What are the causes of anhidrosis (lack of sweat) in individuals, particularly during exercise, considering factors such as age, gender, medical history, including conditions like diabetes, and medication side effects?

Causes of Anhidrosis (Lack of Sweating) During Exercise

Anhidrosis during exercise results from three main categories: medications that impair thermoregulation, chronic medical conditions affecting sweat gland function or autonomic control, and primary disorders of the sweat glands themselves.

Medication-Induced Causes

Anticholinergic drugs are the most common medication cause of impaired sweating during exercise. 1 These medications block the neurotransmitter acetylcholine, which is essential for sweat gland activation. Common culprits include:

• Anticholinergic medications used for various conditions 1
• Dopamine-reuptake inhibitors (e.g., medications for ADHD) 1
• Diuretics, which can impair thermoregulation through volume depletion 1
• Antihypertensive medications, particularly in elderly individuals 1

These medications warrant particular concern because they directly interfere with the body's ability to dissipate heat through evaporative cooling, increasing risk of heat illness during physical activity. 1

Chronic Medical Conditions

Endocrine and Metabolic Disorders

Diabetes mellitus (both type 1 and type 2) is a major cause of exercise-related anhidrosis through autonomic neuropathy affecting sudomotor function. 1, 2 Research demonstrates that people with diabetes show:

• Impaired sweat production across all body areas during heat exposure 2
• Absent or diminished sudomotor rhythm (the normal pulsatile pattern of sweating) 2
• Paradoxical hypersweating of the head while other areas show diminished sweating during exercise 2
• Central mechanisms affecting heat sensitivity in the hypothalamus, not just peripheral sweat gland dysfunction 2

Other endocrine conditions that impair sweating include: 1

• Diabetes insipidus (affects water-electrolyte balance)
• Juvenile hyperthyroidism (Graves disease) (alters thermoregulation)

Genetic and Congenital Disorders

Fabry disease causes anhidrosis or hypohidrosis as one of its earliest clinical manifestations. 1 This X-linked lysosomal storage disorder leads to:

• Hypohidrosis commonly present in both males and females 1
• Exercise intolerance beginning early in childhood 1
• Impaired thermoregulation contributing to heat intolerance 1

Other congenital causes include: 3

• Hypohidrotic ectodermal dysplasia
• Congenital insensitivity to pain with anhidrosis

Other Chronic Conditions

• Obesity impairs exercise-heat tolerance and thermoregulation 1
• Cystic fibrosis affects sweat electrolyte composition and thermoregulation 1
• Sickle cell trait can complicate heat tolerance during strenuous activity 1

Acquired Idiopathic Causes

Acquired idiopathic generalized anhidrosis (AIGA) represents isolated anhidrosis with no detectable underlying cause. 4, 3 This condition is classified into three categories based on the site of disturbance:

1. Sudomotor neuropathy (nerve dysfunction) 3
2. Idiopathic pure sudomotor failure (autonomic dysfunction) 3
3. Sweat gland failure (peripheral gland dysfunction) 3

AIGA responds well to high-dose systemic corticosteroids, suggesting an immune-mediated mechanism. 4

Dermatological Causes

Skin conditions and damage can physically impair sweat gland function: 4

• Localized skin damage from burns, radiation, or trauma
• Inflammatory skin diseases affecting sweat glands
• Scarring that destroys sweat gland architecture

Neurological Causes

Neurological disorders affecting sweating should be classified by upper versus lower motor neuron patterns: 4

• Upper motor neuron lesions (brain and spinal cord) present with spasticity and hyperactive reflexes 4
• Lower motor neuron lesions (peripheral nerves) present with flaccidity and hypoactive reflexes 4
• Autonomic dysfunction affecting sudomotor pathways 4

Acute Illness-Related Causes

Current or recent illness temporarily impairs thermoregulation and sweating capacity: 1

• Gastrointestinal illness (vomiting, diarrhea) causes dehydration affecting sweat production 1
• Fever disrupts normal thermoregulatory mechanisms 1
• Any acute illness affecting water-electrolyte balance 1

Clinical Pitfalls and Evaluation

When evaluating anhidrosis, first exclude exogenous causes (medications, environmental factors), then perform a focused physical examination for mucocutaneous and neurological signs. 4 Key diagnostic steps include:

• Review all medications, particularly anticholinergics and diuretics 1
• Screen for underlying conditions using laboratory tests: complete blood count, comprehensive metabolic panel, thyroid function, hemoglobin A1c 5
• Skin biopsy if dermatological cause suspected 4
• MRI of brain/spinal cord for upper motor neuron lesions 4
• Nerve conduction studies for lower motor neuron lesions 4
• Autonomic function testing for suspected autonomic dysfunction 4

A critical caveat: dehydration alone does not cause anhidrosis—it actually increases plasma osmolality, which can reduce sweat rate but does not eliminate sweating. 1, 6 True anhidrosis during exercise with adequate hydration indicates an underlying pathological process requiring investigation.