Peripheral Nervous System Disease
With normal aging, thermoregulatory sweat output declines due to peripheral neural and eccrine glandular factors, which vary in degree depending on genetic predisposition and level of physical conditioning.[75] Extensive anhidrosis may also accompany disease of the peripheral nervous system. When exposed to an elevated ambient temperature or physical exercise, these individuals may present with symptoms of heat intolerance, dizziness, weakness, flushing, dyspnea, or palpitations and may be at risk for heat exhaustion and hyperthermia.
Peripheral Neuropathy
Distal anhidrosis, although often subclinical, is detectable by clinical sudomotor testing in many patients with peripheral neuropathy.[76,77] Diabetes mellitus, the most common cause of autonomic neuropathy in the developed world, typically impairs thermoregulatory sweating in a stocking and glove distribution.[78] As the neuropathy progresses, asymmetric truncal anhidrosis or global anhidrosis may develop.[76]
Some immune-mediated neuropathies selectively target the autonomic neuron. Autoimmune autonomic neuropathy typically presents with sicca complex, anhidrosis, gastrointestinal hypomotility, orthostatic hypotension, abnormal pupillary light reflexes, and neurogenic bladder that may be subacute or insidious in onset. Autoantibodies to the ganglionic acetylcholine receptor have been demonstrated in these patients.[29,79,80] Subacute autonomic neuropathy may signal an occult malignancy, most commonly small cell lung carcinoma. The dysautonomia in paraneoplastic autonomic neuropathy can be manifested mainly by cholinergic failure presenting as gastrointestinal dysfunction and anhidrosis.
Hypohidrosis commonly occurs in the autonomic neuropathy associated with Sjögren's syndrome.[83,84] Hypohidrosis also accompanies neuropathies due to amyloidosis, alcoholism, Tangier disease, vasculitis, and Fabry's disease.[85] Focal areas of hypohidrosis may be found in patients with leprosy.[86]
Anhidrosis is a prominent feature of hereditary sensory and autonomic neuropathies type IV and V (congenital insensitivity to pain with anhidrosis), in which absent skin innervation is associated with mutations of the NTRK1 gene encoding the neurotrophic tyrosine kinase receptor type 1.[30]
