Night sweats

Night sweats are episodes of drenching sweating during sleep, enough to soak nightclothes or bedding, that are not explained by a warm environment or heavy bedding. They are common and often benign, particularly in menopause and in drug induced and sleep related sweating, but together with fever, weight loss or lymphadenopathy they point to lymphoma, tuberculosis or HIV.

Epidemiology. Up to a third of adults report night sweats in a month. In primary care most cases are explained by menopause, medicines, anxiety, sleep apnoea or infection that is already apparent.

Physiology. Sweating is controlled by the hypothalamic thermoregulatory centre, which is narrowed in sleep. Heat dissipation by sweating occurs when the set point falls (defervescence), when thermoregulatory range narrows (menopausal vasomotor symptoms) or when sympathetic or cholinergic drive rises (drugs, hypoglycaemia, hyperthyroidism, catecholamine excess).

Classification by pattern.

• Drenching sweats with fever and other constitutional symptoms (B symptoms): infection and cancer.
• Vasomotor sweats with flushing, in waves, through the day as well: menopause, androgen deprivation, antioestrogen therapy.
• Sweats from drugs or alcohol, hypoglycaemia, sleep disorders or anxiety.
• Primary (idiopathic) hyperhidrosis and secondary hyperhidrosis.

B symptoms. Fever over 38.0 degrees Celsius, drenching night sweats and weight loss over 10% in 6 months, particularly relevant to lymphoma.

History.

• Onset, frequency, severity (changes of clothing or sheets), timing, associated flushing, palpitations, fever, rigors, weight loss, appetite, cough, haemoptysis, lumps, itch, bone pain, abdominal pain, diarrhoea.
• Menstrual history, menopausal age, hormone therapy, surgical menopause, contraception, pregnancy, postpartum status. In men, prostate cancer treatment, testosterone deficiency.
• Drugs: antidepressants (SSRIs, venlafaxine, tricyclics), tamoxifen, aromatase inhibitors, androgen deprivation, opioids (including withdrawal), tramadol, antipsychotics, cholinesterase inhibitors, corticosteroids, bupropion, nitrates, hydralazine, antipyretics, niacin, levothyroxine excess, insulin or sulphonylurea, stimulants, alcohol, nicotine, cannabis, caffeine.
• Sleep: snoring, witnessed apnoeas, reflux, restless legs, nightmares, shift work, bedroom temperature, bedding and sleepwear.
• Infection risk: tuberculosis contact, HIV risk, travel, animals, unpasteurised dairy, prosthetic valve, injecting drug use, dental work, recent surgery or catheter.
• Mood: anxiety, panic, trauma, depression.
• Diabetes treatment and nocturnal hypoglycaemia symptoms.
• Family history of lymphoma or thyroid disease.

Examination.

• Temperature, pulse, blood pressure, body mass index, weight change.
• Lymph nodes (cervical, supraclavicular, axillary, inguinal), spleen, liver, mass.
• Thyroid size and tenderness, tremor, eye signs, tachycardia.
• Heart murmurs and signs of endocarditis, chest signs.
• Skin: rash, nodules, pallor, flushing, dermographism, lesions of mastocytosis.
• Mouth: candidiasis, ulcers, dentition.
• Neurological signs: autonomic features, Horner syndrome, pupils, focal signs.
• Mental state, anxiety, tremor.

Red flags.

• Fever, weight loss over 5% in 6 months, or drenching sweats with both.
• Persistent lymphadenopathy, splenomegaly, hepatomegaly.
• Cough over 2 weeks, haemoptysis, tuberculosis contact, HIV risk or positive status.
• New murmur, prosthetic valve, injecting drug use.
• Bone pain, itch, alcohol induced pain in nodes, unexplained anaemia or cytopenia.
• Paroxysmal headache, palpitations and sweating with hypertension (phaeochromocytoma).
• Age over 40 with new unexplained sweats and no obvious cause, especially in men.

Infective. Tuberculosis (pulmonary, miliary, extrapulmonary), HIV infection (acute and advanced), infective endocarditis, abscess (hepatic, pelvic, dental), osteomyelitis, brucellosis, malaria, schistosomiasis, histoplasmosis and other endemic mycoses, infectious mononucleosis and cytomegalovirus infection, visceral leishmaniasis, Q fever, bartonellosis, nontuberculous mycobacterial infection.

Neoplastic. Hodgkin and non Hodgkin lymphoma, leukaemia, myelodysplastic syndrome and myeloproliferative neoplasms, renal cell carcinoma, hepatocellular carcinoma, carcinoid syndrome, phaeochromocytoma and paraganglioma, mastocytosis, any metastatic cancer.

Endocrine and metabolic. Menopause and perimenopause, hyperthyroidism, nocturnal hypoglycaemia (insulin, sulphonylureas, insulinoma), diabetes mellitus, acromegaly, hypogonadism and androgen deprivation therapy, pregnancy and postpartum state, carcinoid, phaeochromocytoma.

Drugs and substances. Antidepressants, tamoxifen, aromatase inhibitors, opioids, antipsychotics, cholinesterase inhibitors, corticosteroids, antipyretics, hypoglycaemic drugs, alcohol and alcohol withdrawal, opioid and benzodiazepine withdrawal, nicotine, caffeine.

Neurological and autonomic. Autonomic neuropathy, stroke, syringomyelia, Parkinson disease, autonomic dysreflexia, post traumatic hyperhidrosis, Horner syndrome, epilepsy (nocturnal seizures).

Sleep and psychiatric. Obstructive sleep apnoea, gastro-oesophageal reflux, restless legs and periodic limb movements, REM sleep behaviour disorder, anxiety, panic attacks, post traumatic stress, depression.

Rheumatological and cardiac. Giant cell arteritis, polymyalgia rheumatica, adult onset Still disease, heart failure, ischaemic heart disease (sweating with angina equivalents).

Idiopathic. Primary hyperhidrosis, idiopathic night sweats, obesity, environmental causes (overheated room, heavy bedding).

1. A careful history, drug review and examination identify the likely category in most patients. A woman aged 45 or more with typical vasomotor symptoms and no red flags does not need hormone tests; follicle stimulating hormone is unreliable in the menopausal transition.
2. First line tests when sweats are persistent, severe or unexplained: full blood count with film, ESR and C reactive protein, lactate dehydrogenase, ferritin, urea and electrolytes, liver function tests, calcium, glucose or HbA1c, thyroid stimulating hormone, HIV test with consent, chest radiograph, urinalysis, and a pregnancy test where relevant.
3. Infection directed: tuberculosis testing (interferon gamma release assay or tuberculin test, sputum or other specimen for Xpert MTB/RIF Ultra and culture), blood cultures (at least 2 sets) when fever or murmur is present, brucella and Epstein-Barr serology, malaria film where exposed, echocardiography when endocarditis is possible, urine lipoarabinomannan antigen in advanced HIV.
4. Neoplasm directed: CT of chest, abdomen and pelvis for B symptoms, lymphadenopathy or organomegaly; excisional lymph node biopsy for persistent unexplained nodes; bone marrow aspirate and trephine for cytopenia, suspicion of haematological disease or unexplained fever; fluorodeoxyglucose positron emission tomography with CT where lymphoma is likely.
5. Endocrine and catecholamine tests when features fit: plasma free metanephrines or 24 hour urinary fractionated metanephrines (phaeochromocytoma), urinary 5 hydroxyindoleacetic acid (carcinoid), serum tryptase and urinary mediators (mastocytosis), free thyroxine, testosterone, IGF-1 and cortisol where appropriate.
6. Sleep study when snoring, witnessed apnoeas or sleepiness (Epworth score over 10) is present. Review for gastro-oesophageal reflux and restless legs.
7. Time limited drug withdrawal or substitution when a drug is the likely cause.

Limits. Sweating severity is subjective, and a normal first panel does not exclude lymphoma or tuberculosis. Interferon gamma release assays and tuberculin tests can be negative in active disease and advanced HIV. Metanephrines can be falsely raised by drugs.

General measures. Cool the bedroom (16 to 18 degrees Celsius), use layered natural fibre bedding and nightwear, avoid alcohol, caffeine, spicy food and smoking in the evening, take regular exercise, and lose weight if overweight. Keep a symptom diary with triggers.

Cause directed treatment.

• Drug induced sweats: change the drug, reduce the dose or switch class where possible. For antidepressant sweating consider substitution (for example mirtazapine) and for persistent sweating glycopyrronium 1 mg orally twice daily, increased as needed to a maximum of 2 mg three times daily; anticholinergic effects limit use in older adults.
• Menopausal vasomotor symptoms: oestradiol (for example transdermal 50 micrograms/24 hours twice weekly, or oral 1 to 2 mg daily) with a progestogen (micronised progesterone 200 mg orally at night for 12 days of each month, or 100 mg continuously) when the uterus is present, for the shortest period that controls symptoms. Contraindicated in hormone sensitive cancer, undiagnosed vaginal bleeding, active venous thromboembolism or arterial disease, and acute liver disease.
• Non hormonal options: fezolinetant 45 mg orally once daily (check liver function before starting, monthly for 3 months and at 6 and 9 months; contraindicated in cirrhosis and severe renal impairment); venlafaxine 37.5 mg orally daily increased to 75 mg after 1 week; paroxetine 10 to 20 mg daily (avoid with tamoxifen because of CYP2D6 inhibition); gabapentin 300 mg orally at night titrated to 900 mg daily in divided doses; clonidine 50 micrograms twice daily (limited by hypotension and sedation). Cognitive behavioural therapy and hypnosis also help.
• Tuberculosis: isoniazid 5 mg/kg (maximum 300 mg), rifampicin 10 mg/kg (maximum 600 mg), pyrazinamide 25 mg/kg (maximum 2 g) and ethambutol 15 mg/kg orally daily for 2 months, then isoniazid and rifampicin for 4 months (longer in bone, joint and central nervous system disease), with pyridoxine 10 to 25 mg daily and liver function monitoring.
• HIV: antiretroviral therapy by specialist, with screening for opportunistic infection.
• Hyperthyroidism: carbimazole 20 to 40 mg orally once daily initially (maximum 60 mg daily), checking full blood count and liver function, with propranolol 10 to 40 mg orally three times daily for symptoms. Specialist review.
• Nocturnal hypoglycaemia: reduce the evening insulin or sulphonylurea dose, avoid bedtime alcohol, and review bedtime snack and basal insulin timing.
• Endocarditis, abscess, osteomyelitis and brucellosis: culture directed therapy with drainage or surgery. Brucellosis: doxycycline 100 mg orally twice daily with rifampicin 600 to 900 mg orally daily for 6 weeks.
• Lymphoma and leukaemia: haematology and oncology after tissue diagnosis.
• Phaeochromocytoma: alpha blockade (phenoxybenzamine 10 mg twice daily increased as tolerated, or doxazosin) for at least 7 to 14 days before beta blockade and surgery, specialist directed.
• Obstructive sleep apnoea: continuous positive airway pressure and weight loss. Reflux: lifestyle and a proton pump inhibitor, for example omeprazole 20 mg once daily for 4 to 8 weeks.
• Primary hyperhidrosis: aluminium chloride hexahydrate 20% solution applied to dry skin at night for focal areas; oral glycopyrronium 1 mg twice daily; dermatology for iontophoresis or botulinum toxin.
• Anxiety and trauma related sweats: psychological therapy and treatment of the underlying disorder.

Monitoring. Review at 4 to 6 weeks. Repeat weight, examination for nodes, and blood count. If a drug was changed, confirm resolution within 2 to 4 weeks.

Referral and escalation. Urgent haematology or oncology for persistent unexplained lymphadenopathy, cytopenia or B symptoms. Infectious diseases or respiratory services for suspected tuberculosis. Endocrinology for thyroid, catecholamine or pituitary disease. Gynaecology or menopause services for complex menopausal symptoms or contraindications to hormone therapy.

Admission. Rarely needed. Admit for suspected endocarditis, sepsis, severe hypoglycaemia, catecholamine crisis, or when investigation cannot be completed as an outpatient.

Safety netting. Return for fever, weight loss, lumps, cough with blood, persistent itch, palpitations with headaches, breathlessness, or recurrent episodes of hypoglycaemia.

Special groups. Pregnancy and postpartum: sweating is common and usually physiological; check thyroid function. Men on androgen deprivation therapy: gabapentin, venlafaxine or medroxyprogesterone 20 mg daily under specialist direction. Breast cancer survivors: avoid oestrogen; use non hormonal options. Older adults: review polypharmacy first; avoid anticholinergic accumulation. HIV and endemic regions: tuberculosis, brucellosis, malaria and visceral leishmaniasis come first.