A80: Skeletal Features of Neonatal‐Onset Multisystem Inflammatory Disease (NOMID) on Anakinra Treatment: Long‐Term Follow‐up
Authors: Kim Hanna , Montealegre Sanchez Gina A. , Chapelle Dawn C. , Plass Nicole , Dwyer Andrew , Goldbach‐Mansky Raphaela , Hill Suvimol 
Published: March 2014

Background/Purpose:

Neonatal‐onset multisystem inflammatory disease (NOMID) is an autoinflammatory disease characterized by fever, chronic urticarial rash, CNS manifestations, elevated acute phase reactants, and arthropathy. About 50% of patients with NOMID have de novo missense mutations in NLRP3/CIAS1, leading to constitutive inflammasome activation and IL‐1 production in monocytes, and caspase‐1 mediated persistence of osteoblast progenitor cells that are also found in other fibroblastoid tumors (). Poorly differentiated chondrocytes are seen with abnormal enchondral bone formation without inflammatory cells in NOMID arthropathy with bony overgrowth and premature fusion of physis. While blocking IL‐1 with anakinra reduces organ‐specific (central nervous system, inner ear, eye) and systemic inflammation (fever, rash, acute phase reactants), it has little effect on preexisting bone lesions.

Methods:

NOMID individuals with at least 5 months of follow up data (clinical, laboratory, and radiographic) on IL‐1 blocking treatment were included for review.

Results:

18 (36.7%) of the NOMID patients (n = 49; 21 male/28 female; age at study entry: 9.4 yo, 0.8–46.3 yo; duration of follow‐up: 4.6 yrs, 0.4–9.5 yrs) had bony involvement, most commonly the knee (16/49 = 32.7%, 12/49 = 24.5% with patellar involvement). 11/49 (22.4%) had multi‐joint involvement, typically asymmetric, including 4 elbows, 5 wrists, 6 ankles, 3 shoulders, and 2 hips. Ongoing abnormal enchondral bone formation continues until physeal fusion, which often occurs prematurely at involved sites, despite anaanakinra treatment. Lesions eventually ossify normally but may cause bone deformities. 3 patients had patellar subluxations (1 managed surgically) and 2 had patella resections. Leg length discrepancy (8/49 = 16.3%) and bowed leg deformities (9/49 = 18.3%) present due to premature, asymmetric fusion of physis required osteomy and/or stapling in 3. 2 developed long twisted fibula to accommodate shortened tibia, 1 surgically managed with stapling. One individual developed hip subluxation due to a longer left leg, which resulted in left hip avascular necrosis. 2 individuals had pseudofractures with development of horizontal linear defects noted in long‐bones consistent with residual changes from abnormal enchondral ossification rather than true fracture. 1 individual developed severe contractures with bilateral knee arthropathy and subsequently had bilateral total knee replacement.

Conclusion:

1. Unique bony findings in NOMID are due to persistence of immature osteoblast precursors with abnormal enchondral bone growth which continues until physeal fusion despite anakinra treatment, often with premature fusion at affected sites, with eventual normal ossification. 2. Surgical intervention can be safely considered for those with significant pain/disability from NOMID arthropathy. 3. Consideration of horizontal linear pseudofractures in long bones and risk of hip avascular necrosis is important in those with NOMID ().