Chronic Urticaria for the paediatrician

What do General Paediatricians need to know about urticaria

• Acute vs chronic urticaria • EATERS history taking• Making the diagnosis of urticaria• Differential diagnoses • Management• Off licence treatments• Criteria for referral

Background

• Urticaria is common • Encompasses both weals/hives and angioedema• 50-80% have associated angioedema and approximately 10 %

angioedema along• Rarely a severe disease• Majority responds to first-line treatment with antihistamines• Usually remits over time• Quality of Life implications

o Psychological stresso Missed schoolo Fears of food allergy, anaphylaxis and infection

Background

• Urticaria is characterized by the appearance of weals+/- angioedema

• A weal consists of three typical features:▪ Central pale swelling of variable size,

▪ Red/erythematous halo▪ Associated itching / burning sensation▪ Fleeting nature

▪ Resolving, usually within 1 – 24 hours

Angioedema

Characterized by :• Swelling of the lower dermis and subcutaneous tissues

• Sudden onset• Painful rather than itch • Often involvement around mucous membranes and/or

eyes• Resolves slowly, up to 72 hours

Acute vs chronic urticaria

Acute urticaria • Lesions last less than 6 weeks• Weals and/or angioedema usually daily at least initially• Aetiology includes

– Infection– Allergens (foods, aeroallergens)

Chronic urticaria • Lesions last more than 6 weeks• Weals and/or angioedema usually daily/weekly but can

occur intermittently

Classification of chronic urticaria

Chronic Urticaria

Spontaneous Inducible

DermatographismCholinergicCold or heat AquagenicDelayed pressureSolarVibratory

Idiopathic• Auto-immune• Post-infectious

M.V. – a case of chronic urticaria

• 6 year old girl• Presented with 8 week history of recurrent urticaria

o Unwell prior to symptoms with episode of diarrhoea and vomiting

• Itchy rash on arms and legs and swelling of face and hands• Symptoms last up to 24 hours• Ingestion of bubblegum lolly gave rise to blisters in her mouth• Missing school due to parental concerns• On 5 mg cetirizine prn and has had one course of oral steroids• No asthma, eczema or hay fever and good appetite• Family history: Hypothyroidism in father

M.V. – a case of chronic urticaria

Investigations• Skin prick testing 2 mm house dust mites, no evidence of

sensitisation to other aeroallergens• TFT, anti-TPO antibodies, ASOT, anti-DNase, FBC, ESR, LFTs, CRP,

ESR, C3 and C4, and C1 esterase inhibitor performed• TSH raised 5.14 and T4 reduced 10.7 – repeat TSH 6.6• Mycoplasma IgM positive• Thyroid ultrasound normal• Seen by Dermatology and parents requested adrenaline auto-

injector• Referred to endocrinology – concerns regarding weight gain and

temperature instability

M.V. – a case of chronic urticaria

Clinical course• History of rash changes – now intermittently itchy,

burning and lasting longer than 24 hours with a suggestion of bruising, fatigue, constipation and dryness of skin

• Auto-immune profile performed – perinuclear ANCA showed unspecific pattern

• Skin biopsy – normal• IgA slightly low (0.39 g/L) and coeliac screen positive

Differential diagnoses of chronic urticaria

• Medication use (ACE inhibitors, NSAIDs)• Urticarial vasculitis• Coeliac disease (dermatitis herpetiformis)• Hereditary angioedema secondary to C1

inhibitor deficiency

Assessment and diagnosis of CSU

• History• Examination of the rash• Response to medication• Associated medical history

Eaters• Exposure

o Any foods ingestedo Any allergen in the vicinity Usually no specific exposure identified

• Allergeno Foods/aeroallergens No identifiable allergen or multiple lists offered

• Timingo Between allergen exposure and appearance of symptoms If allergen suspected > 60mins from exposure

• Environmento Home, restaurant, friend’s house, school, in bed, outdoors Think environment was it cold/after the bath or

exercise

• Reproducibilityo Are the symptoms always seen after the food/aeroallergen Difficult to reproduce

• Symptomso Rash and swelling distribution Unusual areas of distribution, but may help diagnosis

What else do you want to know ?

• Any precipitating factors ?• Frequency / duration?• How long do the lesions last ? • Do they leave any residual marks ? Petechiae, purpura, bruising• Any other accompanying symptoms ? Fever, maliase,

arthralgia• Any angioedema or breathing difficulties ?• Anything make it better or worse ?• Use of anti-histamines, topical creams or oral steroids ?• Any other past medication history of note ?• Family history ?

Triggers

• Allergy• Food allergy is usually NOT associated with chronic urticaria• Persistent aeroallergen exposure is rarely associated with chronic urticaria

• Initial urticaria usually develops into eczema flare on persistent allergen exposure

• Physical/inducible urticaria is common • Pressure, cold, aquagenic, cholinergic, solar• Look for dermatographism on examination• Medications • NSAIDs, ACE inhibitors• Associated diseases• Infection • Coeliac disease• Auto-immune disorders (urticarial vasculitis)

Infectious causes of chronic urticaria

• Bacterialo H. pylori, Streptococcus, Staphylococcus,

Mycoplasma, Yersinia• Viral

o Hepatitis, Norovirus, Parvovirus B19 • Parasitic

o Giardia, Anisakis Simplex, Entamoeba, Blastocystis

Assessment

• Urticarial Assessment Score (UAS7)o Can be helpful to log severity and with symptom

trackingo Can be used in combination with diary monitoring

exposure to potential allergens• Symptom score over 7 days

o Validated to support and monitor o May help management decisions

UAS7 :scoring system

Investigation of urticaria

• Routine panels of testing not usually helpfulo Costlyo Uncomfortable for the childo Rarely gives answers that improves outcomes

• Some tests are useful IF guided by clinical suspicion

Investigations

• Keep it simple• Be guided by the history

• Allergy testingo Rarely indicatedo Often requested for parental reassuranceo Food elimination/reintroduction usually not helpfulo A good history is a valid investigation #EATERSo Will need discussion and reassurance

Urticaria testing

Basic blood testso Full blood count-

— If history of fatigue/lethargy looking for anaemia and infectiono ESR

— If family history or suspected autoimmune diseaseo Liver function

— If infections suspected, add viral screen if abnormalo Coeliac screen

— If gastrointestinal symptoms +/- fatigue or atypical rasho Thyroid function and anti-thyroid peroxidase antibodies

— If autoimmunity is suspected

Further testing

Leveling up……moving towards onward referral

• Antinuclear antibodies o Suspect connective tissue disorders

• Complement studies (C3 andC4), C1 esterase inhibitor and functional activityo If angioedema alone, to rule out hereditary angioedema

• Skin Biopsyo If lesions last longer than 24 hours and leave residual

hyperpigmentation indicative of urticarial vasculitis • Infection panels – guided by history• Allergen challenges if necessary

Challenges Physical Urticaria: examples

Inducible urticaria

◼ Symptomatic dermatographism

◼ Cold urticaria

◼ Delayed pressure urticaria

◼ Heat urticaria

Often best identified by asking duringhistory!

Routine diagnostic test

Scratching or shear forces on the skin

Cold provocation test (ice cube)

Pressure test (weight bag or specialinstrument on the arm.

Metal or glass cylinder filled with hot wateron the forearm for 5 minutes

Management

• Identify any possible triggers• Disprove unconvincing triggers

(food colourings, additives etc)• Reassure• Patient information leaflet• Indication of prognosis

Symptom controlUrticaria diagnosis

Antihistamines (second generation)as needed

Antihistamines (second generation)Regular, up to twice daily

Addition of second line agent

Non sedating anti-histamine (AH)

If symptoms persist after 2 weeks

Increase dose (up to 4 times recommended dose) or add in second antihistamine

Add second line agent, Montelukast and/or Ranitidine. Consider Tranexamic acid for angio-oedema without weals

If symptoms persist after 1 - 4 weeks

If symptoms persist after 1-4 weeks

Consider Cyclosporin or Omalizumab (Xolair)

Management of Chronic Urticaria (BSACI 2015)

39 % respond

63 % respond

Antihistamine dosing

• Preparations• Dose/kg max doses• Age range

Role of adjunct therapy

• Corticosteroidso For acute exacerbations give short courses of oral steroids (3

days)o Prednisolone 0.5mg/kg once dailyo Side effects

• Leukotriene receptor antagonistso Can help response to anti-histamineso No evidence for monotherapyo Montelukast 4-10mg daily

• Tranexamic acido Useful for angioedema aloneo 15-25mg/kg TDS

Anti IgE therapy

• Omalizumabo Anti-human IgE monoclonal antibody o Inhibition of allergic inflammationo Binds free circulating IgE with high affinityo Downregulates high and low affinity IgE receptors on mast

cells and basophils

• Licensed for children over 12 years of age in chronic spontaneous urticaria

• Initially monthly injections for 6 months to assess responsiveness• Administration in tertiary centres only

Who should manage Urticaria ?

• Primary Care/ ED presentationo Acute or evolving urticarial rash < 6 weekso History suggestive of recent or current infection

• Referral to allergy unnecessaryo Treat underlying infection appropriatelyo Reassure o Treat symptoms - non sedating antihistamines

Who should manage Urticaria ?

• Primary care/ ED presentationo Acute or evolving urticaria < 6 weeks durationo Likely aeroallergen exposure (grass/tree pollens,

pets, house dust mites)• Allergy referral unlikely to be helpful unless associated

food allergieso Treat with non sedating antihistamineso Manage associated atopic conditions (allergic

rhinitis, eczema, asthma)

Who should manage Urticaria ?

• Primary care/ ED presentationo Acute or evolving urticaria <6 weeks durationo Idiopathic/ no identified cause

• Allergy referral unlikely to be helpful unless chronic persisting beyond 6 weeks durationo Treat non sedating antihistamineso Refer if persists > 6 weeks

Criteria for allergy clinic referral

• Paediatrician with allergy interest in a DGHo Concerns about or to rule out acute allergieso Duration > 6 weeks

BUT not all urticaria = allergy until proven otherwise o Rather baseline history with primary contact

(GP/ED) and refer with concerns when allergy may be a factor

Criteria for onward specialist referral

• Specialist Allergy clinico If suspected physical urticaria

— To confirm the diagnosiso When not responding to higher doses of antihistamines

— Beginning/considering adjunct treatment Montelukast/ranitidineo Candidate for Anti-IgE therapy

• Specialist Dermatology clinico Urticarial vasculitis

• Specialist Immunology clinico Possible autoimmune conditionso Angioedema only/Hereditory angioedema suspected o Candidate for anti IgE therapy if no local specialist allergy centre