Case Presentation: A 76-year-old woman with past medical history of sero-negative polyarthritis presented with bilateral wrist pain and swelling. She had failed multiple immune-modulators. Synovial wrist biopsies were consistent with synovitis and osteomyelitis. She developed increased swelling, warmth, and a purulent drainage from her right wrist shortly after the biopsies prompting antibiotic treatment that resolved the purulence but joint pain and swelling persisted. She ultimately received multiple courses of antibiotics. There was never any significant culture growth. Wrist x-rays revealed polyostotic destructive changes. MRI confirmed extensive osteolytic and cystic changes in multiple bones of both upper extremities. Ultrasound of her sternoclavicular joint revealed erosive disease without synovitis, effusion, or hyperemia, highly suggestive of SAPHO. There was hesitation to diagnose due to her lack of skin manifestations but given her lack of culture results and her clavicle imaging findings, Anakinra (an IL-1 inhibitor) was initiated. Disease progressed to involve bilateral elbows and left shoulder but when last seen, approximately one year since initiation of Anakinra, symptoms had completely resolved. Re-imaging has not been obtained to confirm remission.

Discussion: CNO or CRMO (thought to be the severe form of CNO) is an auto-inflammatory disorder characterized by painful sterile bone inflammation that most commonly presents early in life and predominantly in females. SAPHO is a variant of this disease that exhibits skin manifestations prior to bone involvement. SAPHO is classically thought to be the adult version of CNO/CRMO but has been described in adolescents. Reliable serum markers for this disease have yet to be identified and routinely checked inflammatory markers may be elevated. Diagnosis is made by imaging, most reliably MRI. Whole body imaging is recommended when CNO/CRMO or SAPHO are suspected as it can identify non-symptomatic lesions. To the same effect, whole body imaging is used for treatment surveillance. Biopsy is warranted when the diagnosis is unclear.
First-line therapy is non-steroidal anti-inflammatory drugs. Second-line therapies include steroids, bisphosphonates, and immunosuppressive agents. All these treatments have had mixed results, related to the fact that the pathogenesis of this disease remains unclear but likely involves multiple inflammatory pathways.
These syndromes are often misdiagnosed as bone cancer or infection leading to inappropriate interventions that carry morbidity and mortality risk. Conversely, bone sclerosis and subsequent deformity and disability can result when appropriate treatment is not provided.

Conclusions: Increased awareness of sterile osteomyelitis may raise suspicion for chronic non-bacterial osteomyelitis (CNO), chronic recurrent multifocal osteomyelitis (CRMO), or synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome when a patient presents in either an atypical fashion for infectious osteomyelitis or with recurrent or multifocal osteomyelitis and reduce the need for bone biopsies and the potential morbidity and mortality incurred from the treatment for alternative diagnoses.