| name | description | evidence |
|---|---|---|
| Type 1 | Classic form presenting with recurrent episodes of fever and serositis. | TRUNCATED |
| Type 2 | A variant characterized by continuous subclinical inflammation, leading to amyloidosis without overt episodes. | TRUNCATED |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:32608308 | REFUTE | The predominant ethnicities were Turkish (41.8%), Lebanese (15.8%), Syrian (6.5%), South-West Asian (7.9%), and South-East Asian (3.0%). | The prevalence in Mediterranean populations, such as Turkish (41.8%) and Lebanese (15.8%), is much higher than 0.1-0.2%. |
| PMID:11053071 | NO_EVIDENCE | Phenotype II is uncommon among the relatives of patients with FMF and amyloidosis. | This study does not provide direct evidence on the overall prevalence of FMF in the Mediterranean populations. |
| PMID:3306755 | REFUTE | Recurrent hereditary polyserositis (RHP) or familial Mediterranean fever (FMF) is a chronic inherited illness of obscure aetiology... and predominantly affects Sephardic Jews, Arabs, Turks and Armenians. | The article suggests that FMF predominantly affects specific Mediterranean populations, implying a higher prevalence than 0.1-0.2% among these groups. |
| PMID:34363075 | NO_EVIDENCE | The aim of this study was to determine the prevalence of FMF in children with cryptogenic cirrhosis and it was high. | The study focused on children with cryptogenic cirrhosis and does not provide general prevalence data for Mediterranean populations. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:31999206 | SUPPORT | Of 1687 patients, 761 had first FMF attack at 3 years. | The study provides evidence that FMF onset can occur in childhood. |
| PMID:23194659 | SUPPORT | Median age at first symptoms was 4 years (range 3 month-37 years) and at diagnosis 10 years (range 2-44 years). | This reference supports the statement by indicating that the majority of FMF cases have an onset in childhood. |
| PMID:1433029 | SUPPORT | The only efficient treatment to prevent this amyloidosis is regular administration of colchicine, from early childhood. | This study highlights that managing FMF from early childhood is crucial to prevent complications. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:28154935 | SUPPORT | Familial Mediterranean fever (FMF) is caused by mutations within the Mediterranean fever (MEFV) gene. These gain of function mutations lead to an increased activation of the inflammasome pyrin with a subsequent disproportional proinflammatory reaction. | Mutations in the MEFV gene result in increased activation of pyrin, causing excessive inflammation. |
| PMID:25307949 | SUPPORT | Mutations in the MEFV gene are associated with the human autoinflammatory disease familial Mediterranean fever (FMF). Pyrin can interact with the inflammasome adaptor ASC and induce inflammatory caspase-1 activation in monocytic cells. | This article discusses the role of pyrin in inducing inflammatory responses, supporting the effect of MEFV gene mutations in causing excessive inflammation. |
| PMID:36889987 | SUPPORT | The MEFV gene mutation spectrum in patients with familial Mediterranean fever links to the role of pyrin in disease pathogenesis. | The mutation spectrum in the MEFV gene is related to the pathogenesis involving pyrin and inflammation, supporting the given statement. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:16344627 | SUPPORT | The spectrum of reported genetic mutations and susceptible ethnicities for the hereditary periodic fever subset of the autoinflammatory diseases has continued to expand. At the same time, the pathogeneses of many of these diseases are now understood to involve different aspects of a common pathway, largely affecting inflammatory cascades related to IL-1 or tumor necrosis factor-alpha. | This reference supports the involvement of IL-1 and inflammatory pathways in autoinflammatory diseases, including Familial Mediterranean Fever (FMF). |
| PMID:29148036 | SUPPORT | Pyrin, encoded by the MEFV gene, is an intracellular pattern recognition receptor that assembles inflammasome complexes in response to pathogen infections. Mutations in the MEFV gene have been linked to autoinflammatory diseases such as familial Mediterranean fever (FMF) or pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). | This reference describes the role of pyrin in inflammasome activation and its link to FMF, supporting the statement about dysregulated inflammatory responses and recurrent inflammatory episodes. |
| PMID:33026080 | SUPPORT | FMF is an autoinflammatory disease characterized by recurrent attacks and increased IL-1 synthesis owing to activation of the pyrin inflammasome. Although knowledge of the mechanisms leading to the activation of pyrin inflammasome is increasing, it is still unknown why the disease is characterized by attacks. | This reference directly mentions recurrent attacks and increased IL-1 synthesis due to pyrin inflammasome activation, supporting the mechanisms described in the statement. |
| PMID:32601469 | SUPPORT | Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by homozygous or compound heterozygous gain-of-function mutations in MEFV, which encodes pyrin, an inflammasome protein. Heterozygous carrier frequencies for multiple MEFV mutations are high in several Mediterranean populations, suggesting that they confer selective advantage. | This reference supports the genetic basis of FMF involving mutations in MEFV, which leads to the dysregulated inflammatory response observed in FMF. |
| PMID:29051974 | SUPPORT | Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested by inflammatory attacks of peritonitis, pleuritis, pericarditis accompanied by fever and arthritis. Mutations of MEFV gene results in pyrin dysfunction, which causes uncontrolled interleukin-1 beta production and triggers the inflammatory attacks. | This reference supports the mechanism described in the statement, emphasizing pyrin dysfunction and the uncontrolled production of interleukin-1 beta. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:21358337 | PARTIAL | Familial Mediterranean fever type 1 is characterized by recurrent short episodes of inflammation and serositis, including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis. | The literature supports that recurrent fever is a common feature of Familial Mediterranean Fever type 1, but it does not fully support that FMF should be categorized solely under systemic phenotypes. |
| PMID:25832989 | PARTIAL | Familial Mediterranean fever...presents with recurrent and self-limited inflammatory attacks of fever and polyserositis along with high acute-phase reactants. | The literature supports that recurrent fever is a common diagnostic feature of FMF and systemically involves fever and inflammation, but it does not confirm all specified aspects of the statement. |
| PMID:36688581 | PARTIAL | Higher Pras scores, earlier age of symptoms and diagnosis, more frequent arthritis and erysipelas-like erythema, and higher colchicine dose are closely associated with M694V homozygous familial Mediterranean fever patients. These patients also have mostly moderate and severe disease severity. | It supports the systemic nature and severity aspects but does not fully align with the complete statement's focus. |
| PMID:34606655 | PARTIAL | Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting with phenotypic heterogeneity. It is a clinically diagnosed disease supported by Mediterranean fever gene mutation analysis. | While fever is a prominent symptom, FMF is known for phenotypic heterogeneity, indicating varied systemic manifestations. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:11411958 | SUPPORT | The arthritis was transient, monoarticular, nonerosive, and nondeforming in the majority of cases. Four patients (5.4%) had chronic arthritis, with one requiring total hip replacement. As in previous reports on arthritis of FMF, the majority of FMF patients studied in Lebanon had a transient monoarticular nonerosive and nondeforming type of arthritis affecting predominantly the large joints of the lower extremities. | This reference supports the statement that arthritis is a common phenotype in FMF, is transient, and affects large joints. |
| PMID:33124556 | SUPPORT | More patients had arthritis in the ELE group than in the other group (p=0.011). Arthritis occurred in the ankle (77.4%), knee (19.3%) and hip (3.2%) joints. | This reference confirms the presence of arthritis in FMF patients, especially in large joints, supporting the statement. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:36082189 | PARTIAL | FMF is characterised by dysregulation of the inflammatory process in the body, presenting as recurrent episodes of serositis. Patients with FMF commonly present with episodes of fever, peritonitis, synovitis, pleuritis, arthritis, and occasionally pericarditis. | This reference supports that peritonitis, which involves abdominal pain due to inflammation of the peritoneum, is a phenotype of FMF. However, it does not explicitly indicate a high frequency of gastrointestinal phenotypes. |
| PMID:37723615 | PARTIAL | Familial Mediterranean fever (FMF) is the most prevalent hereditary autoinflammatory disease among children. Abdominal pain and various gastrointestinal system (GIS) manifestations may arise directly from FMF or concomitantly with FMF. | This reference supports that gastrointestinal manifestations, including abdominal pain, are phenotypes of FMF. However, it does not specify the high frequency of peritonitis. |
| PMID:9562837 | SUPPORT | When a patient complains of episodic fever accompanied by unexplained arthritis, peritonitis, pleurisy, or skin rash, this disorder should be considered. | This reference supports that peritonitis is a common phenotype of FMF, aligning well with the statement. |
| PMID:35737103 | SUPPORT | The key feature of familial Mediterranean fever is relapsing episodes of fever and serositis including peritonitis, pleurisy, or arthritis. | This reference clearly supports that peritonitis, involving abdominal pain due to inflammation of the peritoneum, is a key feature of FMF and occurs frequently. |
| PMID:31308342 | SUPPORT | Considering the history of recurrent abdominal pain, Familial Mediterranean Fever (FMF) was considered. | This reference supports that recurrent abdominal pain is a phenotype associated with FMF. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:38204312 | SUPPORT | The most common signs and symptoms are fever, abdominal pain, chest pain, and arthritis. | The study highlights chest pain as a frequent symptom in FMF patients, indicating pleuritis as a common phenotype. |
| PMID:12092043 | SUPPORT | Lung involvement in FMF is limited mainly to transient pleuritis during acute attacks. | The study specifies that pleuritis, which is inflammation of the pleura, is a frequent thoracic phenotype in FMF. |
| PMID:36385047 | SUPPORT | Pericarditis, pleurisy and the response to colchicine indicated FMF. | This study identifies pleurisy, another term for pleuritis, as a characteristic symptom in FMF patients, supporting the statement. |
| PMID:36725780 | PARTIAL | Pleuritis is the only known pulmonary involvement of FMF; however, as far as we know, thoracic involvements in pleural, parenchymal, bronchial, and vascular structures have not been evaluated yet. | While the study acknowledges pleuritis as a known pulmonary involvement in FMF, it does not provide evidence on its frequency being "FREQUENT". |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:12832747 | SUPPORT | Amyloidosis, causing renal failure, is one of the most severe complications of the disease. | The literature confirms that amyloidosis can lead to kidney failure in patients with Familial Mediterranean Fever (FMF), supporting the statement. |
| PMID:23548761 | SUPPORT | Familial Mediterranean Fever and tuberculosis were the most frequent causes of amyloidosis. | The statement is supported as FMF is listed as one of the frequent causes of renal amyloidosis. |
| PMID:3416182 | SUPPORT | Splenic and renal involvement is more likely in FMF-associated systemic amyloidosis. | The presence of renal amyloidosis in FMF, leading potentially to kidney failure, supports the statement. |
| PMID:21360109 | SUPPORT | The most frequent cause [of renal amyloidosis in children] is now autoinflammatory diseases. Among this group of diseases, the most frequent one throughout the world is familial Mediterranean fever (FMF). | This confirms that FMF is a frequent cause of renal amyloidosis, thereby supporting the statement. |
| PMID:33052444 | SUPPORT | Amyloidosis [...] stands out as a major complication of familial Mediterranean fever (FMF). Splenic and renal involvement is more likely in FMF-associated systemic amyloidosis. | The literature confirms the renal involvement in FMF-associated amyloidosis, thus supporting the statement. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:22234484 | PARTIAL | Multiple stressful life events predicted FMF attacks 2 days following the event. Physical exertion and high-fat diet did not increase the likelihood of FMF attacks. | The study found that emotional stress could trigger FMF attacks, but physical stress did not show a significant effect. Therefore, while stress in general may trigger episodes, physical stress specifically does not. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:22234484 | SUPPORT | Multiple stressful life events predicted FMF attacks 2 days following the event. After adjustment for treatment, an additional stressful event was associated with an estimated 70% increase in the odds of having an FMF attack on the second day. | The study indicates a clear association between emotional stress and the triggering of FMF attacks, supporting the statement. |
| PMID:33026080 | SUPPORT | The emergence of FMF attacks after emotional stress and the induction of attacks with metaraminol in previous decades suggested that stress-induced sympathoadrenal system activation might play a role in inflammasome activation and triggering attacks. | The literature provides evidence that emotional stress can trigger FMF attacks through the activation of the inflammasome pathway. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:19797919 | SUPPORT | The study demonstrated that colchicine treatment is effective in preventing amyloidosis among Armenian patients with FMF and that earlier initiation and continuous therapy at an adequate dose of 1.2-1.8 mg/day may be associated with a decreased amyloidosis risk among Armenian patients with FMF. | The study directly supports the statement that colchicine is a first-line treatment for preventing amyloidosis, a common complication of FMF. |
| PMID:25649364 | SUPPORT | The only agent that decreases the development of amyloidosis and the frequency and severity of the episodes is colchicine, which has been used for about 40 years. | This reference clearly supports the claim that colchicine reduces the frequency of attacks and prevents amyloidosis, affirming its role as a first-line treatment. |
| PMID:25791871 | SUPPORT | Early studies reported colchicine as a potential drug for preventing attacks of familial Mediterranean fever. | This indicates that colchicine is considered effective for preventing FMF attacks, supporting its position as a first-line treatment. |
| PMID:17242135 | SUPPORT | The daily application of colchicine is the standard therapy for prophylaxis of attacks and amyloid deposition in familial Mediterranean fever. | This statement corroborates that colchicine is the standard, or first-line, therapy for preventing FMF attacks and amyloidosis. |
| PMID:15720245 | SUPPORT | Since 1972 colchicine has become the drug of choice for prophylaxis against FMF attacks and amyloidosis FMF-associated. | This reference supports the idea that colchicine is the primary treatment for preventing FMF attacks and associated amyloidosis. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:28362189 | SUPPORT | The accumulating data indicates that anti IL-1 drugs are effective in treating colchicine resistant FMF cases and improving their quality of life. | The reference supports the use of anti-IL-1 therapy for treating colchicine-resistant FMF cases. |
| PMID:30338514 | SUPPORT | For those people who are colchicine-resistant or intolerant, drugs such as rilonacept, anakinra, canakinumab, etanercept, infliximab, thalidomide and interferon-alpha might be beneficial. | The reference lists several anti-IL-1 therapies as beneficial for colchicine-resistant or intolerant FMF patients. |
| PMID:36161616 | SUPPORT | Anti IL-1 therapy is useful in suppressing attacks in FMF patients with colchicine resistance. | The study supports the effectiveness of anti-IL-1 therapy in managing inflammation in colchicine-resistant FMF patients. |
| PMID:27860460 | SUPPORT | In this randomized controlled trial, anakinra appears to be an effective and safe treatment for colchicine-resistant FMF. | The reference provides evidence from a randomized controlled trial supporting the effectiveness of anakinra, an anti-IL-1 therapy, in colchicine-resistant FMF patients. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:37752496 | REFUTE | These provide the basis for stratifying patients into the following treatment paths: continue colchicine, persisting attacks / inflammation, colchicine intolerance, persisting arthritis, colchicine reduction and adjustment/reduction of biologics. | The literature does not mention NSAIDs as a treatment path for symptom relief during acute attacks of Familial Mediterranean Fever. The focus is on colchicine and biological therapy. |
| PMID:36945975 | NO_EVIDENCE | Mean age of the overall group was 38.2 +/- 11.7 years (62.4% female, 37.6% male). Two hundred and twenty-seven patients were treated with colchicine, 97 patients with colchicine plus Interleukin-1 (IL-1) antagonist, and 22 only with IL-1 antagonist (67.1%, 26.3%, 6.64% in order). | There is no mention of NSAIDs being used for symptom relief during acute attacks in FMF patients. The treatments focus on colchicine and IL-1 antagonist. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:38488998 | PARTIAL | Patients can significantly decrease the number of familial Mediterranean fever attacks they experience by managing psychological stress and avoiding physical factors such as cold exposure and fatigue. | The literature supports the management of psychological stress and avoiding physical factors as triggers but does not explicitly mention infections. |
| PMID:26324575 | PARTIAL | Triggers of this illness include many things, such as cold or stress. | The literature mentions stress as a trigger but does not provide exhaustive confirmation about infections as triggers or other preventive lifestyle modifications. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:29314663 | PARTIAL | Even though clinical assessment is accepted to be the most important factor in the diagnosis of FMF... MEFV gene assessment, unlike other diagnostic procedures, might support physicians in the early diagnosis of FMF. | The literature acknowledges the importance of genetic testing for MEFV mutations but emphasizes that clinical evaluation remains crucial for diagnosis overall. |
| PMID:25649364 | SUPPORT | Genetic mutation of the disease is on MEFV gene located on short arm of Chromosome 16. The disease is diagnosed based on clinical evaluation. | This reference supports the statement that MEFV mutations are identified through genetic testing, although it specifies that the diagnosis is based on clinical evaluation. |
| PMID:12168253 | SUPPORT | This strategy allows definitive confirmation of periodic disease if one mutation is detected on each of the two chromosomes... | This reference directly supports the use of genetic testing to identify MEFV mutations for diagnosing familial Mediterranean fever. |
| PMID:33037005 | SUPPORT | Its diagnosis relies on a set of clinical criteria and a genetic confirmation on identification of biallelic pathogenic MEFV variants. | The reference confirms that genetic testing for MEFV mutations is a key part of diagnosing familial Mediterranean fever. |
| reference | supports | snippet | explanation |
|---|---|---|---|
| PMID:31524848 | SUPPORT | Median values of acute phase reactants during FMF attacks were 433.5 mg/L for serum amyloid A (SAA), 56.7 mg/L for C-reactive protein (CRP), and 37.5 mm/h for erythrocyte sedimentation rate (ESR). | The study shows that SAA, CRP, and ESR are elevated during FMF attacks. |
| PMID:23794006 | SUPPORT | We found that the NLR values of the patients were significantly higher than those of the control group, and C-reactive protein values were correlated with NLR. | CRP is confirmed as an elevated marker in FMF patients in this study as well. |