The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

December 16, 2009 —  The neuroanatomical distribution of anhidrotic and hypohidrotic disorders involves lesions spanning from the cerebral cortex to the eccrine sweat glands.

• Central Nervous System Diseases causing dry skin (Anhidrosis)

Generalized anhidrosis is a frequent manifestation of multiple system atrophy, although orthostatic hypotension and extrapyramidal or cerebellar impairment usually dominate the clinical picture. Some patients have described episodic unprovoked diaphoresis, which may occur asymmetrically, early in the course of the illness.[1,2] Global or patchy patterns of anhidrosis, usually without orthostatic hypotension, may also accompany Parkinson’s disease,[4,5] progressive supranuclear palsy,[3] and pallidopontonigral degeneration.[6] In these disorders preserved facial sweating is thought to be a compensatory response.

Demyelinating lesions involving central thermoregulatory pathways frequently result in regional or global anhidrosis in patients with multiple sclerosis, particularly with more advanced disease.[7] Anhidrosis over half the face has been described in a case in which a demyelinating plaque involved the ipsilateral hypothalamus.[8] Hemibody anhidrosis has also been observed in patients following stroke[9] or thalamotomy.[10,11] Spinal cord transection typically impairs thermoregulatory sweating below the lesion. Rarely hyperhidrosis has been observed below the lesion, presumably due to disinhibition of spinal sudomotor circuits.[12] Combined with loss of active vasodilation, anhidrosis places tetraplegic patients at risk for hyperthermia.[12-14]

• Peripheral Nervous System Diseases causing dry skin (Anhidrosis)

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.[15] 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 Neuropathies causing dry skin (Anhidrosis)

Distal anhidrosis, although often subclinical, is detectable by clinical sudomotor testing in many patients with peripheral neuropathy.[16,17] Diabetes mellitus, the most common cause of autonomic neuropathy in the developed world, typically impairs thermoregulatory sweating in a stocking and glove distribution.[18] As the neuropathy progresses, asymmetric truncal anhidrosis or global anhidrosis may develop.[16]

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.[19,20] 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. Evaluation of these patients should include a complete paraneoplastic antibody screen and a careful search for an underlying neoplasm.[29] Lambert-Eaton syndrome, which is associated with antibodies to the P/Q voltage-gated calcium channel, may be accompanied by anhidrosis in patients with or without cancer.[20-22]

Hypohidrosis commonly occurs in the autonomic neuropathy associated with Sjögren’s syndrome.[23,24] Hypohidrosis also accompanies neuropathies due to amyloidosis, alcoholism, Tangier disease, vasculitis, and Fabry’s disease.[48]Focal areas of hypohidrosis may be found in patients with leprosy.[26]

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.[49]

• Ross Syndrome

Ross first drew attention to the clinical triad of progressive segmental anhidrosis with Adie’s tonic pupils and areflexia.[17] The anhidrosis is often asymmetrical, and there may be areas of compensatory hyperhidrosis elsewhere in the body.[18,19] Pharmacological and histopathological studies have indicated a postganglionic neuronal defect.[30] Skin biopsies have shown a lack of unmyelinated cholinergic sudomotor fibers and a reduction in unmyelinated and myelinated sensory fibers.[31,32]

• Chronic Idiopathic Anhidrosis

Chronic idiopathic anhidrosis refers to the syndrome of total or subtotal anhidrosis occurring either in isolation or without prominent accompanying autonomic signs or symptoms.[33] These patients become hot, flushed, dizzy, dyspneic, and weak in response to heating or exercise but do not sweat. Sudomotor testing has demonstrated a preganglionic pattern of localization in some and a postganglionic pattern in other cases.[34] Prognosis appears to be favorable.[34]

• Dermatologic Disorders causing dry skin (Anhidrosis)

Hypohidrosis commonly occurs when sweat glands are injured by burns, irradiation, skin inflammation, scarring, or trauma. Sweat gland necrosis may accompany the blistering resulting from overdoses of medication, such as barbiturates, methadone, diazepam, carbon monoxide poisoning, amitriptyline, or clonazepam.[35] Anhidrosis also occurs in primary dermatologic disorders such as psoriasis, exfoliative dermatitis, lichen sclerosis et atrophicus, ichthyosis, miliaria, scleroderma, and cholinergic urticaria.[36]

Mutations in the ED-1 gene encoding for ectodysplasin result in X-linked anhidrotic ectodermal dysplasia, which is characterized by disrupted morphogenesis of eccrine sweat glands, hair, and teeth.[37] Affected children may experience life-threatening hyperpyrexia caused by inability to sweat. Other accompanying features include nail dystrophy, hyperkeratosis of the palms and soles, cleft palate, conical teeth, facial sebaceous mucous, mammary gland hyperplasia, sparse hair, and extensive skin peeling.[38] Autosomal-recessive and autosomal-dominant modes of inheritance have also been described.[39]

• Medications disorders causing dry skin (Anhidrosis)

Hypohidrosis is a common reversible side effect of anticholinergic medications such as oxybutinin, tricyclic antidepressants, phenothiazines, and trihexphenidyl. Inhibition of sweat gland carbonic anhydrase has been hypothesized to explain hypohidrosis induced by topiramate.[40]

Box 1. Cause of anhydrosis

• Central nervous diseases Causing dry skin (Anhidrosis)

1- Multiple system atrophy (MSA)

2- Parkinson’s disease

3- Multiple sclerosis

4- Cerebrovascular disease

5- Thalamotomy

6- Spinal cord injury

• Peripheral nervous system disorders Causing dry skin (Anhidrosis)

1- Pure autonomic failure

2- Diabetic neuropathy

3- Autoimmune autonomic neuropathy

4- Paraneoplastic neuropathy

5- Amyloid neuropathy

6- Lepromatous neuropathy

7- Ross syndrome

• Miscellaneous disorders Causing skin (Anhidrosis)

1- Chronic idiopathic anhidrosis

2- Anticholinergic drugs

3- Dermatologic disorders

4- Local injury

5- Sweat gland necrosis following drug overdose

6- Congenital absence of sweat glands

7- Miscellaneous dermatologic disorders

• Dry mouth

At neurolgoical clinics, we see many patients who present with the complaint of dry or painful mouth. Presentations range from abnormal salivary secretion to complaints of dry mouth for other reasons. Normal aging, Alzheimer’s disease,[41] and multiple sclerosis[42] can all produce significant dryness. In patients with multiple sclerosis, outflow of cholinergic tracts at the subcortical level has been proposed as the cause. Dryness is also a common component in depression [43] and in fibromyalgia,[44] where it is difficult to demonstrate objective abnormalities in salivary flow. Patients with multiple system atrophy (MSA) might also suffer from dry moth.

The initial evaluation of these patients should focus on identifying treatable causes of the dryness, such as certain medications (eg, tricyclics and antihistamines) or herbal supplements that can have anticholinergic side effects. Low-grade oral yeast infection may also be reported by patients as a “dry” or “painful” mouth.[45]

Two oral agents have been approved by the US Food and Drug Administration for treatment of dry mouth: pilocarpine [46] and cevimeline.[47] Both drugs are significantly effective in treating dry mouth and act as cholinergic agonists that stimulate the muscarinic M3 receptor on the salivary glands.

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