Chronic Nonbacterial Osteomyelitis and Inflammatory Bowel Disease: A Literature Review-Based Cohort

Abstract

Background: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that mainly involves children and adolescents. The association with other inflammatory disorders, such as inflammatory bowel disease (IBD), psoriasis, and arthritis, has been reported in the literature. In particular, the relationship between bone and intestinal inflammation is still poorly understood. For this purpose, our review aims to describe the cases reported in the literature concerning this association and to compare them with data from our single-center cohort of patients. Methods: We conducted a literature review of published cases of CNO associated with IBD. Eligible articles were identified through a Medline search in the PubMed database until December 2022. We retrospectively reviewed medical records of patients with CNO referred to G. Pini Hospital and compared them with the literature-review-based cohort. Results: Fifty-seven patients with a defined diagnosis of CNO and associated IBD were described in the literature (female 55%). The median age of onset of the disease (CNO or IBD) was 11 years. In 32/53 (60%), a diagnosis of Crohn’s disease (CD) was made, while 18 (34%) patients were classified as suffering from ulcerative colitis (UC) and 3 (6%) from undifferentiated IBD. The diagnosis of CNO preceded the diagnosis of IBD in 59% of cases; while in 24%, IBD anticipated CNO; and in 17%, the two conditions appeared simultaneously. The median time between the two events was 24 months. In our Italian cohort (n = 23 patients), no diagnosis of IBD was made. No significant differences were found when comparing clinical and demographical characteristics of the Italian vs. review-based cohort, except for a significant involvement of rachis in the Italian group. Conclusions: The correlation between autoinflammatory bone disease and intestinal inflammation should be further investigated. It is essential to promote awareness among pediatric rheumatologists and gastroenterologists about this possible association to facilitate the diagnosis and better optimize treatment.

Chronic Nonbacterial Osteomyelitis in Inflammatory Bowel Disease

“…Further delineating the IBD cases, 23 patients (57.5%) were diagnosed with Crohn's disease, while 15 patients (37.5%) presented with ulcerative colitis and 2 of them (5%) were identified as unclassified IBD (Table 3). This conclusion aligns with the percentages attributed in the review by Costi et al (2023) [26]. The median time interval between the two clinical presentations was 2 years, encompassing a spectrum ranging from concomitant diagnosis to an extended 15-year duration.…”

“…Individuals with both CNO and IBD may exhibit a unique set of clinical features that overlap or manifest differently compared to cases of CNO or IBD alone. These features could include bone pain, gastrointestinal symptoms, and signs of systemic inflammation [26].…”

“…In patients with CNO, a compromised intestinal barrier could lead to inflammation, resulting in the release of cytokines. These cytokines may play a role in triggering extraintestinal manifestations of inflammatory bowel disease (IBD), with a specific emphasis on bone inflammation [26].…”

Die Chronisch Nichtbakterielle Osteomyelitis (CNO) im Kindes- und Jugendalter

“…Eine Beteiligung des Magen-Darm-Traktes mit chronisch entzündlichen Darmerkrankungen (Morbus Crohn und Colitis ulcerosa) tritt bei bis zu 10 % der Kinder mit CNO auf 10 , 22 . Die Begleiterkrankungen können zu jedem Zeitpunkt der CNO-Erkrankung (auch Jahre nach Erstdiagnose) auftreten 10 , 42 . Bei bis zu 3 % der Patienten wird eine Hepatosplenomegalie und Lymphknotenschwellung beschrieben.…”

“…Deutlich erhöhte Entzündungsmarker finden sich nur bei einer kleinen Gruppe von CNO-Patienten. Ist dies der Fall, sollten andere Diagnosen (wie bakterielle Infektionen) oder Begleiterkrankungen (wie chronisch entzündliche Darmerkrankungen) bedacht werden 10 , 40 , 42 . Zur Initialdiagnostik zählen des Weiteren Zellzerfallsparameter wie LDH und Harnsäure (maligne Systemerkrankungen), Werte des Knochenstoffwechsels mit Kalzium, Phosphat, Alkalischer Phosphatase (Hypophosphatasie als symptomähnliche Erkrankung) und ggf.…”