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Urticaria

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A 2-year-old boy presents to ED with his parents with rhinorrhoea, cough, fever and a widespread itchy migratory rash. How are you going to manage this urticaria?

What are important questions to ask in the history?

Ask about the progress of the illness and then ask specifically about the symptoms of generalised allergic reaction or anaphylaxis symptoms. If there are any signs of anaphylaxis, the patient needs adrenaline.

Ask about the progress of the rash – when lesions appeared and their duration and recurrence, distribution, size, and shape.

Clarify events in the hours prior to urticaria (ingestion, exercise, temperature extremes, or insect bites)

Check for a history of urticaria with infections or after previous medication/drugs and any history of allergy.

Ask about recent illness/new medication/travel history

Do a systems review and screen for signs of systemic disorder – fever, weight loss, arthralgias, arthritis, or bone pain.

What are the key examination findings in urticaria?

Look for symptoms suggestive of anaphylaxis or the presence of wheals.

How would you describe the lesions?

This is urticaria or hives. It has a polymorphic appearance – the lesions are well-circumscribed and may vary from small flat papules to raised, erythematous plaques, often with central pallor.

It may be round, oval, or serpiginous (snake-like) and can vary, from less than 1 cm to several centimetres in diameter.

The lesions are intensely pruritic, and you may see excoriation. This itchiness may disturb sleep, and the symptoms often seem most severe at night.

What is the classic lesion pattern in urticaria?

Urticaria is transient. Lesions usually appear and get larger over the course of minutes to hours and then disappear within 30 minutes to 24 hours. They may coalesce as they enlarge.

If the patient or parents are unsure of the duration of the lesions, mark one with a pen to see how long it takes to resolve.

Despite being incredibly itchy, they are usually not painful, and they resolve without leaving a mark (unless there are scratch marks).

If the lesions are long-lasting, painful, or leave residual bruising, the diagnosis of urticarial vasculitis should be considered. This is much rarer than urticaria.

What’s the difference between acute and chronic urticaria?

Acute urticaria lasts less than six weeks and at least a few days continuously. It is spontaneous, i.e. not inducible.

Chronic urticaria lasts more than six weeks, with signs and symptoms recurring during most days of the week. If chronic urticaria is diagnosed, you can consider investigations such as FBC, CRP, and ESR (looking for evidence of inflammation).

Autoimmune urticaria occurs when autoantibodies occur against mast cells. Children diagnosed with autoimmune urticaria do not usually have concomitant autoimmune disease.

Chronic or suspected autoimmune urticaria can be referred to a paediatric allergist for review and further investigation.

The parents ask, “Will the rash get better?”

 100% of cases of acute urticaria get better by definition, with the majority of cases improving in days to weeks. Very few cases progress to chronic urticaria.

The parents ask if urticaria is common.

 Yes, it is very common. One Korean cross-sectional study of over 4000 children reported the lifetime prevalence of any type of urticaria as 22.5% (1).

How is urticaria different to angioedema?

Angioedema is the sudden, pronounced erythematous or skin-coloured swelling of the lower dermis and subcutis. Patients usually complain of pain rather than itchiness. There is slower resolution of wheals, over 72 hours. Angioedema, when associated with urticaria, usually affects the face and lips, extremities, and/or genitals.

If your patient has recurrent angioedema without urticaria, think of another angioedema disorder, such as C1 esterase inhibitor deficiency.

What is the differential diagnosis for urticaria?

The presence or absence of pruritus is a helpful clinical feature.

Non-pruritic differentials include viral exanthems, auriculotemporal syndrome, and Sweet syndrome.

Pruritic differentials include atopic dermatitis, contact dermatitis, drug eruptions, insect bites, and erythema multiforme minor.

What tests are required?

For patients presenting with new-onset urticaria (with or without angioedema) in whom the clinical history and physical exam do not suggest an underlying disorder or urticarial vasculitis, there is no need for blood tests or further investigation.

If the presentation is suggestive of an allergic reaction, then proceed down that pathway of investigation and referral.

What are the most common causes of acute urticaria in paediatrics?

  • Idiopathic (often the majority)
  • Infections (mainly viral upper respiratory tract infections). Acute urticaria may develop during or following a viral or bacterial infection,
  • Food and drugs (allergic and pseudoallergic). Acute urticaria is one of the main manifestations of IgE-mediated food allergy, but food allergens are responsible for less than 7% of all cases of urticaria (2).

    IgE-mediated reactions usually present with urticaria within minutes to two hours following exposure to the allergen. Beta-lactams (penicillins and cephalosporins) are the most commonly reported antibiotics, although antibiotics from virtually all classes have been reported. Consider an allergic cause if episodes occur under similar circumstances, e.g. following ingestion or exercise. Food-dependent exercise-induced anaphylaxis is an IgE-mediated hypersensitivity to food and anaphylaxis, which only occurs when both the food is ingested and exercise takes place. (i.e. intake of these foods is tolerated in the absence of exercise, which distinguishes it from food allergy). Implicated food products are wheat (most common), cereals, shellfish, nuts, vegetables, fresh fruit, eggs, and milk.
  • Stings (e.g. bees, wasps). N.B. Bedbugs, fleas and mites can cause papular urticaria, which resolve over weeks.

What infections are associated with acute urticaria?

  • Picornavirus (most common), coronavirus, respiratory syncytial virus, and several others, including the hepatitis viruses and HIV.
  • Infection with various picornaviruses may manifest as a common cold, a febrile rash illness (hand-foot-and-mouth disease), conjunctivitis, herpangina, aseptic meningitis, encephalitis, myositis, myocarditis, and hepatitis.
  • Interestingly, acute urticaria, refractory to antihistamines but responsive to azithromycin, has been associated with Mycoplasma pneumonia infection in children.
  • Parasites such as AncylostomaStrongyloidesFilariaEchinococcusTrichinellaToxocaraFasciola,
  • Schistosoma mansoni, and Blastocystis hominis have all been associated with urticaria. It is only necessary to undertake stool microscopy and investigation in patients with eosinophilia and significant travel history.

What infections are associated with chronic urticaria?

  • Epstein-Barr virus, bacteria such as Streptococci, Staphylococci, Helicobacter pyloriEscherichia coli and parasites such as Blastocystis hominis.

What else causes urticaria?

Direct mast cell activation. Drugs, foods, and plants can cause urticaria due to mast cell degranulation through a non-IgE-mediated mechanism. Drug examples include opioids such as morphine and codeine, muscle relaxants, vancomycin, radiocontrast media, dextromethorphan (a cough suppressant), and anaesthetic muscle relaxants. Some foods, such as tomatoes and strawberries, cause generalised urticaria or contact urticaria through non-immunologic mechanisms. These foods are sometimes referred to as “pseudo allergens.” Note that IgE-mediated allergies to these foods are also possible.

NSAIDs. They are unusual in that they can cause urticaria via two mechanisms.

  • Pseudoallergy due to abnormalities in arachidonic acid metabolism. This is not a true allergy but a pseudoallergic reaction because the mechanism is nonimmunologic. This can be seen with any COX-1 enzyme inhibitor (e.g. ibuprofen or aspirin).
  • Allergic – a specific NSAID can also cause acute urticaria in patients who are allergic to that one agent. These reactions are presumed to represent true, immunologic allergy.

Other types of physical/inducible urticaria include:

Dermographic urticaria (whereby rubbing or scratching induces wheals), cold exposure, sudden changes in body temperature, delayed pressure or vibration against the skin, exercise (with elevation of body temperature, which does not occur in hot bath), exposure to sunlight (solar urticaria), or other stimuli (cholinergic urticaria), and aquagenic urticaria (rare).

Urticaria can also occur as a part of a disease process or autoimmune disease process, such as serum sickness; urticarial vasculitis, mastocytosis; systemic lupus erythematosus, rheumatoid arthritis; Sjögren syndrome, Coeliac disease; other autoimmune disease; or immunoglobulin A (IgA) vasculitis (Henoch-Schönlein purpura)

What is the management of acute urticaria?

Initial treatment of new ­onset urticaria (with or without angioedema) should focus on the short ­term symptomatic relief with a non-sedating second or third-generation H1-antihistamine during the day and consideration of a sedating H1-antihistamine at night.

If urticaria is severe, an H2 antihistamine can be added.

  • Cetirizine (0.25mg/kg/dose PO Q12-24 hours, with adult dose 10 mg PO in children >6 months of age). It can be mildly sedating. Up to 4 times the recommended dose can be given for short term use (max dose 40 mg per day).
  • Loratidine 10 mg PO once daily for children >6 years, dose 5 mg daily in age 2-6 years.
  • Desloratadine is the major active metabolite of loratadine and produces effects equivalent to loratadine at about one-half the dose. Dose is 5 mg PO daily, for children >12 years; 2.5 mg PO daily, for children 6-12 years; 1.25 mg in children 1-5 years. 1 mg daily for children age 6-12 months.
  • Fexofenadine: Fexofenadine is minimally sedating. Dose is 180 mg PO daily >12 years or 30 mg PO BD for ages 2-11 years.

If prominent angioedema or persistent symptoms despite the above, a brief course of oral glucocorticoids can be considered in addition to the above therapy. They are not routinely prescribed.

Prednisolone 0.5 to 1 mg/kg/day (maximum 60 mg daily), with tapering of the dose over five to seven days and oral proton pump inhibitor cover.

If symptoms do not recur over several days after stopping glucocorticoids, then antihistamines can be discontinued also. For patients whose symptoms recur when medications are discontinued, antihistamines should be reinstituted and used at the lowest effective dose.

Steroid creams do not work.

What is the management of chronic urticaria?

If symptom control is inadequate, non-sedating second-generation H1-antihistamine doses can be increased up to four-fold the standard dose.

Histamine upregulates its own ligand on H1-receptors so continuous treatment with H1-antihistamines is important.

Oral steroids can be considered as per above.

Immune-modulating medications such as omalizumab are also available.

The average duration of chronic urticaria is 2-5 years.

Selected References

Godse K, Tahiliani H, Gautam M, Patil S, Nadkarni N. Management of urticaria in children. Indian Journal of Paediatric Dermatology. 2014;15(3):105–9.

Shin M, Lee S. Prevalence and Causes of Childhood Urticaria. Allergy Asthma Immunol Res. 2017 May;9(3):189–90.

Author

  • Clementine David is a trainee in Clinical Immunology and Allergy with an unrivalled affiliation for gelato. While an Aussie at heart, she is currently residing as an expat in Hong Kong’s Happy Valley, balancing her time between antigens and Octonauts.

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3 thoughts on “Urticaria”

  1. 2 to 5 years nothing i started with chronic idiopathic autoimmune but also have delayed pressure urticaria for a total of 13 years now

  2. thank you, excellent overview.
    we recommend in adults with recurring urticarial events to take an alcohol use history, often find they are chronic misuser of alcohol

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