Beyond the Skin: Allergy-Guided Precision Care for Chronic Spontaneous Urticaria and Atopic Dermatitis
Authors: Sammer Marzouk, BS,1 Shyam Joshi, MD2
Key Points
- Chronic spontaneous urticaria (CSU) and atopic dermatitis (AD) are increasingly understood as systemic immune disorders, not isolated skin conditions, with extracutaneous manifestations that significantly impact morbidity.
- Allergy-guided care pathways and precise phenotyping enable more individualized therapy, especially in patients with overlapping allergic and immunologic comorbidities.
- Emerging biologics and JAK inhibitors targeting type 2 inflammatory pathways are reshaping treatment paradigms, requiring integration of allergy, immunology, and dermatology expertise.
How does this work highlight an innovative perspective in dermatology?
This work reframes dermatologic conditions such as CSU and AD within a systemic immunology framework, emphasizing that optimal management requires moving beyond surface-level symptom control. By integrating allergy and immunology expertise into dermatology practice, it demonstrates how targeted therapies and comorbidity screening can accelerate disease control and improve long-term outcomes. This cross-disciplinary perspective broadens therapeutic possibilities and challenges conventional silos in care delivery.
Chronic spontaneous urticaria (CSU) and atopic dermatitis (AD) are increasingly recognized as complex, immunologically active conditions that frequently extend beyond the skin.1 Characterized by persistent pruritus, inflammatory flares, and frequent treatment resistance, both conditions demand a systemic approach to diagnosis, phenotyping, and therapeutic selection.2 In modern clinical practice, allergy-guided frameworks offer a structured methodology for managing patients with overlapping inflammatory and allergic comorbidities, particularly when standard topical or antihistamine therapies fail.3
Management of CSU begins with guideline-directed use of second-generation antihistamines, escalated in dose as tolerated. However, a significant proportion of patients remain refractory, necessitating the transition to advanced therapies. Therapeutic escalation must be individualized, with particular attention to coexisting allergic conditions, such as food allergies or eosinophilic gastrointestinal disorders. For example, eosinophilic esophagitis in the context of AD or CSU suggests a broader type 2 inflammatory diathesis and may direct therapy toward cytokine-specific monoclonal antibodies.
Systemic manifestations in CSU are frequently underappreciated. Patients often experience symptoms such as arthralgia, wheezing, gastrointestinal distress, and cardiovascular changes in addition to classic urticarial eruptions. These extracutaneous features reflect underlying systemic immune dysregulation, which is particularly evident in patients with comorbid autoimmune or mast cell disorders.4 AD also demonstrates a strong association with atopic and immunologic comorbidities, including asthma, allergic rhinitis, eosinophilic GI diseases, contact dermatitis, and psychiatric conditions.5 Effective clinical management requires routine screening for these co-diagnoses, as they may significantly alter both disease burden and treatment response.
The expanding therapeutic landscape for CSU and AD includes several biologics and small molecule inhibitors that target key nodes of type 2 inflammation (Table 1).
Table 1. Summary of Targeted Immunologic Therapies for CSU and AD with FDA Approvals and Emerging Off-Label Efficacy
This table outlines selected biologic and small molecule therapies commonly used in the management of chronic spontaneous urticaria (CSU) and atopic dermatitis (AD). It includes FDA-approved indications as well as documented or emerging efficacy in related inflammatory conditions. The agents listed target key immunologic pathways involved in type 2 inflammation, including IgE signaling, IL-4/IL-13, and JAK-STAT pathways. Therapeutic selection should consider clinical phenotype, comorbid conditions, and individual risk factors to optimize personalized care.
Therapeutic selection requires integration of clinical phenotype, allergic history, comorbid inflammatory conditions, and risk factors such as prior malignancy or infectious susceptibility. Agents such as omalizumab may be preferable in IgE-driven disease with prominent IgE-mediated food allergies, while dupilumab may offer broader benefit in patients with concurrent eosinophilic GI disease and AD. JAK inhibitors provide an oral alternative in refractory cases and those with select autoimmune conditions.
Recent studies suggest that CSU may be associated with increased mortality risk compared to the general population, challenging earlier perceptions of the condition as benign and self-limiting. This observation reinforces the need for comprehensive and proactive care models that extend beyond dermatologic symptom control. Longitudinal monitoring, comorbidity surveillance, and periodic reassessment of therapeutic efficacy should be considered core components of chronic disease management in both CSU and AD.
Collectively, these findings support a paradigm in which pruritic inflammatory skin diseases are best understood as systemic immune disorders requiring precision therapy. The integration of allergy and immunology expertise into dermatologic care pathways offers meaningful potential to improve outcomes, reduce time to disease control, and align treatment with the immunopathophysiologic profile of each patient.
References:
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3. Lugović-Mihić, L., Meštrović-Štefekov, J., Potočnjak, I., Cindrić, T., Ilić, I., Lovrić, I., Skalicki, L., Bešlić, I., & Pondeljak, N. (2023). Atopic dermatitis: Disease features, therapeutic options, and a multidisciplinary approach. Life, 13(6), 1419–1419. https://doi.org/10.3390/life13061419
4. Nowak, D., & Yeung, J. (2017). Diagnosis and treatment of pruritus. Canadian Family Physician, 63(12), 918. https://pmc.ncbi.nlm.nih.gov/articles/PMC5729138/
5. Öner Özdemir, Gökçe Kasımoğlu, Bak, A., Hüseyin Sütlüoğlu, & Süreyya Savaşan. (2024). Mast cell activation syndrome: An up-to-date review of literature. World Journal of Clinical Pediatrics, 13(2). https://doi.org/10.5409/wjcp.v13.i2.92813
Affiliations:
1. Northwestern University, Feinberg School of Medicine, Medical Scientist Training Program, Chicago, IL
2. Associate Professor of Medicine, Section of Allergy and Clinical Immunology, School of Medicine, Oregon Health and Science University, Portland, OR
Conflicts of Interest:
Dr. Shyam Joshi has served as an advisory board participant for Sanofi (2022–present) and Novartis (2023–present), and as an advisory board participant and consultant for Nectar Allergy (2021–present). He also reports discussing the off-label use of several medications, including antihistamines, biologics, and small molecules.
Sammer Marzouk reports no conflicts of interest.