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benign paroxysmal peritonitis [keywords]
- Late onset of Crohn’s disease in familial Mediterranean fever: the necessity of anti-TNF treatment. [Journal Article]
- J Dig Dis 2014 Feb; 15(2):102-4.
- Correction: rilonacept for colchicine-resistant or -intolerant familial mediterranean Fever. [Journal Article]
- Ann Intern Med 2014 Feb 18; 160(4)
- Clinical evaluation of R202Q alteration of MEFV genes in Turkish children. [JOURNAL ARTICLE]
- Clin Rheumatol 2014 Apr 10.
To date, over 200 alterations have been reported in Mediterranean fever (MEFV) genes, but it is not clear whether all these alterations are disease-causing mutations. This study aims to evaluate the clinical features of the children with R202Q alteration. The medical records of children with R202Q alteration were reviewed retrospectively. A total of 225 children, with 113 males, were included. Fifty-five patients were heterozygous, 30 patients were homozygous for R202Q, and 140 patients were compound heterozygous. Classical familial Mediterranean fever (FMF) phenotype was present in 113 patients: 2 heterozygous and 7 homozygous R202Q, 46 double homozygous R202Q and M694V, and 58 compound heterozygous. The main clinical characteristics of the patients were abdominal pain in 71.5 %, fever in 37.7 %, arthralgia/myalgia in 30.2 %, arthritis in 10.2 %, chest pain in 14.6 % and erysipelas-like erythema in 13.3 %. The frequency of abdominal pain was significantly lower in patients with homozygous R202Q alteration (p = 0.021), whereas patients with heterozygous R202Q mutations, though not statistically significant, had a higher frequency of arthralgia/myalgia (40.0 %, p = 0.05). R202Q alteration of the MEFV gene leads to symptoms consistent with FMF in some cases. This alteration may be associated with a mild phenotype and shows phenotypic differences other than the common MEFV mutations.
- The Relationship Between Familial Mediterranean Fever Gene (MEFV) Mutations and Clinical and Radiological Parameters in Multiple Sclerosis Patients. [JOURNAL ARTICLE]
- Int J Neurosci 2014 Apr 9.
Abstract Objective: Central nervous system (CNS) involvement in Familial Mediterranean fever (FMF) patients is considerably rare. FMF patients may exhibit clinical and radiological symptoms similar to multiple sclerosis (MS). However, the impact of Familial Mediterrannean Fever Gene (MEFV) mutations on the clinical course of MS is not yet fully understood. Methods: In our study, we investigated the presence of probable MEFV mutations in patients diagnosed with definite MS and the association of these mutations with the clinical course, radiological characteristics, and disability status of the individuals. A total of 105 patients diagnosed with definite MS according to the McDonald criteria and a control group of 112 non-symptomatic individuals were included in the study. Results: Thirty-seven patients (35.2%) had MEFV gene mutations; three were compound heterozygote (M694V/E148Q; M694V/V726A; P369S/E148Q) and one was homozygous for P369S. No statistically significant differences were found among MS patients and healthy individuals with respect to existing mutations. Additionally, we did not observe a statistically significant relationship between MEFV mutations and the gender of the patients, OCB positivity, EDSS, disease onset age, clinical presentation, affected neurological systems, existence of spinal lesions, response to immunomodulatory treatment, time to reach EDSS scores of 3 and 6, the number of attacks and the average number of lesions on a brain MRI. Conclusion: Our results indicate that MEFV gene mutations do not affect the neurological prognosis in MS patients. However, additional research studies involving more MS patients and clinical forms are warranted to confirm our results.
- Non-response to colchicine in familial Mediterranean fever should be identified accurately. [JOURNAL ARTICLE]
- Int J Rheum Dis 2014 Apr 7.
Colchicine prophylaxis is the single most important factor in ameliorating familial Mediterranean fever (FMF) for the prevention of both attacks and secondary amyloidosis. The aim of the present study was to evaluate the exact proportion of those patients who do not respond to colchicine and to characterize their demographic, sociodemographic and clinical aspects.One hundred and eight patients with FMF were included in our study. The demographic (age, gender), socioeconomic (education level, employment status, economic income level) and clinical features (age at onset of FMF, age at FMF diagnosis, family history of FMF, mean duration of colchicine use and mean daily colchicine dose) of the patients were evaluated. The patients unresponsive to colchicine therapy, according to their statements, were recorded. Also with another question, patients' routine colchicine-consuming habits were elucidated in a self-answering format. 'Non-responders' were defined as patients who experienced FMF attacks at a frequency greater than once every 3 months despite treatment with 2 mg colchicine daily. Data were analyzed with the chi-square test and Fisher's exact test.There were 50 female and 58 male patients with a mean age of 42.4 ± 11.3 years. The mean age at FMF onset and at FMF diagnosis were 14.3 ± 10.5 and 19.1 ± 12.9 years, respectively. Sixteen percent of the patients defined themselves as 'suffering from attacks in spite of regular colchicine'. Irregular colchicine usage was determined in 11% of the patients who were considered as 'unresponsive to colchicine therapy' according to their statements. In spite of regular colchicine regimen, attacks were present in 5% of the patients in our study. Although there was no difference in demographic and clinical aspects, patients with irregular colchicine usage were found to be from lower socioeconomic backgrounds, had less education and more unemployment (P < 0.001).Regular colchicine usage anamnesis may be misleading in the first evaluation and this risk seems to be higher in patients from lower socioeconomic background. Routine colchicine-consuming habits should be detailed in patients with FMF before claiming its failure.
- Familial Mediterranean fever gene mutations as a risk factor for early coronary artery disease. [JOURNAL ARTICLE]
- Int J Rheum Dis 2014 Apr 7.
Cardiovascular diseases (CVD) are very common in the general population. Atherosclerosis is the main pathogenesis. Familial Mediterranean fever (FMF) is an autosomal recessive disease. The gene causing FMF, designated MEFV, encodes a protein called pyrin or marenostrin that is expressed mainly in myeloid bone marrow precursors, neutrophils and monocytes. We herein aimed to determine the prevalence of MEFV mutations (all exon 2, 10 mutations) in patients with early coronary heart disease (early CHD) and coronary heart disease (CHD) with multiple risk factors and among the healthy subjects as controls.A total of 197 patients and 119 healthy subjects were recruited and enrolled into three groups in terms of inclusion criteria. Ninety-one patients diagnosed with early CHD enrolled into group one (men < 45 years of age, women < 40 years of age), 106 patients with CHD (men > 50 years of age) to group two and 119 healthy controls enrolled into group three. None of patients was diagnosed with FMF. The diagnosis of CHD was established on electrocardiographic changes, echocardiography and coronary angiography.Thirty-eight patients (41.8%) with early CHD, 17 patients (16%) with CHD and 24 healthy controls (20.2%) carried at least one mutated MEFV allele. Young patients with CHD have different risk factor profiles, clinical presentations and prognoses than older patients. Young patients with CHD usually have multiple risk factors.This study suggests that MEFV mutations in early CHD patients had significantly increased in contrast to CHD patients and healthy controls.
- Neutrophil-Lymphocyte Ratio in Patients With Familial Mediterranean Fever. [JOURNAL ARTICLE]
- J Clin Lab Anal 2014 Mar 28.
Blood neutrophil-to-lymphocyte (N/L) ratio is an indicator of the overall inflammatory status of the body, and an alteration in N/L ratio may be found in patients with familial Mediterranean fever (FMF). The aim of this study was to investigate the interrelationship between N/L ratio and FMF.One hundred and fifteen patients and controls were enrolled in the study. The cases in the study were categorized as FMF with attack, FMF with attack-free period, and controls. The neutrophil and lymphocyte counts were recorded, and the N/L ratio was calculated from these parameters. All patients were diagnosed according to Tel Hashomer criteria.A total of 79 FMF patients were included in the study and all subjects were receiving colchicine treatment at the time. The serum N/L ratios of active patients were significantly higher than those of attack-free FMF patients and controls (P < 0.001). The optimum N/L ratio cut-off point for active FMF was 2.63 with sensitivity, specificity, positive predictive value, and negative predictive value of 0.62 (0.41-0.80), 0.85 (0.72-0.93), 0.67 (0.44-0.85), and 0.82 (0.69-0.91), respectively. The overall accuracy of the N/L ratio in determination of FMF patients during attack was 71%.Our results demonstrate that N/L ratio is higher in patients with active FMF compared with FMF patients in remission and controls, and a cut-off value of 2.63 can be used to identify patients with active FMF.
- The role of IL-4 gene 70bp VNTR and ACE gene I/D variants in Familial Mediterranean fever. [Journal Article]
- Cytokine 2014 May; 67(1):1-6.
Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. It is an autosomal recessive disease caused by mutations in the MEFV (MEditerranean FeVer) gene. Patients with similar genotypes exhibit phenotypic diversity. As a result, the variations in different genes could be responsible for the clinical findings of this disease. In previous studies genes encoding Angiotensin-Converting Enzyme (ACE) and IL-4 (Interleukin-4) were found to be associated with rheumatologic and autoimmune diseases. In the present study we hypothesized whether ACE I/D or IL-4 70bp variable tandem repeats (VNTR) genes are associated with FMF and its clinical findings in Turkish patients. Genomic DNA obtained from 670 persons (339 patients with FMF and 331 healthy controls) was used in the study. Genotypes for an ACE gene I/D polymorphism and IL-4 gene 70bp VNTR were determined by polymerase chain reaction with specific primers. To our knowledge, this is the first study examining ACE gene I/D polymorphism and IL-4 gene 70bp VNTR polymorphism in FMF patients. As a result, there was a statistically significant difference between the groups with respect to genotype distribution (p<0.001). According to our results, ACE gene DD genotype was associated with an increased risk in FMF [p<0.001; OR (95%): 7.715 (4.503-13.22)]. When we examined ACE genotype frequencies according to the clinical characteristics, we found a statistically significant association between DD+ID genotype and fever (p=0.04). In addition IL-4 gene P1P1 genotype was associated with FMF (p<0.001). We propose that D allele or DD genotype of ACE gene and P1 allele or P1P1 genotype of IL-4 gene may be important molecular markers for susceptibility of FMF.
- A40: periodic Fever syndromes in Canada: results from a national surveillance program. [Journal Article]
- Arthritis Rheumatol 2014 Mar.:S60.
To estimate the incidence of periodic fever syndromes in the Canadian paediatric population, to describe the patterns of presentation, and to raise awareness in the medical community.This study was initiated though the Canadian Pediatric Surveillance Program (CPSP), and is being carried out over a three year period which will conclude in September 2014. The case definition includes patients less than 18 years of age presenting with a newly diagnosed periodic fever syndrome. Conditions under surveillance included Familial Mediterranean fever (FMF), Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), Hyperimmunoglobulin D syndrome (HIDS), Cryopyrin-associated periodic syndromes (CAPS), Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA), and Undefined periodic fever syndromes. For each condition the study protocol outlined established clinical and/or genetic criteria for diagnosis. Participating pediatricians and pediatric subspecialists across the country are sent monthly reporting forms. Detailed questionnaires are completed by physicians who report a recent diagnosis. Submissions are screened for accuracy and confirmed cases then entered into a database.During the 20 month period from September 2011 to December 2012 a total of 167 cases were reported. Of these cases, detailed questionnaires were completed on 126, with the remainder pending at the time of this report. 114 cases have been confirmed as meeting the criteria for one of the Periodic Fever Syndromes under surveillance, 55% of which had had genetic testing completed as part of their evaluation. Twelve cases were discarded. Amongst the 114 confirmed cases, PFAPA was most frequent (51%), followed by Undefined Periodic fever syndrome (37%). Also seen were FMF (11%), and one case of HIDS (1%). There were no cases of TRAPS, or CAPS, reported during the study period to date. Amongst the 42 Undefined Periodic Fever syndrome cases the reporting physicians described 11 as being suspected PFAPA, 5 suspected FMF, 3 suspected CAPS, and 1 suspected HIDS. In most cases this was because genetic testing was still pending at the time of reporting. The overall male to female ratio was 1.1:1. Amongst Undefined cases there was a male predominance with a male to female ratio of 1.6:1, whereas the male to female ratio was 0.6:1 for FMF. An equal number of males and females were reported for PFAPA. The most frequent fever associated manifestations for PFAPA included pharyngitis (79%), cervical lymphadenopathy (66%), stomatitis (59%), and fatigue (53%). For FMF most frequent were abdominal pain (69%), arthralgia (54%), pharyngitis (46%), and headache (46%). For Undefined cases most frequent manifestations were fatigue (45%), pharyngitis (38%), abdominal pain (36%), and lymphadenopathy (33%).Although rare periodic fever syndromes are identified across Canada each year. PFAPA, Undefined fever syndromes, and FMF are most frequently seen. We hope to have a more complete picture of the full spectrum and incidence of these autoinflammatory diseases in the Canadian population as genetic test results become available, and additional cases are identified through the end of the study in September 2014.
- A76: long-term efficacy of canakinumab in childhood colchicine resistant familial mediterranean Fever. [Journal Article]
- Arthritis Rheumatol 2014 Mar.:S108.
Familial Mediterranean fever (FMF) is the most common hereditary autoinflammatory syndrome. FMF is caused by mutations in the MEFV gene which encodes the pyrin protein, that has an important role in the activation of IL-1β. Evidence from case reports/series and one controlled study supports IL-1 blockage as a potential treatment for FMF. Canakinumab (CAN) is a selective fully human monoclonal anti-IL-1β antibody. This study served as a proof of concept to evaluate the role of CAN in the treatment of pediatric colchicine resistant (CR)-FMF with a longterm extension.This was a 2-center, 2-part, phase II, open-label, single-arm study. Subjects consisted of CRFMF patients (pts) 4-16 years of age, with a history of ≥3 documented FMF attacks in the 3 months prior to enrollment. In part I, pts with an investigator-confirmed FMF attack during the 30-day run-in period (RI) could enter the treatment phase. These subjects received the 1st dose of CAN (2 mg/kg, max 150 mg) via subcutaneous (SC) injection during the subsequent attack and then every 4 weeks for three times. The dose was doubled to 4 mg/kg (max 300 mg) if an attack occurred between Day 1 and Day 29 visits. Primary outcome was the proportion of pts with ≥50% reduction in FMF attack rate during the treatment vs. pretreatment period. Following the end of the treatment period, pts were followed until day 144 or until an attack occurred, whichever occurred first. CAN was then renewed and pts entered the long-term extension study (part II), in which the dose and frequency of CAN administration and colchicine dose could be adjusted by investigators based on pt response.Seven pts (5 males, 2 females; median age 9.5 yrs, range 6.8-14.9) received treatment. In part I, 6/7 (86%) pts attained the primary outcome. The median attack rate was reduced by 89% from 2.7 to 0.3 per 28 days; 2 pts had their CAN dose uptitrated. Elevated median baseline CRP normalized by Day 8 with ESR and SAA by Day 28. Following the end of the treatment period 5 pts developed attacks within a median of 25 days. In part II, all 7 pts (no drop-outs) were followed for a median of 17 (range 13-25) months. During this period, 3 pts experienced 6 attacks (0.05 attacks per pt month) and in 2 pts the CAN doses were increased. Two additional pts experienced 3 mild increases in the ESR and CRP (not associated with an attack) that resolved after CAN dose increase. At the end of part II, the global physician assessment was rated as very good for all pts; median CAN dose was 3 (range 1.8-4.8) mg/kg with administration interval lengthened in 3 pts to every 7 wks. Colchicine dose was decreased to 1 mg/d in 3 pts and discontinued (by self) in 1 pt. 22 AEs were recorded in 5 pts, with 11 in each study part. All were mild except for 3 moderate AEs (Strep throat infection, laceration, tinea capitis) assessed as unrelated to study treatment by the study investigators. No AEs led to medication discontinuation.This study demonstrated the longterm therapeutic effect of canakinumab in pediatric pts with CR-FMF. AEs were manageable. Occasional increases in dose were needed while the dosing interval could be lengthened in some patients. A larger study is needed to better evaluate the benefit and optimal dosing of canakinumab for CR-FMF.