Cholinergic urticaria: Hives caused by heat and what can be done about it

Urticaria, also known as hives, is a common skin reaction that results in raised bumps and patches that itch. The basic taxonomy divides urticaria into acute and chronic forms, with chronic urticaria encompassing cases that last for six weeks or longer and sometimes are a manifestation of an underlying autoimmune condition. Inducible urticaria is a category that includes cases of urticaria that can be traced to particular physical stimuli, such as “dermographism,” when the skin has been rubbed or scratched, exposure to the sun, vibration, water or cold temperature.

One of the more common types of inducible urticaria is known as cholinergic urticaria. In cholinergic urticaria, the trigger is a spike in body temperature, be it from physical activity, spicy foods, emotional stress or a hot bath. A review article published earlier this year in the Journal of the European Academy of Dermatology and Venereology cited an article that proposed dividing cholinergic urticaria further into four subtypes based on an understanding of the pathophysiology and clinical manifestations: nonfollicular sweat allergy cholinergic urticaria, follicular cholinergic urticaria, cholinergic urticaria with palpebral angioedema and cholinergic urticaria with anhidrosis or hypohidrosis. The review says the sweat allergy type is characterized by a positive autologous sweat skin test, suggesting an immunoglobulin E (IgE)-mediated mechanism. The follicular version is characterized by wheals centered on hair follicles, according to the review, and many patients have a positive autologous skin test, an indication that serum-derived factors may contribute to activation of mast cells. Cholinergic urticaria with palpebral angioedema affects mainly women. People with that version of cholinergic urticaria test positive on autologous sweat skin tests and are predisposed to developing allergies. Cholinergic urticaria with anhidrosis or hypohidrosis affects mainly men.

The lead author of the review, Mojca Bizjak-Suran, M.D., Ph.D., an assistant professor at the University Clinic of Respiratory and Allergic Diseases Golnik in Golnik, Slovenia, and her colleagues discuss how sweat-derived antigens might cause cholinergic urticaria. Obstruction or damage to sweat gland ducts may allow the antigens in sweat to leak into the dermis, where they interact with mast cells coated in IgE. They cite a study that found an IgE specific to the sweat antigen MGL-1304 has been detected in the sera of some patients with cholinergic urticaria.

Another way in which cholinergic urticaria may occur is through the absence or reduced expression of muscarinic cholinergic receptors on eccrine sweat gland epithelial cells. Normally, they explain, those receptors trap particularly acetylcholine that is released by sympathetic cholinergic nerves under certain physiological conditions, such as exercise, exposure or sweat. But if those receptors are in short supply, the acetylcholine leaks into the dermis, where it can activate the mast cells.

Second-generation antihistamines, such as cetirizine, have been used to treat cholinergic urticaria, but Bizjak-Suran and her colleagues note that researchers and drug developers have shifted the focus to mast cells as the wellspring of urticaria signs and symptoms, regardless of what may be triggering the mast cells. Some treatment strategies target pathways that activate mast cells, while others reduce the number of mast cells that might be triggered.

Rhapsido (remibrutinib) is an oral Bruton tyrosine kinase inhibitor and one of the drugs that hinders a mast cell activation pathway that is currently a leading candidate as a treatment for inducible urticaria. It is currently being assessed in a phase 3 trial as a treatment for three main kinds of inducible urticaria: cholinergic; “cold urticaria,” which, as the name suggests, is triggered by cold; and dermographism. Novartis, the drug’s developer, announced positive top-line results in a news release issued in February 2026 and presented positive data from the phase 3 trial, called RemIND, at the European Academy of Allergy and Clinical Immunology (EAACI) Congress in June 2026. The results mentioned in the news release announcing the EAACI presentation showed that 29.3% of those with cholinergic urticaria who were treated with Rhapsido experienced a complete response at week 12 compared with 15.8% of those treated with a placebo. The treatment vs. placebo difference was greater in the cold urticaria patients (56.3% vs. 14%).

In both news releases, Novartis said it had submitted a supplemental New Drug Application (to the FDA for Rhapsido as a treatment for symptomatic dermographism) without mentioning cholinergic and cold urticaria.