Çocuklarda Henoch-Schonlein purpurasının prezentasyonu ve klinik seyri üzerine MEFV varyantlarının etkisi?

Yıl 2022, Cilt: 36 Sayı: 3, 245 - 255, 27.01.2023

Ceyhun Açarı Meral Bayram Gizem Yıldız Salih Kavukçu Alper Soylu

https://doi.org/10.18614/deutip.1191315

Cited By: 1

Öz

Amaç: Henoch-Schonlein Purpura'lı (HSP) çocuklarda MEFV mutasyon sıklığını ve MEFV mutasyonlarının renal tutulum dahil klinik seyir üzerindeki etkilerini değerlendirmeyi amaçladık.
Yöntemler: Bu çalışmaya MEFV mutasyonlarının varlığı açısından değerlendirilen HSP tanılı çocuklar alındı.Hastalar öncelikle MEFV mutasyonlarının varlığına göre mutasyonu olmayan hastalar Grup 1 ve en az bir allelde mutasyonu olan (heterozigot, homozigot veya bileşik heterozigot) hastaları içerenler Grup 2 olmak üzere iki gruba ayrıldı.Ayrıca en az bir allelde M694V mutasyonu olan hastaları M694V mutasyonu taşımayan hastalarla karşılaştırarak M694V mutasyonunun HSP seyri üzerindeki etkilerini spesifik olarak araştırdık.
Bulgular: Kırk yedi hasta (23 kadın) kaydedildi. MEFV mutasyon oranı (%53) genel popülasyondaki oranın 3,5 katıydı. M694V en yaygın mutasyondu (%48). MEFV mutasyonlu hastalarda, özellikle M694V mutasyonlu hastalarda, öncesinde enfeksiyon görülme insidansı daha düşüktü, ancak inflamatuar belirteçler, kafa derisi ödemi ve nüks oranı arttı. MEFV mutasyonlarının varlığından böbrek tutulumu ve uzun dönem prognoz etkilenmedi.
Sonuç: MEFV mutasyonları, HSP geliştirmeye yatkınlığa neden olmaktadır ve artan inflamasyon değişen klinik seyir ile ilişkilidir. Ancak böbrek tutulumu ve uzun dönem prognoz MEFV mutasyonlarının varlığından etkilenmemiştir.

Anahtar Kelimeler

Henoch-Schonlein, IgA vasküliti, MEFV geni, renal tutulum

Effect of MEFV variants on the presentation and clinical course of Henoch-Schonlein purpura in children?

Öz

Objective: We aimed to evaluate MEFV mutation frequency and the effects of MEFV mutations on the clinical course including renal involvement in children with Henoch-Schonlein Purpura (HSP).
Methods: Children with a diagnosis of HSP who were evaluated for the presence of MEFV mutations were enrolled in this study. Patients were primarily assigned into two groups based on the presence of MEFV mutations as Group 1 including patients without mutations and Group 2 including patients with mutations in at least one allele (heterozygous, homozygous, or compound heterozygous). We also investigated specifically the effects of M694V mutation on the course of HSP by comparing patients with M694V mutation in at least one allele with patients not carrying M694V mutation.
Results: Forty-seven patients (23 female) were enrolled. MEFV mutation rate (53%) was 3.5 times the rate in general population. M694V was the most common mutation (48%). Patients with MEFV mutations, especially those with M694V mutation, had lower incidence of preceding infection, but increased inflammatory markers, scalp edema and relapse rate. Renal involvement and long-term prognosis were not affected by the presence of MEFV mutations.
Conclusions: MEFV mutations cause susceptibility to develop HSP and are associated with increased inflammation and altered clinical course. However, renal involvement and long-term prognosis were not affected by the presence of MEFV mutations.

Anahtar Kelimeler

Henoch-Schonlein, IgA vasculitis, MEFV gene, renal involvement

Kaynakça

• 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 (Oxford). 2019;58:1607-16.
• López-Mejías R, Carmona FD, Castañeda S, Genre F, Remuzgo-Martinez S, Sevilla-Perez B et al. A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis. Sci Rep. 2017;7:5088.
• Demir S, Sag E, Dedeoglu F, Ozen S. Vasculitis in Systemic Autoinflammatory Diseases. Front Pediatr. 2018;6:377.
• Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, et al. (Turkish FMF Study Group) Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore). 2005;84:1‐11.
• Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med. 2007;65:318-24.
• Yalçinkaya F, Ozçakar ZB, Kasapçopur O, Oztürk A, Akar N, Bakkaloğlu A, et al. Prevalence of the MEFV gene mutations in childhood polartheritis nodosa. J Pediatr. 2007;151:675-78.
• Aksu K, Keser G. Coexistence of vasculitides with familial Mediterranean fever. Rheumatol Int. 2011;31:1263-274.
• Ozen S, Bakkaloglu A, Yilmaz E, Duzova A, Balci B, Topaloglu R, et al. Muatations in the gene for Familial Mediterranean fever: do they predispose to inflammation? J Rheumatol. 2003;30:2014-18.
• Ozcakar ZB, Yalcınkaya F. Vascular comorbidities in familial Mediterranean fever. Rheumatol Int. 2011;31:1275-81.
• Abbara S, Grateau G, Ducharme-Bénard S, Saadoun D, Georgin-Lavialle S. Association of Vasculitis and Familial Mediterranean Fever. Front Immunol. 2019;10:763.
• Altug U, Ensari C, Sayin DB, Ensari A. MEFV gene mutations in Henoch-Schonlein purpura. Inter J Rheum Dis. 2013;16:347-51.
• Bonyadi M, Younesi M, Mandana Rafaey M, Shabestari MS, Mortazavi F. MEFV mutations in Iranian Azari Turkish patients with Henoch–Schönlein purpura. Turk J Med Sci. 2016;46:967-71.
• Dogan CS, Akman S, Koyun M, Bilgen T, Comak E, Gokceoglu AU. Prevalence and significance of the MEFV gene mutations in childhood Henoch–Schonlein purpura without FMF symptoms Rheumatol Int. 2013;33:377-80.
• Gershoni-Baruch R, Broza Y, Brik R. Prevalence and significance of mutations in Familial Mediterranean fever gene in Henoch- Schonlein purpura. J Pediatr 2003; 143: 658-61.
• Ozçakar ZB, Yalçinkaya F, Cakar N, Acar B, Kasapçopur O, Ugüten D, et al. MEFV mutations modify the clinical presentation of Henoch-Schönlein purpura. J Rheumatol. 2008;35:2427-29.
• Bayram C, Demircin G, Erdoğan O, Bülbül M, Caltik A, Akyüz SG. Prevalence of MEFV mutations and their clinical correlations in Turkish children with Henoch- Schonlein purpura. Act Pediatr. 2011;100:745-9.
• Ekinci RMK, Balcı S, Bisgin Atil, Atmış B, Doğruel D, Altıntaş DU, et al. MEFV gene variants in children with Henoch- Schönlein Purpura and association with clinical manifestations: a single center Mediterranean experience. Postgrad Med. 2019;131:68-72.
• He X, Lu H, Kang S, Luan J, Liu Z, Yin W, et al. MEFV E148Q polymorphism is associated with Henoch-Schönlein purpura in Chinese children. Pediatr Nephrol. 2010;25:2077–82.
• Salah S, Rizk S, Lotfy HM, El Houchi S, Marzouk H, Farag Y. MEFV gene mutations in Egyptian children with Henoch-Schonlein purpura. Pediatr Rheumatol Online J. 2014;12:41.
• Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, 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: 798-806. Soylemezoglu O, Kandur Y, Gonen S, Düzova A, Özçakar ZB, Fidan K, et al. Familial Mediterranean fever gene mutation frequencies in a sample Turkish population. Clin Exp Rheumatol. 2016;34:97-100.
• Schlesinger M, Kopolovic J, Viskoper RJ, Ron N. A case of familial Mediterranean fever with cutaneous vasculitis and immune complex nephritis: light, electron, and immunofluorescent study of renal biopsy. Am J Clin Pathol. 1983;80:511-4.
• Piram M, Mahr A. Epidemiology of immunoglobulin A vasculitis (Henoch-Schönlein): current state of knowledge. Curr Opin Rheumatol. 2013;25:171-8.
• Peleg H, Ben-Chetrit E. Vasculitis in the autoinflammatory diseases. Curr Opin Rheumatol. 2017;29:4-11.
• Karadag O, Tufan A, Yazisiz V, Ureten K, Yilmaz S, Cinar M, et al. The factors considered as trigger for the attacks in patients with familial Mediterranean fever. Rheumatol Int. 2013;33:893-7.
• Grossman C, Kassel Y, Livneh A, Ben-Zvi I. Familial Mediterranean fever (FMF) phenotype in patients homozygous to the MEFV M694V mutation. Eur J Med Genet. 2019; 62:103532.
• Bagga A, Kabra SK, Srivastava RN, Bhuyan UN. Henoch-Schonlein syndrome in northern Indian children. Indian Pediatr. 1991;28:1153-7.
• 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. Semin Arthritis Rheum. 2005;35:143-53.
• Arunath V, Athapathu AS, Hoole TJ, Aruppala H, Rathnasri A, Ranawaka R, et al. Severe Disfiguring Scalp and Facial Oedema due to Henoch-Schönlein Purpura in a Child. Case Rep Pediatr. 2020;2020:8823611.
• Cakici EK, Kurt Şükür ED, Özlü SG, Yazılıtaş F, Özdel S, Gür G, et al. MEFV gene mutations in children with Henoch-Schönlein purpura and their correlations-do mutations matter? Clin Rheumatol. 2019;38:1947-52.
• Koskimies O, Rapola J, Savilahti E, Vilska J. Renal involvement in Schonlein-Henoch purpura. Acta Paediatr Scand. 1974;63:357-63.
• Kobayashi O, Wada H, Okawa K, Takeyama I. Schonlein-Henoch’s syndrome in children. Contrib Nephrol. 1975;4:48-71.
• Koskimies O, Mir S, Rapola J, Vilska J. Henoch-Schonlein nephritis: long-term prognosis of unselected patients. Arch Dis Child. 1981;56:482-84.
• Niaudet P, Habib R. Methylprednisolone pulse therapy in the treatment of severe forms of Schonlein-Henoch purpura nephritis. Pediatr Nephrol. 1998;12:238-43.
• 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. Arch Dis Child. 2005;90:916-20.