Modern Pediatrics. Ukraine. (2023). 6(134): 24-35. doi 10.15574/SP.2023.134.24
Ошлянская Е. А. ¹, Охотникова Е. Н.¹, Усова Е. И.¹, Гедеон И. В.^2
1Национальный университет охраны здоровья Украины имени П.Л. Шупика, г. Киев
²Национальная детская специализированная больница «ОХМАТДЕТ», г. Киев, Украина

Для цитирования: Oshlіanska OA, Okhotnikova OM, Usova OI, Gedeon IV. (2023). A case of early interferonopathy in a child using modern recommendations for their management. Modern Pediatrics. Ukraine. 6(134): 24-35. doi 10.15574/SP.2023.134.24.
Статья поступила в редакцию 11.07.2023 г., принята в печать 10.10.2023 г.

В статье изложены данные научной литературы относительно этиологии, патогенеза и клинических проявлений недавно выявленного заболевания — STING-ассоциированной васкулопатии (SAVI) с дебютом в детстве, которая является генетически-детерминированной интерферонопатией І типа, и клинически проявляется симптомокомплексом акральной ишемии (lupus-like chilblain), интерстициальным поражением легких и другой патологией внутренних органов. SAVI чаще манифестирует в первые месяцы жизни ребенка и протекает под масками различных автоиммунных и инфекционных болезней. В статье приведены данные о дифференцированном диагнозе SAVI, подчеркнута важность проведения генетического исследования для постановки диагноза. Учитывая редкость патологии, в статью включен перевод ACR-рекомендаций (2021) по лечению и наблюдению больных интерферонопатией. Статья иллюстрирована описанием собственного наблюдения ребенка с SAVI, диагностика которого проводилась по принципам, предложенных в данных рекомендациях. Описаны принципы дальнейшего наблюдения ребенка, подчеркнута необходимость мультидисциплинарного ведения пациентов с SAVI. Приведены современные данные по прогнозу и дальнейшему течению заболевания.
Наблюдение выполнено в соответствии с принципами Хельсинской декларации. На проведение наблюдений получено информированное согласие родителей ребенка.
Авторы заявляют об отсутствии конфликта интересов.
Ключевые слова: дети, интерферонопатия, случай SAVI, ведение.

ЛИТЕРАТУРА

1. Chia J, Eroglu F, Ozen S et al. (2016). Failure to thrive, interstitial lung disease, and progressive digital necrosis with onset in infancy. J Am Acad Dermatol. 74 (1): 186-189. https://doi.org/10.1016/j.jaad.2015.10.007; PMid:26584874 PMCid:PMC4691417

2. Clarke SL, Pellowe EJ, de Jesus AA et al. (2016). Interstitial lung disease caused by STING-associated vasculopathy with onset in infancy. Am J Respir Crit Care Med. 194 (5): 639-642. https://doi.org/10.1164/rccm.201510-2102LE; PMid:27585386 PMCid:PMC5027210

3. Clarke SLN, Robertson L, Rice G et al. (2020). Type 1 interferonopathy presenting as juvenile idiopathic arthritis with interstitial lung disease: report of a new phenotype. Pediatr Rheumatol Online J. 18 (1): 37. https://doi.org/10.1186/s12969-020-00425-w; PMid:32398023 PMCid:PMC7218611

4. Cooray S, Henderson R, Solebo A L, Ancliffe P, Eleftheriou D, Brogan PA. (2021). Retinal vasculopathy in STING-associated vasculitis of infancy (SAVI). Rheumatology (Oxford). 60: e351-353. https://doi.org/10.1093/rheumatology/keab297; PMid:33764368

5. Dai YF, Liu XY, Zhao ZP, He JX, Yin QQ. (2020). Stimulator of Interferon Genes-Associated Vasculopathy with Onset in Infancy: A Systematic Review of Case Reports. Front. Pediatr. 8: 577918. https://doi.org/10.3389/fped.2020.577918; PMid:33425809 PMCid:PMC7786402

6. De Greef A, Pierre G, Baeck M. (2022). Pandemic chilblains: Are they SARS-CoV-2-related or not? Clinical Immunology. 237: 108984. https://doi.org/10.1016/j.clim.2022.108984; PMid:35338000 PMCid:PMC8942450

7. De Jesus AА (ed). (2002). STING1 (NM_198282.4) sequence variants. URL: https://infevers.umai-montpellier.fr/web/search.php?n=24.

8. Du Y, Liu M, Nigrovic PA, Dedeoglu F, Lee PY. (2023, Mar). Biologics and JAK inhibitors for the treatment of monogenic systemic autoinflammatory diseases in children. J Allergy Clin Immunol. 151 (3): 607-618. Epub 2023 Jan 25. https://doi.org/10.1016/j.jaci.2022.12.816; PMid:36707349

9. Eleftheriou D et al. (2019). Genetic interpheronopathies. In: Hashkes Philip J, Laxer Ronald M, Simon Anna, editors. Textbook of autoinflammation. Cham Switzerland AG: Springer: 433-453.

10. Falcon S, Weinfurtner RJ, Mooney B, Niell BL. (2018). SAVI SCOUT® localization of breast lesions as a practical alternative to wires: Outcomes and suggestions for trouble-shooting. Clinical Imaging. 52: 280-286. https://doi.org/10.1016/j.clinimag.2018.07.008; PMid:30193186

11. Fremond ML, Hadchouel A, Berteloot L et al. (2021). Overview of STING-associated vasculopathy with onset in infancy (SAVI) among 21 patients. J Allergy Clin Immunol Pract. 9 (2): 803-818.e11.

12. Frémond ML, Rodero MP, Jeremiah N, Belot A, Jeziorski E, Duffy D et al. (2016). Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children. J Allergy Clin Immunol. 138: 1752-1755. https://doi.org/10.26226/morressier.57bc1755d462b80290b4d6b9; PMCid:PMC5325846

13. Ganeva M, Petrova G, Mihailova S et al. (2022). STING-associated vasculopathy with onset in infancy: the first case in Bulgaria and review of the literature, Biotechnology & Biotechnological Equipment. 36; 1: 773-781. https://www.tandfonline.com/loi/tbeq20. https://doi.org/10.1080/13102818.2022.2112909

14. Gedik KC, Lamot L, Romano M et al. (2022, May). The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology Points to Consider for Diagnosis and Management of Autoinflammatory Type I Interferonopathies: CANDLE/PRAAS, SAVI, and AGS. Arthritis & Rheumatology. 74; 5: 735-751. https://doi.org/10.1002/art.42087; PMid:35315249

15. Ishikawa T, Tamura E, Kasahara M, Uchida H, Higuchi M, Kobayashi H et al. (2021). Severe liver disorder following liver transplantation in STING-associated vasculopathy with onset in infancy. J Clin Immunol. 41: 967-974. https://doi.org/10.1007/s10875-021-00977-w; PMid:33544357

16. Jain A, Misra DP, Sharma A, Wakhlu A, Agarwal V, Negi VS. (2018). Vasculitis and vasculitis-like manifestations in monogenic autoinflammatory syndromes [review]. Rheumatol Int. 38: 13-24. https://doi.org/10.1007/s00296-017-3839-6; PMid:29032440

17. Jeremiah N, Neven B, Gentili M, Callebaut I, Maschalidi S, Stolzenberg MC et al. (2014). Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest. 124: 5516-5520. https://doi.org/10.1172/JCI79100; PMid:25401470 PMCid:PMC4348945

18. Kim H, Brooks KM, Tang CC, Wakim P, Blake M, Brooks SR et al. (2018). Pharmacokinetics, pharmacodynamics, and proposed dosing of the oral JAK1 and JAK2 inhibitor baricitinib in pediatric and young adult CANDLE and SAVI patients. Clin Pharmacol Ther. 104: 364-373. https://doi.org/10.1002/cpt.936; PMid:29134648 PMCid:PMC6089664

19. Kim H, de Jesus AA, Brooks SR et al. (2018). J Interferon Cytokine Res. 38: 171-185. https://doi.org/10.1089/jir.2017.0127; PMid:29638206 PMCid:PMC5963606

20. Kim H, de Jesus AA, Brooks SR, Liu Y, Huang Y, VanTries R et al. (2018). Development of a validated interferon score using NanoString technology. J Interferon Cytokine Res. 38: 171-185. https://doi.org/10.1089/jir.2017.0127; PMid:29638206 PMCid:PMC5963606

21. Konig N, Fiehn C, Wolf C et al. (2017). Familial chilblain lupus due to a gain-of-function mutation in STING. Ann Rheum Dis. 76 (2): 468-472. https://doi.org/10.1136/annrheumdis-2016-209841; PMid:27566796

22. Li J, An S, Du Z. (2020). Familial interstitial lung disease caused by mutation of the STING1 gene. Front Pediatr. 8: 543. https://doi.org/10.3389/fped.2020.00543; PMid:33014937 PMCid:PMC7505928

23. Lin B, Berard R, Al Rasheed A et al. (2020). A novel STING1 variant causes a recessive form of STING-associated vasculopathy with onset in infancy (SAVI). J Allergy Clin Immunol. 146: 1204-1208.e6. https://doi.org/10.1016/j.jaci.2020.06.032; PMid:32673614 PMCid:PMC8461559

24. Lin B, Berard R, Al Rasheed A, Aladba B, Kranzusch PJ, Henderlight M et al. (2020). A novel STING1 variant causes a recessive form of STING associated vasculopathy with onset in infancy (SAVI). J Allergy Clin Immunol. 146: 1204-1248. https://doi.org/10.1016/j.jaci.2020.06.032; PMid:32673614 PMCid:PMC8461559

25. Liu Y, Jesus AA, Marrero B et al. (2014). Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 371 (6): 507-518. https://doi.org/10.1056/NEJMoa1312625; PMid:25029335 PMCid:PMC4174543

26. Molaee H, Emadi SN, M Imunya JMN, Davoudi-Monfared E, Mohammed A, Razavi Z. (2022, Mar). Chilblain or perniosis-like skin lesions in children during the COVID-19 pandemic: A systematic review of articles. Dermatol Ther. 35 (3): e15298. Epub 2022 Jan 25. https://doi.org/10.1111/dth.15298; PMid:34981615

27. Munoz J, Rodiere M, Jeremiah N et al. (2015). Stimulator of interferon genes-associated vasculopathy with onset in infancy: a mimic of childhood granulomatosis with polyangiitis. JAMA Dermatol. 151 (8): 872-877. https://doi.org/10.1001/jamadermatol.2015.0251; PMid:25992765

28. Paparella R, Tarani L, Properzi E et al. (2022). Chilblain‑like lesions onset during SARS‑CoV‑2 infection in a COVID‑19‑vaccinated adolescent: case report and review of literature. Italian Journal of Pediatrics. 48: 93. https://doi.org/10.1186/s13052-022-01296-5; PMid:35698236 PMCid:PMC9190458

29. Picard C, Thouvenin G, Kannengiesser C, Dubus JC, Jeremiah N, Rieux-Laucat F et al. (2016). Severe pulmonary fibrosis as the first manifestation of Interferonopathy (TMEM173 mutation). Chest. 150: e65-71. https://doi.org/10.1016/j.chest.2016.02.682; PMid:27613991

30. Raffaele CGL, Messia V, Moneta G et al. (2020). A patient with stimulator of interferon genes-associated vasculopathy with onset in infancy without skin vasculopathy. Rheumatology (Oxford). 59 (4): 905-907. https://doi.org/10.1093/rheumatology/kez444; PMid:31598716

31. Runnblom L, Leonard D. (2019). Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Science & Medicine. 6: e000270. https://doi.org/10.1136/lupus-2018-000270; PMid:31497305 PMCid:PMC6703304

32. Saldanha RG, Balka KR, Davidson S et al. (2018). A mutation outside the dimerizati on domain causing atypical STING-associated vasculopathy with onset in infancy. Front Immunol. 9: 1535. https://doi.org/10.3389/fimmu.2018.01535; PMid:30038614 PMCid:PMC6047589

33. Sanchez GA, Reinhardt A, Ramsey S, Wittkowski H, Hashkes PJ, Berkun Y et al. (2018). JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest. 128: 3041-3052. https://doi.org/10.1172/JCI98814; PMid:29649002 PMCid:PMC6026004

34. Sawires R, Pearce C, Fahey M et al. (2022). COVID-toes: An ecological study of chilblains and COVID-19 diagnoses in Victoria, Australia. PLOS Glob Public Health. 2 (10): e0000488. https://doi.org/10.1371/journal.pgph.0000488; PMid:36962522 PMCid:PMC10022016

35. Sönmez HE, Karaaslan C, de Jesus AA, Batu ED, Anlar B, Sözeri B et al. (2020). A clinical score to guide in decision making for monogenic type IFNopathies. Pediatr Res. 87: 745-752. https://doi.org/10.1038/s41390-019-0614-2; PMid:31641281 PMCid:PMC8425764

36. Starkey SY, Mar K, Kashetsky N. (2022, Nov 18). Chilblain-like lesions coinciding with the SARS-CoV-2 pandemic. Clinics in Dermatology. 18: 33. https://doi.org/10.1016/j.clindermatol.2022.09.010; PMid:36228990 PMCid:PMC9551125

37. Tang X, Xu H, Zhou C, Peng Y, Liu H, Liu J et al. (2020). STING-associated vasculopathy with onset in infancy in three children with new clinical aspect and unsatisfactory therapeutic responses to tofacitinib. J Clin Immunol. 40: 114-122. https://doi.org/10.1007/s10875-019-00690-9; PMid:31705453

38. Tokgun PE, Karagenc N, Karasu Uğ. (2023). Treatment of STING-associated vasculopathy with onset in infancy in patients carrying a novel mutation in the TMEM173 gene with the JAK3-inhibitor tofacitinib. Arch Rheumatol. 38 (x): I-VII. https://doi.org/10.46497/ArchRheumatol.2023.9927; PMid:38046254 PMCid:PMC10689023

39. Torreggiani S, Alehashemi S, Mitchell J. (2020). Clinical Features and Outcomes in STING-Associated Vasculopathy with Onset in Infancy (SAVI) ACR Convergence. Abstrac1234567890Ct number: 1158. URL: https://acrabstracts.org/abstract/clinical-features-and-outcomes-in-sting-associated-vasculopathy-with-onset-in-infancy-savi/.

40. Vanderver A, Prust M, Kadom N, Demarest S, Crow YJ, Helman G et al. (2015). Early-onset Aicardi-Goutières syndrome: magnetic resonance imaging (MRI) pattern recognition. J Child Neurol. 30: 1343-1348. https://doi.org/10.1177/0883073814562252; PMid:25535058 PMCid:PMC4476968

41. Volpi S, Insalaco A, Caorsi R. (2019). Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome. Journal of Clinical Immunology. 39: 476-485. https://doi.org/10.1007/s10875-019-00645-0; PMid:31144250 PMCid:PMC7086512

42. Wang Y, Wang F, Zhang X. (2021). STING-associated vasculopathy with onset in infancy: a familial case series report and literature review. Ann Transl Med. 9 (2): 176. https://doi.org/10.21037/atm-20-6198; PMid:33569478 PMCid:PMC7867893