A clinical case of Crohn's disease with late-onset familial Mediterranean fever

A rare co-occurrence of Crohn’s disease (CD) and familial Mediterranean fever (FMF) is a complex comorbidity with similarities in their immune pathophysiology and clinical manifestations. This case highlights the challenges in differential diagnosis and therapeutic dilemmas arising from the need to simultaneously manage two immune-mediated diseases. We report a clinical case of an Armenian man with recurrent abdominal pain, chronic diarrhea, episodes of dynamic intestinal obstruction and weight loss. His examination at the age of 39 years revealed signs of systemic inflammation, such as increased erythrocyte sedimentation rate to 62 mm/h, C-reactive protein level to 63 mg/l, and fecal calprotectin to 1039 micrograms/g. Endoscopic examination showed gastric ulcers (0.7 × 0.5 cm), an ileum stricture impenetrable with an endoscope, as well as multiple ulcers of the terminal ileum (SES-CD 9 points). The histological report concluded on chronic ulcerative ileitis with high activity. After one year, the results of molecular genetic testing showed a homozygous pathogenic variant of the MEFV c.2177TC gene (p.Val726Ala) was identified, confirming FMF with persistent activity (serum amyloid A was increased to 32.3 micrograms/ml). The patient was diagnosed with stricturing CD with severe progressive course (A2L1L4B2p) and colchicine-resistant FMF. For CD, the patient consecutively treated with adalimumab, upadacitinib, and ustekinumab with partial response and subsequent ileocecal resection. For FMF, he received colchicine without an effect and canakinumab with complete cessation of attacks. Administration of two targeted agents for two diseases was discussed, but no final decision was taken. By the time of writing this manuscript (January 2025), the patient retained the endoscopic activity of CD with no attacks FMF under treatment with ustekinumab and colchicine. In patients with Crohn’s disease, particularly those of Armenian descent, presenting with atypical abdominal pain and treatment resistance, FMF should be excluded. Molecular genetic testing for MEFV mutations should be included into the diagnostic workup, as their presence should be regarded as a CD modifying factor associated with the disease severity and complication risks. FMF-effective drugs (e. g., canakinumab) may not control CD progression, while CD-targeted therapies (adalimumab, ustekinumab) may not fully resolve FMF manifestations. The safety and efficacy of combining biologics remain unresolved. This case underscores the need for a multidisciplinary approach, development of clear criteria to assessing the activity of combined disease, and further research to optimize treatment strategies.