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) and chronic (>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 (<3% lifetime prevalence[12]) and important life-threatening complication that must be ruled out in all cases of urticaria. It is classically characterised by the presence of end-organ involvement, such as cardiovascular (hypotension, tachycardia, giddiness, syncope), respiratory (dyspnoea, hoarseness, stridor, wheezing, chest tightness), gastrointestinal (nausea, vomiting, abdominal pain, diarrhoea) or nervous system (confusion, giddiness/light-headedness) manifestations.[13] Step 2: Rule out urticarial mimics Urticarial mimics can broadly be classified into urticarial vasculitis (UV), cutaneous diseases with urticarial-like lesions and systemic urticarial syndromes [Table 2 and Figure S1b-e, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A329].Table 2: Distinguishing clinical features between common urticaria, urticarial vasculitis, cutaneous urticarial mimics and systemic urticarial syndromes.Urticarial vasculitis Most patients characteristically present with persistent and often painful urticarial plaques lasting more than 24–36 h, which leave behind postinflammatory hyperpigmentation [Figure S1b, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A329].[2,14] A small proportion of patients, especially those with hypocomplementaemic disease, have systemic manifestations and potentially life-threatening end-organ involvement, in what is known as hypocomplementaemic UV syndrome (or McDuffie syndrome).[2] Cutaneous diseases with urticarial-like lesions Common examples of cutaneous diseases with urticarial-like lesions may include urticarial dermatitis [Figure S1c, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A329], cutaneous mastocytosis (urticarial pigmentosa), early phase of autoimmune blistering diseases (e.g. bullous pemphigoid) [Figure S1d, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A329] and pruritic urticarial papules and plaques of pregnancy (PUPPP). Such cutaneous urticarial mimics should be considered if the following are present: atypical ‘wheals’, persistent lesions lasting >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 <15 years of age) and PUPPP in pregnant females, typically in the third trimester.[11] Systemic urticarial syndromes Systemic urticarial syndromes refer to urticarial cutaneous manifestations associated with connective tissue disorders (e.g. systemic lupus erythematosus, Sjogren’s syndrome, mixed connective tissue disorder), haematological conditions (e.g. hypereosinophilic syndromes, Gleich syndrome, monoclonal gammopathies, lymphoma) and rare autoinflammatory syndromes (e.g. Schnitzler syndrome, cryopyrin-associated periodic syndrome, familial cold autoinflammatory syndrome 2).[14] Therefore, it is important to screen patients for systemic extracutaneous symptoms/signs such as autoimmune (e.g. alopecia, eye pain/redness, oral ulcers, sicca symptoms, joint pain/swelling, photosensitivity rash, Raynaud’s phenomenon) or end-organ (cardiovascular, respiratory, gastrointestinal, renal, neurological) manifestations, constitutional symptoms (fever, appetite/weight loss, fatigue) and presence of relevant risk factors (e.g. personal or family history of autoimmune or haematological disorders).[14] Step 3: Determine underlying aetiology/subtype of urticaria This is determined based on chronicity of symptoms and presence of triggers/inducible factors. Firstly, determine if the patient has acute (<6 weeks) or chronic (>6 weeks) urticaria depending on the symptom duration. For acute urticaria, assess for identifiable triggers [Table 3], of which parainfectious (e.g. upper respiratory tract and gastrointestinal infections) and drug (e.g. antibiotics, aspirin, NSAIDs, opioids) or contrast use (e.g. iodinated radiocontrast media) are the most common.[15]Table 3: Common triggers of acute and chronic inducible urticaria.In cases of chronic urticaria, distinguish between chronic inducible urticaria (CInU) and chronic spontaneous urticaria (CSU) by excluding the presence of inducible factors that trigger urticarial flares. In brief, triggers in CInU may be classified into physical (symptomatic dermographism, exercise induced, heat or cold, delayed pressure, solar, vibration) and non-physical (cholinergic, contact and aquagenic) factors [Table 3].[16,17] From studies, the most common inducible trigger is symptomatic dermographism [Figure S1e, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A329],[17] which can be easily assessed by applying a light stroking pressure on the skin surface over the volar forearm or upper back using a blunt object such as a closed ballpoint pen (although the use of a calibrated dermographometer is the ideal, clinically validated method, which is usually only available in specialist centres[18]). The second most common trigger is cholinergic urticaria,[17] which occurs whenever there is increase in core body temperature with sweating, and therefore can present across a wide range of activities such as exercise, taking hot baths, during fever spikes, consuming spicy or hot foods and during emotional stress. Of note, there is a series of specialised confirmatory tests (i.e. provocation or challenge tests) that can definitively diagnose CInU,[18] but they are not widely available (especially in non-specialist centres) and are logistically cumbersome—therefore, diagnosis is usually made based on the presence of characteristic descriptions on history-taking. However, patients with CSU have no identified inducible factors. Such cases can either be idiopathic (50%) or autoimmune-mediated (50%).[6] Definitive diagnosis of chronic autoimmune urticaria can only be made through specialised tests such as autologous serum skin test, basophil histamine release test or direct immunoassays for IgG autoantibodies.[19,20] As these tests may not be widely available or cost effective to implement even at tertiary centres, most of these patients are classified generically as having CSU and trialled on standard symptomatic treatments first. For patients with chronic urticaria, physicians may consider ordering laboratory tests, such as full blood count and inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), to look for evidence suggestive of inflammatory states. In addition, given the association of CSU with autoimmune conditions, especially Hashimoto’s thyroiditis,[20] it would be prudent to screen for clinical features of hypothyroidism (e.g. cold intolerance, weight gain, poor appetite, lethargy, mental slowness), examine for thyroid goitre, and consider ordering thyroid function tests and anti-thyroid peroxidase (anti-TPO) antibodies. Management of acute and chronic urticaria Management of most acute and chronic forms of urticaria involves medical therapies [Table 4] and avoidance of identified triggers. First-line medical treatment for both is oral H1 antihistamines, with a preference for second-generation options, as they are equally efficacious, have longer lasting effects and are less sedating compared to first-generation drugs. While first-generation antihistamines tend to be prescribed as a night dosing to aid sleep quality by harnessing their sedative effects, we do not recommend their routine usage due to the significant risks of protracted sedation, falls and even precipitating delirium when prescribed in older adults. Instead, second-generation antihistamines can be given in split dosing (e.g. fexofenadine 180 mg BD), such that the night dose improves sleep quality simply by alleviating pruritus. Antihistamines should be taken regularly until active urticaria resolves and prophylactically before unavoidable activities known to trigger urticaria. Typically, an increase in dose of up to four-fold is shown to be safe[21] and may be recommended as the second-line treatment, failing which third-line options should be considered [refer to Table 4]. For severe urticarial flares (e.g. generalised disease, highly bothersome symptoms), it is reasonable to prescribe a short course of oral steroids (e.g. prednisolone 20–40 mg OD) for 3–7 days, up to a maximum of 10 days.[19,22]Table 4: Medical treatment for urticaria in primary care setting.Specifically for CSU, a treatment ladder approach[23] may be adopted [Figure S2, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A329] based on patient-reported symptomatic control, as assessed by the validated four-item urticaria control test (<12 points: uncontrolled, 12–15 points: well controlled, 16 points: completely controlled)[24] [Table S1, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A329]. In brief, a second-generation antihistamine is the first-line treatment, which can be uptitrated to four-fold if needed for symptom control, failing which a dermatologist referral would typically be warranted to consider subsequent lines of treatment involving monoclonal antibodies (omalizumab) and/or immunosuppressive therapy (cyclosporin).[23] Other treatment options such as adjunctive use of a H2 histamine receptor antagonist (e.g. famotidine, ranitidine, cimetidine) or leukotriene receptor antagonist (montelukast) may be trialled in shared decision-making with the patient, given that these medications are reported to contribute to some degree of symptomatic relief in certain patients and carry minimal harm, although the overall clinical evidence remains weak.[4,23] Importantly, patients should be screened and treated for comorbidities such as autoimmune thyroid conditions, as well as psychological sequelae (e.g. depressed mood, poor sleep) and/or functional loss attributed to urticarial symptoms.[23] Lastly, patients should be educated on the natural history and prognosis of CSU, i.e. most patients (>80%) show clinical response to first-line antihistamine treatment, with one-third to one-half of patients having disease remission within 1 year.[25] However, recurrences are common among those on remission, with about one-third of patients experiencing disease recurrence, usually around the 2-year mark.[25] Fluctuations in severity and intermittent flares may be expected, with reported triggers including emotional or physical stress, infections,[26] and rarely, vaccinations.[27] WHEN SHOULD I REFER TO A SPECIALIST? Acute urticaria with life-threatening complications such as anaphylaxis must be directed to the emergency department after acute resuscitation/stabilisation and administration of relevant medications, such as intramuscular epinephrine and intravenous antihistamine. If the trigger is unknown or the patient desires to perform confirmatory testing for specific allergens, the patient may be referred to an allergist or dermatologist for formal allergy testing such as skin prick test or oral food challenge tests.[6,19] For chronic urticaria, referral to a dermatologist should be considered in the following circumstances: (a) failure of symptomatic treatment (e.g. high-dose H1 antihistamines, with or without addition of H2 receptor blockers, montelukast), which may warrant consideration of immunomodulatory therapies (e.g. omalizumab or cyclosporine);[4] (b) patient factors (e.g. severe/bothersome symptoms, comorbid autoimmune conditions, occupation-related triggers); and (c)presence of atypical ‘wheal’ features or extracutaneous organ involvement (suggestive of urticarial mimics or systemic urticarial syndromes), which may warrant a skin punch biopsy to look for features of vasculitis.[6] In suspected UV, a skin biopsy from a ‘new’ lesion should be performed by a dermatologist within 12 h of its appearance to maximise diagnostic yield in demonstrating the characteristic histopathological features of small-vessel leukocytoclastic vasculitis.[6] TAKE HOME MESSAGES Urticaria is a common condition seen in primary care settings, with an estimated lifetime prevalence of 20% in the general population. The clinical approach to urticaria involves excluding mimics/systemic syndromes, ruling out life-threatening anaphylaxis and determining the underlying aetiology/subtype based on symptom chronicity and presence of triggers/inducible factors. Symptomatic dermatographism is the most common type of CInU, which can easily be tested by firmly stroking the skin over the volar forearm with a blunt object. Poorly controlled chronic urticaria can significantly affect patients’ quality of life, including psychological sequelae and/or functional impairment. H1 antihistamines are the mainstay of treatment for both acute and chronic urticarias; doses can be uptitrated as necessary or tolerated to up to three to four times of standard doses for symptom control. Closing Vignette Through clinical history-taking and physical examination, Ms Tan had no features of inducible urticaria, and symptomatic dermographism was absent. She had no atypical ‘wheals’ features or extracutaneous symptoms/signs that may suggest urticarial mimics or systemic disease. She also had no autoimmune or hypothyroid symptoms, and her thyroid function test was normal. She was diagnosed with chronic spontaneous (idiopathic) urticaria based on symptom duration and started on regular antihistamines (fexofenadine 180 mg BD), with good clinical response. At follow-up over the year, she was able to reduce the dose to once daily with complete suppression of urticaria, although symptoms recurred when antihistamines were stopped.Financial support and sponsorship Nil. Conflicts of interest Goh LH is a member of the SMJ Editorial Board and was thus not involved in the peer review and publication decisions of this article. SMC CATEGORY 3B CME PROGRAMME Online Quiz: https://www.sma.org.sg/cme-programme Deadline for submission: 6 pm, 26 June 2026