Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (499 page)

   
Primary genital
: Disease is manifested as a papulovesicular eruption of the genital mucosa and surrounding skin. Primary infections are usually associated with painful lesions and systemic symptoms, including fever, headache, and malaise. Patients may complain of dysuria, and inguinal lymphadenopathy may be evident. Neurologic symptoms, including aseptic meningitis, sacral radiculopathy, and neuralgias, are not uncommon. Vesicles may persist for 3 weeks in primary infection but usually resolve within 1 week in recurrent outbreaks. Primary infections are associated with more lesions and a higher virus burden compared to recurrent disease. Genital or oropharyngeal HSV infection in pregnant women is of particular importance; it may result in disseminated disease in the mother, leading to complications including necrotizing hepatitis, meningoencephalitis, and coagulopathy. Genital HSV infection in pregnant women is also a primary risk factor for neonatal HSV infection in the offspring.

   
Neonatal
: Disease may occur at any time between birth and 4 weeks of age. Most neonatal HSV infections are acquired from infected maternal genital secretions during labor and delivery. A number of factors increase the risk of transmission and severity of neonatal disease: Primary maternal infection at or near the time of labor and delivery, maternal seronegativity for the infecting type of HSV, prolonged (>6 hours) rupture of fetal membranes prior to delivery, and/or the use of fetal scalp monitor. There are three common presentations of neonatal disease: (a) disseminated disease of multiple organ systems; (b) localized CNS disease; and (c) localized infection of the skin, eyes, and mouth. Early intrauterine infection may rarely be seen, presenting with vesicles or scarring of skin, various ocular abnormalities, and CNS abnormalities, including microcephaly and hydranencephaly.

   
HSV keratoconjunctivitis
: Manifested by photophobia, tearing, chemosis, lid edema, and preauricular lymphadenopathy. Visual acuity may be decreased. Slit-lamp examination typically shows characteristic branching dendritic lesions.

   
Skin
: Infections occur most commonly in patients with eczema. Outbreaks may be localized or disseminated (Kaposi varicella-like eruption). Infection localized to the digits (herpetic whitlow) is associated with direct inoculation of virus, often acquired by health care manipulation.

   
CNS
: HSV is the most common cause of severe sporadic encephalitis. Patients typically present with focal encephalitis and neurologic abnormalities related to the region of brain affected. Patients also typically present with other symptoms, including fever, behavior changes, and decreased level of consciousness.

   Laboratory Findings

Cell culture
: HSV may be isolated by viral culture of vesicles, ulcers, or infected tissues. Culture of specimens from lesions of recurrent disease is much less sensitive. Positive viral cultures for HSV must be interpreted in the context of clinical presentation because HSV may rarely be shed in chronic infection in the absence of overt clinical disease.

Histology
: Direct cytologic examination of scrapings of lesions (Wright-Giemsa stain) shows multinucleated giant cells with intranuclear inclusions (Tzanck smear). Skin vesicles produce a positive smear in 66% and positive viral culture in 100% of cases; pustules produce a positive smear in 50% and a positive viral culture in 70% of cases; crusted ulcers produce a positive smear in 15% and a positive viral culture in 34% of cases. Multinucleated cells may also be identified in routine Pap smear of cervix. A negative direct test does not rule out this diagnosis.

Molecular diagnosis
: NAAT techniques may be used for detection of HSV DNA in tissue, CSF, and other specimen types. PCR is the diagnostic test of choice if CNS infection is suspected, with sensitivity and specificity >95%.

Serology
: Serologic testing is of limited value for the management of acute infection but may be useful in assessing past infection or a patient’s risk for infection. Immunoblot IgG has sensitivity >80% and specificity of 95%. See Herpes Simplex Virus (HSV) Serology Tests, Type 1– and Type 2–Specific Antibodies, IgG and IgM in Chapter
17
, Infectious Disease Assays.

Core laboratory
: In patients with HSV encephalitis, CSF shows increased WBC count with mononuclear cell predominance; RBC count is usually increased. CSF protein is increased.

HIV-1 INFECTION AND ACQUIRED IMMUNODEFICIENCY SYNDROME

   Definition

   Human immunodeficiency virus (HIV) infection is the cause of acquired immunodeficiency syndrome (AIDS), as well as symptomatic disease prior to the development of AIDS. HIV infection now has a global distribution, and most disease is caused by HIV-1. HIV-2 infection is more geographically restricted, primarily occurring in western Africa.

   HIV-1 viruses fall into three genetic groups: M, O, and N. Group M viruses, which can be further subdivided into clades (A–D, F–H, J, and K), are the predominant viruses responsible for the global epidemic. In the United States, Europe, and Australia, the B clade predominates. Other clades may be predominant in other geographic locations. HIV-2 is genetically distinct. This discussion will focus on disease caused by HIV-1.