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.

First-line therapies

Non-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

Therapeutic effects of cetirizine in delayed pressure urticaria: clinicopathological findings.

Kontou-Fili K, Maniatakou G, Demaka P, Gonianakis M, Palaiologos G, Aroni K. J Am Acad Dermatol 1991; 24: 1090–3.

A double-blind, placebo-controlled study in 11 patients, showing a reduction in weight-induced wheal area and lesional eosinophil numbers on cetirizine 10 mg three times daily.

The use of cetirizine above the licensed dose appears to be beneficial for this indication.

High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard–dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, cross-over study.

Siebenhaar F, Degener F, Zuberbier T, Martus P, Maurer M. J Allergy Clin Immunol 2009; 123: 672–9.

The study shows that fourfold up-dosing a second generation antihistamine has additional inhibitory effects on wheal formation in cold urticaria.

Rupatadine and its effects on symptom control, stimulation time, and temperature thresholds in patients with acquired cold urticaria.

Metz M, Scholz E, Ferrán M, Izquierdo I, Giménez-Arnau A, Maurer M. Ann Allergy Asthma Immunol 2010; 104: 86–92.

A cross-over, randomized, double-blind, placebo-controlled study of double-dose rupatadine, a new second generation H₁ antihistamine. Fifty-two percent of patients showed a complete response. There was also a significant improvement in critical cold stimulation time and critical temperature threshold.

The study confirms the effectiveness of a second generation (non-sedating) antihistamine for cold contact urticaria at double its licensed dose.

Second-line therapies

Symptomatic dermographism

H2 receptor antagonists	A
Narrowband UVB phototherapy	C
Photochemotherapy (PUVA)	C
Omalizumab	E

In dermographic urticaria H₂ receptor antagonists have a small but therapeutically irrelevant additional effect compared with H₁ antagonists alone.

Sharpe GR, Shuster S. Br J Dermatol 1993; 129: 575–9.

In this double-blind, crossover study, 19 patients were randomized to treatment with cetirizine 10 mg at night plus either ranitidine 150 mg twice daily or placebo. There was an increase in whealing threshold with additional H₂ blockade, but no subjective benefit.

Addition of an H₂ to an H₁ antihistamine may provide better control of some inducible urticarias despite the lack of trial evidence.

Narrow-band ultraviolet B phototherapy is beneficial in antihistamine-resistant symptomatic dermographism: a pilot study.

Borzova E, Rutherford A, Konstantinou G, Leslie K, Grattan CEH. J Am Acad Dermatol 2008; 59: 752–7.

Eight patients with antihistamine-unresponsive symptomatic dermographism showed subjective and objective improvement in itch and whealing after 6 weeks’ treatment, but relapsed 6 to 12 weeks after stopping.

The effect of psoralen photochemotherapy (PUVA) on symptomatic dermographism.

Logan RA, O’Brien TJO, Greaves MW. Clin Exp Dermatol 1989; 14: 25–8.

Five of 14 patients treated with oral PUVA experienced a useful reduction in itching after 4 weeks of treatment, but there was no difference in whealing threshold between covered and exposed skin when tested with a standardized stroking stimulus.

Anti-immunoglobulin E treatment of patients with recalcitrant physical urticaria.

Metz M, Altricher S, Ardelean E, et al. Int Arch Allergy Immnuol 2011; 154; 177–80.

One of two patients with symptomatic dermographism cleared completely within days of their first injection of omalizumab and remained clear on continuing treatment.

Cholinergic urticaria

Danazol	A
Anticholinergics	E
Autologous sweat injection	D
Omalizumab	E

Beneficial effects of danazol on symptoms and laboratory changes in cholinergic urticaria.

Wong E, Eftekhari N, Greaves MW, Milford Ward A. Br J Dermatol 1987; 116: 553–6.

Seventeen male patients were treated with danazol 200 mg three times daily in a double-blind crossover study, with sustained improvement in the number of exercise-induced wheals over 12 weeks. Levels of protease inhibitors increased over this period but declined to baseline within 1 month of stopping treatment.

Anabolic steroids should only be considered for severe cholinergic urticaria not responding adequately to antihistamines, because of their potential for virilizing effects and hepatotoxicity.

Danazol should be reserved for severe cases and avoided during pregnancy.

Severe cholinergic urticaria successfully treated with scopolamine butylbromide in addition to antihistamines.

Ujiie H, Shimizu T, Natsuga K, Arita K, Tomizawa K, Shimizu H. Clin Exp Dermatol 2006; 31: 978–81.

Although this case report suggests that anticholinergics may be successful for cholinergic urticaria, the general experience with this class of drugs is disappointing and unwanted effects often outweighs any benefits.

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.

Successful treatment of cholinergic urticaria with anti-immunoglobulin E therapy.

Metz M, Bergmann P, Zuberbier T, Maurer M. Allergy 2008; 63: 247–8.

One patient with highly symptomatic cholinergic urticaria who had not responded to several antihistamines, montelukast and propranolol made a complete and sustained response to omalizumab 300 mg every 2 weeks.

Failure of omalizumab in cholinergic urticaria.

Sabroe R. Clin Exp Dermatol 2009; 35:e217–19.

A patient with disabling cholinergic urticaria was completely unresponsive to omalizumab subcutaneously at 300 mg every 2 weeks for 4 months.

Not every patient with cholinergic urticaria will respond to omalizumab.

Cold urticaria

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Cold tolerance (desensitization)	C
Leukotriene receptor antagonists	E
Antibiotics	E