LAUSR

Chronic, recurrent, multifocal osteomyelitis (CRMO) is a rare, autoinflammatory bone disease, characterized by chronic, nonbacterial osteomyelitis, multifocal bone lesions, and multiple recurrence. Patients with CRMO typically present with bone pain; myositis is rare as a clinical symptom of CRMO. Here, we report a case of CRMO with myositis of the internal obturator muscle. A 7-year-old girl was admitted to our hospital with a 2week history of fever and arthralgia of the left hip and right side of the neck. She did not have a notable family or medical history. Physical examination revealed a limited range of motion and movement-evoked pain of the left hip joint. Laboratory tests were as follows: white blood cell count 9,700/ mm, erythrocyte sedimentation rate 63 mm/h, C-reactive protein 4.9 mg/dL, aspartate aminotransferase/alanine aminotransferase 24/13 U/L, creatine kinase (CK) 659 U/L (normal range 45–163 U/L), and matrix metalloprotease-3 29.6 ng/mL (17.3–59.7 ng/mL). Serologic tests for autoantibodies were negative. A plain X-ray of the neck and pelvis indicated no lytic or sclerotic changes. Magnetic resonance imaging (MRI) revealed multiple ostetic lesions, including the 3rd, 4, and 7th cervical vertebrae, bilateral iliac bones, left coxal, and ischial bones (Fig. 1a, b), and a focally-enhanced lesion in the internal obturator muscle (Fig. 1c). Pelvic computed tomography revealed lytic changes in the right iliac and ischial bones (Fig. S1A, B). A Tc99m HDP bone scan revealed high uptake in these bones, as well as the 11 rib and left radial bone (Fig. S2). A bone biopsy of the ileum was showed no specific inflammatory changes and the absence of malignant cells. From these characteristics, the diagnosis of CRMO with myositis of the internal obturator muscle was made. The patient was treated with ibuprofen. Clinical symptoms and myositis on MRI were improved, although ostetic lesions in iliac bones remained (Fig. 1d). The patient experienced a febrile episode with osteomyelitis 8 months after starting ibuprofen (30 mg/kg/day). Pamidronate (2.5 mg/kg administered for 3 days) was added; however, she experienced another febrile episode with osteomyelitis 3 months later. Colchicine (0.025 mg/kg/day) was initiated, and she had no recurrent episodes over a 6-month follow-up period. Written informed consent was obtained from the parents of the patient for publication of this report. Patients with CRMO usually present with bone pain, predominantly affecting the metaphyses of the long bones, clavicle, vertebra, and the pelvis. Extra-osseous manifestations include palmoplantar pustulosis, psoriasis vulgaris, pyoderma gangrenosum, or inflammatory bowel disease. CRMO can also manifest as part of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Myositis as a clinical symptom of CRMO is very rare, and only five cases have been previously reported (Table S1). The muscles in the extremities were affected in most cases. No patients showed muscle weakness. The elevation of CK levels was observed only in our patient. In three patients, including our patient, myositis or soft tissue inflammation were detected on MRI in close to osteomyelitis. These findings suggest an association of myositis with osteomyelitis because of the close anatomic relationships of the foci of myositis and osteomyelitis. In contrast, myositis was present not along osteomyelitis in the other three patients. In an 11year-old boy, myositis associated with CRMO was detected on MRI in the quadriceps femoris and gastrocnemius muscles. However, osteomyelitis did not involve his femurs and tibias. A muscle biopsy revealed interstitial myositis. These findings indicate that the mechanism of the development of myositis associated with CRMO is complex. Further studies are needed to clarify the mechanism of myositis in patients with CRMO. Non-steroidal anti-inflammatory drugs are the first-line treatment for CRMO and they are effective in 73% of patients. Pamidronate is also effective in patients with CRMO. In addition to these drugs, patients with refractory CRMO have been treated with glucocorticoids, methotreaxate, sulfasalazine, biologics, including anti-TNF drugs and tocilizumab, and colchicine. This patient was refractory to ibuprofen and pamidronate but her disease stabilized after starting colchicine. Colchicine may be effective in some refractory cases of CRMO. Correspondence: Masaki Shimizu, MD PhD, Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8641, Japan. Email: [email protected] Received 31 October 2019; revised 13 December 2019; accepted 7 January 2020. doi: 10.1111/ped.14144