What is the recommended diagnostic workup for a patient presenting with night sweats, fatigue, and weight loss?

Diagnostic Workup for Night Sweats, Fatigue, and Weight Loss

The recommended diagnostic workup for a patient presenting with night sweats, fatigue, and weight loss should focus on ruling out malignancies, infections, and other systemic conditions, beginning with a focused evaluation of symptom severity and targeted laboratory and imaging studies.

Initial Assessment

• Screen for fatigue severity using a numeric rating scale (0-10) or categorization as none, mild, moderate, or severe 1, 2
• Patients with fatigue scores of 4-10 (moderate to severe) warrant a more focused evaluation 1, 2
• Document the presence of B symptoms (fever, drenching night sweats, unexplained weight loss >10% of total body weight over 6 months) 1
• Assess for other associated symptoms such as cough, dyspnea, pruritus, alcohol-induced pain, and lymphadenopathy 1

Laboratory Studies

• Complete blood count with differential to evaluate for cytopenias, leukocytosis, or abnormal cells 1
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess for inflammation 1, 3
• Blood chemistry including liver enzymes, alkaline phosphatase, lactate dehydrogenase, and albumin 1
• Thyroid-stimulating hormone (TSH) to rule out hyperthyroidism 2, 3
• HIV testing and tuberculosis screening (IGRA or TST) 1, 3
• Consider serum protein electrophoresis if multiple myeloma or other plasma cell disorders are suspected 1, 4

Imaging Studies

• Chest X-ray as initial screening for pulmonary pathology 1, 3
• Contrast-enhanced CT scan of neck, chest, and abdomen to evaluate for lymphadenopathy, organomegaly, or masses 1
• Consider PET/CT if lymphoma is suspected, as it has high sensitivity for bone marrow involvement and can guide biopsy 1
• Abdominal ultrasound if hepatosplenomegaly is suspected on physical examination 1, 4

Additional Considerations

• Bone marrow biopsy if blood counts are abnormal or if lymphoma/leukemia is suspected 1
• Excisional or incisional lymph node biopsy if lymphadenopathy is present, with fresh tissue sent for pathology, flow cytometry, and cytogenetics 1
• Evaluate for treatable contributing factors to fatigue including pain, emotional distress, and sleep disturbances 1, 2
• Review medications and supplements that may contribute to symptoms 1, 2

Disease-Specific Considerations

Lymphoma Evaluation

• Look for painless regional or diffuse lymphadenopathy, hepatosplenomegaly, or extranodal involvement 1
• Assess for oncologic emergencies such as superior vena cava syndrome, respiratory compromise, or spinal cord compression 1
• Consider excisional lymph node biopsy with immunophenotyping and cytogenetics for definitive diagnosis 1

Myeloproliferative Disorders

• Evaluate for constitutional symptoms including >10% weight loss in 6 months, night sweats, and unexplained fever (>37.5°C) 1
• Look for increasing splenomegaly and leukoerythroblastic peripheral blood picture 1
• Consider bone marrow biopsy with fibrosis grading and molecular testing 1

Tuberculosis Screening

• For patients with risk factors, perform either tuberculin skin test (TST) or interferon-gamma release assay (IGRA) 1, 3
• If positive, rule out active TB with clinical history, physical examination, chest radiograph, and respiratory sampling 1
• Submit three sputum specimens for acid-fast bacilli smear, mycobacterial culture, and nucleic acid amplification testing if active TB is suspected 1

Follow-up Recommendations

• If initial workup is negative but symptoms persist, consider additional testing such as CT of chest/abdomen, bone marrow biopsy, or polysomnography 3
• If no specific cause is identified after comprehensive evaluation, provide reassurance and continued monitoring 3
• Patients with concerning features (rapid weight loss, severe night sweats, significant lymphadenopathy) should be referred to appropriate specialists for further evaluation 4, 5, 6