978140514663_4_008.qxd 12/10/07 3:19 PM Page 104 8 Reactive erythemas and vasculitis Blood vessels can be affected by a variety of insults, than of individual wheals. Urticaria that persists both exogenous and endogenous. When this occurs, for more than 6 weeks is classified as chronic. Most the epidermis remains unaffected, but the skin patients with chronic urticaria, other than those becomes red or pink and often oedematous. This is a with an obvious physical cause, have what is often reactive erythema. If the blood vessels are damaged known as ‘ordinary urticaria’. more severely – as in vasculitis – purpura or larger areas of haemorrhage mask the erythematous colour. Cause Urticaria (hives, ‘nettle-rash’) The signs and symptoms of urticaria are caused by mast cell degranulation, with release of histamine Urticaria is a common reaction pattern in which (Fig. 8.1). The mechanisms underlying this may pink, itchy or ‘burning’ swellings (wheals) can occur be different but the end result, increased capillary anywhere on the body. Individual wheals do not permeability leading to transient leakage of fluid last longer than 24 h, but new ones may continue into the surrounding tissue and development of a to appear for days, months or even years. Tradition- wheal, is the same (Fig. 8.1). For example, up to half ally, urticaria is divided into acute and chronic of those patients with chronic urticaria have circu- forms, based on the duration of the disease rather lating antibodies directed against the high affinity Spontaneous (chronic Type I urticaria) hypersensitivity (Fig 2.14) Mast cell Granules Chemicals (aspirin, etc.) Release of chemicals Autoimmune (30% of chronic Histamine urticaria) Heparin 5-hydroxytryptamine Increased capillary Proteases permeability Inflammatory mediators • Prostaglandins • Leukotrienes • Eosinophil and neutrophil (chemotactic factors) Fig. 8.1 Ways in which a mast cell can be degranulated and the ensuing reaction. 104 Clinical Dermatology, Fourth Edition By Richard P.J.B. Weller, John A.A. Hunter, John A. Savin and Mark V. Dahl © 2008 Richard Weller, John Hunter, John Savin, Mark Dahl. ISBN: 978-1-405-14663-0 978140514663_4_008.qxd 12/10/07 3:19 PM Page 105 Reactive erythemas and vasculitis 105 Table 8.1 The main types of urticaria. Heat urticaria Physical In this condition wheals arise in areas after contact cold solar with hot objects or solutions. heat cholinergic dermographism (immediate pressure urticaria) Cholinergic urticaria delayed pressure Anxiety, heat, sexual excitement or strenuous exer- Hypersensitivity Autoimmune cise elicits this characteristic response. The vessels Pharmacological over-react to acetylcholine liberated from sympa- Contact thetic nerves in the skin. Transient 2–5 mm follicular macules or papules resemble a blush or viral ex- anthem (Fig. 8.2). Some patients develop blotchy immunoglobulin E (IgE) receptor on mast cells patches on their necks. whereas the reaction in others in this group may be caused by immediate IgE-mediated hypersensitivity Aquagenic urticaria (see Fig. 2.14), direct degranulation by a chemical or trauma, or complement activation. This resembles cholinergic urticaria and is precipitated by contact with water, irrespective of its temperature. Classification Dermographism (Fig. 8.3) The various types of urticaria are listed in Table 8.1. They can often be identified by a careful history; This is the most common type of physical urticaria, laboratory tests are less useful. The duration of the the skin mast cells releasing extra histamine after wheals is an important pointer. Contact and physical rubbing or scratching. The linear wheals are there- urticarias, with the exception of delayed pressure fore an exaggerated triple response of Lewis. They urticaria, start shortly after the stimulus and go can readily be reproduced by rubbing the skin of the within an hour. Individual wheals of other forms back lightly at different pressures, or by scratching resolve within 24 h. the back with a fingernail or blunt object. Physical urticarias Delayed pressure urticaria Sustained pressure causes oedema of the under- Cold urticaria lying skin and subcutaneous tissue 3–6 h later. The 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. Solar urticaria Wheals occur within minutes of sun exposure. Some patients with solar urticaria have erythropoietic protoporphyria (p. 328); most have an IgE-mediated Fig. 8.2 Typical small transient wheals of cholinergic urticarial reaction to sunlight. urticaria – in this case triggered by exercise. 978140514663_4_008.qxd 12/10/07 3:19 PM Page 106 106 Chapter 8 FcIgE receptors on mast cells. Here the autoantibody acts as antigen to trigger mast cell degranulation. Pharmacological urticaria 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). Contact urticaria Fig. 8.3 Dermographism: a frenzy of scratching by an already dermographic individual led to this dramatic This may be IgE mediated or caused by a pharmaco- appearance. logical effect. The allergen is delivered to the mast cell from the skin surface rather than from the blood. swelling may last up to 48 h and kinins or prosta- Wheals occur most often around the mouth. Foods glandins, rather than histamine, probably mediate and food additives are the most common culprits it. It occurs particularly on the feet after walking, on but drugs, animal saliva, caterpillars, insect repellents the hands after clapping and on the buttocks after and plants may cause the reaction. Recently, latex sitting. It can be disabling for manual labourers. allergy has become a significant public health concern. Other types of urticaria Latex allergy Possible reactions to the natural rubber latex of the Hypersensitivity urticaria Hevea brasiliensis tree include irritant dermatitis, This common form of urticaria is caused by hyper- contact allergic dermatitis (Chapter 7) and type I sensitivity, often an IgE-mediated (type I) allergic allergy (Chapter 2). Reactions associated with the reaction (Chapter 2). Allergens may be encountered latter include hypersensitivity urticaria (both by in 10 different ways (the 10 I’s listed in Table 8.2). contact and by inhalation), hay fever, asthma, ana- phylaxis and, rarely, death. Table 8.2 The 10 I’s of antigen encounter in Medical latex gloves became universally popular hypersensitive urticaria. after precautions were introduced to protect against HIV and hepatitis B infections. The demand for the Ingestion gloves increased and this led to alterations in their Inhalation manufacture and to a flood of high allergen gloves Instillation Injection on the market. Cornstarch powder in these gloves Insertion bound to the latex proteins so that the allergen Insect bites became airborne when the gloves were put on. Infestations Individuals at increased risk of latex allergy include Infection health care workers, those undergoing multiple Infusion Inunction (contact) 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. Autoimmune urticaria Latex reactions should be treated on their own Some patients with chronic urticaria have an auto- merits (for urticaria see p. 109; for anaphylaxis see immune disease with IgG antibodies to IgE or to Fig. 25.5; for dermatitis see Chapter 7). Prevention 978140514663_4_008.qxd 12/10/07 3:19 PM Page 107 Reactive erythemas and vasculitis 107 of latex allergy is equally important. Non-latex (e.g. vinyl) gloves should be worn by those not handling 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. Presentation Most types of urticaria share the sudden appearance of pink itchy wheals, which can come up anywhere 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 Fig. 8.6 Angioedema of the upper lip. resolve centrally to take up an annular shape. In an acute anaphylactic reaction, wheals may cover most urticarial wheal. Angioedema most commonly occurs of the skin surface. In contrast, in chronic urticaria at junctions between skin and mucous membranes only a few wheals may develop each day. (e.g. peri-orbital, peri-oral and genital; Fig. 8.6). It Angioedema is a variant of urticaria that prim- may be associated with swelling of the tongue and arily affects the subcutaneous tissues, so that the laryngeal mucosa. It sometimes accompanies chronic swelling is less demarcated and less red than an urticaria and its causes may be the same. Course 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 Fig. 8.4 A classic wheal. alone do better, half being clear after 6 months. Complications Urticaria is normally uncomplicated, although its itch may be enough to interfere with sleep or daily activities and to lead to depression. In acute anaphy- lactic reactions, oedema of the larynx may lead to asphyxiation, and oedema of the tracheo-bronchial tree to asthma. Differential diagnosis There are two aspects to the differential diagnosis Fig.