Clinical Heterogeneity in Pediatric Patients with Chronic Nonbacterial Osteomyelitis and Chronic Recurrent Multifocal Osteomyelitis

Abstract

Chronic recurrent multifocal osteomyelitis (CRMO) and chronic nonbacterial osteomyelitis (CNO) are autoinflammatory diseases characterized by sterile bone inflammation. Patients with CNO or CRMO often complain about pain in extremities, although several unusual manifestations have been reported. We report four pediatric cases of CNO/CRMO, demonstrating marked clinical variability in symptom onset and disease course. All patients presented with bone pain during their disease course, whereas unusual manifestations such as fever of unknown origin prior to the bone pain and cervical pain were confirmed. The diagnosis was established based on clinical features and by ruling out malignancy and infection through biopsy and culture. All patients received nonsteroidal anti-inflammatory drugs as initial therapy, and one required additional treatment with oral methotrexate and adalimumab. Serum cytokine analysis was performed in three cases, revealing elevated levels of both pro- and anti-inflammatory cytokines, such as interleukin (IL)-6, IL-10, and IL-33 in the pre-treatment state. These cases underscore the clinical heterogeneity of CNO/CRMO.