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International Journal of Cell Biology and Cellular Functions Review Article

Exploring the Pathophysiology of Henoch-Schönlein Purpura (HSP): A Comprehensive Review

  1. Himanshu Jain Department of Pharmaceutical Sciences, University Institute of pharmaceutical sciences and research, Baba Farid University of Health sciences
  2. Kuljeet Kaur Department of Pharmaceutical Sciences, University Institute of pharmaceutical sciences and research, Baba Farid University of Health sciences

Abstract

Blood from tiny veins can leak into nearby tissues, causing purpura, a disorder marked by red spots or patches on the skin that may have an impact on the kidneys. Henoch-Schönlein purpura (HSP) is associated with vasculitis and inflammation of blood vessels. The range of renal conditions associated with purpura includes severe glomerulonephritis and mild proteinuria. For instance, immunological complex accumulation in the renal glomeruli of HSP patients might result in inflammation and renal injury. The pathophysiology of HSP is largely dependent on immunological pathways, including complement activation and immune complex deposition. Effective management of these renal symptoms depends on rapid identification and action. In addition to skin discoloration and renal involvement, purpura may present with other symptoms, including fatigue, joint pain, and mucosal bleeding. Though the precise etiology of HSP is unknown, it is thought to be related to an unbalanced immune system reaction that may be brought on by an infection or other circumstances. Treatment strategies depend on the underlying cause and may involve immunosuppressive therapy, plasmapheresis, or supportive care. For the most effective treatment for patients with HSP, a multidisciplinary strategy comprising gastroenterologists, nephrologists, and rheumatologists is recommended. Supportive treatment for gastrointestinal and renal disorders may include fluid replacement, pain relief, and, in certain situations, immunosuppressive medication. A long-term follow-up is necessary to evaluate renal function and keep an eye out for disease recurrence. This study aims to give a thorough overview of HSP, including information on its pathophysiology, diagnosis, possibilities for treatment, and clinical signs and symptoms.

Keywords

References (77)

  1. Jaszczura M, Dyga K, Bryłka A, Góra A, Machura E. IgA vasculitis, formerly known as Henoch-Schönlein purpura – the most common vasculitis in children. Pediatria Polska. 2018;93(4):336-342. doi:10.5114/polp.2018.78000
  2. Trnka PH. Henoch-Schönlein purpura in children. J Paediatr Child Health. 2013;49:995–1003. doi:10.1111/jpc.12403.
  3. Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, Van Egmond M. New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura). Autoimmunity Reviews. 2017;16(12):1246-1253. doi:10.1016/j.autrev.2017.10.009
  4. Trapani S, Micheli A, Grisolia F, Resti M, Chiappini E, Falcini F, et al. Henoch Schonlein Purpura in Childhood: Epidemiological and Clinical Analysis of 150 Cases Over a 5-year Period and Review of Literature. Seminars in Arthritis and Rheumatism. 2005;35(3):143-153. doi:10.1016/j.semarthrit.2005.08.007
  5. Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR. Incidence of Henoch-Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. The Lancet. 2002;360(9341):1197-1202. doi:10.1016/s0140-6736(02)11279-7
  6. CALVIÑO MC, LLORCA J, GARCÍA-PORRÚA C, FERNÁNDEZ-IGLESIAS JL, RODRIGUEZ-LEDO P, GONZÁLEZ-GAY MA. Henoch-Schönlein Purpura in Children from Northwestern Spain. Medicine. 2001;80(5):279-290. doi:10.1097/00005792-200109000-00001
  7. Watson L, Richardson ARW, Holt RCL, Jones CA, Beresford MW. Henoch Schonlein Purpura – A 5-Year Review and Proposed Pathway. PLOS ONE. 2012;7. doi:10.1371/journal.pone.002
  8. Tizard EJ. Henoch-Schönlein purpura. Arch Dis Child. 1999;80:380–3. doi:10.1136/adc.80.4.
  9. Prais D, Amir J, Nussinovitch M. Recurrent Henoch-Schönlein Purpura in Children. JCR: Journal of Clinical Rheumatology. 2007;13(1):25-28. doi:10.1097/01.rhu.0000255692.46165.19
  10. Calvo-Río V, Hernández JL, Ortiz-Sanjuán F, Loricera J, Palmou-Fontana N, González-Vela MC, et al. Relapses in patients with Henoch–Schönlein purpura. Medicine. 2016;95(28):e4217. doi:10.1097/md.0000000000004217
  11. Lei WT, Tsai PL, Chu SH, Kao YH, Lin CY, Fang LC, et al. Incidence and risk factors for recurrent Henoch-Schönlein purpura in children from a 16-year nationwide database. Pediatric Rheumatology. 2018;16(1). doi:10.1186/s12969-018-0247-8
  12. Piram M, Mahr A. Epidemiology of immunoglobulin A vasculitis (Henoch–Schönlein): Current state of knowledge. Curr Opin Rheumatol. 2013;25:171–8. doi:10.1097/BOR.0b013e32835d
  13. Saulsbury FT. Henoch–Schönlein purpura. Current Opinion in Rheumatology. 2010;22(5):598-602. doi:10.1097/bor.0b013e32833af608
  14. Butt G, Anees M, Rana M. Frequency of renal manifestations in patients of Henoch-Schonlein purpura. J Pak Assoc Dermatol. 2021;31:146–52.
  15. Hetland L, Susrud K, Lindahl K, Bygum A. Henoch-Schönlein Purpura: A Literature Review. Acta Dermato Venereologica. 2017;97(10):1160-1166. doi:10.2340/00015555-2733
  16. Sag E, Arici ZS, Ozen S. IgA vasculitis (Henoch–Schönlein purpura) in children. Expert Opinion on Orphan Drugs. 2017;5(5):405-410. doi:10.1080/21678707.2017.1311783
  17. Abbas S, S. G, R.V. D, Kamar J, Uthup S. Clinical profile and outcome of Henoch Schonlein purpura in a tertiary care hospital in South India. International Journal of Contemporary Pediatrics. 2017;4(3):822. doi:10.18203/2349-3291.ijcp20171493
  18. Ozen S, Marks SD, Brogan P, Groot N, de Graeff N, Avcin T, et al. European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis—the SHARE initiative. Rheumatology. 2019;58(9):1607-1616. doi:10.1093/rheumatology/kez041
  19. Audemard-Verger A, Pillebout E, Guillevin L, Thervet E, Terrier B. IgA vasculitis (Henoch–Shönlein purpura) in adults: Diagnostic and therapeutic aspects. Autoimmunity Reviews. 2015;14(7):579-585. doi:10.1016/j.autrev.2015.02.003
  20. Calvo-Río V, Loricera J, Mata C, Martín L, Ortiz-Sanjuán F, Alvarez L, et al. Henoch-Schönlein Purpura in Northern Spain. Medicine. 2014;93(2):106-113. doi:10.1097/md.0000000000000019
  21. Alharthi AA. Henoch-Schonlein purpura in Saudi Arabia: A retrospective study of 27 children in Taif region. Curr Pediatr Res. 2016;20:126–31.
  22. Watson L, Richardson ARW, Holt RCL, Jones CA, Beresford MW. Henoch Schonlein Purpura – A 5-Year Review and Proposed Pathway. PLoS ONE. 2012;7(1):e29512. doi:10.1371/journal.pone.0029512
  23. Zhao YL, Liu ZJ, Bai XM, Wang YC, Li GH, Yan XY. Obesity increases the risk of renal involvement in children with Henoch–Schönlein purpura. European Journal of Pediatrics. 2015;174(10):1357-1363. doi:10.1007/s00431-015-2547-z
  24. Narchi H. Risk of long term renal impairment and duration of follow up recommended for Henoch-Schonlein purpura with normal or minimal urinary findings: a systematic review. Archives of Disease in Childhood. 2005;90(9):916-920. doi:10.1136/adc.2005.074641
  25. Modi S, Mohan M, Jennings A. Acute Scrotal Swelling in Henoch-Schonlein Purpura: Case Report and Review of the Literature. Urology Case Reports. 2016;6:9-11. doi:10.1016/j.eucr.2016.01.004
  26. dos Santos D, Langer FW, dos Santos T, Rafael Tronco Alves G, Feiten M, Teixeira de Paula Neto W. Posterior reversible encephalopathy syndrome as a complication of Henoch–Schönlein purpura in a seven-year-old girl. Scottish Medical Journal. 2017;62(1):34-37. doi:10.1177/0036933017690467
  27. Hwang JJ, Ahn J, Kim KP, Choi HI, Choi JY, Song R, et al. Henoch-Schönlein purpura with muscle involvement, presenting as myositis. J Clin Rheumatol. 2017;23:60–2. doi:10.1097/RHU.
  28. 0000000000000476. PubMed: 28002161.
  29. Michas G, Grigoriou K, Syrigos D, Alexopoulos N, Evdoridis C, Trikas A. A rare cause of myocarditis resulting in acute heart failure in the setting of Henoch–Schönlein purpura. Hellenic Journal of Cardiology. 2017;58(6):439-442. doi:10.1016/j.hjc.2017.05.002
  30. Woof JM, Kerr MA. The function of immunoglobulin A in immunity. J Pathol. 2006;208:270–82. doi:10.1002/path.1855. PubMed: 16961578.
  31. Crago SS, Kutteh WH, Moro I, Allansmith MR, Radl J, Haaijman JJ, et al. Distribution of IgA1-, IgA2-, and J chain-containing cells in human tissues. The Journal of Immunology. 1984;132(1):16-18. doi:10.4049/jimmunol.132.1.16
  32. Roos A, Bouwman LH, van Gijlswijk-Janssen DLJ, Faber-Krol MC, Stahl GL, Daha MR. Human IgA Activates the Complement System Via the Mannan-Binding Lectin Pathway. The Journal of Immunology. 2001;167(5):2861-2868. doi:10.4049/jimmunol.167.5.2861
  33. Hiemstra PS, Gorter A, Stuurman ME, Van Es LA, Daha MR. Activation of the alternative pathway of complement by human serum IgA. Eur J Immunol. 1987;17:321–6. doi:10.1002/eji.1830170
  34. PubMed: 3569402.
  35. Aleyd E, Heineke MH, van Egmond M. The era of the immunoglobulin A Fc receptor FcαRI: its function and potential as target in disease. Immunol Rev. 2015;268:123–38. doi:10.1111/imr.
  36. Blank U, Launay P, Benhamou M, Monteiro RC. Inhibitory ITAMs as novel regulators of immunity. Immunological Reviews. 2009;232(1):59-71. doi:10.1111/j.1600-065x.2009.00832.x
  37. Pasquier B, Launay P, Kanamaru Y, Moura IC, Pfirsch S, Ruffié C, Hénin D, Benhamou M, Pretolani M, Blank U, Monteiro RC. Identification of FcαRI as an inhibitory receptor that controls inflammation: dual role of FcRγ ITAM. Immunity. 2005;22:31–42. doi:10.1016/j.immuni.2004.
  38. 017. PubMed: 15664157.
  39. Ben Mkaddem S, Rossato E, Heming N, Monteiro RC. Anti-inflammatory role of the IgA Fc receptor (CD89): From autoimmunity to therapeutic perspectives. Autoimmunity Reviews. 2013;12(6):666-669. doi:10.1016/j.autrev.2012.10.011
  40. Heineke MH, van Egmond M. Immunoglobulin A: magic bullet or Trojan horse? European Journal of Clinical Investigation. 2017;47(2):184-192. doi:10.1111/eci.12716
  41. Aleyd E, van Hout MWM, Ganzevles SH, Hoeben KA, Everts V, Bakema JE, et al. IgA Enhances NETosis and Release of Neutrophil Extracellular Traps by Polymorphonuclear Cells via Fcα Receptor I. The Journal of Immunology. 2014;192(5):2374-2383. doi:10.4049/jimmunol.1300261
  42. van der Steen LP, Bakema JE, Sesarman A, Florea F, Tuk CW, Kirtschig G, et al. Blocking Fcα Receptor I on Granulocytes Prevents Tissue Damage Induced by IgA Autoantibodies. The Journal of Immunology. 2012;189(4):1594-1601. doi:10.4049/jimmunol.1101763
  43. Jennewein MF, Alter G. The Immunoregulatory Roles of Antibody Glycosylation. Trends in Immunology. 2017;38(5):358-372. doi:10.1016/j.it.2017.02.004
  44. Launay P, Grossetête B, Arcos-Fajardo M, Gaudin E, Torres SP, Beaudoin L, et al. Fcα Receptor (Cd89) Mediates the Development of Immunoglobulin a (Iga) Nephropathy (Berger's Disease). The Journal of Experimental Medicine. 1999;191(11):1999-2010. doi:10.1084/jem.191.11.1999
  45. Tissandié E, Morelle W, Berthelot L, Vrtovsnik F, Daugas E, Walker F, et al. Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1 and soluble CD89–IgA and IgG–IgA complexes: common mechanisms for distinct diseases. Kidney International. 2011;80(12):1352-1363. doi:10.1038/ki.2011.276
  46. Vuong MT, Hahn-Zoric M, Lundberg S, Gunnarsson I, van Kooten C, Wramner L, et al. Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy. Kidney International. 2010;78(12):1281-1287. doi:10.1038/ki.2010.314
  47. Wilkinson A. Early recognition and treatment of Henoch-Schönlein purpura in children. Nursing Children and Young People. 2019;31(5):36-40. doi:10.7748/ncyp.2019.e1118
  48. Watanabe T. Henoch-Schönlein purpura following influenza vaccinations during the pandemic of influenza A (H1N1). Pediatric Nephrology. 2010;26(5):795-798. doi:10.1007/s00467-010-1722-8
  49. Jariwala S, Vernon N, Shliozberg J. Henoch-Schönlein purpura after hepatitis A vaccination. Annals of Allergy, Asthma & Immunology. 2011;107(2):180-181. doi:10.1016/j.anai.2011.05.006
  50. Mitsui H, Shibagaki N, Kawamura T, Matsue H, Shimada S. A clinical study of Henoch‐Schönlein Purpura associated with malignancy. Journal of the European Academy of Dermatology and Venereology. 2009;23(4):394-401. doi:10.1111/j.1468-3083.2008.03065.x
  51. Blanco R, González-Gay MA, Ibáñez D, Alba C, Pérez de Llano LA. Henoch-Schönlein purpura as a clinical presentation of small cell lung cancer. Clin Exp Rheumatol. 1997;15:545–7.
  52. Angelier AS, Petit L, Wynckel A, Vuiblet V, Birembaut P, Toubas O, et al. Schoenlein-Henoch purpura as a presentation of squamous cell bronchial carcinoma. Rev Mal Respir. 2011;28:372–6. doi:10.1016/j.rmr.2010.09.033. PubMed: 21482344.
  53. Nozato K, Morishima Y, Furuta J, Fujita J, Miyazaki K, Ogawa R, et al. A case of Henoch-Schönlein purpura which was difficult to distinguish from a skin rash associated with gefitinib. Nihon Kokyuki Gakkai Zasshi. 2010;48:529–34.
  54. Maritati F, Canzian A, Fenaroli P, Vaglio A. Adult-onset IgA vasculitis (Henoch-Schönlein): Update on therapy. La Presse Médicale. 2020;49(3):104035. doi:10.1016/j.lpm.2020.104035
  55. Kango SC, Palet JE, Bognin OB, Ouaimon D, Houndjahoue GF. Diagnostic difficulties in a case of Henoch-Schönlein purpura at the pediatric University Hospital complex of Bangui. J Med Case Rep Case Series. 2022;3:19.
  56. Yang YH, Huang YH, Lin YL, Wang LC, Chuang YH, Yu HH, et al. Circulating IgA from acute stage of childhood Henoch-Schönlein purpura can enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling pathway. Clinical and Experimental Immunology. 2006;144(2):247-253. doi:10.1111/j.1365-2249.2006.03076.x
  57. Demir S, Candan C, Turhan P, Ergüven M. Henoch Schönlein Purpura / Ig A Vasculitis in Children and Risk Factors for Renal Involvement. Acta Medica. 2021;52:230–38. doi:10.32552/2021.
  58. ActaMedica.585.
  59. Szemenyei C, Hahn D. Prevention of nephritis in Henoch-Schönlein purpura. J Paediatr Child Health. 2015;51:236–39. doi:10.1111/jpc.12785. PubMed: 25677491.
  60. Bogdanović R. Henoch‐Schönlein purpura nephritis in children: risk factors, prevention and treatment. Acta Paediatrica. 2009;98(12):1882-1889. doi:10.1111/j.1651-2227.2009.01445.x
  61. Atkinson SR, Barker DJ. Seasonal distribution of Henoch-Schonlein purpura. Journal of Epidemiology & Community Health. 1976;30(1):22-25. doi:10.1136/jech.30.1.22
  62. Reamy BV, Servey JT, Williams PM. Henoch-Schönlein purpura (IgA Vasculitis): Rapid Evidence Review [IgA vasculitis]. Am Fam Physician. 2020;102:229–33. PubMed: 32803924.
  63. Lee DH, LEE ES, Hong J, Park KH, Pai KS. A Case of Henoch-Schönlein Purpura with Fulminant Complications and Its Long-term Outcome. Childhood Kidney Diseases. 2019;23(2):128-133. doi:10.3339/jkspn.2019.23.2.128
  64. Chan H, Tang YL, Lv XH, Zhang GF, Wang M, Yang HP, et al. Risk Factors Associated with Renal Involvement in Childhood Henoch-Schönlein Purpura: A Meta-Analysis. PLOS ONE. 2016;11(11):e0167346. doi:10.1371/journal.pone.0167346
  65. Gaia MJ, Capela M, Borges JP, Marques E, Ferreira G, Vinhas da Silva A. Purpura HS. What to expect. Port J Nephrol Hypert, Lisboa. 2019;33:212–16.
  66. Jelusic M, Sestan M, Cimaz R, Ozen S. Different histological classifications for Henoch-Schönlein purpura nephritis: which one should be used? Pediatric Rheumatology. 2019;17(1). doi:10.1186/s12969-019-0311-z
  67. Liao CH, Tsai M, Yang YH, Chiang BL, Wang LC. Onset age is a risk factor for refractory pediatric IgA vasculitis: a retrospective cohort study. Pediatric Rheumatology. 2020;18(1). doi:10.1186/s12969-020-00480-3
  68. Wang X, Zhu Y, Gao L, Wei S, Zhen Y, Ma Q. Henoch-Schönlein purpura with joint involvement: Analysis of 71 cases. Pediatr Rheumatol. 2016;14:1–8.
  69. Dawood SA, Abodiah AM, Alqahtani SM, Shati AA, Alqahtani YA, Alshehri MA, Mahmood SE. Clinico-epidemiological profile and outcome of children with IgA vasculitis in Aseer region, Southwestern Saudi Arabia. Inhealthcare. 2021 Dec 7;9(12):1694.
  70. Pillebout E, Alberti C, Guillevin L, Ouslimani A, Thervet E, the CESAR study group. Addition of cyclophosphamide to steroids provides no benefit compared with steroids alone in treating adult patients with severe Henoch Schönlein Purpura. Kidney International. 2010;78(5):495-502. doi:10.1038/ki.2010.150
  71. Han DH. Clinical analysis on 106 cases of Henoch–Schönlein purpura. J Intern Korean Med. 2007;28:570–85.
  72. Yang YH, Yu HH, Chiang BL. The diagnosis and classification of Henoch–Schönlein purpura: An updated review. Autoimmunity Reviews. 2014;13(4-5):355-358. doi:10.1016/j.autrev.2014.01.031
  73. Van de Perre E, Jones RB, Jayne DRW. IgA vasculitis (Henoch–Schönlein purpura): refractory and relapsing disease course in the adult population. Clinical Kidney Journal. 2021;14(8):1953-1960. doi:10.1093/ckj/sfaa251
  74. Maritati F, Fenoglio R, Pillebout E, Emmi G, Urban ML, Rocco R, et al. Brief Report: Rituximab for the Treatment of Adult‐Onset IgA Vasculitis (Henoch‐Schönlein). Arthritis & Rheumatology. 2017;70(1):109-114. doi:10.1002/art.40339
  75. Audemard‐Verger A, Terrier B, Dechartres A, Chanal J, Amoura Z, Le Gouellec N, et al. Characteristics and Management of IgA Vasculitis (Henoch‐Schönlein) in Adults: Data From 260 Patients Included in a French Multicenter Retrospective Survey. Arthritis & Rheumatology. 2017;69(9):1862-1870. doi:10.1002/art.40178
  76. Gohari A, Matsell DG, Mammen C, Goldman RD. Henoch-Schönlein purpura in children. Canadian Family Physician. 2020;66(12):895-897. doi:10.46747/cfp.6612895
  77. Butt G, Anees M, Rana M. Frequency of renal manifestations in patients of Henoch-Schonlein purpura. J Pak Assoc Dermatol. 2021;31:146–52.