Skip to main content

Advertisement

SpringerLink
Log in

MEFV gene mutations in children with Henoch–Schönlein purpura and their correlations—do mutations matter?

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

This article has been updated

Abstract

Objective

To explore the frequency of MEFV gene mutations in children with Henoch–Schönlein purpura who had no prior familial Mediterranean fever diagnosis and to evaluate the association of MEFV mutations with the clinical and laboratory features of Henoch–Schönlein purpura.

Methods

Data of 1120 patients diagnosed with Henoch–Schönlein purpura were reviewed retrospectively. The spectrum and degree of organ involvement and acute phase reactant levels were documented for each patient. Blood for MEFV gene mutation analysis was obtained either at the time of the Henoch–Schönlein purpura diagnosis or during follow-up visits. Pathological specimens of patients who underwent biopsy (renal/skin) were evaluated with special consideration for immunofluorescent examinations.

Results

Two hundred and thirty-eight (21.3%) patients were found to have one of the MEFV mutations in which exon 10 mutations were the most common (16.7%). Abdominal pain, joint involvement, scrotal involvement, and relapse were more frequent, and acute-phase reactant levels were significantly high in patients with MEFV mutations. More severe characteristics were observed in the presence of homozygous exon 10 mutations. There was no significant association between exon 2 variants and clinical course of Henoch–Schönlein purpura. Patients carrying MEFV mutations did not have significantly higher levels of IgA deposits in the biopsy materials.

Conclusion

Henoch–Schönlein purpura in patients with homozygous exon 10 MEFV mutations seems to be more severe than that in patients carrying other mutations. In patients with exon 10 MEFV mutations, Henoch–Schönlein purpura might be considered as an associated presentation of familial Mediterranean fever rather than a separate clinical entity.

Key points

• p.M694V mutation is more common in Henoch–Schönlein purpura than in the general population.

• p.E148Q variants have no impact on clinical symptoms and laboratory findings in Henoch–Schönlein purpura patients.

• The majority of Henoch–Schönlein purpura patients with familial Mediterranean fever have no IgA deposits.

• Henoch–Schönlein purpura in familial Mediterranean fever patients may be considered as an integral clinical feature of familial Mediterranean fever.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Change history

  • 02 February 2021

    The author citation for Eda Didem Kurt Şükür has been updated from "Şükür EDK" to "Kurt Şükür ED".

References

  1. Jennette JC (2013) Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol 17(5):603–606. https://doi.org/10.1007/s10157-013-0869-6

    Article  PubMed  PubMed Central  Google Scholar 

  2. Saulsbury FT (2007) Clinical update: Henoch-Schönlein purpura. Lancet 369(9566):976–978

    Article  Google Scholar 

  3. Dedeoglu F, Sundel RP (2005) Vasculitis in children. Pediatr Clin N Am 52:547–575

    Article  Google Scholar 

  4. Altug U, Ensari C, Sayin DB, Ensari A (2013 Jun) MEFV gene mutations in Henoch Schonlein purpura. Int J Rheum Dis 16(3):347–351. https://doi.org/10.1111/1756-185X.12072

    Article  CAS  PubMed  Google Scholar 

  5. Özdogan H, Arısoy N, Kasapçopur Ö, Sever L, Calişkan S, Tuzuner N et al (1997) Vasculitis in familial Mediterranean fever. J Rheumatol 24(2):323–327

    PubMed  Google Scholar 

  6. Gershoni-Baruch R, Broza Y, Brik R (2003) Prevalence and significance of mutations in familial Mediterranean fever gene in Henoch- Schonlein purpura. J Pediatr 143(5):658–661

    Article  CAS  Google Scholar 

  7. Dogan CS, Akman S, Koyun M, Bilgen T, Comak E, Gokceoglu AU (2013) Prevalence and significance of the MEFV gene mutations in childhood Henoch-Schönlein purpura without FMF symptoms. Rheumatol Int 33(2):377–380

    Article  CAS  Google Scholar 

  8. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40(10):1879–1885

    Article  CAS  Google Scholar 

  9. Ben-Chetrit E, Yazici H (2016) Nonthrombocytopenic purpura in familial Mediterranean fever-comorbidity with Henoch-Schönlein purpura or an additional rare manifestation of familial Mediterranean fever? Rheumatology (Oxford) 55(7):1153–1158. https://doi.org/10.1093/rheumatology/kev378

    Article  Google Scholar 

  10. Ozen S, Ruperto N, Dillon MJ, Bagga A, Davin JC et al (2006) EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis 65(7):936–941

    Article  CAS  Google Scholar 

  11. Flatau E, Khon D, Schiller D, Lurie M, Levy E (1982) Schönlein–Henoch syndrome in patients with familial Mediterranean fever. Arthritis Rheum 25:42–47

    Article  CAS  Google Scholar 

  12. Ozçakar ZB, Yalçinkaya F, Cakar N, Acar B, Kasapçopur O, Ugüten D et al (2008) MEFV mutations modify the clinical presentation of Henoch-Schönlein purpura. J Rheumatol 35(12):2427–2429

    Article  Google Scholar 

  13. Lange-Sperandino B, Möhrig K, Gutzler F, Mehls O (2004) Variable expression of vasculitis in siblings with familial Mediterranean fever. Pediatr Nephrol 19(5):539–543

    Article  Google Scholar 

  14. Bayram C, Demircin G, Erdoğan O, Bülbül M, Catlık A, Akyüz SG (2011) Prevalence of MEFV gene mutations and their clinical correlations in Turkish children with Henoch-Schönlein purpura. Acta Paediatr 100(5):745–749. https://doi.org/10.1111/j.1651-2227.2011.02143.x

    Article  CAS  PubMed  Google Scholar 

  15. Tekin M, Yalçinkaya F, Tumer N, Akar N, Mısırlıoglu M, Çakar N (2000) Clinical, laboratory and molecular characteristics of children with familial Mediterranean fever-associated vasculitis. Acta Paediatr 89:177–182

    Article  CAS  Google Scholar 

  16. Tunca M, Akar S, Onen F, Özdoğan H, Kasapçopur O, Yalçınkaya F et al (2005) Familial Mediterranean fever (FMF) in Turkey: results of a nationwide study. Medicine 84:1–11

    Article  Google Scholar 

  17. Yılmaz E, Özen S, Balcı B, Duzova A, Topaloglu R, Besbas N et al (2001) Mutation frequency of familial Mediterranean fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 9(7):553–555

    Article  Google Scholar 

  18. Ben-Chetrit E, Lerer I, Malamud E, Domingo C, Abeliovich D (2000) The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a sequence variant? Hum Mutat 15(4):385–386

    Article  CAS  Google Scholar 

  19. Salah S, Rizk S, Lotfy HM et al (2014) MEFV gene mutations in Egyptian children with Henoch-Schonlein purpura. Pediatr Rheumatol Online J 12:41

    Article  Google Scholar 

  20. Conley ME, Cooper MD, Michael AF (1980) Selective deposition of immunoglobulin A1 in immunoglobulin A nephropathy, anaphylactoid purpura nephritis, and systemic lupus erythematosus. J Clin Invest 66(6):1432–1436

    Article  CAS  Google Scholar 

  21. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CGM, Mccluskey RT, Sinico RA, Rees AJ, Es LAV, Waldherr RÜD, Wiik A (1994) Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 37(2):187–192

    Article  CAS  Google Scholar 

  22. Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N, for the Paediatric Rheumatology International Trials Organisation (PRINTO) (2010) EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Ann Rheum Dis 69(5):798–806. https://doi.org/10.1136/ard.2009.116657

    Article  PubMed  Google Scholar 

  23. Jennette JC, Falk RJ (1997) Small-vessel vasculitis. N Engl J Med 337(21):1512–1523

    Article  CAS  Google Scholar 

  24. Majeed HA, Quabazard Z, Hijazi Z, Farwana S, Harshani F (1990) The cutaneous manifestations in children with familial Mediterranean fever (recurrent hereditary polyserositis). A six-year study. Q J Med 75(278):607–616

    CAS  PubMed  Google Scholar 

  25. Nickavar A, Ehsanipour F (2008) Recurrent Henoch Schonlein purpura in familial Mediterranean fever. Acta Med Iranica 46:349–352

    Google Scholar 

Download references

Acknowledgements

EKC designed the study, collected and analyzed the data, and wrote the manuscript. GC, FY, SGO, and FKE collected the data and wrote the manuscript. EDKS, SO, TG, EC, and EB collected the data and did the proof-reading. MB and all authors have read and approved the final manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatric Nephrology and Rheumatology, Dr. Sami Ulus Maternity and Child Health and Diseases Training and Research Hospital, Ankara, Turkey

    Evrim Kargin Cakici, Eda Didem Kurt Şükür, Sare Gülfem Özlü, Fatma Yazılıtaş, Semanur Özdel, Gökçe Gür, Fehime Kara Eroğlu, Tülin Güngör, Evra Çelikkaya, Esra Bağlan & Mehmet Bülbül

Authors
  1. Evrim Kargin Cakici
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eda Didem Kurt Şükür
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sare Gülfem Özlü
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fatma Yazılıtaş
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Semanur Özdel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gökçe Gür
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fehime Kara Eroğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tülin Güngör
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Evra Çelikkaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Esra Bağlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mehmet Bülbül
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Evrim Kargin Cakici.

Ethics declarations

Disclosures

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cakici, E.K., Kurt Şükür, E.D., Özlü, S.G. et al. MEFV gene mutations in children with Henoch–Schönlein purpura and their correlations—do mutations matter?. Clin Rheumatol 38, 1947–1952 (2019). https://doi.org/10.1007/s10067-019-04489-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-019-04489-2

Keywords

Search

Navigation