The impact of COVID-19 on familial Mediterranean fever: a nationwide study.

The study aimed to evaluate the impact of the coronavirus disease 2019 (COVID-19) in patients with familial Mediterranean fever (FMF) and to assess the relationships between FMF characteristics and severe COVID-19 outcomes such as hospitalization. The study was planned within a national network of 21 different centers. Demographics, FMF-related clinical and genetic characteristics, and COVID-19 outcomes were obtained. A total of 822 patients with FMF (mean age of 36 years) were included in the study. Fifty-nine of them (7%) had a COVID-19 diagnosis confirmed by real-time PCR test or chest CT findings. Most FMF patients with COVID-19 (58) had mild and moderate disease activity. All patients were on colchicine treatment. However, 8 of them (13.6%) were not compliant with colchicine use and 9 of them (15.3%) were colchicine resistant. Twelve FMF patients with COVID-19 were hospitalized. There were 4 patients requiring oxygen support. COVID-19 related complications were observed in 2 patients (1 thromboembolism, 1 acute respiratory distress syndrome). Hospitalized COVID-19 patients with FMF were older than non-hospitalized patients (median ages: 51 and 31 years, respectively; p: 0.002). Other FMF-related characteristics were similar between the groups. FMF-related characteristics were not found to be associated with poor outcomes in COVID-19. Thus, FMF may not be a risk factor for poor COVID-19 outcomes.

Familial Mediterranean fever is associated with increased risk for ischaemic heart disease and mortality-Perspective derived from a large database.

AIMS OF THE STUDY: Familial Mediterranean fever (FMF) is a hereditary, auto-inflammatory disease, characterised by recurrent, self-limiting attacks of fever with inflammation of the serosal membranes, joints, and skin. Chronic inflammation was previously associated with increased risk for ischaemic heart disease (IHD). However, the association between FMF and IHD remains unclear. The objective of this study is to determine whether this association exists. METHODS: Utilising the database of the largest health-care provider in Israel, a cross-sectional study was performed. The incidence of IHD was compared between patients diagnosed with FMF and age and sex-matched controls. Chi-square and t-test were used for categorial and continuous variables, and cox logistics regression model was used for multivariate analysis. Survival analysis was made using Kaplan-Meier plots and log-rank test. RESULTS: The study included 7670 patients diagnosed with FMF and an equal number of controls without FMF. In a univariate analysis FMF was found to be associated with higher prevalence of IHD (OR 1.33) and increased mortality (OR 1.29). In a multivariate analysis FMF was found to be independently associated with increased risk for IHD (OR 1.44). CONCLUSION: The study shows that FMF is associated with both increased risk for IHD and higher mortality rates. An early diagnosis and treatment of this disease can potentially improve patients' life expectancy and decrease cardiac comorbidities.

Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents.

OBJECTIVE: There are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF. METHODS: We studied a nationwide, population-based, retrospective cohort of 1225 individuals with FMF (59% men) in a database of 1 244 350 adolescents (16-20 years of age) medically evaluated for military service between 1973 and 1997. This cohort was linked with the national mortality, cancer and end-stage renal disease (ESRD) registries in Israel. Study outcomes were all-cause mortality, occurrence of ESRD and malignancy by the age of 50 years. RESULTS: During 30 years of follow-up, death rates were 8.73/10(4) versus 4.32/10(4) person-years in the FMF and control groups, respectively (p=0.002). In a multivariable analysis adjusted for age, birth year, socio-economic status, education, ethnicity and body mass index, FMF was associated with increased mortality in men (HR=1.705 (95% CI 1.059 to 2.745), p=0.028) and women (HR=2.48 (1.032 to 5.992), p=0.042). Renal amyloidosis accounted for 35% and 60% of deaths in men and women, respectively. FMF was not associated with an increased incidence of cancer. CONCLUSIONS: FMF is associated with increased all-cause mortality that is likely attributed to reduced colchicine compliance or responsiveness. Individuals with FMF do not have an increased incidence of cancer. These results support the awareness among medical community to decrease the higher than average mortality rate among participants with FMF.

AA amyloidosis complicating the hereditary periodic fever syndromes.

OBJECTIVE: AA amyloidosis is a life-threatening complication of the hereditary periodic fever syndromes (HPFS), which are otherwise often compatible with normal life expectancy. This study was undertaken to determine the characteristics, presentation, natural history, and response to treatment in 46 patients who had been referred for evaluation at the UK National Amyloidosis Centre. METHODS: Disease activity was monitored by serial measurement of serum amyloid A. Renal function was assessed by measurement of serum creatinine and albumin levels, the estimated glomerular filtration rate, and proteinuria from 24-hour urine collections. The amyloid load was measured by serum amyloid P scintigraphy. RESULTS: Twenty-four patients had familial Mediterranean fever, 12 patients had tumor necrosis factor receptor-associated periodic syndrome, 6 patients had cryopyrin-associated periodic syndromes, and 4 patients had mevalonate kinase deficiency. The median age at onset of HPFS was 5 years; median age at presentation with AA amyloidosis was 38 years. Diagnosis of an HPFS had not been considered prior to presentation with AA amyloidosis in 23 patients (50%). Eleven patients (24%) had end-stage renal failure (ESRF) at presentation; of these, 3 had received transplants prior to referral. A further 13 patients developed ESRF over the followup period, with 10 undergoing renal transplantation. The median time to progression to ESRF from onset of AA amyloidosis was 3.3 years (interquartile range [IQR] 2-8), with a median time to transplant of 4 years (IQR 3-6). Eleven patients (24%) died. The median survival in the entire cohort was 19 years from diagnosis of AA amyloidosis. Of the 37 patients who were treated successfully, or in whom at least partial suppression of the underlying HPFS was achieved, 17 (46%) showed amyloid regression, 14 (38%) showed a stable amyloid load, and 2 (5%) showed increased amyloid deposition over the followup period. CONCLUSION: AA amyloidosis remains a challenging and serious late complication of HPFS; however, outcomes are excellent when HPFS is diagnosed early enough to allow effective treatment, thus preventing or retarding further amyloid deposition and organ damage.

Familial Mediterranean fever: a critical digest of the 2012-2013 literature.

The year 2012-2013 has been a fertile one in the area of FMF inquiry. Recent studies have led to further insight into the possible mechanisms whereby pyrin mutations might cause the auto-inflammatory phenotype that is characteristic of FMF. Evidence-based guidelines for diagnosis of FMF, including the role of genetic testing, have become available. Risks for colchicine resistance have been partially defined, and a randomised, controlled trial showing efficacy of an interleukin-1 antagonist for treatment of colchicine-resistant or intolerant FMF patients was reported. In this review, we summarise these and other salient findings from the recent FMF literature, and discuss their significance for the clinician.

Renal involvement in AA amyloidosis: clinical outcomes and survival.

BACKGROUND: The natural history of AA amyloidosis is typically progressive, leading to multiple organ failure and death. We analyzed the etiology as well as clinical and laboratory features of patients with biopsy-proven AA amyloidosis and evaluated the ultimate outcome. METHODS: Seventy-three patients (24 female; mean age 41.85±15.89 years) were analyzed retrospectively. Demographic, clinical and laboratory features were studied and the outcome was assessed. RESULTS: Familial Mediterranean Fever and tuberculosis were the most frequent causes of amyloidosis. Mean serum creatinine and proteinuria at diagnosis were 4.65±4.89 mg/dl and 8.04±6.09 g/day, respectively; and stage I, II, III, IV and V renal disease were present in 19.2%, 13.7%, 16.4%, 11%, and 39.7% of the patients, respectively. ESRD developed in 16 patients during the follow-up period. All of the ESRD patients started a dialysis programme. Thirty patients (41%) died during the follow-up period; median patient survival was 35.9±6.12 months. Old age, tuberculosis etiology, advanced renal disease and low serum albumin levels were associated with a worse prognosis. Serum albumin was a predictor of mortality in logistic regression analysis. CONCLUSION: The ultimate outcome of the patients with AA amyloidosis is poor, possibly due to the late referral to the nephrology clinics. Early referral may be helpful to improve prognosis.

Morphological aspects of the familial Mediterranean fever.

The study of clinical and morphological features of multiple organ lesions in familial Mediterranean fever (FMF) is important for identification of main morphologic lesions in thanatogenesis in parallel with the clinical manifestations. Clinical-morphological analysis of 200 patients with FMF and 60 dead from complications of FMF without renal transplantation were done. It was established that renal affection was observed in all patients, who died from complications of FMF, but the severity and nature of the observed changes were different. The kidney affections in investigated material in 3 groups were classified: amyloidosis, nonamyloid affections and glomerulitis accompanied with amyloidosis. Cardiopathic amyloidosis we established in thanatogenesis of FMF manifested with heart failure. The secondary polyorganial amyloidosis in FMF resulting in polyorganial failure revealed. The lung amyloidosis was accompanied with cardiac. Kidney affections were manifested with nonamyloid nephropathias manifested with intracapilliary mesangioproliferative or extracapillary productive glomerulonephritis, besides amyloidosis. Amyloidosis of the heart, lungs, adrenals can significantly prevail to kidney damage and be expressed at the forefront of thanatogenesis.

Myocardial infarction in patients with familial Mediterranean fever and cardiac lesions.

The investigation of relatively rare affections in familial Mediterranean fever--cardiac and lung lesions and pathogenesis of myocardium infarction in background of cardiac lesions is actual. Clinical-morphological analysis of 68 autopsy cases was done. The investigation data observes that cardiac amyloidosis as a dominated morphological manifestation in FMF can leads to heart failure and death. Macroscopically cardiac lesions as a cardiomegaly was observe. The morphological manifestation of cardiac affections in FMF was amyloidosis of the vessels and myocardium stroma. Amyloidosis of the heart valves leads to deformity and clinical-morphological picture of heart defect perform. The large amyloid areas of myocardium leading to the heart insufficiensy according to clinical and instrumental data as pseudoinfarctions were manifested. Myocardium infarction develops in background of cardiac lesions in FMF--amyloid angiopathias, which were more expressed in arteriolar walls, with narrowing or obstructing of lumina, and accompanied with them--coronary vasculitis. The main predisposing pathogenic factors for myocardial infarction can be atherosclerotic changes of the vessels also, which were complicated by amyloid depositions of the vascular walls. Cardiac failure can develop before renal amyloidosis and uremia.

Amyloid A Amyloidosis After Renal Transplantation: An Important Cause of Mortality.

BACKGROUND: There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients. METHODS: Eighty-one renal transplant recipients with FMF-associated AA amyloidosis (group 1) and propensity score-matched transplant recipients (group 2, n = 81) with nonamyloidosis etiologies were evaluated in this retrospective, multicenter study. Recurrence of AA amyloidosis was diagnosed in 21 patients (group 1a), and their features were compared with 21 propensity score-matched recipients with FMF amyloidosis with no laboratory signs of recurrence (group 1b). RESULTS: The risk of overall allograft loss was higher in group 1 compared with group 2 (25 [30.9%] versus 12 [14.8%]; P = 0.015 [hazard ratio, 2.083; 95% confidence interval, 1.126-3.856]). Patients in group 1 were characterized by an increased risk of mortality compared with group 2 (11 [13.6%] versus 0%; P = 0.001 [hazard ratio, 1.136; 95% confidence interval, 1.058-1.207]). Kaplan-Meier analysis revealed that 5- and 10-year patient survival rates in group 1 (92.5% and 70.4%) were significantly lower than in group 2 (100% and 100%; P = 0.026 and P = 0.023, respectively). Although not reaching significance, overall, 5- and 10-year graft survival rates (57.1%, 94.7%, and 53.8%, respectively) in group 1a were worse than in group 1b (76.2%, 95%, and 77.8%, respectively; P = 0.19, P = 0.95, and P = 0.27, respectively). CONCLUSIONS: AA amyloidosis is associated with higher risk of mortality after kidney transplantation. Inflammatory indicators should be monitored closely, and persistent high levels of acute-phase reactants should raise concerns about amyloid recurrence in allograft.

Familial Mediterranean Fever Is Associated With Increased Mortality After Kidney Transplantation-A 19 Years' Single Center Experience.

BACKGROUND: Current data regarding the outcome of kidney transplantation in patients with familial Mediterranean fever (FMF) who reach end-stage renal disease (ESRD) due to reactive amyloidosis A (AA) are scarce and inconclusive. METHODS: The outcomes of 20 patients with FMF and biopsy-proven AA amyloidosis that were transplanted between 1995 and 2014 were compared with 82 control patients (32 with diabetes mellitus and 50 with nondiabetic kidney disease). Major outcome data included overall patient and graft survivals. RESULTS: During a mean overall follow-up of 116.6 ± 67.5 months 11 patients (55%) with FMF died versus 26 patients (31%) in the control group. Median time of death for patients with FMF was 61 months (range, 16-81) after transplantation. Estimated 5-year, 10-year, and actuarial 15-year overall patients survival rates were 73%, 45%, and 39%, respectively, for patients with FMF, versus 84%, 68% and 63%, respectively, for the control group (P = 0.028). FMF was associated with more than twofold increased risk for death after transplantation, and with a threefold increased risk for hospitalization because of infections during the first year. Infections and cardiovascular disease were the cause of death in the majority of patients with FMF. Overall graft survival was similar between the groups. Recurrence of AA amyloidosis was diagnosed in 2 patients during the first year after transplantation. CONCLUSIONS: FMF is associated with increased risk of mortality after kidney transplantation.

Infections After Renal Transplant in Recipients With Familial Mediterranean Fever: A Life-Threatening Issue.

OBJECTIVES: We evaluated long-term results and infections requiring hospitalization in kidney transplant patients with Familial Mediterranean Fever (associated amyloidosis-type). MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with familial Mediterranean fever with at least 1-year posttransplant follow-up. Kidney transplant recipients with primary glomerulonephritis and equivalent demography, immunity status, and follow-up comprised the control group. RESULTS: In 32 patients with familial Mediterranean fever versus 25 control patients (mean follow-up 82 ± 57 vs 79 ± 54 mo; P = .82), average serum creatinine values were 1.7 ± 0.9 versus 1.5 ± 1.0 mg/dL (P = .41) at discharge, 1.4 ± 0.4 versus 1.3 ± 0.5 mg/dL (P = .44) at 1 year, 1.4 ± 0.6 versus 1.3 ± 0.5 mg/dL (P = .63) at 3 years, and 2.0 ± 1.5 versus 2.1 ± 1.5 mg/dL (P = .92) at last follow-up. Groups were not statistically different regarding average inpatient and number of hospitalizations due to infections at 1 year; however, at last follow-up, 26 patients with familial Mediterranean fever (81%) had 8.6 average admissions and 13 control patients (52%) had 2.8 average admissions (P = .02, P < .01). Early posttransplant, both groups were taking a triple drug immunosuppression regimen. However, at 1 and 3 years posttransplant, withdrawal and/or minimization occurred in 40.6% and 83.3% of patients with familial Mediterranean fever and 28% and 55.5% of control patients (P < .05, P < .05). During follow-up, 6 familial Mediterranean fever patients (18.7%) and 2 control patients (8%) died (P = .23). CONCLUSIONS: Although renal transplant patients with associated amyloidosis-type familial Mediterranean fever and those with glomerulonephritis have similar rejection and/or graft loss rates, hospital admissions due to infection and increased mortality are more common in the familial Mediterranean fever group, with immunosuppression drug withdrawal.

Clinical outcomes and survival in AA amyloidosis patients.

AIM: Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. METHODS: A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. RESULTS: Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65±3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p=0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p=0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p=0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3±16 months. CONCLUSION: Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis.

Continuous ambulatory peritoneal dialysis in familial Mediterranean fever amyloidosis patients with end-stage renal failure: a single-centre experience from Turkey.

BACKGROUND/AIMS: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent fever attacks and polyserositis which may lead to the development of AA amyloidosis and end-stage renal disease (ESRD). In this study, we aimed to evaluate the efficacy of continuous ambulatory peritoneal dialysis (CAPD) in FMF-amyloidosis patients with ESRD. METHODS: Forty age- and sex-matched patients undergoing CAPD at our centre between 1996 and 2002 were included in the study. Of these, 10 had FMF-amyloidosis, 10 had diabetes mellitus (DM), 10 had chronic glomerulonephritis (CGN) and 10 had chronic interstitial nephritis (CIN). Efficiency of CAPD, development of complications, presence of other diseases and survival were compared. RESULTS: With the onset of ESRD, the frequency of FMF peritonitis attacks decreased, with less attacks occurring during CAPD in FMF-amyloidosis patients (p < 0.05). There was no significant difference between the FMF-amyloidosis group and other groups in terms of efficiency of CAPD, peritoneal function, complications and survival. DM patients had a shorter survival period compared with CGN and CIN patients (p < 0.05), but there was no survival difference between FMF-amyloidosis patients and other groups (p > 0.05). CONCLUSIONS: We conclude that CAPD is an effective and safe renal replacement therapy for FMF-amyloidosis patients with ESRD.

[Comparative aspects of the course of periodic disease without and with amyloidosis (analysis of 437 case studies)]. / Sravnitel'naia kharakteristika techeniia periodicheskoi bolezni bez amiloidoza i s amiloidozom (analiz 437 nabliudenii).

The paper is concerned with an analysis of a course of periodic disease (PD) without and with amyloidosis using also a method of the determination of survival rates in 437 patients followed up for 20 yrs. A course of PD without amyloidosis was benign and did not affect the patients' survival. In the development of amyloidosis the prognosis was unfavorable and determined by a degree of generalization of amyloidosis.

Long-term outcome of renal transplantation in patients with familial Mediterranean fever amyloidosis: a single-center experience.

INTRODUCTION: Familial Mediterranean fever (FMF) is an autosomal-recessive disorder, affecting multiple organs. The AA type of amyloidosis is most common and serious complication cause nephropathy and end-stage renal disease (ESRD). Renal transplantation (RTX) remains treatment of choice for ESRD. We aimed to investigate long-term results of RTX in patients with FMF amyloidosis. PATIENTS AND METHODS: We compared the outcomes of 18 patients (12 men and 6 women) with FMF amyloidosis among 601 (2.9%) transplants with 200 control patients. Demographic data and gene analysis were evaluated. RESULTS: In our study the 1-year graft and patient survivals were 94.44% and 100%, respectively. At 5 years after RTX, they were 94.73% and 88.88%, respectively, in the FMF group without difference from controls. Mean creatinine level at 1 and 5 years were 1.43 ± 0.54 and 1.73 ± 0.89, respectively. The results of MEFV mutation analyses were: M694V/M694V homozygote in 1 patient, M694V/EQ148 in 3, M694V/V726A in 2, 680M-I/E148Q in 3, M694V/M680I in 5, R202Q/M680I in 2, and M694V/R202Q in 2. Recurrence was noticed in 1 patient with M694V/M680I. One patient died because of graft loss and cardiac complications with M694V/M680I gene analysis. Colchicine was reduced in 4 patients owing to side effects. CONCLUSION: Long-term outcomes of transplantation in patients with amyloidosis secondary to FMF is similar to that in the general transplant population and maintenance colchicine, even after decreasing its dose, effectively prevents recurrence of amyloidosis in the allograft.

Familial Mediterranean fever: risk factors, causes of death, and prognosis in the colchicine era.

We assessed the risk factors and causes of death in patients with familial Mediterranean fever (FMF) in an era when colchicine is the standard therapy for all patients.This study included all FMF patients who had presented to any of the internal medicine, rheumatology, or nephrology clinics at Dokuz Eylul University Hospital between 1992 and 2009. Of the 650 patients with FMF identified, 587 (90.3%) had either a face-to-face (n = 380) or telephone (n = 193) interview, or were confirmed as deceased. A structured questionnaire was used to obtain socioeconomic and demographic data, presenting and cumulative clinical features, and disease severity scores.During the follow-up period mortality was analyzed by calculating age- and sex-standardized mortality ratio (SMR) according to the mortality statistics of the Turkish population. Factors predictive of mortality were evaluated using Kaplan-Meier and Cox proportional hazard models. Sixty-three (9.7%) patients whose initial demographic and major clinical characteristics were similar to the rest of the group could not be contacted during the study period.Most (94.2%) patients were on colchicine at the time of the study. Thirty-seven (6.3%) patients had biopsy-verified amyloidosis, and 44 (7.5%) had renal disease. During a median follow-up of 6 years, 14 patients (9 women) died, and amyloidosis and its related complications were the leading causes of death in 7 patients. Univariate analysis revealed that increasing age, coronary heart disease, hypertension, renal disease, and amyloidosis were associated with mortality. However, Cox regression analysis showed amyloidosis as the only significant predictor of mortality (p < 0.001). The overall patient survival rate was not significantly different from the age- and sex-matched Turkish general population (SMR, 1.48; 95% confidence interval, 0.817-2.49).Our findings suggest that although the survival of FMF patients in the colchicine era is comparable to that of the general population, renal involvement still predicts mortality.

Clinical outcomes and survival in AA amyloidosis patients / Desfechos clínicos e sobrevida em pacientes com amiloidose AA

Abstract Aim Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. Methods: A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. Results: Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65 ± 3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p = 0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p = 0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p = 0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3 ± 16 months. Conclusion Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis.

Resumo Objetivo: A amiloidose AA é uma complicação rara de condições inflamatórias crônicas. A maior parte dos pacientes com amiloidose AA apresenta nefropatia, que leva à insuficiência renal e à morte. Estudaram-se as características clínicas e a sobrevida em pacientes com amiloidose AA. Métodos: Analisaram-se retrospectivamente 81 pacientes (51 homens, 30 mulheres) com amiloidose AA comprovada por biópsia renal. Os pacientes foram divididos em grupos de desfecho bom e ruim de acordo com os resultados de sobrevida. Resultados: A maior parte dos pacientes (55,6%) tinha proteinúria na faixa nefrótica no momento do diagnóstico. Os distúrbios subjacentes mais frequentes foram a febre familiar do Mediterrâneo (FFM, 21,2%) e a artrite reumatoide (10,6%) no grupo de desfecho bom e a malignidade (20%) no grupo de desfecho ruim. Somente a pressão arterial diastólica no grupo de desfecho bom e o nível de fósforo no grupo de desfecho ruim foram mais elevados. Os níveis séricos de creatinina aumentaram após o tratamento em ambos os grupos, enquanto a proteinúria diminuiu no grupo de desfecho bom. O aumento na creatinina sérica e a diminuição na TFGe do grupo de desfecho ruim foram mais significativos no grupo de desfecho bom. No momento do diagnóstico, 18,5% e 27,2% de todos os pacientes tinham doença renal crônica avançada (estágios 4 e 5, respectivamente). A duração média da sobrevida renal foi de 65 ± 3,54 meses. Entre todos os pacientes, 27,1% iniciaram tratamento de diálise durante o período de seguimento e 7,4% de todos os pacientes foram submetidos a transplante renal. Níveis elevados de pressão arterial sistólica [taxas de risco (HR) 1,03, intervalo de confiança (IC) de 95%: 1 a 1,06, p = 0,036], creatinina sérica (HR 1,25, IC 95%: 1,07 a 1,46, p = 0,006) e excreção urinária de proteínas (HR 1,08, IC 95%: 1,01 a 1,16, p = 0,027) foram preditores de doença renal terminal. A mediana da sobrevida de pacientes com comprometimento de órgãos foi de 50,3 ± 16 meses. Conclusão: O presente estudo indicou que a FFM constituiu uma grande proporção de casos e crescente quantidade de pacientes com amiloidose AA idiopática. Adicionalmente, observou-se que a sobrevida do paciente não foi afetada pelas diferentes causas etiológicas na amiloidose AA.

The M694V variant of the familial Mediterranean fever gene is associated with sporadic early-onset Alzheimer's disease in an Italian population sample.

BACKGROUND: Inflammation is deemed to play a crucial role in the pathogenesis of Alzheimer's disease (AD). We sought to determine whether the proinflammatory M694V mutation of pyrin, the gene responsible for familial Mediterranean fever, could lead to an increased risk for AD. METHODS: We compared the M694V variant genotypes in 378 sporadic AD patients and 384 healthy control subjects of Italian descent. RESULTS: After adjustment for potential confounders, the M694V mutation was found to be associated with an increased risk for AD in subjects with an age at onset of 65 years or younger (multivariate-adjusted odds ratio, OR: 3.01, 95% confidence interval, CI: 1.24-6.72, p = 0.021), but not in patients with an age at onset older than 65 years (multivariate-adjusted OR: 0.81, 95% CI: 0.34-1.99, p = 0.847). Kaplan-Meier analysis indicated that AD patients bearing the M694V mutation presented with disease onset 7 years earlier than carriers of the wild-type genotype (log rank = 41.61, p < 0.001). CONCLUSION: Our data indicate that the M694V sequence variant in the pyrin gene might influence the age at onset of AD in the Italian population.

Amyloidosis in children with familial Mediterranean fever.

The clinical and laboratory findings of 35 children with familial Mediterranean fever who developed amyloidosis are described. The types, frequency, and severity of attacks of familial Mediterranean fever in these children were no different from patients with this disease without amyloidosis. Although amyloid was widely deposited in all tissues, the major clinical manifestations of the amyloidosis were proteinuria, the nephrotic syndrome, and progressive renal failure. Only 20% of the patients were alive 5 years after the first appearance of proteinuria.

MEFV mutations in multiplex families with familial Mediterranean fever: is a particular genotype necessary for amyloidosis?

Familial Mediterranean fever (FMF) is an autosomal recessive disease. It is characterized by recurrent febrile episodes in association with peritonitis, pleuritis, and arthritis. Progressive systemic amyloidosis is the most important complication of FMF that inevitably leads to chronic renal failure. Recently, the gene for FMF, MEFV, has been cloned and four missense mutations have been described: M694V, M680I, V726A, and M694I. Initial studies have suggested that the presence of the M694V mutation carries a significant risk for the development of amyloidosis. In this study, we present seven families, in which at least two individuals have been diagnosed with FMF and at least one with amyloidosis. Among 18 individuals, in whom molecular testing was performed for the four aforementioned mutations, ten had amyloidosis. None of these ten individuals was found to be homozygous for the M694V mutation. In three families, there were two sibs with amyloidosis. None of the sib-pairs with amyloidosis was found to have the same genotype. There were two or more sibs with the same genotype in four families. Only one sib from each family developed amyloidosis in these families. These results provide evidence that FMF patients without the M694V mutation are also at risk for the development of amyloidosis. Particular mutations themselves do not appear to be sufficient to explain the occurrence of amyloidosis in all cases with FMF.