Familial Mediterranean Fever Attacks 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.

An “On Demand” canakinumab regimen for treating children with Colchicine-Resistant familial Mediterranean fever – A multicentre study

ObjectivesCanakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an “canakinumab on demand ” (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and “canakinumab fixed frequency” (CFF) policies. MethodsThis retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies. ResultsTwenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups. ConclusionFor individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive.

Factors triggering familial mediterranean fever attacks, do they really exist?

Several possible factors are hypothesized to trigger familial Mediterranean fever (FMF) attacks; however, there is no consensus on this matter. We aimed to identify these triggering factors and analyze their relationship with the Mediterranean fever gene mutation status. We prepared a questionnaire that included the most commonly mentioned possible trigger factors of familial Mediterranean fever. We administered a questionnaire to 882 patients. We used a questionnaire assessing the following: psychological stress, consumption of tea and coffee, relationship with menses, menopause and post-menopausal alleviation, seasonal changes, traveling for long durations, relocation, starvation, sleeplessness, cold exposure, fatigue, wind exposure, and humidity. The most frequent triggering factor for familial Mediterranean fever attacks was psychological stress (75.2%). Cold exposure was a statistically significant trigger in patients with exon 10 mutations. Humidity was a statistically significant trigger in patients with exon 2 mutations. Seasonal changes, traveling for long durations, relocation, and cold exposure were statistically significant triggers of familial Mediterranean fever attacks in patients with homozygous M694V mutations. Identifying trigger factors can lead to better preventive measures and personalized therapies to decrease familial Mediterranean fever attacks. 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. Determining the relationship between trigger factors and patients' Mediterranean fever gene mutation status can lead to personalized therapy for the prevention of familial Mediterranean fever attacks.

Effects of intrauterine device use on attack frequency and severity ın woman of reproductive age with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. There are known triggers to initiate an FMF attack, yet potential effects of intrauterine devices (IUD) in women of reproductive age have not been evaluated before. Consecutive female patients with FMF who ever used IUD over the age of 18 were enrolled. Female patients with FMF were sub grouped according to the type of IUD they use. FMF attack frequency, severity, duration, presence of dysmenorrhea, severity of dysmenorrhea, having attacks during menstruation before and after IUD use were questioned. Demographic and clinical data were collected from hospital database. When all patients with IUD use were evaluated, it was found that the frequency of attacks increased after IUD insertion at 3rd and 12th months (median [min-max] attack frequency at 3rd month, 1 (0-3) vs 1 (0-6), p = 0.002, median [min-max] attack frequency at 12th month, 2 (0-12) vs 3.5 (0-18), p = 0.028). Attack severity measured by VAS pain was also significantly increased. Attack duration and menstrual pain was similar before and after IUD use. Attack frequency at 3rd and 12th months, attack severity and menstrual pain was all increased significantly in Cu-IUD users, whereas none of these parameters deteriorated in LNG-IUD group. IUD use, especially Cu-IUD, may increase the frequency and severity of attacks in female patients with FMF. Clinicians may benefit from considering LGN-IUD if IUDs are preferred as contraception in women of childbearing age with FMF.

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.

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.

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.

Abstract 26 — Clinical Characteristics of Familial Mediterranean: Fever in Hemodialysis Patients

Introduction Familial Mediterranean fever (FMF) is an inherited genetic disorder characterized by recurrent episodes of fever, serositis, arthritis, and skin rash. Uncontrolled disease can lead to amyloid A disposition, nephrotic syndrome and progressive renal failure. Recurrence of AA amyloidosis post kidney transplantation has been reported. Long-term colchicine therapy will reduce the FMF attacks and risk of AA amyloidosis. Although there is high prevalence of FMF in MENA region, the data of end stage renal disease (ESRD) in FMF is limited. We report our center experience. Method A retrospective chart review study was conducted at Tawam Hospital over 12 years (January 2010 to January 2023). We included adult ESRD on hemodialysis with FMF disease and studied their management outcomes. Descriptive analysis was used. Results 1900 ESRD patients were on hemodialysis during study period, and only two patients were diagnosed with FMF and renal amyloidosis. Case 1: A 60-year-old male patient from Syria who is known to have FMF and polycystic kidney disease leading to ESRD. He underwent successful LRD kidney transplantation in 2009. He was on mycophenolic acid: 540 mg, BID, prednisolone: 5 mg, tacrolimus: 1 mg am, 0.5 mg and colchicine 0.5 mg BID. He developed progressive renal allograft dysfunction with evidence of nephrotic syndrome. The renal biopsy revealed recurrence of AA amyloidosis due to FMF in kidney allograft in 2018. He had decline in renal function over years was initiated on hemodialysis on 2022. He developed two attacks of FMF peritonitis while on hemodialysis that responded well to steroid/colchicine therapy. Case 2: 48 years old male, from Egypt, known to have irritable bowel syndrome. He presented to our hospital with bilateral lower limb edema, and progressive shortness of breath for one month. Investigations revealed heavy proteinuria (8.98 g/g Creat) and acute kidney injury. Serology and autoimmune workup were negative. Kidney biopsy showed renal amyloidosis, and chronic tubulointerstitial nephritis with severe interstitial fibrosis (60%). History taken again and was positive for FMF in his uncle. Genetic study and clinical confirmed the diagnosis of FMF. He was started on colchicine, but developed ESRD within 8 months and initiated on hemodialysis. He had attacks of FMF. Conclusion Renal amyloidosis in FMF patient leads to progressive renal failure despite colchicine therapy. In our dialysis cohort over 12 years, only two FMF patients were identified. Colchicine therapy is required in ESRD-FMF in order to managed FMF attacks and prevent other organ AA amyloidosis.

The effects of working conditions on work life in Familial Mediterranean Fever (FMF) patients

Introduction: Familial Mediterranean Fever (FMF) is a common autoinflammatory disease, especially in Mediterranean populations. FMF typically occurs with fever and serositis attacks and can negatively affect the individual's life. In our study, we aimed to investigate the effects of working conditions and the disease course on the work life of FMF patients.&#x0D; Methods: The adult patients with pathogenic or likely pathogenic mutations in the MEFV gene who applied to our medical genetic outpatient clinic of the Faculty of Medicine, Çanakkale Onsekiz Mart University between 01.01.2010 and 01.08.2020 were included in our study. We created a questionnaire of 34 questions, which included sociodemographic data, information about the FMF course of the patients, and the effects of work conditions and FMF on the work life of these patients. The questionnaire link, created over Google Drive, was sent to the patient's current mobile phone numbers via text message, and the answers received until 31.12.2020 were evaluated.&#x0D; Results: A total of 154 survey responses were obtained, and 113 were eligible for our study. Twenty-four of 104 (23.1%) participants who have worked in any job so far stated that they have changed or quit their jobs because of increased or worsening FMF attacks. Of 72 participants who have been working actively for the last year, 4 (5.6%) of them we are reported that they have a health problem in the workplace due to FMF disease. The statistically significant relationships were found between the FMF-induced changing or quitting job and the attack number in the last year regardless of attack severity, work-related adverse psychological effects, the mode of transportation to work, and the physical conditions in the working environment.&#x0D; Conclusion: We suggest that the regulation of work environments, considering the factors that trigger attacks in FMF patients, will contribute to the increase in quality of life and work performance in these patients.

The Effect of Anti-Inflammatory Drugs on MEFV, PSTPIP1, Siva, and ASC Gene Expression Levels

Aim: Familial Mediterranean Fever (FMF) is the one of the most common autoinflammatory diseases. FMF is characterized by fever attacks and inflammation and colchicine treatment reduces the frequency and severity of FMF attacks. The FMF gene, MEditerranean FeVer (MEFV), encodes a protein called Pyrin, which regulates inflammation through its interactions with several proteins. These proteins are; Apoptosis-associated speck like protein with a CARD (ASC), Proline serine threonine phosphatase interacting protein 1 (PSTPIP1), 14.3.3 proteins and Siva proteins. In this study, we aimed to study the effect of anti-inflammatory drugs with different mechanisms of action on MEFV, PSTPIP1, Siva, and ASC gene expression levels. &#x0D; Material and Methods: We used differentiated monocytic cell line called THP-1 cells. Cells treated with colchicine, naproxen, prednol-L, acetylsalicylic acid, or azathioprine w and w/o lipopolysaccharide (LPS). After incubation, quantitative RT-PCR (qRT-PCR) was performed to measure MEFV, PSTPIP1, Siva, and ASC gene expression levels. &#x0D; Results: MEFV gene expression level was down regulated in colchicine, naproxen, and azathioprine treated cells whereas PSTPIP1 gene expression level was down regulated in naproxen and azathioprine treated cells with LPS. Siva gene expression level was up regulated in all treatments although ASC gene expression level was up regulated in only prednol-L treated cells with LPS.&#x0D; Conclusion: These anti-inflammatory drugs are known to have different mechanisms of action however they are all used to treat pain or inflammation. Since Pyrin, PSTPIP1, Siva, and ASC have pro and anti-inflammatory roles, the results showing an alteration in gene expression levels with specific drugs may indicate the possible mechanisms of therapeutic action.

Evaluation of Gastrointestinal System Complaints and Comorbidities in Pediatric Familial Mediterranean Fever Patients.

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 study aimed to evaluate GIS complaints and findings other than classic peritonitis attacks in patients with FMF and to interpret concomitant GIS and hepatic disorders in these patients. The medical and genetic findings of patients with FMF who attended our clinic between December 2011 and December 2021 were reviewed. Gastrointestinal system symptoms, liver function tests, abdominal images, and endoscopic and histopathological data were extracted from medical records. A total of 576 pediatric patients (female, 52.3%) diagnosed with FMF were included. Among them, almost one-fifth displayed GIS complaints, such as abdominal pain, defecation problems, and dyspepsia, distinct from typical FMF attacks. High serum aminotransferase levels were detected in 18.4% of the patients, with viral infections being the most common cause of moderate/severe hypertransaminasemia. In addition, during follow-up, 26.9% of them were referred to the pediatric gastroenterology department. At least 1 gastroenterological and hepatobiliary disorder was detected in 17.5% of the patients because of organic and functional GIS disorders or hepatobiliary disorders, such as gastroesophageal reflux disease, esophagitis, functional dyspepsia, and inflammatory bowel diseases. Various GIS and hepatic disorders can be encountered in children with FMF. The spectrum of these complaints and pathologies can range from frequently observed health problems to more severe diseases.

Familial Mediterranean fever: perspective on female fertility and disease course in pregnancy from a multicenter nationwide network.

The aim of this study was to analyze the pregnancy process, especially the Familial Mediterranean fever (FMF) disease course and attack types during pregnancy, and to examine the relationship between disease-related factors and female infertility in FMF patients. The study, which was planned in a multicenter national network, included 643 female patients. 435 female patients who had regular sexual intercourse were questioned in terms of infertility. Pregnancy and delivery history, FMF disease severity and course during pregnancy were evaluated. The relationship between demographic and clinical findings, disease severity, genetic analysis results and infertility was investigated. 401 patients had at least 1 pregnancy and 34 patients were diagnosed with infertility. 154 patients had an attack during pregnancy. 61.6% of them reported that attacks during pregnancy were similar to those when they were not pregnant. The most common attack symptoms were fever, fatigue and abdominal pain-peritonitis (96%, 87%, and 83%, respectively) in the pregnancy period. The disease-onset age, disease activity score, gene mutation analyses, and regular colchicine use (> 90%) were similar between the fertile and infertile groups, while the frequency of previous appendectomy and alcohol consumption rates were higher in individuals with infertility. Our results indicated no significant change in the frequency and severity of attacks during pregnancy. The low rate of infertility (7.8%) in our patients was noted. It has been suggested that the risk of FMF-related infertility may not be as high as thought in patients who are followed up regularly and received colchicine.

Not easy-peasy to diagnose: familial Mediterranean fever unaccompanied by fever.

Classical attacks of familial Mediterranean fever (FMF) are often accompanied by fever, but some of the patients have attacks without fever. This study aimed to compare the characteristics of FMF patients with and without fever during their attacks and draw attention to the different clinical presentations of FMF in children.Medical files of patients aged 0-18years who were followed up with the diagnosis of FMF in two reference pediatric rheumatology centers were reviewed retrospectively. The patients were divided into two groups: children who had had no fever in any of their attacks were assigned as group 1, and those who had fever during their attacks were classified as group 2.Out of 2003 patients evaluated, 191 (9.53%) patients had attacks not accompanied by fever and their median age at onset of symptoms (7.0 vs. 4.0years, p < 0.001) and the median age at diagnosis (8.6 vs. 6.0years, p < 0.001) were significantly higher; however, group 2 had a delay in diagnosis. The annual number of attacks and abdominal attacks were more common in group 2; arthritis, arthralgia, erysipelas-like rash, exercise-induced leg pain, and myalgia were more common in group 1. Conclusion: The data from the assessment of children with FMF attacks not accompanied with fever were presented for the first time. Children with late age onset of FMF and dominance of musculoskeletal features may display attacks not accompanied with fever. What is Known: • Familial Mediterranean fever (FMF) is the most common inherited auto-inflammatory disease, characterized by recurrent attacks of fever, serositis, and musculoskeletal symptoms. •Although fever is the most common symptom, few studies have reported attacks without fever. What is New: • The aim of this study was to identify patients with FMF but without fever during attacks and to demonstrate their distinctive presentations. • We found that 7% of our patients had afebrile attacks with predominant musculoskeletal symptoms and were diagnosed earlier than patients with febrile attacks, probably due to early referral to pediatric rheumatology clinics.

The efficacy of a single-dose anakinra injection during disease attack in pediatric familial Mediterranean fever.

The aim of this retrospective study is to evaluate the efficacy of a single-dose anakinra during familial Mediterranean fever (FMF) attacks and its effect on the duration, severity, and frequency of attacks. The patients with FMF who had disease episode and received a single-dose anakinra during disease episode between December 2020 and May 2022 were included. Demographic characteristics, MEFV gene variants detected, concomitant medical conditions, demographics of recent and previous episodes, laboratory findings and length of hospital stay were recorded. A retrospective analysis of medical records revealed 79 attacks from 68 patients who met inclusion criteria. The patients had a median age of 13 (2.5-25) years. All patients reported that the average duration of their previous episodes lasted longer than 24h. When the recovery time of attacks after subcutaneous anakinra application at the disease attack was examined, it was observed that 4 attacks (5.1%) ended in 10min; 10 attacks (12.7%) in 10-30min; 29 attacks (36.7%) in 30-60min; 28 attacks (35.4%) in 1-4h; 4 attacks (5.1%) in 24h; and 4 attacks (5.1%) ended in more than 24h. There was no patient who did not recover from their attack after a single dose of anakinra. Although the efficacy of a single-dose anakinra administration during FMF attacks in children needs to be confirmed by prospective studies, our results suggest that use of a single-dose anakinra during FMF attacks is effective in reduction of severity and duration of disease attacks.

The effect of education given to Turkish adolescents with Familial Mediterranean fever on anxiety, depression, and quality of life.

To examine the effects of individual education given to Turkish adolescents with Familial Mediterranean fever (FMF) on anxiety, depression, and quality of life. The randomized controlled experimental study was performed on 70 adolescents aged 12-18years who were diagnosed as having FMF between October 2021 and April 2022 in Turkey. The disease management education was offered individually to adolescents in the intervention group with a booklet entitled "FMF is under my control;" no intervention was applied to adolescents in the control group. The training booklet was prepared by the researchers in a multidisciplinary team and was finalized by taking expert opinions. In the data collection process, a personal information form, the State-Trait Anxiety Inventory for Children (STAI-CH), the children's depression inventory (CDI), and the Pediatric Quality of Life Inventory (PedsQL) were used. After applying the scales specified in the pretest, individual training was given and the posttest was performed 2months later using the same scales. After the education, there was a statistically significant decrease in the mean CDI score of the intervention group (p < 0.05), whereas there were statistically significant increases in mean scores obtained on PedsQL and its sub-scales (p < 0.05). However, the decrease in the mean STAI-CH score of the intervention group was not statistically significant (p > 0.05). There was no statistically significant difference in the mean STAI-CH, CDI, and PedsQL scores of the control group after the education (p > 0.05). Conclusion: The effectiveness of the individual education program for adolescents with FMF in improving quality of life and reducing levels of depression within the scope of disease management has been confirmed. It is recommended that all health professionals working with children with FMF regularly provide individual or group-planned education programs. What is Known: • The unpredictability of FMF attacks has a very negative effect on adolescents. • Individual education programs on FMF focus on children with a holistic approach. What is New: • To the best of our knowledge, this study is the first study to evaluate disease management education given to adolescents with FMF. • This is a pioneering study of the use of nurses in the education of adolescents with FMF and in fulfilling their educational roles.

Adherence to Colchicine During Pregnancy in Familial Mediterranean Fever Patients: Reasons for Cessation and Outcomes from a Single-Centre Experience

Abstract Objective To evaluate the adherence to colchicine treatment during pregnancy and lactation in our Familial Mediterranean fever (FMF) patients and investigate the reasons for non-adherence and consequences. Methods Adult female FMF patients who were followed up in our rheumatology clinic and had a history of pregnancy after the diagnosis of FMF were consecutively enrolled to this cross-sectional study between November 2021 and June 2022. Only pregnancies occurring after the diagnosis of FMF were evaluated. Patients who did not stop using FMF treatment after pregnancy were considered to adhere to treatment. Results In 50 patients, a total of 88 pregnancies and 58 live births were observed after the diagnosis of FMF. 37 (74%) had at least one completed pregnancy, and 13 (26.0) were pregnant during the study. Among the 37 patients, 34 had at least one live birth. No significant differences were observed when rates of patients with a history of at least one live birth, abortus, Cesarean section (C/S), preterm labor, stillbirth, intrauterine anomaly, congenital malformation and fetal growth retardation were compared between colchicine users and non-users. 60% of the patients adhered to colchicine treatment during pregnancy and 73.4% did so while breastfeeding. The most common reason for colchicine cessation was concerns regarding potential harm to the fetus (70%), followed by the presumption that colchicine is contraindicated in pregnancy (15%) as well as absence of FMF attacks (10%). The most common source of the patients’ opinion was a physician (60%). Conclusions Both patients and attending physicians should be informed to be more adherent to colchicine to avoid adverse outcomes and FMF-related complications.

Successful Treatment of a Pediatric Patient with High-dose Colchicine Intake and Intoxication Findings by Hemoperfusion

Colchicine is used in treating many rheumatological diseases and is widely prescribed in children. Its use specifically aims to prevent familial Mediterranean fever (FMF) attacks and amyloidosis prophylaxis. Colchicine’s therapeutic range is extremely narrow. It may cause fatal effects when taken at toxic doses. Since the plasma volume of distribution is very high, it is necessary to rapidly intervene for elimination from the body in case of toxicity with colchicine. In this case report, a 3.5-year-old patient with severe high-dose colchicine intake developed intoxication findings. Then, this patient successfully underwent hemoperfusion and recovered without sequelae.

Familial Mediterranean Fever and Transverse Myelitis: A Causal Relation?

Familial Mediterranean fever (FMF) is a rare autoinflammatory disorder characterized mainly by recurrent self-limited episodes of fever and polyserositis. FMF-related neurologic complication is an old debate, and the correlation between FMF and demyelinating disorders has been a matter of dispute for a long time. Few reports demonstrated a relationship between FMF and multiple sclerosis; however, the existence of a causal relationship between FMF and demyelinating disorders is still a puzzle. This report presents the first case of transverse myelitis following FMF attacks in which neurologic manifestations were resolved using colchicine treatment. Due to relapses of FMF, which were accompanied by transverse myelitis, rituximab was administered, which resulted in stabilizing disease activity. Accordingly, in the case of colchicine-resistant FMF and FMF-related demyelinating conditions, rituximab could be considered as a potential therapeutic option to alleviate both polyserositis and demyelinating manifestations.

Serum Asprosin Level as a New Biomarker in Differentiating Familial Mediterranean Fever Attacks.

Introduction Familial Mediterranean fever (FMF) is a recessively inherited disease characterized by recurrent attacks of fever and sterile polyserositis. Recently, some proteins originating from adipose tissue have been demonstrated to play a critical role in the inflammatory process. Asprosin is a new adipokine secreted by adipose tissue, and proinflammatory cytokines have been determined to increase with the decrease of circulating asprosin. This study was designed to evaluate the level of asprosin in the acute attack and attack-free period in FMF patients. Materials and methods A total of 65 FMF patients were evaluated for this cross-sectional case-control study. Those who were obese and had concomitant diabetes mellitus, hypertension, heart failure, and rheumatological disease were excluded from the study. The patients were divided into two groups: attack-free period and attack period. Fifteen healthy individuals who were not obese and had no additional disease were included as the control group. Demographic data, gene analyses, laboratory findings, and symptoms were recorded at the time of diagnosis. Serum asprosin level was studied by enzyme-linked immunosorbent assaytest in the outpatient clinic controls of the patients. Asprosin levels and other laboratory findings were compared between the attack, attack-free, and control groups. Results Of the patients included in the study, 50% were in the attack period, and 50% were in the free-attack period. The mean age of the FMF patients was 34±10 years. Asprosin level in the control [median (interquartile range (IQR))=30.4 (21.5-57.7) ng/mL] group was significantly higher than the attack [median (IQR)=21.5 (17.5-28) ng/mL] and attack-free [median (IQR)=19(18.7-23) ng/mL] groups (p=0.001). C-reactive proteinand sedimentation levels were significantly higher in the attack group compared to the other two groups (p<0.001). There was a moderate correlation between C-reactive proteinand asprosin levels (Ro=-0.314, p=0.01). The cut-off value of serum asprosin level was determined as 21.6 ng/mL; sensitivity was 78%, and specificity was 77% (p<0.001). Conclusion The study demonstrated that the serum asprosin levels of FMF patients with acute attack were lower than those in the attack-free periods and healthy controls.Asprosin is likely to have a role in the anti-inflammatory cascade.

Fetal thymic-thoracic ratio in pregnancies with familial Mediterranean fever

ObjectiveTo investigate the thymic-thoracic ratio (TTR) in fetuses of pregnant women with familial Mediterranean fever (FMF). Study designThis prospective case-control study was conducted with 43 pregnant women diagnosed with FMF and 43 gestational age-matched healthy controls. Pregnant women between 28 and 40 weeks who applied for antenatal care were included in the study. Healthy pregnant women whose age and gestational week matched were defined as the control group. ResultsTTR was significantly lower in the FMF group compared to the control group. The mean TTR value was 0.34 ± 0.03 in the FMF group and 0.36 ± 0.02 in the control group (p < 0.001). TTR was significantly lower in those with FMF duration of ten years or more than those with FMF of less than ten years (p < 0.001). In addition, pregnant women who had an attack during pregnancy had lower TTR (p < 0.001). TTR was significantly associated with white blood cell count, neutrophil count, monocyte count, platelet count, mean platelet volume, C-reactive protein, red cell distribution width, and platelet‑to‑lymphocyte ratio. ConclusionBesides the inflammation during the FMF attacks, the ongoing subclinical inflammation between the attacks might affect the fetal thymus size. Since TTR is an easily applicable method, it can be used to evaluate fetal inflammation.