The differential diagnosis for the patient in this case included toxoplasmosis, Cryptococcus infection, acute HIV infection, and molluscum contagiosum. Toxoplasmosis of the central nervous system (CNS) was excluded because of the absence of ring enhancement on the patient's MRI scan. In addition, no clinical improvement occurred during empiric treatment, which was discontinued after a negative Toxoplasma immunoglobulin G (IgG) assay. Toxoplasma IgG is found in 95% of patients with preexisting latent infection.
Acute HIV infection was ruled out owing to this patient's positive HIV antibody tests, which are negative in acute retroviral syndrome. This syndrome presents as acute mononucleosis because of very high viral loads, with fever, lymphadenopathy, rash, and sore throat; however, a mononucleosis spot test would be negative.
Other umbilicated lesions in patients with HIV infection include molluscum contagiosum or penicilliosis, which are confirmed on skin biopsy and by clinical appearance. Molluscum contagiosum is caused by a poxvirus, and histology will reveal eosinophilic cytoplasmic inclusion bodies. Treatment consists of local removal with cryotherapy, podophyllin application, or curettage. Molluscum contagiosum improves after highly active antiretroviral therapy (HAART) is initiated. The disseminated CNS, lung, and skin lesions in the patient in this case made molluscum contagiosum less likely, and the histopathology results ruled it out.
Cryptococcosis is caused by an endemic fungus, Cryptococcus neoformans or Cryptococcus gattii. Primary infection is in the lungs, but if the host immune system is weakened, it can result in fungemia and dissemination to the CNS and other extrapulmonary sites, including the skin, bones, joints, and prostate.
Immunocompromised hosts have more severe and disseminated disease, with pulmonary as well as extrapulmonary symptoms, most commonly due to reactivation of latent infection. This occurs in patients who have advanced HIV/AIDS, cancer treated with chemotherapy, hematopoietic stem cell transplant, solid organ transplant, chronic obstructive pulmonary disease, end-stage renal disease, diabetes, or who are receiving long-term glucocorticoid or immunosuppressive medications, including immune modulators such as tumor necrosis factor–alpha antagonists.
Clinical manifestations include severe pulmonary cryptococcosis in patients who are HIV-positive with CD4 T-cell counts < 100 cells/µL. Patients present with fever, cough, shortness of breath, and headache. Disseminated CNS infection is very common in this patient population. It is important to rule out concurrent P jirovecii , Mycobacterium avium complex (MAC), M tuberculosis, cytomegalovirus, and Histoplasma capsulatum infections, which are also common in this patient population.
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