Resolution of chronic idiopathic urticaria with setmelanotide in a patient with Bardet-Biedl Syndrome: A case report.

Introduction: This case describes the resolution of refractory chronic idiopathic urticaria (CIU) with setmelanotide in a patient with Bardet-Biedl Syndrome (BBS). While setmelanotide is approved for syndromic obesity, this report highlights a novel anti-inflammatory effect potentially mediated by melanocortin-4 receptor (MC4R) agonism, expanding current understanding of its immunomodulatory role in mast cell-mediated disease. Main symptoms and clinical findings: The patient presented with lifelong hyperphagia and class III obesity beginning in childhood, along with multiple features fulfilling BBS clinical criteria: visual impairment with night vision difficulties, renal abnormalities with proteinuria, irregular menses with polycystic ovaries, and neurodevelopmental delay. She also reported refractory CIU with pruritic hives occurring several times weekly despite dual antihistamine therapy. On examination, BMI was 40.5 kg/m2, and dermatologic evaluation confirmed recurrent hives unresponsive to standard treatment. Diagnosis: Genetic testing revealed a heterozygous pathogenic BBS9 variant (c.1120C > T; p. Arg374∗), supporting a BBS diagnosis. Secondary causes of urticaria were excluded. Setmelanotide was initiated at 2 mg daily and titrated to 3 mg, leading to complete urticaria resolution within three weeks and cessation of antihistamines. Symptoms recurred during a brief treatment pause and resolved upon reinitiation, demonstrating a temporal association. Hyperphagia scores improved from 20 to 0, with significant quality-of-life gains. Adjunct phentermine 18.75 mg daily was later added to optimize appetite control. After ten months, urticaria remained in sustained remission, with only one isolated cold-induced episode. Conclusion: Setmelanotide produced durable remission of refractory CIU in a patient with BBS, suggesting MC4R agonism may exert immunomodulatory effects beyond weight regulation. This finding underscores the broader potential of precision therapies for rare obesity syndromes to reveal new mechanisms of inflammation control.