Diagnosis Of Familial Mediterranean Fever Research Articles

Impact of multiple MEFV variants of unknown significance on the diagnosis and clinical presentation of familial Mediterranean fever

The detection of variants of unknown significance (VUS) in familial Mediterranean fever (FMF) is common; however, their diagnostic value remains elusive, and the interpretation of multiple VUS remains difficult. Therefore, we examined FMF diagnosis-associated factors 1-year post-genetic testing in patients with only VUS and assessed the impact of multiple VUS on diagnosis and clinical features. A 1-year follow-up was conducted on patients clinically suspected of having FMF without confirmatory diagnosis owing to the presence of only VUS. Clinical features were compared between patients with a single VUS and those with multiple VUS among patients diagnosed with FMF. Among 261 patients followed up, 202 were diagnosed with FMF based on clinical judgment. No specific clinical symptoms or variant patterns at genetic testing were associated with diagnosis at 1 year. Multiple VUS was significantly and independently associated with a lower response to colchicine than single VUS among patients diagnosed with FMF. However, clinical symptoms showed no correlation with the number of VUS. In conclusion, predicting FMF diagnosis 1-year post-genetic testing in patients with only VUS remains challenging. Moreover, the impact of multiple VUS on FMF may be limited owing to the lack of correlation with clinical features, except colchicine response.

Heterozygous Pyrin (MEFV) E148Q allele carriers indicate a reduced glaucoma risk for Turkish population: a prospective clinical analysis

ABSTRACT Purpose The MEFV gene encodes pyrin, a protein linked to increased severity of symptoms in Familial Mediterranean Fever (FMF). We consider that inflammation due to MEFV variants would increase eye inflammation and damage aqueous humor regulation. The present study is the first analysis investigating a MEFV (E148Q) variant as a marker protecting from glaucoma. Methods In this prospective clinical analyze, we performed detailed gene sequencing focusing on 22 specific regions of the pyrin (MEFV) gene. The study involved two distinct groups: individuals diagnosed with glaucoma (n = 200) and control subjects without glaucoma (n = 100). Both groups were carefully selected to exclude individuals with symptoms or a previous diagnosis of Familial Mediterranean Fever (FMF). The diagnosis of glaucoma for each participant was rigorously established through comprehensive direct ophthalmic examinations. Results A significant odds ratio for protection against glaucoma was found in carriers of the subclinical E148Q allele (OR:2.22; 95%CI: 1.098–4.485). No significant differences were found for other variants. One mutant E148Q-allele could decrease the probability of glaucoma development by approximately 68,9%. We observed no differences in the genotype frequency between glaucoma and healthy for the other MEFV gene variants. Conclusion The pyrin variant of the MEFV gene resulting in a subclinical phenotype appears to reduce the incidence of glaucoma, and heterozygous pyrin (MEFV) E148Q allele carriers confer protection against glaucoma. It is important to consider the limitations arising from the relatively small number of studies conducted on this topic.

Unprecedented Coexistence of Autoinflammatory Myositis and Chronic Thrombosis with heterozygotic M694V mutation: An atypical presentation of Familial Mediterranean Fever.

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder predominantly characterized by periodic fever, abdominal pain, and joint manifestations. It can exhibit various atypical presentations and affects individuals globally. However, cases of FMF concurrently presenting with chronic thrombosis and myositis have not been previously reported. A 41-year-old male presented with alternating severe bilateral leg pain, stiffness, and localized swellings without fever or abdominal symptoms. His history included recurrent inflammatory joint pain treated with prednisolone. Physical examination revealed leg pain, limited ankle joint movement, and tender swellings in thighs, forearms, and feet. Collateral abdominal veins were also observed. Unresponsive to prednisolone and colchicine, the patient underwent MRI, revealing muscle inflammation in both legs and thighs and chronic thrombosis in the infrarenal inferior vena cava. Genetic testing confirmed the heterozygotic M694V mutation, diagnosing an atypical FMF. Anakinra treatment led to substantial clinical and laboratory improvement. Although FMF diagnosis typically relies on characteristic clinical features and genetic analysis, atypical presentations challenge established criteria. This case uniquely showcases coexisting myositis and chronic thrombosis in FMF. Myalgia is common in FMF, with M694V mutation associated with severe muscular symptoms. The lack of fever and myositis findings differentiate our case from protracted febrile myalgia syndrome. FMF's chronic inflammatory state is known to influence thrombosis risk, and our findings align with this association. Chronic thromboembolism and myositis together signify an unusual clinical presentation of FMF. This case highlights the potential for FMF to present with complex manifestations beyond the conventional symptoms. Myositis and vascular involvement should prompt consideration of FMF diagnosis when combined with patient history, clinical features, and laboratory results. These rare associations underscore the need for further research to enhance understanding of FMF's diverse clinical spectrum.

Real-World Treatment Patterns Following Update to National Comprehensive Cancer Network Guidelines for Light-Chain Amyloidosis: Results from a Us Administrative Claims Database

Background: Light-chain amyloidosis (AL) is a rare, multi-organ disease that can cause serious organ damage. In January 2021, a new therapy, daratumumab, was FDA-approved for the treatment of AL in combination with current standard-of-care (SoC) of bortezomib/cyclophosphamide/dexamethasone (CyBorD) and was classified as SoC according to the National Comprehensive Cancer Network (NCCN) guidelines. The objective of this study is to describe current real-world treatment patterns amongst patients with AL who newly initiated treatment January/2021 through June/2022. Methods: This study included patients aged ≥18 identified in the IQVIA PharMetrics database (>72 million lives 2021-2022 total) who were newly initiating pharmacological treatment with bendamustine, bortezomib, carfilzomib, cyclophosphamide, daratumumab, ixazomib, lenalidomide, melphalan, pomalidomide, or venetoclax 01Jan2021-30Jun2022 (date of first therapy classified as “index date”). Patients were required to have an ICD-10 diagnosis of AL (E85.81) identified during full study period (01Jan2020-30Sep2022) as well as continuous medical and prescription insurance enrollment from 1 year pre-treatment-index through 90-days post-treatment-index. Patients were excluded if they had any of the following: a claim indicating treatment with stem cell transplant; a diagnosis of familial mediterranean fever; a diagnosis of secondary, transthyretin, or hereditary amyloidosis; a diagnosis of a non-myeloma/non-lymphoma malignancy. Treatment patterns assessed included index treatment regimen and daratumumab adoption/use patterns at index, 30-days post-index, and 90-days post-index. Results: A total of 194 patients met all eligibility criteria, out of which the majority were male (N=119; 61%), with the largest insurance coverage being self-insured (N=80; 41%), and a mean age of 62 years (SD=9.8). The most common index treatment regimen was CyBorD+daratumumab (N=53; 27%) followed by dexamethasone+daratumumab (N=24;12%) and daratumumab monotherapy (N=16; 8%) ( Table). Across all treatment regimens at index date, daratumumab was found to be utilized by 62% (N=121) of patients. Furthermore, 76% (N=148) and 80% (N=155) of patients were found to have utilized daratumumab within 30-days or 90-days of treatment initiation, respectively. Discussion: AL is life threatening disease that impacts organ function and quality of life. Until 2021, there were no FDA approved therapies for AL. Daratumumab use was rapidly adopted to treat patients with AL following approval, in accordance with national guidelines, primarily in combination with other treatments such as CyBorD. This has changed the treatment paradigm providing hope to patients and clinicians to treat this devasting disease and should be informative for current and future clinical trial considerations in development of medications to treat AL.

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.

Concurrence of familial Mediterranean fever and Behçet’s disease: a case report and review of the literature

BackgroundFamilial Mediterranean fever and Behçet’s disease are distinct disorders that are prevalent in the Mediterranean and Middle Eastern populations. They are characterized by unprovoked inflammatory episodes caused by overexpression of proinflammatory cytokines. Although reported previously, the overlapping presentation of familial Mediterranean fever and Behçet’s disease remains uncommon.Case presentationA 46-year-old Lebanese–Canadian man who presented with recurrent oral and genital ulcers, polyarticular synovitis, ocular swelling, recurrent infections, and fevers was later found to have heterozygous mutations of pathogenic MEFV c.2080A > G (p. Met 694Val) and c.2082G > A (p.Met694IIe) genes indicating familial Mediterranean fever. He was treated with prednisone, colchicine, and azathioprine, with inadequate symptoms control. Treatment was complicated by recurrent infections.ConclusionsOur case contributes to the growing literature demonstrating the presentation of predominantly Behçet’s disease-like features in the setting of diagnosis of familial Mediterranean fever. These findings emphasize that clinicians should be aware that patients with familial Mediterranean fever may present with Behçet’s disease-like clinical manifestations.

Accuracy of generative artificial intelligence models in differential diagnoses of familial Mediterranean fever and deficiency of Interleukin-1 receptor antagonist

With the increasing development of artificial intelligence, large language models (LLMs) have been utilized to solve problems in natural language processing tasks. More recently, LLMs have shown unique potential in numerous applications within medicine but have been particularly investigated for their ability in clinical reasoning. Although the diagnostic accuracy of LLMs in forming differential diagnoses has been reviewed in general internal medicine applications, much is unknown in autoinflammatory disorders. From the nature of autoinflammatory diseases, forming a differential diagnosis is challenging due to the overlapping symptoms between disorders and even more difficult without genetic screening. In this work, the diagnostic accuracy of the Generative Pre-Trained Transformer Model-4 (GPT-4), GPT-3.5, and Large Language Model Meta AI (LLaMa) were evaluated in clinical vignettes of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) and Familial Mediterranean Fever (FMF). We then compared these models to a control group including one internal medicine physician. It was found that GPT-4 did not significantly differ in correctly identifying DIRA and FMF patients compared to the internist. However, the physician maintained a significantly higher accuracy than GPT-3.5 and LLaMa 2 for either disease. Overall, we explore and discuss the unique potential of LLMs in diagnostics for autoimmune diseases.

Variables for differential diagnosis of familial Mediterranean fever: multiple correspondence analysis of a large Japanese cohort.

We investigated differential diagnoses that should be noted with familial Mediterranean fever (FMF) and useful variables for differentiation in a large Japanese cohort. Patients aged ≥13 years who were clinically suspected of having FMF by Livneh criteria were studied 1 year after MEFV genetic testing. Patients ultimately diagnosed with other diseases were studied, and the association among each disease, patient characteristics, and clinical variables were analyzed using multiple correspondence analysis. In total, 504 patients were included in this study; 34 (6.7%) were diagnosed with a disease other than FMF. The most common diagnosis was Behçet's disease, followed by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, inflammatory bowel disease, myelodysplastic syndromes (MDS), and infectious diseases. Although none of the non-FMF patients had exon 10 variants, some responded to colchicine treatment. Multiple correspondence analysis suggested that atypical symptoms such as stomatitis were associated with Behçet's disease and PFAPA syndrome, whereas characteristic situations such as disease onset ≥40 years were associated with MDS and infectious diseases. Careful follow-ups and reanalysis of the diagnosis should be performed for patients with atypical findings and no exon 10 variants, even if their symptoms meet the clinical criteria for FMF.

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.

A score for predicting colchicine resistance at the time of diagnosis in familial Mediterranean fever: data from the TURPAID registry.

Colchicine forms the mainstay of treatment in FMF. Approximately 5-10% of FMF patients are colchicine resistant and require anti-IL-1 drugs. We aimed to compare the characteristics of colchicine-resistant and colchicine-responsive patients and to develop a score for predicting colchicine resistance at the time of FMF diagnosis. FMF patients (0-18 years) enrolled in the Turkish Paediatric Autoinflammatory Diseases (TURPAID) registry were included. The predictive score for colchicine resistance was developed by using univariate/multivariate regression and receiver operating characteristics analyses. A total of 3445 FMF patients [256 (7.4%) colchicine-resistant and 3189 colchicine-responsive) were included (female:male ratio 1.02; median age at diagnosis 67.4 months). Colchicine-resistant patients had longer, more frequent attacks and were younger at symptom onset and diagnosis (P < 0.05). Fever, erysipelas-like erythema, arthralgia, arthritis, myalgia, abdominal pain, diarrhoea, chest pain, comorbidities, parental consanguinity and homozygosity/compound heterozygosity for exon 10 MEFV mutations were significantly more prevalent among colchicine-resistant than colchicine-responsive patients (P < 0.05). Multivariate logistic regression analysis in the training cohort (n = 2684) showed that age at symptom onset, attack frequency, arthritis, chest pain and having two exon 10 mutations were the strongest predictors of colchicine resistance. The score including these items had a sensitivity of 81.3% and a specificity of 49.1%. In the validation cohort (n = 671), its sensitivity was 93.5% and specificity was 53.8%. We developed a clinician-friendly and practical predictive score that could help us identify FMF patients with a greater risk of colchicine resistance and tailor disease management individually at the time of diagnosis.

Molecular and in Silico Analysis of &lt;i&gt;MEFV&lt;/i&gt; Variants in Familial Mediterranean Fever Patients in Southwest Iran

Familial Mediterranean Fever (FMF) is classified as an autoinflammatory genetic disease inherited by mutations in &lt;em&gt;MEFV&lt;/em&gt;. These mutations can affect the dysregulation of inflammatory processes in the human body and lead to fever and pain in the chest and abdomen. Many known missense mutations in &lt;em&gt;MEFV&lt;/em&gt; are linked to FMF disease. Mutations in &lt;em&gt;MEFV&lt;/em&gt; in most cases are located on the short arm of chromosome 16 and can impair the function of the pyrin protein. In this research, we aimed to examine the entire exons of &lt;em&gt;MEFV&lt;/em&gt; for 13 cases (8 females and 5 males) with FMF diagnosis from Southwest Iran. Hence, we amplified and sequenced the exons of &lt;em&gt;MEFV&lt;/em&gt; and then, in-silico analysis of detected changes was applied to estimate the probability of pathogenicity for the identified variants. Finally, we found five single nucleotide substitutions, including M694V (c.2080A&gt;G), R202Q (c.605G&gt;A), E447G (c.1430A&gt;G), E148Q (c.442G&gt;C), and V726A (c.2177T&gt;C), in the under-represented patients. The most frequent mutations in our study were R202Q (38.46%) within exon 2 and M694V (30.7%) within exon 10. Other mutations accounted for a further 23% of the alleles, including E477G (7.6%), E148Q (7.6%), and V726A (7.6%). According to the &lt;em&gt;in-silico&lt;/em&gt; analyses, including variation pathogenicity, protein structure, and allele frequency assessments, we concluded that all these variants could be considered in FMF molecular profiling in southwest Iran.

Adherence to colchicine prophylaxis among patients with familial Mediterranean fever treated with interleukin-1 inhibitors

ObjectiveInterleukin-1 (IL-1) inhibitors are approved for treating familial Mediterranean fever (FMF) that is resistant to colchicine. However, continued concomitant treatment with colchicine is imperative, as it is the only drug proven to prevent secondary amyloidosis. We aimed to compare the adherence to colchicine between patients with colchicine-resistant FMF (crFMF) who were treated with IL-1 inhibitors and patients with colchicine-sensitive FMF (csFMF) who were treated only with colchicine. MethodsThe databases of Maccabi Health Services, a 2.6-million-member state-mandated health provider in Israel were searched for patients with FMF diagnosis. The medication possession ratio (MPR), calculated from the day of the first colchicine purchase (index date) until the last colchicine purchase was the main outcome measure. Patients with crFMF were matched in a 1:4 ratio to patients with csFMF. ResultsThe final cohort included 4526 patients. Of them, 108 (2.4%) were with crFMF, and were matched to 432 with csFMF. The total mean MPR in each of the matched groups was similar (78.9 ± 41.4 and 82.5 ± 80.6, respectively, P = 0.5). Statistically significant differences in MPR were not found between the groups according to age or duration of colchicine use. However, adherence to colchicine was insufficient (MPR<80%) among more than 50% of the patients in both groups. ConclusionIn contrast to initial concerns, adherence to colchicine was similar between patients with crFMF and csFMF. However, in both groups, adherence to colchicine was poor. Education of both caregivers and patients is essential to increase adherence.

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.

Renal involvement in familial Mediterranean fever in an Algerian population.

The objectives of this study were to investigate the clinical biological and histological renal involvement secondary to familial Mediterranean fever (FMF), the epidemiological data, genetics of our patients and their evolution under treatment. We prospectively studied 58 Algerian patients admitted in our nephrology department from January 2012 to January 2021. The diagnosis of nephropathy was suspected clinically and biologically and confirmed histologically. All our patients were tested for MEFV mutations. Results: 58 patients, 30 males and 28 females, mean age 31.68 ± 12.71; 3 (5.17%) chronic dialysis patients and 55 (94.82%) referred to the nephrology department for renal biopsy with renal symptomatology consisting of nephrotic syndrome in 50 (94. 73%), associated with renal failure 27 (47.36%), mainly primary in 23 (34.5%), secondary to seronegative lupus 13 (22.4%), Crohn's disease 9 (14.5%), sarcoidosis 3 (5.26%), and lymphoma 1 (1.7%); 29 (50%) were from consangineous marriages, the histological study found AA amyloidosis in 52 (89.6%); the genetic study confirmed the diagnosis of FMF in 58 (100%). The evolution of the patients: 20 (34.48%) followed in consultation, 25 (43.10%) in hemodialysis and 13 (22.41%) deceased. Conclusion: Renal involvement was the revealing complication in the diagnosis of FMF which exists in our country, and is still underdiagnosed.

Evaluation of Tuberculosis Risk under Interleukin-1 Inhibitor Agents in Patients with Autoinflammatory Diseases: Experience from a Region with Moderate Tuberculosis Prevalence

Abstract Background We aimed to investigate the rate of TBC reactivation in patients with autoinflammatory conditions who had been followed up under treatment with IL-1 antagonists in our clinic. We further aimed to evaluate whether latent TBC screening and isoniazid prophylaxis before IL-1 inhibitor treatment is beneficial in the prevention of reactivation. Patients and Methods This study was designed as a cross-sectional and observational study. It received the approval of the local ethics committee and was therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Adult patients who had been followed up in our clinic under treatment with IL-1 antagonists were evaluated with regard to whether they had a TBC infection before and after these treatments and whether they had been screened for latent TBC infection before IL-1 antagonist treatment and received prophylaxis. Clinical and laboratory data were obtained from hospital records and via telephone interviews after the patients had given their verbal consent to participate. Results Fifty-nine patients under IL-1 antagonists were consecutively enrolled. 58 were under follow-up with the diagnosis of familial Mediterranean fever and one patient with a diagnosis of adult-onset Still’s disease. 35 patients (59.3%) were treated with anakinra and 24 (40.7%) were treated with canakinumab. 12 (50%) of the canakinumab users had previously received anakinra treatment and were switched to canakinumab due to side-effects or ineffectiveness. The number of patients who underwent latent tuberculosisc infection (LTBI) screening before treatment was 37 (62.7%); the number of patients who received prophylaxis was 13 (22%). None of the patients receiving IL-1 antagonists developed active tuberculosis. Conclusion Blocking the IL-1 pathway may be safe regarding the activation of LTBI or development of a new tuberculosis infection even in locations with a high geographical risk.

Acute stroke in familial Mediterranean fever: An analysis of 23 new cases and systematic review of the literature.

The nature of neurovascular involvement in cases of familial Mediterranean fever (FMF) has not been adequately clarified. Clinical features, infarct topography, vascular status, and stroke etiology were prospectively determined in 35 acute neurovascular events that occurred in 23 FMF patients. Clinicoradiological features were compared with an age- and gender-matched control group of 115 acute stroke patients. Characteristics of additional FMF and acute stroke cases (6 episodes in 6 patients) identified from a systematic literature review (PROSPERO registration no: CRD420212264820) were also analyzed. There were 27 acute ischemic stroke episodes in 19 patients, 7 transient ischemic attack episodes in 3 patients, and 1 patient with a single episode of parietal hematoma in our cohort. Twenty (74%) ischemic stroke episodes in 12 patients were cryptogenic. Ten of these 12 cases had a previous FMF diagnosis and were taking colchicine. There was no significant difference in the FMF group in terms of the presence of vascular risk factors and angiography-documented disease in comparison to controls. Cerebral distal artery involvement was significantly prevalent in FMF (78% vs 45%, P= .002). Especially, midbrain central deep perforating territory involvement was higher (30% vs 1%, P< .001). The long-term prognosis (median 8.5 years) under antiplatelet agents and colchicine is favorable. The acute stroke phenotype in FMF cases is herein described for the first time. Several clinicoradiological features such as thrombotic lacunar infarcts located in the central mesencephalon seem so typical that we recommend searching for FMF mutations in geographic regions where FMF is common.

Similarities and differences between familial Mediterranean fever (FMF) and multisystem inflammatory syndrome (MIS-C) in children

Aim: We aimed to reveal the similarities and differences between the rare and severe multisystem inflammatory syndrome (MIS-C) and active familial Mediterranean fever (FMF) disease in children. Our study may help in the early recognition of MIS-C syndrome in children and distinguish it from other diseases with similar symptoms.Methods: We evaluated the demographic and clinical characteristics, laboratory findings, treatments and outcomes of patients with MIS-C syndrome and active FMF.Results: The clinical and laboratory findings of a total of 66 patients hospitalized in our pediatric clinic with the diagnosis of active FMF (n: 42) and MIS-C syndrome (n: 24) were reviewed retrospectively. The reason for pediatric emergency admission was determined as resistant fever in all patients. When the clinical findings of the patients were compared, it was determined that joint and abdominal pain in the FMF group and vomiting, rash, cough, Lenfadenopati (LAP) and myalgia findings in the MIS-C group were statistically significantly higher (p

Clues for inflammatory diseases in the differential diagnosis of a child with sacroiliitis.

The purpose of this study was to compare the demographic, clinical and laboratory characteristics of patients with enthesitis-related arthritis (ERA), familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD), which are inflammatory diseases that may develop sacroiliitis. Thus, it was aimed to reveal various findings that may indicate primary disease in patients with sacroiliitis. Pediatric patients aged 6-18 years, who were being followed with a diagnosis of ERA (n= 62), FMF (n= 590), and IBD (n= 56) over the period 2013-2021 were included in the study. Sacroiliitis (n= 55) was diagnosed by magnetic resonance imaging of the sacroiliac joint, obtained from clinically suspected patients. Sacroiliitis was detected in 54.8% of ERA patients, 2.3% of FMF patients, and 12.5% of IBD patients. The mean follow-up period was 4.1± 2.8 years (10 months-8 years) for the entire study group. The most common MRI finding for sacroiliitis was bone marrow edema. Peripheral joint involvement (73.5%) and HLA B27 positivity (64.7%) was significantly higher in ERA patients, and ERA was diagnosed more frequently in patients presenting with sacroiliitis. Non-steroidal anti-inflammatory drugs (NSAIDs) were the first choice of treatment agent when sacroiliitis developed in all three patient groups. The clinical and laboratory findings of ERA, FMF and IBD can sometimes be intertwined or can even coexist. Treatment may differ depending on the disease associated with sacroiliitis, although NSAIDs may be used in the first-line treatment of all three diseases. Sacroiliitis patients with HLA B27 positivity and peripheral arthritis may need to be addressed as ERA.

Comparison of demographic, clinic and radiological features of patients with axial spondyloarthritis accompanying familial Mediterranean fever to patients with each condition alone

Objective To compare the demographic, clinical, and radiological features of patients with axial spondyloarthritis (axSpA) accompanying familial Mediterranean fever (FMF) to patients with each condition alone. Method Hacettepe University Hospital database was screened regarding ICD-10 codes for FMF (E85.0) and axSpA (M45). The diagnosis of FMF was confirmed by Tel-Hashomer criteria, and axSpA by the presence of sacroiliitis according to the modified New York criteria or active sacroiliitis on magnetic resonance imaging. As control groups, 136 gender-matched, consequent FMF patients without axSpA and 102 consequent axSpA patients without FMF previously treated with any biological agents were included in the analysis. Results In patients with FMF + axSpA compared to the axSpA group, age at axSpA symptom onset and age at diagnosis were lower [median with interquartile range (IQR): 21 (17–30) vs 27 (21–37), p < 0.001; 23 (21–38) vs 32 (24–43) years, p = 0.001], moderate to severe hip disease and total hip replacement were more prevalent (23.4% vs 4.7%, p < 0.001; 11.2% vs 2.8%, p = 0.016). In patients with FMF + axSpA compared to the FMF group, age at FMF symptom onset and age at diagnosis were higher [13 (6–30) vs 11 (5–18), p = 0.057; 23 (13–33) vs 18 (10–31) years, p = 0.033] and amyloidosis was more prevalent (6.6% vs 2.2%, p = 0.076). Although the M694V variant (in one or two alleles) was more prevalent in the FMF + axSpA group, the difference was not statistically significant. Conclusion In patients with FMF + axSpA, the age of onset of axSpA was significantly earlier, moderate to severe hip involvement and amyloidosis were more common than in patients with each condition alone.

Investigation of different genomic variants in familial Mediterranean fever cases with monoallelic MEFV mutation.

Familial Mediterranean Fever (FMF) is an inflammatory disease characterised by periodic fever and concurrent episodes of serous membrane inflammation. FMF is considered to be inherited in autosomal recessive manner and biallelic mutations in the MEFV gene are associated with the disease. However, approximately 20-25% of patients only have a single mutation in MEFV gene, which creates confusion in differential diagnosis of many patients. This study aimed to reveal rare variants that may act in conjunction with the single pathogenic MEFV variant in the pathogenesis of FMF. We performed whole exome sequencing in 17 individuals from 5 different families who were diagnosed according to the clinical criteria, responded positively to colchicine treatment, but had no biallelic MEFV mutation. A disease-causing variant or a common affected cellular pathway that was shared in all index cases was not detected. When cases were examined individually, two de novo variants were identified in the BIRC2 and BCL10 genes, both of which play a role in inflammatory pathways. Functional studies are needed to confirm the physiopathological relationship of these genes with FMF. This study is one of the most extensive aetiological researches in FMF cases with monoallelic MEFV mutation. We have shown that genotype-phenotype correlation in these cases may not be established by rare genetic variants and discussed underlying causes. Clinical criteria with emphasis on colchicine response and family history should be the main tool and genetic results should only be used for support in FMF diagnosis.