Hives (urticaria)

• See also articles Anaphylaxis and Hypersensitivity to drugs .

Essentials

• Acute urticaria is often associated with an infection.
• The majority of chronic cases are due to autoimmune urticaria or idiopathic urticaria.
• Unnecessary laboratory tests should be avoided as well as associating urticaria with allergies or food intolerance.
• Effective symptomatic treatment.

Epidemiology

• Urticaria is a common condition. The lifetime incidence of urticaria in the general population is about 20%.

Diagnosis

• A typical feature of urticaria is rapidly developing, raised and pruritic wheals (pictures ) with or without surrounding erythema.
• Wheals may cover large skin areas, and their size varies from 1 mm to larger confluent wheals.
• Pruritus is usually most severe when the wheals are developing, but signs of scratching are rare.
• The wheals rise and disappear whilst migrating from place to place. Any single wheal will characteristically not persist on the same spot for longer than 24 hours.
• No vesicle formation, scaling or ulceration is noted.
• About half of patients will also have angioedema (picture ), either as an independent symptom or associated with urticaria.
• The diagnosis is not likely to be urticaria if a single lesion persists in the same location for more than 24 hours or leaves a mark upon healing, e.g. pigmentation, slight bruising or purpura.

Differential diagnosis

• Atopic dermatitis
• Scabies
• Exanthematous eruptions caused by drugs or infections
• Erythema multiforme
• Pityriasis rosea
• Guttate psoriasis
• Papular urticaria (strophulus) is a hypersensitivity reaction to insect bites, especially by mosquitoes or fleas, usually encountered in children .
• Urticarial vasculitis

Acute urticaria (duration < 6 weeks)

• Usually associated with infections (e.g. viral upper respiratory tract infection)
• The causal relationship between urticaria and infection is rarely confirmed.
• Drugs used during the infection are often considered culprits even though only rarely is a drug reaction the cause of urticaria.
• Moreover, acute urticaria may be the first sign of anaphylaxis.
  • Subsequent deterioration of general condition, hypotension and bronchial obstruction
• If the patient remains otherwise well, no laboratory investigations are usually indicated.
• Additional investigations should aim to identify the infection that may have triggered urticaria and are based on presenting symptoms (basic blood count with platelets, CRP, streptococcal throat culture, ultrasonography of the sinuses, chest x-ray etc.). Investigations are carried out only if the results influence treatment.

Contact urticaria

• Wheals may develop in sensitised patients on skin areas that have been in direct contact with a particular allergen (immediate allergy; animal saliva, natural rubber etc.).
• The causal relationship is often obvious, and sensitisation may be demonstrated with investigations that test immediate allergy (skin prick tests and serum specific IgE antibodies ).

Recurrent acute urticaria

• A comprehensive and detailed history is important in cases of recurrent acute urticaria.
• Is urticaria provoked by medicines, for example NSAIDs, certain foods, physical irritants or exertion?
• The combined effect of several factors is often needed to trigger urticaria, e.g. feverish cold and alcohol or certain foods (e.g. wheat) and exertion.

Chronic urticaria (duration > 6 weeks)

• Chronic urticaria usually turns out to be either autoimmune urticaria or idiopathic urticaria.
• Extensive investigations rarely prove helpful.
• The diagnosis is based on the patient's history and clinical presentation.
• Each patient should undergo a test for dermographism (picture ; see also ).

Investigations

• Exclusion of an infection
  • Full blood count, CRP, ESR
  • Eosinophilia, for example in intestinal parasitic infections
• Additional investigations as indicated (exclusion of a chronic infection focus)
  • Urinalysis, bacterial throat culture, serum IgE levels, serum viral antibodies, stool culture (including Salmonella, Shigella, Yersinia, Campylobacter, Aeromonas and Plesiomonas) and stool parasites (if recent travel), ALT, alkaline phosphatase, serum Helicobacter antibody test or stool Helicobacter antigen test (if abdominal symptoms), ultrasonography or x-rays of the sinuses, chest x-ray

Autoimmune urticaria

• Autoimmune urticaria is the most common type of chronic urticaria.
• Mild symptoms are usually present daily with occasional periods of exacerbation.
• Exacerbations may be triggered by infections or NSAIDs.
• Autoimmune urticaria may react poorly to antihistamines.
• In some cases, antibody assays may be positive (histamine release test).
• Patients frequently have other concurrent autoimmune diseases (e.g. autoimmune thyroiditis ); the exclusion tests for these conditions include serum TSH, anti-thyroid peroxidase antibodies and antinuclear antibodies.

Physical urticarias

• The cornerstone of diagnosis is the patient’s history. Challenge testing is rarely needed.
• The most important management measure is the avoidance of triggering factors.
• Dermographism (picture )
  • Triggered occasionally by an infection. Urticaria persists even after the infection has resolved and will usually last for a few years.
  • Test: scratch the skin on the back with a blunt instrument (e.g. a spatula) and wait for 5 minutes. The test is positive if raised wheals develop at the scratched skin areas.
• Pressure urticaria
  • Mechanical pressure will induce a swelling that occurs either immediately or with a delay of about 24 hours (more common) at the pressure site.
• Cholinergic urticaria
  • Particularly in young adults; highly pruritic wheals of 1–2 mm in diameter occur on the chest and torso after physical or emotional stress. The symptoms do not last long.
• Cold urticaria
  • As cold skin warms up, redness and swelling develop on certain areas of the skin.
  • The phenomenon usually lasts for some years. Symptoms may also be triggered by touching a cold object.
• Solar urticaria
  • A rare form of photosensitivity dermatitis, often refractory to treatment and characterised by local swelling only minutes after exposure to natural or artificial light.

Angioedema

• Often occurs concurrently with urticaria.
• In about 10% of patients with chronic urticaria, the only manifestation is recurrent angioedema without urticarial wheals.
• Swelling often involves the lips or eyelids and lasts for 1–3 days.
• The patient reports a burning sensation and pain, rather than itching.
• Treatment response to antihistamines is generally poor.
• A common cause is medication with ACE inhibitors or angiotensin receptor blockers. Even when these drugs are used on a regular basis, symptoms occur only occasionally. Symptoms are caused by aetiology other than an allergic mechanism.
• Moreover, drug hypersensitivity (e.g. NSAIDs) may cause angioedema. In this case, symptoms emerge whenever the drug is taken.
• If a patient presents with episodes of angioedema alone, the differential diagnosis should include anaphylaxis and hereditary angioedema (HAE) .

Treatment

• The mainstay of treatment for all urticarias is a non-sedating H₁ antihistamine.
  • Normal doses are used initially for the duration of urticaria, for several weeks if necessary.
  • If the symptoms do not improve, the dose may be increased two- to four-fold (e.g. cetirizine 10 mg 1–2 tablets morning and night). Note: special requirements concerning the prescription may apply if the dosage differs from the officially confirmed.
  • The response to antihistamines in symptom relief often varies from patient to patient, and antihistamines from different groups should be tried (cetirizine/levocetirizine, loratadine/desloratadine, ebastine, fexofenadine, acrivastine, bilastine).
• If the symptoms are particularly severe, a systemic glucocorticoid may be prescribed, for example prednisolone 40 mg once daily by mouth for 3 days. Some patients may need sick leave.
• Should a four-fold increase in the dose of an antihistamine prove to be insufficient in chronic urticaria, primarily montelukast 10 mg at night may be added as symptomatic therapy.
• The second alternative is to add ranitidine 150 mg twice daily to the H₁ antihistamine medication .
• There is no strong evidence on the efficacy of these treatments, but they are safe and may provide additional help to some patients.
• In severe chronic spontaneous urticaria that is refractory to conventional treatment, immunosuppressive agents (e.g. ciclosporin A) or monoclonal anti-IgE antibody omalizumab may be used under supervision of a specialist.
• Antihistamines are usually of no benefit in angioedema.
  • If the swelling is severe and distressing, an adult patient may be prescribed prednisolone 30–60 mg once daily for 1–3 days.
  • Respiratory tract obstruction requires emergency medical care and monitoring.

Specialist consultation

• Recurrent urticaria may warrant additional investigations carried out under the supervision of a dermatologist.
• Chronic urticaria resistant to prolonged and appropriate treatment may warrant other treatment modalities, e.g. UVB phototherapy or immunosuppressive medication.

Related resources

• Other Internet resources
• Literature

Ədəbiyyat

1. Maurer M, Church MK, Gonçalo M et al. Management and treatment of chronic urticaria (CU). J Eur Acad Dermatol Venereol 2015;29 Suppl 3():16-32.
2. Zuberbier T, Aberer W, Asero R et al. The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy 2014;69(7):868-87.
3. Sharma M, Bennett C, Carter B et al. H1-antihistamines for chronic spontaneous urticaria: an abridged Cochrane Systematic Review. J Am Acad Dermatol 2015;73(4):710-716.e4.
4. de Silva NL, Damayanthi H, Rajapakse AC et al. Leukotriene receptor antagonists for chronic urticaria: a systematic review. Allergy Asthma Clin Immunol 2014;10(1):24.
5. Mitchell S, Balp MM, Samuel M et al. Systematic review of treatments for chronic spontaneous urticaria with inadequate response to licensed first-line treatments. Int J Dermatol 2015;54(9):1088-104.
6. Urgert MC, van den Elzen MT, Knulst AC et al. Omalizumab in patients with chronic spontaneous urticaria: a systematic review and GRADE assessment. Br J Dermatol 2015;173(2):404-15.