Enthesitis-related arthritis in children: A literature review of the clinical features and differential diagnosis

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Abstract

BACKGROUND: Enthesitis-related arthritis is one of the subtypes of juvenile idiopathic arthritis and is characterized by the involvement of the joints, enthesitis, and axial skeleton (sacroiliitis and spondylitis). The clinical variability of enthesitis-related arthritis and similar manifestations with orthopedic diseases present difficulties in diagnosis.

AIM: To present the clinical features of enthesitis-related arthritis and issues of differential diagnosis based on literature analysis.

MATERIALS AND METHODS: A literature search was conducted in the open electronic databases of eLibrary, PubMed, and Cochrane Library. In total, 46 foreign and 4 Russian publications were analyzed, which were limited to 1981–2021. The keywords used in the literature search were as follows: enthesitis, enthesitis-related arthritis, juvenile spondyloarthritis, and SAPHO syndrome. Own archive data for instrumental investigations were used in the article.

RESULTS: The clinical manifestations can be variable, and laboratory tests do not always allow us to prove the inflammatory nature of the pain syndrome. The most priority diagnostic tests were imaging methods, namely, magnetic resonance imaging and ultrasonography. The greatest diagnostic difficulty was found in patients in whom enthesitis prevailed over arthritis, and in some cases, it was the only disease manifestation. The classification criteria used for the diagnosis of EAA were considered. The differential diagnosis of enthesitis included various orthopedic diseases. Ultrasound diagnostics of joints and enthesis should be performed in every patient with local pain musculoskeletal symptoms, which allows patients to be correctly routed.

CONCLUSIONS: The alertness of both orthopedists in relation to enthesitis-related arthritis and the awareness of rheumatologists of the most common orthopedic diseases that affect the entheses are necessary.

About the authors

Rinat K. Raupov

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery; Saint Petersburg State Pediatric Medical University

Email: rinatraup94@gmail.com
ORCID iD: 0000-0001-7749-6663
SPIN-code: 2449-0294
Scopus Author ID: 57210883716

MD, Rheumatologist

Russian Federation, Saint Petersburg; Saint Petersburg

Sergei V. Vissarionov

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: vissarionovs@gmail.com
ORCID iD: 0000-0003-4235-5048
SPIN-code: 7125-4930
Scopus Author ID: 6504128319
ResearcherId: P-8596-2015

MD, PhD, Dr. Sci. (Med.), Professor, Corresponding Member of RAS

Russian Federation, Saint Petersburg

Gumru A. Babaeva

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: gumru@yandex.ru
ORCID iD: 0000-0002-9742-9377

MD, Sonographer

Russian Federation, Saint Petersburg

Yulia G. Noyanova

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: julja1973@mail.ru
ORCID iD: 0000-0002-0533-0151

MD, PhD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Lubov S. Sorokina

Saint Petersburg State Pediatric Medical University

Email: lubov.s.sorokina@gmail.com
ORCID iD: 0000-0002-9710-9277
SPIN-code: 4088-4272
Scopus Author ID: 57217358279

Assistant Lecturer

Russian Federation, Saint Petersburg

Mikhail M. Kostik

Saint Petersburg State Pediatric Medical University

Author for correspondence.
Email: kost-mikhail@yandex.ru
ORCID iD: 0000-0002-1180-8086
SPIN-code: 7257-0795
Scopus Author ID: 36945624400

MD, PhD, Dr. Sci. (Med.), Assistant Professor

Russian Federation, Saint Petersburg

References

  1. Villotte S, Knüsel CJ. Understanding entheseal changes: definition and life course changes. Int J Osteoarchaeology. 2012;23(2):135–146. doi: 10.1002/oa.2289
  2. Textbook of pediatric rheumatology. Ed. by R.E. Petty, R.M. Laxer, C.B. Lindsley et al. Philadelphia: Elsevier; 2015.
  3. Benjamin M, McGonagle D. The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites. J Anat. 2001;199:503–526. doi: 10.1046/j.1469-7580.2001.19950503.x
  4. Cormick W. Enthesopathy – a personal perspective on its manifestations, implications and treatment. Australas J Ultrasound Med. 2010;13(4):19–23. doi: 10.1002/j.2205-0140.2010.tb00174.x
  5. Benjamin M, Moriggl B, Brenner E, et al. The “enthesis organ” concept: why enthesopathies may not present as focal insertional disorders. Arthritis Rheum. 2004;50(10):3306–3313. doi: 10.1002/art.20566
  6. Kehl AS, Corr M, Weisman MH. Review: Enthesitis: new insights into pathogenesis, diagnostic modalities, and treatment. Arthritis Rheumatol. 2016;68(2):312–322. doi: 10.1002/art.39458
  7. Russell T, Bridgewood C, Rowe H, et al. Cytokine “fine tuning” of enthesis tissue homeostasis as a pointer to spondyloarthritis pathogenesis with a focus on relevant TNF and IL-17 targeted therapies. Semin Immunopathol. 2021;43(2):193–206. doi: 10.1007/s00281-021-00836-1
  8. Millar NL, Hueber AJ, Reilly JH, et al. Inflammation is present in early human tendinopathy. Am J Sports Med. 2010;38(10):2085–2091. doi: 10.1177/0363546510372613
  9. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–392.
  10. Sudoł-Szopińska I, Eshed I, Jans L, et al. Classifications and imaging of juvenile spondyloarthritis. J Ultrason. 2018;18(74):224–233. doi: 10.15557/JoU.2018.0033
  11. Rumsey DG, Laxer RM. The challenges and opportunities of classifying childhood arthritis. Curr Rheumatol Rep. 2020;22(1). doi: 10.1007/s11926-020-0880-3
  12. Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for non-systemic polyarthritis, sacroiliitis, and enthesitis. Arthritis Care Res (Hoboken). 2019;71(6):717–734. doi: 10.1002/acr.23870
  13. Ramanathan A, Srinivasalu H, Colbert RA. Update on juvenile spondyloarthritis. Rheum Dis Clin North Am. 2013;39(4):767–788. doi: 10.1016/j.rdc.2013.06.002
  14. Chen HA, Chen CH, Liao HT, et al. Clinical, functional, and radiographic differences among juvenile-onset, adult-onset, and late-onset ankylosing spondylitis. J Rheumatol. 2012;39(5):1013–1018. doi: 10.3899/jrheum.111031
  15. Stoll ML, Bhore R, Dempsey-Robertson M, et al. Spondyloarthritis in a pediatric population: risk factors for sacroiliitis. J Rheumatol. 2010;37(11):2402–2408. doi: 10.3899/jrheum.100014
  16. Weiss PF, Xiao R, Biko DM, et al. Assessment of sacroiliitis at diagnosis of juvenile spondyloarthritis by radiography, magnetic resonance imaging, and clinical examination. Arthritis Care Res (Hoboken). 2016;68(2):187–194. doi: 10.1002/acr.22665
  17. Sorokina LS, Avrusin IS, Raupov RK, et al. Hip Involvement in juvenile idiopathic arthritis: a roadmap from arthritis to total hip arthroplasty or how can we prevent hip damage? Front Pediatr. 2021;9. doi: 10.3389/fped.2021.747779
  18. Martini A. It is time to rethink juvenile idiopathic arthritis classification and nomenclature. Ann Rheum Dis. 2012;71(9):1437–1439. doi: 10.1136/annrheumdis-2012-201388
  19. Walscheid K, Glandorf K, Rothaus K, et al. Enthesitis-related arthritis: prevalence and complications of associated uveitis in children and adolescents from a population-based nationwide study in Germany. J Rheumatol. 2021;48(2):262–269. doi: 10.3899/jrheum.191085
  20. Gandjbakhch F, Terslev L, Joshua F, et al. Ultrasound in the evaluation of enthesitis: status and perspectives. Arthritis Res Ther. 2011;13(6). doi: 10.1186/ar3516
  21. Balint PV, Kane D, Wilson H, et al. Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy. Ann Rheum Dis. 2002,61,905–910.
  22. Eder L, Jayakar J, Thavaneswaran A, et al. Is the MAdrid Sonographic Enthesitis Index useful for differentiating psoriatic arthritis from psoriasis alone and healthy controls? J Rheumatol. 2014;41(3):466–472. doi: 10.3899/jrheum.130949
  23. Akhadov TA, Mitish VA, Bozhko OV, et al. Possibilities of magnetic resonance imaging in the diagnosis of acute aseptic sacroilitis in children. Diagnostic radiology and radiotherapy. 2022;13(2):72–80. (In Russ.). doi: 10.22328/2079-5343-2022-13-2-72-80
  24. Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68(6):777–783. doi: 10.1136/ard.2009.108233
  25. Herregods N, Dehoorne J, Van den Bosch F, et al. ASAS definition for sacroiliitis on MRI in SpA: applicable to children? Pediatr Rheumatol Online J. 2017;15(1). doi: 10.1186/s12969-017-0159-z
  26. Greer MC. Whole-body magnetic resonance imaging: techniques and non-oncologic indications. Pediatr Radiol. 2018;48(9):1348–1363. doi: 10.1007/s00247-018-4141-9
  27. Cheng W, Li F, Tian J, et al. New Insights in the Treatment of SAPHO syndrome and medication recommendations. J Inflamm Res. 2022;15:2365–2380. doi: 10.2147/JIR.S353539
  28. Nguyen MT, Borchers A, Selmi C, et al. The SAPHO syndrome. Semin Arthritis Rheum. 2012;42(3):254–265. doi: 10.1016/j.semarthrit.2012.05.006
  29. Aljuhani F, Tournadre A, Tatar Z, et al. The SAPHO syndrome: a single-center study of 41 adult patients. J Rheumatol. 2015;42(2):329–334. doi: 10.3899/jrheum.140342
  30. Sonozaki H, Mitsui H, Miyanaga Y, et al. Clinical features of 53 cases with pustulotic arthro-osteitis. Ann Rheum Dis. 1981;40(6):547–553. doi: 10.1136/ard.40.6.547
  31. Earwaker JW, Cotten A. SAPHO: syndrome or concept? Imaging findings. Skeletal Radiol. 2003;32(6):311–327. doi: 10.1007/s00256-003-0629-x
  32. Cotten A, Flipo RM, Mentre A, et al. SAPHO syndrome. Radiographics. 1995;15(5):1147–1154. doi: 10.1148/radiographics.15.5.7501856
  33. Depasquale R, Kumar N, Lalam RK, et al. SAPHO: What radiologists should know. Clin Radiol. 2012;67(3):195–206. doi: 10.1016/j.crad.2011.08.014
  34. Laredo JD, Vuillemin-Bodaghi V, Boutry N, et al. SAPHO syndrome: MR appearance of vertebral involvement. Radiology. 2007;242(3):825–831. doi: 10.1148/radiol.2423051222
  35. Toussirot E, Dupond JL, Wendling D. Spondylodiscitis in SAPHO syndrome. A series of eight cases. Ann Rheum Dis. 1997;56(1):52–58. doi: 10.1136/ard.56.1.52
  36. Egiazaryan KA, Grigoriev AV, Ratyev AP. Etiology, pathogenesis, diagnosis and principles of treatment of slipped capital femoral epiphysis. Literature review. Surgical practice. 2022;(1):38–46. (In Russ.). doi: 10.38181/2223-2427-2022-1-38-46
  37. Kamosko MM, Poznovich MS. Radiological diagnosis of hip joint abnormalities in children. Pediatric Traumatology, Orthopaedics and Reconstructive Surgery. 2015;3(2):32–41. (In Russ.). doi: 10.17816/PTORS3232-41
  38. Amarnath C, Muthaiyan P, Mary TH, et al. Idiopathic chondrolysis of hip in children: New proposal and implication for radiological staging. Indian J Radiol Imaging. 2018;28(2):205–213. doi: 10.4103/ijri.IJRI_185_17
  39. Krutikova NYu, Vinogradova AG. Legg–Calve–Perthes disease. Current Pediatrics. 2015;14(5):548–552. (In Russ.). doi: 10.15690/vsp.v14i5.1437
  40. Valentino M, Quiligotti C, Ruggirello M. Sinding-Larsen-Johansson syndrome: a case report. J Ultrasound. 2012;15(2):127–129. doi: 10.1016/j.jus.2012.03.001
  41. Gudi SM, Luchshev MD, Kuznetsov VV, et al. Freiberg-Köhler disease: clinical manifestations, diagnostics, and treatment (literature review). Genij Ortopedii. 2022;28(3):431–443. (In Russ.). doi: 10.18019/1028-4427-2022-28-3-431-443
  42. Borges JL, Guille JT, Bowen JR. Köhler’s bone disease of the tarsal navicular. J Pediatr Orthop. 1995;15(5):596–598. doi: 10.1097/01241398-199509000-00009
  43. Baindurashvili AG, Sergeev SV, Petrov AG, et al. Clinical presentation tool osteochondritis dissecans knee in children. Vestnik Chuvashskogo universiteta. 2013;(3):370–375. (In Russ.).
  44. Gulati A, McElrath C, Wadhwa V, et al. Current clinical, radiological and treatment perspectives of patellofemoral pain syndrome. Br J Radiol. 2018;91(1086). doi: 10.1259/bjr.20170456
  45. De Sanctis V, Abbasciano V, Soliman AT, et al. The juvenile fibromyalgia syndrome (JFMS): a poorly defined disorder. Acta Biomed. 2019;90(1):134–148. doi: 10.23750/abm.v90i1.8141
  46. Yunus MB, Masi AT, Aldag JC. Preliminary criteria for primary fibromyalgia syndrome (PFS): multivariate analysis of a consecutive series of PFS, other pain patients, and normal subjects. Clin Exp Rheumatol. 1989;7(1):63–69.
  47. Mistry RR, Patro P, Agarwal V, et al. Enthesitis-related arthritis: current perspectives. Open Access Rheumatol. 2019;11:19–31. doi: 10.2147/OARRR.S163677
  48. Shipa MR, Heyer N, Mansoor R, et al. Adalimumab or etanercept as first line biologic therapy in enthesitis related arthritis (ERA) – a drug-survival single centre study spanning 10 years. Semin Arthritis Rheum. 2022;55. doi: 10.1016/j.semarthrit.2022.152038
  49. Brunner HI, Foeldvari I, Alexeeva E, et al. Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial. Ann Rheum Dis. 2022. doi: 10.1136/ard-2022-222849
  50. Noureldin B, Barkham N. The current standard of care and the unmet needs for axial spondyloarthritis. Rheumatology (Oxford). 2018;57:vi10-vi17. doi: 10.1093/rheumatology/key217

Supplementary files

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1. JATS XML
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2. Fig. 1. Histological presentation of enthesis [4]

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3. Fig. 2. Localization of enthesis points [2]

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4. Fig. 3. Enthesopathy of the tendon of the triceps brachii muscle and increased vascular pattern in the color Doppler mapping mode (a); cartilage changes in the enthesis site (joint in the Fig. a with enlargement) in the gray-scale mode, unclear contours with sites of bone tissue remodeling (indicated by an arrow) (b); ultrasound presentation of the unchanged elbow joint (c); and enthesitis with severe hypervascularization of the tendon of the triceps brachii (d, e)

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5. Fig. 4. Distal enthesis of the quadriceps femoris and signs of hypervascularization (a); proximal enthesis of the infrapatellar ligament (signs of moderate hypervascularization and thickening of the ligament) (b); quadriceps enthesis in the MFI mode (high-resolution energy mode) (c); ultrasound presentation of enthesis in the B-mode (d); and signs of enthesitis of the Achilles tendon in the B-mode with changes in the contour of the calcaneus and structural changes in the tendon (e)

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6. Fig. 5. Vertebral spondylodiscitis and sacroiliitis in a 9-year-old girl with enthesitis-related arthritis (magnetic resonance imaging, changes are indicated with arrows)

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7. Fig. 6. Severe acne lesions in a patient with SAPHO syndrome

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8. Fig. 7. Pain points in fibromyalgia [45]

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Copyright (c) 2023 Raupov R.K., Vissarionov S.V., Babaeva G.A., Noyanova Y.G., Sorokina L.S., Kostik M.M.

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