Comorbidities in Chronic Spontaneous Urticaria: Integrating Disease Drivers and Systemic Consequences
- 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Republic of Korea
- 2Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam 13496, Republic of Korea
- 3Department of Allergy and Clinical Immunology, Ajou University School of Medicine, 164 WorldCup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea
Abstract
Chronic spontaneous urticaria (CSU) is a mast cell-driven inflammatory skin disorder traditionally considered self-limiting and non-life-threatening. However, accumulating evidence suggests that CSU is associated with multiple comorbidities, reflecting systemic immune and neuroinflammatory dysregulation. These comorbidities may act as both triggers and consequences of disease activity, forming a complex network centered on mast cell activation. Autoimmune diseases, particularly autoimmune thyroid disease, are strongly associated with CSU, especially in the type IIb autoimmune endotype. By contrast, type I autoallergic CSU is associated with immunoglobulin E (IgE) autoantibodies. Atopic diseases, neuroimmune interactions, and psychiatric conditions may further contribute to disease persistence through mechanisms involving IgE signaling and substance P-mediated mast cell activation via Mas-related G protein-coupled receptor X2. Metabolic and cardiovascular comorbidities have also been reported, with recent large-scale cohort studies strengthening the evidence for an association with cardiovascular risk, although causality remains unestablished. Associations with malignancy remain uncertain, whereas recent real-world studies suggest increased mortality among patients with CSU, potentially reflecting the underlying comorbidity burden rather than direct disease effects. Importantly, effective disease control may improve CSU outcomes and associated comorbidities. A comprehensive, mechanism-based approach that integrates comorbidity assessment into clinical management is essential for optimizing patient care.
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BibTeX
@article{kim2026comorbidities,
title = {{Comorbidities in Chronic Spontaneous Urticaria: Integrating Disease Drivers and Systemic Consequences}},
author = {Joo-Hee Kim and Mi-Ae Kim and Young-Min Ye},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219615},
url = {https://www.mdpi.com/1422-0067/27/21/9615},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comorbidities in Chronic Spontaneous Urticaria: Integrating Disease Drivers and Systemic Consequences
AU - Joo-Hee Kim
AU - Mi-Ae Kim
AU - Young-Min Ye
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219615
UR - https://www.mdpi.com/1422-0067/27/21/9615
AB - Chronic spontaneous urticaria (CSU) is a mast cell-driven inflammatory skin disorder traditionally considered self-limiting and non-life-threatening. However, accumulating evidence suggests that CSU is associated with multiple comorbidities, reflecting systemic immune and neuroinflammatory dysregulation. These comorbidities may act as both triggers and consequences of disease activity, forming a complex network centered on mast cell activation. Autoimmune diseases, particularly autoimmune thyroid disease, are strongly associated with CSU, especially in the type IIb autoimmune endotype. By contrast, type I autoallergic CSU is associated with immunoglobulin E (IgE) autoantibodies. Atopic diseases, neuroimmune interactions, and psychiatric conditions may further contribute to disease persistence through mechanisms involving IgE signaling and substance P-mediated mast cell activation via Mas-related G protein-coupled receptor X2. Metabolic and cardiovascular comorbidities have also been reported, with recent large-scale cohort studies strengthening the evidence for an association with cardiovascular risk, although causality remains unestablished. Associations with malignancy remain uncertain, whereas recent real-world studies suggest increased mortality among patients with CSU, potentially reflecting the underlying comorbidity burden rather than direct disease effects. Importantly, effective disease control may improve CSU outcomes and associated comorbidities. A comprehensive, mechanism-based approach that integrates comorbidity assessment into clinical management is essential for optimizing patient care.
SN - 1422-0067
ER -