What is the appropriate workup for a patient presenting with night sweats and weight loss, considering their age, medical history, and potential for infections or malignancies, such as tuberculosis (TB), human immunodeficiency virus (HIV), lymphoma, or endocarditis?

Workup for Night Sweats and Weight Loss

Immediate Priority Testing

Begin with tuberculosis screening and HIV testing, as these infections are the most critical to identify early and have the highest morbidity and mortality if missed. 1, 2

Tuberculosis and HIV Assessment

• Perform tuberculosis screening with either tuberculin skin test (TST) or interferon-gamma release assay (IGRA) in all patients, regardless of perceived risk factors, as TB can present atypically even in low-risk populations 1, 2
• Order HIV testing universally in patients presenting with night sweats and weight loss, as HIV significantly increases TB risk and fundamentally changes management 1, 2
• If TB screening is positive, rule out active disease with chest radiograph and submit three sputum specimens for acid-fast bacilli smear, mycobacterial culture, and nucleic acid amplification testing 2
• In high TB prevalence settings or high-risk patients, obtain chest x-ray even before TB test results return, particularly if fever or hemoptysis is present 3

Essential Laboratory Studies

Order a complete blood count with differential, inflammatory markers (ESR and CRP), comprehensive metabolic panel including LDH, and thyroid-stimulating hormone in all patients. 1, 2

• Complete blood count evaluates for cytopenias, leukocytosis, or abnormal cells suggesting hematologic malignancy (sensitivity 70-80% for lymphoma) 1, 2
• ESR and CRP assess for systemic inflammation from infection or malignancy 1, 2
• Comprehensive metabolic panel including liver enzymes, alkaline phosphatase, LDH, and albumin evaluates for liver dysfunction or malignancy (sensitivity 80-90% for liver disease) 1, 2
• TSH rules out hyperthyroidism as a treatable cause 2, 4

Imaging Strategy

Obtain chest x-ray as initial screening in all patients, then proceed to contrast-enhanced CT chest and abdomen if lymphadenopathy, organomegaly, or abnormal laboratory findings are present. 1, 2

• Chest x-ray serves as initial screening for pulmonary pathology, lymphadenopathy, and masses 2, 4
• Contrast-enhanced CT of chest and abdomen evaluates for lymphadenopathy, organomegaly, or masses with 90-95% sensitivity for lymphoma 1, 2
• PET/CT should be ordered if lymphoma is strongly suspected based on lymphadenopathy, elevated LDH, or abnormal blood counts, as it has high sensitivity for bone marrow involvement and guides biopsy location 1, 2

Tissue Diagnosis Criteria

If lymphadenopathy >1.5 cm is present on examination or imaging, proceed directly to excisional or incisional lymph node biopsy rather than fine-needle aspiration. 3, 1, 2

• Excisional biopsy provides fresh tissue for pathology, flow cytometry, and cytogenetics with 90-95% sensitivity for lymphoma 1, 2
• Fine-needle aspiration alone has only 50-60% positive predictive value and should not be relied upon when lymphoma is suspected 1
• Bone marrow biopsy with fibrosis grading and molecular testing is indicated if blood counts are abnormal (cytopenias, leukocytosis, or leukoerythroblastic picture) or if lymphoma/leukemia is suspected 1, 2

Critical Pitfalls to Avoid

• Do not dismiss tuberculosis in patients without classic risk factors (immigration, incarceration, known exposure), as TB prevalence is still 5-10% even in low-risk populations presenting with these symptoms 1
• Do not skip HIV testing even in patients without obvious risk factors, as prevalence is 1-5% in low-risk populations and HIV fundamentally changes TB management 1
• Do not rely on fine-needle aspiration alone for lymph node evaluation when lymphoma is in the differential, as sensitivity is significantly lower than excisional biopsy 1
• Do not order extensive imaging in patients with typical clinical presentations of menopause, medication side effects, or gastroesophageal reflux disease if initial laboratory studies are normal 4

Age and Context-Specific Considerations

• In women of appropriate age, consider menopause as a common benign cause, but still complete infectious and malignancy screening if B symptoms (fever, >10% weight loss) are present 2, 5, 4
• In patients with risk factors for endocarditis (injection drug use, valvular disease), obtain blood cultures before antibiotics if fever is present 4
• Document frequency and severity of night sweats, associated fever pattern, and quantify weight loss (>10% body weight over 6 months is significant) 2, 5