Viral Infections

Primary HIV Infection. Primary infection with HIV usually presents as a mono-nucleosis-like syndrome after an incubation period of one to four weeks, as previously mentioned. The clinician should consider acute HIV infection in a mononucleosis-like presentation with negative serologies. The symptoms reported, by decreasing order of frequency, are fever (95%), lymphadenopathy, pharyngitis, maculopapular rash, myalgias/ arthralgias, nausea, vomiting or diarrhea, headache, hepatosplenomegaly, neuropathy, oral or upper GI ulcerations, purpura, and conjunctivitis. Large painful oral ulcers are reported with acute HIV infection, which are associated with gram-negative bacterial colonization. Those are usually self-limited, but help in the differential diagnosis of acute PHI from other viral illnesses.

Herpes Simplex Virus. Herpes simplex virus (HSV) Types 1 and 2 can cause both primary gingivostomatitis and recurrent labial, other skin area, or intraoral or esophageal ulcers in HIV-infected persons (Fig. 14). The lesions are more atypical and protracted with severe immunosuppression and CD4 counts less than 50 cells/mm3 (18) and they can appear on the dorsal tongue as slit-like or dendritic ulcers. Herpetic keratitis is also reported. Persistent recurrent HSV infection is a marker of HIV disease progression. Diagnosis is made clinically, by biopsy of a skin or oral lesion, or via endoscopy. A smear can be sent to the laboratory for immunofluorescent stain or viral culture.

Usually the ulcers are self-limited, but can be persistent and accompanied by fever, malaise, dysphagia, and odynophagia. Treatment with oral acyclovir (200 or 400 mg up to five times daily) or oral valacyclovir (1 g twice daily) as soon as symptoms first appear and

FIGURE 14 Herpes simplex virus of the palate. Source: Courtesy of the International AIDS Society-U.S.A. From Refs. 3, 4, 11.

for 7 to 10 days can sometimes shorten the duration or decrease the frequency of the outbreaks. IV treatment with foscarnet is reserved for rare cases of resistant HSV or poorly responsive cases. Prophylaxis with oral acyclovir or valacyclovir is sometimes given for frequently recurrent outbreaks.

Varicella Zoster Virus. Orofacial herpes zoster infection usually follows the distribution of one of the three branches of the trigeminal nerve on one side of the face. It may also be disseminated. HIV infection has been associated with a 17-fold relative risk increase for zoster, which occurs at any CD4 count but becomes more severe as immunosuppression worsens (18) Involvement of the ophthalmic branch and the eye should be ruled out, and the patient presenting with suspicious lesions on the forehead or pinna should be referred for evaluation to an ophthalmologist, to rule out zoster ophthalmicus from involvement of the nasociliary branch of cranial nerve V (Fig. 15). Facial nerve involvement with facial palsy may occur (Ramsay-Hunt syndrome). Chronic forms and up to 20% recurrence rate have been reported.

Pain is usually the initial symptom, often referred to the teeth, followed by the characteristic eruption of papules, which quickly progress to vesicles and ulcers with crusts. Postherpetic neuralgia might be severe and require referral to a specialist. Oral ulcers have been reported.

Diagnosis is easily made clinically. Viral culture obtained from the base of a freshly opened vesicle often isolates the virus.

Treatment is most efficacious when started early. Oral acyclovir at high doses of up to 4 g in daily divided doses can be used (or alternatively, valacyclovir 1 g three times daily), both for 10 to 14 days. For more severe cases or ophthalmic branch involvement, IV acyclovir treatment is warranted. Oral steroids are recommended for facial nerve paralysis, but are better avoided in disseminated zoster.

Cytomegalovirus. CMV disease in HIV is usually reactivation of a latent, previously acquired infection in patients with CD4 count of less than 100 cells/mm3 (19) The typical primary CMV infection, presenting with a mononucleosis-like syndrome characterized by fever, pharyngitis, lymphadenopathy, and malaise, is not usually encountered in the setting of HIV infection. In the pre-HAART era, CMV reactivation disease could be asymptomatic or cause fever and constitutional symptoms or end organ disease, occurring in 40% of AIDS patients. The most common organ involved is the retina, in 85% of cases, with the GI tract accounting for another 10%. In the HAART era, incidence of new CMV-reactivation disease has decreased dramatically and is usually seen with CD4 counts less than 50 cells/mm3. Oral and esophageal ulcers are the most common upper GI tract manifestation, CMV being the second most common cause of esophagitis after Candida, with HSV being the third. Necrotizing gingivitis and salivary gland involvement are also reported.

Diagnosis is made by biopsy, evidence of characteristic cytopathic changes on Giemsa stain and immunohistochemistry results. Quantitative polymerase chain reaction

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