What is the appropriate evaluation and work‑up for a patient with a one‑month history of night sweats and chills?

Evaluation of Night Sweats and Chills for One Month

A patient with one month of night sweats and chills requires immediate tuberculosis screening, HIV testing, complete blood count with differential, inflammatory markers, and chest imaging to exclude life-threatening infections and hematologic malignancies. 1, 2

Immediate Priority: Rule Out Tuberculosis

Tuberculosis screening must be performed first, regardless of perceived risk factors, as TB commonly presents with fever, chills, and night sweats. 3

• Obtain either tuberculin skin test (TST) or interferon-gamma release assay (IGRA) immediately 1, 2
• Order chest X-ray simultaneously, without waiting for TB test results, particularly given the one-month duration of symptoms 3, 2
• If TB screening is positive or chest X-ray is abnormal, collect three sputum specimens on separate days for acid-fast bacilli smear, mycobacterial culture, and nucleic acid amplification testing 3
• TB should not be dismissed even in patients without classic risk factors (immigration from endemic areas, incarceration, known exposure, or HIV), as atypical presentations occur 1

Essential Laboratory Studies

Order these tests at the initial visit:

• Complete blood count with differential to evaluate for cytopenias, leukocytosis, lymphocytosis, or circulating blasts suggesting lymphoma or leukemia 1, 2, 4
• HIV testing is mandatory, as HIV significantly increases TB risk and fundamentally changes management 1, 2
• Inflammatory markers (ESR and CRP) to assess for systemic inflammation from infection or malignancy 1, 2
• Comprehensive metabolic panel including liver enzymes, alkaline phosphatase, lactate dehydrogenase (LDH), and albumin to evaluate for liver dysfunction or malignancy 1, 2
• Thyroid-stimulating hormone (TSH) to exclude hyperthyroidism 2

Imaging Strategy

Chest X-ray is the initial imaging study for all patients with night sweats and chills. 2, 5

• If chest X-ray shows lymphadenopathy, masses, or infiltrates, proceed to contrast-enhanced CT of chest and abdomen 1, 2
• If lymphadenopathy is present on examination or imaging (>1.5 cm), proceed directly to excisional or incisional lymph node biopsy rather than fine-needle aspiration 2, 4
• PET/CT should be considered if lymphoma is strongly suspected based on clinical presentation, as it has high sensitivity for bone marrow involvement and guides biopsy 1, 2

When to Pursue Tissue Diagnosis

Obtain tissue diagnosis if:

• Lymphadenopathy >1.5 cm is present on examination or imaging 2
• Blood counts show cytopenias, lymphocytosis, or abnormal cells 1, 4
• Constitutional symptoms persist with elevated LDH or abnormal imaging 2, 4

For lymph node biopsy: Send fresh tissue for pathology, flow cytometry, and cytogenetics—excisional biopsy is preferred over fine-needle aspiration for suspected lymphoma 1, 2

For bone marrow biopsy: Consider if blood counts are abnormal or lymphoma/leukemia is suspected, with fibrosis grading and molecular testing 1, 2, 4

Critical Pitfalls to Avoid

• Do not rely on fine-needle aspiration alone when lymphoma is suspected—it has significantly lower sensitivity than excisional biopsy 1
• Do not skip HIV testing even in patients without obvious risk factors, as HIV prevalence in patients with night sweats can be 1-5% even in low-risk populations 1
• Do not dismiss TB based on absence of cough—fever, chills, and night sweats alone warrant TB evaluation 3
• Do not wait for TB test results before ordering chest X-ray in patients with one month of symptoms 2

If Initial Workup is Negative

If the above evaluation reveals no diagnosis after 4-8 weeks:

• Review medications for drugs causing night sweats (antihypertensives, antidepressants, antipyretics) 5, 6
• Consider gastroesophageal reflux disease, obstructive sleep apnea, and hypoglycemia 5, 6
• Reassess for mood disorders and obesity-related causes 6
• If all testing remains negative and no additional disorders are suspected, reassurance and continued monitoring are appropriate, as night sweats alone do not indicate increased mortality risk 7, 6