vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v20i1.2234vsp-2544Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWПоражение легких при ювенильном артрите с системным началом: современное состояние проблемыPulmonary Involvement in Systemic Onset Juvenile Arthritis: Current Status of the Problemhttps://orcid.org/0000-0002-0513-6826КаледаМ. И.KaledaMaria I.

Каледа Мария Игоревна - кандидат медицинских наук, старший научный сотрудник лаборатории ревматических заболеваний детского возраста с реабилитационной группой ФГБНУ НИИР им. В.А. Насоновой.115522, Москва, Каширское ш., д. 34а.тел.: +7 (495) 109-29-10

kaleda-mi@yandex.ruhttps://orcid.org/0000-0003-1842-0348НикишинаИ. П.NikishinaIrina P.

115522, Москва, Каширское ш., д. 34а.

https://orcid.org/0000-0002-5465-6860РодионовскаяС. Р.RodionovskayaSvetlana R.https://orcid.org/0000-0002-6906-0621НиколаеваЕ. В.NikolaevaEkaterina V.

115522, Москва, Каширское ш., д. 34а.

Научно-исследовательский институт ревматологии им. В.А. НасоновойРоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФедеральный научно-клинический центр детей и подростков ФМБА РоссииРоссияFederal Clinical Research Centre of Children and Adolescents of Federal Medico-Biological Agency of RussiaRussian Federation2021030220212013137Copyright © Каледа М.И., Никишина И.П., Родионовская С.Р., Николаева Е.В., 20212021Каледа М.И., Никишина И.П., Родионовская С.Р., Николаева Е.В.Kaleda M.I., Nikishina I.P., Rodionovskaya S.R., Nikolaeva E.V.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/2544

Ювенильный артрит с системным началом является сложным аутовоспалительным заболеванием с полигенным типом наследования, характеризующимся яркими системными проявлениями и прогностически неблагоприятными осложнениями, в ряду которых особое место занимают синдром активации макрофагов и поражение легких. В статье представлены данные о частоте и особенностях течения заболевания, возможных предикторах развития и клинико-рентгенологической картине легочного поражения при ювенильном артрите с системным началом. Рассматриваются возможные факторы, в т. ч. наследственный, влияющие на процесс формирования поражения легких, и роль генно-инженерной биологической терапии.

Systemic onset juvenile arthritis is the complex autoinflammatory disease with multigenic type of inheritance. It is characterized by significant systemic manifestations and unfavourable adverse events, among which macrophage activation syndrome and pulmonary involvement are playing crucial role. This article presents data on the frequency and features of the disease course, possible development predictors and clinical-radiological picture of pulmonary involvement in systemic onset juvenile arthritis. Possible factors (including hereditary) affecting the process of pulmonary involvement development and the role of genetically engineered biologic therapy are considered.

ювенильный артрит с системным началомсиндром активации макрофаговпоражение легких у детейинтерстициальное заболевание легкихлегочный альвеолярный протеинозлегочная гипертензияsystemic onset juvenile arthritismacrophage activation syndromepulmonary involvement in childreninterstitial lung diseasepulmonary alveolar proteinosispulmonary hypertensionНе указан.Not specified.ReferencesDe Benedetti F, Schneider R. Systemic Juvenile Idiopathic Arthritis In: Textbook of pediatric rheumatology. Petty R, Lindsley C, Laxer R, et al., eds. 7th ed. Philadelphia, PA: Elsevier, 2016. pp. 206-216.De Benedetti F, Schneider R. Systemic Juvenile Idiopathic Arthritis In: Textbook of pediatric rheumatology. Petty R, Lindsley C, Laxer R, et al., eds. 7th ed. Philadelphia, PA: Elsevier, 2016. pp. 206-216.Bruck N, Schnabel A, Hedrich CM. Current understanding of the pathophysiology of systemic juvenile idiopathic arthritis (sJIA) and target-directed therapeutic approaches. Clin Immunol. 2015; 159(1):72-83. doi: 10.1016/j.clim.2015.04.018Bruck N, Schnabel A, Hedrich CM. Current understanding of the pathophysiology of systemic juvenile idiopathic arthritis (sJIA) and target-directed therapeutic approaches. Clin Immunol. 2015; 159(1):72-83. doi: 10.1016/j.clim.2015.04.018Martini A, Ravelli A, Avcin T, et al. Toward new classification criteria for juvenile idiopathic arthritis: first steps, Pediatric Rheumatology International Trials Organization International Consensus. J Rheumatol. 2019;46(2):190-197. doi: 10.3899/jrheum.180168Martini A, Ravelli A, Avcin T, et al. Toward new classification criteria for juvenile idiopathic arthritis: first steps, Pediatric Rheumatology International Trials Organization International Consensus. J Rheumatol. 2019;46(2):190-197. doi: 10.3899/jrheum.180168Ravelli A, Grom AA, Behrens EM, Cron RQ. Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment. Genes Immun. 2012;13(4):289-298. doi: 10.1038/gene.2012.3Ravelli A, Grom AA, Behrens EM, Cron RQ. Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment. Genes Immun. 2012;13(4):289-298. doi: 10.1038/gene.2012.3Hashkes PJ, Wright BM, Lauer MS, et al. Mortality outcomes in pediatric rheumatology in the US. Arthritis Rheum. 2010;62(2): 599-608. doi: 10.1002/art.27218Hashkes PJ, Wright BM, Lauer MS, et al. Mortality outcomes in pediatric rheumatology in the US. Arthritis Rheum. 2010;62(2): 599-608. doi: 10.1002/art.27218Tarp S, Amarilyo G, Foeldvari I, et al. Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials. Rheumatology (Oxford). 2016;55(4):669-679. doi: 10.1093/rheumatology/kev382Tarp S, Amarilyo G, Foeldvari I, et al. Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials. Rheumatology (Oxford). 2016;55(4):669-679. doi: 10.1093/rheumatology/kev382Никишина И.П., Каледа М.И. Современная фармакотерапия системного ювенильного артрита // Научно-практическая ревматология. — 2015. — Т. 53. — № 1. — С. 84-93. doi: 10.14412/1995-4484-2015-84-93Nikishina IP, Kaleda MI. Current pharmacotherapy for systemic juvenile arthritis. Rheumatology Science and Practice. 2015;53(1):84-93. (In Russ). doi: 10.14412/1995-4484-2015-84-93Каледа М.И., Никишина И.П. Тоцилизумаб в лечении детей с системным вариантом ювенильного артрита: анализ факторов, влияющих на эффективность терапии в долгосрочном периоде // Вопросы современной педиатрии. — 2015. — Т. 14. — № 2. — С. 236-245. doi: 10.15690/vsp.v14i2.1292Kaleda MI, Nikishina IP. Totsilizumab in the treatment of children with a systemic variant of juvenile arthritis: an analysis of factors affecting the effectiveness of therapy in the long term. Voprosy Sovremennoi Pediatrii — Current Pediatrics. 2015;14(2):236-245. (In Russ). doi: 10.15690/vsp.v14i2.1292Grom AA, Horne A, De Benedetti F. Macrophage activation syndrome in the era of biologic therapy. Nat Rev Rheumatol. 2016; 12(5):259-268. doi: 10.1038/nrrheum.2015.179Grom AA, Horne A, De Benedetti F. Macrophage activation syndrome in the era of biologic therapy. Nat Rev Rheumatol. 2016; 12(5):259-268. doi: 10.1038/nrrheum.2015.179Padeh S, Laxer RM, Silver MM, Silverman ED. Primary pulmonary hypertension in a patient with systemic-onset juvenile arthritis. Arthritis Rheum. 1991;34(12):1575-1579. doi: 10.1002/art.1780341216Padeh S, Laxer RM, Silver MM, Silverman ED. Primary pulmonary hypertension in a patient with systemic-onset juvenile arthritis. Arthritis Rheum. 1991;34(12):1575-1579. doi: 10.1002/art.1780341216Nolan PK, Daniels C, Long F, et al. Severe diffusion capacity reduction in a case of systemic onset juvenile rheumatoid arthritis with mild pulmonary hypertension [abstract]. Chest. 2005;128 (4 Suppl):435S. doi: 10.1378/chest.128.4_MeetingAbstracts.435S-aNolan PK, Daniels C, Long F, et al. Severe diffusion capacity reduction in a case of systemic onset juvenile rheumatoid arthritis with mild pulmonary hypertension [abstract]. Chest. 2005;128 (4 Suppl):435S. doi: 10.1378/chest.128.4_MeetingAbstracts.435S-aSato K, Takahashi H, Amano H, et al. Diffuse progressive pulmonary interstitial and intra-alveolar cholesterol granulomas in childhood. Eur Respir J. 1996;9(11):2419-2422. doi: 10.1183/09031936.96.09112419Sato K, Takahashi H, Amano H, et al. Diffuse progressive pulmonary interstitial and intra-alveolar cholesterol granulomas in childhood. Eur Respir J. 1996;9(11):2419-2422. doi: 10.1183/09031936.96.09112419Schultz R, Mattila J, Gappa M, Verronen P. Development of progressive pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG) associated with therapy-resistant chronic systemic juvenile arthritis (CJA). Pediatr Pulmonol. 2001;32(5):397-402. doi: 10.1002/ppul.1149Schultz R, Mattila J, Gappa M, Verronen P. Development of progressive pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG) associated with therapy-resistant chronic systemic juvenile arthritis (CJA). Pediatr Pulmonol. 2001;32(5):397-402. doi: 10.1002/ppul.1149Бойцова Е.В., Овсянников Д.Ю., Беляшова М.А. Педиатрические интерстициальные заболевания легких: дети не маленькие взрослые // Педиатрия. Журнал им. Г.Н. Сперанского. — 2015. — Т. 94. — № 4. — С. 171-176.Boytsova EV, Ovsyannikov DU, Belyashova MA. Pediatric interstitial lung disease: children patients are not little adults. Pediatria n.a. G.N. Speransky. 2015; 94(4):171-176. (In Russ).Schulert GS, Yasin S, Carey B, et al. Systemic Juvenile Idiopathic Arthritis — Associated Lung Disease: Characterization and Risk Factors. Arthritis Rheumatol. 2019;71(11):1943-1954. doi: 10.1002/art.41073Schulert GS, Yasin S, Carey B, et al. Systemic Juvenile Idiopathic Arthritis — Associated Lung Disease: Characterization and Risk Factors. Arthritis Rheumatol. 2019;71(11):1943-1954. doi: 10.1002/art.41073De Groot J, Vastert B, Giancane G, et al. Interstitial lung disease in systemic juvenile idiopathic arthritis patients in the Pharmachild registry. Pediatric Rheumatology. 2018;16(52):Abstract P004. doi: 10.1186/s12969-018-0265-6De Groot J, Vastert B, Giancane G, et al. Interstitial lung disease in systemic juvenile idiopathic arthritis patients in the Pharmachild registry. Pediatric Rheumatology. 2018;16(52):Abstract P004. doi: 10.1186/s12969-018-0265-6Kimura Y, Weiss JE, Haroldson KL, et al. Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2013;65(5):745-752. doi: 10.1002/acr.21889Kimura Y, Weiss JE, Haroldson KL, et al. Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2013;65(5):745-752. doi: 10.1002/acr.21889Saper VE, Chen G, Deutsch GH, et al. Emergent high fatality lung disease in systemic juvenile arthritis. Ann Rheum Dis. 2019;78(12): 1722-1731. doi: 10.1136/annrheumdis-2019-216040Saper VE, Chen G, Deutsch GH, et al. Emergent high fatality lung disease in systemic juvenile arthritis. Ann Rheum Dis. 2019;78(12): 1722-1731. doi: 10.1136/annrheumdis-2019-216040Inaba H, Jenkins JJ, McCarville MB, et al. Pulmonary alveolar proteinosis in pediatric leukemia. Pediatr Blood Cancer. 2008; 51(1):66-70. doi: 10.1002/pbc.21442Inaba H, Jenkins JJ, McCarville MB, et al. Pulmonary alveolar proteinosis in pediatric leukemia. Pediatr Blood Cancer. 2008; 51(1):66-70. doi: 10.1002/pbc.21442Sullivan KD, Evans D, Pandey A, et al. Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation. Sci Rep. 2017;7(1):14818. doi: 10.1038/s41598-017-13858-3Sullivan KD, Evans D, Pandey A, et al. Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation. Sci Rep. 2017;7(1):14818. doi: 10.1038/s41598-017-13858-3Костик М.М., Исупова Е.А., Румянцева М.В. и др. Интерстициальное поражение легких у пациентов с юношеским артритом с системным началом: описание серии клинических случаев и обзор литературных данных // Педиатрия им. Г.Н. Сперанского. — 2020. — Т. 99. — № 2. — С. 125-136. doi: 10.24110/0031-403X-2020-99-2-125-136Kostik MM, Isupova EA, Rumyantseva MV, et al. Interstitial lung disease in patients with juvenile arthritis with systemic onset: a description of a series of clinical cases with bibliographical review. Pediatria n.a. G.N. Speransky. 2020;99(2):125-136. (In Russ). doi: 10.24110/0031-403X-2020-99-2-125-136Fischer A, Antoniou KM, Brown KK, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015; 46(4):976-987. doi: 10.1183/13993003.00150-2015Fischer A, Antoniou KM, Brown KK, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015; 46(4):976-987. doi: 10.1183/13993003.00150-2015Davies R, Southwood T, Kearsley-Fleet L, et al. Mortality rates are increased in patients with systemic juvenile idiopathic arthritis. Arch Dis Child. 2017;102(2):206-207. doi: 10.1136/archdis-child-2016-311571Davies R, Southwood T, Kearsley-Fleet L, et al. Mortality rates are increased in patients with systemic juvenile idiopathic arthritis. Arch Dis Child. 2017;102(2):206-207. doi: 10.1136/archdis-child-2016-311571Shimizu M, Nakagishi Y, Yachie A. Distinct subsets of patients with systemic juvenile idiopathic arthritis based on their cytokine profiles. Cytokine. 2013;61(2):345-348. doi: 10.1016/j.cyto.2012.11.025Shimizu M, Nakagishi Y, Yachie A. Distinct subsets of patients with systemic juvenile idiopathic arthritis based on their cytokine profiles. Cytokine. 2013;61(2):345-348. doi: 10.1016/j.cyto.2012.11.025Put K, Avau A, Brisse E, et al. Cytokines in systemic juvenile idiopathic arthritis and haemophagocytic lymphohistiocytosis: tipping the balance between interleukin-18 and interferon-у. Rheumatology (Oxford). 2015;54(8):1507-1517. doi: 10.1093/rheumatology/keu524Put K, Avau A, Brisse E, et al. Cytokines in systemic juvenile idiopathic arthritis and haemophagocytic lymphohistiocytosis: tipping the balance between interleukin-18 and interferon-у. Rheumatology (Oxford). 2015;54(8):1507-1517. doi: 10.1093/rheumatology/keu524Humbert M, Monti G, Brenot F, et al. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med. 1995;151(5):1628-1631. doi: 10.1164/ajrccm.151.5.7735624Humbert M, Monti G, Brenot F, et al. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med. 1995;151(5):1628-1631. doi: 10.1164/ajrccm.151.5.7735624Weiss JE, Lee T, Rabinovich CE, et al. Life-threatening Pulmonary Hypertension (PH) and Alveolar Proteinosis (AP) in Systemic JIA (SJIA). Arthritis Rheum. 2008;58(9S):S257-S258.Weiss JE, Lee T, Rabinovich CE, et al. Life-threatening Pulmonary Hypertension (PH) and Alveolar Proteinosis (AP) in Systemic JIA (SJIA). Arthritis Rheum. 2008;58(9S):S257-S258.Ong MS, Mullen MP, Austin ED, et al. Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension. Circ Res. 2017;121(4):341-353. doi: 10.1161/CIRCRESAHA.117.310804Ong MS, Mullen MP, Austin ED, et al. Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension. Circ Res. 2017;121(4):341-353. doi: 10.1161/CIRCRESAHA.117.310804Kitamura N, Ohkouchi S, Tazawa R, et al. Incidence of autoimmune pulmonary alveolar proteinosis estimated using Poisson distribution. ERJ Open Res. 2019;5(1):00190-02018. doi: 10.1183/23120541.00190-2018Kitamura N, Ohkouchi S, Tazawa R, et al. Incidence of autoimmune pulmonary alveolar proteinosis estimated using Poisson distribution. ERJ Open Res. 2019;5(1):00190-02018. doi: 10.1183/23120541.00190-2018Ishii H, Tazawa R, Kaneko C, et al. Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan. Eur Respir J. 2011;37(2):465-468. doi: 10.1183/09031936.00092910Ishii H, Tazawa R, Kaneko C, et al. Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan. Eur Respir J. 2011;37(2):465-468. doi: 10.1183/09031936.00092910Huaux F, De Gussem V, Lebrun A, et al. New interplay between interstitial and alveolar macrophages explains pulmonary alveolar proteinosis (PAP) induced by indium tin oxide particles. Arch Toxicol. 2018;92(4):1349-1361. doi: 10.1007/s00204-018-2168-1Huaux F, De Gussem V, Lebrun A, et al. New interplay between interstitial and alveolar macrophages explains pulmonary alveolar proteinosis (PAP) induced by indium tin oxide particles. Arch Toxicol. 2018;92(4):1349-1361. doi: 10.1007/s00204-018-2168-1Dirksen U, Hattenhorst U, Schneider P, et al. Defective expression of granulocyte macrophage colony-stimulating factor/ interleukin-3/interleukin-5 receptor common beta chain in children with acute myeloid leukemia associated with respiratory failure. Blood. 1998;92(4):1097-1103.Dirksen U, Hattenhorst U, Schneider P, et al. Defective expression of granulocyte macrophage colony-stimulating factor/ interleukin-3/interleukin-5 receptor common beta chain in children with acute myeloid leukemia associated with respiratory failure. Blood. 1998;92(4):1097-1103.De Benedetti F, Brunner HI, Ruperto N, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis [published correction appears in N Engl J Med. 2015 Feb 26;372(9):887]. N Engl J Med. 2012;367(25):2385-2395. doi: 10.1056/NEJMoa1112802De Benedetti F, Brunner HI, Ruperto N, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis [published correction appears in N Engl J Med. 2015 Feb 26;372(9):887]. N Engl J Med. 2012;367(25):2385-2395. doi: 10.1056/NEJMoa1112802Yokota S, Itoh Y, Morio T, et al. Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan. Ann Rheum Dis. 2016;75(9):1654-1660. doi: 10.1136/annrheumdis-2015-207818Yokota S, Itoh Y, Morio T, et al. Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan. Ann Rheum Dis. 2016;75(9):1654-1660. doi: 10.1136/annrheumdis-2015-207818Schulert GS, Minoia F, Bohnsack J, et al. Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis. Arthritis Care Res (Hoboken). 2018;70(3):409-419. doi: 10.1002/acr.23277Schulert GS, Minoia F, Bohnsack J, et al. Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis. Arthritis Care Res (Hoboken). 2018;70(3):409-419. doi: 10.1002/acr.23277Saper V, Mellins E, Kwong B. Drug reaction and high fatality lung disease in systemic onset juvenile idiopathic arthritis (sJIA). J Allergy Clin Immunol. 2020;145(Suppl 2):AB95. doi: 10.1016/j.jaci.2019.12.598Saper V, Mellins E, Kwong B. Drug reaction and high fatality lung disease in systemic onset juvenile idiopathic arthritis (sJIA). J Allergy Clin Immunol. 2020;145(Suppl 2):AB95. doi: 10.1016/j.jaci.2019.12.598Ter Haar NM, van Dijkhuizen EHP, Swart JF, et al. Treatment to Target Using Recombinant Interleukin-1 Receptor Antagonist as First-Line Monotherapy in New-Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five-Year Follow-Up Study. Arthritis Rheumatol. 2019;71(7):1163-1173. doi: 10.1002/art.40865Ter Haar NM, van Dijkhuizen EHP, Swart JF, et al. Treatment to Target Using Recombinant Interleukin-1 Receptor Antagonist as First-Line Monotherapy in New-Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five-Year Follow-Up Study. Arthritis Rheumatol. 2019;71(7):1163-1173. doi: 10.1002/art.40865

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