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Physical urticarias, aquagenic pruritus, and cholinergic pruritus

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Physical urticarias, aquagenic pruritus, and cholinergic pruritus

Clive E.H. Grattan and Frances Lawlor

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Physical urticarias

About 25% of patients with chronic urticaria have a definable and reproducible physical trigger that distinguishes them from those with spontaneous urticaria and urticarial vasculitis. Physical urticarias are defined by the predominant stimulus that induces them (Table 181.1). More than one physical stimulus elicits urticaria in some patients, and physical urticarias can overlap with spontaneous urticaria. Physical urticarias are included under the term ‘inducible urticarias’ in the latest European classification.

Table 181.1

Classification of physical urticarias by the eliciting stimulus (in approximate reducing frequency of occurrence)

Symptomatic dermographism Stroking or rubbing the skin
Cholinergic urticaria (pale, papular wheals with red flares) Rise in core temperature and other causes of sweating (exercise, hot baths, spicy food, and stress)
Cold urticaria Rewarming of skin after cooling (localized or systemic)
Delayed pressure urticaria Sustained perpendicular pressure
Solar urticaria Ultraviolet or visible solar radiation
Localized heat urticaria Local heat contact
Adrenergic urticaria (red papular wheals with surrounding pallor) Emotional stress
Aquagenic urticaria Local water contact at any temperature
Exercise-induced anaphylaxis Exercise, but not hot baths
Food and exercise-induced anaphylaxis Exercise following a heavy food load or eating specific foods
Vibratory angioedema Vibration

Management strategy

Pharmacologic

The clinical presentation of the physical urticarias may vary considerably in severity. Drug management should be guided by the degree of disability and impairment in quality of life. The milder forms may require little more than explanation, avoidance of situations likely to trigger an attack, and an occasional dose of antihistamine, whereas a very severe attack involving anaphylaxis would require emergency treatment with intramuscular epinephrine (adrenaline). Acute presentations of severe physical urticaria may require short courses of oral corticosteroids (e.g., prednisolone 30–40 mg daily for 5 days) in addition to regular treatment with non-sedating H1 antihistamines.

Specific investigations

With the exceptions of testing for cryoglobulins, in secondary cold urticaria and specific IgE in food- and exercise-induced anaphylaxis, routine laboratory investigations are unnecessary and should not be undertaken except to monitor treatment or screen for eligibility (e.g., glucose-6-phosphatase dehydrogenase in patients being considered for dapsone or sulfasalazine).

First-line therapies

imageNon-sedating (‘second generation’) antihistamines A

Non-sedating antihistamines (Table 181.2) should be prescribed in preference to classical antihistamines, which are often sedating and can impair psychomotor performance. Up-dosing of second generation H1 antihistamines is often practiced.

Table 181.2

Examples of non- and mildly sedating antihistamines

Acrivastine Non-sedating, three-times-daily dosing
Cetirizine Mildly sedating, once-daily dosing
Levocetirizine The active enantiomer of cetirizine
Fexofenadine Non-sedating, once-daily dosing
Loratadine Non-sedating, once-daily dosing
Desloratadine The active metabolite of loratadine
Mizolastine Non-sedating, once-daily dosing
Rupatadine Non-sedating, once-daily dosing

Second-line therapies

Symptomatic dermographism

imageH2 receptor antagonists A
imageNarrowband UVB phototherapy C
imagePhotochemotherapy (PUVA) C
imageOmalizumab E

Cholinergic urticaria

imageDanazol A
imageAnticholinergics E
imageAutologous sweat injection D
imageOmalizumab E

Rapid desensitization with autologous sweat in cholinergic urticaria.

Kozaru T, Fukunaga A, Taguchi K, Ogura K, Nagano T, Oka M, et al. Allergol Int 2011; 60: 277–81.

Six patients with H1 antihistamine-unresponsive cholinergic urticaria were injected intradermally with 1/1000 then 1/100 dilutions of autologous sweat at increasing volume (0.02–0.2 mL) hourly followed by a weekly maintenance injections of 0.1 mL of 1/100 diluted sweat for several months. All patients showed a reduced skin test reaction to sweat after the initial rapid desensitization and five had an improvement in their cholinergic urticaria symptoms during the maintenance period.

The study was conducted in one center and was uncontrolled so it is unclear how much of the subjective clinical improvement was due to the treatment.

Cold urticaria

imageCold tolerance (desensitization) C
imageLeukotriene receptor antagonists E
imageAntibiotics E
imageOmalizumab D

Delayed pressure urticaria

imageTopical steroids B
imageLeukotriene receptor antagonists B
imageSulfasalazine E
imageDapsone D
imageOmalizumab D

Solar urticaria

imageInduction of tolerance (phototherapy and photochemotherapy) D
imageOmalizumab  

Third-line therapies

imageEpinephrine (adrenaline) cream E
imageIntravenous immuneglobulins D
imageCyclosporine E
imagePlasmapheresis E
imageEtanercept E

Aquagenic pruritus

Aquagenic pruritus is diagnosed when itching, prickling, burning, buzzing, or other skin discomfort, which may be intense, is provoked by contact with water. There are no visible skin changes. The sensation is associated with feelings of anger, irritability, or depression in approximately half of patients. The symptoms are provoked at any water temperature and degree of salinity. They occur within minutes rather than hours, and start either during a bath or shower or soon afterwards. The discomfort may be present for between 10 minutes and 2 hours. Any part of the body may be affected. Patients may also itch when the ambient temperature changes. Spontaneous remission is rare. The pathogenesis of the condition is not clear.

Management strategy

Other chronic skin diseases must be ruled out by taking a full history and by clinical examination, particularly aquagenic pruritus of the elderly manifesting as xerosis, and other inducible urticarias). Direct questioning is necessary regarding cold-induced symptoms and whealing, water-induced whealing or syncope, exercise-, heat-, or emotion-induced symptoms and whealing, and friction-induced itching and whealing. The well-recognized ‘bath itch’ that occurs in approximately 40% of patients with polycythemia rubra vera must be ruled out before aquagenic pruritus is diagnosed. Rarely, other hematological abnormalities have also been associated. Occasionally, antimalarial drugs have induced an aquagenic pruritus-like picture in patients with lupus erythematosus. When the diagnosis is reached, it is important to explain that aquagenic pruritus is a recognized skin condition, which, albeit very unpleasant and difficult to manage, has no immediate implications with regard to the patient’s general health. It may help the sufferer to realize that he or she is not mentally unstable. Therapy is usually based on the use of antihistamines, adding sodium bicarbonate to the water, and phototherapy.

First-line therapies

imageExplanation E
imageMinimally sedating antihistamine C
imageSodium bicarbonate added to bath water D

Antihistamines are used by these authors in the management of aquagenic pruritus. There is no consensus regarding the first-line treatment, as the response of each patient is individual and no single treatment is effective in all cases; however, it would seem reasonable to start by advising a minimally sedating antihistamine 2 hours before the bath or shower on a regular basis. Patients may have a good response to antihistamines. Not all patients respond to antihistamine treatment, however, and, of those who do, the response may consist of a diminution rather than an abolition of symptoms.

Second-line therapies

imageUVB C
imageNarrowband UVB E
imageCombined UVA/narrowband UVB therapy E

Due to the necessity for hospital attendance UVB should be considered a second-line treatment for aquagenic pruritus. A response usually occurs between 2 and 4 weeks of treatment, but relapse normally occurs within months of stopping treatment, which may then be repeated as necessary or maintenance therapy instituted as the condition is ongoing.

A good response to NB-UVB is described in two patients to whom it was administered three times per week. The improvement occurred at about 2 months of treatment and was maintained on weekly treatment in the ensuing months. In one of the patients desloratadine was added during the maintenance period. NB-UVB may prove to be an effective form of phototherapy.

Combined UVA and UVB treatment was used to treat one patient with good response.

Third-line therapies

imageBath oil E
imageEmulsifying ointment in the bath water E
imagePUVA E
imagePropranolol E,C
imageIntramuscular triamcinolone E
imageTransdermal nitroglycerin E
imageNaltrexone 50 mg daily E

PUVA treatment has been effective in the bath itch of polycythemia vera and has been used successfully both in a series of five patients and in individual patients, although either maintenance or repeated courses of therapy are necessary to maintain control of the condition. PUVA with oral psoralens may be regarded as a third-line treatment for practical reasons.

Cholinergic pruritus

Cholinergic pruritus occurs when patients itch, sting, or prickle following a rise in body temperature. The provoking stimuli are exercise (walking, running, dancing, going to the gym), including housework (ironing, vacuuming), heat (hot room, hot food, hot bath, sunny day), and emotion (excitement, stress, embarrassment) or fever. A combination of factors may cause a more pronounced itch, e.g., walking on a sunny day. The intensity, extent, and duration of the itching seem to be directly proportional to the strength of the eliciting stimulus. By definition, no whealing occurs on the skin during an attack. Although the prevalence of this condition is not known, it is the author’s impression that many people itch when they become warm, although this itching is frequently insufficiently severe or incapacitating to present at a dermatology clinic. Cholinergic pruritus can be regarded as a variant of cholinergic urticaria. There is one case report that describes a patient presenting initially with cholinergic pruritus who progressed to cholinergic urticaria. Because there are no visible skin lesions, it is important to be aware of the condition and to differentiate it from aquagenic pruritus in those who describe itching after a bath or shower.

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