Background/Purpose: Many patients with myelodysplastic syndromes with somatic trisomy 8 in the bone marrow and Behcet’s-like ulcerations have been described. A handful of patients with constitutional trisomy 8 mosaicism with Behcet’s-like disease have been reported but the spectrum of phenotypes has not been characterized in detail.

Methods: Patients with trisomy 8 mosaicism and chromosome 8 duplications who contacted the NIH Autoinflammatory Clinic were interviewed by phone regarding symptoms of recurrent fever, mucosal lesions, and rashes.

Results: A total of 52 patients were interviewed of whom 19 (37%) had trisomy 8 mosaicism and 33 (63%) had chromosome 8 duplications. The average age of patients was 13 years (range 13 months to 40 years). Thirty-eight percent reported a history of 4 or more fever episodes in one year. The average age of episode onset was 23 months; episodes on average lasted 3.7 days with 6 week intervals. During episodes, 65% reported pharyngitis or sore throat, 45% oral ulcers, 45% rash, 35% cervical lymphadenopathy, 35% headache, and 35% abdominal pain. Twenty-five (48%) reported a history of mucosal ulcers of which 84% were oral, 20% were esophageal, 8% were gastric, 8% were colonic, and 20% were genital. Eleven patients (21%) reported having large (>1cm), painful, oral ulcers that took over a week to resolve. Eleven patients (21%) reported recurrent, painful papular or ulcerative rashes. Two patients reported rapid resolution of fever flares with 1 dose of corticosteroid, while two others required longer steroid courses. One patient had episode remission while on colchicine while another had transient improvement on colchicine. Two patients underwent tonsillectomy with no effect. One patient with severe ulcers underwent bone marrow transplant with significant improvement in ulcerative disease.

Conclusion: Patients with trisomy 8 mosaicism and chromosome 8 duplications have a propensity for systemic inflammatory disease that is similar to Behcet’s disease in some patients and similar to periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome in others. This could be due to duplication and subsequent overexpression of particular genes on chromosome 8 that regulate inflammatory responses. We are currently genotyping affected patients using high-density SNP arrays to identify a possible minimal duplicated region in common to these patients. We are collecting blood samples and biopsies from ulcers and rashes from these patients for future studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mucocutaneous-lesions-and-recurrent-fevers-in-patients-with-trisomy-8-mosaicism-and-chromosome-8-duplication/