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Urticaria is a common condition,affecting up to 20 per cent of the

population at some time in their lives. Itis more common in women.1–4 It is characterised by itchy red weals, whichusually resolve within 24 hours, leavingno mark. About 40 per cent of patientswith urticaria also have angioedema.Systemic symptoms such as wheezing,breathlessness, gastrointestinal upset,dizziness, joint pain and malaise mayaccompany severe disease.5–7

Urticaria can be divided into acuteand chronic forms, with chronic urticariapersisting for six weeks or more. Chronicurticaria is further subdivided into spon-taneous and physical (or inducible)urticarias. Less common forms ofurticaria include urticarial vasculitis andurticaria associated with autoimmuneor rarely auto-inflammatory diseasessuch as Schnitzler’s syndrome orMuckle-Wells syndrome.5–7

Acute urticariaAcute urticaria is the most common typeof urticaria, and may occur at any age.The cause is unknown in more than halfof cases. However, triggers include infec-tions, particularly viral upper respiratorytract infections, and multiple differentdrugs, most often NSAIDs and antibi-otics. Less frequent causes include type I hypersensitivity reactions to food,latex or insect stings. Acute urticariamay be one of the presenting symptomsof anaphylaxis.8

Physical (or inducible)urticariasPhysical urticarias can occur at any age,but are probably most common in youngadults. Weals appear reproduciblywithin a few minutes of being triggeredby a specific physical stimulus (seeTable 1), and settle often within 10–20minutes but at most within two hours.

A profile of the various forms of urticaria and how to treat themRuth A Sabroe MD, FRCP

There are various types of urticaria and, while generally easyto diagnose, it can be confusing. It is also important torecognise when to refer to secondary care.

Table 1. Physical urticarias

Physicalurticaria

Trigger Clinical characteristics Diagnostic and other testsa

Dermographism Friction Patient itchy, thenscratches, after whichlinear weals appear.Worse if warm

Graded gentle frictionagainst the skin (seeFigure 1)

Cholinergicurticaria

A rise in coretemperature,usually withsweating, eg withheat, emotion orexercise

Tiny weals, about 2mmin diameter, with bigsurrounding flare,sometimes confluent.Often on trunk andproximal limbs

Hot bath test (10minutes at 42°C) orexercise test, withmonitoring

Delayed pressureurticaria

Pressure, such astight clothing,carrying heavyitems, or standingon a ladder

Weals occurring at sitesof pressure

Weights on the skinfor 20 minutes, assess at 6 hours

Cold urticaria Cold object, windor water, or coldfood/drink. In aminority a drop incore temperatureis needed

Weals usually localised toareas of cold skin/mouth.Weals may only appear on rewarming

Ice cube test.Also check cryoglobu-lins and cold agglu-tinins

Aquagenicurticaria

Water of anytemperature

Similar appearance tocholinergic urticaria.Aquagenic pruritus (noweals) may be associatedwith myeloproliferativedisease.

Tepid bath tests (10minutes at 37°C).Check FBC annually inaquagenic pruritus

Solar urticaria Sun Weals at sites of sunexposure, with sparing ofcovered sites

Photo-testing. Must bedifferentiated fromother photosensitiverashes. ANA and porphyrins

a Antihistamines must be withdrawn for three days before testing

The exception is delayed pressureurticaria (DPU) where weals appear 30 minutes to 12 hours after pressureagainst the skin, and last for two tothree days. The prolonged weal durationmay make it difficult to distinguish DPUfrom urticarial vasculitis.9

Physical urticarias may occurtogether and/or with chronic sponta-neous urticaria. Some of the physicalurticarias, such as cholinergic, cold orsolar urticaria, can produce a spectrumof symptoms from pruritus, urticaria,angioedema, to, in rare and severecases, anaphylaxis. Physical urticariasmay result in a significant reduction inquality of life. Indeed, it may be impos-sible to do heavy physical work withsevere delayed pressure urticaria, or towork in a cold environment with signifi-cant cold urticaria.9

Chronic spontaneous urticariaChronic spontaneous urticaria (seeFigure 2) affects approximately 0.1 percent of the population.10 The disease isnot life threatening, but can be very dis-abling and again may have a significantaffect on quality of life.11 By definitionno cause can be identified, but aboutone-third of patients have auto -antibodies against the high affinityimmunoglobulin E (IgE) receptor, oragainst IgE.12

Urticarial vasculitisThis should be suspected if weals lastfor more than 24 hours, leave residualbruising, are associated with severe sys-temic symptoms or respond poorly totreatment. It can be difficult to distin-guish urticarial vasculitis from DPU,since in both weals are prolonged andmay occur at pressure sites.13 It isimportant to identify urticarial vasculitis,as it is more likely than other forms ofurticaria to be associated with otherunderlying diseases, such as systemiclupus erythematosus.

Differential diagnosisThe transient nature of urticarial wealsusually makes diagnosis easy. However,confusion may arise. For example, acuteeczema may present with redness and swelling, but there is likely to be

weeping or vesicle formation, then dry-ness and scaling, and the rash will bemore persistent. Urticarial lesions maybe annular, but true target lesions willnot occur (at least three concentric ringsare needed for a target lesion) thusexcluding erythema multiforme. Bullouspemphigoid may present with urticariallesions as a prodromal phase, but blis-ters follow in a few days or weeks.14,15

InvestigationsIt is important to avoid over investiga-tion, and a thorough history may be allthat is needed. In acute urticaria, pricktests or specific IgE tests may be helpful

to identify an allergen, but only if type 1hypersensitivity is suspected. Tests for the physical urticarias are listed in Table 1. In chronic spontaneousurticaria, only a FBC, ESR and TSH arerequired, but abnormalities should bepursued. If urticarial vasculitis is sus-pected, a skin biopsy and full vasculitisscreen are indicated.6,7

TreatmentKnown triggers should be avoided. Acool ambient temperature may reduceitching, as may 1–2 per cent menthol inaqueous cream. In mild disease thismay be sufficient.5–7

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Figure 1. Dermographism: weals triggered by gentle friction

Figure 2. The weals of chronic spontaneous urticaria

Orally, H1 antihistamines remainfirst-line treatment. The newer lowsedating antihistamines are recom-mended, for example loratadine, ceti-rizine or fexofenadine. If one does notwork, another may.5–7

The older sedating H1 antihista-mines should be avoided unless thepatient has had prolonged disease-related periods without sleep, havingtried low sedating drugs. If used, the patient should be warned about cognitive impairment the next day, par-ticularly when driving. Unlike newer anti-histamines, sedating ones may bedangerous in overdose. Hydroxyzine,given before bed, is usually the drug of choice.5,6

The European Guidelines recom-mend up-dosing low sedating H1 antihis-tamines to up to quadruple dosages forone to four weeks, if licensed dosagesfail.5 There is some evidence that morepatients will respond. However, all anti-histamines lower seizure threshold,some antihistamines are excreted pre-dominantly by the kidneys, while othersare metabolised by the liver, some maybecome sedating at higher dosages,and some interact with other medica-tions. Thus caution is required inpatients with co-morbidities includingrenal or hepatic impairment or epilepsy,in the elderly and in patients on otherdrugs or at risk of sedation.

In severe acute urticaria, or for asevere exacerbation of chronic sponta-neous urticaria, a short course of pred-nisolone may help. It is best to limit theduration of treatment to one to twoweeks, because of the risk of significantadverse effects with prolonged use.Additionally, tachyphylaxis may occur, inwhich ever increasing dosages areneeded to maintain disease control.

Beyond this, H2 antihistamines,leukotriene inhibitors, the mast cell sta-biliser ketotifen, low dose doxepin, andthen immunosuppressive drugs such asciclosporin, methotrexate or mycophe-nolate mofetil can be used for chronicdisease, although none are licenced forurticaria.5–7 Additionally, althoughexpensive, the anti-IgE antibody omal-izumab, appears safe and effective, andthus represents a very promising new

treatment.16,17 Drugs other than antihis-tamines and a brief course of pred-nisolone may be best initiated insecondary care.

Acute urticaria can be one of thepresenting symptoms of anaphylaxis, inwhich case emergency treatmentshould be given, including intramuscu-lar adrenaline if appropriate.18

PregnancyNone of the oral preparations availablefor urticaria have been proven totallysafe in pregnancy. The US Food andDrug Administration put chlorpheni-ramine, loratadine and cetirizine in category B, and so these antihistaminesshould be used in preference to hydrox-yzine and fexofenadine, which are in category C.

PrognosisBy definition acute urticaria resolveswithin six weeks, but usually settleswithin three weeks. The chronicurticarias may persist for years.19,20

The GP’s roleMany patients with urticaria can bemanaged in primary care, particularlywhen disease is mild and readily con-trolled. Suggested reasons for referralare listed in Table 2.

ConclusionUrticaria is a common condition, but can be very disabling when severe. It is

useful to distinguish the different subtypes, and important not to overinvestigate. The disease can often betreated in primary care, with the avoid-ance of triggers, and use of low sedatingantihistamines.

Referral into secondary care shouldbe considered when disease control ispoor, symptoms are severe, if there isdiagnostic uncertainty, or if moreunusual forms such as urticarial vasculi-tis are suspected.

References1. McKee WD. J Allergy 1966;38:226–35.2. Schafer T, Ring J. Monogr Allergy1993;31:49–60.3. Swinny B. South Med J 1941;34:855–87.4. Paul E, et al. Monogr Allergy 1987;21:87–115.5. Zuberbier T, et al. Allergy 2014;69:868–87. 6. Grattan CE, Humphreys F. Br J Dermatol2007;157:1116–23.7. Bernstein JA, et al. J Allergy Clin Immunol2014;133:1270–77.8. Sabroe RA. Immunol Allergy Clin North Am2014;34:11–21.9. Magerl M, et al. Allergy 2009;64:1715–21.10. Hellgren L. Acta Allerologica 1972;27:236–40.11. O’Donnell BF, et al. Br J Dermatol 1997;136:197–201.12. Sabroe RA, Greaves MW. Br J Dermatol2006;154:813–19.13. Mehregan DR, et al. J Am Acad Dermatol1992;26:441–48.14. Peroni A, et al. J Am Acad Dermatol2010;62:541–55;quiz 555.15. Peroni A, et al. J Am Acad Dermatol2010;62:557–70;quiz 571.16. Kaplan A, et al. J Allergy Clin Immunol2013;132:101–9.17. Maurer M, et al. N Engl J Med 2013;368:924–35.18. Simons FE, et al. J Allergy Clin Immunol2011;127:587–93.e1.19. Juhlin L. Br J Dermatol 1981;104: 369–81.20. Champion RH, et al. Br J Dermatol 1969;81:588–97.

Declaration of interestsNone to declare.

Dr Sabroe is a consultant dermatologist, Royal HallamshireHospital, Sheffield Teaching HospitalsNHS Foundation Trust

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Table 2.When to consider referral in to secondary care

• Severe urticaria• Urticaria not controlled with symp-tomatic treatment and/or licenseddosages of H1 antihistamines

• For testing for physical urticarias • Where urticarial vasculitis is suspected, or needs to be differen-tiated from DPU

• If there is associated fever, or thereare high inflammatory markers

• Other atypical features, such asfamilial or life long disease

• Urticaria in pregnancy• Diagnostic uncertainty