Chronic recurrent multifocal osteomyelitis (CRMO) is a noninfectious inflammatory bone disease. Approximately 25% of patients with CRMO have a comorbid autoimmune disease, most commonly palmarplantar pustulosis, psoriasis, or inflammatory bowel disease.1 Although the association of uveitis with childhood rheumatic diseases including juvenile arthritis is well known, comorbid CRMO and uveitis have rarely been reported in the literature. We present a case of new-onset CRMO that developed in a boy with a history of chronic bilateral uveitis controlled with methotrexate.
A 15-year-old boy was diagnosed as having unilateral anterior uveitis in March 2013 at age 12 years after presenting with a red eye and photophobia. His initial eye examination showed 2+ anterior chamber reaction, 1+ flare, and 2+ conjunctival injection. Although his acute symptoms improved with topical steroids, he developed recurrent anterior chamber inflammation with steroid taper. One month later, the other eye became involved and also required topical steroid treatment. Synechiae, cataract, keratic precipitates, vitritis, and macular edema were absent in both eyes. Investigation for underlying rheumatic and infectious causes revealed negative antinuclear antibodies, Lyme immunoglobulins, and Treponema pallidum IgG, and positive human leukocyte antigen B27 (HLA-B27). Although he endorsed intermittent activity-related joint pain, he had no evidence of arthritis, enthesitis, or sacroiliitis on physical examination. Radiographs of his sacroiliac joints were unremarkable. His uveitis was effectively treated in a multidisciplinary uveitis clinic with subcutaneous methotrexate 25 mg weekly.
After 1 year of inactive uveitis, his methotrexate was tapered to 20 mg weekly. Two months later, he developed new pain in his left ankle and foot and tarsal swelling without preceding injury or illness. Although his pain improved with over-the-counter naproxen, physical examination revealed edema over the dorsum of the left foot and ankle with tenderness to palpation and plantarflexion. Laboratory studies showed a normal white blood cell count and mild anemia (hemoglobin 12.7 g/dL; normal > 13 g/dL) and an elevated erythrocyte sedimentation rate of 65 mm/hr (normal < 13 mm/hr) and C-reactive protein level of 6.6 mg/dL (normal < 1 mg/dL). Magnetic resonance imaging (MRI) of the foot and ankle showed multifocal bone marrow edema of the distal tibial and fibular metaphyses, inferior calcaneus, first, second, and third cuneiform, and second metatarsal, and an ankle effusion with synovial enhancement. The constellation of findings was concerning for chronic recurrent multifocal osteomyelitis; infection was unlikely due to the distribution of multifocal lesions. A full body MRI was performed to evaluate for asymptomatic lesions and showed symmetrical bone edema in the bilateral proximal humeri, distal radius and ulnae, several phalanges, proximal and distal femurs and tibiae, and proximal fibulae, in addition to the already known findings. The characteristic symmetric, metaphyseal distribution of bone edema was highly consistent with CRMO (Figure 1).
Selected full body magnetic resonance imaging demonstrates symmetric T2 hyperintensity of the proximal humeri and proximal and distal femurs and tibiae.
Although diagnosis of CRMO usually hinges on exclusion of mimics, including infection and malignancy with bone biopsy, this patient's numerous lesions in highly characteristic locations led to a radiographic diagnosis. He started taking adalimumab 40 mg every other week and had symptomatic improvement and normalization of inflammatory markers within 1 month. A repeat MRI of the left lower extremity obtained 1 year later showed minimal residual edema in the distal femur, proximal tibia, and proximal fibula with no new lesions and no joint effusions. He never experienced symptoms suggestive of inflammatory bowel disease, including diarrhea, abdominal pain, or bloody stools. His uveitis remained well controlled with adalimumab 40 mg every other week and methotrexate 20 mg weekly.
CRMO is a rare auto-inflammatory condition characterized by sterile bone inflammation. In addition to the well-described associations of palmarplantar pustulosis, psoriasis, and inflammatory bowel disease, other autoimmune conditions including arthritis, vasculitis, and dermatomyositis have been reported in patients with CRMO.2,3 Uveitis is notably absent from associated conditions listed in recent reviews of CRMO and other forms of chronic non-bacterial osteomyelitis.1,2 A recent in-depth review of the pathogenesis of uveitis reported that CRMO has “no direct association” with uveitis.4
Two CRMO cohorts have each described a single child with uveitis, one with acute unilateral anterior uveitis and the other with uveitis subtype unspecified.5,6 Zhao et al.7 described an adolescent boy who presented with undifferentiated juvenile idiopathic arthritis and subsequently developed severe psoriasis, acute unilateral anterior uveitis, and eventually CRMO. The paucity of similar reports of uveitis occurring in patients with CRMO is surprising given the well-established association between CRMO and other conditions that cause uveitis, including spondyloarthropathies and inflammatory bowel disease. Patients with overlapping features of CRMO and enthesitis-related arthritis or evolution from CRMO to spondyloarthropathy with sacroiliitis have been described, although most have been HLA-B27 negative.8,9
Our case highlights the unique presentation of a patient with new-onset CRMO in the setting of chronic uveitis controlled with baseline immunosuppressive therapy. Although HLA-B27 positive, he had previously exhibited no other clinical findings suggestive of a spondyloarthropathy. This case further expands the spectrum of autoimmune diseases that can occur in association with CRMO.
- Ferguson PJ, Sandu M. Current understanding of the pathogenesis and management of chronic recurrent multifocal osteomyelitis. Curr Rheumatol Rep. 2012;14:130–141. doi:10.1007/s11926-012-0239-5 [CrossRef]
- Stern SM, Ferguson PJ. Autoinflammatory bone diseases. Rheum Dis Clin North Am. 2013;39:735–749. doi:10.1016/j.rdc.2013.05.002 [CrossRef]
- Ardelean DS, Dent PB, Ferguson PJ, Laxer RM. Chronic nonbacterial osteomyelitis in a child with previous juvenile dermatomyositis. J Rheumatol. 2013;40:339–340. doi:10.3899/jrheum.120963 [CrossRef]
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- Vittecoq O, Said LA, Michot C, et al. Evolution of chronic recurrent multifocal osteitis toward spondylarthropathy over the long term. Arthritis Rheum. 2000;43:109–119. doi:10.1002/1529-0131(200001)43:1<109::AID-ANR14>3.0.CO;2-3 [CrossRef]
- Girschick HJ, Raab P, Surbaum S, et al. Chronic non-bacterial osteomyelitis in children. Ann Rheum Dis. 2005;64:279–285. doi:10.1136/ard.2004.023838 [CrossRef]