The term ‘urticaria’ implies intermittent transient swelling of the skin with a loss of fluid from vessels into the extravascular space. Dermal swelling is associated with yyweals, whilst subcutaneous fluid collection is associated with brawny lesions often around the lips and orbit (angio-oedema) or the genitalia. The skin appears completely normal afterwards (within minutes or hours). The passage of fluid out of the vessel may accompany the dilatation caused by mediators such as histamine released from neighbouring mast cells or by other vasoactive
compound such as kinins or prostaglandins. More severe vessel damage, e.g. the vasculitis associated with diseases such as SLE or allergic vasculitis, may produce weals in association with purpura and necrosis. On occasions, rather ordinary-looking weals may be accompanied by quite mark~d vessel damage and an inflammatory cell infiltrate seen on histological examination. Biopsies should therefore be obtained:
• When weals last longer than 2 days
• When weals are accompanied by purpuric staining
• When antibiotics and circulating immune complexes are present in the sera
• When attacks are accompanied by systemic features such as fever or arthralgia
An aetiological classification of urticaria is given in Table 20.2.
Foods, e.g. nuts and shellfish, may be implicated. Other trigger factors include salicylates, indomethacin, tartrazine dyes in food substances or benzoates used as preservatives. Such substances may exacerbate the disease when it is in the active phase in up to 40% of patients. Crossreactivity between substances, e.g. tartrazine and salicylates, is seen but a search for a food ‘allergen’ is often unrewarding. A direct pharmacological effect on vessel reactivity is probable, and both aspirin and indomethacin are known to affect prostaglandin metabolism. Agents that can liberate histamine directly include morphine and codeine .
Type I hypersensitivity is more commonly seen with acute disease, or in atopic individuals, and may be triggered by, for example, penicillin in milk. Even when no obvious trigger factor is found there is a tendency towards resolution of the attacks over weeks or months in themajority of patients. In the recalcitrant case an exclusion diet may be used as a last resort, but this is often unhelpful.
Immunological mechanisms IgE mediated:
Physical, e.g. cold, dermographism Antigen sensitivity, e.g. pollens, foods, drugs, helminths Complement mediated:
Blood transfusion reactions
Mast cell-releasing agents:
Radiological contrast media
Non-steroidal anti-inflammatory drugs
Weals that irritate are seen on the trunk or limbs and usually last for several hours, or up to 12-24 hours (Fig. 20.5). There may be accompanying angio-oedema and this feature may predominate in some patients with swelling of eyes or lips; swelling of the genitalia is less common. Chronic urticaria is arbitrarily defined as diseaseasting for more than 6 weeks. Physical urticarias
These may be produced by pressure, sweating, touch, heat, cold, UV light or water for example. These patternsof urticaria are less common and are most likely to be misdiagnosed. This is particularly true of conditions that are not easily reproduced in the clinic, e.g. pressure urticaria.
CHOLINERGIC URTICARIA. This is not an uncommon pattern of disease and is seen in young adults. The weals are usually small, are often associated with erythema, and last 5-20 min. Attacks are triggered by exercise, hot baths, showers or emotional upset. Such factors may also cause itching but no obvious weals (especially in Blacks) andinduce stress and panic reactions. Large quantities of histamine may be liberated during attacks and cause difficulty with breathing. Patients should be advised to avoid histamine liberators such as codeine or aspirin. If attacks can be anticipated, predosing with hydroxyzine, cyproheptadine or a non-sedative antihistamine such as terfenadine during the day may abort a reaction.
DERMOGRAPHISM (FACTITIOUS URTICARIA). This reaction represents an exaggeration of the third component of Lewis’s triple response. A livid weal is produced in response to scratching in about 5% of the population; it is usually asymptomatic. Symptomatic disease occurs when symptoms of itching or discomfort occur after trauma to the skin. Patients may experience marked erythema and wealing when, for example, towelling dry after a bath. Complaints of generalized pruritus with, on occasions, nothing to see may prompt doctors to label the patient as neurotic.
COLD URTICARIA. This may be triggered by wind over the surface of the skin, e.g. when cycling, or by cold objects in contact with the skin, e.g. talcing articles from a freezer. The weals may be reproduced in many patients by the application of an ice cube to the flexor aspect of the forearm. Anaphylaxis may accompany submersion of the body in cold water and patients need to be warned against bathing unaccompanied.
SOLAR URTICARIA. uv light-induced weals may be seen on sites that are not normally exposed such as the upper arm, especially during the early summer; the weals appear within minutes of sun exposure. The action spectra is ariable between patients and it may need to be assessed
in order to provide adequate sunscreens.
AQUAGENIC URTICARIA. Contact of the skin with water may induce itching with or without weals. Symptoms may be reproduced by touching the skin with wet gauze. This condition is often a presenting feature of olycythaemia vera.
Patients should avoid any trigger factor. They may also need:
A SEDATIVE HI antihistamine is given at night, such as long-acting chlorpheniramine maleate 8-12 mg, or brompheniramine (long-acting) 12-24 mg, or hydroxyzine hydrochloride 10-50 mg. NON-SEDATIVE HI antihistamines such as terfenadine 60 mg twice daily or astemizole 10 mg daily, cetirizine 10 mg are useful for daytime use.
HYDROXYZINE HYDROCHLORIDE OR CYPROHEPTADINE YDROCHLORIDE have a wider spectrum of action than routine HI receptor-blocking agents. Angiooedema will often respond better with these agents. COMBINATION TREATMENT using an HI-receptor antagonist with an H2-receptor antagonist such as cimetidine or ranitidine may stop attacks when other treatments fail.
Acute urticaria accompanied by anaphylaxis (see p. 147), for example from bee stings, snake bites or, less frequently, from food ingestion or drugs, will require the immediate use of adrenaline. Intravenous hydrocortisone or antihistamines may be given to limit the swelling hen
the crisis is over, for their effect is not seen for up to 20 min.
This condition is inherited in an autosomal dominant manner and many patients can give an account of crises occurring in relatives.
The disease is associated with C1 esterase inhibitor deficiency (see p. 144), which may be qualitative or quantitative. This protein modulates the intravascular activation of complement and its deficiency leads to angiooedema. Clinical features may not appear until adult life. A non-hereditary, acquired form of the disease occurs in association with lymphoproliferative disorders.
Severe airways obstruction that is unresponsive to antihistamines may lead to death, and visceral oedema may produce attacks of abdominal pain. Attacks may be preceded by a prodromal rash evident as mild erythema or erythema marginatum. Trauma to the skin, e.g. knocking an arm on a doorpost, may trigger an attack, for C1 esterase inhibitor activity is involved in the fibrinolytic cascade as well as in complement pathways. The disease must be differentiated from non-hereditary angio-oedema. Swellings may last for up to 72 hours and are painful rather than irritant. Purpuric staining may occur, but pitting oedema is not seen.
An analysis of complement levels will demonstrate a low level of C1 esterase inhibitor or its deficient functional activity on laboratory testing; C2 and C4 levels are also reduced. The disease can be differentiated from that associated with lymphoma, where C1 levels are also low and there is no family history.
Inhibitors of plasmin such as a-aminocaproic acid or stanozolol (2.5-5 mg daily) and danazol (100-200 mg daily) (attenuated androgens) may be used for long-term treatment. Long-term usage in females may cause menstrual irregularity, fluid retention and androgenicity. Acute attacks may also require the use of fresh frozen plasma; a purified form of the inhibitor is also nowavailable. In severe cases adrenaline and hydrocortisone are required.