Approach to urticaria in primary care

Opening Vignette Ms Tan is a 38-year-old Chinese woman with no past medical history. She presents to your clinic with concerns of recurrent itchy rashes (which she describes as ‘hives’) on her trunk and limbs that spontaneously appear and disappear over the past 3 months.WHAT IS URTICARIA? Urticaria, also known colloquially as ‘hives’ (风瘼 ‘Feng Mo’ in Mandarin), is a skin condition characterised by the development of characteristic wheals with or without concomitant angio-oedema.[1] Urticarial wheals are defined as elevated, well-circumscribed, erythematous, oedematous plaques with central pallor [Figure S1a, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A329]. These wheals tend to be intensely pruritic, with spontaneous resolution of individual lesions within 24 h without postinflammatory hyperpigmentation.[1,2] Its appearance is caused by dermal oedema and blood vessel dilatation.[2] In contrast, angio-oedema affects the deeper layers of the skin at the lower dermis and subcutis or mucous membranes (e.g. eyes, lips), presenting with a more diffuse swelling, skin discomfort and pain, and may take 72 h to resolve.[1] Around 30%–40% present with isolated hives, 10%–20% with isolated angio-oedema and the remainder with both hives and angio-oedema.[3] Urticaria can be classified based on duration of symptoms into acute (6 weeks). In both cases, urticaria may either be spontaneous/idiopathic or inducible where an inciting factor is identified.[1] HOW COMMON AND RELEVANT IS THIS TO MY PRACTICE? Urticaria is common, with an estimated lifetime prevalence of 20% in the general population.[4] Globally, in 2019, approximately 65 million individuals were reported to have urticaria, at a prevalence of 842 per 100,000 population and a disability-adjusted life year rate of 50 per 100,000 population.[5] As urticaria is typically self-limiting and benign,[4] patients usually present first to primary care for evaluation and management. Most patients with urticaria are adequately managed at the primary care level with appropriate symptomatic treatment and trigger avoidance, and would not require extensive diagnostic testing. Nonetheless, it is important to identify cases of urticarial mimics or systemic syndromes, as well as difficult-to-manage refractory urticaria that may warrant timely specialist referrals for further workup and consideration of systemic immunomodulatory treatment.[4] PATHOPHYSIOLOGY OF URTICARIA In acute urticaria, IgE-mediated (type 1) hypersensitivity reactions form the main mechanism in cases triggered by food and drug (e.g. antibiotics) allergens, allergenic contactants (e.g. latex products) or insect venoms. In brief, IgE-mediated allergic reactions require a prior sensitisation event to an allergen/antigen in a genetically predisposed individual, where a subsequent re-exposure leads to the allergen binding to antigen-specific IgE receptors on the surface of mast cells and basophils. Activation of these immune cells leads to degranulation and the release of chemical mediators such as histamine, which causes vasodilatation and increased vascular permeability manifesting as urticaria.[6] However, non-IgE-mediated pseudoallergic reactions may less commonly occur in the context of specific drug usage (e.g. opioids, nonsteroidal anti-inflammatory drugs [NSAIDs], traditional Chinese medicine injections), radiocontrast exposure[7] and infections.[8] Specifically, opioids and contrast media exposure typically lead to IgE-independent histamine release through direct mast cell/basophil activation or complement activation, whereas aspirin or NSAIDs cause cyclooxygenase-1 (COX-1) inhibition-mediated preferential activation of the leukotriene pathway with pseudoallergic manifestations.[7] Rarely, consumption of poorly canned fish or scombroid poisoning can lead to pseudoallergic response via direct histamine ingestion.[9] Ultimately, the location of chemical mediator (e.g. histamine) release determines the type of cutaneous manifestation, where release in the dermis leads to urticaria and release in the deeper dermis or subcutis leads to angio-oedema.[4] However, in chronic urticaria, autoimmune mechanisms (or non-IgE-mediated immune mechanisms) are often implicated in up to 50% of cases.[10] This comprises type 2 hypersensitivity reaction (formation of IgG autoantibodies against IgE or IgE receptors on mast cells), type 3 hypersensitivity reaction (presence of circulating immune complexes binding to mast cell-expressing Fc receptors for IgG and IgM) or type 4 hypersensitivity reaction (direct T-cell activation of mast cells or histamine release).[10] In the remaining cases, urticarial flares are mediated by non-immunological mechanisms such as physical factors that directly trigger mast cell activation, especially in individuals who are postulated to have a lower activation threshold of mast cells.[11] WHAT CAN I DO IN MY PRACTICE? A systematic approach is required for patients presenting with urticaria to make an accurate diagnosis and to determine subsequent management and suitable disposition of care [Figure 1]. Broadly, the aims of clinical history-taking [Table 1] and physical examination are as follows.Figure 1: A practical clinical approach to urticaria.Table 1: History-taking in patients with urticaria.Step 1: Rule out life-threatening anaphylaxis Anaphylaxis is a rare (24–36 h, unusually symmetric distribution, infiltrative plaques, secondary skin lesions (e.g. eczematous lesions, macules and papules, purpura, vesicles, scales, crusts, bullae, blisters), or resolution with residual scarring, hypopigmentation or hyperpigmentation.[11] Importantly, the patient characteristics and clinical evolution of disease may provide helpful clues. For example, autoimmune blistering diseases are more common in older persons (notably, neurological disorder is a known risk factor of bullous pemphigoid), whereas urticarial pigmentosa is classically seen in younger persons (majority