Urticaria (hives, ‘nettle-rash’)
Urticaria is a common reaction pattern in which pink, itchy or ‘burning’ swellings (wheals) can occur any-where on the body. Individual wheals do not last longer than 24 h, but new ones may continue to appear for days, months or even years.
Traditionally, urticaria is divided into acute and chronic forms, based on the duration of the disease rather than of individual wheals. Urticaria that persists for more than 6 weeks is clas-sified as chronic. Most patients with chronic urticaria, other than those with an obvious physical cause, have what is often known as ‘ordinary urticaria’.
The signs and symptoms of urticaria are caused by mast cell degranulation, with release of histamine (Fig. 8.1).
The mechanisms underlying this may be different but the end result, increased capillary per-meability leading to transient leakage of fluid into the surrounding tissue and development of a wheal, is the same (Fig. 8.1). For example, up to half of those patients with chronic urticaria have circulating anti-bodies directed against the high affinity immuno-globulin E (IgE) receptor on mast cells whereas the reaction in others in this group may be caused by immediate IgE-mediated hypersensitivity (see Fig. 2.14), direct degranulation by a chemical or trauma, or even spontaneous degranulation.
The various types of urticaria are listed in Table 8.1. They can often be identified by a careful history; laboratory tests are less useful. The duration of the wheals is an important pointer. Contact and physical urticarias, with the exception of delayed pressure urticaria, start shortly after the stimulus and go within an hour. Individual wheals of other forms resolve within 24 h.
Patients develop wheals in areas exposed to cold, e.g.
on the face when cycling or freezing in a cold wind.
A useful test in the clinic is to reproduce the reac-tion by holding an ice cube, in a thin plastic bag to avoid wetting, against forearm skin. A few cases are associated with the presence of cryoglobulins, cold agglutinins or cryofibrinogens.
Wheals occur within minutes of sun exposure. Some patients with solar urticaria have erythropoietic protoporphyria; most have an IgE-mediated urticarial reaction to sunlight.
In this condition wheals arise in areas after contact with hot objects or solutions.
Anxiety, heat, sexual excitement or strenuous exercise elicits this characteristic response. The vessels over-react to acetylcholine liberated from sympathetic nerves in the skin. Transient 2–5 mm follicular macules or papules (Fig. 8.2) resemble a blush or viral exanthem. Some patients get blotchy patches on their necks.
This is the most common type of physical urticaria, the skin mast cells releasing extra histamine after rub-bing or scratching. The linear wheals are therefore an exaggerated triple response of Lewis. They can readily be reproduced by rubbing the skin of the back lightly at different pressures, or by scratching the back with a fingernail or blunt object.
Sustained pressure causes oedema of the underlying skin and subcutaneous tissue 3– 6 h later.
The swelling may last up to 48 h and kinins or prostaglandins rather than histamine probably mediate it. It occurs particularly on the feet after walking, on the hands after clapping and on the buttocks after sitting. It can be disabling for manual labourers.
This common form of urticaria is caused by hyper-sensitivity, often an IgE-mediated (type I) allergic reaction . Allergens may be encountered in ten different ways (the 10 ‘I’s listed in Table 8.2).
Some patients with chronic urticaria have an auto-immune disease with IgG antibodies to IgE or to FcIgE receptors on mast cells. Here the autoantibody acts as antigen to trigger mast cell degranulation.
This occurs when drugs cause mast cells to release histamine in a non-allergic manner (e.g. aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors and morphine).
This may be IgE-mediated or caused by a pharmaco-logical effect. Wheals occur most often around the mouth. Foods and food additives are the most com-mon culprits but drugs, animal saliva, caterpillars and plants may cause the reaction. Recently, latex allergy has become a significant public health concern.
Possible reactions to the natural rubber latex of the Hevea brasiliensis tree include irritant dermatitis, con-tact allergic dermatitis and type I allergy . Reactions associated with the latter include hypersensitivity urticaria (both by contact and by inhalation), hay fever, asthma, anaphylaxis and, rarely, death.
Medical latex gloves became universally popular after precautions were introduced to protect against HIV and hepatitis B infections. The demand for the gloves increased and this led to alterations in their manu-facture and to a flood of high allergen gloves on the market. Cornstarch powder in these gloves bound to the latex proteins so that the allergen became airborne when the gloves were put on. Individuals at increased risk of latex allergy include health care workers, those undergoing multiple surgical procedures (e.g. spina bifida patients) and workers in mechanical, catering and electronic trades. Around 1– 6% of the general population is believed to be sensitized to latex.
Latex reactions should be treated on their own merits. Preven-tion of latex allergy is equally important. Non-latex (e.g. vinyl) gloves should be worn by those not han-dling infectious material (e.g. caterers) and, if latex gloves are chosen for those handling infectious material, then powder-free low allergen ones should be used.
Most types of urticaria share the sudden appear-ance of pink itchy wheals, which can come up any-where on the skin surface (Figs 8.4 and 8.5). Each lasts for less than a day, and most disappear within a few hours. Lesions may enlarge rapidly and some resolve centrally to take up an annular shape. In an acute anaphylactic reaction, wheals may cover most of the skin surface. In contrast, in chronic urticaria only a few wheals may develop each day.
Angioedema is a variant of urticaria that primarily affects the subcutaneous tissues, so that the swelling is less demarcated and less red than an urticarial wheal. Angioedema most commonly occurs at junctions between skin and mucous membranes (e.g. peri-orbital, peri-oral and genital; Fig. 8.6). It may be associated with swelling of the tongue and laryngeal mucosa. It sometimes accompanies chronic urticaria and its causes may be the same.
The course of an urticarial reaction depends on its cause. If the urticaria is allergic, it will continue until the allergen is removed, tolerated or metabolized. Most such patients clear up within a day or two, even if the allergen is not identified. Urticaria may recur if the allergen is met again. At the other end of the scale, only half of patients attending hospital clinics with chronic urticaria and angioedema will be clear 5 years later. Those with urticarial lesions alone do better, half being clear after 6 months.
Urticaria is normally uncomplicated, although its itch may be enough to interfere with sleep or daily activit-ies and to lead to depression. In acute anaphylactic reactions, oedema of the larynx may lead to asphyxi-ation, and oedema of the tracheo-bronchial tree may lead to asthma.
There are two aspects to the differential diagnosis of urticaria. The first is to tell urticaria from other eruptions that are not urticaria at all. The second is to define the type of urticaria, according to Table 8.1. Insect bites or stings (Fig. 8.7) and infestations com-monly elicit urticarial responses, but these may have a central punctum and individual lesions may last longer than 24 h. Erythema multiforme can mimic an annular urticaria. A form of vasculitis (urticarial vasculitis) may resemble urticaria, but indi-vidual lesions last for longer than 24 h and may leave bruising in their wake.
Some bullous diseases, such as dermatitis herpetiformis, bullous pemphigoid and pemphigoid gestationis, begin as urticarial papules or plaques, but later bullae make the diagnosis obvious. On the face, erysipelas can be distinguished from angioedema by its sharp margin, redder colour and accompanying pyrexia. Hereditary angioedema must be distinguished from the angioedema accompanying urticaria as their treatments are completely different.
Recurrent attacks of abdominal pain and vomiting, or massive oedema of soft tissues, which may involve the larynx, characterize this autosomal dominant con-dition. Urticaria does not accompany the tissue swel-lings. Tooth extraction, cheek biting and other forms of trauma may precipitate an attack. A deficiency of an inhibitor to C1 esterase allows complement con-sumption to go unchecked so that vasoactive mediators are generated. To confirm the diagnosis, serum C1 esterase inhibitor level and C4 level should both be checked as the level of C1 esterase inhibitor is not always depressed (there is a type where the inhibitor is present but does not work).
The investigations will depend upon the presentation and type of urticaria. Many of the physical urticarias can be reproduced by appropriate physical tests. It is important to remember that antihistamines should be stopped for at least 3 days before these are undertaken.
Almost invariably, more is learned from the history than from the laboratory. The history should include details of the events surrounding the onset of the erup-tion. A review of systems may uncover evidence of an underlying disease. Careful attention should be paid to drugs, remembering that self-prescribed ones can also cause urticaria. Over-the-counter medications (such as aspirin and herbal remedies) and medications given by other routes (Table 8.2) can produce wheals.
If a patient has acute urticaria and its cause is not obvious, investigations are often deferred until it has persisted for a few weeks; then a physical examination (if not already carried out) and screening tests such as a complete blood count, erythrocyte sedimentation rate (ESR), routine biochemical screen, chest X-ray and urine analysis are worthwhile. If the urticaria continues for 2–3 months, the patient should prob-ably be referred to a dermatologist for further evalu-ation. In general, the focus of such investigations will be on internal disorders associated with urticaria (Table 8.3) and on external allergens (Table 8.4). Even after extensive evaluation and environmental change, the cause cannot always be found.
In some patients with acute or contact urticaria, allergy testing in the form of radioallergosorbant tests (RAST) or prick tests , using only allergens suggested by the history, can sometimes be of help. Many patients with chronic urticaria are sure that their problems could be solved by intensive allergy tests, and ask repeatedly for them, but this is seldom worthwhile.
The ideal is to find a cause and then to eliminate it. In addition, aspirinain any formashould be banned. The treatment for each type of urticaria is outlined in Table 8.5. In general, antihistamines are the mainstays of symptomatic treatment. Cetirizine 10 mg/day and loratadine 10 mg/day, both with half-lives of around 12 h, are useful. If necessary, these can be supplemented with shorter acting antihistamines, e.g. hydroxyzine 10 –25 mg up to every 6 h (Formulary 2) and acrivastine, 8 mg three times daily.
Alternatively they can be combined with a longer acting antihistamine (such as chlorpheniramine maleate 12 mg sustained-release tablets every 12 h) so that peaks and troughs are blunted, and histamine activity is blocked throughout the night. If the eruption is not controlled, the dose of hydroxyzine can often be increased and still tolerated. H2-blocking antihistamines (e.g. cimetidine) may add a slight benefit if used in conjunction with an H1 histamine antagonist. Chlorpheniramine or diphen-hydramine are often used during pregnancy because of their long record of safety, but cetirizine, loratidine and mizolastine should be avoided. Sympathomimetic agents can help urticaria, although the effects of adrena-line (epinephrine) are short lived. Pseudoephedrine (30 or 60 mg every 4 h) or terbutaline (2.5 mg every 8 h) can sometimes be useful adjuncts.
A tapering course of systemic corticosteroids may be used, but only when the cause is known and there are no contraindications, and certainly not as a panacea to control chronic urticaria or urticaria of unknown cause. For the treatment of anaphylaxis.