Is bullous skin lesion a risk factor for renal amyloidosis in patients with familial Mediterranean fever?

Background: Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease caused by mutations in the MEFV gene and characterized by recurrent febrile polyserositis. A possible association of FMF and multiple sclerosis (MS) has been suggested in cohorts from Turkey and Israel. Objective: The objective of this study was to investigate the prevalence of MEFV mutations in subjects with MS and in controls in Germany. Methods: One-hundred and fifty seven MS patients with at least one symptom or without symptoms suggestive of FMF from our outpatient clinic were investigated for mutations in exons 2, 3, and 10 of the MEFV gene (group 1). 260 independent MS patients (group 2) and 400 unrelated Caucasian controls (group 3) were screened selectively for the low-penetrance pyrin mutations E148Q and K695R Results: In group 1, 19 MS patients (12.1%) tested positive for a mutation in the MEFV gene, mainly the E148Q ( n=7) substitution. Fifteen of the 19 mutation-positive individuals reported at least one symptom suggestive of FMF. In three cases, we could identify additional family members with MS. In these pedigrees, the E148Q exchange co-segregated with MS ( p=0.026). Frequencies of the pyrin E148Q and K695R mutations were not statistically different between MS group 2 and controls but they occurred with a surprisingly high frequency in the German population. Conclusion: The MEFV gene appears to be another immunologically relevant gene locus which contributes to MS susceptibility. In particular, the pyrin E148Q mutation, which co-segregated with disease in three MS families, is a promising candidate risk factor for MS that should be further explored in larger studies.

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Living kidney transplantation between brothers with unrecognized renal amyloidosis as the first manifestation of familial Mediterranean fever: a case report

BMC Medical Genetics ◽

10.1186/s12881-017-0457-9 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 2

Author(s):

Ramón Peces ◽

Sara Afonso ◽

Carlos Peces ◽

Julián Nevado ◽

Rafael Selgas

Keyword(s):

Kidney Transplantation ◽

Case Report ◽

Familial Mediterranean Fever ◽

Renal Amyloidosis ◽

Mediterranean Fever

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Familial Mediterranean fever during pregnancy: An independent risk factor for preterm delivery

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/j.ejogrb.2008.07.025 ◽

2008 ◽

Vol 141 (2) ◽

pp. 115-118 ◽

Cited By ~ 22

Author(s):

Danielle Ofir ◽

Amalia Levy ◽

Arnon Wiznitzer ◽

Moshe Mazor ◽

Eyal Sheiner

Keyword(s):

Risk Factor ◽

Familial Mediterranean Fever ◽

Preterm Delivery ◽

Independent Risk Factor ◽

Mediterranean Fever

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Renal amyloidosis in familial Mediterranean fever

Kidney International ◽

10.1111/j.1523-1755.2004.00485.x ◽

2004 ◽

Vol 65 (3) ◽

pp. 1118-1127 ◽

Cited By ~ 26

Author(s):

Seza Ozen

Keyword(s):

Familial Mediterranean Fever ◽

Renal Amyloidosis ◽

Mediterranean Fever

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A Proposed Histopathologic Classification, Scoring, and Grading System for Renal Amyloidosis: Standardization of Renal Amyloid Biopsy Report

Archives of Pathology & Laboratory Medicine ◽

10.5858/134.4.532 ◽

2010 ◽

Vol 134 (4) ◽

pp. 532-544 ◽

Cited By ~ 10

Author(s):

Sait Şen ◽

Banu Sarsık

Keyword(s):

Familial Mediterranean Fever ◽

Prognostic Score ◽

Renal Amyloidosis ◽

Grading System ◽

Al Amyloidosis ◽

Pathology Report ◽

Aa Amyloidosis ◽

Microscopic Appearance ◽

Biopsy Report ◽

Mediterranean Fever

Abstract Context.—A disease associated with amyloid deposits, called amyloidosis, is associated with characteristic electron microscopic appearance, typical x-ray pattern, and specific staining. Renal involvement mainly occurs in AA amyloidosis and AL amyloidosis and usually progresses to renal failure. Objective.—The renal histopathologic changes with amyloidosis comprise a spectrum. Clear relationships between the extent of amyloid deposition and the severity of clinical manifestations have not been demonstrated. Whether there is a lack of clinicopathologic correlation is not clear, but studies have revealed the need for standardization of the renal amyloid biopsy report. With these objectives in mind, we proposed a histopathologic classification, scoring, and grading system. Renal amyloidosis was divided into 6 classes, similar to the classification of systemic lupus erythematosus. Amyloid depositions and other histopathologic lesions were scored. The sum of these scores was termed the renal amyloid prognostic score and was divided into 3 grades. Data Sources.—AA amyloidosis was detected in 90% of cases, mostly related to familial Mediterranean fever. Positive correlations between class I and grade I, class VI and grade III, and class III and grade II were observed. Also, a positive correlation was identified between severity of glomerular amyloid depositions, interstitial fibrosis, and inflammation. Because of the inadequacy of the patients' records and outcomes, different therapy regimes, and etiologies, clinical validation of this study has not been completed. Conclusions.—Standardization of the renal amyloid pathology report might be critical for patients' medication and comparison of outcome and therapeutic trials between different clinics. Because of our AA to AL amyloidosis ratio and the predisposition of familial Mediterranean fever–related AA amyloidosis, there is a need for further international collaborative studies.

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