Epileptic seizures and cholinergic urticaria with generalized hypohidrosis or anhidrosis

ARTICLE

Auteur(s) : Yu SAWADA, Toshinori BITO, Rieko KABASHIMA, Kazunari SUGITA, Motonobu NAKAMURA, Yoshiki TOKURA long-ago@med.uoeh-u.ac.jp

Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Japan

Cholinergic urticaria (CU) is a rare condition clinically characterized by pinpoint-sized, highly pruritic wheals, a unique urticaria which is typically provoked by exercise, warmth, and emotional distress [1]. CU is occasionally associated with depressed sweating, known as hypohidrosis (incomplete lack of sweating) or anhidrosis (complete lack of sweating) [2]. 29 patients have been reported with CU with hypohidrosis and/or anhidrosis (CUHA) [2], and 26 are Japanese. Rarely, CU patients have episodes of seizures upon occurrence of urticaria, with or without abnormalities in electroencephalography [3, 4]. We report a case of CUHA, manifesting with epileptic seizures.

A 23-year-old man presented a 1-year history of wheal, generalized hypohidrosis, and heat intolerance, with pain in a hot environment. He was admitted to our hospital for evaluation of his skin eruption. The skin surface was divided into two areas, anhidrotic and hypohidrotic, by iodine-starch reaction. The hypohidrotic areas included the face, chest, abdomen and arms (figure 1A), and anhidrosis was seen on the back, buttocks and legs (figure 1B), when compared to a sex and age-matched healthy control. On exercise, he developed wheals, which coincided with sweat orifices at the hypohidrotic areas (figure 1C), but no wheals were seen in the anhidrotic areas. Autologous sweat and serum tests were negative. Acethylcholine injection yielded a wheal reaction at a hypohidrotic but not an anhidrotic area. A skin biopsy taken from an anhidrotic area revealed lymphocytic infiltration around the sweat glands (figure 1D), but no infiltration was observed in the hypohidrotic area. Skin sections were immunohistochemically stained with anti-cholinergic receptor muscarin 3 (CHRM3) antibody (H-210, 1:50; Santa Cruz Biotechnology, Santa Cruz, CA) [2], which is the most important cholinergic receptor (CHR) for sweating. The expression of CHRM3 was reduced in the eccrine glands of the hypohidrotic area (figure 1E) and was not absent in the anhidrotic skin (figure 1F) compared to a healthy control (figure 1G). We diagnosed the disorder as CUHA. Since anti-histaminic drugs showed no therapeutic effect, we gave this patient methylprednisolone pulse therapy (1 g daily for 3 consecutive days). Five days after the treatment, when his sweating began to recover, the patient had a seizure, he suddenly twitched and shook his limbs, and his eyes rolled back. The seizure lasted 2 minutes. He also had several episodes of the same symptoms when sweating with exercise. There was no abnormal finding in the blood levels of glucose, sodium, electrolytes or in brain computed tomography. Neurological examination was normal. After his sweat condition was substantially improved, epileptic seizures did not occur.

Although little is known about the exact prevalence of CUHA in the general population, the incidence of CU is 11.2%, mostly in younger people [5]. The 1-year prevalence for epilepsy is 7.1/1000 [6]. Therefore, it is considered that the two diseases are not a coincidence in our case. Our review of the English and Japanese literature found three cases of epileptic seizures associated with CU, including our case. All cases were young Japanese. When the intensity of sweat-promoting stimuli is high, the autonomic center in the diencephalon or brain stem is abnormally activated [3]. CHRM3 expression is decreased in patients with CUHA, and steroid therapy might recover the CHR expression in sweat glands [2]. The decreased expression of CHR was re-expressed after the steroid pulse therapy, not only in the sweat glands but also in the brain, and acethylcholine might highly stimulate the autonomic center, resulting in an epileptic seizure.

Disclosure

Financial support: none. Conflict of interest: none.

References

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