THU0334 Differences in the features of familial mediterranean fever among patients from europe as compared to those from the eastern mediterranean countries

Abstract There have been few reports of the patients with Familial Mediterranean Fever (FMF) in Japan, probably because FMF patients are preoccupied to be rare in Japan. We experienced 10 cases likely to be clinically diagnosed as FMF with periodic fever of unknown origin. FMF is an autosomal recessive disease resulting from the genetic mutations in the FMF gene (MEFV), which codes for a protein named Pyrin. Pyrin is expressed in mainly polymorphonuclear cells and monocytes and it is proposed that it regulates inflammation. The MEFV gene is located on chromosome 16p13.3 and comprises 10 exons. Several mutations in the MEFV gene have been identified, however the mutations are mostly located in exon 2 and 10. Therefore, we performed genetic screening of exon 2 and 10 in the 10 patient samples. The median age of the patients was 34 (17–49) years old. They are four males and six females. DNA was isolated from polymorphonuclear cells of the patients and PCR was performed with selective primers of exon 2 and 10 of MEFV gene, respectively. Thereafter, direct sequence of exon 2 and 10 of the PCR products was performed. As a result, the mutations of E148Q in exon 2 and M694I in exon 10, which are commonly observed in previous reports, were identified in seven and six out of 10 patients, respectively. All patients had either E148Q or M694I mutation. Three patients have both E148Q and M694I mutations. One 50-year-old female patient, who had a homozygous M694I mutation, suffered from severe renal AA amyloidosis. The mutation at M694 has been mostly reported as M694V, particularly in Mediterranean countries, however interestingly, all of the mutations of M694 were M694I, not M694V in our 10 Japanese patients. It is reported that healthy carrier frequency of the E148Q mutation was about 16% in Japan, so it is suggested that E148Q mutation may be profoundly involved in cause of disease, because E148Q mutation is observed among 70% of our patients. We herein report the unique genetic features of FMF patients in Japan. A further large scale of investigation would be necessary for confirming the significance of E148Q and M694I mutations in FMF patients in Japan.

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P050 Consensus based practice guidelines for the management and treatment of Juvenile familial Mediterranean fever: the Egyptian College of Paediatric Rheumatology initiative

Rheumatology ◽

10.1093/rheumatology/keab722.042 ◽

2021 ◽

Vol 60 (Supplement_5) ◽

Author(s):

S Salah ◽

H Lotfy ◽

M Hassan ◽

H Abdulhady ◽

H Salah ◽

...

Keyword(s):

Early Diagnosis ◽

Familial Mediterranean Fever ◽

Scientific Evidence ◽

Mefv Gene ◽

General Medicine ◽

Qualitative Synthesis ◽

Diagnosis And Management ◽

Mediterranean Countries ◽

Grade Of Recommendation ◽

Mediterranean Fever

Abstract Background Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease, with the highest prevalence amongst Mediterranean countries including Egypt (where there is high carrier rate of MEFV gene), characterized by recurrent attacks of fever and polyserositis. Mutations in the MEFV gene encoding pyrin has been associated with the disease, which causes exaggeration of the inflammatory response through uncontrolled interleukin production. Issuing updated treatment recommendations are vital for the treating healthcare professionals to get well acquainted with its diagnosis & treatment. To produce consensus-based recommendations to guide the early diagnosis, management and follow-up of patients with FMF. Methods The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by the core team. A qualitative synthesis of scientific evidence based on systematic review and clinical experience was conducted to compile evidence for the diagnosis and management of FMF. A consensus process was conducted among the expert panel to generate the final recommendations and grade their strength. 3 rounds of Delphi process were carried out. Results Following 3 Delphi rounds, recommendations were developed for: early diagnosis, who to treat, treatment targets, genetic testing and its interpretation in association with clinical presentation, treatment of FMF and dealing with acute attacks, monitoring of management, identify treatment response, systemic affection, persistent attacks or inflammation, resistant cases, protracted symptoms, as well as remission status. Algorithm for patients’ diagnosis and management is provided. The final document comprises 12 recommendations, each presented with its degree of agreement (0–10), Level of agreement, grade of recommendation and rationale. The degree of agreement was >7/10 in all instances. Conclusion This guideline provides comprehensive approach to the accurate diagnosis and effective management/monitoring of FMF. It also represents a model for the incorporation of medical genetics practice into the more traditional domains of general medicine.

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The report of sequence analysis on familial Mediterranean fever gene (MEFV) in South-eastern Mediterranean region (Kahramanmaraş) of Turkey

Rheumatology International ◽

10.1007/s00296-015-3329-7 ◽

2015 ◽

Vol 36 (1) ◽

pp. 25-31 ◽

Cited By ~ 8

Author(s):

Metin Kilinc ◽

Eda Ganiyusufoglu ◽

Hatice Sager ◽

Ahmet Celik ◽

Seref Olgar ◽

...

Keyword(s):

Sequence Analysis ◽

Familial Mediterranean Fever ◽

Mediterranean Region ◽

Eastern Mediterranean ◽

Eastern Mediterranean Region ◽

South Eastern ◽

Mediterranean Fever

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EULAR recommendations for the management of familial Mediterranean fever

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-208690 ◽

2016 ◽

Vol 75 (4) ◽

pp. 644-651 ◽

Cited By ~ 152

Author(s):

Seza Ozen ◽

Erkan Demirkaya ◽

Burak Erer ◽

Avi Livneh ◽

Eldad Ben-Chetrit ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Eastern Mediterranean ◽

Mediterranean Area ◽

Supporting Evidence ◽

Level Of Evidence ◽

Eular Recommendations ◽

Grade Of Recommendation ◽

Mediterranean Fever ◽

Eastern Mediterranean Area

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, but many rheumatologists are not well acquainted with its management. The objective of this report is to produce evidence-based recommendations to guide rheumatologists and other health professionals in the treatment and follow-up of patients with FMF. A multidisciplinary panel, including rheumatologists, internists, paediatricians, a nurse, a methodologist and a patient representative, was assembled. Panellists came from the Eastern Mediterranean area, Europe and North America. A preliminary systematic literature search on the pharmacological treatment of FMF was performed following which the expert group convened to define aims, scope and users of the guidelines and established the need for additional reviews on controversial topics. In a second meeting, recommendations were discussed and refined in light of available evidence. Finally, agreement with the recommendations was obtained from a larger group of experts through a Delphi survey. The level of evidence (LoE) and grade of recommendation (GR) were then incorporated. The final document comprises 18 recommendations, each presented with its degree of agreement (0–10), LoE, GR and rationale. The degree of agreement was greater than 7/10 in all instances. The more controversial statements were those related to follow-up and dose change, for which supporting evidence is limited. A set of widely accepted recommendations for the treatment and monitoring of FMF is presented, supported by the best available evidence and expert opinion. It is believed that these recommendations will be useful in guiding physicians in the care of patients with FMF.

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Familial Mediterranean Fever (FMF), Female and Male Fertility: Literature Review

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2021.01.3-11 ◽

2021 ◽

pp. 3-11

Author(s):

П.О. Соцкий

Keyword(s):

Familial Mediterranean Fever ◽

Male Fertility ◽

Eastern Mediterranean ◽

Reproductive Function ◽

Peritoneal Adhesion ◽

The Past ◽

The World ◽

Mediterranean Fever ◽

Testicular Insufficiency ◽

The Relationship

Семейная средиземноморская лихорадка (CCЛ) - моногенное наследственное аутовоспалительное заболевание, характеризующееся периодически повторяющимися приступами лихорадки, серозитами разной локализации, артритами, эризипелоидоподобным высыпанием. Хотя ССЛ болеют преимущественно представители популяций восточно-средиземноморского происхождения (турки, армяне, арабы, евреи-сефарды), в наши дни болезнь регистрируется по всему миру, что связано с непрерывными миграционными процессами. Потенциальные осложнения ССЛ (фиброз и амилоидоз) и их лечение колхицином могут повлиять на репродуктивную систему больных либо путем обструкции маточных труб, либо через избыточное образование дефектных сперматозоидов и ооцитов, либо вследствие овариальной/тестикулярной недостаточности. Амилоидоз с преимущественным отложением амилоида в яичниках и яичках может приводить к женскому и мужскому бесплодию. У мужчин колхицин в редких случаях индуцирует олиго/азооспермию. У женщин основными причинами бесплодия в прошлом считались дисовуляция и перитонеальная адгезия. В последние годы ситуация с фертильностью значительно улучшилась благодаря применению колхицина. В обзоре обобщается текущая информация о взаимосвязи женской и мужской фертильности с ССЛ и приемом колхицина; излагаются современные подходы к восстановлению репродуктивной функции при бесплодии. Акцент сделан на аспектах безопасности терапии, основные положения которой представлены в клинических рекомендациях по лечению ССЛ Европейской антиревматической лиги (EULAR,2016). Familial Mediterranean fever (FMF) is a monogenic inherited autoinflammatory disease characterized by recurrent episodes (attacks) of fever, serositis of different localization, arthritis, erysipelaslike rashes. Eastern Mediterranean persons (especially Turks, Armenians, Arabs, Sephardic Jews) are most frequently affected. Nowadays the disease is registered throughout the world because of migration processes. Potential complications of FMF (fibrosis and amyloidosis) and their treatment with colchicine may affect the reproductive system either by salpinx obstruction causing mechanical infertility, or by excessive formation of defective sperm and oocytes, either due to ovarian /testicular insufficiency. Amyloidosis can lead to female and male infertility with amyloid preponderance in the ovaries and testicles. Colchicine rarely induces oligo/ azoospermia in men. In women, disovulation and peritoneal adhesion were the main causes of infertility in the past. In recent years, the fertility situation has improved considerably due to the use of colchicine. The review summarizes current information on the relationship between female and male fertility with FMF and colchicine; modern approaches to restoring reproductive function in infertility are outlined. The focus is on the aspects of the safety of therapy, the main provisions of which are presented in the clinical recommendations for treatment of the FMF of the European Anti-Rheumatic League (EULAR, 2016).

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