CME Dermatology Urticaria, angio-oedema and anaphylaxis The simplest working classification is to separate urticarias into four categories (Table 2): Urticarial lesions (ie areas of superficial Clive EH Grattan MA MD FRCP, Consultant ordinary Dermatologist, Norfolk and Norwich swelling) are also seen in skin diseases physical University Hospital, Norwich other than urticaria (eg some drug reac- tions, bullous pemphigoid). In these vasculitic urticaria (urticarial Clin Med JRCPL 2002;2:20–23 conditions, the lesions do not show the vasculitis) rapid fluctuation which characterises contact urticaria. urticaria. They will not be considered Angio-oedema may be a feature of Urticaria, angio-oedema and anaphy- further in this article. most patterns of urticaria and, for the laxis are distinct clinical entities caused Angio-oedema implies deeper vascular most part, can be considered together by transient plasma leakage from small leakage producing swellings predomi- with urticaria. However, it is worth con- blood vessels. When the affected vessels nantly affecting the subcutis. They tend sidering angio-oedema separately when are superficial the result is a raised, itchy to be large, pale and painful rather than it occurs without weals (Table 3) because swelling of the skin known as a weal. red and itchy, and last longer than weals. it may then be a presentation of Involvement of deeper vessels produces Angio-oedema is a cause of distressing C1esterase inhibitor (C1 inh) deficiency tender subcutaneous and submucosal oropharyngeal swellings but may occur or a drug reaction. swellings known as angio-oedema. anywhere on the integument including Generalised plasma exudation leading to the genitalia. shock is a feature of anaphylaxis but also Ordinary urticaria Anaphylaxis is defined by a life-threat- occurs in anaphylactoid reactions and ening fall in blood pressure, difficulty Ordinary urticaria is a useful collective the capillary leak syndrome. with breathing or both. Other features, term for all recurring urticarias that do including widespread redness, itching not fall into the other three categories, in Definitions and urticaria may occur (Table 1). True that they: anaphylaxis is due to an allergic reaction Urticaria is an eruption of transient do not have a predominantly involving allergen-specific immuno- superficial itchy weals, pale or pink in physical trigger globulin (Ig) E. Anaphylactoid reactions colour which may have a surrounding are not caused by underlying present similarly but do not involve IgE. flare of redness. They may be few in vasculitis number or numerous and widespread. are not caused by direct contact Their size varies from a few millimetres Classification of urticaria and with the causative agent. to many centimetres. The hallmark angio-oedema This heterogeneous group includes: of urticaria is its rapid fluctuation. the newly recognised ‘autoimmune’ It is helpful to divide urticaria into dif- Individual lesions come and go within urticaria 24 hours, but the eruption of fresh weals ferent clinical categories for the purpose urticaria due to dietary means that the whole attack may last of management. Many acute cases are pseudoallergens, drugs and much longer. short-lived or episodic but recurrent urticaria that continues at least twice a infections week for over six weeks is defined as the remaining ‘idiopathic’ cases for chronic. which no cause can be identified. Key Points Anaphylaxis is due to immunoglobulin Table 1. Features of anaphylaxis. E-mediated allergy System Clinical features Allergy is an uncommon cause of urticaria and angio-oedema Cardiovascular* Hypotension (loss of consciousness, collapse) Respiratory* Laryngeal oedema (inspiratory stridor) The diagnosis of urticaria is based Bronchial spasm (expiratory wheeze) primarily on the history of weals Skin Pruritus, erythema, urticaria with rapid fluctuation Nose Rhinitis Antihistamines are the first-line drug Eye Conjunctivitis therapy for all urticarias except C1 Gut Abdominal pain esterase inhibitor deficiency General ‘Impending doom’ KEY WORDS: CPD, urticaria, angio- * One or both of these severe features must be present; other features are variable. oedema, anaphylaxis 20 Clinical Medicine Vol 2No 1 January/February 2002 CME Dermatology The common clinical feature of ordi- laxis. Cholinergic urticaria (due to a rise (eg allergy to natural rubber latex) or nary urticaria is that individual weals last in core temperature) is mainly truncal. non-allergic. Certain chemicals in foods less than 24 hours before disappearing Delayed pressure urticaria predominates and cosmetics can cause localised completely without residual colour or wherever there is sustained pressure urticaria without involving specific IgE. texture change in the skin. The general (egunder belts or straps). Affected individuals often make their health of the patient remains good but own diagnosis and learn what to avoid systemic symptoms such as lethargy, Vasculitic urticaria because symptoms develop almost malaise and indigestion are quite immediately after exposure. common during severe attacks. In vasculitic urticaria there are urticaria- like lesions caused by underlying leuko- Aetiology and pathogenesis Physical urticaria cytoclastic vasculitis. Subtle features which distinguish them from ordinary The release of histamine and other medi- Physical urticaria is defined by the nature urticaria are pain, individual lesion ators from mast cells provokes vascular of the physical stimulus that repro- duration longer than 24 hours and leakage responsible for the tissue swelling ducibly gives rise to urticaria. Weals typ- bruise-like discolouration or petechiae of urticaria and angio-oedema and the ically fade within 30–60 minutes. The during resolution. This condition is catastrophic vascular exudation of ana- exception is delayed pressure urticaria usually idiopathic, but may be associated phylaxis. Mast cell activation may be when the weals take several hours to with systemic lupus erythematosus. allergic or non-allergic. The patho- appear after sustained pressure and can genetic mechanisms responsible are last up to 48 hours. The morphology and Contact urticaria shown in Table 4. There is poor correla- distribution of the weals can also be tion between patho-mechanism and helpful in identifying the trigger. Cold- Contact urticaria occurs at the site of clinical type. For instance, IgE-mediated induced urticaria, for instance, occurs on skin or mucosal contact with an agent allergy can present with localised contact exposed skin or on immersion in cold that provokes increased vascular perme- urticaria, generalised urticarial weals or water and may rarely progress to anaphy- ability. The cause can be either allergic anaphylaxis depending on the type of exposure and the degree of hypersensi- tivity. No cause can be identified in 50% of acute urticaria. In the others, the com- Table 2. Clinical classification of urticaria, causes and triggers. monest preceding event is an upper res- Clinical group of Aggravating and trigger piratory infection or a reaction (not nec- urticaria Causes factors essarily an allergy) to a drug or food 1. Ordinary usually unknown ? aspirin Chronic urticaria is rarely, if ever, allergic respiratory and other infections? dietary intolerance in the sense of a defined environmental autoimmune ? heat allergen being the cause, but ‘pseudoal- drugs ? stress lergic’ reactions to dietary additives and dietary intolerance ? alcohol natural salicylates may be important in Physical: some cases2. Up to 50% of cases pre- dermographismunknown skin stroking senting with ordinary urticaria may be cold urticaria skin cooling cholinergic rise in core temperature due to the recently recognised ‘autoim- delayed pressure sustained firm pressure mune’ urticaria 3. Underlying systemic (others) disease (unless suspected on the patient’s Contact allergens (eg latex) direct contact history) almost never emerges as the chemicals (eg in toiletries) cause of ordinary urticaria even when Vasculitic usually unknown long-standing. Urticarial vasculitis results from immune complexes lodging in small Table 3. Classification of angio-oedema. blood vessels (type III hypersensitivity), generating C3a and C5a anaphylatoxins With weals Angio-oedema may occur in all forms of urticaria except which are potent mast cell degranulators. dermographism The angio-oedema of C1 inh deficiency Without weals idiopathic is due to production of kinin-like peptides drugs (ACEIs, NSAIDs) from C2. They cause vasopermeability C1 inh deficiency (hereditary and acquired) without mast cell degranulation. Anaphylactic reactions are always ACEI = angiotensin-converting enzyme inhibitor; C1 inh = C1 esterase inhibitor; NSAID = non-steroidal anti-inflammatory drug. caused by type I IgE-mediated immediate hypersensitivity reactions. Clinical Medicine Vol 2No 1 January/February 2002 21 CME Dermatology Diagnosis Table 4. Aetiology and pathogenesis of urticaria and angio-oedema. The diagnosis of urticaria remains pri- Unknown (idiopathic) marily clinical. A recent study showed Immunological Autoimmune (autoantibodies to high affinity IgE receptor that extensive routine investigations or to IgE) added little to a comprehensive history IgE-dependent (type I allergy) Immune complex (type III allergy) in the diagnosis of chronic urticaria 4. Complement-dependent (C1 inh deficiency) Investigations should be guided by the Non-immunological Direct mast cell releasing agents (eg opiates) clinical presentation