What is the appropriate workup for a patient presenting with night sweats?

Workup for Night Sweats

Begin with a focused history and physical examination targeting infectious, malignant, and inflammatory causes, followed by basic laboratory screening including CBC, ESR/CRP, chest radiograph, and tuberculosis testing if risk factors are present. 1

Initial Clinical Assessment

History Taking

• Document the pattern and severity of night sweats: specifically whether they are drenching (requiring change of bedclothes), their frequency, duration, and timing of onset 1, 2
• Screen for B symptoms: fever, unexplained weight loss >10% of body weight over 6 months, and assess their temporal relationship 2, 3
• Identify associated symptoms: cough, dyspnea, lymphadenopathy, pruritus, alcohol-induced pain, and fatigue 1, 3
• Assess tuberculosis risk factors: immigration from endemic areas, HIV risk factors, incarceration history, known TB exposure, or homelessness 1, 2
• Complete medication review: focus on antihypertensives, antipyretics, serotonin reuptake inhibitors, alpha-adrenergic blockers, and substances of abuse including alcohol 4
• Evaluate for sleep disorders: ask about snoring, witnessed apneas, restless legs, and daytime somnolence as obstructive sleep apnea can present with night sweats 4

Physical Examination

• Perform comprehensive lymph node examination: assess all lymphoid regions (cervical, supraclavicular, axillary, inguinal) for painless adenopathy 1, 2
• Evaluate for hepatosplenomegaly: palpate abdomen for organomegaly which may suggest lymphoma or myeloproliferative disorders 1, 3
• Conduct thorough skin examination: look for rashes, lesions, Kaposi sarcoma, molluscum contagiosum, or signs of vasculitis 1
• Examine oropharynx: assess for candidiasis and oral hairy leukoplakia which may indicate immunosuppression 1

Essential Laboratory Studies

All patients with night sweats require the following baseline workup:

• Complete blood count with differential: evaluate for cytopenias, leukocytosis, or abnormal cells suggesting hematologic malignancy 1, 2, 3
• Inflammatory markers: ESR and CRP to assess for systemic inflammation 1, 2, 3
• Comprehensive metabolic panel: including liver enzymes, alkaline phosphatase, LDH, and albumin 1, 2, 3
• HIV testing: essential given the association with night sweats and opportunistic infections 1, 2, 3
• Tuberculosis screening: either tuberculin skin test (TST) or interferon-gamma release assay (IGRA), particularly in high-risk populations 1, 2, 3
• Thyroid-stimulating hormone (TSH): to rule out hyperthyroidism as a hormonal cause 3, 5

Imaging Studies

• Chest radiograph: essential first-line screening for pulmonary pathology, mediastinal adenopathy, and tuberculosis 1, 2, 3
• Contrast-enhanced CT chest and abdomen: consider if lymphadenopathy, organomegaly, or masses are suspected on examination or if initial workup is concerning 1, 2, 3

Risk-Stratified Advanced Workup

When to Pursue Further Evaluation

Consider advanced testing if:

• Persistent symptoms despite negative initial workup 1
• Development of additional B symptoms (fever, weight loss) 1
• Abnormal laboratory findings suggesting hematologic malignancy 1
• High clinical suspicion for lymphoma based on examination findings 1, 2

Advanced Diagnostic Studies

• PET/CT scan: reserve for cases with high suspicion for lymphoma based on clinical presentation and initial workup, as it has high sensitivity for bone marrow involvement and can guide biopsy 1, 2, 3
• Excisional or incisional lymph node biopsy: preferred over fine-needle aspiration when lymphadenopathy is present, with fresh tissue sent for pathology, flow cytometry, and cytogenetics 2, 3
• Bone marrow biopsy: consider when blood counts are abnormal or lymphoma/leukemia is suspected, with fibrosis grading and molecular testing 2, 3

Special Considerations

Tuberculosis Workup

If TB screening is positive, rule out active disease with:

• Clinical history and physical examination 3
• Chest radiograph 3
• Three sputum specimens for acid-fast bacilli smear, mycobacterial culture, and nucleic acid amplification testing 3

Malignancy Screening in Specific Populations

In patients with idiopathic inflammatory myopathy (IIM), night sweats are considered a "red flag" symptom warranting cancer screening regardless of risk category 6. However, this is a specialized population and not applicable to general night sweats evaluation.

Common Diagnostic Pitfalls

• Do not dismiss tuberculosis in patients without classic risk factors: TB can present atypically 2
• Do not rely on fine-needle aspiration alone for lymph node evaluation: excisional biopsy has superior sensitivity when lymphoma is suspected 2
• Do not overlook HIV testing even in patients without obvious risk factors: HIV significantly increases TB risk and changes management 2
• Do not forget to screen for sleep disorders and gastroesophageal reflux disease: these are common but often overlooked causes 4