Cholinergic urticaria

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Cholinergic urticaria
A male displaying cholinergic urticaria on the volar aspect of the forearm.jpg
CU on the volar aspect of the forearm
Specialty Dermatology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Tiny very itchy wheals and small bumps on a reddish background. [1]

Cholinergic urticaria is a type of hives (urticaria) that is triggered by an increase in body temperature, such as during exercise, sweating, or exposure to heat. It is also sometimes called exercise-induced urticaria or heat hives. The condition is caused by an overreaction of the immune system to the release of histamine and other chemicals in response to the increase in body temperature. This results in the characteristic red, itchy, and sometimes raised bumps or welts on the skin that are associated with hives.

Contents

Cholinergic urticaria can be painful and uncomfortable and may interfere with daily activities.

Symptoms

Cholinergic urticaria 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, cholinergic urticaria may significantly impair quality of life, especially in relation to sporting activities. [4]

Causes

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. [5]

Features

The hives are observed to coincide with perspiration points of sweating. [6]

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. [6]

Treatment

  • Proposed first-line treatment: Rapid desensitization protocol using autologous sweat. [5]
  • Non-pharmacological treatment: Forced perspiration by excessive body warming (hot bath or exercise) used daily may reduce the symptoms through exhaustion of inflammatory mediators. [7] 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. [8] 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), [9] [10] danazol (synthetic androgen), [11] propranolol (beta blocker), [12] [13] 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). [14]

A skin biopsy may reveal cellular infiltrates in sweat glands or ducts. [6]

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. [15]

Diagram visualizing the overflow of acetylcholine to adjacent mast cells. CU associated with hypohidrosis.png
Diagram visualizing the overflow of acetylcholine to adjacent mast cells.

Pathophysiology

[16] 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: H1RAs are first-line therapy for patients with CholU, but many patients show only a mild to moderate response to standard H1RA doses. The addition of an H2RA was reported to be effective in patients with refractory CholU that was unresponsive to up-dosing of an H1RA. Other studies have demonstrated the efficacy of scopolamine butylbromide (an anticholinergic agent); combinations of propranolol (a b2-adrenergic blocker), antihistamines, and montelukast; and treatment and injection with botulinum toxin. [17]
  • Non-pharmacological treatment: In the absence of sweat, cold-water sprays and wet towels can be used to 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. [18]

Idiopathic

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

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). [19] [20] [21] The condition is more common in young adults, and prevalence appears to peak in adults aged 26–28 (up to 20%). [19] The vast majority of cases are reported to be mild, and proportionally few individuals seek medical attention regarding the condition.

History

Cholinergic urticaria was first described by Duke [22] in 1924 as "urticaria calorica". 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

Related Research Articles

<span class="mw-page-title-main">Perspiration</span> Fluid secreted from sudoriferous glands

Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals.

<span class="mw-page-title-main">Hematidrosis</span> Medical condition

Hematidrosis, also called hematohidrosis, haematidrosis, hemidrosis and blood sweat, is a very rare condition in which a human sweats blood. The term is from Ancient Greek haîma/haímatos, meaning blood, and hīdrṓs, meaning sweat.

<span class="mw-page-title-main">Hives</span> Skin disease characterized by red, raised, and itchy bumps

Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs.

<span class="mw-page-title-main">Miliaria</span> Medical condition

Miliaria, commonly known as heat rash, sweat rash, or prickly heat, is a skin disease marked by small, itchy rashes due to sweat trapped under the skin by clogged sweat-gland ducts. Miliaria is a common ailment in hot and humid conditions, such as in the tropics and during the summer. Although it affects people of all ages, it is especially common in children and infants due to their underdeveloped sweat glands.

<span class="mw-page-title-main">Cold urticaria</span> Allergic reaction to low temperatures

Cold urticaria is a disorder in which large red welts called hives (urticaria) form on the skin after exposure to a cold stimulus. The hives are usually itchy and often the hands and feet will become itchy and swollen as well. Hives vary in size from about 7 mm in diameter to as big as about 27 mm or larger.

Aquagenic pruritus is a skin condition characterized by the development of severe, intense, prickling-like epidermal itching without observable skin lesions and evoked by contact with water.

<span class="mw-page-title-main">Physical urticaria</span> Medical condition

Physical urticaria is a distinct subgroup of urticaria (hives) that are induced by an exogenous physical stimulus rather than occurring spontaneously. There are seven subcategories that are recognized as independent diseases. Physical urticaria is known to be painful, itchy and physically unappealing; it can recur for months to years.

<span class="mw-page-title-main">CCL17</span> Mammalian protein found in Homo sapiens

CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response. However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome. CCL17 has also been linked to autoimmune and allergic diseases.

Hypohidrosis is a disorder in which a person exhibits diminished sweating in response to appropriate stimuli. In contrast with hyperhidrosis, which is a socially troubling yet often benign condition, the consequences of untreated hypohidrosis include hyperthermia, heat stroke and death. An extreme case of hypohidrosis in which there is a complete absence of sweating and the skin is dry is termed anhidrosis.

<span class="mw-page-title-main">Solar urticaria</span> Medical condition

Solar urticaria (SU) is a rare condition in which exposure to ultraviolet or UV radiation, or sometimes even visible light, induces a case of urticaria or hives that can appear in both covered and uncovered areas of the skin. It is classified as a type of physical urticaria. The classification of disease types is somewhat controversial. One classification system distinguished various types of SU based on the wavelength of the radiation that causes the breakout; another classification system is based on the type of allergen that initiates a breakout.

<span class="mw-page-title-main">CCR4</span> Mammalian protein found in Homo sapiens

C-C chemokine receptor type 4 is a protein that in humans is encoded by the CCR4 gene. CCR4 has also recently been designated CD194.

Aquagenic urticaria, also known as water allergy and water urticaria, is a rare form of physical urticaria in which hives develop on the skin after contact with water, regardless of its temperature. The condition typically results from contact with water of any type, temperature or additive. In rare cases, it is internal rather than external and causes ones body to let water enter the lungs, leading to drowning symptoms and/or pneumonia

Adrenergic urticaria is a skin condition characterized by an eruption consisting of small (1-5mm) red macules and papules with a pale halo, appearing within 10 to 15 min after emotional upset. There have been 10 cases described in medical literature, and involve a trigger followed by a rise in catecholamine and IgE. Treatment involves propranolol and trigger avoidance.

Ross' syndrome consists of Adie's syndrome plus segmental anhidrosis.

Rheumatoid neutrophilic dermatitis, also known as rheumatoid neutrophilic dermatosis, is a cutaneous condition associated with rheumatoid arthritis.

Idiopathic pure sudomotor failure (IPSF) is the most common cause of a rare disorder known as acquired idiopathic generalized anhidrosis (AIGA), a clinical syndrome characterized by generalized decrease or absence of sweating without other autonomic and somatic nervous dysfunctions and without persistent organic cutaneous lesions.

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by generalized absence of sweating without other autonomic and neurologic dysfunction. Other symptoms include facial flushing, headaches, disorientation, lassitude, hyperthermia, weakness, and palpitations.

<span class="mw-page-title-main">Chronic spontaneous urticaria</span> Medical condition

Chronic spontaneous urticaria(CSU) also known as Chronic idiopathic urticaria(CIU) is defined by the presence of wheals, angioedema, or both for more than six weeks. Chronic spontaneous urticaria can be characterized by angioedema, excruciatingly itchy recurrent hives, or both. Chronic urticaria patients were found to have a higher prevalence of various autoimmune diseases. Many patients with chronic spontaneous urticaria report that certain triggers, such as stress, infections, specific foods, or nonsteroidal anti-inflammatory drug use, aggravate their condition.

A sweat allergy is the exacerbation of atopic dermatitis associated with an elevated body temperature and resulting increases in the production of sweat. It appears as small reddish welts that become visible in response to increased temperature and resulting production of sweat. It can affect all ages. Sweating can trigger intense itching or cholinergic urticaria. The protein MGL_1304 secreted by mycobiota (fungi) present on the skin such as Malassezia globosa acts as a histamine or antigen. People can be desensitized using their own samples of sweat that have been purified that contains small amounts of the allergen. The allergy is not due to the sweat itself but instead to an allergy-producing protein secreted by bacteria found on the skin.

<span class="mw-page-title-main">Autoimmune urticaria</span> Autoimmune disease causing hives and itching

Autoimmune urticaria, also known as chronic autoimmune urticaria, is a type of chronic urticaria characterized by the presence of autoantibodies in the patient's immune system that target the body's own mast cells, leading to episodes of hives (urticaria). This immunologically distinct type of urticaria is considered autoimmune because the immune system, which normally protects the body from foreign organisms, mistakenly attacks the body's own cells, causing inflammation and other symptoms.

References

  1. ↑ James, William D.; Elston, Dirk; Treat, James R.; Rosenbach, Misha A.; Neuhaus, Isaac (2020). "7. Erythema and urticaria". Andrews' Diseases of the Skin: Clinical Dermatology (13th ed.). Elsevier. pp. 151–152. ISBN   978-0-323-54753-6.
  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. S2CID   58415911.
  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. S2CID   731524.
  5. 1 2 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.
  6. 1 2 3 Bito, T.; Sawada, Y.; Tokura, Y. (2012). "Pathogenesis of cholinergic urticaria in relation to sweating". Allergology International. 61 (4): 539–544. doi: 10.2332/allergolint.12-RAI-0485 . PMID   23093795.
  7. ↑ 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 (3): 173–178. doi:10.1159/000057877. PMID   12037443. S2CID   43259005.
  8. ↑ 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. S2CID   35802279.
  9. ↑ 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. S2CID   8657377.
  10. ↑ 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. S2CID   37421783.
  11. ↑ La Shell, M. S.; England, R. W. (2006). "Severe refractory cholinergic urticaria treated with danazol". Journal of Drugs in Dermatology. 5 (7): 664–667. PMID   16865874.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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. S2CID   206038609.
  15. ↑ 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. S2CID   25029977.
  16. ↑ 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.
  17. ↑ doi=10.1007/s10286-017-0418-6
  18. ↑ 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. S2CID   1547067.
  19. 1 2 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.
  20. ↑ 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. S2CID   23090828.
  21. ↑ 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.
  22. ↑ DDuke, W. W. (1924). "Urticaria Caused Specifically by the Action of Physical Agents". JAMA: The Journal of the American Medical Association. 83: 3–9. doi:10.1001/jama.1924.02660010007002.
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