Familial Mediterranean Fever Patients Research Articles

A treatment algorithm for familial Mediterranean fever patients with menstruation-associated attacks.

Familial Mediterranean fever (FMF) is characterized by febrile polyserositis attacks. Menstruation could be a trigger for attacks. We aimed to analyze the features of adolescent FMF patients with menstruation-associated attacks and propose a management algorithm. All female FMF patients who had menarche and visited the Pediatric Rheumatology Unit between January-December 2022, were included into this study. Demographics, general characteristics, and the features of menstrual cycle and FMF attacks were noted. A total of 151 female FMF patients were included. Thirty-five (23.2%) had menstruation-associated attacks. Fever and arthritis were less frequent during the menstruation-associated attacks than the attacks not associated with menstruation in these patients (65.7% vs 88.6%, p= 0.01 and 2.9% vs 20%, p= 0.04; respectively). Patients with menstruation-associated FMF attacks were younger at symptom onset and diagnosis (2.5 vs 5 years, p= 0.004 and 4 vs 7 years, p= 0.01; respectively), had a higher rate of dysmenorrhea (74.3% vs 38.8%, p< 0.001, respectively) and higher pre- and post-menarche attack frequency (4 vs 2 and 10 vs 0, respectively; p< 0.001 for both) than patients whose attacks were not associated with menstruation. The interventions for menstruation-associated attacks included initiating colchicine, increasing the dose of colchicine, switching from coated to compressed colchicine tablets or anti-interleukin 1 drugs, and on-demand non-steroidal anti-inflammatory drugs, on-demand glucocorticoids, and on-demand anakinra. On-demand therapies were beneficial in controlling menstruation-associated attacks. This is the largest cohort of adolescent FMF patients with menstruation-associated attacks. Severe FMF may cause tendency to this association. On-demand therapies could be preferred in the management.

Morphological, Fractal, and Textural Features of the Mandible in Familial Mediterranean Fever Patients: A Case-control Study

Morphological, Fractal, and Textural Features of the Mandible in Familial Mediterranean Fever Patients: A Case-control Study

C-reactive protein is more suitable than Serum Amyloid A to monitor crises and attack-free periods in Systemic Auto-Inflammatory Diseases.

BackgroundWith their broad presentations and no global biomarker to discriminate crises and attack-free periods, Systemic Auto-Inflammatory Diseases (SAID) are difficult to manage. This study assessed Serum Amyloid A (SAA), C-reactive protein (CRP) and serum calprotectin as potential biomarkers to monitor patients with SAID. MethodSAA (already studied in Familial Mediterranean Fever (FMF)), CRP and serum calprotectin were measured on SAID adult patients from Juvenile Inflammatory Rheumatism (JIR) cohort during their follow-up visits between 2020 and 2022. Crises and attack-free periods were clinically determined. Results96 measures, mainly from FMF (43 %) and Unclassified SAID (USAID) (37 %) patients were included. Using ROC curves, a threshold with sensitivity and specificity of/over 75 % was determined for SAA (9 mg/L) and CRP (9 mg/L) but not for serum calprotectin, not investigated further. With this threshold, the results were similar in FMF and USAID patients’ subgroups. SAA and CRP showed a positive correlation with crises and attack-free periods in SAID patients (r = 0.4796, p < 0.001 and r = 0.5525, p < 0.001, respectively) as in FMF and USAID patients, with no significant difference between both markers in diagnosis value and ROC curves Area Under Curve (AUC) (p = 0.32). Only the CRP results were not influenced by obesity. ConclusionSAA and CRP can discriminate crisis and attack-free periods in our cohort of SAID patients mainly composed of FMF and USAID patients. However, only CRP can be used regardless of body mass index. It is the first report of common biomarkers for all SAID, including USAID patients, with CRP widely accessible in routine worldwide.

Examination of cardiac functions during acute attack and remission period in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease characterized by recurring serosal inflammation. Cardiac involvement in FMF commonly manifests as pericarditis and pericardial effusion; however, there is limited research on myocardial function. This study aimed to assess cardiac functions during active inflammation and remission periods of FMF patients and investigate the cardiac effects of inflammation during the attack period. Thirty-eight FMF patients without additional cardiac diseases were included in the study. Demographic characteristics, clinical symptoms, family history, and MEFV gene analysis results were obtained retrospectively. Blood tests, blood pressure measurements, electrocardiogram evaluations, conventional echocardiography, and speckle tracking echocardiography were performed during the attack and remission periods. Disease severity was assessed using the Pras scoring system. During the attack period, FMF patients exhibited significantly higher leukocyte count, neutrophil count, C-reactive protein, and erythrocyte sedimentation rate compared to the remission period (p < 0.005). Speckle tracking echocardiography revealed decreased function in the inferior segments of the left ventricle during the attack period (p < 0.005). Right ventricular function was more affected in the moderate disease group. FMF patients with lymphopenia during the attack demonstrated more impaired right ventricular function compared to those with normal lymphocyte count. Conclusions: FMF patients experience cardiac abnormalities during active inflammation, highlighting the importance of monitoring cardiac functions in these patients. Speckle tracking echocardiography can provide valuable insights into cardiac involvement in FMF. These findings emphasize the cardiac impact of FMF inflammation and the significance of long-term cardiac function monitoring in the management of FMF patients. What is Known: • The current literature lacks studies investigating myocardial function in the pediatric population during the attack period of this particular disease. • Our objective was to assess the alterations in cardiac function during the attack and remission periods, considering clinical manifestations, disease severity, acute phase reactant levels, and mutation type. We also evaluated the pattern of cardiac involvement and the affected cardiac areas by comparing remission and attack periods. What is New: • Several studies have demonstrated a rise in the prevalence of ischemic cardiac disease and mortality among individuals with FMF. • Investigating cardiac involvement during the attack period in FMF patients can provide valuable insights for the prevention of long-term complications.

Physical fitness in adolescent patients with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the most frequent monogenic auto-inflammatory disease worldwide responsible for episodes of fever, serositis and musculoskeletal symptoms. Inflammatory attacks are responsible for sedentary behavior and FMF patients may be at increased cardiovascular risk. Cardiorespiratory Fitness (CRF) and physical capacities during adolescence are associated with cardiovascular mortality in adulthood. In this study, we aimed to describe the physical fitness of FMF adolescents. A monocentric retrospective study at the Versailles Hospital between January 2020 and June 2023. All FMF patients over 14-year-old who had completed a routine physical test were included. Clinical and physical data including results of the 6-minute walking test, timed unipedal stance test, Ruffier-Dickson index, 30-seconds chair-stand test and sit-and-reach test were extracted from medical records. Results were compared with previously published normative reference values and criterion-referenced standards for healthy subjects. Eighteen FMF patients (12 girls, 6 boys) were included. The median age was 16 years old [14-18]. Clinical history included joint symptoms (n = 11), chest pleuritis (n = 8), and leg pain (n = 11). Estimated VO2max was below the recommended thresholds in 13 patients, which predicts cardiovascular risk. Cardiovascular adaptation was poor in 11 patients. Low VO2max was associated with CRP > 5mg/l on test day and history of joint symptoms. FMF patients displayed altered physical capacities compared to normative values of healthy subjects. History of musculoskeletal pain, systemic inflammation and sedentary behavior may participate in impaired physical abilities and promote cardiovascular diseases in adulthood. Specific exercise programs could benefit patients for disease control and cardiovascular risk reduction.

Canakinumab treatment real world evidence in 3 monogenic periodic fever syndromes in 2009–2022: an interim analysis using the French JIR cohort database

BackgroundOur study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS).MethodsThis study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study.Results31 FMF, 26 MKD and 7 TRAPS patients received canakinumab during the study period. Most of them initiated canakinumab at the recommended dose of 2 mg/kg or 150 mg, but less than half of FMF and MKD patients initiated it at the recommended frequency (every 4 weeks). Two years after initiation, the rate of patients still on treatment was 78.1% in FMF, 73.7% in MKD, and 85.7% in TRAPS patients. While the dose per injection remained globally the same over the course of the treatment, some adjustments of the dose intervals were observed. Six patients had a severe adverse event reported. Of those, three were possibly related to canakinumab.ConclusionThis interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan.

Pan-Immune-Inflammation Value Could Be a New Marker to Predict Amyloidosis and Disease Severity in Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is characterized by recurrent episodes of fever and serositis. Blood-based biomarkers determined in FMF patients during attack-free periods could be used to predict the risk of amyloidosis and the severity of the disease. The recently defined pan-immune-inflammation value (PIV) comprises four distinct subsets of blood cells and serves as an easily accessible and cost-effective marker. The objective of this study was to assess the role of PIV in predicting amyloidosis and moderate-to-severe disease. Clinical characteristics and laboratory values during the attack-free period were retrospectively analyzed in 321 patients over 18 years of age diagnosed with familial Mediterranean fever (FMF). In our tertiary adult rheumatology outpatient clinic, disease severity and laboratory markers were evaluated during the first attack-free interval. At baseline, patients with amyloidosis were excluded. Patients were categorized based on the presence of amyloidosis and the severity of the disease. When focusing on amyloidosis in receiver operating characteristic (ROC) analysis, optimal cut-off values for pan-immune-inflammation value (PIV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio were determined as ≥518.1, ≥2.3, and ≥127.2, respectively. In multivariate analysis, PIV, C-reactive protein (CRP), and the presence of the M694V homozygous mutation emerged as independent risk factors for both amyloidosis and moderate-to-severe disease. Additionally, NLR was identified as an independent risk factor for amyloidosis, while red blood cell distribution width was associated with moderate-to-severe disease. In patients with FMF, especially in the presence of the M694V homozygous mutation, CRP and PIV may be useful in predicting both amyloidosis and moderate-to-severe disease.

Role of serum calprotectin in identifying familial Mediterranean fever attacks.

The aim of the study was to evaluate serum calprotectin (CLP) levels in familial Mediterranean fever (FMF) patients and to investigate the utility of CLP in distinguishing patients with attack from patients without attack. FMF patients, rheumatoid arthritis (RA) patients, and healthy controls were included. Serum calprotectin levels were quantified utilizing the enzyme-linked immunosorbent assay (ELISA) method. Receiver operating characteristic (ROC) curve analysis was used to identify the cut-off value of serum CLP level to differentiate FMF patients with attack from those without. Logistic regression analysis was performed to identify predictors. Significant differences were observed among the three groups concerning white blood cell (WBC), neutrophil, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum CLP levels (p = 0.003, p = 0.004, p < 0.001, p < 0.001, and p = 0.002, respectively). Higher ESR, CRP, and serum CLP levels were observed in FMF patients with attacks than those without (all, p < 0.001). Serum CLP was significantly higher in RA patients than in FMF patients in remission (p < 0.001). ROC analysis identified a threshold CLP concentration in FMF with an attack to be 47.1pg/mL (83.3% sensitivity, 60.6% specificity, AUC = 0.74, 95% CI = 0.63-0.85, p < 0.001). In univariate logistic regression analysis, CLP (β = 1.045, 95% CI = 1.017-1.073, p = 0.001) was predictive of FMF patients experiencing an attack. Serum CLP proves to be as productive as ESR in illustrating inflammation and demonstrating the existence of attacks in FMF patients.

Predicting genetic risk factors for AA amyloidosis in Algerian patients with familial Mediterranean fever.

Renal amyloid-associated (AA) amyloidosis is a harmful complication of familial Mediterranean fever (FMF). Its occurrence involves polymorphisms and mutations in the Serum Amyloid A1 (SAA1) and Mediterranean Fever (MEFV) genes, respectively. In Algeria, the association between SAA1 variants and FMF-related amyloidosis was not investigated, hence the aim of this case-control study. It included 60 healthy controls and 60 unrelated FMF patients (39 with amyloidosis, and 21 without amyloidosis). All were genotyped for the SAA1 alleles (SAA1.1, SAA1.5, and SAA1.3), and a subset of them for the - 13C/T polymorphism by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Comparisons between genotype and allele frequencies were performed using Chi-square and Fisher tests. The SAA1.1/1.1 genotype was predominant in amyloid FMF patients, compared to non-amyloid FMF patients (p = 0.001) and controls (p < 0.0001). SAA1.1/1.5 was higher in non-amyloid patients (p = 0.0069) and in controls (p = 0.0082) than in patients with amyloidosis. Bivariate logistic regression revealed an increased risk of AA amyloidosis with three genotypes, SAA1.1/1.1 [odds ratio 7.589 (OR); 95% confidence interval (CI): 2.130-27.041] (p = 0.0018), SAA1.1/1.3 [OR 5.700; 95% CI: 1.435-22.644] (p = 0.0134), and M694I/M694I [OR 4.6; 95% CI: 1.400-15.117] (p = 0.0119). The SAA1.1/1.5 genotype [OR 0.152; 95% CI: 0.040-0.587] (p = 0.0062) was protective against amyloidosis. In all groups, the - 13C/C genotype predominated, and was not related to renal complication [OR 0.88; 95% CI: 0.07-10.43] (p = 0.915). In conclusion, in contrast to the - 13C/T polymorphism, the SAA1.1/1.1, SAA1.1/1.3 and M694I/M694I genotypes may increase the risk of developing renal AA amyloidosis in the Algerian population.

The evaluation of dynamic and static balance in Familial Mediterranean fever patients

The evaluation of dynamic and static balance in Familial Mediterranean fever patients

Epigenetic, transcriptional, and functional characterization of myeloid cells in familial Mediterranean fever

Familial Mediterranean fever (FMF) is a periodic fever syndrome caused by variation in MEFV. FMF is known for IL-1β dysregulation, but the innate immune landscape of this disease has not been comprehensively described. Therefore, we studied circulating inflammatory proteins, and the function of monocytes and (albeit less extensively) neutrophils in treated FMF patients in remission. We found that monocyte IL-1β and IL-6 production was enhanced upon stimulation, in concordance with alterations in the plasma inflammatory proteome. We did not observe changes in neutrophil functional assays. Subtle differences in chromatin accessibility and transcriptomics in our small patient cohort further argued for monocyte dysregulation. Together, these observations suggest that the MEFV-mutation-mediated primary immune dysregulation in monocytes leads to chronic inflammation that is subsequently associated with counterregulatory epigenetic/transcriptional changes reminiscent of tolerance. These data increase our understanding of the innate immune changes in FMF, aiding future management of chronic inflammation in these patients.

Cardiac functions and pericardial thickness changes in familial Mediterranean fever patients

BackgroundThe goal of the study is to ascertain how the pericardium and heart functions alter in patients with familial Mediterranean fever (FMF) both during the acute phase and the period of subclinical inflammation.MethodsDuring the study, 99 patients diagnosed with FMF (35 of whom were in an FMF attack period) were recruited to this study, and 24 completely healthy children in the same age group—who did not have FMF and had not any cardiac condition that applied to visit the pediatric cardiology outpatient clinic for routine follow-up—were included as the control group.ResultsIn patients with FMF, there was no discernible relationship between genetic abnormalities and pericardial thickness (p > 0.05). A significant difference was not observed in the diastolic and systolic cardiac function values between the control group and the FMF patients, with the exception of the parameters related to ejection time (ET), contraction time (IVCT), and relaxation time (IVRT). It was observed that pericardial thickness was greater in FMF patients than in study participants who did not have FMF, and this difference is statistically significant (p < 0.05).ConclusionsIt was determined that the effects of cardiac inflammation continued in children with FMF, even if they were asymptomatic. Therefore, it should be part of the follow-ups.Key points• In our study, cardiac functions and pericardial thickening of 99 FMF patients with and without attack were prospectively investigated.• In ongoing follow-up of patients with FMF, we found that inflammation, which affects all serosas, also affects the pericardium during the attract and nonattack phase.• We believe that cardiac functions, including the status of the pericardium, should be monitored as part of the long-term follow-up of FMF.

Serum endocan, asymmetric dimethylarginine and lipid profile in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a chronic inflammatory disease, and it is thought that subclinical inflammation persists even when there are no attacks, eventually causing endothelial dysfunction (ED) and atherosclerosis. Limited data are available about serum endocan, asymmetric dimethylarginine (ADMA) and lipid profile in children with FMF, so we aimed to evaluate these markers in children with FMF during the attack-free period. A total of 50 patients diagnosed with FMF and 50 age and sex-matched healthy children were recruited. Serum endocan, ADMA and lipid profiles were measured. Also, atherogenic indices (Castelli's risk indices I and II [CRI I and II], atherogenic index of plasma [AIP] and atherogenic coefficient [AC]) were calculated. Serum endocan, ADMA levels, low-density lipoprotein cholesterol, triglycerides, CRI II and AIP of the FMF patients were significantly higher than controls (p < 0.001). Unlike serum endocan, serum ADMA showed a positive significant correlation with total cholesterol, non-high density lipoprotein cholesterol, CRI I, AIP and AC (p < 0.001, p < 0.001, p = 0.004, p = 0.028, p = 0.004 respectively). Serum ADMA and lipid profile might be used as potential markers for endothelial dysfunction and increased cardiovascular risk in FMF patients. Theoretically, serum ADMA may affect lipid profiles and serum endocan represents an intriguing biomarker related to inflammation. Coexistence of dyslipidemia represents an additional risk factor that contributes to the onset of early atherosclerosis. A few studies investigated the role of changes in lipid profile and lipid ratios in accelerated atherosclerosis pathogenesis in FMF patients. The relationship between colchicine and lipid profile is contradictory. Although colchicine can cause dyslipidemia, it also has anti-atherosclerosis effects. Elevated ADMA level and atherogenic indices in FMF children reflect their potential role in the early detection of cardiovascular affection in FMF patients.

The assessment of fatigue and sleep quality among children and adolescents with familial Mediterranean fever: A case-control and correlation study

To evaluate the sleep quality and fatigue levels in children with familial Mediterranean fever (FMF) in comparison to healthy children. The Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL-MFS) and the Pittsburgh Sleep Quality Index (PSQI) were the instruments utilized to assess fatigue and sleep quality in children with FMF and controls, respectively. Spearman’s rank coefficient was decisive in determining the association between patient-reported outcome measures and disease-related features. Two hundred twenty-five (59.3% female) patients and 182 (51.6% female) healthy counterparts were enrolled in the study. In PSQI, where high scores indicate sleep disturbance, the median score was significantly higher in the patient group (5; 3–6) than the control group (3; 2–4) (p < 0.001). PEDsQL-MFS demonstrated significantly lower fatigue levels in the control group than patients (p = 0.01). The level of fatigue in the patient group was found to increase in correlation with sleep problems (r: − 0.750, p < 0.001). Additionally, a high correlation was present between the PSQI/PedsQL-MFS scores and the number of attacks in the last year (r: − 0.645, p < 0.001/r: 0.721, p < 0.001, respectively). There was no difference in terms of fatigue and sleep disorders between mutations (homozygous, heterozygous, or compound heterozygous) in the MEFV gene (p > 0.05). Conclusion: High disease activity has a significant negative impact on the sleep quality and fatigue levels of patients with FMF. This study emphasizes the importance of assessing fatigue and sleep quality with objective outcome tools periodically in FMF patients throughout the disease course.What is Known:• Fatigue is a common matter that often accompanies rheumatic diseases and causes disability.• Chronic rheumatic diseases often experience poor sleep quality.What is New:• In high correlation with the disease severity of familial Mediterranean fever, sleep quality decreases and fatigue level increases significantly.• In familial Mediterranean fever patients, a negative correlation is present between age and the general fatigue and sleep/rest related fatigue scores (low scores indicating greater fatigue) and sleep quality is poorer in the adolescent age group.

The usefulness and reliability of English-language YouTube videos as a source of knowledge for patients with familial Mediterranean fever.

YouTube is increasingly being used as an educational tool and is a substantial source of information. This study aimed to assess the quality of the most viewed YouTube videos pertaining to familial Mediterranean fever (FMF). A search on YouTube was conducted on January 13, 2022, using the keywords: "familial Mediterranean fever treatment," "familial Mediterranean fever colchicine," and "familial Mediterranean fever colchicine opacalcium." Two rheumatologists independently evaluated the relevance and accuracy of the videos. Redundant or irrelevant videos were excluded. The educational value of YouTube videos was assessed using the Global Quality Scale (GQS). Comparative analyses of video parameters across different cohorts were performed. To assess the reliability and quality of the videos, a modified version of the DISCERN scale and the GQS were employed. Out of the 59 videos reviewed, 43 (72.9%) were of high quality, 10 (16.9%) were of medium quality, and 6 (10.2%) were of low quality. Upon comparing parameters among groups, no significant disparities were observed in terms of daily views, daily favorites, daily dislikes, or daily comments (p>0.05). GQS scores for usefulness and modified DISCERN scores showed significant differences among groups (p<0.001). Additionally, both GQS and modified DISCERN scores exhibited moderately negative correlations (r=-.450 and r=-.474, respectively) and high statistical significance (p<0.001 for both) with utility assessment. YouTube is a valuable repository of high-quality videos for FMF patients. Healthcare providers should guide their patients to high-quality video sources to supplement their educational material.

Arthroplasty Rates and Risk in Familial Mediterranean Fever Patients: A large Population-Based Study.

Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and inflammation in various organs, including the joints. Traditionally, the arthritis of FMF has been considered relatively harmless. However, anecdotal evidence has suggested that it may contribute to long-term joint damage, which may necessitate surgical joint replacement. This study aimed to investigate the rates of arthroplasty among FMF patients and compare it to the general population. The study used the electronic database of the largest healthcare organization in Israel to identify 9,769 FMF patients diagnosed between 2000 and 2016. A similar number of age-, gender-, and residency-matched controls were also identified. The rates of arthroplasty were compared between the two groups. A logistic regression model predicting the need for arthroplasty within the FMF group was formed to identify potential risk factors. Of the 9,769 FMF patients, 114 (1.2%) underwent arthroplasty, compared with 64 (0.7%) of the control group [unadjusted odds ratio (OR)=1.79, 95% confidence interval (CI) 1.32-2.43; partially adjusted OR = 1.97, 95% CI 1.40-2.77; fully adjusted OR = 1.92, 95% CI 1.35-2.72]. Within the FMF cohort, those of North African origin had a significantly higher risk of arthroplasty (OR = 6.89, 95% CI 5.09-9.33; p< 0.001). FMF patients can experience long-term joint damage that may require arthroplasty. Although this complication is relatively uncommon in FMF patients, it occurs almost twice as frequently as compared with the general population. FMF patients of North African origin are at an even higher risk.

Is compressed colchicine tablet superior to other colchicine preparations in patients with familial Mediterranean fever?

The aim of our study is to evaluate the differences in effectiveness, dosage, and side effect profiles in the use of colchicine preparations and evaluate the superiority of compressed colchicine tablets in familial Mediterranean fever (FMF) patients with resistance or intolerance to coated colchicine tablets. Patients who were diagnosed with FMF according to the Tel Hashomer criteria, aged 18 years and older, and switched from compressed colchicine to coated colchicine tablets in the rheumatology clinic of Gazi University were identified. The daily colchicine dose and FMF attack frequency before and after switching from coated colchicine tablets to compressed colchicine tablets were compared. The study included 43 female (72.9%) and 16 male patients (27.1%), and the mean age was 34.54±8.3 years. The number of attacks per year was significantly reduced after switching to compressed colchicine tablets, and daily colchicine doses were lower after switching to compressed colchicine tablets (1.97±0.23 vs 1.78±0.39 mg, p<0.001). Compressed colchicine tablets were shown to be superior to other colchicine preparations and compressed colchicine tablets to be a useful treatment option before initiating biological agents in patients who were unresponsive to coated colchicine.

Pyrin Inflammasome Activation Defines Colchicine-Responsive SURF Patients from FMF and Other Recurrent Fevers.

Syndrome of undifferentiated recurrent fever (SURF) is characterized by recurrent fevers, a lack of confirmed molecular diagnosis, and a complete or partial response to colchicine. Despite the clinical similarities to familial Mediterranean fever (FMF), the underlying inflammatory mechanisms of SURF are not yet understood. We here analyzed the in vitro activation of the pyrin inflammasome in a cohort of SURF patients compared to FMF and PFAPA patients. Peripheral blood mononuclear cells (PBMC) were collected from SURF (both colchicine-treated and untreated), FMF, PFAPA patients, and healthy donors. PBMC were stimulated ex vivo with Clostridium difficile toxin A (TcdA) and a PKC inhibitor (UCN-01), in the presence or absence of colchicine. The assembly of the pyrin inflammasome was evaluated by measuring the presence of apoptosis-associated Speck-like protein containing caspase recruitment domain (ASC) specks in monocytes using flow cytometry. IL-1β secretion was quantified using an ELISA assay. No differences in TcdA-induced activation of pyrin inflammasome were observed among FMF, PFAPA, and healthy donors. Untreated SURF patients showed a reduced response to TcdA, which was normalized after colchicine treatment. In contrast to FMF, SURF patients, similar to PFAPA patients and healthy donors, did not exhibit pyrin inflammasome activation in response to UCN-01-mediated pyrin dephosphorylation. These data demonstrate that in vitro functional analysis of pyrin inflammasome activation can differentiate SURF from FMF and PFAPA patients, suggesting the involvement of the pyrin inflammasome in the pathophysiology of SURF.

Kolşisin ile Tedavi Edilen Çocukluk Çağı FMF Hastalarında COVID-19'un Hafif Klinik Seyri

Aim: Clinical trials continue for several medical protocols for COVID-19. Colchicine is an anti-inflammatory agent that is highly used medicament for autoimmune disorders, including Familial Mediterranean Fever (FMF). Based on immunity disrupting the pathogenesis of SARS-CoV-2, we aimed to describe the clinical course of SARS-CoV-2 infection in patients with childhood-onset FMF on colchicine treatment.&#x0D; Material and Methods: We prepared a survey investigating contact histories, and clinical presentation of childhood-onset FMF patients treated with colchicine and questioned their parents via phone calls or during outpatient visits. In addition, medical record history, treatment, and medication history were obtained from the hospital database.&#x0D; Results: A total of 171 patients, 99 (57.9%) male and 72 (42.1%) female, diagnosed with FMF and who have been under colchicine treatment for at least one month were included in the study. Among patients, 56 (32.7%) have contact with a confirmed COVID-19 case; 43 (25.1%) have suspected family member contact and 13 (7.6%) have non-family contact. Only 15 (8.8%) FMF patients treated with colchicine were PCR diagnosed with COVID-19 disease; all had mild symptoms, none required antiviral treatment, and none were hospitalized. The dose and duration of colchicine use did not significantly differ between the patients with confirmed COVID or not (p=0.112, and p=0.344, respectively).&#x0D; Conclusion: We concluded that pediatric patients with FMF receiving colchicine treatment may not be at increased risk for being infected with SARS-CoV-2 or the severe symptoms of COVID-19.

Genotypes and Phenotypes of Arab Patients with Familial Mediterranean Fever in North Jordan

Objectives: Familial Mediterranean Fever (FMF) is an autosomal-recessive disorder caused by mutations in MEFV gene. Hundreds of mutations have been described in patients with FMF. The aim of this study was to analyze the common genotypes of Arab patients with FMF from Jordan and to establish genotypephenotype correlation patterns.&#x0D; Methods: This cross-sectional retrospective study was performed in a tertiary hospital in the north of Jordan. A total of 123 patients with FMF were recruited from the rheumatology outpatient clinic at King Abdullah University Hospital. Patients were diagnosed according to Tel-Hashomer criteria and a carrier of at least one previously identified MEFV gene mutation. Demographics and clinical manifestations were recorded.&#x0D; Results: Mean age at diagnosis was 17.49 years and M:F ratio was 1.05:1. The following mutations were common among our patients: R202Q (41.4%), M694V (22.1%), E148Q (10.3%), V726A (11.3%), M680I (5.3%), and M694I (3.7%). Among them 26% were homozygous, 11% were compound homozygous, 26% heterozygous, 42% were compound heterozygous, and 18% were other complex genotype including homozygosity and heterozygosity of more than one mutation. As for genotype-phenotype correlation, 65% of the patients with skin rash had R202Q mutation, while M694V mutation was associated with abdominal and chest pain. Amyloidosis correlated most with the M694I mutation (66.7%).&#x0D; Conclusion: The results confirm the frequency of the previously and commonly identified mutations and highlight the association of R202Q polymorphism with skin rash phenotype among adult Jordanian FMF patients. Additionally, both M694V and M694I mutations were associated with different clinical presentations.&#x0D; Bangladesh Journal of Medical Science Vol. 23 No. 01 January’24 Page : 54-62