Novelties in the diagnosis and treatment of the most common systemic vasculitides in childhood
DOI:
https://doi.org/10.13112/pc.1075Keywords:
SYSTEMIC VASCULITIS; CHILD; IgA VASCULITIS; MUCOCUTANEOUS LYMPH NODE SYNDROME; TAKAYASU ARTERITIS; ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS; POLYARTERITIS NODOSAAbstract
Vasculitis is an inflammatory process that affects the blood vessel walls as the primary site of inflammation, which can lead to tissue damage due to vascular stenosis, occlusion, aneurysm, and/or rupture. The most common systemic vasculitis in children is IgA vasculitis (IgAV) and Kawasaki disease (KD). Gastrointestinal complications are the most common acute complications of IgAV, while kidney involvement (nephritis) is the most important chronic complication. The most important novelties in the field of IgAV relate to the follow-up of patients, whereby children at higher risk of developing nephritis are singled out. These are children with IgAV who have had severe gastrointestinal symptoms (severe abdominal pain, intussusception, hematochezia, and/or massive gastrointestinal bleeding), children with severe skin symptoms (ulcerations and necrosis, persistent purpura), male children and older children at the time of diagnosis of IgAV. Such children should be followed up for at least a year. According to the revised recommendations for the diagnosis of KD, it should be suspected in any child with unexplained fever lasting 4 or more days, with the presence of four or more criteria: bilateral conjunctival injection, changes in the oral cavity and lips, polymorphic rash, cervical lymphadenopathy, redness of the palms and soles, swelling of the hands and feet in the acute phase, and peeling of the skin around the nails in the later stages. According to the newer, revised recommendations, treatment of KD is not started equally in all patients, but those with a standard risk of developing coronary artery aneurysms should receive intravenous immunoglobulins and acetylsalicylic acid, and those with a high risk should receive additional anti-inflammatory therapy, i.e. systemic glucocorticoids or TNF-alpha blockers (infliximab or etanercept).
References
1. Eleftheriou D, Brogan PA. Vasculitis in children. Best Pract Res Clin Rheumatol. 2009;23(3):309-23. doi: 10.1016/j.berh.2008.12.003.
2. Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides: the proposal of an international consensus conference. Arthritis Rheum. 1994;37(2):187-92. doi: 10.1002/art.1780370206.
3. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11. doi: 10.1002/art.37715.
4. Ozen S, Pistorio A, Iusan SM, et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis, and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010;69(5):798-806. doi: 10.1136/ard.2009.116657.
5. Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR. Incidence of Henoch-Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet. 2002;360(9341):1197-202. doi: 10.1016/S0140-6736(02)11279-7.
6. Sapina M, Frkovic M, Sestan M, et al. Geospatial clustering of childhood IgA vasculitis and IgA vasculitis-associated nephritis. Ann Rheum Dis. 2021;80(5):610-6. doi: 10.1136/annrheumdis-2020-218877.
7. Jelusic M, Sestan M. IgA vasculitis or Henoch-Schönlein purpura: genetics and beyond. Pediatr Nephrol. 2021;36(7):2149-53. doi: 10.1007/s00467-020-04669-2.
8. Held M, Stingl Jankovic K, Sestan M, et al. HLA polymorphisms and clinical manifestations in IgA vasculitis. Int J Mol Sci. 2024;25(2):882. doi: 10.3390/ijms25020882.
9. Batnozic Varga M, Held M, Wagner J, et al. The association of HMGB1 and RAGE gene polymorphisms with IgA vasculitis. Biochem Genet. 2024;62(3):2268-78. doi: 10.1007/s10528-024-10419-2.
10. González LM, Janniger CK, Schwartz RA. Pediatric Henoch-Schönlein purpura. Int J Dermatol. 2009;48(11):1157-65. doi: 10.1111/j.1365-4632.2009.04138.x.
11. 11. Sestan M, Srsen S, Kifer N, et al. Persistence and severity of cutaneous manifestations in IgA vasculitis is associated with development of IgA vasculitis nephritis in children. Dermatology. 2022;238(2):340-6. doi: 10.1159/000517448.
12. Sestan M, Kifer N, Sozeri B, et al. Clinical features, treatment, and outcome of pediatric patients with severe cutaneous manifestations in IgA vasculitis: Multicenter international study. Semin Arthritis Rheum. 2023;61:152209. doi: 10.1016/j.semarthrit.2023.152209.
13. Jelusic M, Sestan M, Giani T, Cimaz R. New insights and challenges associated with IgA vasculitis and IgA vasculitis with nephritis—is it time to change the paradigm of the most common systemic vasculitis in childhood? Front Pediatr. 2022;10:853724. doi: 10.3389/fped.2022.853724.
14. Sestan M, Kifer N, Frkovic M, et al. Gastrointestinal involvement and its association with the risk for nephritis in IgA vasculitis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211024828. doi: 10.1177/1759720X211024828.
15. Oni L, Sampath S. Childhood IgA vasculitis (Henoch-Schönlein purpura)—advances and knowledge gaps. Front Pediatr. 2019;7:257. doi: 10.3389/fped.2019.00257.
16. Ozen S, Marks SD, Brogan P, et al. European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis—the SHARE initiative. Rheumatology (Oxford). 2019;58(9):1607-16. doi: 10.1093/rheumatology/kez041.
17. Kifer N, Bulimbasic S, Sestan M, et al. Semiquantitative classification (SQC) and Oxford classifications predict poor renal outcome better than the International Study of Kidney Disease in Children (ISKDC) and Haas in patients with IgAV nephritis: A multicenter study. J Nephrol. 2023;36(2):441-9. doi: 10.1007/s40620-023-01507-w.
18. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021.
19. Vivarelli M, Samuel S, Coppo R, et al. IPNA clinical practice recommendations for the diagnosis and management of children with IgA nephropathy and IgA vasculitis nephritis. Pediatr Nephrol. 2025;40(2):533-69. doi: 10.1007/s00467-024-06238-4.
20. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927-e999. doi: 10.1161/CIR.0000000000000484.
21. 21. Jone PN, Tremoulet A, Choueiter N, et al. Update on diagnosis and management of Kawasaki disease: A scientific statement from the American Heart Association. Circulation. 2024;150(23):e481-e500. doi: 10.1161/CIR.0000000000001191.
22. Ayusawa M, Sonobe T, Uemura S, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int. 2005;47(2):232-4. doi: 10.1111/j.1442-200X.2005.02033.x.
23. Kanegaye JT, Wilder MS, Molkara D, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics. 2009;123(5):e783-9. doi: 10.1542/peds.2008-1871.
24. Muise A, Tallett SE, Silverman ED. Are children with Kawasaki disease and prolonged fever at risk for macrophage activation syndrome? Pediatrics. 2003;112(6 Pt 1):e495. doi: 10.1542/peds.112.6.e495.
25. Ravelli A, Minoia F, Davì S, et al. 2016 classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation collaborative initiative. Arthritis Rheumatol. 2016;68(3):566-76. doi: 10.1002/art.39332.
26. de Graeff N, Groot N, Ozen S, et al. European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease—the SHARE initiative. Rheumatology (Oxford). 2019;58(4):672-82. doi: 10.1093/rheumatology/key339.
27. Henderson LA, Cron RQ. Macrophage activation syndrome and secondary hemophagocytic lymphohistiocytosis in childhood inflammatory disorders: Diagnosis and management. Paediatr Drugs. 2020;22(1):29-44. doi: 10.1007/s40272-019-00362-2.
28. Johnston SL, Lock RJ, Gompels MM. Takayasu arteritis: A review. J Clin Pathol. 2002;55(7):481-6. doi: 10.1136/jcp.55.7.481.
29. de Graeff N, Groot N, Brogan P, et al. European consensus-based recommendations for the diagnosis and treatment of rare paediatric vasculitides—the SHARE initiative. Rheumatology (Oxford). 2019;58(4):656-71. doi: 10.1093/rheumatology/key338.
30. Hellmich B, Agueda A, Monti S, et al. 2018 update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020;79(1):19-30. doi: 10.1136/annrheumdis-2019-215672.
31. 31. Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021;73(8):1349-65. doi: 10.1002/art.41772.
32. Jariwala MP, Laxer RM. Primary vasculitis in childhood: GPA and MPA in childhood. Front Pediatr. 2016;4:226. doi: 10.3389/fped.2016.00226.
33. Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024;83(1):30-47. doi: 10.1136/ard-2023-224301.
34. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res (Hoboken). 2021;73(8):1088-105. doi: 10.1002/acr.24634.
35. Kawakami T. A review of pediatric vasculitis with a focus on juvenile polyarteritis nodosa. Am J Clin Dermatol. 2012;13(6):389-98. doi: 10.2165/11633650-000000000-00000.
36. Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009;68(3):310-7. doi: 10.1136/ard.2008.088092.
37. Chung SA, Gorelik M, Langford CA, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of polyarteritis nodosa. Arthritis Care Res (Hoboken). 2021;73(8):1061-70. doi: 10.1002/acr.24633.
38. Liu Y, Jesus AA, Marrero B, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014;371(6):507-18. doi: 10.1056/NEJMoa1312625.
39. Navon Elkan P, Pierce SB, Segel R, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med. 2014;370(10):921-31. doi: 10.1056/NEJMoa1307362.
40. Zhou Q, Yang D, Ombrello AK, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 2014;370(10):911-20. doi: 10.1056/NEJMoa1307361.
41. Fremond ML, Rodero MP, Jeremiah N, et al. 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. 2016;138(6):1752-5. doi: 10.1016/j.jaci.2016.03.034.
42. Sanchez GAM, Reinhardt A, Ramsey S, et al. JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest. 2018;128(7):3041-52. doi: 10.1172/JCI98814.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Marija Jelušić, Mario Šestan, Marijan Frković
This work is licensed under a Creative Commons Attribution 4.0 International License.
By publishing in Paediatria Croatica, authors retain the copyright to their work and grant others the right to use, reproduce, and share their research articles in accordance with the Creative Commons Attribution License (CC BY 4.0), which allows others to distribute and build upon the work as long as they credit the author for the original creation.
