scholarly journals Evaluation of E148Q and Concomitant AA Amyloidosis in Patients with Familial Mediterranean Fever

2021 ◽  
Vol 10 (16) ◽  
pp. 3511
Author(s):  
Zehra Serap Arici ◽  
Micol Romano ◽  
David Piskin ◽  
Ferhat Guzel ◽  
Sezgin Sahin ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Clinical Phenotype ◽  
Clinical Manifestations ◽  
Histopathological Diagnosis ◽  
Close Monitoring ◽  
Aa Amyloidosis ◽  
Homozygous Genotype ◽  
Age Of Diagnosis ◽  
Mediterranean Fever

The aim of the study was to compare the clinical phenotype of patients with familial Mediterranean fever (FMF)-related AA amyloidosis, according to the age of FMF diagnosis and E148Q genotype. Patients with biopsy-confirmed FMF-related AA amyloidosis were included in the study. Tel-Hashomer criteria were applied in the diagnosis of FMF. All patients had detailed baseline assessment of clinical features, renal functions, genetic testing, histopathological diagnosis of amyloidosis, and treatment received. Multiple comparisons were performed according to the age of diagnosis, disease phenotype, mutation, and mortality. Our study included 169 patients with a diagnosis of AA amyloidosis. There were 101 patients diagnosed with FMF < 18 years of age and 68 patients diagnosed who were ≥18 years of age. The three most common clinical manifestations were fever (84.6%), abdominal pain (71.6%), and arthritis (66.9%). The most common allele among FMF patients was M694V (60.6%), followed by E148Q (21.4%), and M680I (10.3%). The most frequent genotypes were M694V/M694V (45.0%), M694V/E148Q (14.8%), and E148Q/E148Q (11.2%) among 169 patients in our cohort. During the follow-up period, 15 patients (10 male, 5 female) died, of whom 14 had M694V homozygous genotype and one was homozygous for E148Q. Clinicians should be aware of patients with homozygous E148Q genotype for close monitoring and further evaluation. The possible relationship between E148Q and AA amyloidosis needs to be confirmed in other ethnicities.

scholarly journals POS1372 EVALUATION OF E148Q AND CONCOMITANT AA AMYLOIDOSIS SECONDARY TO FAMILIAL MEDITERRANEAN FEVER AFTER ADJUSTED CLINICAL-DEMOGRAPHIC CHARACTERISTICS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 968.1-968
Author(s):  
Z. S. Arici ◽  
M. Romano ◽  
D. Piskin ◽  
F. Guzel ◽  
M. Yilmaz ◽  
...  
Keyword(s):  
Family History ◽  
Familial Mediterranean Fever ◽  
Allele Frequency ◽  
Demographic Characteristics ◽  
Renal Amyloidosis ◽  
Histopathological Diagnosis ◽  
Aa Amyloidosis ◽  
History Of ◽  
Mediterranean Fever

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

scholarly journals A CASE OF LATE DIAGNOSIS OF FAMILIAL MEDITERRANEAN FEVER COMPLICATED BY AA-AMYLOIDOSIS

The Clinician ◽  
2018 ◽  
Vol 12 (2) ◽  
pp. 37-42
Author(s):  
S. I. Shchadneva ◽  
E. E. Ustinova ◽  
L. V. Belozertseva ◽  
V. V. Gorbunov ◽  
N. S. Kurbatova
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Nephrotic Syndrome ◽  
Familial Mediterranean Fever ◽  
Lupus Erythematosus ◽  
Morphological Changes ◽  
Clinical Manifestations ◽  
Aa Amyloidosis ◽  
Systemic Lupus ◽  
Periodic Disease ◽  
Mediterranean Fever

The aimof study was to describe a clinical case of a hereditary disease with autosomal recessive type of inheritance – familial Mediterranean fever (FMF).Materials and methods.Patient A., 19 years old, Armenian, was hospitalized in the Department of rheumatology of the clinical hospital with complaints of periodic temperature rises to 39 °C, paroxysmal pain in the abdomen, ankle and hip joints, legs edema. In anamnesis from 8 months of age there were attacks of 1–2 day abdominal pain in combination with febrile fever; from 2 years there were arthralgia of the ankle joints, followed by knee and hip. Attacks of fever and joint syndrome recurred 3–4 times a year, lasted for 2–3 days, and disappeared spontaneously. Treatment with nonsteroidal anti-inflammatory drugs and small doses of prednisone was carried out. The examination in the hospital revealed nephrotic syndrome without impaired renal function, increasing of erythrocyte sedimentation rate (up to 62 mm/h), C-reactive protein (up to 60 mg/dl), leukocytosis (up to 16.7 × 109/L). The immunological examination revealed no abnormalities. Bacteriological and serological studies have ruled out the possibility of infectious diseases. Electrocardiography, echocardiography, ultrasound of abdomen and kidneys, multispiral computed tomography of kidneys and retroperitoneum, magnetic resonance imaging of the sacroiliac joints, nephrobiopsy were performed.Results.During the examination, a wide differential diagnosis with infectious and rheumatic diseases was carried out. Taking into account the polysyndromicity of clinical manifestations, systemic lupus erythematosus was suggested. An induction course of immunosuppressive therapy was conducted, that was ineffective. The diagnosis of systemic lupus erythematosus was doubtful and to clarify the nature of kidney morphological changes nephrobiopsy was performed that revealed the presence of kidneys AA-amyloidosis. Given these data in conjunction with clinical manifestations, the patient»s nationality, FMF was diagnosed and colchicine 2 mg/day was appointed. It was possible to stop the clinical symptoms of inflammation in FMF, but the nephrotic syndrome due to amyloidosis persists.Conclusion.The presented observation demonstrates the complexity of FMF diagnosis that verified 18 years after the appearance of the first disease symptoms. The diagnosis was helped by the presence of disease clinical manifestations and kidneys morphological study that revealed the development of a serious complication of periodic disease – AA-amyloidosis. Treatment with colchicine allowed to stop the symptoms of periodic disease.

scholarly journals AB0055 SOLUBLE TREM-1 LEVELS IN FAMILIAL MEDITERRANEAN FEVER RELATED AA-AMYLOIDOSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1329.2-1330
Author(s):  
S. Ugurlu ◽  
B. H. Egeli ◽  
I. M. Bolayirli ◽  
H. Ozdogan
Keyword(s):  
Familial Mediterranean Fever ◽  
Demographic Data ◽  
Enzyme Linked Immunosorbent Assay ◽  
Aa Amyloidosis ◽  
Control Groups ◽  
Tertiary Center ◽  
Healthy Control ◽  
Mediterranean Fever ◽  
The Mean

Background:Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is a monocyte and neutrophil receptor functioning in innate immunity. TREM-1 produces proinflammatory cytokines and serves for neutrophil degranulation. TREM-1 activity is well known in the pathogenesis of sepsis; hence it can be also present in autoinflammatory diseases such as the most common monogenic one, Familial Mediterranean Fever (FMF).Objectives:The objective of this study is to measure soluble TREM-1 (sTREM-1) activity in severe FMF cases complicated with systemic AA-Amyloidosis.Methods:The cohort of the study includes regularly followed FMF related AA-Amyloidosis patients in a tertiary center outpatient rheumatology clinic. Soluble TREM-1 levels were measured using enzyme-linked immunosorbent assay (ELISA). In addition, demographic data, renal function tests, acute phase reactants, and medical prescription history was also noted and analyzed. None of the FMF diagnosed patients had an attack during the collection of the blood samples.Results:The patients were categorized into 4 groups: FMF related AA-Amyloidosis patients (A(+) FMF(+)), FMF unrelated AA-Amyloidosis (FMF(-) A(+)), FMF patients without Amyloidosis diagnosis (FMF(+) A (-)), and healthy controls (HC). The mean ages, TREM-1, C - reactive protein (CRP), and Creatinine levels of each group are shown in Table 1. TREM-1 levels were found to be significantly higher in A(+) FMF(+) group than FMF(+) A (-), and healthy control groups (p= 0.001 and 0.002). Nevertheless, this difference was not found in between A(+) FMF(+) and FMF(-) A(+) (p= 0.447). In addition, the TREM-1 levels of FMF(+) A (-), and healthy control groups were not different (0.532). In A(+) FMF(+) group, 36 patients used colchicine with the mean dose of 1.9±0.8 mg/day, 14 patients used anakinra, and 9 patients used canakinumab. In FMF(+) A (-) group all 20 patients used colchicine with the mean dose of 2.8±0.9 mg/day, 1 patient used anakinra, and 2 patients used canakinumab.Table 1.Clinical Features of Patients and TREM-1 levelsA(+) FMF(+)(n= 42)FMF(-) A(+)(n=5)FMF(+) A(-)(n=20)HC(n=20)Age43.9±12.954.8±1935.3±9.6435.4±6.57TREM-1735.3±566.51247.1±1349.2414.3±142.3439.2±104.6CRP11.1±14.251.3±98.325.8±541.8±1.7Creatinine1.6±1.83.28±4.170.7±0.150.7±0.15Conclusion:In conclusion, TREM-1 is a proinflammatory marker found significantly high in AA-amyloidosis patients regardless of their FMF diagnosis. TREM-1 may be useful in AA-amyloidosis follow-up and early diagnosis since currently there is a deficit of an early diagnostic marker of amyloidosis. This study is a cross-sectional one so it is hard to reach a conclusion on the effectiveness of TREM-1 during regular FMF follow-up for the secondary prevention of amyloidosis. However, the sensitivity of TREM-1 as a marker cannot be denied in amyloidosis.Disclosure of Interests:None declared

scholarly journals RECURRENT EPISODES OF FEVER AND ARTHRITIS IN AN ADULT PATIENT

2017 ◽  
Vol 26 (2) ◽  
pp. 89-95
Author(s):  
Claudia Cobilinschi ◽  
◽  
Daniela Opris Belinski ◽  
Denisa Predeteanu ◽  
Ruxandra Ionescu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Familial Mediterranean Fever ◽  
Adult Patient ◽  
Reactive Arthritis ◽  
Standard Treatment ◽  
Mefv Gene ◽  
Clinical Manifestations ◽  
Common Condition ◽  
Aa Amyloidosis ◽  
Mediterranean Fever

Familial Mediterranean Fever (FMF) is the most common condition in the group of autoinflammatory diseases. It has a relatively heterogeneous clinical display included in the Tel-Hashomer diagnostic criteria that can be further confirmed by genetic testing showing a mutation in the MEFV gene. AA Amyloidosis is the most sever complication in these patients. Colchicine is the standard treatment and/or alternative biological agents if necessary. This article aims to describe the evolution of a patient with FMF, firstly diagnosed as reactive arthritis, his clinical manifestations and therapeutic options.

scholarly journals AB1065 VISIT COMPLIANCE IN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER: RESULTS FROM A GAZI UNIVERSITY FMF COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1822.1-1822
Author(s):  
R. Bilici Salman ◽  
A. Avanoğlu Güler ◽  
H. Satiş ◽  
H. Karadeniz ◽  
H. Babaoglu ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Family History ◽  
Familial Mediterranean Fever ◽  
Predictive Factors ◽  
Severity Score ◽  
Comorbid Disease ◽  
Rheumatology Clinic ◽  
Mediterranean Fever ◽  
One Year

Background:Follow-up in all rheumatologic patients is critical, particularly Familial Mediterranean Fever (FMF). Current recommendations for all experts by the EULAR state that patients with FMF should be evaluated 6-monthly intervals to monitore the character and frequency of the attacks and the acute phase response. Disease-related complications such as amyloidosis can beasymptomaticand need only a careful follow-up.Objectives:to quantify this phenomenon and to find predictive factors of visit compliance in patients with FMF.Methods:The study included 474 adult patients with a diagnosis of FMF who followed at the outpatient rheumatology clinic of tertiary university hospital, from January 2018 to December 2018. . Demographic, socioeconomic data, familiy history, comorbid disease, medication history, characteristics, the International Severity Score for FMF (ISSF),autoinflammatory disease damage index (ADDI) were recorded. Visit compliance was defined as the presence of two visits in the outpatient rheumatology clinic for FMF last one year for the purposes set out in EULAR suggestion.Those who had fewer than two visits in the last one year were considered noncompliant.Results:230 (48.5%) were compliant while 244 (51.5 %) patients were noncompliant with their rheumatology visit. Both compliant and noncompliant patients had similar median age and disease duration. Female sex and being married was increased the visit compliance.The results of the logistic regression model exploring factors associated with compliance indicated that presence of family history in parents, absence of family history in sibling, treatment with biologic agents, other drug using,presence of more than 2 attacks except fever and adequate medical care were important predictors of visit compliance.Conclusion:In conclusion, if FMF patients visit compliance increase, their functionality, medication adherence and quality of life will increase and flares and complication of disease can decrease. Thus, we highlight some recommendations for FMF specialist, patients and health care providers to improve outcomes.Table 2.Multivariate logistic regression analysis for predictive factors of visit compliance of the patients with FMF, n=430Adj. OR%95 CI**pFamily history in parents(positive history vs negative)1,81,0-3,10.03Family history in sibling(negative history vs positive)1,91,2-3,10.004Comorbid disease status1,30,7-2,50.32Treatment(anakinra&canakinumab vs colchicine)3,71,7-8,20.001Drug using(other drugs vs FMF drugs)2,21,1-4,40.01More than 2 attacks except fever2,31,2-4,00.004Chronic peripheral arthritis2,30,8-6,60.10Proteinuria2,20,7-6,70.14Adequate medical care1,91,2-3,10.003Number of index flare within last 12-month0,90,9-1,00.38ISSF severity score0,80,7-1,10,30Disclosure of Interests:None declared

Thyroid disorders in familial Mediterranean fever: think about AA amyloidosis!

2021 ◽  
Author(s):  
Hélène Vergneault ◽  
Rim Bourguiba ◽  
Samuel Ardois ◽  
Anael Dumont ◽  
Léa Savey ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Thyroid Disorders ◽  
Aa Amyloidosis ◽  
Mediterranean Fever

AB0968 Adrenomedullin Levels in Patients with Familial Mediterranean Fever: A Long Term Follow-Up

2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 1222.2-1222
Author(s):  
A. Polat ◽  
C. Saglam ◽  
Y.G. Kurt ◽  
G. Basbozkurt ◽  
B. Sozeri ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Long Term Follow Up ◽  
Mediterranean Fever

Infliximab therapy for familial Mediterranean fever-related amyloidosis: case series with long term follow-up

2012 ◽  
Vol 31 (8) ◽  
pp. 1267-1271 ◽  
Author(s):  
Z. Birsin Özçakar ◽  
Selçuk Yüksel ◽  
Mesiha Ekim ◽  
Fatoş Yalçınkaya
Keyword(s):  
Familial Mediterranean Fever ◽  
Case Series ◽  
Infliximab Therapy ◽  
Long Term Follow Up ◽  
Mediterranean Fever
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