refractory chronic urticaria and angioedema associated with a cvid-like immune dysregulation phenotype in an adolescent: a multisystem management challenge

Background: chronic idiopathic urticaria (ciu), also referred to as chronic spontaneous urticaria, is characterized by recurrent wheals with or without angioedema persisting for more than six weeks. while ciu is often self-limited, a subset of patients develops chronic, severe, and treatment-refractory disease. chronic urticaria is a recognized manifestation of primary immunodeficiencies, including common variable immunodeficiency (cvid); however, severe, refractory presentations in pediatric and adolescent populations remain a significant diagnostic and management challenge. early recognition of underlying immune dysregulation is essential to guide therapy, anticipate systemic complications, and improve long-term outcomes.case presentation: we report a 17-year-old female with an eight-year history of painful, pruritic urticarial eruptions and angioedema refractory to multiple therapies, including high-dose h1/h2 antihistamines, omalizumab, dupilumab, and immunosuppressive agents. disease flares were exacerbated by psychological stress, temperature changes, and menstrual cycles, with partial symptom improvement following initiation of oral contraceptive pills. immunologic evaluation revealed hypogammaglobulinemia with fluctuating immunoglobulin levels, reduced cd19⁺ b-cell count, elevated cd8⁺ t-cell percentage, impaired vaccine response, and a positive anti-ige autoantibody. these findings support a cvid-like immune dysregulation phenotype with t-cell imbalance and a concurrent autoimmune chronic urticaria phenotype, rather than definitive cvid. additional comorbidities included stage 2 chronic kidney disease, intermittent hepatic enzyme elevation, dyslipidemia, and depressive symptoms.discussion: this case illustrates refractory ciu occurring in the context of a cvid-like immune dysregulation phenotype rather than confirmed cvid, emphasizing the importance of diagnostic precision when applying established immunodeficiency criteria. immune abnormalities such as hypogammaglobulinemia, impaired humoral responses, and t-cell imbalance may contribute to persistent inflammation through impaired immune tolerance, altered immune complex clearance, and chronic immune activation. the presence of anti-ige autoantibodies further supports an autoimmune urticaria mechanism contributing to treatment resistance. partial hormonal responsiveness highlights the modulatory effects of estrogen and progesterone on mast cell activation and immune signaling pathways. the patient's multisystem involvement and psychosocial burden underscore the necessity of an integrative, multidisciplinary approach addressing immunologic, endocrine, and psychological dimensions of care.