Cholinergic urticaria

Cholinergic urticaria
CU on the volar aspect of the forearm
Classification and external resources
Specialty	dermatology
ICD-10	L50.5
ICD-9-CM	708.5
DiseasesDB	29573
eMedicine	derm/442

Cholinergic urticaria (CU) is a type of physical urticarias (or hives) that appears when a person is sweating.^[1]

Symptoms

CU typically presents with a number of small, short-lasting hives but may also involve cutaneous inflammation (wheals) and pain which develops usually in response to exercise, bathing, staying in a heated environment, or emotional stress.^[2][3] Although the symptoms subside rapidly, commonly within 1 hour, CU may significantly impair quality of life, especially in relation to sporting and sexual activities.^[4]

Prevalence

Though overall research is limited, various studies indicate that CU is relatively common across populations with prevalence rates reportedly ranging from 5% to 20% (depending on locale, race, and age).^[5][6][7] The condition is more common in young adults, and prevalence appears to peak in adult aged 26–28 (up to 20%).^[5] The vast majority of cases are reported to be mild, and proportionally few individuals seek medical attention regarding the condition.

Causes

• Sweat hypersensitivity
• Acquired anhidrosis and/or hypohidrosis
• Idiopathic

Subtypes

Sweat hypersensitivity

This subtype of CU refers to those who are hypersensitive to their own sweat.

Diagnosis

Diagnosis is made by injecting autologous (the person's own) sweat into the skin.^[8]

Features

The hives are observed to coincide with perspiration points of sweating.^[9]

Pathophysiology

Tanaka et al. found that the sweat hyper-sensitivities of CU and atopic dermatitis seem to be virtually the same, and therefore, the sweat-induced histamine release from basophils may also be mediated by a specific IgE for sweat in atopic dermatitis as well as CU.^[9]

Treatment

• Proposed first-line treatment: Rapid desensitization protocol using autologous sweat.^[8]
• Non-pharmacological treatment: Forced perspiration by excessive body warming (hot bath or exercise) used daily may reduce the symptoms through exhaustion of inflammatory mediators.^[10] This non-pharmacological treatment is contraindicated in those with CU as a result of hypohidrosis (see below).
• Antihistamines are a commonly prescribed first-line treatment for conventional urticaria, but its effectiveness in the treatment of CU is rather limited in most cases.^[1] Some research suggests that first-generation antihistamines with anticholinergic properties such as diphenhydramine are most successful at treating CU.
• Treatment(s) with mixed success: omalizumab (anti-IgE therapy),^[11][12] danazol (synthetic androgen),^[13] propranolol (beta blocker),^[14][15] zileuton (antileukotriene).

Acquired anhidrosis and/or hypohidrosis

This subtype of CU refers to those who have abnormally reduced sweating.

Diagnosis

Sweat is readily visualized by a topical indicator such as iodinated starch or sodium alizarin sulphonate. Both undergo a dramatic colour change when moistened by sweat. A thermoregulatory sweat test evaluates the body’s response to a thermal stimulus by inducing sweating through the use of a hot box ⁄ room, thermal blanket or exercise. Failure of the topical indicator to undergo a colour change during thermoregulatory sweat testing can indicate anhidrosis and/or hypohidrosis (see Minor test).^[16]

A skin biopsy may reveal cellular infiltrates in sweat glands or ducts.^[9]

Features

Severe heat intolerance (e.g., nausea, dizziness, and headache), and tingling, pricking, pinchy or burning pain over the entire body on exposure to hot environments or prolonged exercise which improve after cooling the body. Occurs in the absence of any causative skin, metabolic, or neurological disorders.^[17]

Diagram visualizing the overflow of acetylcholine to adjacent mast cells.

Pathophysiology

^[18]The wheals, hypohidrosis, and pain seems to result from the low expression levels of acetylcholinesterase (AchE) and cholinergic receptor, muscarinic 3 (CHRM3) in the eccrine gland epithelial cells.

Elevated expression levels of CCL2/MCP-1, CCL5/RANTES and CCL17/TARC which result in chemoattracted CD4+ and CD8+ T cell populations to the surrounding area may be responsible for exerting a downmodulatory effect on the AchE and CHRM3 expressions.

Corticosteroid inhibits the expressions of CCL2/MCP-1, CCL5/RANTES and CCL17/TARC. This further support the notion that CCL2/MCP-1, CCL5/RANTES and CCL17/TARC play a crucial role.

Treatment

• First-line treatment:
• Non-pharmacological treatment: In the absence of sweat, cold-water sprays and wet towels can be used increase the evaporative loss of heat from the skin. Shifting to a cooler or air-conditioned environments when necessary can also reduce discomfort. In the event of severe hyperthermia (body temperature >106 °F/41 °C), drastic measures such as immersion in ice-cold water are necessary to prevent irreversible brain damage.^[19]

Idiopathic

Unknown or unclassified at this time. This represents those who do not fall under any of the above categories.

History

CU was first described by Duke^[20] in 1924. The term cholinergic is derived from the finding that hives similar to those of CU can be evoked using cholinergic agonists (e.g. methacholine).

See also

• Miliaria
• Exercise-induced anaphylaxis
• Idiopathic pure sudomotor failure
• Hypohidrosis
• Fabry disease

References

1. Nakamizo, S.; Egawa, G.; Miyachi, Y.; Kabashima, K. (2012). "Cholinergic urticaria: Pathogenesis-based categorization and its treatment options". Journal of the European Academy of Dermatology and Venereology 26 (1): 114–116. doi:10.1111/j.1468-3083.2011.04017.x. PMID 21371134.
2. Moore-Robinson, M.; Warin, R. P. (1968). "Some clinical aspects of cholinergic urticaria". The British journal of dermatology 80 (12): 794–799. doi:10.1111/j.1365-2133.1968.tb11948.x. PMID 5706797.
3. Hirschmann, J. V.; Lawlor, F.; English, J. S.; Louback, J. B.; Winkelmann, R. K.; Greaves, M. W. (1987). "Cholinergic urticaria. A clinical and histologic study". Archives of dermatology 123 (4): 462–467. doi:10.1001/archderm.1987.01660280064024. PMID 3827277.
4. Poon, E.; Seed, P. T.; Greaves, M. W.; Kobza-Black, A. (1999). "The extent and nature of disability in different urticarial conditions". The British journal of dermatology 140 (4): 667–671. doi:10.1046/j.1365-2133.1999.02767.x. PMID 10233318.
5. Zuberbier, T.; Althaus, C.; Chantraine-Hess, S.; Czarnetzki, B. M. (1994). "Prevalence of cholinergic urticaria in young adults". Journal of the American Academy of Dermatology 31 (6): 978–981. doi:10.1016/S0190-9622(94)70267-5. PMID 7962780.
6. Silpa-Archa, N.; Kulthanan, K.; Pinkaew, S. (2011). "Physical urticaria: Prevalence, type and natural course in a tropical country". Journal of the European Academy of Dermatology and Venereology 25 (10): 1194–1199. doi:10.1111/j.1468-3083.2010.03951.x. PMID 21175877.
7. Godse, K.; Farooqui, S.; Nadkarni, N.; Patil, S. (2013). "Prevalence of cholinergic urticaria in Indian adults". Indian Dermatology Online Journal 4 (1): 62–63. doi:10.4103/2229-5178.105493. PMC 3573461. PMID 23437429.
8. Kozaru, T.; Fukunaga, A.; Taguchi, K.; Ogura, K.; Nagano, T.; Oka, M.; Horikawa, T.; Nishigori, C. (2011). "Rapid Desensitization with Autologous Sweat in Cholinergic Urticaria". Allergology International 60 (3): 277–281. doi:10.2332/allergolint.10-OA-0269. PMID 21364312.
9. Bito, T.; Sawada, Y.; Tokura, Y. (2012). "Pathogenesis of cholinergic urticaria in relation to sweating". Allergology international : official journal of the Japanese Society of Allergology 61 (4): 539–544. doi:10.2332/allergolint.12-RAI-0485. PMID 23093795.
10. Kobayashi, H.; Aiba, S.; Yamagishi, T.; Tanita, M.; Hara, M.; Saito, H.; Tagami, H. (2002). "Cholinergic urticaria, a new pathogenic concept: Hypohidrosis due to interference with the delivery of sweat to the skin surface". Dermatology (Basel, Switzerland) 204 (3): 173–178. doi:10.1159/000057877. PMID 12037443.
11. Metz, M.; Bergmann, P.; Zuberbier, T.; Maurer, M. (2008). "Successful treatment of cholinergic urticaria with anti-immunoglobulin E therapy". Allergy 63 (2): 247–249. doi:10.1111/j.1398-9995.2007.01591.x. PMID 18186820.
12. Sabroe, R. A. (2010). "Failure of omalizumab in cholinergic urticaria". Clinical and Experimental Dermatology 35 (4): e127–e129. doi:10.1111/j.1365-2230.2009.03748.x. PMID 19925484.
13. La Shell, M. S.; England, R. W. (2006). "Severe refractory cholinergic urticaria treated with danazol". Journal of drugs in dermatology : JDD 5 (7): 664–667. PMID 16865874.
14. Pachor, M. L.; Lunardi, C.; Nicolis, F.; Cortina, P.; Accordini, C.; Marchi, G.; Corrocher, R.; De Sandre, G. (1987). "Usefulness of propranolol in the treatment of cholinergic urticaria". La Clinica terapeutica 120 (3): 205–210. PMID 2973859.
15. Ammann, P.; Surber, E.; Bertel, O. (1999). "Beta blocker therapy in cholinergic urticaria". The American Journal of Medicine 107 (2): 191. doi:10.1016/S0002-9343(99)00038-8. PMID 10460061.
16. Chia, K. Y.; Tey, H. L. (2012). "Approach to hypohidrosis". Journal of the European Academy of Dermatology and Venereology 27 (7): 799–804. doi:10.1111/jdv.12014. PMID 23094789.
17. Nakazato, Y.; Tamura, N.; Ohkuma, A.; Yoshimaru, K.; Shimazu, K. (2004). "Idiopathic pure sudomotor failure: Anhidrosis due to deficits in cholinergic transmission". Neurology 63 (8): 1476–1480. doi:10.1212/01.wnl.0000142036.54112.57. PMID 15505168.
18. Sawada, Y.; Nakamura, M.; Bito, T.; Sakabe, J. I.; Kabashima-Kubo, R.; Hino, R.; Kobayashi, M.; Tokura, Y. (2013). "Decreased Expression of Acetylcholine Esterase in Cholinergic Urticaria with Hypohidrosis or Anhidrosis". Journal of Investigative Dermatology 134 (1): 276–9. doi:10.1038/jid.2013.244. PMID 23748235.
19. Thami, G. P.; Kaur, S.; Kanwar, A. J. (2003). "Acquired idiopathic generalized anhidrosis: A rare cause of heat intolerance". Clinical and experimental dermatology 28 (3): 262–264. doi:10.1046/j.1365-2230.2003.01208.x. PMID 12780708.
20. DDuke, W. W. (1924). "URTICARIA CAUSED SPECIFICALLY BY THE ACTION OF PHYSICAL AGENTS<subtitle>(LIGHT, COLD, HEAT, FREEZING, BURNS, MECHANICAL IRRITATION, AND PHYSICAL AND MENTAL EXERTION)</subtitle>". JAMA: the Journal of the American Medical Association 83: 3–1. doi:10.1001/jama.1924.02660010007002.