What Causes Cholinergic Urticaria?
Cholinergic urticaria is primarily caused by stimuli that trigger sweating—specifically, the release of acetylcholine activates the sweat reflex when core body temperature rises, leading to characteristic small, itchy wheals. 1
Primary Triggering Mechanism
The British Association of Dermatologists classifies cholinergic urticaria as a thermal physical urticaria, but emphasizes a critical distinction: it is primarily induced by the stimulus for sweating rather than overheating per se, even though the usual reason for sweating is a raised core temperature. 1
Common triggers that induce sweating and precipitate cholinergic urticaria include:
- Strenuous exercise 2
- Hot baths or showers 2, 3
- Emotional stress 3
- Any activity that raises core body temperature sufficiently to activate the sweat reflex 3
Underlying Pathophysiological Subtypes
Recent research has identified that cholinergic urticaria operates through two distinct pathomechanisms involving acetylcholine (ACh): 4
1. Indirect ACh Action: Sweat Hypersensitivity Type
- ACh triggers perspiration, and sweat antigens leak from damaged or obstructed sweat ducts into the dermis, where they stimulate mast cells to release histamine 4
- More than half of cholinergic urticaria patients demonstrate sweat hypersensitivity with positive autologous sweat skin tests 5
- This represents a true "sweat allergy" mechanism 4
2. Direct ACh Action: Impaired Sweating Type
- Patients with reduced or absent sweating (anhidrosis/hypohidrosis) show decreased expression of acetylcholine receptor M3 (CHRM3) and acetylcholine esterase (ACh-E) in sweat gland epithelial cells 6
- Released ACh cannot be adequately trapped by deficient cholinergic receptors on eccrine glands and overflows to adjacent mast cells, directly triggering histamine release and wheal formation 4
- This impaired sweating pattern is linked to longer disease duration and higher disease severity 6
- Sweat allergy is not required in this subtype 4
3. Idiopathic Subtype
- Some patients fit neither the sweat hypersensitivity nor the impaired sweating pattern 5
Clinical Implications
Understanding the cause helps identify the specific subtype:
- Determine if the patient sweats normally during episodes (distinguishes impaired sweating type from sweat hypersensitivity type) 5
- Assess for sweat hypersensitivity through autologous sweat skin testing (identifies indirect ACh mechanism) 5, 4
- Consider disease duration and severity (longer duration and higher severity correlate with impaired sweating) 6
Important Caveat
Cholinergic urticaria can be complicated by bronchial hyperresponsiveness and anaphylaxis, particularly in young adults engaging in strenuous exercise. 2 If patients report wheezing or difficulty breathing with urticaria, this represents a potentially life-threatening variant requiring immediate access to epinephrine. 2