1. Chronic urticaria is characterised by the appearance of weals and sometimes angioedema, lasting for longer than 6 weeks
The majority of patients have a combination of urticarial weals and angioedema, a third show only weals and an even smaller subset only gets angioedema. Weals are short-lived superficial skin swellings of varying size that are typically associated with itching or burning sensation. There is usually an associated erythematous flare reaction. In chronic urticaria, individual weals tend to last for less than a day and should not leave any bruising behind. Where weals last for longer than 24 hours and are associated with bruising, urticarial vasculitis (an autoimmune condition) needs to be considered. Angioedema is pronounced deeper swelling of the lower skin layers and often occurs around the eyes, the lips and the tongue.. Most cases of acute urticaria resolve spontaneously within days or weeks and only around 10% of patients develop chronic urticaria, for instance in the presence of autoantibodies (affecting around 30% of chronic urticaria patients).
An urticarial rash
2. Chronic urticaria symptoms are caused by mast cell degranulation
Mast cells are preferentially localised around sensory nerves and small blood vessels. Their main role is to act as first-line defence against pathogen invasion across the epidermis. Often the cause of chronic urticaria is unknown, but established triggers of chronic mast cell activation and histamine release are:
• infection (viral, bacterial, yeast and parasitic)
• physical triggers (pressure, exercise and heat)
• pseudoallergens (preservatives in foods, salicylates, non-IgE mediated process)
• autoantibodies (anti-IgE or anti-IgE receptor antibodies)
3. The most important part of the consultation is the history
It is important to ask about the following regarding potential triggers:
• Did the patient have signs of an infection just before or when the urticaria started?
• Are there any obvious triggers or exacerbating factors (foods, drugs, alcohol, physical triggers or emotional stress)? If yes, these should be avoided.
4. Many patients with chronic urticaria feel tired
However, severe systemic symptoms, such as abdominal pains, joint pains, weight loss or headaches would be unusual. In such cases, patients should be thoroughly examined to exclude underlying pathology, looking in particular for lymphadenopathy and organomegaly. Systemic diseases that are associated with chronic urticarial rashes include urticarial vasculitis, Schnitzler’s syndrome (this is a rare, IgM gammopathy) and auto-inflammatory syndromes.
5. No further investigations are required if symptoms are mild and easily suppressed with single dose antihistamines
But where foods are suspected to trigger the urticaria, allergy testing should be performed – either specific IgE testing or skin prick testing. If there are associated systemic symptoms, screening blood tests to exclude underlying pathology are also recommended.
In such cases, it would be important to measure the following:
• full blood count
• inflammatory markers (CRP/ESR)
•thyroid function and thyroid autoantibodies
• anti-nuclear antibodies (ANA)
• C3/4 levels to rule out hereditary angioedema (C1 esterase inhibitor deficiency) in cases with isolated angioedema, especially if they exhibit systemic symptoms
A food diary can additionally help to identify diet-related triggers.
6. Removing the underlying cause is preferable to suppression of symptoms with antihistamines
Relevant infections, such as parasitic disease, are rare but need to be considered. In the majority of cases no cause is found and antihistamines are the mainstay of therapy to suppress symptoms, until the chronic urticaria has spontaneously subsided.
7. If single dose antihistamines do not control the urticaria, increase to a maximum of four times the standard dose
Increasing to four times the dose often provides benefit and is a safe, albeit off-licence, practice. An alternative would be to combine two non-sedating H1 antihistamines, both up to twice the standard dose. There is also some evidence to suggest that adding in montelukast (10mg nocte) can provide further benefit in some patients, while the evidence to support combined H1 and H2 antihistamine treatment is weak (Fig. 1).
Licensed antihistamine doses are based on hay fever studies. However, we know from clinical experience and clinical trials that chronic urticaria often needs higher than standard doses of H1 antihistamines. Non-sedating antihistamines, such as cetirizine, loratadine or fexofenadine are preferred over sedating ones, partly to avoid interference with daily activities.
Fig.1: management of urticaria. Source: Zuberbier et al. 2009
8. Even non-sedating antihistamines can cause drowsiness at high doses
Where patients complain of sleep disturbance, sedating antihistamines can be taken at night as a useful adjunct, although some patients complain of drowsiness in the morning. Also, even non-sedating antihistamines can at higher doses cause drowsiness in sensitive individuals.
9. Oral prednisolone - approx. 0.5mg/kg/day - can be used as rescue therapy for 3-7 days for breakthrough flares
Other systemic therapies, such as ciclosporin, methotrexate, dapsone, and omalizumab (a monoclonal IgE antibody), are reserved for specialist care (Fig. 1). Patients who experience severe angioedema, associated with throat tightness or even episodes of anaphylaxis, should be provided with an adrenaline autoinjector and receive counselling in its use.
10. Further assessment and management should be considered if patients’ chronic urticaria is not adequately controlled with higher than standard dose antihistamines
Where patients exhibit significant systemic symptoms, or the above screening investigations suggest underlying pathology, or where the diagnosis is uncertain, referral to a dermatologist for further assessment and management should be considered.
Dr Carsten Flohr is a senior lecturer and consultant in dermatology at St John’s Institute of Dermatology, Guy’s & St Thomas’ Hospitals NHS Foundation Trust. Dr Flohr has a special interest in cutaneous allergy, including urticaria and angioedema.
Leech S, Gratten C, Lloyd K, et al. The RCPCH care pathway for children with urticaria, angio-oedema or mastocytosis: an evidence and consensus based national approach. Arch Dis Child 2011;96(suppl 2):i34-7. http://www.rcpch.ac.uk/allergy/urticaria
Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA2LEN/EDF/WAO Guideline: management of urticaria. Allergy 2009;64:1427-43.