Chronic Urticaria Linked to Autoinflammatory Syndromes
Chronic urticaria (CU) may be an early clinical manifestation of systemic autoinflammatory syndromes (AS), according to a new narrative review published in Current Opinion in Allergy and Clinical Immunology. The authors highlight growing evidence that innate immune dysregulation—particularly interleukin (IL)-1–mediated inflammation—plays a central role in a subset of patients with treatment-refractory CU, with important diagnostic and therapeutic implications for clinicians.
Study Findings
The review synthesizes recent literature examining the overlap between chronic urticaria and autoinflammatory syndromes, including both monogenic and multifactorial disorders. Conditions most frequently associated with CU include cryopyrin-associated periodic syndromes (CAPS), Schnitzler syndrome, and Still’s disease.
Across these disorders, dysregulation of the innate immune system—rather than classical IgE-mediated mechanisms—appears to drive disease. The review emphasizes the pathogenic role of proinflammatory cytokines, particularly IL-1β, in sustaining systemic inflammation and cutaneous symptoms. Histopathologically, neutrophilic urticarial dermatosis (NUD) has emerged as a key marker distinguishing autoinflammatory-associated urticaria from conventional CU.
The authors note that CU in this context is often refractory to antihistamines and other standard therapies. Diagnostic delays remain common due to the nonspecific nature of early symptoms and overlap with chronic spontaneous urticaria. However, accumulating data suggest that early identification is critical, as targeted biologic therapies—especially IL-1 inhibitors—have shown marked efficacy in controlling both cutaneous and systemic manifestations and in preventing disease progression.
Clinical Implications
For allergists, dermatologists, and immunologists, the review underscores the importance of reconsidering the differential diagnosis in patients with chronic urticaria that is resistant to guideline-directed therapy. The presence of systemic features such as fever, arthralgia, bone pain, or elevated inflammatory markers should heighten suspicion for an underlying autoinflammatory syndrome.
The authors advocate for a structured diagnostic approach that integrates clinical assessment with laboratory evaluation of inflammatory markers, skin biopsy when indicated, and genetic testing in selected cases. Recognizing CU as part of a broader autoinflammatory phenotype enables earlier initiation of precision therapies, including IL-1 blockade, which may substantially improve outcomes and reduce long-term morbidity.
From a patient-care perspective, this paradigm shift moves CU management beyond symptomatic control toward disease-modifying treatment in appropriately selected individuals.
Expert Commentary
“CU refractory to conventional treatment, particularly when associated with systemic symptoms, should prompt suspicion of an underlying autoinflammatory syndrome,” the authors wrote. They further emphasized that “recognition of the autoinflammatory nature of CU allows for timely initiation of personalized therapies, improving patient prognosis and reducing long-term morbidity.”
For healthcare professionals, heightened awareness and early evaluation may enable targeted treatment, improved disease control, and better long-term outcomes for a challenging subset of patients.
Reference:
Yacoub MR, Ferlito A, Nettis E. Chronic urticaria and autoinflammatory syndromes. Curr Opin Allergy Clin Immunol. 2025;25(5):411-417. doi:10.1097/ACI.0000000000001093
