Chronic urticaria in childhood
Authors: M. W. Greaves
Journal: Allergy (2000)

Most of the literature on urticaria deals with urticaria in adults. Publisheddata on urticaria in children are not only relatively hard to come by, butalso less informative. This is due to the frequently uncertain distinctiondrawn between acute and chronic urticaria, paucity of confirmatory challengetest results for the physical urticarias and supposed food-derived urticaria,and fundamental differences in databases (e.g., primary care, general hospital-based,or national urticaria referral centre services), leading to different patientselections. In the UK, the published figure of 3.4% ( 1 ) for all forms of urticaria in children (acute, intermittent, andchronic) is probably fairly accurate. Henz et al. ( 2) give a range of 2.1–6.7%. However, only a small proportion of these are chronic or intermittent.In a national referral centre for urticaria, i.e., ours at the St John'sInstitute of Dermatology, only 5% of the urticaria patients are aged16 years or below, and nearly all of them have chronic or intermittent urticaria.Acute urticaria in either adults or children is a rarity in our practice,and we surmise that most of these are dealt with in a primary care or districtgeneral hospital setting. Chronic urticaria is conventionally defined as the occurrence of dailyor almost daily wheals with or without accompanying angioedema for at least6 weeks. There is no consensus definition of intermittent urticaria, but,for the purposes of this paper, it is defined as the occurrence of repeatedrelapses of chronic urticaria, as defined above, with intervals of at leasta week between each relapse. The present account is considered equally applicableto intermittent and chronic urticaria, and no distinction is made betweenthem. The types of chronic urticaria considered in the present account are listedin Table 1 . More than one kind of physical urticaria may occur concurrently in thesame individual. Common combinations include symptomatic dermographism andcholinergic urticaria, or cholinergic urticaria and cold urticaria. It ismost important to identify patients in whom a physical urticaria is the soleor principal cause of discomfort and disability. This is because, apart fromconfirming the diagnosis of the physical urticaria by appropriate challengetesting, with rare exceptions no further investigations are indicated. This disorder is relatively rare in childhood. Harris et al. ( 3 ) found no cases among 94 children with chronic urticaria. However,a more recent study ( 4 ) identified 1.3% of226 children with chronic urticaria in whom this physical urticaria was deemedto be the principal problem. Patients may draw attention to the immediateitching and whealing response to light pressure or friction, or to the developmentof itchy wheals at the sites of pressure from their clothes. More often, especiallyin children, no connection is made in the patient's mind between localpressure or rubbing and the appearance of urticarial lesions, although, whenquestioned, the patient may admit that scratching or rubbing makes the whealsworse. It is useful to get the child (or the mother) to assess the durationof each individual wheal, which should normally be no more than 30 min. Thisdistinguishes symptomatic dermographism from delayed pressure urticaria, sincethe latter takes several hours to develop after application of pressure andlasts for 24 h or more. Examination may yield little or nothing on first inspection.The child has often been told not to scratch, in which case, if he or sheis obedient, the skin may appear clear. More often, linear, itchy wheals canbe seen which follow the lines of scratching. They fade within a few minutes.I have not seen convincing oropharyngeal whealing in patients with this physicalurticaria. Dermographic whealing can occur anywhere but is less frequent inthe face and extremities. It is worth asking the patient or parents whetherthe wheals or the itch is the major problem. This is important from a managementpoint of view (see below). The condition runs an average course of 2–3years before finally resolving spontaneously. Skin perfusion studies in adults have clearly demonstrated an associationbetween histamine release and development of wheals and itching ( 5 ). How light touching or stroking of the skin can elicit whealingand itching due to mast-cell degranulation is unclear, although a circulatingfactor may be involved ( 6 ). The diagnosis is established by gentle stroking of the skin to elicit anisomorphic whealing response in the skin along the line of the applied pressure.I use a spring-loaded dermographometer for this purpose ( Fig. 1 ). The wheal occurs within 1–5 min and lasts about 30min. The only other condition in which a similar reaction to stroking of theskin may occur is urticaria pigmentosa. Unlike symptomatic dermographism,the wheal in urticaria pigmentosa, although linear, is less regular, beingmore prominent in association with the papules and macules of mast-cell infiltration.All antihistamines should be withdrawn 48 h before challenge testing. Delayedpressure urticaria, as the name suggests, does not develop for 2 or more hoursafter application of the pressure, and the wheals last for 24 h or more. Oncethe diagnosis of symptomatic dermographism has been confirmed by challengetesting, no further investigations are indicated. There is no evidence forinvolvement of systemic infections or infestations, or dietary factors. Dermographism. Elicitation by spring-loadeddermographometer. The parents should be told that the prognosis is for eventual resolution,and that no blood or skin tests or special diets are indicated. Woollen clothingnext to the skin should be avoided, and the child's bedroom kept cool.Application of 1% menthol in aqueous cream is often appreciated bythe child. A low-sedation H1 antihistamine is usually effectivein suppressing symptoms. Loratadine syrup or cetirizine oral solution canbe administered daily in a dosage of 2.5–5.0 mg daily, depending uponage. The timing of the dose depends on when the child's symptoms aremost severe. In adults, coadministration of an H2 antihistamine(cimetidine or ranitidine) may be useful, but this has not been shown to beof value in children. Cholinergic urticaria is also rather uncommon in very young children, butcommoner in teenagers. A figure of 2.7% incidence in 226 children hasbeen reported ( 4 ). Cholinergic urticaria is commonerin children with an atopic background. Its natural history shows spontaneousresolution in 2–3 years, but it can be very persistent. Typically, patientsreport that exercise, heat – for example, a hot bath or shower –anxiety, and, less commonly, temperature-hot food or drinks cause rapid outbreakof a pruritic papular eruption. Areas usually affected include the neck; flexorsurfaces of the elbows, knees, and wrists; and inner thighs. However, therash, which is intensely pruritic, can be generalized ( Fig. 2 ). Wheals can become confluent, leading to larger areas ofangioedema. If the patient cools down, the rash usually subsides in 30–60min. Systemic symptoms are common and range from wheezing and headache tosyncope. Unusual variants, which I have only seen in adults, include persistentcholinergic erythema ( 7 ) and exercise-induced angio-edema ( 8 ). The diagnosis (9) can present problemsin heavily pigmented skin. If the rash is macular it may not be readily visible.In this case, the patient may present with pruritus induced by exercise, heat,or emotion. Even in these cases, it is usually possible to visualize the rashwith angled lighting. Cholinergic urticaria. Note mainly pinhead-size,monomorphic, symmetric wheals. Development of the eruption is dependent upon activation of the stimulusfor sweating; but sweating itself is not essential, since the condition hasbeen described in patients with anhidrosis ( 10 ).A recent report of the association of sweat allergy with cholinergic urticariahas not been confirmed ( 11 ). However, the developmentof the rash is clearly dependent upon a cholinergic mechanism, since it canbe blocked by anticholinergics ( 12 ), and upon histamine,since it can be suppressed by antihistamines ( 13). Patients with cholinergic urticaria tend to have lowered plasma proteaseinhibitor levels ( 14 ), but the extent to which thisis relevant to the pathogenesis of the wheals is unclear. The diagnosis is confirmed by challenge testing. A warm bath or shower,or exercise is usually adequate to provoke the typical rash ( 9 ). All antihistamines should be withdrawn 48 h before challengetesting. Intradermal testing with acetyl-beta methyl choline or another cholinergicis, in our experience, unhelpful, although these agents do tend to producea larger wheal-and-flare reaction in patients with cholinergic urticaria thanin controls. The difficulties in making a diagnosis in black or dark brownskin have already been alluded to. The diagnosis is clinical, but confirmationcan be made by atropinization of a small area of skin with 6% hyoscineaqueous lotion, which blocks cholinergic urticaria. Care must be taken notto allow the hyoscine to get in the child's eyes. Localized contact heaturticaria is very rare. This physical urticaria occurs directly only at thesite of application of heat. The rash of the equally rare aquagenic urticariaclosely resembles that of cholinergic urticaria but is evoked only by contactwith water irrespective of its temperature. Some patients, by regulating the degree of exertion and the temperatureof the bath and shower, and by avoiding anxiety, can limit the severity ofthe eruption to within acceptable limits. This is obviously more difficultin small children, although possible in teenagers. Although patients withonly minor symptoms may require no treatment, low-sedation H1 antihistamines represent the lynchpin of treatment. As with other physicalurticarias, loratadine syrup or cetirizine oral solution can be administeredin a dosage of 2.5–5.0 mg daily. Regular daily treatment achieves betterresults than intermittent dosage, since there is, to some extent, a "build-up"therapeutic effect with regular dosage. In view of the above-mentioned loweredplasma levels of protease inhibitors, anabolic steroids have proved to beof value in severely incapacitated adults ( 15 ),but this treatment is unsuitable in children. Although a rather rare physical urticaria, cold urticaria is at least ascommon in children as in adults. Reports of frequency among children withchronic urticaria range from 8/94 to4/226 ( 3, 4 ). This compares with a figure of 14/554 patientsof all ages ( 1 ). Children with cold urticaria presentwith redness, swelling, and itching on exposed skin within minutes of goingoutside (e.g., to school) on a cold day, getting splashed by cold water, orswimming in a pool. Avoidance of cold leads to resolution of whealing in 30–60min. Sucking an iced lollipop causes redness, itching, or even angioedemaof the lips and, less commonly, of the tongue and palate. Systemic symptomsof headache, fatigue, faintness, vomiting, diarrhoea, and dyspnoea are notuncommon, especially after widespread exposure, as in swimming in sea water.Fatalities have occurred due to drowning. The prognosis is for eventual spontaneousimprovement in most patients over a period of up to 1–2 years. Occasionally,this physical urticaria may be persistent. Rarely, cold urticaria may be familial( 16 ). The molecular links between fall of skin temperature and degranulationof mast cells, leading to release of histamine and other mast-cell-derivedmediators, is unclear. Besides histamine, a number of other mediators havebeen identified. These include eosinophil chemotactic factors and eicosanoids( 17–19 ). Cold urticaria has been demonstratedto be passively transferable by serum ( 20 ), butthe serum factors responsible have not been clearly identified. Histologicexamination of a biopsy of skin repeatedly cold-challenged has been demonstratedto show evidence of vasculitis ( 21 ) in the absenceof evidence of circulating immunoreactants. Although frequently sought, evidenceof cryoglobulins, cold agglutinins, and cryofibrinogens is rarely found incold urticaria ( 22 ). The onset of cold urticariahas been preceded by a virus infection ( 23 ) in someinstances. The diagnosis is confirmed by challenge testing for an isomorphic coldreaction with an ice cube sealed in a thin, waterproof bag and placed on thepatient's skin for 10–15 min. A few additional minutes must beallowed for rewarming of the chilled skin to allow a positive test to developafter removal of the ice cube ( Fig. 3 ). Inpatients who have concurrent dermographism, a modified challenge test by immersionof a forearm in water at 4°C for 10 min should be used to avoid false-positivereactions. All antihistamine therapy should be stopped 48 h before the test. Positive ice cube test in cold urticaria. The condition may be mild and self-limiting, in which case avoidance ofexcessive cold exposure (wearing tracksuits for games and swimming only inwell-heated pools) may be sufficient. Children with cold urticaria shouldnever bathe in a swimming pool unsupervised. In more severely affected children,regular daily dosage with H1 antihistamines (loratadine syrup2.5–5.0 mg daily; cetirizine oral solution 2.5–5.0 mg daily) isusually sufficient. However, some patients with severe cold urticaria seemunresponsive even to large doses of antihistamines. Cold tolerance treatment(regular exposure of affected skin to cold depletes the skin of stores ofhistamine) is effective ( 24 ) and surprisingly welltolerated by some motivated children. This treatment can be employed on anad hoc basis, as, for example, when the family is going on holiday and frequentrecreational cold exposure is anticipated. For rare patients with cryoglobulinaemia,intravenous immunoglobulin immunotherapy may be considered. When delayed pressure urticaria is present, it invariably coexists withchronic "idiopathic" urticaria (CIU). I am not personally awareof any patient who had delayed pressure urticaria without spontaneous whealingas well. In adults, about 40% of patients with CIU also have delayedpressure urticaria ( 25 ). Since CIU is rare in children,delayed pressure urticaria is also uncommon. Most authors do not mention it,but Volonakis et al. report one child out of 226 with chronic urticaria whowas given this diagnosis ( 4 ). Characteristicallyitchy, tender, or painful wheals occur at sites of local pressure includingthe waistband, soles of feet, or palms of hands. The wheals do not developfor at least 2 h after application of pressure, and thus the connection maybe overlooked by parents and child alike. They are also persistent, lastingat least 24 h and frequently for 48 h or more. Like other physical urticarias,the wheals eventually fade without leaving a mark except for bruising dueto vigorous rubbing or scratching. Delayed pressure urticaria tends to bepersistent, lasting for several years. The delayed onset and prolonged duration of the wheals of delayed pressureurticaria set it apart from other types of physical urticarias. Histologically,it closely resembles the late-phase immunologic reaction with involvementof CD4 T cells, eosinophils, mast-cell degranulation, and ad- hesion moleculeexpression ( 26 ). However, its molecular basis isunknown. The location of the wheals at pressure sites and their prolonged time courseare important clinical pointers. The diagnosis is confirmed by challenge testingby pressure applied perpendicular to the skin. My laboratory uses a hand-heldspring-loaded dermographometer ( Fig. 1) thatis suitable for children. To elicit delayed pressure urticaria, it is appliedvertical to the skin. The test is read 4 h after application. Urticarial vasculitis(see below) is also localized at pressure sites, it is delayed, and its whealslast for over 24 h. Only a skin biopsy can enable delayed pressure urticariaand urticarial vasculitis to be confidently distinguished from each other.The distinction is important because no investigations are required once thediagnosis of delayed pressure urticaria is confirmed, whereas urticarial vasculitisrequires substantial laboratory work-up (see below). It is important to identify delayed pressure urticaria in patients withCIU. Delayed pressure urticaria responds poorly, if at all, to antihistaminesand accounts for the poor response of many patients with CIU to treatment.I have not found any treatment to be consistently effective in delayed pressureurticaria. Large dosages of oral corticosteroids do suppress pressure-inducedwhealing but at the unacceptable cost of severe steroid toxicity. This physical urticaria is rare in adults and very rare in children. Thereis one case report of a 2-year-old infant who developed unequivocal solarurticaria ( 27 ). A recent report ( 28 ) of 25 cases states that the ages at first consultation rangedfrom 17 to 71 years, but does not give the ages of onset. Redness, itching,and whealing develop within a minute or two of sun exposure. These symptomssubside in 30–60 min if sun exposure is avoided. Systemic symptoms arerare. The condition usually runs a course of several years in adults beforesubsiding. The action spectrum for whealing ranges from UV-B (290–310 nm) throughto visible light ( 28 ). Autologous serum skin phototesting( 29 ) suggests the involvement of a photoallergenin cutaneous mast-cell degranulation and histamine release after sun exposure. The hallmark of solar urticaria is the development of itching, whealing,and redness on exposed skin immediately after sun exposure. The differentialdiagnosis includes the very common polymorphic light eruption. In this photodermatosis,erythema and itching occur several hours, not minutes, after sun exposure,and the rash persists for several days even if sun exposure is avoided. Mostpatients diagnosed initially as having solar urticaria turn out to have polymorphiclight eruption. In children, itching and burning of exposed skin immediatelyafter sun exposure occur in the rare inborn error of metabolism, erythropoieticproto-porphyria. In this condition, fluorescence of UV-irradiated red bloodcells can be demonstrated on photomicroscopy. Children with this disorderalso usually manifest superficial linear fine scars on the nose, cheeks, andchin. Occasionally cholinergic urticaria may cause diagnostic confusion becausesolar heat can induce wheals on the face and neck in this physical urticaria.Exercise or hot-shower challenge testing should resolve this issue. Moreover,the whealing of solar urticaria, unlike cholinergic urticaria, cannot be blockedby atropinization with 6% aqueous hyoscine. No further investigationsare warranted once the diagnosis of solar urticaria has been made in a child,apart, possibly, from excluding erythropoietic protoporphyria, as mentionedabove. Determination of the action spectrum may be useful in fine-tuning sun-protectivetreatment. Avoidance of sunlight and use of an appropriate sunscreen (depending uponthe action spectrum in each individual case) may be sufficient in mildly affectedpatients. H1 antihistamines (cetirizine oral solution or loratadinesyrup 2.5–5.0 mg daily) are usually helpful. Tolerance treatment hasbeen advocated in more severely affected patients ( 29, 30 ). The occurrence of spontaneous wheals daily or almost daily for at least6 weeks characterizes chronic "idiopathic" urticaria (CIU) ( Fig. 4 ). Although the urticarial wheals do not affectmucous membranes, angioedema, which can involve mucous membranes, occurs in38–87% of adult patients with CIU ( 31). When angioedema, in association with CIU, affects the oropharynx, patientsmay be acutely distressed, but I have personally never seen a death from angioedemaassociated with CIU. By definition, the duration of wheals of CIU is lessthan 24 h. Unlike the wheals of most physical urticarias, the wheals of CIUlast at least 6–8 h and usually longer. They fade without leaving amark in the skin. However, CIU is also complicated by delayed pressure urticariain about 40–50% of patients ( 25 ), thepressure-induced wheals individually lasting 24 h or longer (see above). However,it should be emphasized that these figures come from adult studies; thereare few or no comparable data from children with CIU. CIU is less common inchildren than adults, although Harris et al. ( 3 )appear to have identified as many as 79 children with "idiopathic"chronic urticaria out of a total of 94 with chronic urticaria. The overallprognosis in children is unclear; 50% of adult patients experienceremission in 3–5 years ( 32 ). Chronic "idiopathic" urticariain 11-year-old. This child, previously rendered cushingoid by steroids, wasfound to have anti-Fcε RIα autoantibodies and subsequentlyresponded very well to intravenous immunoglobulin infusions, allowing oralsteroids to be withdrawn. Most patients (or their parents) with CIU believe that food factors areinvolved although, at least in adults, this can rarely be substantiated. Placebo-controlledfood challenge tests remain the "gold standard" ( 33 , 34 ). Exclusion diets are invariablylong-drawn-out, with poor compliance and ambiguous results. However, by placebo-controlledchallenge testing, about 5% of adult CIU patients can be shown to reactadversely to one or more food additives, and these patients may be helpedby appropriate dietary advice ( 35 ). Other causes frequently cited in the literature include infections of diversenatures. Most recently, Helicobacter pylori infection of the stomachand duodenum has been frequently implicated as a causative agent for CIU inadults ( 36 ), but recent reports appear not to confirmthis association ( 37 , 38). In some parts of the world ( 39 ), almost 50%of children are infected with H. pylori. Overall, the "focusof infection" theories have never stood the test of time for CIU. Parasite infestation has never been confirmed as a cause of CIU in anyof my patients. However, it is conceivable that this could be a causativefactor in regions where heavy parasite loads are endemic. Further criticalstudy of this association in children and adults would be worthwhile. Until recently, the cause of promiscuous activation of dermal mast cellsin CIU was unknown in most cases. To an extent, this still remains true, butrecent work indicates that in at least some of these otherwise puzzling patients,the mechanism is autoimmune in character. As early as 1974, ex vivo histamine-release studies of blood basophils of patients with CIU indicatedthat one or more circulating histamine-releasing factors could be involved,at least in some patients ( 40 ). However, this findingwas not followed up until over 10 years later, when, in 1986, Grattan et al.reported ( 41 ) the presence of a serologic mediatorof whealing in some patients with chronic urticaria. Further characterizationof this activity showed that it was almost entirely attributable to an IgGautoantibody directed against the alpha chain of the high-affinity IgE receptor(Fcε RIα) of mast cells and basophils or, less commonly,against IgE itself ( 42 , 43). This finding was subsequently confirmed by several independent groups ( 44–46 ). The proportions of patients in whoman autoimmune basis can be demonstrated ranges from 25% ( 43 ) to almost 50% ( 46 ). I am notaware that these autoantibodies have been looked for systematically in childrenwith CIU, and this needs to be done. However, some details of our autoantibodymeasurements in patients aged 16 years and below are given in Table 2 . Subsequent studies have demonstrated these anti-Fcε RI autoantibodiesto be predominantly IgG1 and IgG3 subtypes ( 47 ).The specificity of these autoantibodies has been investigated. They have notbeen found in healthy individuals or in patients with atopic eczema, psoriasis,or physical urticaria ( 42 , 43). However, immunoreactive but non-histamine-releasing anti-FcεRI autoantibodies have been detected in small numbers of patients with otherautoimmune diseases including dermatomyositis, pemphigus, and pemphigoid ( 47 ). In these cases, the IgG subtypes have been predominantlyIgG2 and IgG4. As far as I am aware, functional (i.e., histamine-releasing)anti-Fcε RIα autoantibodies have been demonstrated onlyin CIU. That some patients with CIU have an autoimmune basis is not especiallysurprising since an association between CIU and thyroid autoimmunity has beendemonstrated ( 48 , 49 ).Furthermore, increased frequency of HLA-class II alleles HLA DRBI *04(DR4) and DQBI*0302 (DQ8) in autoimmune urticaria is in keeping with itsimmunologic basis ( 50 ). It has been suggested ( 51 ) that these autoantibodies, although demonstrable inCIU, may not be of pathogenetic significance. That they are in fact the causeof the clinical picture is evident from their functional histamine-releasingactivity, direct quantitative relationship with disease severity ( 52 ), and clinical response to removal or suppression by plasmapheresisor intravenous immunoglobulin ( 52 , 53 ). Whether or not IgG-anti-Fcε RI autoantibodiesfix complement is a controversial issue. Our own ( 42, 43 ) evidence is that anti-Fcε RIautoantibody histamine-releasing activity is thermostable, a fact which arguesagainst complement involvement. However, recent evidence ( 54 ) suggests that under circumstances in which there is a low mast-cellor basophil surface population density of high-affinity IgE receptors, monovalentrather than divalent cross-linking of these receptors by anti-Fcε RIα autoantibodies may occur, and in these circumstances complementmay be involved. This would be more likely to occur in individuals with lowserum IgE. In view of the absence of evidence of mast-cell activation in therespiratory tract in patients with autoimmune chronic urticaria, it is ofinterest that, unlike skin mast cells, lung mast cells do not express complementreceptors. Inflammatory skin lesions lasting less than 24 h are, by definition, urticarial.However, the patient's perception of duration of individual wheals isoften inaccurate. The most important differential diagnosis is urticarialvasculitis, and in this condition the wheals last more than 24 h – oftenas long as 48 h or even longer. Unlike CIU, the wheals of urticarial vasculitismay leave purpuric staining of the skin. Only a skin biopsy can resolve thisissue. Urticarial vasculitis should not be deemed to be confirmed in the absenceof histologic evidence. Facial angioedema is occasionally confused with anumber of causes of facial swelling including acute contact allergic dermatitis,Crohn's disease, Melkersson-Rosenthal syndrome, and dermatomyositis. Apart from skin biopsy (see above), the value of laboratory work-up inCIU is limited. The presence of blood eosinophilia should prompt a searchfor parasite infestation, but this is an exceptional finding, at least ina UK population. Placebo-controlled oral challenge for evidence of food-additivereactivity is worth carrying out in adults, but I have no experience of itsfeasibility or value in children with CIU. It should be possible to carryout autologous serum skin testing in older children as a screening test forautoimmune urticaria ( 41 ). The sensitivity and specificityof this test have recently been optimized ( 55 ).However, confirmation of the presence of anti-Fcε RI autoantibodiesrequires demonstration of histamine release from basophils of healthy, low-serum-IgEdonors ( 43 ) or immunoblotting ( 44 ), although, as indicated above, false positives can be elicitedby this technique. Confirmation of the autoantibody alpha-chain specificityis obtained by inhibition experiments with the human recombinant alpha chain.Anti-IgE autoantibodies are detected by basophils of high-serum-IgE donors,with confirmation by inhibition with monoclonal IgE. Reliable, sensitive,and specific ELISAs for these autoantibodies are badly needed. It is important to reassure parents and teachers that, in the vast majorityof patients, CIU is not an outward manifestation of a sinister underlyingdisease. Common-sense measures are helpful, including avoidance of coarse,tight, woollen underclothes and an overheated environment to allay itching.Intercurrent febrile infections almost invariably cause nonspecific flare-upsof CIU, and parents should be warned about this. Oropharyngeal angioedemais rarely, if ever, life-threatening, but it can be frightening to the child,parents, and teachers alike. Administration of two to three puffs of a 2%aqueous ephedrine spray is safe and effective at the onset of an attack andat 10-min intervals up to a maximum of three doses. It is most reassuringfor all concerned to have this emergency treatment on hand. Aspirin and aspirin-containingmedications should be avoided. The risk of taking other NSAID is more controversial,but it is probably prudent to avoid them where possible. The first line of treatment for any patient with CIU, whatever the cause,is to prescribe H1 antihistamines. For small children, at leastin the UK, the choice is limited. Only hydroxyzine (dosage 5–15 mg daily)is recommended for infants of 1 year or less as a syrup. Above 2 years, thechoice is wider but, of the low-sedation H1 antihistamines, onlycetirizine (formulated as an oral solution) and loratadine (as a syrup) arerecommended for 2–6-year-old children. It is reasonable, in more severelyaffected children, to prescribe a low-sedation antihistamine in the morningand hydroxyzine at night. The value of combined H1 and H2 antihistamines is not proven in children. Oral steroids should be rarely necessary. If administe