug
53
3 Types of people affected by Molluscum contagiosum
Children - most common, become infected through direct skin-to-skin contact or indirect skin contact with fomites, e.g. bath towels, sponges, and gymnasium equipment Immunocompetent adults - sexually transmitted disease (STD); few lesions limited to the perineum, genitalia, lower abdomen, or buttocks Immunocompromised children or adults - widespread, persistent, and atypical molluscum contagiosum in those with AIDS with low CD4 counts
54
3 Types of molluscum contagiosum virus
Orthopoxvirus - resembles variola (smallpox) and vaccinia Parapoxvirus - orf and milker’s nodule viruses Unclassified (with features that are intermediate between those of the orthopox and parapox groups)
55
Distribution of molluscum contagiosum
Face, trunk, and extremities is observed in children; relatively common in the groin, perineal or genital (not pathognomonic of abuse) Groin and genitalia in adults Lesions are seldom found on the palms, soles, oral mucosa, or conjunctiva
56
Molluscum contagiosum Treatment
Spontaneous resolution generally occurs by 18 months in immunocompetent individuals; may persist up to 5 years Treatment options: Benign neglect - primum non nocere (first do no harm) Direct trauma to lesions: acids, cryotherapy, pulse laser Antiviral therapy Immune response stimulation
57
Mumps
``` Mumps is an acute, self-limited, systemic viral illness characterized by the swelling of one or more of the salivary glands, typically the parotid glands RNA virus Salivary glands (also pancreas, testes) show edema and desquamation of necrotic epithelial cells lining the ducts ```
58
Prognosis and Complications of Mumps
Overall prognosis in uncomplicated mumps is excellent Encephalitis: Rates of mumps encephalitis 5:1000 reported mumps cases Sensorineural deafness Orchitis (usually unilateral) Oophoritis Pancreatitis
59
Treatment of Mumps
Supportive care Reduce acidic foods, both salivary gland & gastric issues Ice packs to parotid gland; ice/scrotal support for orchitis Analgesic/antipyretics Isolation for 5 days Vaccine coverage
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Rabies
viral disease that affects the CNS, single stranded RNA | Transmitted in saliva or in aerosolized secretions from infected animals, typically via a bite
61
2 Periods of Rabies
Incubation period Asymptomatic; average duration is 20-90 days, usually < 1 year; but up to 7-19 years. Incubation period < 50 days more likely if the patient is bitten on the head or neck or if a heavy inoculum is transferred through multiple bites, deep wounds, or large wounds Rabies virus is segregated from the immune system ; no antibody response Prodromal period Virus enters the CNS; duration 2-10 days Paresthesia, pain, intense itching at inoculation site is pathognomonic for rabies, may be only presenting sign; occurs in 50% Acute neurologic period Duration 2-7 days Objective signs of developing CNS disease: muscle fasciculations, priapism, and focal or generalized convulsions Patients may die immediately or may progress to paralysis, 1st in bitten limb at first but usually becomes diffuse Furious rabies: Agitation, hyperactivity, restlessness, thrashing, biting, confusion, or hallucinations lasting < 5 minutes; becomes episodic and interspersed with calm, cooperative, lucid periods Episodes may be triggered by visual, auditory, or tactile stimuli or spontaneous; seizures may occur Hydrophobia/aerophobia present in 50%; larynogospasm / diaphragmatic spasms with drinking water or air blown in face May end in cardiorespiratory arrest or may progress to paralysis Paralytic rabies (dumb rabies or apathetic rabies) Relatively quiet; 20 % do not develop the furious form Paralysis occurs from the outset Coma
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Rabies Postexposure
Rabies vaccine IM (deltoid) - 1 mL on days on days 0, 3, 7, and 14 (if immunocompromised, add an additional dose: 1 mL IM deltoid on days 0, 3, 7, 14, and 28) Rabies immunoglobulin - 20 IU/kg infiltrated as much as feasible around and under the bite wound; if any left over, give IM (gluteus) HRIG may be administered as long as 7 days after the first dose of vaccine (if not immediately available ) Prophylaxis may be discontinued if the animal does not develop rabies within 10 days or is found to be free of rabies upon sacrifice Pregnancy is not a contraindication to postexposure prophylaxis against rabies
63
Roseola
human herpesvirus 6 (HHV-6) Replication of the virus occurs in the leukocytes and the salivary glands Classic presentation of roseola infantum is 9-12 mo infant with acute onset high fever; commonly a febrile seizure; 72 hours later rapid defervescence with onset morbilliform rash (early invasion of the CNS may occur) HHV-6 then remains latent (like other herpes viruses) in most patients who are immunocompetent
64
Roseola Presentation
Acute onset of fever Febrile seizure in 15% Lack of URI or GI symptoms, playful despite fevers of 104-105 After acute defervescence, exanthem: generalized but subtle with either discrete, small, pale pink papules or blanchable, maculopapular
65
Rubella Epidemiology
Young children - mild constitutional symptoms, rash, and suboccipital adenopathy Older children, adolescents, and adults, rubella may be complicated by arthralgia, arthritis, and thrombocytopenic purpura Rare cases occur of rubella encephalitis Pregnant women
66
Presentation of Rubella
``` Incubation is usually 14-21 days after exposure to a person with rubella Conjunctivitis Sore throat Headache General body aches Low-grade fever Chills Anorexia Nausea Forchheimer sign ```
67
Congenital Rubella Presentation
classic triad of congenital rubella syndrome consists of: Sensorineural hearing loss Congenital heart disease Ocular abnormalities including cataract, infantile glaucoma, and pigmentary retinopathy
68
Rubella Workup
Congenital rubella syndrome should be strongly suspected in infants > 3 mo if rubella-specific IgG antibody levels are observed and do not decline at the rate expected from passive transfer of maternal antibody (i.e. equivalent of a 2-fold decline in HI titer per mo) Rubella-specific immunoglobulin M (IgM) antibody in a single serum sample Rubella-specific IgG rise
69
Varicella Pathophysiology
Inhalation of contaminated respiratory droplets, the virus infects the conjunctivae or the mucosae of the upper respiratory tract Viral proliferation occurs in regional lymph nodes of the upper respiratory tract 2-4 days after initial infection
70
Varicella Presentation
Incubation period of 10-21 days Not heralded by a prodrome Begins with the onset of an exanthem, infectious 1-2 days prior to rash developing Small, erythematous macules appear on the scalp to face to trunk to limbs Rapid sequential progression over 12-14 hours to papules to clear vesicles to pustules, which umbilicate and crust Intense pruritus typical with vesicles Remains infectious for 4-5 days after the rash develops, as last vesicle crusts over
71
Varicella Complications
Secondary bacterial infection 2nd bacterial infection of skin lesions most common complication - impetigo, cellulitis, and erysipelas Staphylococci & streptococci most common bacteria Disseminated primary varicella infection Disseminated primary varicella infection seen in immunocompromised or adult populations, ``` CNS complications Reye syndrome – associated with ASA Guillain-Barré syndrome – ascending paralysis Acute cerebellar ataxia (post-varicella) Encephalitis  ``` Hemorrhagic complications
72
Varicella Workup
Tzanck smear of vesicular fluid - multinucleated giant cells and epithelial cells with eosinophilic intranuclear inclusion bodies Vesicular fluid culture – 40% sensitivity, better with direct immunofluorescence & PCR Serologic testing – multiple tests for IgG Chest radiography – signs of pneumonia Histologic examination – nonspecific with herpes
73
Varicella Treatment
Clip nails Antihistamines Topical & parenteral antibiotics if 2nd infections Acyclovir if risk for severe disease