Arthritis und Rheuma 2023; 43(05): 336-344
DOI: 10.1055/a-2129-2943
Kinderrheumatologie
Übersichtsartikel

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

Anja Schnabel
1   Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Pädiatrische Rheumatologie, Dresden, Deutschland
,
Hermann Girschick
2   Vivantes Klinikum im Friedrichshain, Pädiatrische Rheumatologie, Berlin, Deutschland
,
Gabriele Hahn
3   Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Pädiatrische Radiologie, Dresden, Deutschland
,
Christiane Reiser
4   Landeskrankenhaus Bregenz, Abteilung für Kinder- und Jugendheilkunde, Bregenz, Österreich
5   Universitätsklinikum Tübingen, Pädiatrische Rheumatologie und Autoinflammation Reference Center Tübingen (arcT), Tübingen, Deutschland
› Author Affiliations

ZUSAMMENFASSUNG

Die CNO zählt zu den autoinflammatorischen Knochenerkrankungen mit dem Leitsymptom muskuloskelettaler Schmerz. Das breite klinische Spektrum, das Fehlen validierter Diagnosekriterien und die unvollständig verstandene Pathophysiologie machen die Diagnose CNO zu einer Herausforderung. Die Patienten können systemische Entzündungszeichen aufweisen, pathognomonische Laborbefunde existieren jedoch nicht. Die Ganzkörper-Magnetresonanztomografie stellt mittlerweile den Goldstandard (bei Verfügbarkeit) in der CNO-Diagnostik dar. Der histologische Befund einer Knochenbiopsie zeigt kein CNO-spezifisches Entzündungsmuster, kann aber bei unifokaler/atypischer Manifestation für die Differenzierung zu Malignität oder bakteriellen Infektionen notwendig sein. In erster Linie kommen therapeutisch nichtsteroidale Antirheumatika (NSAR) zum Einsatz. In refraktären Fällen oder bei Wirbelsäulenbeteiligung sollte auf Zweitlinien-Medikamente wie Bisphosphonate oder TNF-Inhibitoren zurückgegriffen werden. Der Krankheitsverlauf ist schwer vorhersehbar. Da eine unkontrollierte Krankheitsaktivität zu Komplikationen wie Wirbelkörperfrakturen führen kann, ist eine zeitnahe Diagnosestellung und Therapie wichtig für den Krankheitsverlauf.



Publication History

Article published online:
18 October 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Jurik AG, Ternowitz T, Graudal H. Neutrophil chemotaxis in patients with pustulotic arthro-osteitis. Dermatologica 1988; 176 (04) 161-169
  • 2 Jurik AG, Møller BN. Chronic sclerosing osteomyelitis of the clavicle. A manifestation of chronic recurrent multifocal osteomyelitis. Arch Orthop Trauma surgery Arch fur orthopadische und Unfall-Chirurgie 1987; 106 (03) 144-151
  • 3 Jansson A, Renner ED, Ramser J. et al Classification of non-bacterial osteitis: retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology (Oxford) 2007; 46 (01) 154-160
  • 4 Kahn MF. Diffuse sclerosing osteomyelitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996; 81 (06) 633
  • 5 Li C, Zuo Y, Wu N. et al Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome: a single centre study of a cohort of 164 patients. Rheumatology (Oxford) 2016; 55 (06) 1023-1030
  • 6 Kahn MF, Khan MA. The SAPHO syndrome. Baillieres Clin Rheumatol 1994; 08 (02) 333-362
  • 7 Hofmann SR, Kapplusch F, Mäbert K. et al Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO). Mol Cell Pediatr 2017; 43 (06) 52
  • 8 Zhao Y, Ferguson PJ. Chronic Nonbacterial Osteomyelitis and Chronic Recurrent Multifocal Osteomyelitis in Children. Pediatr Clin North Am 2018; 65 (04) 783-800
  • 9 Hedrich CM, Morbach H, Reiser C, Girschick HJ. New Insights into Adult and Paediatric Chronic Non-bacterial Osteomyelitis CNO. Curr Rheumatol Rep 2020; 22 (09) 52
  • 10 Girschick H, Finetti M, Orlando F. et al The multifaceted presentation of chronic recurrent multifocal osteomyelitis: a series of 486 cases from the Eurofever international registry. Rheumatology (Oxford) 2018; 57 (07) 1203-1211
  • 11 Hedrich CM, Morbach H, Reiser C. et al Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO). J Transl Autoimmun 2021; 22 (09) 52
  • 12 Jansson AF, Müller TH, Gliera L. et al Clinical score for nonbacterial osteitis in children and adults. Arthritis Rheum 2009; 60 (04) 1152-1159
  • 13 Schwarz T, Oommen PT, Windschall D. et al Protokolle zur Klassifikation, Überwachung und Therapie in der Kinderrheumatologie (PRO-KIND): Chronisch nicht-bakterielle Osteomyelitis (CNO): Ergebnisse der Arbeitsgruppe Chronisch nicht-bakterielle Osteomyelitis in der GKJR Kommission PRO-KIND. arthritis + rheuma 2018; 38: 282-288
  • 14 Zhao Y, Wu EY, Oliver MS. et al Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Refractory to Nonsteroidal Antiinflammatory Drugs and/or With Active Spinal Lesions. Arthritis Care Res (Hoboken) 2018; 70 (08) 1228-1237
  • 15 Andronikou S, Mendes da Costa T, Hussien M, Ramanan AV. Radiological diagnosis of chronic recurrent multifocal osteomyelitis using whole-body MRI-based lesion distribution patterns. Clin Radiol 2019; 74 (09) 737.e3-737.e15
  • 16 Andronikou S, Kraft JK, Offiah AC. et al Whole-body MRI in the diagnosis of paediatric CNO/CRMO. Rheumatology (Oxford) 2020; 59 (10) 2671-2680
  • 17 von Kalle T, Heim N, Hospach T. et al Typical patterns of bone involvement in whole-body MRI of patients with chronic recurrent multifocal osteomyelitis (CRMO). Rofo 2013; 185 (07) 655-661
  • 18 Jansson AF, Grote V. Nonbacterial osteitis in children: data of a German Incidence Surveillance Study. Acta Paediatr 2011; 100 (08) 1150-1157
  • 19 Grote V, Silier CCG, Voit AM, Jansson AF. Bacterial Osteomyelitis or Nonbacterial Osteitis in Children: A Study Involving the German Surveillance Unit for Rare Diseases in Childhood. Pediatr Infect Dis J 2017; 36 (05) 451-456
  • 20 Schnabel A, Range U, Hahn G. et al Unexpectedly high incidences of chronic non-bacterial as compared to bacterial osteomyelitis in children. Rheumatol Int 2016; 36 (12) 1737-1745
  • 21 Reiser C, Klotsche J, Hospach A. et al First-year follow-up of children with chronic nonbacterial osteomyelitis-an analysis of the German National Pediatric Rheumatologic Database from 2009 to 2018. Arthritis Res Ther 2021; 23 (01) 281
  • 22 Schnabel A, Range U, Hahn G. et al Treatment Response and Longterm Outcomes in Children with Chronic Nonbacterial Osteomyelitis. J Rheumatol 2017; 44 (07) 1058-1065
  • 23 Morbach H, Hedrich CM, Beer M, Girschick HJ. Autoinflammatory bone disorders. Clin Immunol 2013; 147 (03) 185-196
  • 24 Hofmann SR, Kapplusch F, Girschick HJ. et al Chronic Recurrent Multifocal Osteomyelitis (CRMO): Presentation, Pathogenesis, and Treatment. Curr Osteoporos Rep 2017; 15 (06) 542-554
  • 25 Hofmann SR, Morbach H, Schwarz T. et al Attenuated TLR4/MAPK signaling in monocytes from patients with CRMO results in impaired IL-10 expression. Clin Immunol 2012; 145 (01) 69-76
  • 26 Hofmann SR, Roesen-Wolff A, Hahn G, Hedrich CM. Update: Cytokine Dysregulation in Chronic Nonbacterial Osteomyelitis (CNO). Int J Rheumatol 2012; 2012: 310206
  • 27 Hofmann SR, Kubasch AS, Ioannidis C. et al Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1β expression and release. Clin Immunol 2015; 161 (02) 300-307
  • 28 Brandt D, Sohr E, Pablik J. et al CD14(+) monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3 inflammasome expression. Clin Immunol 2018; 196: 77-84
  • 29 Cox AJ, Darbro BW, Laxer RM. et al Recessive coding and regulatory mutations in FBLIM1 underlie the pathogenesis of chronic recurrent multifocal osteomyelitis (CRMO). PLoS One 2017; 12 (03) DOI: 10.1371/journal.pone.0169687.
  • 30 Abe K, Cox A, Takamatsu N. et al Gain-of-function mutations in a member of the Src family kinases cause autoinflammatory bone disease in mice and humans. Proc Natl Acad Sci U S A 2019; 116 (24) 11872-11877
  • 31 Wang Y, Wang J, Zheng W. et al Identification of an IL-1 receptor mutation driving autoinflammation directs IL-1-targeted drug design. Immunity 2023; 56 (07) 1485-1501.e7
  • 32 Salehzadeh F, Anari H, Sarkhanloo S. Idiopathic CRMO and MEFV Gene Variant Alleles: Is There Any Relationship?. Case reports in rheumatology 2019; 2019: 9847867
  • 33 Hofmann C, Girschick HJ, Mentrup B. et al Clinical aspects of hypophosphatasia: An update. Clin Rev Bone Miner Metab 2013; 11 (02) 60-70 DOI: 10.1007/s12018-013-9139-0.
  • 34 Hofmann SR, Böttger F, Range U. et al Serum Interleukin-6 and CCL11/Eotaxin May Be Suitable Biomarkers for the Diagnosis of Chronic Nonbacterial Osteomyelitis. Front Pediatr 2017; 05: 256
  • 35 Zhao DY, McCann L, Hahn G, Hedrich CM. Chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO). J Transl Autoimmun 2021; 04: 100095
  • 36 Borzutzky A, Stern S, Reiff A. et al Pediatric chronic nonbacterial osteomyelitis. Pediatrics 2012; 130 (05) e1190-1197
  • 37 Beck C, Morbach H, Beer M. et al Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment. Arthritis Res Ther 2010; 12 (02) R74
  • 38 Vittecoq O, Said LA, Michot C. et al Evolution of chronic recurrent multifocal osteitis toward spondylarthropathy over the long term. Arthritis Rheum 2000; 43 (01) 109-119
  • 39 Job-Deslandre C, Krebs S, Kahan A. Chronic recurrent multifocal osteomyelitis: five-year outcomes in 14 pediatric cases. Joint Bone Spine 2001; 68 (03) 245-251
  • 40 Wipff J, Costantino F, Lemelle I. et al A large national cohort of French patients with chronic recurrent multifocal osteitis. Arthritis Rheumatol (Hoboken, NJ) 2015; 67 (04) 1128-1137
  • 41 Bhat CS, Anderson C, Harbinson A. et al Chronic non bacterial osteitis – a multicentre study. Pediatr Rheumatol Online J 2018; 16 (01) 74
  • 42 Costi S, Germinario S, Pandolfi M. et al Chronic Nonbacterial Osteomyelitis and Inflammatory Bowel Disease: A Literature Review-Based Cohort. Child (Basel, Switzerland) 2023; 10(3)
  • 43 Schnabel A, Nashawi M, Anderson C. et al TNF-inhibitors or bisphosphonates in chronic nonbacterial osteomyelitis? – Results of an international retrospective multicenter study. Clin Immunol 2022; 238: 109018
  • 44 Girschick HJ, Mornet E, Beer M. et al Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy. BMC Pediatr 2007; 07: 3
  • 45 Perkins A, Sontheimer C, Otjen JP, Shenoi S. Scurvy Masquerading as Juvenile Idiopathic Arthritis or Vasculitis with Elevated Inflammatory Markers: A Case Series. J Pediatr 2020; 218: 234-237.e2
  • 46 Schnabel A, Hedrich CM, Morbach H. et al S1-Leitlinie „Chronisch nicht bakterielle Osteomyelitis im Kindesalter“. AWMF online. 2023 p. AWMF-Register-Nr. 185-004
  • 47 Kaiser D, Bolt I, Hofer M. et al Chronic nonbacterial osteomyelitis in children: a retrospective multicenter study. Pediatr Rheumatol Online J 2015; 13: 25
  • 48 Hedrich CM, Hofmann SR, Pablik J. et al Autoinflammatory bone disorders with special focus on chronic recurrent multifocal osteomyelitis (CRMO). Pediatr Rheumatol Online J 2013; 11 (01) 47
  • 49 Chen HC, Wuerdeman MF, Chang JH, Nieves-Robbins NM. The role of whole-body magnetic resonance imaging in diagnosing chronic recurrent multifocal osteomyelitis. Radiol Case Reports 2018; 13 (02) 485-489 DOI: 10.1016/j.radcr.2017.11.014.
  • 50 d’Angelo P, de Horatio LT, Toma P. et al Chronic nonbacterial osteomyelitis – clinical and magnetic resonance imaging features. Pediatr Radiol 2021; 51 (02) 282-288
  • 51 Capponi M, Pires Marafon D, Rivosecchi F. et al Assessment of disease activity using a whole-body MRI derived radiological activity index in chronic nonbacterial osteomyelitis. Pediatr Rheumatol Online J 2021; 19 (01) 123
  • 52 Hospach T, Langendoerfer M, von Kalle T. et al Spinal involvement in chronic recurrent multifocal osteomyelitis (CRMO) in childhood and effect of pamidronate. Eur J Pediatr 2010; 169 (09) 1105-1111
  • 53 Voit AM, Arnoldi AP, Douis H. et al Whole-body Magnetic Resonance Imaging in Chronic Recurrent Multifocal Osteomyelitis: Clinical Longterm Assessment May Underestimate Activity. J Rheumatol 2015; 42 (08) 1455-1462
  • 54 Zhao Y, Sato TS, Nielsen SM. et al Development of a Scoring Tool for Chronic Nonbacterial Osteomyelitis Magnetic Resonance Imaging and Evaluation of its Interrater Reliability. J Rheumatol 2020; 47 (05) 739-747
  • 55 Andreasen CM, Klicman RF, Herlin T. et al Standardized reporting and quantification of whole-body MRI findings in children with chronic non-bacterial osteomyelitis treated with pamidronate. Pediatr Rheumatol Online J 2022; 20 (01) 85
  • 56 Kostik MM, Kopchak OL, Maletin AS, Mushkin AY. The peculiarities and treatment outcomes of the spinal form of chronic non-bacterial osteomyelitis in children: a retrospective cohort study. Rheumatol Int 2020; 40 (01) 97-105
  • 57 Hofmann C, Wurm M, Schwarz T. et al A standardized clinical and radiological follow-up of patients with chronic non-bacterial osteomyelitis treated with pamidronate. Clin Exp Rheumatol 2014; 32 (04) 604-609
  • 58 Hofmann SR, Kapplusch F, Mäbert K, Hedrich CM. The molecular pathophysiology of chronic non-bacterial osteomyelitis (CNO) – a systematic review. Mol Cell Pediatr 2017; 04 (01) 7
  • 59 Hofmann SR, Schnabel A, Rösen-Wolff A. et al Chronic Nonbacterial Osteomyelitis: Pathophysiological Concepts and Current Treatment Strategies. J Rheumatol 2016; 43 (11) 1956-1964
  • 60 Koryllou A, Mejbri M, Theodoropoulou K. et al Chronic Nonbacterial Osteomyelitis in Children. Child (Basel, Switzerland) 2021; 8(7)
  • 61 Andreasen CM, Jurik AG, Glerup MB. et al Response to Early-onset Pamidronate Treatment in Chronic Nonbacterial Osteomyelitis: A Retrospective Single-center Study. J Rheumatol 2019; 46 (11) 1515-1523
  • 62 Miettunen PMH, Wei X, Kaura D. et al Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patients with persistent chronic recurrent multifocal osteomyelitis (CRMO). Pediatr Rheumatol 2009; 07: 2 DOI: 10.1186/1546-0096-7-2.
  • 63 Gleeson H, Wiltshire E, Briody J. et al Childhood chronic recurrent multifocal osteomyelitis: pamidronate therapy decreases pain and improves vertebral shape. J Rheumatol 2008; 35 (04) 707-712
  • 64 Gaal A, Basiaga ML, Zhao Y, Egbert M. Pediatric chronic nonbacterial osteomyelitis of the mandible: Seattle Children’s hospital 22-patient experience. Pediatr Rheumatol Online J 2020; 18 (01) 4
  • 65 Taddio A, Zennaro F, Pastore S, Cimaz R. An Update on the Pathogenesis and Treatment of Chronic Recurrent Multifocal Osteomyelitis in Children. Paediatr Drugs 2017; 19 (03) 165-172
  • 66 Eleftheriou D, Gerschman T, Sebire N. et al Biologic therapy in refractory chronic non-bacterial osteomyelitis of childhood. Rheumatology (Oxford) 2010; 49 (08) 1505-1512
  • 67 Deutschmann A, Mache CJ, Bodo K. et al Successful treatment of chronic recurrent multifocal osteomyelitis with tumor necrosis factor-alpha blockage. Pediatrics 2005; 116 (05) 1231-1233
  • 68 Julia N, Katharina R, Hermann G. et al Physical activity and health-related quality of life in chronic non-bacterial osteomyelitis. Pediatr Rheumatol Online J 2019; 17 (01) 45