Improving the Diagnosis of Chronic Nonbacterial Osteomyelitis, an Underdiagnosed Chronic Autoinflammatory Syndrome

Researchers have identified several factors that should help improve the diagnosis of chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO). This chronic autoinflammatory syndrome, which can be debilitating, is underdiagnosed and is characterized by multiple foci of painful swelling of bones, mainly in the metaphyses of the long bones, in addition to the pelvis, the shoulder girdle and the spine. Because CNO often mimics a bone infection or cancer, children with the condition often see various specialists before getting an accurate diagnosis. The new study was presented at the virtual annual meeting of the American College of Rheumatology.

“The reason we conducted this study is that for patients with CRMO or CNO, there is often an enormous delay between first symptoms to diagnosis, because it is confused with many other things,” said study coauthor Karen Brandt Onel, MD, Chief of Pediatric Rheumatology and Professor of Clinical Pediatrics at Hospital for Special Surgery (HSS) in New York City. “It is not uncommon to have children who have a two, or three-year span, or even as much as a 15-year span between the first symptoms and when they are ultimately diagnosed and treated.”

In the new study, the researchers identified 264 cases of CNO and 145 mimicking conditions from 20 centers in 7 countries on 4 continents, using the REDCap online database. Cases were included if they had at least 12 months of followup. The researchers compared clinical and investigational features of CNO patients with those of patients who had conditions that mimicked CNO.

When compared to mimicker diagnoses, CNO patients were predominantly female, more frequently exhibited intermittent versus continued pain, but less commonly had a fever. Clavicular swelling was more common in CNO than in mimickers. Symmetric patterns of bone lesions were also more common in CNO. CNO frequently involved the thoracic spine, clavicle, sternum/manubrium, pelvic bones, bilateral femur, bilateral tibia, unilateral fibula, and foot bones. Imaging features including cortical bone disruption, disorganized bone formation, mass structure, marrow infiltrate, abscess or geographic appearance were less common in CNO.

The researchers say that clinicians can use the new information to help improve the diagnosis of CNO patients. “We are working slowly and steadily towards classification criteria, so we can make the diagnosis quickly and get treatment instituted quickly. We are trying to work through this disease to identify clear as a bell diagnostic criteria, outcomes measures, and treatment,” said Dr. Onel. “This is a diagnosis that is not in everyone’s brains. Especially if there are typical upper extremity lesions, with the clavicle remaining number one, if there is no fever, and there are symmetric lesions, both tibias, both fibulas, both femurs etc., those are things that should push us in the direction of a diagnosis of CNO or CRMO. If you have symmetric lesions and especially if you have upper extremity lesions, you have to think CRMO or CNO.”

Other authors of the study hail from University of Washington, in Seattle and Bothell, WA; Middlemore Hospital, Auckland, New Zealand; Riley Children’s Hospital, Carmel, IN; UNC Chapel Hill, NC; Children’s Hospital of the King’s Daughters/EVMS, Norfolk, VA; PRINTO, Istituto Giannina Gaslini, Genova, Italy; IRCCS Ospedale Pediatrico Bambino Gesu’, Rome, Italy; Children’s Hospital Colorado, Aurora, CO; Children’s Mercy Kansas City, Kansas City, MO;  IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy; Dr. von Hauner Children’s Hospital, Munich, Germany; Hacettepe University, Ankara, Turkey; Stanford University School of Medicine, Palo Alto, CA; University of Florence, Firenze, Italy; Alder Hey Children’s NHS Foundation Trust Hospital, Liverpool, England, United Kingdom; CRMO Patient Partner, New York, NY, Stony Brook Children’s Hospital, Stony Brook, NY; CRMO Patient Partner, Fort Collins, CO; Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Anna Meyer Children’s Hospital, Firenze, Italy; University of Utah and Primary Children’s Hospital, Salt Lake City, UT; Georgetown University, Derwood, MD; Tufts Medical Center, Boston, MA; University of Iowa Carver College of Medicine, Iowa City, IA; University of Liverpool, Liverpool, United Kingdom, Boston Children’s Hospital, Boston, MA; Vivantes Children’s Hospital, Wuerzburg, Germany and The Hospital for Sick Children, Toronto, ON, Canada.

About HSS

HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 11th consecutive year), No. 4 in rheumatology by U.S. News & World Report (2020-2021), and named a leader in pediatric orthopedics by U.S. News & World Report “Best Children’s Hospitals” list (2020-2021). Founded in 1863, the Hospital has the lowest complication and readmission rates in the nation for orthopedics, and among the lowest infection rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 130 countries. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally. www.hss.edu.