Cholinergic urticaria (CU) presents with tiny very itchy

wheals A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this s ...

and small bumps on a reddish background. It is a type of

physical Physical may refer to: *Physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally co ...

urticaria 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-lasti ...

(or ''hives'') that appears when a person is

sweating Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distr ...

or their

core body temperature Normal human body-temperature (normothermia, euthermia) is the typical temperature range found in humans. The normal human body temperature range is typically stated as . Human body temperature varies. It depends on sex, age, time of day, exert ...

increases.

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. Although the symptoms subside rapidly, commonly within 1 hour, cholinergic urticaria may significantly impair quality of life, especially in relation to sporting activities.

Causes

* Sweat hypersensitivity * Acquired anhidrosis and/or

hypohidrosis Hypohidrosis is a disorder in which a person exhibits diminished sweating in response to appropriate stimuli. In contrast with hyp''er''hidrosis, which is a socially troubling yet often benign condition, the consequences of untreated hypohidrosi ...

Idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent wikt:spontaneous, spontaneous origin. From Ancient Greek, Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approxi ...

* Opioid use * Cholinesterase inhibitors

Subtypes

Sweat hypersensitivity

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

Diagnosis

Diagnosis is made by injecting

autologous Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person ('' auto-'' meaning "self" in Greek). The autologous tissue (also called autogenous, autogene ...

(the person's own) sweat into the skin.

Features

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

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 Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammat ...

may also be mediated by a specific

IgE Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (ε chain) and two light chains, with the ε c ...

for sweat in

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in puritis, itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which often thickens o ...

as well as CU.

Treatment

* Proposed first-line treatment: Rapid desensitization protocol using autologous sweat. * Non-pharmacological treatment: Forced perspiration by excessive body warming (hot bath or exercise) used daily may reduce the symptoms through exhaustion of inflammatory mediators. This non-pharmacological treatment is

contraindicated In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...

in those with CU as a result of

(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. Some research suggests that first-generation antihistamines with anticholinergic properties such as

diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into a vein ...

are most successful at treating CU. * Treatment(s) with mixed success:

omalizumab Omalizumab, sold under the brand name Xolair, is a medication used to treat asthma, nasal polyps, and urticaria (hives). Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody that specifically binds to free human immunoglo ...

(anti-IgE therapy),

danazol Danazol, sold as Danocrine and other brand names, is a medication used in the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema and other conditions. It is taken by mouth. The use of danazol is limited by masculini ...

(synthetic androgen),

propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anx ...

(beta blocker),

zileuton Zileuton (trade name Zyflo) is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation, used for the maintenance treatment of asthma. Zileuton was introduced in 1996 by Abbott Laborat ...

(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 A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

indicator to undergo a colour change during thermoregulatory sweat testing can indicate anhidrosis and/or

(see

Minor test The Minor test (also known as Minor's test, the starch–iodine test, and the iodine–starch test), described by Victor Minor in 1928, is a qualitative medical test that is used to evaluate sudomotor function (perspiration or sweating). Method T ...

). A skin biopsy may reveal cellular infiltrates in sweat glands or ducts.

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 A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakness ...

Pathophysiology

The wheals, hypohidrosis, and pain seems to result from the low expression levels of acetylcholinesterase (

AchE Ache or Aches may refer to: Ethnography * Aché, an indigenous people of eastern Paraguay * Aché language, the language of the Aché people * Ache language (China) * Aṣẹ (Cuban spelling: ''aché''), a concept in Orisha belief People * Ach ...

) and cholinergic receptor, muscarinic 3 ( CHRM3) in the eccrine gland epithelial cells. Elevated expression levels of

CCL2 ''For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.'' The chemokine (C-C motif) ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL ...

/MCP-1,

CCL5 Chemokine (C-C motif) ligand 5 (also CCL5) is a protein which in humans is encoded by the ''CCL5'' gene. The gene has been discovered in 1990 by ''in situ'' hybridisation and it is localised on 17q11.2-q12 chromosome. It is also known as RANTE ...

/RANTES and

CCL17 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 imm ...

/TARC which result in chemoattracted

CD4+ In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic ce ...

and

CD8+ A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...

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

(a b2-adrenergic blocker),

antihistamines Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...

, and

montelukast Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. Ot ...

; and treatment and injection with

botulinum toxin Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromusc ...

. * 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.

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). The condition is more common in young adults, and prevalence appears to peak in adults aged 26–28 (up to 20%). 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 DukeD 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 Methacholine (International Nonproprietary Name, INN, United States Adopted Name, USAN) (trade name Provocholine), also known as Acetyl-β-methylcholine, is a synthetic choline ester that acts as a non-selective muscarinic receptor agonist in the ...

References

External links

{{Urticaria and erythema Urticaria and angioedema

Symptoms

Causes

Subtypes

Sweat hypersensitivity

Diagnosis

Features

Pathophysiology

Treatment

Acquired anhidrosis and/or hypohidrosis

Diagnosis

Features

Pathophysiology

Treatment

Idiopathic

Prevalence

History

See also

References

External links