In patients with CD4 counts >200 cells/mm3, the clinician can usually construct a laboratory and radiographic evaluation guided by symptoms, while in patients with severe immunosuppression a broader evaluation is required. A serum cryptococcal antigen should be obtained, as it has high sensitivity and specificity for both systemic disease as well as meningitis (38). Bacterial, mycobacterial, and fungal isolator blood cultures should be performed, as well as a urine culture, despite lack of symptoms. Urine AFB cultures can be added if there is a suspicion for tuberculosis. Sputum should be evaluated with gram stain, AFB smear, and culture, as well as PCP direct fluorescent antibody. If diarrhea is present, stool studies should include bacterial culture, ova and parasites evaluation, an assay for C. difficile, and Cryptosporidia and Giardia stool antigen assays. A serum LDH may be elevated in PCP, disseminated histoplasmosis, or lymphoma. A serum CMV antigen may be useful in the patient with fever and diarrhea, hepatitis, or retinitis.
A chest radiograph should be performed in all febrile AIDS patients. Chest films may be normal in 5–10% of HIV-infected patients with tuberculosis (TB). The typical radiographic appearance of Pneumocystis jiroveci pneumonia is a bilateral interstitial pattern characterized by reticular or ground-glass opacities. However, normal chest radiographs may be seen in one third of AIDS patients with active PCP. High-resolution computed tomography (HRCT) of the chest should be obtained if there is still a clinical suspicion for Pneumocystis. HRCT has been shown in several reports to have a 100% negative predictive value in the evaluation for PCP (39,40).
A lumbar puncture should be performed if the patient is symptomatic or if the serum cryptococcal antigen is reactive. A bone marrow biopsy and culture is also useful particularly in the evaluation of the patient with cytopenias. Bacterial, fungal, and AFB cultures may yield disseminated mycobacterial or fungal disease. Histopathologic evaluation may reveal granulomas with organisms or lymphoma. Bronchoscopy may be pursued in cases of high suspicion for TB or PCP.
Guidelines for the management of opportunistic infections associated with human immunodeficiency virus are available at www.AIDSinfo.nih.gov.
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Evaluation of the AIDS Patient with Focal Neurological Disease
Toxoplasma encephalitis (TE) may be distinguished from primary CNS lymphoma without a brain biopsy. TE is caused by reactivation of latent infection by the protozoan Toxoplasma gondii. Almost 90% of patients have CD4 counts less than 200 cells/mm3 and 75% have CD4 counts less than 100 cells/mm3. Serum anti-Toxoplasma IgG antibodies are detected in more than 90% of patients with TE. Lesions on CT or MRI (a more sensitive modality) are typically multiple ring-enhancing lesions with a predilection for the basal ganglia. An emipiric trial of therapy is recommended, and a response confirms a diagnosis in the patient who has a positive Toxoplasma antibody and is not receiving trimethoprim-sulfamethoxazole prophylaxis. A lumbar puncture in this setting is not necessary and maybe ill advised if cerebral edema is present (Figure 1, page 24).
Primary CNS lymphoma (PCNSL) has a similar radiographic appearance as TE. Solitary lesions are more frequent in PCNSL. Positron emission tomography (PET) and single photon emission CT (SPECT) are useful adjunctive imaging modalities as they are positive in PCNSL due to the increased metabolic activity of the tumor. Cytologic analysis of the CSF may show lymphomatous cells. Epstein-Barr virus (EBV) DNA is uniformly detected in PCNSL in AIDS patients and detection of EBV DNA by PCR on the CSF has a sensitivity of 90–100% and a specificity of 87–98% for the diagnosis of PCNSL (41,42). Combining SPECT imaging and EBV PCR provides 100% sensitivity and 100% negative predictive value in the evaluation of AIDS-related primary CNS lymphoma (43), obviating the need for brain biopsy.