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Clinical Autonomic Research

, Volume 28, Issue 1, pp 103–113 | Cite as

Cholinergic urticaria: epidemiology, physiopathology, new categorization, and management

  • Atsushi Fukunaga
  • Ken Washio
  • Mayumi Hatakeyama
  • Yoshiko Oda
  • Kanako Ogura
  • Tatsuya Horikawa
  • Chikako Nishigori
Review

Abstract

Purpose

The aim of this study was to review the evidence on the epidemiology, physiopathology, categorization, and management of cholinergic urticaria. We specifically focused on several subtypes of cholinergic urticaria and investigated the relationship between cholinergic urticaria and idiopathic anhidrosis.

Methods

Using an integrative approach, we reviewed publications addressing the epidemiology, clinical features, diagnostic approach, physiopathology, subtype classification, and therapeutic approach to cholinergic urticaria.

Results

Multiple mechanisms were found to contribute to the development of cholinergic urticaria. This disorder should be classified based on the pathogenesis and clinical characteristics of each subtype. Such a classification system would lead to better management of this resistant condition. In particular, sweating function should be given more attention when examining patients with cholinergic urticaria.

Conclusions

Because cholinergic urticaria is not a homogeneous disease, its subtype classification is essential for selection of the most suitable therapeutic method.

Keywords

Cholinergic urticaria Acetylcholine  Hypohidrosis/anhidrosis Sweat allergy 

Notes

Acknowledgements

This work was supported in part by JSPS KAKENHI (Grant No. 15K09742).

Compliance with ethical standards

Ethical standards

The manuscript does not contain clinical studies or patient data.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Ww D (1924) Urticaria caused specifically by the action of physical agents. J Am Med Assoc 83:3–9CrossRefGoogle Scholar
  2. 2.
    Hirschmann JV, Lawlor F, English JS, Louback JB, Winkelmann RK, Greaves MW (1987) Cholinergic urticaria. A clinical and histologic study. Arch Dermatol 123:462–467CrossRefPubMedGoogle Scholar
  3. 3.
    Moore-Robinson M, Warin RP (1968) Some clinical aspects of cholinergic urticaria. Br J Dermatol 80:794–799CrossRefPubMedGoogle Scholar
  4. 4.
    Hatakeyama M, Fukunaga A, Washio K, Ogura K, Yamada Y, Horikawa T, Nishigori C (2016) Addition of lafutidine can improve disease activity and lead to better quality of life in refractory cholinergic urticaria unresponsive to histamine H1 antagonists. J Dermatol Sci 82:137–139CrossRefPubMedGoogle Scholar
  5. 5.
    Sawada Y, Nakamura M, Bito T, Fukamachi S, Kabashima R, Sugita K, Hino R, Tokura Y (2010) Cholinergic urticaria: studies on the muscarinic cholinergic receptor M3 in anhidrotic and hypohidrotic skin. J Invest Dermatol 130:2683–2686CrossRefPubMedGoogle Scholar
  6. 6.
    Kaplan AP, Garofalo J (1981) Identification of a new physically induced urticaria: cold-induced cholinergic urticaria. J Allergy Clin Immunol 68:438–441CrossRefPubMedGoogle Scholar
  7. 7.
    Lawrence CM, Jorizzo JL, Kobza-Black A, Coutts A, Greaves MW (1981) Cholinergic urticaria with associated angio-oedema. Br J Dermatol 105:543–550CrossRefPubMedGoogle Scholar
  8. 8.
    Vadas P, Sinilaite A, Chaim M (2016) Cholinergic urticaria with anaphylaxis: an underrecognized clinical entity. J Allergy Clin Immunol Pract 4:284–291CrossRefPubMedGoogle Scholar
  9. 9.
    Horikawa T, Fukunaga A, Nishigori C (2009) New concepts of hive formation in cholinergic urticaria. Curr Allergy Asthma Rep 9:273–279CrossRefPubMedGoogle Scholar
  10. 10.
    Nakamizo S, Egawa G, Miyachi Y, Kabashima K (2012) Cholinergic urticaria: pathogenesis-based categorization and its treatment options. J Eur Acad Dermatol Venereol 26:114–116CrossRefPubMedGoogle Scholar
  11. 11.
    Zuberbier T, Althaus C, Chantraine-Hess S, Czarnetzki BM (1994) Prevalence of cholinergic urticaria in young adults. J Am Acad Dermatol 31:978–981CrossRefPubMedGoogle Scholar
  12. 12.
    Bito T, Sawada Y, Tokura Y (2012) Pathogenesis of cholinergic urticaria in relation to sweating. Allergol Int 61:539–544CrossRefPubMedGoogle Scholar
  13. 13.
    Washio K, Fukunaga A, Onodera M, Hatakeyama M, Taguchi K, Ogura K, Horikawa T, Nishigori C (2017) Clinical characteristics in cholinergic urticaria with palpebral angioedema: report of 15 cases. J Dermatol Sci 85:135–137CrossRefPubMedGoogle Scholar
  14. 14.
    Fukunaga A, Bito T, Tsuru K, Oohashi A, Yu X, Ichihashi M, Nishigori C, Horikawa T (2005) Responsiveness to autologous sweat and serum in cholinergic urticaria classifies its clinical subtypes. J Allergy Clin Immunol 116:397–402CrossRefPubMedGoogle Scholar
  15. 15.
    Sawada Y, Nakamura M, Bito T, Sakabe J, Kabashima-Kubo R, Hino R, Kobayashi M, Tokura Y (2014) Decreased expression of acetylcholine esterase in cholinergic urticaria with hypohidrosis or anhidrosis. J Invest Dermatol 134:276–279CrossRefPubMedGoogle Scholar
  16. 16.
    Fukunaga A, Hatakeyama M, Tsujimoto M, Oda Y, Washio K, Nishigori C (2015) Steroid treatment can improve the impaired quality of life of patients with acquired idiopathic generalized anhidrosis. Br J Dermatol 172:537–538CrossRefPubMedGoogle Scholar
  17. 17.
    Magerl M, Altrichter S, Borzova E, Gimenez-Arnau A, Grattan CE, Lawlor F, Mathelier-Fusade P, Meshkova RY, Zuberbier T, Metz M, Maurer M (2016) The definition, diagnostic testing, and management of chronic inducible urticarias—the EAACI/GA(2) LEN/EDF/UNEV consensus recommendations 2016 update and revision. Allergy 71:780–802CrossRefPubMedGoogle Scholar
  18. 18.
    Bernstein JA, Lang DM, Khan DA, Craig T, Dreyfus D, Hsieh F, Sheikh J, Weldon D, Zuraw B, Bernstein DI, Blessing-Moore J, Cox L, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CR, Schuller DE, Spector SL, Tilles SA, Wallace D (2014) The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol 133:1270–1277CrossRefPubMedGoogle Scholar
  19. 19.
    Hide M, Hiragun T, Japanese Dermatological A (2012) Japanese guidelines for diagnosis and treatment of urticaria in comparison with other countries. Allergol Int 61:517–527CrossRefPubMedGoogle Scholar
  20. 20.
    Shoenfeld Y, Harari Z, Sheonfeld Y, Keren G (1981) Cholinergic urticaria. A seasonal disease. Arch Intern Med 141:1029–1030CrossRefPubMedGoogle Scholar
  21. 21.
    Godse K, Farooqui S, Nadkarni N, Patil S (2013) Prevalence of cholinergic urticaria in Indian adults. Indian Dermatol Online J 4:62–63CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Takahagi S, Tanaka T, Ishii K, Suzuki H, Kameyoshi Y, Shindo H, Hide M (2009) Sweat antigen induces histamine release from basophils of patients with cholinergic urticaria associated with atopic diathesis. Br J Dermatol 160:426–428CrossRefPubMedGoogle Scholar
  23. 23.
    Altrichter S, Koch K, Church MK, Maurer M (2016) Atopic predisposition in cholinergic urticaria patients and its implications. J Eur Acad Dermatol Venereol 30:2060–2065CrossRefPubMedGoogle Scholar
  24. 24.
    Magerl M, Borzova E, Gimenez-Arnau A, Grattan CE, Lawlor F, Mathelier-Fusade P, Metz M, Mlynek A, Maurer M, Eaaci/Ga2Len/Edf/Unev (2009) The definition and diagnostic testing of physical and cholinergic urticarias–EAACI/GA2LEN/EDF/UNEV consensus panel recommendations. Allergy 64:1715–1721CrossRefPubMedGoogle Scholar
  25. 25.
    Illig L, Paul E, Bruck K, Schwennicke HP (1980) Experimental investigations on the trigger mechanism of the generalized type of heat and cold urticaria by means of a climatic chamber. Acta Derm Venereol 60:373–380PubMedGoogle Scholar
  26. 26.
    Commens CA, Greaves MW (1978) Tests to establish the diagnosis in cholinergic urticaria. Br J Dermatol 98:47–51CrossRefPubMedGoogle Scholar
  27. 27.
    Altrichter S, Salow J, Ardelean E, Church MK, Werner A, Maurer M (2014) Development of a standardized pulse-controlled ergometry test for diagnosing and investigating cholinergic urticaria. J Dermatol Sci 75:88–93CrossRefPubMedGoogle Scholar
  28. 28.
    Oda Y, Fukunaga A, Tsujimoto M, Hatakeyama M, Washio K, Nishigori C (2015) Combined cholinergic urticaria and cold-induced cholinergic urticaria with acquired idiopathic generalized anhidrosis. Allergol Int 64:214–215CrossRefPubMedGoogle Scholar
  29. 29.
    Fukunaga A, Shimizu H, Tanaka M, Kikuzawa A, Tsujimoto M, Sekimukai A, Yamashita J, Horikawa T, Nishigori C (2012) Limited influence of aspirin intake on mast cell activation in patients with food-dependent exercise-induced anaphylaxis: comparison using skin prick and histamine release tests. Acta Derm Venereol 92:480–483CrossRefPubMedGoogle Scholar
  30. 30.
    Pezzolo E, Peroni A, Gisondi P, Girolomoni G (2016) Heat urticaria: a revision of published cases with an update on classification and management. Br J Dermatol 175:473–478CrossRefPubMedGoogle Scholar
  31. 31.
    Fukunaga A, Shimoura S, Fukunaga M, Ueda M, Nagai H, Bito T, Tsuru K, Ichihashi M, Horikawa T (2002) Localized heat urticaria in a patient is associated with a wealing response to heated autologous serum. Br J Dermatol 147:994–997CrossRefPubMedGoogle Scholar
  32. 32.
    Luong KV, Nguyen LT (1998) Aquagenic urticaria: report of a case and review of the literature. Ann Allergy Asthma Immunol 80:483–485CrossRefPubMedGoogle Scholar
  33. 33.
    Shelley WB, Shelley ED (1985) Adrenergic urticaria: a new form of stress-induced hives. Lancet 2:1031–1033CrossRefPubMedGoogle Scholar
  34. 34.
    Chedraoui A, Uthman I, Abbas O, Ghosn S (2008) Adrenergic urticaria in a patient with anti-double-stranded DNA antibodies. Acta Derm Venereol 88:263–266PubMedGoogle Scholar
  35. 35.
    Kawakami Y, Gokita M, Fukunaga A, Nishigori C (2015) Refractory case of adrenergic urticaria successfully treated with clotiazepam. J Dermatol 42:635–637CrossRefPubMedGoogle Scholar
  36. 36.
    Soter NA, Wasserman SI, Austen KF, McFadden ER Jr (1980) Release of mast-cell mediators and alterations in lung function in patients with cholinergic urticaria. N Engl J Med 302:604–608CrossRefPubMedGoogle Scholar
  37. 37.
    Kaplan AP, Gray L, Shaff RE, Horakova Z, Beaven MA (1975) In vivo studies of mediator release in cold urticaria and cholinergic urticaria. J Allergy Clin Immunol 55:394–402CrossRefPubMedGoogle Scholar
  38. 38.
    Nakazato Y, Tamura N, Ohkuma A, Yoshimaru K, Shimazu K (2004) Idiopathic pure sudomotor failure: anhidrosis due to deficits in cholinergic transmission. Neurology 63:1476–1480CrossRefPubMedGoogle Scholar
  39. 39.
    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 204:173–178CrossRefPubMedGoogle Scholar
  40. 40.
    Soter NA, Wasserman SI (1980) Physical urticaria/angioedema: an experimental model of mast cell activation in humans. J Allergy Clin Immunol 66:358–365CrossRefPubMedGoogle Scholar
  41. 41.
    Koch K, Weller K, Werner A, Maurer M, Altrichter S (2016) Antihistamine updosing reduces disease activity in patients with difficult-to-treat cholinergic urticaria. J Allergy Clin Immunol 138(1483–1485):e1489Google Scholar
  42. 42.
    Adachi J, Aoki T, Yamatodani A (1994) Demonstration of sweat allergy in cholinergic urticaria. J Dermatol Sci 7:142–149CrossRefPubMedGoogle Scholar
  43. 43.
    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. Allergol Int 60:277–281CrossRefPubMedGoogle Scholar
  44. 44.
    Hiragun T, Hide M (2016) Sweat Allergy. Curr Probl Dermatol 51:101–108CrossRefPubMedGoogle Scholar
  45. 45.
    Hiragun T, Ishii K, Hiragun M, Suzuki H, Kan T, Mihara S, Yanase Y, Bartels J, Schroder JM, Hide M (2013) Fungal protein MGL_1304 in sweat is an allergen for atopic dermatitis patients. J Allergy Clin Immunol 132(608–615):e604Google Scholar
  46. 46.
    Hiragun M, Hiragun T, Ishii K, Suzuki H, Tanaka A, Yanase Y, Mihara S, Haruta Y, Kohno N, Hide M (2014) Elevated serum IgE against MGL_1304 in patients with atopic dermatitis and cholinergic urticaria. Allergol Int 63:83–93CrossRefPubMedGoogle Scholar
  47. 47.
    Hide M, Francis DM, Grattan CE, Hakimi J, Kochan JP, Greaves MW (1993) Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med 328:1599–1604CrossRefPubMedGoogle Scholar
  48. 48.
    Sabroe RA, Grattan CE, Francis DM, Barr RM, Kobza Black A, Greaves MW (1999) The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria. Br J Dermatol 140:446–452CrossRefPubMedGoogle Scholar
  49. 49.
    Kim JE, Jung KH, Cho HH, Kang H, Park YM, Park HJ, Lee JY (2015) The significance of hypersensitivity to autologous sweat and serum in cholinergic urticaria: cholinergic urticaria may have different subtypes. Int J Dermatol 54:771–777CrossRefPubMedGoogle Scholar
  50. 50.
    Rho NK (2006) Cholinergic urticaria and hypohidrosis: a clinical reappraisal. Dermatology 213:357–358CrossRefPubMedGoogle Scholar
  51. 51.
    Fukunaga A, Horikawa T, Sato M, Nishigori C (2009) Acquired idiopathic generalized anhidrosis: possible pathogenic role of mast cells. Br J Dermatol 160:1337–1340CrossRefPubMedGoogle Scholar
  52. 52.
    Itakura E, Urabe K, Yasumoto S, Nakayama J, Furue M (2000) Cholinergic urticaria associated with acquired generalized hypohidrosis: report of a case and review of the literature. Br J Dermatol 143:1064–1066CrossRefPubMedGoogle Scholar
  53. 53.
    Nakamizo S, Miyachi Y, Kabashima K (2010) A case of cholinergic urticaria associated with acquired generalized hypohidrosis and abnormal neurological findings: association with incomplete Ross syndrome? Br J Dermatol 162:903–905CrossRefPubMedGoogle Scholar
  54. 54.
    Shelley WB, Shelley ED, Ho AK (1983) Cholinergic urticaria: acetylcholine-receptor-dependent immediate-type hypersensitivity reaction to copper. Lancet 1:843–846CrossRefPubMedGoogle Scholar
  55. 55.
    Munetsugu T, Fujimoto T, Oshima Y, Sano K, Murota H, Satoh T, Iwase S, Asahina M, Nakazato Y, Yokozeki H (2016) Revised guideline for the diagnosis and treatment of acquired idiopathic generalized anhidrosis in Japan. J Dermatol. doi: 10.1111/1346-8138.13649
  56. 56.
    Shelley WB, Rawnsley HM (1964) Aquagenic urticaria. Contact sensitivity reaction to water. JAMA 189:895–898PubMedGoogle Scholar
  57. 57.
    Shelley WB, Shelley ED (1983) Follicular dermographism. Cutis 32:244–245, 254, 260PubMedGoogle Scholar
  58. 58.
    Nakazato Y, Tamura N, Ikeda K, Yamamoto T, Tokura Y (2016) A case of idiopathic pure sudomotor failure associated with prolonged high levels of serum carcinoembryonic antigen. Clin Auton Res 26:451–453CrossRefPubMedGoogle Scholar
  59. 59.
    Zuberbier T, Munzberger C, Haustein U, Trippas E, Burtin B, Mariz SD, Henz BM (1996) Double-blind crossover study of high-dose cetirizine in cholinergic urticaria. Dermatology 193:324–327CrossRefPubMedGoogle Scholar
  60. 60.
    Tsunemi Y, Ihn H, Saeki H, Tamaki K (2003) Cholinergic urticaria successfully treated with scopolamine butylbromide. Int J Dermatol 42:850CrossRefPubMedGoogle Scholar
  61. 61.
    Feinberg JH, Toner CB (2008) Successful treatment of disabling cholinergic urticaria. Mil Med 173:217–220CrossRefPubMedGoogle Scholar
  62. 62.
    Sheraz A, Halpern S (2013) Cholinergic urticaria responding to botulinum toxin injection for axillary hyperhidrosis. Br J Dermatol 168:1369–1370CrossRefPubMedGoogle Scholar
  63. 63.
    Metz M, Ohanyan T, Church MK, Maurer M (2014) Retreatment with omalizumab results in rapid remission in chronic spontaneous and inducible urticaria. JAMA Dermatol 150:288–290CrossRefPubMedGoogle Scholar
  64. 64.
    Metz M, Bergmann P, Zuberbier T, Maurer M (2008) Successful treatment of cholinergic urticaria with anti-immunoglobulin E therapy. Allergy 63:247–249CrossRefPubMedGoogle Scholar
  65. 65.
    Sabroe RA (2010) Failure of omalizumab in cholinergic urticaria. Clin Exp Dermatol 35:e127–e129Google Scholar
  66. 66.
    Ohshima Y, Yanagishita T, Ito K, Tamada Y, Nishimura N, Inukai Y, Iwase S, Sugenoya J, Watanabe D (2013) Treatment of patients with acquired idiopathic generalized anhidrosis. Br J Dermatol 168:430–432CrossRefPubMedGoogle Scholar
  67. 67.
    Suma A, Murota H, Kitaba S, Yamaoka T, Kato K, Matsui S, Takahashi A, Yokomi A, Katayama I (2014) Idiopathic pure sudomotor failure responding to oral antihistamine with sweating activities. Acta Derm Venereol 94:723–724CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Division of Dermatology, Department of Internal RelatedKobe University Graduate School of MedicineKobeJapan
  2. 2.Division of DermatologyNishi-Kobe Medical CenterKobeJapan
  3. 3.Ueda Dermatology ClinicKako-GunJapan

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