Background:Amyloid A (AA) amyloidosis, previously known as secondary or reactive amyloidosis, is a long-recognized severe complication of some chronic inflammatory diseases. The pathogenesis and risk factors for amyloidosis in Familial Mediterranean Fever (FMF) remain partially understood (1). The development of AA amyloidosis is dependent on ethnicity and country of residence (2). In the pre-colchicine era, renal AA-amyloidosis was largely reported patients of Turkish (67%) and Sephardic Jewish ancestry (26.5%) (2,3). Currently it’s well known that the MEFV M694V variant associated with high risk of amyloidosis however, mutations on exon 2, specifically E148Q variant remained controversial.Objectives:To evaluate the E148Q mutation variant and concomitant AA Amyloidosis secondary to FMF after adjusted clinical-demographic characteristics.Methods:Patients were recruited from the renal unit at Epigenetic Health Center outpatient clinic in Turkey between September 2003 and February 2020. Patients who had biopsy confirmed FMF related AA amyloidosis were included the study. Tel-Hashomer criteria were applied in the diagnosis of FMF. The clinical characteristics of FMF patients and medication history were recorded by the physician at the time of registry entry. All patients had detailed baseline assessment of clinical features, renal functions, genetic testing, histopathological diagnosis of amyloidosis, and treatment received. We performed multiple comparisons according to the age of diagnosis, demographic features, disease phenotype, allele frequency, type of mutation and mortality. Statistical analysis was performed with Statistical Package of Social Science (SPSS) for Windows, version 15.0 (SPSS Inc, Chicago, IL).Results:Our registry consists of 195 patients with a diagnosis of AA amyloidosis. Complete information on 169 patients (lost to follow up, n=26) were included. The median age was 36 (19-49) years; male/female ratio was 1.6 (104/65). The median follow-up duration was 15.0 years (4-17 years). There were 101 patients diagnosed with FMF <18 years of age and 68 patients diagnosed ≥18 years of age. All participants developed renal amyloidosis before the age of 32 years. Family history of FMF was documented in 56 patients (33.1%) and family history of amyloidosis was present in 41 patients (24.3%). The three most common clinical symptoms were fever (84,6%), abdominal pain (71.6%) and arthritis (66.9%). During the follow-up, 5 patients started dialysis treatment and 9 patients had kidney transplantation. The most common allele frequency across patients was M694V (60.6%), E148Q (21.4%) and M680I (10.3%). The most frequent mutations were M694V/M694V (63.3%), M694V/E148Q (20.8%) and E148Q/E148Q (15.8%). During the follow up period, 15 patients (10 male, 5 female) died. In those that died, the mutations in 14 had M694V/M694Vand one demonstrated E148Q/E148Q.Conclusion:Patients with FMF related AA amyloidosis have an increased risk for mortality. This study confirmed the association between M694V and FMF-associated AA amyloidosis, which has been reported in many studies. Close clinical follow-up and further evaluation of patients with the E148Q mutation is warranted specifically if residing in FMF endemic areas. The possible relationship between E148Q and AA amyloidosis need to be confirmed in other cohorts.References:[1]Erer B, Demirkaya E, Ozen S, Kallinich T. What is the best acute phase reactant for familial Mediterranean fever follow-up and its role in the prediction of complications? A systematic review. Rheumatology international. 2016;36(4):483-7.[2]Touitou I, Sarkisian T, Medlej-Hashim M, Tunca M, Livneh A, Cattan D, et al. Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis and rheumatism. 2007;56(5):1706-12.[3]Pras M, Bronshpigel N, Zemer D, Gafni J. Variable incidence of amyloidosis in familial Mediterranean fever among different ethnic groups. Johns Hopkins Med J. 1982;150(1):22-6.Disclosure of Interests:None declared
Familial Mediterranean fever: diagnostic issues and treatment options
