Urticaria

General paediatrics, Immunology

Or “hives” – itchy plaques or papules (weals), with surrounding flare, typical of histamine reaction in skin. Urticaria can also be accompanied by angioedema – although angioedema on its own may point to hereditary angioedema (else drugs eg NSAID, ACE inhibitors, oestrogens, statins), and absence of angioedema may suggest urticarial vasculitis, Schnitzler syndrome, cryopyrin associated periodic syndromes.

Not always allergy, although it is the classic rash of type 1 (histamine and IgE mediated) allergy.  Can be inducible or spontaneous.  Can be transient, intermittent or chronic (6 weeks minimum).

Burden on quality of life and health services can be substantial.

Inducible

Various kinds of physical stimuli can trigger urticaria, including:

  • Dermatographism – within 10 minutes of pressure
  • cf Delayed pressure type – tight clothing, sitting
  • Heat (including exercise and emotion)
  • Cold – can be secondary to autoimmune conditions or infection. Anaphylaxis risk from swimming!?
  • Sunshine (solar)
  • Water (aquagenic) – cold, hot, even rain…
  • Vibratory angioedema
  • Cholinergic urticaria
  • Contact urticaria

Can be mixed! Some tests have been suggested eg ice cube test (ice cube in a sealed plastic bag over the forearm for up to 10 min – wait for skin to rewarm), flannel test for aquagenic (wet towel for a few minutes on area of skin most affected).

Can be hormonal in girls, therefore cyclical (catamenial).

Differential

These things are considered to have different mechanisms:

  • Hereditary angioedema
  • Delayed food allergy eg alpha gal, or exercise induced
  • Atopic dermatitis
  • Chronic or recurrent infection (consider occult eg dental)
  • Erythema marginatum (as in rheumatic fever, but also a prodrome to HAE!)
  • Erythema multiforme
  • Drug reactions
  • Polymorphous light eruption
  • Thyroid disorders
  • Cutaneous mastocytosis
  • Systemic lupus erythematosus
  • Cryopyrin (autoinflammatory) disorders, typically with fever, arthralgia, eye inflammation eg Muckle Wells
  • Schnitzler syndrome – with monoclonal gammopathy
  • Gleich syndrome – with eosinophilia
  • Urticarial vasculitis (often spectacular, lasts more than 24 hours, bruising develops)
  • Autoimmune urticaria (caused by autoantibodies vs FC epsilon RI alpha, but antibodies do not correlate well with symptoms)
  • Mastocytosis and urticaria pigmentosa
  • Oestrogen, progesterone and pregnancy related dermatoses

And if everything else excluded, that leaves Chronic idiopathic urticaria.

Urticaria Activity Score available – wheals and itch over course of day, score 0-3. Moderate wheals are 20-50. Do for 7 sequential days and add up to give UAS7 score.

Diagnosis

Basophil histamine release assay and autologous serum skin tests suggested, 25% of all chronic urticaria patients are positive for one and/or other, but  50% are negative for both – so struggling for a diagnostic standard.

Essential:

  • FBC, CRP, ESR – CRP raised and eosinophils low in type IIb (mast cell-directed autoantibodies)
  • Total IgE – reduced in type IIb
  • Anti TPO antibody – high in type IIb (high ratio to total IgE)

After that, as indicated, eg:

  • ASOT
  • Immunoglobulin electrophoresis done in adults to look for paraprotein
  • H pylori – some have suggested eradication helps but BSACI come down against routine screening
  • TFTs, Functional autoantibodies eg Thyroid, ANA
  • Pseudoallergen (additives, flavourings, colourings) free diet for 3 weeks? BSACI not v keen
  • Tryptase – systemic mastocytosis? Not in BSACI guideline!
  • TTG – some case reports of association with coeliac disease
  • C3/4 – if suspected urticarial vasculitis, and if reduced, measurement of anti-C1q antibodies [BSACI urticaria guideline]. C4 low in HAE.
  • Cryoglobulins for cold induced
  • Biopsy – but for mastocytosis, bone marrow aspirate most sensitive!
  • Specific tests: ice cube, flannel, dermatographism, hot bath, exercise. 

Incidence of underlying cause varies regionally. And some of these things may simply be aggravating underlying spontaneous urticaria, rather than a cause as such!

Assess for co-morbidity – mental health, autoimmune disease, allergy.

Treatment

Identify triggers – drugs (esp NSAIDs), foods (high histamine, pseudoallergens?), stress, infection.

For acute, non-sedating antihistamines (H1 blockers), else steroids. Evidence for H2 blockers eg ranitidine very weak.

For chronic, continuous non-sedating AH effective in <50% of patients. No evidence that one antihistamine is better than any other. Guidelines recommend up to 4x updosing (studies support for cetirizine, fexofenadine, otherwise desloratadine, levocetirizine, rupatadine!). 

No evidence that using different H1 blockers at the same time has any advantage (moderate consensus only, however…)

Weak evidence for steroids! Suggests maximum 10 days. Similarly montelukast.

Omalizumab is second line for both spontaneous and inducible – monthly SC injections 300mg (not dependent on IgE, as is asthma dosing) every 4 weeks (safety data now from age 1). Increase dose or shorten interval if necessary (up to 600mg every 2 weeks). After that, ciclosporin.

Other treatments with limited evidence include doxepin, ranitidine, methotrexate, dapsone etc. 

Tranexamic acid for angioedema?

No evidence for thyroxine treatment if autoantibodies, if euthyroid.

Plasmapheresis and IVIG have been used…

Tolerance to triggers can be induced (rapidly in some cases, eg within days), but not usually v pleasant, and temporary only…

Note the high rate of anxiety, depression, somatising disorders (50%).

[EAACI/GA2LEN 2021]