Familial Mediterranean Fever Disease Research Articles

Comparison of Familial Mediterranean Fever patients by triglyceride/high-density lipoprotein ratio

Aim: In this study, we aimed to show whether there is a relationship between FMF disease and cardiovascular risk by comparing Triglyceride/HDL-Cholesterol ratios between FMF patients and the control group.Materials and Methods: A total of 300 patients, including 150 Familial Mediterranean Fever (FMF) patients and 150 control groups aged 18-65, were included in our study. Triglyceride/HDL-Cholesterol ratios of the patients were compared.Results: Triglyceride/HDL-Cholesterol ratio was statistically significantly higher in the FMF group than the control group (p=0.026).Conclusion: In FMF patients, the Triglyceride/HDL-Cholesterol ratio can be used as an inexpensive, reproducible predictor in showing a cardiac risk.

Evaluation of Nasal Mucociliary Activity in Patients with Familial Mediterranean Fever

Objective: The aim of this study was to evaluate nasal airway resistance and nasal mucociliary activity in Familial Mediterranean Fever (FMF) patients using anterior rhinomanometry and saccharin clearance test. Methods: 30 patients with FMF disease and 30 healthy individuals were included in this prospective, cross-sectional study. Nasal airway resistance was measured via active anterior rhinomanometry and a saccharin test was carried out for the measurement of nasal mucociliary clearance (NMC) times of all participants. Results: Mean values for NMC time in the FMF patient group and control group were found as 14.6 ± 4.7 (range, 8-30) min. and 9.7 ± 2.3 (range, 6-14) min. respectively. Nasal mucociliary clearance time in the FMF patients was significantly prolonged in comparison to that of healthy controls (p < 0.001). We identified no significant correlation between the disease duration and NMC time (p=0.921, r = 0.019). When the mean nasal airway resistance values of both groups were compared, there was no significant difference was detected (p = 0.371). Conclusion: The results of our study have revealed that NMC time was longer in patients with FMF than healthy controls. However, there was no statistically significant correlation between nasal mucociliary clearance time and disease duration. Disruption of NMC increases the risk of infection in the upper and lower respiratory tract. Caution should be exercised against upper and lower respiratory infections in patients with FMF.

Assessment of serum TWEAK levels in patients with familial Mediterranean fever

Background/Aim: Mediterranean fever is an autoinflammatory disease characterized by recurrent attacks. Tumor necrosis factor (TNF) - like weak inducer of apoptosis (TWEAK) is a member of the TNF ligand family, and it has been reported to contribute significantly to the initiation of many inflammatory and immunological processes. In previous studies, an increasing amount of evidence has implicated the participation of TWEAK / Fn14 pathway in the pathogenesis of rheumatic inflammatory diseases that include rheumatoid arthritis, systemic lupus erythematosus and Behçet's disease. The aim of this study was to investigate the serum TWEAK levels of patients with Familial Mediterranean fever (FMF) and its possible relationship with inflammatory markers and disease activity. Methods: Our study included 20 patients with FMF and 19 healthy volunteers. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) were measured, and PRAS disease severity score was determined in patients with FMF. Also, the FMF attack period was questioned. Serum TWEAK levels were measured with available commercial Enzyme Linked Immunosorbent Assay kits. Results: There was no significant difference in terms of age and gender between the FMF group and the healthy control group (P>0.05, for all). ESR, CRP and serum TWEAK levels were significantly higher in patients with FMF (P<0.001 for all). PRAS score in FMF patients was 3.4. Serum TWEAK level was not correlated with ESR (r=-0.042, P=0.0801), CRP (r=-0.017 P=0.921), or PRAS score (r=0.247, P=0.149). The ESR and CRP levels of patients in FMF attack period were significantly higher compared to attack free period (P<0.001 for both) whereas there was no significant difference in serum TWEAK levels (P=0.686). Conclusions: Serum TWEAK levels are increased in FMF disease with attacks. However, this increase is not associated with increased ESR and CRP during FMF attacks. These results indicate that the TWEAK / Fn14 pathway plays a role in earlier stages where the inflammatory pathways have not differentiated yet. Serum TWEAK levels appear to be more successful in reflecting a lower degree of inflammation compared to ESR and CRP.

Positive effects of ocrelizumab in patients with familial mediterranean fever and coexistent multiple sclerosis.

Objectives This study aims to evaluate the effects of ocrelizumab (OCZ) on familial Mediterranean fever (FMF) attacks in multiple sclerosis (MS) patients with FMF (MS+FMF patients).Patients and methods This retrospective observational study included 11 patients (2 males, 9 females; mean age 46.6±9.2; range, 22 to 55 years) with MS+FMF hospitalized between January 2016 and July 2019. Demographic, clinical, and laboratory parameters and patient reported outcomes were analyzed in patients treated with OCZ for 18 months.Results Combining OCZ with colchicine in MS+FMF patients significantly reduced the frequency of FMF attacks (p=0.003) and the frequency of joint attacks (p=0.002). Consistent with the clinical improvement, the maximum serum C-reactive protein levels were significantly decreased after combination therapy compared to before combination therapy (p=0.003). MS+FMF patients reported that FMF disease activity improved after OCZ therapy (Visual Analog Scale [VAS] 74±9.6 vs. VAS 46.5±8.1 mm, p=0.003).ConclusionOcrelizumab therapy led to a prominent decrease in the frequency of FMF attacks, alleviated functional impairment, and improved quality of life in MS+FMF patients.

Familial Mediterranean fever-related miR-197-3p targets IL1R1 gene and modulates inflammation in monocytes and synovial fibroblasts

Familial Mediterranean fever (FMF); is an autosomal recessively inherited autoinflammatory disease caused by the mutations in the Mediterranean Fever (MEFV) gene. Recent studies have shown that epigenetic control mechanisms, particularly non-coding RNAs, may play a role in the pathogenesis of autoinflammation. microRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating host gene expression at the post-transcriptional level. The phenotypic heterogeneity of FMF disease suggests that FMF may not be a monogenic disease, suggesting that epigenetic factors may affect phenotypic presentation. Here we examined the potential anti-inflammatory effect of miR-197-3p, which is a differentially expressed miRNA in FMF patients, by using inflammation related functional assays. We monitored gene expression levels of important cytokines, as well as performed functional studies on IL-1β secretion, caspase-1 activation, apoptosis assay, and cell migration assay. These experiments were used to evaluate the different stages of inflammation following pre-miR-197 transfection. Anti-miR-197 transfections were performed to test the opposite effect. 3′UTR luciferase activity assay was used for target gene studies. Our results obtained by inflammation-related functional assays demonstrated an anti-inflammatory effect of miR-197-3p in different cell types (synovial fibroblasts, monocytes, macrophages). 3′UTR luciferase activity assay showed that miR-197-3p directly binds to the interleukin-1beta (IL-1β) receptor, type I (IL1R1) gene, which is one of the key molecules of the inflammatory pathways. This study may contribute to understand the role of miR-197-3p in autoinflammation process. Defining the critical miRNAs may guide the medical community in a more personalized medicine in autoinflammatory diseases.

Is visceral adipose tissue or subcutaneous adipose tissue a risk factor for atherosclerotic heart disease in familial mediterranean fever?

Is visceral adipose tissue or subcutaneous adipose tissue a risk factor for atherosclerotic heart disease in familial mediterranean fever?

Joint Manifestations in Children with Familial Mediterranean Fever in Armenia: Clinical and Genetic Characteristics

Familial Mediterranean fever (FMF) is an autosomal-recessive autoinflammatory disease in the group of Hereditary periodic fever syndromes (HPFS), characterized by recurrent, self-limited attacks of fever and polyserositis, which last 2-4 days. It manifests mainly in childhood and often has early onset, resolve without sequels. Genetic testing of FMF is efficient and allows diagnosing of atypical cases. FMF is a significant health care problem in Armenia because of high frequency of carriers of MEFV mutations 1:3 - 4 (0.21) and marked FMF prevalence 54.7 per 10`000 of the total population. Articular symptoms are found in about 45% of cases. They usually manifest as acute recurrent arthritis (ARA) or arthralgia, but more rarely also chronic arthritis can be found. We aimed to investigate clinical and genetic characteristics of the joint manifestations in Armenian children with FMF. The charts of all 715 patients with proven diagnosis of FMF at the National Pediatric Center (NPC) for FMF were reviewed for joint manifestations. The diagnosis of FMF and disease severity were determined according to the Tel-Hashomer criteria and molecular-genetic detection of 12 MEFV mutations common for Armenians. The characteristics of joint manifestations and overall FMF disease were then compared to MEFV mutation analysis. There were 438 boys and 277 girls with an age at diagnosis between 3 months and 17 years (mean age: 8.64±0.17). Joint involvement was observed in 56.4% of all 715 cases. The manifestation was ARA in 30.5%, arthralgia in 21.2% and chronic arthritis (CA) in 4.7%, which would also qualify for a diagnosis of JIA. The frequency of ARA was associated with M694V mutation, mainly M694V homozygous and M694V heterozygous genotypes. The risk of CA depended on MEFV genotype of the FMF patients and was the highest in M694Vheterozygotes and M694Vhomozygotes. M694V heterozygous genotype was noticed significantly more frequently among FMF patients with spondyloarthritis in comparison to those without it. The probability of the development of CA among FMF patients without M694V mutation was significantly higher also in heterozygotes in comparison to compound-heterozygotes. We concluded, that the frequency of joint involvement among Armenian pediatric FMF patients was high - 56.4%, especially for CA. Chronic arthritis may be the first manifestation of FMF and occurred usually in patients with severe M694V mutations. Patients of Armenian origin with refractory arthritis should be asked for isolated febrile attacks, hemorrhagic vasculitis, episodes of pleuritis and family history to rule out FMF.

Comparison of Efficacy Between Next Generation Sequencing and Fragment Analysis in MEFV Gene Analysis

Objective: This study aims to compare the diagnostic effectiveness of fragment analysis and next-generation sequencing methods in Familial Mediterranean Fever (FMF) disease. Data from the study will guide clinicians in the diagnosis of FMF patients Method: Two hundred and ninety patients with normal (N/N) or heterozygous (M1/N) fragment analysis results had been included in the study in the medical genetics laboratory of Kayseri City Hospital. In these patients, the entire MEFV gene was examined by the NGS analysis method. The mutation profiles of these patients were compared retrospectively. Statistical analysis of the data was performed using SPSS 22.0 package program. Results: All mutations found in the fragment analysis were also detected by NGS method. Additional mutations were observed in 22 patients in the NGS analysis method. Mutations that were not previously reported in the HGMD, Clinvar and Infevers database were introduced into the literature. The application of NGS method to the patients was found to be statistically significant (p&lt;0.01) Conclusion: Fragment analysis is a low-cost method that examines the frequent changes in the diagnosis of FMF patients but is insufficient to make a definitive diagnosis. NGS analysis method should be a preferable analysis method, in terms of diagnodtic usefulness.

Succinivibrionaceae is dominant family in fecal microbiota of Behçet's Syndrome patients with uveitis.

Behçet's Syndrome (BS) is a multisystem vasculitis with various clinical manifestations. Pathogenesis is unclear, but studies have shown genetic factors, innate immunity and autoinflammation to have an important role in the disease course. Diversity in the microbial community of gut microbiota may significantly contribute to the activation of the innate immune system. The clinical features of BS present themselves in clusters and each cluster may be a consequence of different disease mechanisms. For this reason we aimed to investigate the gut microbiota of BS patients with uveitis. In addition to healthy controls, we have aimed to compare the gut microbiota of BS with that of Familial Mediterranean Fever (FMF) and Crohn's Disease (CD) as both diseases have innate and autoinflammatory features in their pathogenesis. Seven patients with BS, 12 patients with FMF, 9 patients with CD and 16 healthy controls (HC) were included in the study. Total genomic DNAs were isolated from fecal samples of the patients. Partial 16S rRNA gene was sequenced using the PGM Ion Torrent (Thermo Fisher Scientific, Waltham, MA, USA) for microbiota analysis. Statistical analysis showed that significant differences were detected on the microbial community of four groups. Succinivibrionaceae is dominant and the signature family, whereas Bacteroides was absent in BS patients.

Infertility Causes and Pregnancy Outcome in Patients With Familial Mediterranean Fever and Controls.

Recurrent attacks of peritonitis due to familial Mediterranean fever (FMF) may lead to peritoneal adhesions and fallopian tube obstruction. Colchicine, which is the treatment of choice for FMF, may disturb cell division. Secondary amyloidosis, a complication of untreated FMF, may involve the testes and ovaries. Thus, FMF and colchicine may potentially affect fertility and pregnancy in patients with FMF. The aims of the study are to evaluate the causes of infertility and pregnancy outcome in FMF patients and to compare them with 2 groups: non-FMF patients with peritoneal female genital tuberculosis (FGTB) and normal healthy controls. This is a retrospective study in which FMF patients with reproductive disorders were recruited from the National Center of Medical Genetics and Primary Health Care in Yerevan, Armenia. The patients with FGTB and the healthy controls with reproductive problems were recruited successively from a large gynecology clinic in Yerevan. Genetic analyses for FMF were performed using ViennaLab StripAssay. The FMF group (211 patients) resembles the FGTB group (127 patients) regarding etiologies of infertility. However, in vitro fertilization (IVF) success rate and pregnancy outcome were comparable between the FMF patients and the control group (162 patients). Infertility in patients with FMF was clearly associated with a more severe disease and a lack of adequate colchicine treatment. Colchicine medication and controlled FMF disease do not adversely affect the reproductive system and pregnancy outcome. However, a lack of an appropriate colchicine treatment may cause infertility and poor pregnancy outcome.

Gastrointestinal Amyloidosis in Children with Familial Mediterranean Fever Disease and Anorectal Manometry Results

Objectives: The aim of this study was to evaluate the effect of amyloid deposition in colon mucosa on the results of anorectal manometry test and the use of ROME III questionnaire in patients with Familial Mediterranean Fever (FMF). Methods: The files of patients diagnosed with FMF were scanned to evaluate the patients at risk for amyloid deposition. Predisposing factors were identified. The patients were sampled using anorectal manometry test, Rome III questionnaire and the rectal mucosa suction biopsy and the test results were compared. Results: 17 (63%) of the patients were female and 10 (37%) were male. The mean age was 12.15 ± 2.40 years. The number of patients with amyloid deposition in the rectal mucosa sample was 2 (7.4%). Both of these patients had regularly used colchicine. Amyloid deposition was found to be high in patients with M694V homozygous mutation (P = 0.05). According to the Rome III questionnaire, findings suggestive of irritable bowel syndrome were found in 5 patients and abdominal migraine was found in 3 patients. However, no statistical difference was found when the results of the Rome III questionnaire were compared with the results obtained from the anorectal manometry test (P &gt; 0.05). Conclusions: Amyloidosis can be seen due to various environmental factors, regardless of age, even when colchicine is regularly used. Anorectal manometry is an easy to perform test, helping diagnosis in this patient group. Although it has been shown that in patients with predisposing factors for amyloid deposition RAIR can be detected at lower pressures in anorectal manometry, the clinical significance of this finding is unclear. Since the Rome III questionnaire showed findings consistent with functional abdominal pain disease in one third of the patients, independent of the presence of FMF, it was found that the application of this questionnaire in patients with FMF could be misleading.

Enthesitis may be one of the signs of severe disease in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an auto-inflammatory disease that is also characterized with some of the common musculoskeletal features of spondyloarthritis (SpA). Enthesitis is the hallmark of SpA. Recently, it was postulated that exertional leg pain is a possible sign of lower extremity enthesitis associated with FMF severity. In this study, we have evaluated the association between the enthesitis, enthesitis score and disease severity in FMF patients. We enrolled 238 FMF patients that fulfilled the modified Tel-Hashomer criteria. We assessed the presence of enthesitis at the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) defined sites with standard palpation method. Then, FMF patients dichotomised two groups as enthesitis group and controls. Herein, we evaluated the enthesis extensity with MASES. FMF disease severity was determined via the international severity scoring system for FMF (ISSF). Firstly, we have compared demographic properties, disease-related features and ISSF scores of the groups. Then, we have correlated ISSF with MASES in enthesitis group. We showed that 54 (22.6%) of 238 patients had enthesitis. The demographic features were similar between the groups. The enthesitis group had higher ISSF scores (p < 0.001); higher frequency of fever (p = 0.004), exertional leg pain (p < 0.001), myalgia (p < 0.001) and arthritis (p = 0.01); and more intense, widespread, frequent and longer attacks compared with controls. Moreover, there was a weak correlation between ISSF and MASES in the patients with enthesitis. Enthesitis may be a sign of more severe FMF phenotype and frequently associated with other musculoskeletal manifestations resemble SpA. Key points •More than one-fifth of the patients with FMF would suffer from enthesitis. •The FMF patients with enthesitis had higher ISSF scores; higher frequency of fever, exertional leg pain, myalgia and arthritis; and more intense, widespread, frequent and longer attacks as compared with controls. •Enthesitis may be a sign of more severe FMF phenotype and frequently associated with other SpA-like musculoskeletal feature.

Genome sequencing unveils mutational landscape of the familial Mediterranean fever: Potential implications of IL33/ST2 signalling.

Familial Mediterranean fever (FMF) is the most common auto‐inflammatory disease. It is transmitted as autosomal recessive trait with mutations in MEditerranean FeVer (MEFV) gene. Despite a typical clinical expression, many patients have either a single or no mutation in MEFV. The current work is aimed to revisit the genetic landscape of FMF disease using high‐coverage whole genome sequencing. In atypical patients (carrying a single or no mutation in MEFV), we revealed many rare variants in genes associated with auto‐inflammatory disorders, and more interestingly, we discovered a novel variant ( a 2.1‐Kb deletion) in exon 11 of IL1RL1 gene, present only in patients. To validate and screen this patient‐specific variant, a tandem of allele‐specific PCR and quantitative real‐time PCR was performed in 184 FMF patients and 218 healthy controls and we demonstrated that the novel deletion was absent in controls and was present in more than 19% of patients. This study sheds more light on the mutational landscape of FMF. Our discovery of a disease‐specific variant in IL1RL1 gene may constitute a novel genetic marker for FMF. This finding suggesting a potential role of the IL33/ST2 signalling in the disease pathogenicity highlights a new paradigm in FMF pathophysiology.

The pyrin inflammasome and the Yersinia effector interaction.

Pyrin is a cytosolic pattern-recognition receptor that normally functions as a guard to trigger capase-1 inflammasome assembly in response to bacterial toxins and effectors that inactivate RhoA. The MEFV gene encoding human pyrin is preferentially expressed in phagocytes. Key domains in pyrin include a pyrin domain (PYD), a linker region, and a B30.2 domain. Binding of ASC to pyrin by a PYD-PYD interaction triggers inflammasome assembly. Pyrin is held in an inactive conformation by negative regulation mechanisms to avoid premature inflammasome assembly. One mechanism of negative regulation involves phosphorylation of the linker by PRK kinase which in turn is positively regulated by active RhoA. The B30.2 domain also negatively regulates pyrin. Gain of function mutations in MEFV responsible for the autoinflammatory disease Familial Mediterranean Fever (FMF) map to exon 10 encoding the B30.2 domain. Insights into pyrin regulation have come from studies of several Yersinia effectors, which are injected into phagocytes and interact with the RhoA-PRK-pyrin axis during infection. Two effectors, YopE and YopT, inactivate RhoA to disrupt phagocytic signaling. To counteract an effector-triggered immune response, a third effector, YopM, binds to and inhibits pyrin by hijacking PRK and RSK and directing linker phosphorylation. Inhibition of pyrin by YopM is required for virulence of Yersinia pestis, the agent of plague. Recent results from infection studies with human phagocytes and mice producing pyrin B30.2 FMF variants show that gain of function MEFV mutations bypass inhibition by YopM. Population genetic data suggest that MEFV mutations were selected for in individuals of Mediterranean decent during historic plague pandemics. This review discusses current concepts of pyrin regulation and its interaction with Yersinia effectors.

Prevalence of Nonalcoholic Fatty Liver Disease in Familial Mediterranean Fever.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome (MetS), insulin resistance (IR) and chronic inflammation. Although familial Mediterranean fever (FMF) patients have no symptoms in the periods between attacks, their subclinical inflammation continues. The aim of the present study was to determine the NAFLD frequency in FMF patients and to evaluate their MetS, IR and lipid profiles. The study included 54 FMF patients and 54 control subjects. The clinical and demographic characteristics of the subjects were recorded, and the patients' Pras disease severity score was calculated. IR was determined using the homeostasis model assessment (HOMA) index. MetS was diagnosed using the revised National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP ATP III). Hepatic ultrasonography was used to diagnose NAFLD. NAFLD was observed in 15 FMF patients (27.8%) and 14 controls (25.9%). The difference between the groups was not significant (p=0.828). Similarly, no significant difference was found between the two groups for MetS frequency and HOMA index levels. Fasting plasma glucose was significantly higher in FMF patients, whereas differences between the two groups were not significant for lipid levels and other parameters. When FMF patients with and without NAFLD were compared, no significant difference was found in Pras disease severity score, duration of the disease and daily colchicine dose. The present study showed that NAFLD frequency was not increased in FMF patients, and that patients' MetS frequency, IR and lipid profiles were not different from control subjects.

Pyrin variants can burn out the plague.

Mutations in pyrin that cause the autoinflammatory disease familial Mediterranean fever may have been selected for during plague pandemics.

Abdominal syndrome in so-called «Outinflammatory diseases»; Two cases of family Mediterranean fever

The aim — on the example of the analysis of clinical observations, the authors draw attention to various variants of the course of the classic auto — inflammatory disease-familial Mediterranean fever (SSL) with severe abdominal syndrome.Materials and methods: the article present clinical material on two observations of patients with SSL in clinical symptoms, which were dominated by abdominal syndrome, from the moment of their request for medical care to the verification of the diagnosis.Results: The article presents brief information about the diseases of the group of auto-inflammatory (periodic fever syndrome with mevalonatkinase deficiency, TRAPS-syndrome, Crohn’s disease, familial Mediterranean fever), in the manifestation of which gastroenterological symptoms play a significant role. An example of «early» and «late» diagnosis of auto-inflammatory diseases is illustrated by the results of the analysis of two clinical cases of patients with SSL.The analysis of the analyzed clinical cases confirms the multidisciplinary nature of the problem of auto-inflammatory diseases and the importance of readiness not only of rheumatologists, but also of other specialists to make such a diagnosis.

Next-generation screening of a panel of genes associated with periodic fever syndromes in patients with Familial Mediterranean Fever and their clinical characteristics

Familial Mediterranean Fever (FMF) is a hereditary fever syndrome that primarily affects Mediterranean populations. For the study, total number of 182 patients with FMF disease were enrolled and screening of a panel of genes , called “fever panel” which comprises 17 genes, was performed. The most common mutations in MEFV gene were homozygous M694V missense mutation (4.3%) and R202Q missense mutation (4.9%). The most common heterozygous mutations were R202Q (26.5%), M694V (25.9%) and E148Q (11.9%). Compound heterozygous and homozygous mutations were also detected. Also, different types of mutations were identified in NOD2, CARD14, NLRP12, NLRP3, NLRP7, IL1RN, LPIN2, TNFRSF1A, MVK and PSTPIP1 genes. Two novel missense variations in the MEFV gene, Gln34Pro and Ile247Val, which have not been previously reported in the databases, were identified. Also, Thr91Ile missense variation in the NOD2 gene, Gly461Cys missense variation in NLRP3 and Tyr732Stop nonsense variation in LPIN2 were firstly identified. The results of the current study suggest that in addition to the MEFV gene which has an important roles in FMF, molecular screening of other genes related to other autoinflammatory diseases might provide support in suspected cases and provide detailed information about the course of the disease.

High prolidase levels in patients with Familial Mediterranean Fever (FMF).

Familial Mediterranean Fever (FMF) is an autoinflammatory disease. Prolidase is a specific imidodipeptidase that plays a role in collagen degradation, and an important role in inflammation and wound healing. Hypoxia-inducible factor-1α (HIF-1) is an important protein in the regulation of immunological response, hemostasis, vascularization. The aim of the study was to compare serum prolidase and HIF-1α levels in patients with FMF in attack-free period and healthy control group. Between August 2017 and December 2017, sixty patients diagnosed with FMF according to the criteria of the Tel-hashomer and admitted to Sivas Cumhuriyet University Medical Faculty, Internal Medicine Rheumatology Department and sixty healthy volunteers were enrolled in the study. Median serum prolidase levels were 72.1 (25.1-114.9) ng/ml in FMF group and 30.7 (21.3-86.2) ng/mL in healthy control (HC) group (p = 0.018). ROC analysis showed that the sensitivity was 65% and the specificity was 68.3% at serum prolidase levels 54.03 ng/mL (p < 0.05). The median serum levels of HIF-1α in the FMF group was 482.0 (292.0-3967.0) pg/mL and 632.0 (362.0-927.0) pg/mL in the HC group (p > 0.05). There was no significant correlation between laboratory findings, sex, age, and prolidase (p > 0.05). Serum prolidase enzyme levels in FMF patients with attack-free period were significantly higher than in the HC group. However, the role of prolidase and HIF1-α in the FMF disease needs to be clarified with more extensive and comprehensive studies.

Similarities between pediatric FMF patients with sacroiliitis and pediatric juvenile spondyloarthropathy patients with sacroiliitis: a preliminary study

ABSTRACT Objective: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent, self-limited attacks of fever with serositis. Acute recurrent arthritis is the most common form of musculoskeletal involvement in FMF; however, ≤5% of FMF patients can develop chronic arthritis, including sacroiliitis. It is difficult to determine if sacroiliitis is a musculoskeletal finding of FMF or if they are concomitant diseases–FMF and juvenile spondyloarthropathy (JSpA). The present study aimed to compare clinical and laboratory findings in FMF patients with concomitant sacroiliitis and JSpA patients with concomitant sacroiliitis. Materials and Methods: The medical files of patients diagnosed with FMF and JSpA with concomitant sacroiliitis were retrospectively evaluated. All patients had MRI findings consistent with sacroiliitis. Patient demographic data, clinical features, and laboratory findings were compared between the patients with FMF and concomitant sacroiliitis, and those with JSpA and concomitant sacroiliitis. Results: The study included 18 patients with FMF and sacroiliitis, and 38 patients with JSpA and sacroiliitis. The median (range) age at diagnosis of FMF accompanied by sacroiliitis and JSpA accompanied by sacroiliitis was 12.0 years (3.5–18 years) and 13 years (4–18 years), respectively. There weren’t any significant differences in HLA-B27 positivity, family history of ankylosing spondylitis, presenting complaints, arthritis, enthesitis, or treatment between the 2 patient groups. Conclusion: The present findings show that pediatric patients with FMF and sacroiliitis, and those with JSpA and sacroiliitis have the same clinical and laboratory findings.