What are the causes and treatments of night sweats?

Night Sweats: Causes and Diagnostic Approach

Definition and Clinical Significance

Night sweats are episodes of excessive perspiration during sleep that may soak bedclothes or sheets, and while they can signal serious underlying disease, most patients in primary care settings do not have life-threatening conditions. 1

• Night sweats affect 10-60% of adults depending on the population studied, with prevalence ranging from 10% in older primary care patients to 60% in hospitalized obstetric patients 2
• The symptom does not independently predict increased mortality risk in primary care populations 1, 2
• Approximately 34% of primary care patients report night sweats, with half experiencing severe episodes that saturate bedclothes 3

Common Causes by Category

Infectious Diseases

• Tuberculosis remains a critical diagnostic consideration, presenting classically with cough, fever, night sweats, weight loss, and upper-lobe infiltrates 4
• HIV infection should be evaluated, particularly in patients with risk factors or other constitutional symptoms 4, 5
• Fungal infections including coccidioidomycosis (with night sweats persisting >3 weeks suggesting severe disease), histoplasmosis, and paracoccidioidomycosis all present with night sweats alongside weight loss and fever 4
• Anthrax (inhalational form) can present with night sweats, headache, and progressive respiratory symptoms 4

Malignancies

• Hodgkin lymphoma is the classic malignancy associated with night sweats, typically presenting with the triad of fever, night sweats, and weight loss (B symptoms) 4, 6
• Waldenström's macroglobulinaemia lists recurrent fever, night sweats, weight loss, and fatigue as clinical indications for initiating therapy 4
• While lymphoma is an important consideration, it is infrequently found as the actual cause in modern primary care practice 5

Endocrine Disorders

• Menopause is the most frequent hormonal cause of night sweats, with vasomotor symptoms including hot flashes and night sweats being the defining features 4, 7
• Hyperthyroidism is another common hormonal cause requiring evaluation 5, 1, 7
• Hypoglycemia should be considered, particularly in diabetic patients on insulin or sulfonylureas 5

Gastrointestinal and Sleep Disorders

• Gastroesophageal reflux disease (GERD) is commonly associated with night sweats, with patients often waking with a bitter taste in the mouth 1, 3
• Obstructive sleep apnea should be considered, especially when night sweats occur with daytime tiredness and other sleep disturbances 5, 3

Medications and Substances

• Antihypertensives are a common medication-related cause 5
• Antipyretics paradoxically can cause night sweats 5
• Serotonin reuptake inhibitors frequently cause night sweats, which may respond to alpha-adrenergic blockers 2
• Alcohol and heroin are drugs of abuse associated with night sweats 5

Other Systemic Conditions

• Mood disorders including anxiety and panic attacks are frequently associated with night sweats 1, 7
• Obesity is a recognized association 1

Diagnostic Algorithm

Initial History and Physical Examination

Focus specifically on constitutional symptoms (fever, weight loss), medication review, menopausal status in women, and sleep-related symptoms including GERD and sleep apnea. 1

• Ask about water-induced pruritus (aquagenic pruritus), which is highly suggestive of polycythemia vera 6
• Inquire about daytime tiredness, waking with bitter taste, leg jerking during sleep, and awakening with pain, as these are independently associated with night sweats 3
• Document severity: whether bedclothes are saturated, frequency, and duration of symptoms 3
• Assess for B symptoms: fever, night sweats persisting >3 weeks, and weight loss >10% 4

First-Line Laboratory and Imaging Studies

If history and physical examination do not reveal a specific cause, obtain: complete blood count with differential, tuberculin skin test or interferon-gamma release assay, thyroid-stimulating hormone, HIV test, C-reactive protein or erythrocyte sedimentation rate, and chest radiograph. 1

• Complete blood count evaluates for lymphoma, polycythemia vera, and anemia 6, 5, 1
• Tuberculosis testing (PPD or IGRA) is essential given TB's association with night sweats 4, 5, 1
• TSH screens for hyperthyroidism 5, 1, 7
• HIV testing should be offered to all patients with night sweats and unknown status 4, 5, 1
• Chest radiograph identifies pulmonary TB, lymphoma, or fungal infections 5, 1
• Serum ferritin should be checked, as 25% of patients with systemic symptoms respond to iron replacement 6

Second-Line Studies (If Initial Workup Negative)

Consider CT chest and abdomen, bone marrow biopsy, polysomnography, and additional laboratory studies based on clinical suspicion. 1

• CT imaging is indicated when lymphoma or occult infection is suspected despite normal chest radiograph 5, 1
• Bone marrow biopsy should be pursued if hematologic malignancy is suspected based on CBC abnormalities 5, 1
• Polysomnography evaluates for obstructive sleep apnea when clinical features suggest this diagnosis 1
• JAK2 V617F mutation testing if polycythemia vera is suspected (present in up to 97% of cases) 6

Management Approach

When Specific Diagnosis Is Identified

Treat the underlying condition: antituberculous therapy for TB, chemotherapy for lymphoma, thyroid management for hyperthyroidism, hormone replacement for menopause (if no contraindications), and CPAP for sleep apnea. 4, 1

• For TB with HIV co-infection, coordinate antituberculous and antiretroviral therapy with expert consultation 4
• For Waldenström's macroglobulinaemia, initiate therapy when night sweats occur with other B symptoms 4
• For menopause-related night sweats in women without contraindications, hormone replacement therapy can be offered 4

When No Specific Cause Is Found

If initial evaluation including history, physical examination, and first-line studies is unrevealing and no additional disorders are suspected, provide reassurance and continued monitoring rather than extensive further testing. 1

• Consider empiric treatment trial for 4-8 weeks if clinical diagnosis is suspected (e.g., GERD, anxiety) 1
• For medication-induced night sweats from SSRIs, alpha-adrenergic blockers may provide relief 2
• Symptomatic management with emollients and non-sedating antihistamines can be offered while completing evaluation 6

Critical Pitfalls to Avoid

• Do not dismiss night sweats in patients with weight loss, fever, or adenopathy, as this triad strongly suggests lymphoma requiring urgent evaluation 4, 6
• Do not overlook medication review, as drug-induced night sweats are common and reversible 6, 5
• Do not assume menopause in all women with night sweats without excluding serious causes, particularly if B symptoms are present 1
• Do not order extensive imaging and invasive testing in patients with isolated night sweats, normal examination, and normal initial laboratory studies, as serious disease is unlikely 1, 2
• Do not forget to check ferritin, as iron deficiency is a frequently overlooked but treatable cause of night sweats 6