Is Fibrodysplasia Ossificans Progressiva an Interleukin-1 Driven Auto-Inflammatory Syndrome ?

Introduction: A 13.5 year-old Arab male was diagnosed with fibrodysplasia ossificans progressiva (FOP), the most catastrophic form of heterotopic ossification, due to an ongoing intracellular signaling through the bone morphogenic protein pathway. Treatment with oral anti-inflammatory drugs did not change the course. New "lumps" appeared in a rate of approximately one "lump" every 8 days. The paroxysmal appearance of inflammatory "lumps" and elevated inflammatory markers during attacks, may suggest that FOP is an auto-inflammatory disease. We hypothesized that treating the patient with anti-interleukin 1 (IL1) agents will help ameliorating the progression of FOP, and report our experience

Objectives: To lower the rate of FOP paroxysms, and/or limit the symptoms and residual lesions, by using anti-IL1 agents.

Methods: Patients` data and blood IL1 levels were analyzed, in order to characterize the efficacy of anti-IL1 treatments.

Results: Treatment with anakinra 100mg/day resulted in marked improvement, and after 2-months, he was treated with monthly canakinumab 300mg for 5 more months. Markedly lowered rate of paroxysms was documented (one "lump"/22-25 days), as well as shorter paroxysms duration. Treatment was then held, but renewed after 6.5 weeks, due to appearance of a big "lump" below a scapula. Spiking high levels of IL1 were then found in the patient`s blood. Contrarily, unmeasurable levels (<0.125) were found in the previous three blood samples obtained while treated with anti-IL1 agents.

Conclusion: This case may suggest that FOP flares are mediated by IL1. Anti-IL1 agents may have a role in treating it as FOP may be an auto-inflammatory syndrome.