Excessive sweating

Excessive sweating (hyperhidrosis) is sweating beyond the amount needed for thermoregulation. It may be primary (focal, usually on the palms, soles, axillae and face, with no underlying disease) or secondary to a systemic disorder, drug or neurological lesion. Primary focal hyperhidrosis is common, begins early, and causes major social and occupational disability. Secondary generalised hyperhidrosis needs a search for the cause.

Epidemiology. Primary hyperhidrosis affects about 3% of people, begins in childhood or adolescence, and often has a family history. Secondary hyperhidrosis can begin at any age.

Physiology. Eccrine glands (palms, soles, axillae, whole body) are innervated by sympathetic cholinergic fibres using acetylcholine. Apocrine glands (axillae, groin) respond to adrenergic stimuli. Sweating is controlled by the hypothalamic thermoregulatory centre, by emotional input from the limbic system, and by gustatory reflexes.

Classification.

• Primary focal hyperhidrosis: palmar, plantar, axillary, craniofacial. Diagnostic features: visible, excessive sweating for at least 6 months without a cause plus 2 of: bilateral and symmetrical, impairs daily activity, at least one episode weekly, onset before age 25, positive family history, and cessation during sleep.
• Secondary generalised hyperhidrosis: systemic disease, drugs, withdrawal, toxins, menopause.
• Secondary focal hyperhidrosis: neurological or local lesions (gustatory sweating, post sympathectomy compensatory sweating, spinal lesions, Horner syndrome with contralateral sweating).
• Hyperhidrosis Disease Severity Scale: 1 (never noticeable, never interferes), 2 (tolerable, sometimes interferes), 3 (barely tolerable, frequently interferes), 4 (intolerable, always interferes). Scores of 3 or 4 mark severe disease.

History.

• Distribution (focal or generalised, unilateral or bilateral), onset, duration, triggers (heat, emotion, food, exercise), daytime and night pattern, effect on work, hobbies, social life, clothing and hand contact.
• Systemic features: fever, weight loss, appetite change, palpitations, tremor, flushing, headaches, hypoglycaemia symptoms, chest pain, cough, haemoptysis, lumps, heat intolerance.
• Neurological: unilateral face sweating, ptosis, facial flushing, limb weakness, sensory loss, bladder disturbance, autonomic symptoms, sweating after eating (gustatory), trauma or surgery to the parotid, neck or chest.
• Drugs and substances: SSRIs, venlafaxine, tricyclics, opioids, tramadol, bupropion, cholinergic agents (pilocarpine, neostigmine, pyridostigmine), antipyretics, hormone therapy, antihypertensives, stimulants, cocaine, amphetamines, MDMA, caffeine, nicotine, alcohol use and withdrawal, opioid and benzodiazepine withdrawal, organophosphate exposure.
• Family history of hyperhidrosis. Menstrual and menopausal history, pregnancy.
• Psychological: anxiety, social phobia, depression, body image.

Examination.

• Distribution of sweating (palms, soles, axillae, face, trunk). Skin maceration, infection (pitted keratolysis, fungal infection, bromhidrosis), staining.
• Vital signs, temperature, body mass index.
• Thyroid, tremor, eye signs, lymph nodes, heart murmurs, chest, abdomen, spleen.
• Neurological: pupils (miosis and ptosis in Horner syndrome), facial sweating and flushing, limb power, sensation, spinal level.
• Signs of acromegaly (coarse features, large hands), Cushing syndrome.
• Mental state and anxiety.
• Minor starch iodine test to map the sweating area. Gravimetry (sweat collected on pre weighed filter paper over 5 minutes: over 50 mg in the axilla or over 100 mg on the palm indicates hyperhidrosis).

Red flags.

• New generalised sweating in an adult, with fever, weight loss, night sweats or lymphadenopathy.
• Unilateral or segmental sweating, ptosis, miosis (Horner syndrome, Pancoast tumour, syrinx, carotid dissection).
• Paroxysmal sweating with headache, palpitations and hypertension (phaeochromocytoma).
• Chest pain, breathlessness, pallor and sweating (myocardial infarction, pulmonary embolism, shock).
• Hypoglycaemia, tachycardia, tremor, agitation, hyperthermia or rigidity (serotonin syndrome, thyroid storm, sympathomimetic toxicity).
• Pinpoint pupils, salivation, bronchorrhoea, bradycardia (organophosphate poisoning).
• Alcohol or drug withdrawal with tremor, hallucinations or seizures.
• Suspected sepsis.

Primary. Primary focal hyperhidrosis (palmar, plantar, axillary, craniofacial), idiopathic generalised hyperhidrosis.

Endocrine and metabolic. Hyperthyroidism, diabetes mellitus and hypoglycaemia, acromegaly, phaeochromocytoma and paraganglioma, carcinoid syndrome, menopause and perimenopause, pregnancy, obesity, hyperpituitarism, hypogonadism and androgen deprivation therapy, mastocytosis.

Infective. Tuberculosis, HIV infection, infective endocarditis, malaria, brucellosis, abscess, osteomyelitis, sepsis, other febrile illness.

Malignancy. Lymphoma, leukaemia, renal cell carcinoma, hepatocellular carcinoma, neuroendocrine tumour, Pancoast tumour.

Drugs, toxins and withdrawal.

• Drugs: SSRIs, venlafaxine, tricyclics, opioids, tramadol, bupropion, cholinergic agents (pilocarpine, neostigmine, pyridostigmine), antipyretics, anti-diabetic agents causing hypoglycaemia, tamoxifen, aromatase inhibitors, levothyroxine excess.
• Toxins: organophosphates and carbamates, sympathomimetics (cocaine, amphetamines, MDMA), salicylate poisoning, caffeine excess.
• Withdrawal: alcohol, opioids, benzodiazepines, SSRIs, nicotine.
• Serotonin syndrome and neuroleptic malignant syndrome.

Cardiovascular and respiratory. Acute myocardial infarction, heart failure, pulmonary embolism, shock, hypoxia and hypercapnia.

Neurological and autonomic. Horner syndrome, stroke (hypothalamic or brainstem), syringomyelia, spinal cord injury (autonomic dysreflexia), Parkinson disease, autonomic neuropathy, gustatory sweating (Frey syndrome after parotid surgery), compensatory hyperhidrosis after thoracic sympathectomy, post traumatic and nerve injury related sweating, epilepsy.

Psychiatric. Anxiety disorders, panic attacks, social phobia, post traumatic stress disorder.

Others. Hypoglycaemia of any cause, hot environment and heavy clothing, fever, pain.

1. Distinguish focal from generalised sweating and primary from secondary disease by history, examination and the diagnostic features of primary hyperhidrosis. Primary focal hyperhidrosis in a young person with typical features and no red flags needs no investigation.
2. Secondary or generalised sweating: full blood count with film, ESR and C reactive protein, urea, creatinine and electrolytes, calcium, liver function tests, glucose or HbA1c, thyroid stimulating hormone and free thyroxine, HIV test with consent, and chest radiograph.
3. Targeted tests: plasma free metanephrines or 24 hour urinary fractionated metanephrines (phaeochromocytoma), IGF-1 (acromegaly), urinary 5 hydroxyindoleacetic acid (carcinoid), serum tryptase (mastocytosis), tuberculosis tests, blood cultures and echocardiography (endocarditis), CT of chest, abdomen and pelvis for malignancy, excisional lymph node biopsy, urine drug screen, serum salicylate level, cholinesterase level in suspected organophosphate exposure, 08:00 cortisol, and pregnancy test.
4. Neurological localisation: MRI of the brain and cervical and thoracic spine, chest imaging for Pancoast tumour, carotid imaging when Horner syndrome is acute and painful.
5. Objective sweat testing (gravimetry, starch iodine test, sweat evaporimetry) to document severity and guide botulinum toxin placement.
6. Screen for anxiety and depression, and measure disease impact with the Hyperhidrosis Disease Severity Scale.

Limits. Primary hyperhidrosis has no test; the diagnosis rests on the history. Metanephrines can be falsely raised by drugs and stress. Normal tests do not exclude lymphoma or tuberculosis in a patient with persistent generalised sweating.

Emergency (secondary hyperhidrosis from toxins or critical illness).

• Serotonin syndrome: stop serotonergic drugs, supportive care and cooling, benzodiazepines (lorazepam 1 to 2 mg intravenously, repeated as needed), and cyproheptadine 12 mg orally as a loading dose then 2 mg every 2 hours until symptoms settle (maintenance 8 mg every 6 hours, maximum 32 mg daily).
• Organophosphate poisoning: atropine 1 to 2 mg intravenously, doubled every 5 minutes until secretions dry; pralidoxime 30 mg/kg intravenously over 30 minutes then 8 mg/kg/hour; decontamination and airway support.
• Hypoglycaemia: glucose 10% 150 to 200 mL intravenously or oral glucose 15 to 20 g.
• Thyroid storm, myocardial infarction, pulmonary embolism, sepsis and shock are emergencies needing immediate resuscitation and specific treatment.

Primary focal hyperhidrosis, stepwise.

1. General: wear loose natural fibre clothing, use absorbent pads and antiperspirants, avoid triggers (caffeine, spicy food, alcohol), wash and dry thoroughly.
2. Topical aluminium chloride hexahydrate 20% solution applied to dry skin at night for 6 to 8 hours and washed off in the morning, daily until effect then once or twice weekly; reduce frequency or add hydrocortisone 1% cream for irritation. Do not apply to broken skin or the face and eyes.
3. Iontophoresis for palms and soles with tap water: 15 to 20 mA for 20 to 30 minutes, 3 to 4 sessions weekly for 2 to 3 weeks, then maintenance weekly.
4. Botulinum toxin type A intradermal injections: about 50 units into each axilla, repeated every 4 to 9 months; palms and soles need larger doses (about 100 units each side) and are painful; specialist administration with nerve block.
5. Oral anticholinergic drugs: glycopyrronium 1 mg orally twice daily, increased as needed to a maximum of 2 mg three times daily; oxybutynin 2.5 to 5 mg orally twice daily, increased to a maximum of 5 mg three times daily; propantheline 15 mg three times daily. Counsel on dry mouth, constipation, blurred vision, urinary retention and heat intolerance; avoid in glaucoma, urinary retention and older adults at risk of confusion.
6. Craniofacial hyperhidrosis: topical glycopyrronium 2% to 3% preparations, oral anticholinergics, and botulinum toxin.
7. Procedural options: microwave thermolysis, curettage or liposuction of axillary glands, and endoscopic thoracic sympathectomy for severe palmar disease after medical therapy fails. Compensatory sweating of the trunk is common after sympathectomy (estimates vary widely from about 20% to 80%), so counselling is essential.
8. Anxiety related sweating: cognitive behavioural therapy; propranolol 10 to 40 mg orally before specific situations.

Secondary hyperhidrosis. Treat the cause:

• antithyroid drugs for hyperthyroidism (carbimazole 20 to 40 mg orally once daily initially, maximum 60 mg)
• change the offending drug
• treat infection
• tuberculosis (isoniazid 5 mg/kg, rifampicin 10 mg/kg, pyrazinamide 25 mg/kg and ethambutol 15 mg/kg daily for 2 months, then isoniazid and rifampicin for 4 months)
• manage menopause (non hormonal options such as venlafaxine 37.5 mg daily increased to 75 mg, gabapentin 300 mg at night titrated to 900 mg daily, or hormone therapy where appropriate)
• phaeochromocytoma (alpha blockade then surgery)

Frey syndrome: topical glycopyrronium or botulinum toxin injection of the affected skin.

Monitoring. Review at 4 to 6 weeks after starting treatment with repeat disease severity scale and adverse effects. Reassess if new features arise.

Referral and escalation. Immediate: toxic or critical causes. Urgent: red flags for malignancy, endocrine tumour or neurological lesion. Dermatology for refractory primary hyperhidrosis, botulinum toxin and procedural options. Surgery for sympathectomy. Endocrinology for hyperthyroidism, acromegaly or catecholamine tumours.

Admission. Toxic ingestion or withdrawal states with instability, thyroid storm, hypoglycaemia, suspected sepsis, acute coronary syndrome, or hyperthermia.

Safety netting. Return for fever, weight loss, palpitations with headaches, chest pain, confusion, new unilateral facial changes, or side effects of treatment such as retention and visual blurring.

Special groups. Children: primary hyperhidrosis often begins in childhood; use topical aluminium chloride and iontophoresis first. Pregnancy: topical and iontophoresis treatments are acceptable; avoid oral anticholinergics and botulinum toxin. Older adults: avoid anticholinergics when possible. HIV: consider drugs, opportunistic infection and lymphoma. Hot climates: environmental sweating is normal, but the pattern and severity should be proportionate.