Anhidrosis
- Article Author:
- Chelsea Harper
- Article Editor:
- Rene Bermudez
- Updated:
- 5/23/2020 6:31:06 PM
- For CME on this topic:
- Anhidrosis CME
- PubMed Link:
- Anhidrosis
Introduction
Anhidrosis is the inability to sweat. It is important to recognize anhidrosis as it can be potentially life-threatening due to heat-related illnesses.[1] There are three main causes of anhidrosis, which are peripheral alterations in the eccrine gland itself, idiopathic, and central or neuropathic disease and/or medication that disrupts neural inputs from the anterior hypothalamus to the gland.[2]
Causes of central/neuropathic anhidrosis can occur at any level of innervation.[3] The disturbance can occur at the sweating center in the brain, the descending neural tract, or the sweat gland. A disruption will lead to an absence in sweating. Disruption in the neural input can be due to tumors or infarctions of the hypothalamus, pons, or medulla. Spinal cord tumors, injuries, or infarctions can disrupt the neural tract.[4] Other etiologies such as degenerative syndromes (Shy-Drager syndrome), autoimmune autonomic neuropathy, peripheral neuropathy (diabetes, alcohol use disorder, leprosy), and drugs have all been implicated in central/neuropathic anhidrosis.[5]
Peripheral alterations that cause anhidrosis can be congenital or acquired. Forms of peripheral alterations can be due to genetic abnormalities such as incontinentia pigmenti, due to local destruction, for example, by a tumor, or obstruction by entities such as psoriasis.
As heat intolerance may be due to various underlying disorders, a detailed history is important in establishing the diagnosis. Heat intolerance can cause symptoms of drowsiness, episodic inability to concentrate while in a hot environment, and or fatigue along with a decrease in the patient's normal sweating are clues to the diagnosis of anhidrosis. A detailed history should also include the addition of medications, medical events such as injuries, growths or radiation, alcohol consumption, the presence of autoimmune disease or diabetes mellitus, and family history.[2]
Etiology
Central and neuropathic causes of anhidrosis can occur anywhere along the neural track, as previously stated. There are diagnostic clues that will aid in locating the area of the lesion. If there is the involvement of the pontine or medulla, the patient will have ipsilateral facial and neck anhidrosis.[6] Neural tracks in the spinal cord have both crossed and uncrossed fibers. Therefore, alterations in the spinal cord will result in anhidrosis of the skin that can be either ipsilateral or contralateral. Peripheral neuropathies tend to be symmetrical as in diabetes mellitus and alcohol use disorder.[7] However, there are cases of asymmetrical peripheral neuropathy leading to anhidrosis, such as in cases of leprosy. A patient with Horner syndrome will present after the disruption of the superior cervical ganglion. Regional anhidrosis can also occur due to the chemical blockade of a selected sympathetic ganglion. Congenital insensitivity to pain with anhidrosis is a rare entity that is autosomal and recessive. It presents with self-mutilation due to a lack of pain, intellectual disability, and recurrent fevers due to anhidrosis.[8][9]
Drugs that interfere with the synaptic transmission in the autonomic ganglia will lead to anhidrosis:[10]
- Nicotinic acetylcholine receptor antagonists such as hexamethonium and trimethaphan
- Muscarinic acetylcholine receptor antagonists such as atropine or scopolamine
- Calcium channel blockers
- Alpha-adrenergic blockers such as phentolamine
- Alpha2-adrenergic agonists such as clonidine
- 5-fluorouracil
- Topiramate
- Zonisamide
- Quinacrine
There are numerous causes of abnormalities in the sweat gland that cause anhidrosis. Among the various causes are several hereditary and acquired systemic diseases that present with generalized or localized anhidrosis. Males with X-linked hypohidrotic ectodermal dysplasia will have an absence of sweat glands, whereas female carriers will have hypohidrosis or reduced sweating.[11][12] The other ectodermal dysplasias, such as Rapp-Hodgkin syndrome and Naegeli-Franceschetti-Jadassohn syndrome, can lead to sweat gland abnormalities.[13] Though not an exhaustive list, there are other rare inherited syndromes in which genetic errors result in sweat gland dysfunction such as Bazex-Dupre-Christol syndrome and Fabry disease.[14]
Location tissue destruction can be the culprit of acquired localized anhidrosis. Tumors, radiation therapy, systemic sclerosis, burns, graft-versus-host disease, acrodermatitis chronica atrophicans, and Sjögren syndrome can distort the normal architecture of the skin with subsequent anhidrosis. Entities that lead to obstruction of the glands are also implicated in anhidrosis. Psoriasis, lamellar ichthyosis, miliaria, eczematous dermatoses, porokeratosis, and bullous diseases are examples of obstruction.[15]
Epidemiology
Anhidrosis is a clinical finding and not a distinct entity. The exact epidemiology will depend on the underlying etiology. In the majority of anhidrosis cases, men and women are equally affected, with a few exceptions. The age of presentation will vary based on the underlying etiology.
Pathophysiology
The pathophysiology of anhidrosis varies depending on the etiology as anhidrosis is a clinical finding and not a distinct entity. For central and neuropathic anhidrosis, interruption of innervation at any level along the pathway from the sweating centers located in the brain to the sweat glands can result in absent sweating. Drugs that interfere with the synaptic transmission in autonomic ganglia can inhibit sweating. Peripheral alterations can result in the absence of sweating. Peripheral alterations include genetic disorders, destruction, or obstruction. Genetic abnormalities underlie several types of anhidrosis, and the pathogenesis may be unknown. Other etiologies may have a known cause, such as local tissue destruction by prior radiation therapy. The clinical presentation and history can help delineate the pathophysiology.[16]
Histopathology
The histopathology will vary depending on the etiology. Males with X-linked hypohidrotic ectodermal dysplasia will have an absence of sweat glands, whereas female carriers will have reduced glands. The clinical presentation and or a skin biopsy will help to identify those with local destruction or obstruction.[17]
History and Physical
History and physical exam findings for anhidrosis will differ between the various underlying etiologies. A thorough history should be obtained, including past medical history, medications, medical treatments (i.e., radiation therapy), and family history. A careful and detailed history will yield clues to a potential diagnosis.[9]
A patient may complain of heat intolerance, fatigue, drowsiness, or inability to concentrate in warm environments. A patient that has central/neuropathic anhidrosis may have accompanying neurological symptoms such as ptosis and miosis in Horner syndrome. Although very rare, a patient with congenital insensitivity to pain with anhidrosis will present with self-mutilation.
Those with anhidrosis due to destruction will have the physical exam findings of the underlying etiology, such as scarring from a prior burn or sclerotic changes as in morphea.
Anhidrosis caused by obstruction will likewise have the physical exam findings associated with the underlying etiology such as psoriatic plaques or lamellar ichthyosis.
Evaluation
Detailed patient history is paramount in determining the possible underlying etiology. The next step would be to determine any potential contributing factors, such as medications. Colorimetric and or gravimetric testing can demonstrate diminished or absent sweating. Injection of local, intradermal cholinergic drugs to promote sweating can be utilized. However, this should only be done in a small area as the side effect profile and its associated risks preclude injection into large areas. If a patient is suspected of having peripheral neuropathy, testing the axon reflex sweating by injecting an intradermal picrate or nicotine sulfate at an appropriate dose may be performed. A skin biopsy from an affected area should always be obtained in patients with suspected anhidrosis to identify abnormalities of the sweat glands.
Treatment / Management
Unfortunately, treatment options for anhidrosis can be limited unless an offending agent can be discontinued. Clinicians need to stress the importance of maintaining a cool environment for the patient. The use of water spray bottles for purposes of cooling can prove helpful. For those disorders due to clogged sweat glands, frequent and gentle exfoliation is useful. Those with disorders of cornification and overheating, such as lamellar ichthyosis, should be treated aggressively and monitored closely.
Differential Diagnosis
When considering anhidrosis, a differential diagnosis will depend on the underlying etiology.
Central and neuropathic anhidrosis:
- Tumors, infarctions or other alterations of the hypothalamus, pons, medulla or spinal cord
- Horner syndrome
- Degenerative syndromes such as Ross syndrome or Shy-Drager
- Autoimmune autonomic neuropathy
- Congenital insensitivity to pain with anhidrosis
- Peripheral neuropathy due to diabetes mellitus, alcoholism, leprosy, amyloidosis
- Drugs
Drugs:
- Nicotinic acetylcholine receptor antagonists such as hexamethonium and trimethaphan
- Muscarinic acetylcholine receptor antagonists such as atropine or scopolamine
- Calcium channel blockers
- Alpha-adrenergic blockers such as phentolamine
- Alpha2-adrenergic agonists such as clonidine
- 5-fluorouracil
- Topiramate
- Zonisamide
- Quinacrine
Peripheral causes due to sweat gland abnormalities:
- Genetic disorders such as ectodermal dysplasias, Incontinentia pigmenti, Bazex-Dupré-Christol syndrome, Fabry disease
- Destruction from tumors, burns, radiation therapy, systemic sclerosis, morphea, Sjögren syndrome, graft-versus-host disease, acrodermatitis chronica atrophicans
- Obstruction from miliaria, ichthyoses, psoriasis, eczematous dermatoses, bullous diseases
Prognosis
The prognosis of anhidrosis varies, depending on the type of anhidrosis. Anhidrosis associated with a genetic syndrome is generally lifelong. In the setting of drug-induced anhidrosis, it is usually reversible with discontinuation of the medication.
Complications
Complications will depend on the underlying etiology. The most feared complication, no matter the underlying etiology, is heatstroke.
Deterrence and Patient Education
Clinicians need to stress the importance of maintaining a cool environment for the patient. The use of water spray bottles for purposes of cooling can prove helpful. For those disorders due to clogged sweat glands, frequent and gentle exfoliation is useful.
Enhancing Healthcare Team Outcomes
An interprofessional approach to anhidrosis is recommended.
Anhidrosis and the underlying etiologies can cause severe emotional distress for patients. Quality of life may be low for patients of all ages secondary to societal scrutinization of their underlying condition (i.e., lamellar ichthyosis). It is recommended to evaluate and arrange for mental health care in addition to the necessary medical care to address the underlying cause of the anhidrosis if there is one. The outcome of patients with anhidrosis depends on the cause. For those with inherited disorders, there is no cure and is a lifelong issue. For those with acquired anhidrosis, the outcomes may improve with the improvement of the primary condition or removal of the offending medication. Most importantly, the patient should be actively involved in their care as the patient must maintain a cool environment and recognize the signs and symptoms of heat intolerance.