Chronic Urticaria in the Setting of Atypical Familial Mediterranean Fever with MEFV Gene Variant

Introduction Chronic urticaria (CU) has been previously associated with a variety of underlying conditions, including autoimmune disorders, infections, and atopic disease. The prevalence of the population with CU with a known underlying condition varies by study. The mainstay treatment for CU includes second-generation H1 antihistamines. This case demonstrates the importance of further investigation of underlying diseases in determination of treatment for chronic urticaria. Case 22-year-old female who presented with eight years of urticarial rash. Hives were located on the face, trunk, and limbs. Rash is exacerbated during illness, mechanical pressure, or stress, but frequency of symptoms progressed with no identifiable trigger. Hives were intermittently associated with fever, polyarthralgia, and angioedema of lips and eyes. Investigations Laboratory evaluation was notable for elevated IL-10 and TNF-alpha, reduced IgG subclass 2, with elevated IgE and IgD. Genetic testing of Periodic Fever 6 Gene NGS panel with DDC company revealed a heterozygous variant for MEFV gene coding for Familial Mediterranean fever (FMF). Secondary genetic testing within Invitae Primary Immunodeficiency Panel at Invitae genetic testing company showed variants of uncertain significance for AP3D1 and TONSL genes. Biopsy of skin lesion showed mild edema within the dermis with a very sparse mixed inflammatory cell infiltrate consistent with vasculitis. Treatment Patient initially trialed cetirizine and famotidine with some improvement, but no resolution of symptoms. After diagnosis of atypical FMF, the patient was started on colchicine, then a trial of hydroxychloroquine, with limited improvement. Follow-up discussions include initiation of omalizumab or IL-1 blockade as an escalation of therapy. Discussion There are established associations between several autoimmune disorders and CU. Gene mutation MEFV has been associated with chronic urticaria and FMF, which ultimately helped better symptomatically treat with medications that are not used for chronic urticaria. This case demonstrates the importance of recognizing underlying autoinflammatory disease in the setting of CU and the utility of genetic testing in identifying treatment options.