Acute urticaria management: Gaps, challenges and the need for further evidence

Abstract

The recent systematic review published in JEADV by Badloe et al¹ provides a comprehensive analysis of the management for acute urticaria (AU) with corticosteroids, highlighting the persistent uncertainties surrounding the use of systemic corticosteroids in conjunction with antihistamines. This article offers valuable insights into the current practices and evidence-based approaches, yet it underscores significant gaps that necessitate further research.

Despite limited robust evidence supporting their efficacy, corticosteroids are conventionally and widely used in the treatment of AU. The contrasting findings from the studies included in this review reflect the clinical conundrum faced by healthcare providers: while corticosteroids are commonly employed to manage AU, their benefits in conjunction with antihistamines remain unsubstantiated in many cases. For instance, out of four RCTs which assessed the efficacy of corticosteroids in addition to antihistamines for the management of AU, two studies revealed that a combination of corticosteroids and antihistamines did not have a beneficial effect on the resolution of AU, while the other two found a positive effect.¹ The effect of corticosteroids in the management of urticaria has been recently evaluated in a systematic review by Chu et al² which provided moderate certainty of evidence that systemic corticosteroids likely improve urticaria activity in patients who do not respond well to antihistamines alone; however, systemic corticosteroids likely increase the risk of adverse effects such as GI discomfort and neuropsychiatric changes, with an odds ratio (OR) of 2.76. As a result, it is concluded that the addition of corticosteroids to an antihistamine as a treatment option for AU and to assess long-term outcomes of corticosteroid treatment needs to be further investigated.

The article also highlights a critical issue: the reliance on older treatment modalities, such as first-generation antihistamines, which are still prevalent in many emergency departments. The sedative properties and other adverse effects of these drugs, particularly diphenhydramine, raise concerns about their continued use when less sedative and rapid acting options like cetirizine are available. The finding that intravenous cetirizine is as effective as diphenhydramine, with fewer side effects, suggests a potential shift in treatment protocols that could enhance patient outcomes and safety.

The review also brings to light the current gaps of knowledge in AU such as the potential for AU to progress to chronic spontaneous urticaria (CSU) and whether corticosteroids might influence this progression. Previous reports show that average duration of AU is ≤1 week and the rates of progression of AU to CSU are between 5% and 39%.³ Two previous studies tried to identify the factors that are linked to the progression of AU to CSU: positive autologous serum skin test, thyroid autoimmunity and basopenia⁴ and non-steroidal anti-inflammatory drug hypersensitivity and food allergy⁵ were predictive factors for CSU progression in AU patients. Nevertheless, comprehensive future research involving large sample sizes and diverse patient populations is essential to thoroughly address these questions.

The International Guideline for Urticaria suggests the use of a short course of oral corticosteroids to a maximum of up to 10 days for AU and acute exacerbations of CSU. However, the guideline lacks specific guidance on the management of AU, highlighting the need for more detailed recommendations to be developed for this condition such as when, how and for how long systemic corticosteroids should be used, specifying indications, dosage, administration, monitoring and alternative treatments to ensure safe and effective management.

In conclusion, the need for well-designed, large-scale RCTs for AU management is evident. Future research should aim to develop standardized treatment protocols to provide guidance for the physicians and investigate the long-term outcomes of AU management, including its potential progression to CSU. Only through such efforts can we achieve a more evidence-based approach to treating AU.

Emek Kocatürk: Speaker and advisor for Novartis, Menarini, LaRoche Posey, Sanofi, Bayer, Abdi İbrahim and Pfizer. Marcus Maurer: Marcus Maurer is a speaker and/or advisor for and/or has received research funding from Allakos, Alexion, Almirall, Alvotech, Amgen, Aquestive, Arcensus, argenX, AstraZeneca, Astria, BioCryst, Blueprint, Celldex, Celltrion, Clinuvel, Cogent, CSL Behring, Escient, Evommune, Excellergy, Genentech, GSK, Incyte, Jasper, Kashiv, Kalvista, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Mitsubishi Tanabe Pharma, Moxie, Noucor, Novartis, Orion Biotechnology, Pharvaris, Resonance Medicine, Sanofi/Regeneron, Santa Ana Bio, Septerna, Servier, Takeda, Teva, Third HarmonicBio, Valenza Bio, Vitalli Bio, Yuhan Corporation and Zurabio.