Evaluation And Management Of The Febrile Patient

The differential diagnosis of fever in the late post engraftment period is broad, as many patients will be out of hospital and at-risk for community-acquired infectious diseases. The risk of opportunistic infection is proportionate to the extent of GVHD present and the degree of residual immunodeficiency. Autologous HSCT recipients are much less likely to have an opportunistic infection compared with allogeneic patients. The diagnostic evaluation and management should be guided by the history, by the presence or absence of localizing complaints, by the presence or absence of GVHD and the degree of immunodeficiency, and by the prior infectious disease history.

The differential diagnosis of fever without localizing symptoms or signs should include bacteremia, late-onset CMV disease, and PTLD. Although patients with chronic GVHD or indwelling intravascular devices remain at-risk for bloodstream infections with staphylococci and Gram-negative bacilli, encapsulated organisms should be suspected. All patients should have blood cultures obtained. High-risk patients for late-onset CMV disease should be screened for CMV viremia. PTLD is rare, but circulating EBV may be sought by PCR and high titers correlate with a greater likelihood of PTLD. If suspected, CT scans to identify adenopathy or masses in the chest, abdomen or pelvis should be performed.

In febrile patients without an obvious source of infection, empiric antibiotic therapy should be strongly considered pending blood cultures and should include coverage of S. pneumoniae, H. influenzae, and

N. meningitidis. Knowledge regarding the local incidence of penicillin-resistant pneumococci is essential in selecting a regimen. Patients with proven bacteremia with an encapsulated organism should be screened for hypogammaglobulinemia. Patients with late CMV viremia or invasive disease should be treated as outlined previously; clearance of viremia should be documented at the conclusion of 3 weeks of antiviral therapy.

The differential diagnosis in patients with a pneumonia syndrome depends upon the history, the likelihood of opportunistic infection, and the radiographic pattern of the infiltrate. In patients with acute onset of fever, a productive cough and a focal infiltrate, pneumococcal or H. influenzae pneumonia should be suspected. The presence of a nodular or cavitary infiltrate should suggest aspergillosis, tuberculosis, nocardiosis, zygomycosis, or PTLD. Interstitial infiltrates should suggest CMV, PCP, CRV, or noninfectious causes, which may account for up to 50% of cases in this setting. Diagnostic evaluation should include blood cultures and examination of expectorated sputum for pathogens suspected from the history and radiographic findings. Bronchoscopy may be necessary to establish a diagnosis in those with nodular, cavitary or interstitial infiltrates.

Sinusitis and otitis media from encapsulated organisms occur with higher frequency in the late engraft-ment period; symptoms to suggest these diagnoses should be carefully sought in allogeneic HSCT recipients with fever. Patients with VZV may present with dermatomal or atypical pain that heralds the onset of rash by up to 72 h.

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