Chronic Spontaneous Urticaria: Diagnosis and Treatment Strategies

In a recent Dermatology Times® Partner Perspectives video series on chronic spontaneous urticaria (CSU), Jonathan Rodrigues, MD, Novartis Medical Director of Dermatology and Allergy and former practicing board-certified allergist, reviewed the burden associated with CSU, best practices and challenges with diagnosis and management, and the importance of addressing quality of life and engaging the patient in shared decision-making. This article summarizes his discussion.

Dr Rodrigues discussed the characteristics of CSU, which are wheals (or hives) and/or angioedema present for more than 6 weeks.^1-3 Although 33% to 67% of patients have an overlap of wheals and angioedema, Dr Rodrigues noted that 29% to 65% of patients can present with wheals alone, and 1% to 13% of patients can present with angioedema alone.⁴

The wheals of CSU are sharply circumscribed superficial central swellings that may be accompanied by itching or burning, or both, and can be surrounded by reflex erythema. Individual hives can last between 30 minutes and 24 hours.^1-3 “It is important to note [duration of the hives],” said Dr Rodrigues, “because if an individual hive lasts for more than 24 hours, we should consider the diagnosis of urticarial vasculitis.”¹ The angioedema of CSU involves repeated deep dermal, subcutaneous, or submucosal swelling. It can be accompanied by numbness, burning, tingling, or even pain.^1-3 Angioedema can affect any part of the body but commonly affects the lips, eyes, cheeks, or extremities.² Angioedema can take up to 72 hours to resolve.¹

CSU usually presents in patients between 30 and 50 years of age. Women are affected twice as often as men. “We see in [the] literature that CSU lasts about 5 years,” said Dr Rodrigues. However, “CSU can last longer than 5 years, especially in more severe cases.”^2,5 If CSU recurs following 6 months of remission, it is considered recurrent.⁶ Approximately 50% of CSU patients can have ongoing symptoms despite the use of standard doses of antihistamine.^4,7

The pathogenesis of CSU involves several possible mechanisms, although the exact mechanism is unknown. For example, it may include type I and type IIb autoimmune responses with immunoglobulin (Ig)E and IgG convergence on the surface of mast cells and basophils at the high-affinity IgE receptor Fc epsilon receptor 1 (FcεRI).⁸ Bruton’s tyrosine kinase (BTK), which is a member of the TEC family of kinases,⁹ is a key mediator in the signaling pathway that leads to mast cell degranulation and histamine release, driving CSU pathophysiology and causing symptoms such as itch, hives, and swelling.^8,10,11

Diagnosis of CSU

Accurately diagnosing CSU involves a thorough history and physical examination. In addition to assessing the presence of wheals or hives and angioedema, providers should also review family history and all patient symptoms to rule out other possible conditions. “There is a CSU diagnostic algorithm,” shared Dr Rodrigues. “This tool allows physicians to explore the multiple pathways that can lead to a diagnosis of CSU and also exclude other differential diagnoses.”¹ Patients with atypical findings may need to receive testing beyond basic labs tests, and patients with hives lasting for more than 24 hours and suspected urticarial vasculitis should receive a skin biopsy.^1,12

Delayed diagnosis is common among patients with CSU, who experience an average delay of 24 months from symptom onset to established diagnosis.⁵ This is due to various reasons, shared Dr Rodrigues. When CSU is refractory to treatment, patients are more likely to self-medicate with over-the-counter medications, see a primary care provider rather than a specialist, and experience a delay in referral to a CSU-treating specialist.^5,13 “We have seen that about 48.7% of patients with CSU see a general practitioner, 29.6% see an allergist, and around 19.2% see a dermatologist,” said Dr Rodrigues.¹⁴ In addition, patients with undiagnosed CSU frequently receive unnecessary allergy or laboratory testing. “Only 0.16% of tests actually contribute to an improvement in clinical outcomes,” said Dr Rodrigues.¹⁵ Overall, insufficient knowledge of CSU among health care providers in both primary and secondary care can contribute to diagnostic delays.⁵

Identifying disease severity and impact

CSU can considerably affect patient quality of life. In a study comparing patients with and without CSU, patients with CSU reported an increased prevalence of depression, anxiety, and sleep difficulties. “As a matter of fact, the prevalence of depression was as high as 48%,” said Dr Rodrigues. Findings also showed a negative impact on sexual function and work productivity in patients with CSU.¹⁶ Similarly, results from another study comparing patients with CSU to those with psoriasis showed that patients with CSU had an increased prevalence of anxiety, depression, and sleep difficulties.¹⁷

Approximately 20% of patients with CSU also experience chronic inducible urticaria, which is the most common comorbidity in antihistamine-resistant CSU.¹⁸ Patients with CSU plus chronic inducible urticaria typically experience the greatest impact on quality of life; this impact is measured by the Dermatology Life Quality Index (DLQI). Results from studies show CSU plus chronic inducible urticaria is associated with a DLQI score of 9.1 compared with 8.3 in patients with CSU alone and 7.6 in patients with chronic inducible urticaria alone.¹⁹

Dr Rodrigues noted that CSU also affects work attendance and productivity. In a study of 604 patients with CSU, of which 56.5% were employed, participants reported absenteeism as high as 6.1%, presenteeism of 25.2%, and overall work impairment of 26.9% over the previous 7 days.⁵

To understand the potential effects of CSU on quality of life, it is important for clinicians to understand severity of disease, which can be identified with the weekly Urticaria Activity Score (UAS7). “The UAS7 is a patient-reported outcome that is commonly used in clinical trials and is evaluated by both patients and physicians,” shared Dr Rodrigues. It is the sum of the daily itch severity score and the daily hive severity score over the course of 7 days.^20,21 “The UAS7 overall enables health care providers to assess and monitor the severity of CSU,” said Dr Rodrigues. “[It] can also help guide them in maintaining, escalating, or modifying therapy in patients with CSU.”²⁰

Challenges with disease management

There are several management challenges in patients with CSU, according to Dr Rodrigues. Initially, the delay in accurate diagnosis can contribute to CSU affecting comorbidities or masking certain diseases.^5,22 Following diagnosis, assessing disease severity and predicting treatment response can be a challenge due to the paucity of reliable biomarkers to assess disease severity and predict treatment response.²² Achieving an adequate response to treatment can also be difficult.²³

The international guidelines for diagnosing and managing CSU recommend second-generation H1 antihistamines as first-line therapy in patients with CSU1; however, approximately 50% to 60% of patients do not respond to standard doses of second-generation antihistamines.^23,24 Patients who do not respond to antihistamine therapy often report significantly decreased quality of life.²⁵ Dr Rodrigues noted that if the disease remains uncontrolled after antihistamine dose escalation, the treatment regimen could be modified. A short course of systemic corticosteroids could be used in rescue cases of acute exacerbations of CSU; however, it is not recommended to use systemic corticosteroids as long-term therapy due to adverse effects.¹

Patient communication and shared decision-making

It is important to identify a treatment strategy that can successfully alleviate the physical, psychological, and functional impairments in patients’ lives. Patient communication and shared decision-making play an important role in these efforts. Providers can meet with their patients to review symptoms, comorbidities, disease severity, potential side effects of treatment, and ultimately patient preferences. Patients should also understand the value of disease monitoring with patient-reported outcome tools such as UAS7. These conversations with patients can help guide treatment decisions, escalations, and modifications, and help support positive outcomes.^1,7,16

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