vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v15i5.1625vsp-1675Research ArticleОБМЕН ОПЫТОМEXCHANGE OF EXPERIENCEДИФФЕРЕНЦИРОВАННЫЙ ПОДХОД К ЛЕЧЕНИЮ НЕБАКТЕРИАЛЬНОГО ОСТЕОМИЕЛИТА У ДЕТЕЙ: РЕЗУЛЬТАТЫ РЕТРОСПЕКТИВНОГО ИССЛЕДОВАНИЯDIFFERENTIATED APPROACH TO NON-BACTERIAL OSTEOMYELITIS TREATMENT IN CHILDREN: THE RETROSPECTIVE STUDY RESULTSKoстикM. M.KostikMikhail M.

Костик Михаил Михайлович - кандидат медицинских наук; доцент кафедры госпитальной педиатрии СПбГПМУ.

194100; Санкт-Петербург; ул. Литовская; д. 2;  тел.: +7 (812) 416-52-98;  e-mail: kost-mikhail@yandex.ru

kost-mikhail@yandex.ruKoпчакO. Л.KopchakOlga L.ЧиковаИ. А.ChikovaIrina A.ИсуповаЕ. А.IsupovaEugenia A.МасаловаВ. В.MasalovaVera V.ДубкоM. Ф.DubkoMargarita F.СнегирёваЛ. С.SnegirevaLudmila S.КалашниковаO. В.KalashnikovaOlga V.МушкинА. Ю.MushkinAlexandr Y.ЧасныкВ. Г.ChasnykVyacheslav G.Санкт-Петербургский государственный педиатрический медицинский университетРоссияSaint-Petersburg State Pediatric Medical UniversityRussian FederationСанкт-Петербургский государственный педиатрический медицинский университет; Кировская детская областная клиническая больницаРоссияSaint-Petersburg State Pediatric Medical University; Kirov Children's Regional Clinical HospitalRussian FederationСанкт-Петербургский научно-исследовательский институт фтизиопульмонологииРоссияSaint-Petersburg Research Institute of PhthisiopulmonologyRussian Federation201624112016155505512Copyright © Koстик M.M., Koпчак O.Л., Чикова И.А., Исупова Е.А., Масалова В.В., Дубко M.Ф., Снегирёва Л.С., Калашникова O.В., Мушкин А.Ю., Часнык В.Г., 20162016Koстик M.M., Koпчак O.Л., Чикова И.А., Исупова Е.А., Масалова В.В., Дубко M.Ф., Снегирёва Л.С., Калашникова O.В., Мушкин А.Ю., Часнык В.Г.Kostik M.M., Kopchak O.L., Chikova I.A., Isupova E.A., Masalova V.V., Dubko M.F., Snegireva L.S., Kalashnikova O.V., Mushkin A.Y., Chasnyk V.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/1675

Недостаточная эффективность терапии детей с небактериальным остеомиелитом остается актуальной проблемой современной педиатрии и ревматологии.

Цель исследования

Цель исследования: провести оценку эффективности и безопасности лечения небактериального остеомиелита у детей.

Методы

Методы. Проведено ретроспективное исследование историй болезни детей с небактериальным остеомиелитом. Эффективность терапии (наступление ремиссии) оценивали по следующим критериям: отсутствие лихорадки; болевого синдрома; клинически активных очагов; лабораторной активности заболевания. Лабораторные и лучевые методы исследования проводились во время диагностики патологического процесса и в последующем через каждые 3–6–12 мес с целью оценки активности заболевания в зависимости от степени исходного поражения скелета. Оценка клинической активности производилась при помощи визуальной аналоговой шкалы.

Результаты

Результаты. Проанализированы результаты лечения 52 детей (68 курсов терапии) с небактериальным остеомиелитом. Нестероидные противовоспалительные препараты получали 19 больных; сульфасалазин — 7; метотрексат — 9; памидроновую кислоту — 18; ингибиторы фактора некроза опухоли (TNF) α  — 15. Ремиссия была достигнута у 10 (53%), 4 (57%), 4 (44%), 16 (89%) и 11 (73%) больных (р = 0;001) соответственно. Нежелательные явления на фоне лечения возникли у 21 (40%) ребенка. Серьезных нежелательных явлений не наблюдалось.

Заключение

Заключение. Показана эффективность разных схем терапии. Установлено; что наиболее эффективными в лечении детей с небактериальным остеомиелитом были препарат памидроновой кислоты и ингибиторы TNFα.

 Differentiated Approach to Non-Bacterial Osteomyelitis Treatment in Children: the Retrospective Study Results Background. Low efficacy of the therapy of children with non-bacterial osteomyelitis remains a topical problem of modern pediatrics and rheumatology.

Objective

Objective: Our aim was to assess the efficacy and safety of non-bacterial osteomyelitis treatment in children.

Methods

Methods. A retrospective study of the case records of children with non-bacterial osteomyelitis has been carried out. The therapy efficacy (remission) was assessed by the following criteria: absence of fever, pain, clinically active lesions, laboratory disease activity. Laboratory and radiological methods were carried out during diagnosis of the pathological process, and subsequently every 3–6–12 months to assess disease activity depending on the initial injury extent of the skeleton. Clinical activity assessment was carried out by means of a visual analogue scale.

Results

Results. We analyzed treatment results of 52 children (68 therapy courses) with non-bacterial osteomyelitis. Nonsteroidal anti-inflammatory drugs were administered to 19 patients, sulfasalazine — to 7, methotrexate — to 9, pamidronic acid — to 18, inhibitors of tumour necrosis factor (TNF) α  — to 15. Remission was achieved in 10 (53%) 4 (57%) 4 (44%), 16 (89%), and 11 (73%) patients (p = 0.001), respectively. Adverse events during treatment occurred in 21 (40%) children. No serious adverse events were reported.

Conclusion

Conclusion. The efficacy of different regimens has been shown. It was found that pamidronic acid drug and TNF  inhibitors were the most effective in treating children with non-bacterial osteomyelitis.

детинебактериальный остеомиелитпамидроновая кислотаингибиторы TNF αchildrennon-bacterial osteomyelitispamidronic acidTNF α inhibitorsReferencesStern SH, Ferguson PJ. Autoinflammatory bone diseases. Rheum Dis Clin North Am. 2013,39(4):735–749. doi: 10.1016/j.rdc.2013.05.002.Stern SH, Ferguson PJ. Autoinflammatory bone diseases. Rheum Dis Clin North Am. 2013,39(4):735–749. doi: 10.1016/j.rdc.2013.05.002.Bazrafshan A, Zanjani KS. Chronic recurrent multifocal osteo-myelitis associated with ulcerative colitis: A case report. J Pediatr Surg. 2000,35(10):1520–1522. doi: 10.1053/jpsu.2000.16431.Bazrafshan A, Zanjani KS. Chronic recurrent multifocal osteo-myelitis associated with ulcerative colitis: A case report. J Pediatr Surg. 2000,35(10):1520–1522. doi: 10.1053/jpsu.2000.16431.Huber AM, Lam PY, Duffy CM, et al. Chronic recurrent multifocal osteomyelitis: Clinical outcomes after more than five years of follow-up. J Pediatr. 2002,141(2):198–203. doi: 10.1067/mpd.2002.126457.Huber AM, Lam PY, Duffy CM, et al. Chronic recurrent multifocal osteomyelitis: Clinical outcomes after more than five years of follow-up. J Pediatr. 2002,141(2):198–203. doi: 10.1067/mpd.2002.126457.Schilling F, Marker-Hermann E. Die chronische rekurrierende multifokale Osteomyelitis in Assoziation mit chronisch entzundlichen Darmerkrankungen: die enteropathische CRMO. [Chronic recurrent multifocal osteomyelitis in association with chronic inflammatory bowel disease: entheropathic CRMO (In German).] Z Rheumatol. 2003,62(6):527–538. doi: 10.1007/s00393-003-0526-7.Schilling F, Marker-Hermann E. Die chronische rekurrierende multifokale Osteomyelitis in Assoziation mit chronisch entzundlichen Darmerkrankungen: die enteropathische CRMO. [Chronic recurrent multifocal osteomyelitis in association with chronic inflammatory bowel disease: entheropathic CRMO (In German).] Z Rheumatol. 2003,62(6):527–538. doi: 10.1007/s00393-003-0526-7.Hofmann SR, Schwarz T, Moller JC, et al. Chronic non-bacterial osteomyelitis is associated with impaired Sp1 signaling, reduced IL10 promoter phosphorylation and reduced myeloid IL10 expression. Clin Immunol. 2011,141(3):317–327. doi: 10.1016/j.clim.2011.08.012.Hofmann SR, Schwarz T, Moller JC, et al. Chronic non-bacterial osteomyelitis is associated with impaired Sp1 signaling, reduced IL10 promoter phosphorylation and reduced myeloid IL10 expression. Clin Immunol. 2011,141(3):317–327. doi: 10.1016/j.clim.2011.08.012.Hofmann SR, Rosen-Wolff A, Tsokos GC, Hedrich CM. Biological properties and regulation of IL10 related cytokines and their contribution to autoimmune disease and tissue injury. Clin Immunol. 2012,143(2):116–127. doi: 10.1016/j.clim.2012.02.005.Hofmann SR, Rosen-Wolff A, Tsokos GC, Hedrich CM. Biological properties and regulation of IL10 related cytokines and their contribution to autoimmune disease and tissue injury. Clin Immunol. 2012,143(2):116–127. doi: 10.1016/j.clim.2012.02.005.Girschick HJ, Zimmer C, Klaus G, et al. Chronic recurrent multifocal osteomyelitis: what is it and how should it be treated? Nat Clin Pract Rheumatol. 2007,3(12):733–738. doi: 10.1038/ncprheum0653.Girschick HJ, Zimmer C, Klaus G, et al. Chronic recurrent multifocal osteomyelitis: what is it and how should it be treated? Nat Clin Pract Rheumatol. 2007,3(12):733–738. doi: 10.1038/ncprheum0653.Borzutzky A, Stern S, Reiff A, et al. Pediatric chronic nonbacterial osteomyelitis. Pediatrics. 2012,130(5):e1190–1197. doi: 10.1542/peds.2011-3788.Borzutzky A, Stern S, Reiff A, et al. Pediatric chronic nonbacterial osteomyelitis. Pediatrics. 2012,130(5):e1190–1197. doi: 10.1542/peds.2011-3788.Girshick HJ, Raab P, Surbaum S, et al. Chronic non-bacterial osteomyelitis in children. Ann Rheum Dis. 2005,64(2):274–285. doi: 10.1136/ard.2004.023838.Girshick HJ, Raab P, Surbaum S, et al. Chronic non-bacterial osteomyelitis in children. Ann Rheum Dis. 2005,64(2):274–285. doi: 10.1136/ard.2004.023838.Bellido T, Plotkin LI. Novel actions of bisphosphonates in bone: Preservation of osteoblast and osteocyte viability. Bone. 2011,49(1):50–55. doi: 10.1016/j.bone.2010.08.008.Bellido T, Plotkin LI. Novel actions of bisphosphonates in bone: Preservation of osteoblast and osteocyte viability. Bone. 2011,49(1):50–55. doi: 10.1016/j.bone.2010.08.008.Santra G, Sarkar RN, Phaujdar S, et al. Assessment of the efficacy of pamidronate in ankylosing spondylitis: an open prospective trial. Singapore Med J. 2010,51(11):883–887.Santra G, Sarkar RN, Phaujdar S, et al. Assessment of the efficacy of pamidronate in ankylosing spondylitis: an open prospective trial. Singapore Med J. 2010,51(11):883–887.Miettunen P, Wei X, Kaura D, et al. Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patiens with persistent chronic recurrent multifocal osteomyelitis (CRMO). Pediatr Rheumatol. 2009,7:2. doi: 10.1186/1546-0096-7-2.Miettunen P, Wei X, Kaura D, et al. Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patiens with persistent chronic recurrent multifocal osteomyelitis (CRMO). Pediatr Rheumatol. 2009,7:2. doi: 10.1186/1546-0096-7-2.Hospach T, Langendoerfer M, von Kalle T, et al. Spinal involve ment in chronic recurrent multifocal osteomyelitis (CRMO) in childhood and effect of pamidronate. Eur J Pediatr. 2010,169(9):1105–1111. doi: 10.1007/s00431-010-1188-5.Hospach T, Langendoerfer M, von Kalle T, et al. Spinal involve ment in chronic recurrent multifocal osteomyelitis (CRMO) in childhood and effect of pamidronate. Eur J Pediatr. 2010,169(9):1105–1111. doi: 10.1007/s00431-010-1188-5.Deutschmann A, Mache CJ, Bodo K, et al. Successful treatment of chronic recurrent multifocal osteomyelitis with tumor necrosis factor alpha blockage. Pediatrics. 2005,116(5):1231–1233. doi: 10.1542/peds.2004-2206.Deutschmann A, Mache CJ, Bodo K, et al. Successful treatment of chronic recurrent multifocal osteomyelitis with tumor necrosis factor alpha blockage. Pediatrics. 2005,116(5):1231–1233. doi: 10.1542/peds.2004-2206.Jansson A, Renner ED, Ramser J, et al. Classification of nonbacterial osteitis retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology (Oxford). 2007,46(1):154–160. doi: 10.1093/rheumatology/kel190.Jansson A, Renner ED, Ramser J, et al. Classification of nonbacterial osteitis retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology (Oxford). 2007,46(1):154–160. doi: 10.1093/rheumatology/kel190.Jansson AF, Muller TH, Gliera L, et al. Clinical score for nonbacterial osteitis in children and adults. Arthritis Rheumatol. 2009,60(4):1152–1159. doi: 10.1002/art.24402.Jansson AF, Muller TH, Gliera L, et al. Clinical score for nonbacterial osteitis in children and adults. Arthritis Rheumatol. 2009,60(4):1152–1159. doi: 10.1002/art.24402.Копчак О.Л., Костик М.М., Мушкин А.Ю. Хронический небак-териальный («стерильный») остеомиелит в практике детского ревматолога, современные подходы к диагностике и лечению: обзор литературы и анализ собственных данных // Вопросы современной педиатрии. — 2016 — Т. 15. — № 1 — С. 33–44. [Kopchak OL, Kostik MM, Mushkin AY. Chronic non-bacterial («sterile») osteomyelitis in the practice of pediatric rheumatologist, the contemporary diagnostic and treatment approaches: literature review and own data analysis. Current pediatrics. 2016,15(1):33–44 (In Russ).] doi: 10.15690/vsp.v15i1.1498.Копчак О.Л., Костик М.М., Мушкин А.Ю. Хронический небак-териальный («стерильный») остеомиелит в практике детского ревматолога, современные подходы к диагностике и лечению: обзор литературы и анализ собственных данных // Вопросы современной педиатрии. — 2016 — Т. 15. — № 1 — С. 33–44. [Kopchak OL, Kostik MM, Mushkin AY. Chronic non-bacterial («sterile») osteomyelitis in the practice of pediatric rheumatologist, the contemporary diagnostic and treatment approaches: literature review and own data analysis. Current pediatrics. 2016,15(1):33–44 (In Russ).] doi: 10.15690/vsp.v15i1.1498.Beck C, Morbach H, Beer M, et al. Chronic nonbacterial osteo-myelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment. Arthritis Res Ther. 2010,12(2):R74. doi: 10.1186/ar2992.Beck C, Morbach H, Beer M, et al. Chronic nonbacterial osteo-myelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment. Arthritis Res Ther. 2010,12(2):R74. doi: 10.1186/ar2992.Kaiser D, Bolt I, Hofer M, et al. Chronic nonbacterial osteomyelitis in children: a retrospective multicenter study. Pediatr Rheumatol Online J. 2015,13:25. doi: 10.1186/s12969-015-0023-y.Kaiser D, Bolt I, Hofer M, et al. Chronic nonbacterial osteomyelitis in children: a retrospective multicenter study. Pediatr Rheumatol Online J. 2015,13:25. doi: 10.1186/s12969-015-0023-y.Abril JC, Ramirez A. Successful treatment of chronic recurrent multifocal osteomyelitis with indomethacin. J Pediatr Orthop. 2007,27(5):587–591. doi: 10.1097/bpo.0b013e318070cbd3.Abril JC, Ramirez A. Successful treatment of chronic recurrent multifocal osteomyelitis with indomethacin. J Pediatr Orthop. 2007,27(5):587–591. doi: 10.1097/bpo.0b013e318070cbd3.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(4):604–609.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(4):604–609.Jansson AF, Grote V, Group ES. Nonbacterial osteitis in children: data of a German Incidence Surveillance Study. Acta Paediatr. 2011,100(8):1150–1157. doi: 10.1111/j.1651-2227.2011.02205.x.Jansson AF, Grote V, Group ES. Nonbacterial osteitis in children: data of a German Incidence Surveillance Study. Acta Paediatr. 2011,100(8):1150–1157. doi: 10.1111/j.1651-2227.2011.02205.x.Patlas N, Golomb G, Yaffe P, et al. Transplacental effects of bisphosphonates on fetal skeletal ossification and mineralization in rats. Birth Defects Res A Clin Mol Teratol. 1999,60(2):68–73. doi: 10.1002/(sici)1096-9926(199908)60:2<68::aidtera10>3.0.co,2-h.Patlas N, Golomb G, Yaffe P, et al. Transplacental effects of bisphosphonates on fetal skeletal ossification and mineralization in rats. Birth Defects Res A Clin Mol Teratol. 1999,60(2):68–73. doi: 10.1002/(sici)1096-9926(199908)60:2<68::aidtera10>3.0.co,2-h.Djokanovic N, Klieger-Grossmann C, Koren G. Does treatment with bisphosphonates endanger the human pregnancy? Obstet Gynaecol Can. 2008,30(12):1146–1148. doi: 10.1016/s1701-2163(16)34026-9.Djokanovic N, Klieger-Grossmann C, Koren G. Does treatment with bisphosphonates endanger the human pregnancy? Obstet Gynaecol Can. 2008,30(12):1146–1148. doi: 10.1016/s1701-2163(16)34026-9.Green SB, Pappas AL. Effects of maternal bisphosphonate use on fetal and neonatal outcomes. Health Syst Pharm. 2014,71(23):2029–2036. doi: 10.2146/ajhp140041.Green SB, Pappas AL. Effects of maternal bisphosphonate use on fetal and neonatal outcomes. Health Syst Pharm. 2014,71(23):2029–2036. doi: 10.2146/ajhp140041.Rosen CJ, Brown S. Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med. 2003,348(15):1503–1504. doi: 10.1056/nejm200304103481521.Rosen CJ, Brown S. Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med. 2003,348(15):1503–1504. doi: 10.1056/nejm200304103481521.Timmen M, Hidding H, Wieskotter B; et al. Influence of antiTNF-alpha antibody treatment on fracture healing under chronic inflammation. BMC Musculoskelet Disord. 2014;15:184. doi: 10.1186/1471-2474-15-184.Timmen M, Hidding H, Wieskotter B; et al. Influence of antiTNF-alpha antibody treatment on fracture healing under chronic inflammation. BMC Musculoskelet Disord. 2014;15:184. doi: 10.1186/1471-2474-15-184.Kawai VK; Stein CM; Perrien DS; Griffin MR. Effects of anti-tumor necrosis factor (anti-TNF) agents on bone. Curr Opin Rheumatol. 2012;24(5):576–585. doi: 10.1097/bor.0b013e328356d212.Kawai VK; Stein CM; Perrien DS; Griffin MR. Effects of anti-tumor necrosis factor (anti-TNF) agents on bone. Curr Opin Rheumatol. 2012;24(5):576–585. doi: 10.1097/bor.0b013e328356d212.Klotsche J; Niewerth M; Haas JP; et al. Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2016;75(5):855–861. doi: 10.1136/annrheumdis-annrheumdis-2014-206747.Klotsche J; Niewerth M; Haas JP; et al. Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2016;75(5):855–861. doi: 10.1136/annrheumdis-annrheumdis-2014-206747.Chiu YM; Tang CH; Hung ST; et al. A real-world risk analysis of biological treatment (adalimumab and etanercept) in a country with a high prevalence of tuberculosis and chronic liver disease: a nationwide population-based study. Scand J Rheumatol. 2016:1–5. doi: 10.1080/03009742.2016.1202318.Chiu YM; Tang CH; Hung ST; et al. A real-world risk analysis of biological treatment (adalimumab and etanercept) in a country with a high prevalence of tuberculosis and chronic liver disease: a nationwide population-based study. Scand J Rheumatol. 2016:1–5. doi: 10.1080/03009742.2016.1202318.Solomon DH; Mercer E; Kavanaugh A. Observational studies on the risk of cancer associated with TNF-inhibitors in RA: a review of their methodologies and results. Arthritis Rheum. 2012;64(1):21–32. doi: 10.1002/art.30653.Solomon DH; Mercer E; Kavanaugh A. Observational studies on the risk of cancer associated with TNF-inhibitors in RA: a review of their methodologies and results. Arthritis Rheum. 2012;64(1):21–32. doi: 10.1002/art.30653.

The authors declare that there are no conflicts of interest present.