Ailevi Akdeniz Ateşi hastalarında fenotip-genotip ilişkisi : Tek merkez deneyimi
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Tarih
2019
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Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/embargoedAccess
Özet
Ailevi Akdeniz Ateşi dünyada en sık görülen otoinflamatuvar hastalıktır ve en sık Türkler, Arablar, Ermeniler ve Yahudilerde görülür. Çalışmamızda Trakya Üniversitesi Tıp Fakültesi İç Hastalıkları Anabilimdalı ve Romatoloji Bilimdalında 2003-2017 yılları arasında takip edilen 152 hastada demografik özellikler, klinik bulgular, aile öyküsü, genetik analiz ve verilen tedaviler retrospektif olarak tarandı. Hastaların genotip-fenotip ilişkisini ortaya koymak amaçlandı. Çalışmamıza alınan hastalarımızın 82’si kadın, 70’i erkekten oluşmakta idi. Kadın/erkek oranı 1.17 saptandı. Hastaların semptom başlama yaşı 13.4±5.9 yıl, ortalama tanı alma yaşı 18.7±6.4 yıl, gecikme süresi ortalama 5.1±2.9 yıl olarak saptandı. Cinsiyet ve yaş ortalamalarında istatistiki fark saptanmadı. Olguların %83.6’sı yirmi yaşından önce semptom gösterirken, %67.2’si 20 yaşından önce tanı aldı.En sık görülen klinik bulgu karın ağrısı iken onu sırasıyla ateş, artralji ve artrit izledi. Amiloidoz sıklığı %9.2 olarak saptandı.18 yaşından önce semptom gösteren olgularda istatistiki olarak daha fazla plevrit, artrit, myalji, erizipel benzeri eritem ve amiloidoz izlenirken hastalık şiddeti bu grupta daha yüksek saptandı.En sık genetik mutasyon %44,5 ile M694V mutasyonu olarak saptanırken onu sırasıyla %11 ile M680I mutasyonu ve %8.6 ile V726A mutasyonu izledi.Amiloidoz saptanan olgularda amiloid negatif olgulara göre daha erken semptom yaşı ve daha fazla tanıda gecikme süresi saptandı.Amiloidozlu olgularda amiloid negatiflere kıyasla istatistiki olarak daha fazla plevrit, artralji, artrit, erizipel benzeri eritem, kronik böbrek yetmezliği, ailede AAA ve amiloidoz öyküsü, ailede SDBY öyküsü saptandı. Amiloidozlu bireylerde daha yüksek miktarda kreatin, CRP ve ESH düzeyi izlendi.Homozigot M694V mutasyonuna sahip olgularda heterozigot M694V mutasyonu ve diğer mutasyonlara kıyasla istatistiki olarak anlamlı olarak daha fazla şiddetli hastalık ve Ankliozan spondilit izlenirken, klinik bulgularda daha fazla amiloidoz, artralji, artrit, plevrit, erizipel benzeri eritem, vaskülit, kronik böbrek yetmezliği saptandı.E148Q mutasyonu sahip bireylerde istatistiki olarak anlamlı düzeyde daha az karın ağrısı, daha az artrit saptandı. Olgularun hepsi birinci basamak tedavi olarak kolşisin tedavisi verildi. Olguların %69’u kolşisin ile tam remisyona girerken, %5,3’ü kolşisine dirençli olarak saptandı. Homozigot M694V mutasyonuna sahip bireylerde daha fazla kolşisin direnci saptandı. Kolşisin direnci olan altı olguya anakinra tedavisi verilirken, iki olguya TNF-alfa inhibitörleri verildi. Sonuç olarak çalışmamızda Ailevi Akdeniz Ateşi olgularında genetik mutasyonların klinik bulgular ve hastalık şiddeti ile ilgili olduğu gösterilmiştir. Özellikle M694V mutasyonuna sahip bireylerde amiloidoz gelişimi ve kolşisin direncine yönelik hasta yakın takip edilmelidir.
Familial Mediterranean Fever is the most common autoinflammatory disease in the world and is most commonly seen among Turks, Arabs, Armenians and Jews. In our study, demographic features, clinical findings, family history, genetic analysis and given therapies were retrospectively screened in 152 patients who were followed up between 2003-2017 in Trakya University Medical Faculty Department of Internal Medicine and Rheumatology. It was aimed to reveal the genotype-phenotype relationship of the patients. Our patient group consisted of 82 female patients and 70 male patients. The ratio of female to male was 1.17. The mean age of symptom onset was 13.4 ± 5.9 years, the mean age of diagnosis was 18.7 ± 6.4 years and the mean delay time was 5.1 ± 2.9 years. There was no statistical difference between the sexes and age groups. 83.6% of the cases were symptomatic before the age of twenty and 67.2% were diagnosed before the age of 20 years. The most common clinical finding was abdominal pain and it is followed by fever, arthralgia and arthritis, respectively. The frequency of amyloidosis was 9.2%. Statistically; pleuritis, arthritis, myalgia, erysipelas-like erythema and amyloidosis were more frequent in symptomatic cases before the age of 18 years, and the severity of the disease was higher in this group. The most common genetic mutation was identified as M694V mutation with 44.5%, followed by M680I mutation with 11% and V726A mutation with 8.6%. Amyloidosis cases had earlier symptom age and longer delays in diagnosis than amyloid negative cases. Furthermore, in amyloidosis cases; pleuritis, arthralgia, arthritis, erysipelas-like erythema, chronic renal failure and family history of FMF, amyloidosis and SDBY were statistically more frequent compared with amyloid negative cases. Higher amounts of creatinine, CRP and ESR were observed in patients with amyloidosis. In cases with homozygote M694V mutation, severe disease and ankylosing spondylitis were statistically more frequent compared with cases with heterozygous M694V mutation and other mutations, and amyloidosis, arthritis, arthritis, pleuritis, erysipelas-like erythema, vasculitis and chronic renal failure were more frequent in these patients. Statistically significantly fewer abdominal pain and arthritis were found in individuals with the E148Q mutation. All cases were treated with colchicine as first-line treatment. In 69% of the cases, complete remission was achieved with colchicine, while 5.3% were resistant to colchicine.Patients with homozygote M694V mutation had a higher resistance to colchicine. Six colchicine-resistant patients were treated with anakinra, while two patients received TNF-alpha inhibitors. In conclusion, our study showed that genetic mutations are associated with clinical findings and disease severity in Familial Mediterranean fever cases. Especially patients with M694V mutation should be closely monitored for amyloidosis and resistance to colchicine.
Familial Mediterranean Fever is the most common autoinflammatory disease in the world and is most commonly seen among Turks, Arabs, Armenians and Jews. In our study, demographic features, clinical findings, family history, genetic analysis and given therapies were retrospectively screened in 152 patients who were followed up between 2003-2017 in Trakya University Medical Faculty Department of Internal Medicine and Rheumatology. It was aimed to reveal the genotype-phenotype relationship of the patients. Our patient group consisted of 82 female patients and 70 male patients. The ratio of female to male was 1.17. The mean age of symptom onset was 13.4 ± 5.9 years, the mean age of diagnosis was 18.7 ± 6.4 years and the mean delay time was 5.1 ± 2.9 years. There was no statistical difference between the sexes and age groups. 83.6% of the cases were symptomatic before the age of twenty and 67.2% were diagnosed before the age of 20 years. The most common clinical finding was abdominal pain and it is followed by fever, arthralgia and arthritis, respectively. The frequency of amyloidosis was 9.2%. Statistically; pleuritis, arthritis, myalgia, erysipelas-like erythema and amyloidosis were more frequent in symptomatic cases before the age of 18 years, and the severity of the disease was higher in this group. The most common genetic mutation was identified as M694V mutation with 44.5%, followed by M680I mutation with 11% and V726A mutation with 8.6%. Amyloidosis cases had earlier symptom age and longer delays in diagnosis than amyloid negative cases. Furthermore, in amyloidosis cases; pleuritis, arthralgia, arthritis, erysipelas-like erythema, chronic renal failure and family history of FMF, amyloidosis and SDBY were statistically more frequent compared with amyloid negative cases. Higher amounts of creatinine, CRP and ESR were observed in patients with amyloidosis. In cases with homozygote M694V mutation, severe disease and ankylosing spondylitis were statistically more frequent compared with cases with heterozygous M694V mutation and other mutations, and amyloidosis, arthritis, arthritis, pleuritis, erysipelas-like erythema, vasculitis and chronic renal failure were more frequent in these patients. Statistically significantly fewer abdominal pain and arthritis were found in individuals with the E148Q mutation. All cases were treated with colchicine as first-line treatment. In 69% of the cases, complete remission was achieved with colchicine, while 5.3% were resistant to colchicine.Patients with homozygote M694V mutation had a higher resistance to colchicine. Six colchicine-resistant patients were treated with anakinra, while two patients received TNF-alpha inhibitors. In conclusion, our study showed that genetic mutations are associated with clinical findings and disease severity in Familial Mediterranean fever cases. Especially patients with M694V mutation should be closely monitored for amyloidosis and resistance to colchicine.
