Reduced sweating

Reduced sweating (hypohidrosis) is a subnormal sweat response to heat or exercise. Absent sweating (anhidrosis) is the complete failure to sweat. Both reduce evaporative cooling, so patients develop heat intolerance, flushing, dizziness, and in severe cases heat exhaustion or heat stroke. The sweat gland, its nerve supply or its central control can be at fault.

Clinical relevance. The symptom is often missed until a heat related event. Generalised anhidrosis threatens life in hot conditions. Segmental or unilateral loss can point to a lesion of the sympathetic chain, Horner syndrome or autonomic neuropathy. Drugs are the commonest correctable cause.

Physiology. Eccrine sweating depends on intact sweat glands, sympathetic postganglionic cholinergic fibres (acetylcholine acting on muscarinic receptors), preganglionic fibres from the spinal cord, and the hypothalamic thermoregulatory centre. Failure at any level reduces sweating.

Classification by distribution.

• Generalised: whole body loss, usually from drugs, widespread autonomic neuropathy, sweat gland failure, congenital disease or dehydration.
• Segmental or regional: spinal cord lesion (loss in the dermatomes caudal to the level), peripheral nerve or plexus lesion, sympathectomy, Horner syndrome (ipsilateral face), harlequin syndrome (one side of the face and upper body).
• Focal: skin scarring, burns, radiation, skin disease, local nerve injury.

Classification by cause.

• Congenital: hypohidrotic ectodermal dysplasia, congenital insensitivity to pain with anhidrosis.
• Acquired: autonomic and small fibre neuropathy, autoimmune and idiopathic, drugs, skin disease, systemic disease.

History.

• Heat intolerance, flushing, dizziness, palpitations, nausea and headache in heat or on exercise. Episodes of fever or collapse in warm weather, particularly in childhood.
• Distribution of dry skin, areas that still sweat (compensatory hyperhidrosis in remaining areas), prickling or burning on heating (cholinergic urticaria with hypohidrosis).
• Autonomic features: orthostatic dizziness, constipation, urinary retention, impotence, dry eyes and mouth, abnormal pupils.
• Neuropathic symptoms: numbness, burning feet, painless injury, ulcers.
• Systemic disease: diabetes, alcohol use, amyloidosis, Sjogren syndrome, leprosy, HIV, hypothyroidism, spinal cord injury, Parkinson disease, cancer (paraneoplastic).
• Drugs: anticholinergics (oxybutynin, atropine, scopolamine, benztropine, trihexyphenidyl), tricyclic antidepressants, antihistamines, antipsychotics, topiramate, zonisamide, carbonic anhydrase inhibitors, botulinum toxin, opioids, clonidine.
• Skin: eczema, ichthyosis, psoriasis, burns, radiation, scleroderma, miliaria.
• Family history of absent teeth, sparse hair, heat intolerance or pain insensitivity (X linked or autosomal conditions).
• Exposure to hot climates or strenuous work in the heat.

Examination.

• Temperature, pulse, blood pressure lying and standing (orthostatic fall of 20 mmHg systolic or 10 mmHg diastolic), hydration.
• Skin: dry, scaly, thin, hairless areas, scars, atrophic changes, miliaria, signs of scleroderma, angiokeratomas (Fabry disease).
• Face and teeth: sparse hair, hypodontia, conical teeth, saddle nose, thin periorbital skin (ectodermal dysplasia).
• Pupils and eyelids (Horner syndrome, tonic pupil), dry eyes and mouth, parotid swelling.
• Neurological: sensation (pain, temperature, vibration), reflexes, power, autonomic signs, spinal level, tremor and rigidity.
• Thyroid, lymph nodes, heart and abdomen.
• Minor starch iodine test or thermoregulatory sweat test to map dry areas.

Red flags.

• Temperature over 40 degrees Celsius with confusion, collapse or hot dry skin (heat stroke).
• Recurrent unexplained fever in a child, absent sweating, self injury or painless injury.
• Unilateral facial anhidrosis with ptosis and miosis (carotid dissection, Pancoast tumour).
• Rapidly progressive autonomic failure, orthostatic hypotension, weight loss, neuropathy (amyloidosis, paraneoplastic or autoimmune autonomic neuropathy).
• New segmental loss with back pain or sensory level (spinal cord lesion).
• Anticholinergic toxicity (delirium, mydriasis, hot dry skin, urinary retention, tachycardia).

Drugs and toxins. Anticholinergic drugs (oxybutynin, atropine, scopolamine, benztropine, trihexyphenidyl), tricyclic antidepressants, first generation antihistamines, antipsychotics (clozapine, olanzapine), topiramate and zonisamide, acetazolamide, botulinum toxin, opioids, clonidine, belladonna alkaloids, anticholinergic plants.

Autonomic and peripheral neuropathy. Diabetic autonomic neuropathy, amyloidosis (primary and hereditary), Sjogren syndrome, small fibre neuropathy, alcohol related neuropathy, leprosy, Fabry disease, HIV neuropathy, Guillain-Barre syndrome, paraneoplastic autonomic neuropathy (anti Hu), autoimmune autonomic ganglionopathy (ganglionic acetylcholine receptor antibodies), Ross syndrome, pure autonomic failure, multiple system atrophy, Parkinson disease.

Central and spinal lesions. Spinal cord injury (loss caudal to the lesion), syringomyelia, stroke, hypothalamic lesion, multiple sclerosis, brain tumour.

Segmental and unilateral. Horner syndrome (ipsilateral facial anhidrosis), harlequin syndrome, sympathectomy, neck surgery, carotid dissection, Pancoast tumour, brachial plexus injury, tonic pupil syndrome (Holmes-Adie).

Sweat gland and skin disease. Idiopathic acquired generalised anhidrosis (including acute idiopathic anhidrosis), hypohidrotic ectodermal dysplasia, congenital insensitivity to pain with anhidrosis, ichthyosis, atopic dermatitis, psoriasis, scleroderma, burns and scars, radiation dermatitis, miliaria profunda (tropical anhidrotic asthenia), cutaneous graft versus host disease, mycosis fungoides.

Metabolic and systemic. Dehydration and hypovolaemia, hypothyroidism, hypercalcaemia, chronic kidney disease, cystic fibrosis (salty sweat with variable output), systemic sclerosis, severe malnutrition, ageing.

1. Establish the distribution (generalised, segmental, focal), the drug history and any systemic disease. Measure core temperature and orthostatic blood pressure.
2. First line tests: HbA1c and glucose, full blood count, urea, creatinine and electrolytes, calcium, thyroid stimulating hormone, vitamin B12, serum protein electrophoresis with immunofixation, ESR and C reactive protein, HIV test with consent, antinuclear antibody with anti Ro and anti La antibodies, and liver function tests.
3. Sweat testing: thermoregulatory sweat test (starch iodine or alizarin red indicator in a heated chamber, showing distribution and percentage of anhidrosis), quantitative sudomotor axon reflex test (post ganglionic sudomotor function), silicone impression test, sympathetic skin response.
4. Autonomic function: heart rate response to deep breathing and Valsalva, head up tilt test (sustained fall of 20 mmHg systolic or 10 mmHg diastolic within 3 minutes), plasma catecholamines.
5. Skin biopsy with intraepidermal nerve fibre density and sweat gland innervation, and sweat gland histology (inflammatory infiltrate in autoimmune disease). Abdominal fat pad or rectal biopsy for amyloid.
6. Targeted: Schirmer test and salivary scintigraphy for Sjogren syndrome; ganglionic acetylcholine receptor antibodies and paraneoplastic antibody panel with CT or PET for suspected cancer; alpha galactosidase A enzyme activity and gene testing for Fabry disease; genetic testing for EDA, EDAR and NTRK1; leprosy slit skin smear; spinal MRI; MRI of the brain and carotid imaging for Horner syndrome.
7. Sweat chloride test if cystic fibrosis is suspected.

Limits. Formal sudomotor tests are available in specialist laboratories only. Normal tests do not exclude a small fibre neuropathy; skin biopsy is more sensitive. Drug effects can mimic neuropathy and need withdrawal to confirm.

Heat illness (emergency).

Heat exhaustion: move to a cool place, remove clothing, oral rehydration, cooling, and observe.

Heat stroke (core temperature over 40 degrees Celsius with central nervous system dysfunction):

• rapid cooling to under 39 degrees Celsius, preferably by cold water immersion, or evaporative cooling with fans and ice packs
• intravenous isotonic fluids (500 to 1000 mL boluses, avoiding overload)
• airway protection
• benzodiazepines for agitation
• monitoring for rhabdomyolysis, acute kidney injury and coagulopathy

Antipyretics do not work. Admit to critical care.

Prevention of overheating (all patients with true hypohidrosis).

• Avoid hot environments and strenuous exercise in the heat. Schedule activity for cooler times.
• Hydration, light loose clothing, cooling vests or wet cloths, personal fans, spray bottles, cool showers, air conditioning, shade and cold packs on the neck and axillae.
• Education about early symptoms (flushing, dizziness, headache, nausea) and a plan to cool at once.
• Carry a thermometer. For children, school and sport plans and temperature checks.

Cause directed treatment.

• Drugs: stop or substitute the offending agent (oxybutynin, topiramate, zonisamide, tricyclics, first generation antihistamines, anticholinergics). Monitor children on topiramate and zonisamide for fever and reduced sweating.
• Diabetic autonomic neuropathy: optimise glucose control, treat orthostatic hypotension (fluids, compression, fludrocortisone 100 micrograms orally daily or midodrine 2.5 to 10 mg three times daily), and treat constipation.
• Sjogren syndrome: pilocarpine 5 mg orally three to four times daily for dry mouth and eyes (also may increase sweating; caution in asthma, glaucoma and bradycardia) and rheumatology care.
• Idiopathic acquired generalised anhidrosis, acute idiopathic anhidrosis and autoimmune ganglionopathy: high dose corticosteroid (methylprednisolone 500 mg to 1 g intravenously daily for 3 days, then prednisolone 0.5 to 1 mg/kg orally daily with a slow taper) has benefit in case series; evidence is limited; specialist directed. Cholinergic urticaria: a non sedating antihistamine such as cetirizine 10 mg daily.
• Fabry disease: agalsidase beta 1 mg/kg intravenously every 2 weeks, or migalastat 123 mg orally every other day for amenable variants, with pain, renal and cardiac care.
• Amyloidosis: specialist directed therapy.
• Paraneoplastic autonomic neuropathy: treat the tumour and immunomodulation.
• Miliaria profunda: cooling, avoidance of occlusion and sweating, and time to recover; skin emollients.
• Hypohidrotic ectodermal dysplasia and congenital insensitivity to pain with anhidrosis: multidisciplinary care, temperature monitoring, dental and ophthalmic care, injury prevention, and genetic counselling.
• Horner syndrome: urgent imaging to exclude carotid dissection (CT or MR angiography) and apical lung tumour.
• Hypothyroidism: levothyroxine 1.6 micrograms/kg orally once daily on an empty stomach (start 25 micrograms daily in older adults or coronary disease).

Monitoring. Review in 2 to 4 weeks after drug withdrawal. Repeat orthostatic blood pressure and temperature, and sweat testing if the cause remains unclear.

Referral and escalation. Immediate: heat stroke. Urgent: Horner syndrome with pain or neurological signs, rapidly progressive autonomic failure, suspected cancer. Neurology or autonomic clinics for neuropathy. Dermatology and genetics for congenital disease. Endocrinology or rheumatology for the underlying disease.

Admission. Heat stroke, severe heat exhaustion, recurrent hyperpyrexia, autonomic crisis, or unstable orthostatic hypotension.

Safety netting. Return for high temperature, confusion, collapse, vomiting, very dark urine, fainting, or reduced urine in heat.

Special groups. Children: topiramate, zonisamide, ectodermal dysplasia and congenital insensitivity to pain with anhidrosis; plan for school and sport. Older adults: anticholinergic burden, diabetes and dehydration; reduce drugs. Pregnancy: fever and heat are harmful to the foetus; manage drug withdrawal carefully. Tropical and military settings: miliaria and heat illness are common; acclimatise over 1 to 2 weeks.