Familial Mediterranean Fever Research Articles

Can We Identify Individuals at Risk to Develop Multiple Myeloma? a Machine Learning Based Predictive Model

Background: Multiple myeloma (MM) evolves over years. Pre-MM states, such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM, are asymptomatic and often missed. When active MM is diagnosed, it is often associated with organ damage. We hypothesized that applying a machine learning (ML) approach on electronic medical records (EMR) can help in developing a predictive model that identifies population at most risk for MM. Methods: An observational retrospective study was performed using data extracted from the Clalit Health Services (CHS) EMR. CHS insures 4.7x106 individuals (53% of the Israeli population). The study included CHS members diagnosed with MM between 2002 and 2019 and their controls. First, we compared numerous clinical and lab parameters of MM patients in the pre-MM period (5yr to 2m prior to diagnosis) to controls. Then, a ML approach was used to develop a risk prediction model using a gradient boosting algorithm The unit of analysis was a patient who underwent a blood test at a given month. The training set included units from "future MM" patients and from matched controls. Model performance was evaluated on a separate test set including blood tests performed in the year 2014 by patients who were not included in the training set and were not diagnosed with MM at the time of their blood tests. Lastly, a simplified model was constructed by excluding MM-specific variables and applying a logistic regression. Results: We identified 4982 MM patients, of whom 4256 had the relevant lab tests and were therefore eligible for comparison. In the pre-MM period, "future MM" patients had higher ESR, lower Hb, neutrophil count (ANC) and Neutrophil/Lymphocyte ratio, and higher levels of serum globulins, urinary protein, serum IgG and ferritin, than controls. They tended, more than controls, to suffer from immune deficiencies, as well as myelodysplastic syndromes and familial Mediterranean fever. Consumption of medications (tranquilizers, anti-diabetics, Ca-antagonists, statins) was associated with reduced risk for MM. The gradient boosting predictive model was developed using 19,129 learning units of MM cases and 382,580 controls. The test set included 268,058 blood tests, 368 of these (0.14%) belonged to patients who were diagnosed with MM within 5yr. The performance of the model was good, with an area under the curve (AUC) of 0.836. Ranges of MM predictors stratify the risk of developing the disease in the future (Figure 1). The simplified logistic regression model included 9 parameters: age, sex, uric acid, LDH, RBC, lymphocyte %, ANC, HDL and Non-HDL-cholesterol. It had an AUC of 0.794. An example of its use is provided in Table 1. Conclusions: Using a large database and a ML approach, we were able to develop a predictive model of MM risk. Taking only a few, widely available parameters, a predicted MM risk can be provided for any individual performing simple blood tests. The model can be used as a first-line screening tool, pointing clinicians to the individuals most at risk for MM, allowing them to focus further workup accordingly. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Does having MEFV gene sequence variants affect the clinical course and colchicine response in children with PFAPA syndrome?

Colchicine seems to be an effective and safe treatment modality in PFAPA treatment. It led to a change in the nature of the attacks either in the frequency, duration, or severity of the attacks in 95.1% of the patients. This study has shown that having MEFV gene sequence variants did not affect the clinical course or response to colchicine. We recommend that colchicine should be considered in all PFAPA patients to see the response of the patient, irrespective of the MEFV gene mutations. • Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common periodic fever syndrome in the world. Familial Mediterranean fever (FMF) is the most common cause of periodic fever syndrome in Turkey. • Colchicine has become a new treatment option in PFAPA. •Some PFAPA patients have Mediterranean fever (MEFV) gene variants, and it is speculated that PFAPA patients with MEFV gene mutations respond better to colchicine. •The aim of this study was to look for this hypothesis. We have seen that the clinical phenotype and colchicine response of PFAPA patients were not affected by MEFV gene sequence variants.

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.

Transcriptional licensing is required for Pyrin inflammasome activation in human macrophages and bypassed by mutations causing familial Mediterranean fever.

Pyrin is a cytosolic immune sensor that nucleates an inflammasome in response to inhibition of RhoA by bacterial virulence factors, triggering the release of inflammatory cytokines, including IL-1β. Gain-of-function mutations in the MEFV gene encoding Pyrin cause autoinflammatory disorders, such as familial Mediterranean fever (FMF) and Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). To precisely define the role of Pyrin in pathogen detection in human immune cells, we compared initiation and regulation of the Pyrin inflammasome response in monocyte-derived macrophages (hMDM). Unlike human monocytes and murine macrophages, we determined that hMDM failed to activate Pyrin in response to known Pyrin activators Clostridioides difficile (C. difficile) toxins A or B (TcdA or TcdB), as well as the bile acid analogue BAA-473. The Pyrin inflammasome response was enabled in hMDM by prolonged priming with either LPS or type I or II interferons and required an increase in Pyrin expression. Notably, FMF mutations lifted the requirement for prolonged priming for Pyrin activation in hMDM, enabling Pyrin activation in the absence of additional inflammatory signals. Unexpectedly, in the absence of a Pyrin response, we found that TcdB activated the NLRP3 inflammasome in hMDM. These data demonstrate that regulation of Pyrin activation in hMDM diverges from monocytes and highlights its dysregulation in FMF.

Investigation of the effect of vascular endothelial growth factor gene 936 C/T polymorphism in familial Mediterranean fever patients

Objectives: This study aims to investigate the effect of vascular endothelial growth factor (VEGF) gene 936C/T polymorphism (rs3025039) on the appearance of phenotypic characteristics of familial Mediterranean fever (FMF) patients that differ with respect to MEditerranean FeVer (MEFV) gene mutations. Here, we investigated a single functional polymorphism in the VEGF gene. Methods: The study group consisted of 223 FMF patients with definite diagnosis according to Tel-Hashomer criteria who carried MEFV gene mutations, while 208 FMF patients with definite diagnosis of FMF but without any mutations, making up the control group, were included in the study. The VEGF gene 936C/T polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: Genotype and allele frequencies of the VEGF rs3025039 polymorphism between the two groups were significantly different (p = 0.03 and p = 0.011, respectively). The TT genotype was found to be more frequent in the study group than in controls (4.9% vs. 3.3%, respectively). Conclusions: Our results seem to indicate that the VEGF 936C/T polymorphism affects the appearance of the phenotypic characteristics of FMF. It is possible that other variants of this gene may also have similar effects.

AN ATYPICAL PRESENTATION OF FAMILIAL MEDITERRANEAN FEVER

<h3>Introduction</h3> Familial Mediterranean Fever(FMF) is thought to be autosomal recessive disease characterized by periodic fevers associated with serositis. In this case we present a patient with FMF with only one mutation in MEFV gene, suggesting a more variable penetrance of the FMF phenotype. <h3>Case Description</h3> An 8-year-old female diagnosed with juvenile idiopathic arthritis and asymptomatic hematuria presented for elevated immunoglobulins and inflammatory markers. She had no history of recurrent/severe infections or fevers. She endorsed monoarticular joint pains and abdominal pains. Family history was significant for a 1-year-old sister diagnosed with PFAPA and a 15-months-old brother who died from human metapneumovirus associated pulmonary hemorrhage. On exam, she appeared well-nourished, no rash/oral ulcers/abdominal tenderness. Labs were significant for CRP-54, ESR-52, IgG-1950, IgA-327, IgM-230. Urinalysis had 3+ blood without proteinuria. Taken together, her history raised concern for monogenic inborn error of immunity and a primary immunodeficiency panel was sent. Her panel revealed a heterozygous pathogenic variance of MEFV(V726A) responsible for FMF. Her father was later also diagnosed with FMF responsive to colchicine with the same pathogenic MEFV variant. Her cytokines were elevated, including IL-1B, and she was subsequently started on colchicine 0.6mg BID and canakinumab 75mg q4-weeks. Following treatment, she had normalization of inflammatory markers (Table 1) and resolution of joint pains. <h3>Discussion</h3> This case highlights the existence of a subset of FMF patients who have only one mutation in the MEFV gene. Broadening our understanding of the complex genetics and variable penetrance of FMF can prevent delays in diagnosis and treatment.

POST COVID RECURRENT FEVER IN A CHILD WITH GENETIC SUSCEPTIBILITY TO FAMILIAL MEDITERRANEAN FEVER

<h3>Introduction</h3> Children and adults with post-acute sequelae of COVID (PASC) sometimes report recurrent fevers. We present the case of 13-year-old male with PASC recurrent fever who was found to have a heterozygous mutation in the gene associated with Familial Mediterranean fever (FMF). <h3>Case Description</h3> Our patient presented with recurrent fever 6 months after acute SARs-CoV-2 infection in January 2022. He endorsed prior episodes of unexplained fever and flushing prior but his recurrent fevers (39 C) post COVID had become more frequent occurring every few days. Laboratory analysis when he was afebrile demonstrated normal serum ESR, CRP, and CMP and normal cytokine levels. Genetic (In-Vitae) panel testing for autoinflammatory syndromes revealed a pathogenic heterozygous missense mutation in MEFV (p.A744S), the gene that controls pyrin production. A trial of colchicine was recommended, and he was referred to pediatric rheumatology. <h3>Discussion</h3> FMF is a genetic disorder that causes recurrent episodes of fever and almost always presents before age 20. Clinically significant FMF gene mutations lead to poorly functional pyrin; a protein that controls inflammation. Most children look and feel well between episodes but some children have such frequent episodes that they do not fully recover. In such cases, daily use of Colchicine should be considered as a safe and effective medication to control fever episodes. This report highlights the utility of genetic testing to identify potential causes of recurrent fever after COVID. Children with PASC related recurrent fevers should have genetic testing for susceptibility to FEF as this is a potentially treatable condition.

CDC42 regulates PYRIN inflammasome assembly.

The PYRIN inflammasome pathway is part of the innate immune response against invading pathogens. Unprovoked continuous activation of the PYRIN inflammasome drives autoinflammation and underlies several autoinflammatory diseases, including familial Mediterranean fever (FMF) syndrome. PYRIN inflammasome formation requires PYRIN dephosphorylation and oligomerization by molecular mechanisms that are poorly understood. Here, we use a functional genetics approach to find regulators of PYRIN inflammasome function. We identify the small Rho GTPase CDC42 to be essential for PYRIN activity and oligomerization ofthe inflammasome complex. While CDC42 catalytic activity enhances PYRIN phosphorylation, thereby inhibiting it, the inflammasome-supportive role of CDC42 is independent of its GDP/GTP binding or hydrolysis capacity and does not affect PYRIN dephosphorylation. These findings identify the dual role of CDC42 asa regulator of PYRIN and as a critical player required for PYRIN inflammasome assembly in health and disease.

Recurrent Fever with Oral Lesions in Egyptian Children: A Familial Mediterranean Fever Diagnosis Not to Be Missed.

the aim of this study was to describe the genetic and clinical features of familial Mediterranean fever (FMF) in a group of Egyptian children. This cross-sectional observational study included 65 children diagnosed with FMF according to the (Eurofever/PRINTO) classification criteria. The complete blood count (CBC), and acute phase reactants such as Serum amyloid A (SAA), and C-reactive protein (CRP) were all measured during the febrile episode. Mutation analysis for the MEFV gene was carried out for all subjects. A total of 65 patients with FMF were included in the study. The first clinical manifestation was recurrent fever in all patients. Recurrent oral lesions accompanied fever in 63% of cases, abdominal pain in 31%, and musculoskeletal pain in 6%. The mean SAA level was 162.5 ± 85.78 mg/L. MEFV mutations were detected in 56 patients (86%). Among these patients, 6 (10.7%) were homozygous, while 44 (78.6%) were heterozygous. The most frequently observed mutation was E148Q 24 (37.5%), followed by M694I 18 (32.1%), and V726A 13 (20.3%). Half of the patients with oral lesions were E148Q positive, however abdominal pain was found to be higher in the patients with the M694I mutation. Recurrent fever with oral lesions could be an important atypical presentation of FMF in Egyptian children that should not be ignored and/or missed.

Vasculitis and familial Mediterranean fever: Description of 22 French adults from the juvenile inflammatory rheumatism cohort.

The frequency of vasculitis may be increased in patients with Familial Mediterranean Fever (FMF), according to several studies. Our aim was to assess the characteristics of French adult patients with both diseases. Patients with vasculitis were selected from patients followed for FMF in the French JIR-cohort. Twenty-two patients were included [polyarteritis nodosa (PAN) n = 10, IgA vasculitis n = 8, unclassified vasculitis n = 2, granulomatosis with polyangiitis n = 1, and microscopic polyangiitis n = 1]. Pathogenic mutations in exon 10 were found in all 21 patients (96%) for which MEFV testing results were available, and 18 (82%) had two pathogenic mutations. Histology showed vasculitis in 59% of patients. Most patients with FMF-associated PAN were HBV-negative and had an inactive FMF before PAN onset, and 40% had a peri-renal or central nervous system bleeding. Most patients with FMF-associated IgA vasculitis had an active FMF before vasculitis onset, and 25% had digestive bleeding. Both patients with unclassified vasculitis had ischemic and/or hemorrhagic complications. This study confirms the predominance of PAN and IgA vasculitis in patients with FMF and the high frequency of bleeding in FMF-associated PAN. FMF should be considered in case of persistent symptoms and/or inflammatory syndrome despite vasculitis treatment in Mediterranean patients.

The role of S100A12 and Toll-like receptor 4 in assessment of disease activity in familial Mediterranean fever and juvenile idiopathic arthritis.

Our aim was to investigate the possible relationship between the serum S100A12 and Toll-like receptor 4 (TLR4) levels, and the activity of familial Mediterranean fever (FMF) and juvenile idiopathic arthritis (JIA) in accordance with the routine biochemical parameters. Furthermore, the effectiveness of these 2 biomarkers in distinguishing FMF from JIA has been evaluated. Sixty-nine children with FMF, 68 children with JIA, and 35 healthy children were included in this study. S100A12 and TLR4 levels were measured by the sandwich enzyme-linked immunosorbent assay technique. In the FMF patient group, serum S100A12 level was found to be significantly higher than in both the JIA and control groups (P=.000 and P=.000, respectively). Although S100A12 levels were higher in the attack period compared to the attack-free period, this increase was not statistically significant (P > .05). TLR4 levels were statistically significantly higher in the attack period compared to the attack-free period in children with FMF (P < .05). Although there was no relationship between S100A12 levels and disease activity, there is a clear correlation between S100A12 and the Auto-Inflammatory Disease Activity Index in attack-free FMF patients (r=0.612 P=.000). Serum S100A12 levels were not found to be a potentially valuable biomarker for assessing disease activity in either FMF or JIA. However, TLR4 levels were found to be a valuable biomarker for assessing disease activity in children with FMF. Further research which includes serial monitoring of S100A12 and TLR4 levels in a large cohort will provide detailed information about accuracy of these 2 potential biomarkers in both patients group.

Erysipelas-Like Erythema: A Manifestation of Severe Disease Phenotype in Pediatric Patients with Familial Mediterranean Fever.

Erysipelas-like erythema is the pathognomonic skin manifestation of familial Mediterranean fever although not frequently seen in the pediatric population. This study aims to describe the differences between patients presenting with and without erysipelas-like erythema and to examine the relation of erysipelas-like erythema with subclinical inflammation in a large pediatric cohort of familial Mediterranean fever patients. This retrospective study from a single pediatric rheumatology referral center included familial Mediterranean fever patients with a follow-up for at least 6 months in the last 5 years. Patients were grouped according to the presence of erysipelas-like erythema and subclinical inflammation. Among 515 patients with familial Mediterranean fever, 35 patients (6.8%) were found to present with erysipelas-like erythema, and the earliest age for erysipelas-like erythema was 2.9 years. All erysipelas-like erythema lesions were defined on lower extremities with concurrent arthritis in 21 patients (60.0%). Compared to other patients in the cohort, patients presented with erysipelas-like erythema had significantly higher frequencies of acute arthritis, subclinical inflammation, and biallelic exon 10 mutations, and they used significantly higher doses of colchicine at the latest visits (all P ≤ .002). Patients with subclinical inflammation more frequently presented with erysipelas-like erythema compared to others without subclinical inflammation (21.7% vs. 2.9%, P &lt; .001). Erysipelas-like erythema is an uncommon but important finding that can be a sign of severe disease course and subclinical inflammation in the pediatric population with familial Mediterranean fever.

The relationship between nutrition, inflammation and colchicine resistance in familial Mediterranean fever

Aim: Familial Mediterranean fever (FMF) is an autoinflammatory and genetic disease associated with chronic inflammation. Colchicine is the gold standard treatment for FMF, although some patients respond partially. Factors such as heavy exercise, cold exposure, stress, recent infection or surgery have been associated with the occurrence of attacks. Recently, nutrition is thought to be involved in the pathogenesis of autoimmune and autoinflammatory diseases. Therefore, we aimed to investigate the relationship between nutrition, inflammation and colchicine resistance by considering the nutritional status of FMF patients.&#x0D; Material and Method: The study included 59 patients and 67 healthy individuals who were matched for gender, age and body mass index (BMI). Clinical, anthropometric, and biochemical measurements were obtained. Three-days, 24-hour diet records were recorded in the nutrient database program (BeBiS software program), the amounts of macro and micronutrient contents were determined and the Diet Inflammatory Index (DII) score was calculated and compared between groups.&#x0D; Results: Statistically, the diets of FMF patients were found to be higher in omega-6, carbohydrate percentage and salt content, and lower in terms of lactose, fat percentage, monounsaturated fatty acids, retinol and biotin compared to controls. There was no correlation between DII and acute phase reactants and colchicine dose.&#x0D; Conclusion: The course of FMF can be affected by environmental factors, as well as its genetic background. Nutrition is a new and interesting topic in this regard and may contribute to inflammation and disease activity in FMF patients.

Relation Between Familial Mediterranean Fever and QT Markers (QTc, QTd, and QTcd): A Systematic Review and Meta-Analysis.

The aim of this study is to perform a meta-analysis to evaluate the possible association betweenQT markersand familial Mediterranean fever (FMF). PUBMED, Web of Science,OVID, and SCOPUS databases were searched. Inclusion criteria were randomized control trials or observational studies that compared measurement of the QT markers in FMFpatients and healthy controls in both males and females without any age restriction or other comorbidities. RevMan software (5.4) was used to perform the analysis. A total of 14 studies with 1,154 individuals were included in the study. The pooled effect estimate showed a statistically significant association between FMF group and prolonged corrected QT (QTc) and QT dispersion (QTd) (MD= 7.06, 95% CI = 2.68 to 11.43, p-value = 0.002) and (MD= 6.08, 95% CI = 0.84 to 11.32, p-value= 0.02), respectively. No statistically significant difference between FMF group and QT interval and corrected QT dispersion (QTcd) (MD= 2.34, 95% CI = -1.21 to 5.89, p-value = 0.20) and (MD= 4.82, 95% CI = -0.57 to 10.20, p-value = 0.08), respectively. Our findings revealed a statistically significant relationship between FMF and extended QTcand QTd. More randomized multicenter trials are required to confirm our findings.

Utility of a targeted next-generation sequencing-based genetic screening panel in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

This study aims to investigate a genetic panel in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and examine its performance for an accurate differential diagnosis. Between January 2021 and January 2022, a total of 104 children with PFAPA syndrome (63 males, 41 females; mean age: 4.8±2.3 years; range, 1.2 to 8.9 years) were retrospectively analyzed. Next-generation sequencing test was performed using a custom QIAGEN- QIAseq™ Targeted DNA Panel which includes six genes namely ELANE, LPIN2, MEFV, MVK, NLRP3, and TNFRSF1A. Of 104 patients, 38 (36.5%) had variants in the genetic panel. The most common variants were found in the MEFV gene (n=35, 33.6%), the most frequent genotype was E148Q heterozygosity (n=16). Four and two patients were eventually diagnosed with Familial Mediterranean fever (FMF) and hyperimmunoglobulin D syndrome (HIDS), since they had confirmative biallelic pathogenic in the MEFV and MVK genes, respectively. A genetic panel, including MEFV and MVK genes, may be useful in patients, clinically resembling PFAPA, since they may have HIDS or FMF, but lack typical features of the exact disease. Nonetheless, we believe that distinct genetic panels should be developed for different populations.

Does IL33/Sst2 Pathway Play a Role in the Pathogenesis of Familial Mediterranean Fever?

Does IL33/Sst2 Pathway Play a Role in the Pathogenesis of Familial Mediterranean Fever?

An evaluation with shear wave elastography of kidney elasticity in patients with familial Mediterranean fever.

To investigate the changes in kidney elasticity in patients with familial Mediterranean fever using the non-invasive diagnostic method of shear wave elastography (SWE). The kidney elasticity of 35 FMF patients and 23 healthy control subjects was evaluated with SWE. The relationships were evaluated of the SWE values with eGFR, microproteinuria, FMF severity score, number of attacks per month, and colchicine doses of the FMF patients. The kidney stiffness and velocity values of the FMF patients were found to be higher than those of the control group (p < 0.001). A negative correlation was found between the renal stiffness and velocity values and the colchicine dose (r=-0.48, p=0.004, and r=-0.50, p=0.003, respectively). The results of the current study demonstrated that the SWE values of the FMF patients were significantly higher than those of the control group. SWE can be used as an alternative method in the follow up of FMF patients. In addition, a negative correlation was determined between the colchicine dose and renal stiffness. This suggests that SWE values could be used in the adjustments of colchicine doses. However, there is a need for further studies with greater numbers of patients to support this hypothesis.

Increased risk of venous thromboembolism among patients with familial Mediterranean fever.

Familial Mediterranean Fever (FMF) is an auto inflammatory disease characterized by acute febrile attacks, serositis, arthritis and skin rash. Previous studies have identified an association between venous thromboembolism (VTE) and various inflammatory and autoimmune disorders, driven in large part by inflammatory processes. Despite these established associations, there remains a paucity of data linking FMF to VTE. The purpose of this study is to evaluate the association between VTE in patients with FMF compared to matched controls. A population based cross-sectional study was performed utilizing the electronic medical database of Israel's largest healthcare provider, Clalit Health Services. Using this database, we looked at the prevalence of VTE in a cohort of FMF patients compared to matched controls. Univariate logistic regression was used to evaluate the association between FMF and VTE. Multivariate analysis was conducted to adjust for age, sex, socioeconomic status and comorbidities associated with VTE. A total of 6534 FMF patients were identified and matched with an equal number of controls. In univariate analysis the cumulative percent of VTE was higher in FMF patient compared to matched controls (FMF 3%, Control 2%). In a multivariate logistic regression analysis FMF was found to be independently associated with VTE (HR 1.96, P < 0.001). FMF is associated with increased risk of VTE. This association is likely the result of a chronic and persisting inflammatory state. Physicians should be aware of this sequela and care must be undertaken to control unbalanced disease.

Live-attenuated measles, mumps, and rubella booster vaccine in children diagnosed with rheumatic disease: A single-center study.

To evaluate the safety profile of measles, mumps and rubella (MMR) booster in children diagnosed with rheumatic diseases receiving biological agents. The study included retrospective safety data of children administered MMR booster dose receiving biologics or biologics with methotrexate. The files of 182 patients were accessed from the pediatric rheumatology biological therapy archive, and the vaccination status of these children was obtained by accessing electronic records. Of 182 patients, 14 patients were vaccinated with MMR booster dose. Thirteen of the patients were followed up with a diagnosis of juvenile idiopathic arthritis and one with colchicine-resistant familial Mediterranean fever. None of the patients had disease exacerbation after vaccination, and three patients had mild side effects consisting of rash, angioedema, joint pain, and fatigue. Conclusion: This study supports the data regarding evidence of the safety of MMR booster dose administration in children with rheumatic diseases receiving bDMARDs. What is Known: •MMR booster is avoided in immunocompromised pediatric patients receiving bDMARDs except in specific conditions. What is New: •The MMR booster dose may be safe in children with PedRD receiving bDMARDs or bDMARDs with MTX. These bullets can be added to the manuscript.

Role of non-invasive methods in detecting liver impairment in familial Mediterranean fever adult patients with persistent hepatic cytolysis

Familial Mediterranean fever (FMF) patients may have hepatic cytolysis, although its origin is not formally elucidated. We aimed to evaluate liver involvement in familial Mediterranean fever (FMF) using non-invasive methods. All adult FMF patients harboring two non-ambiguous mutations of the MEFV gene with hepatic cytolysis were identified in a French tertiary adult center for FMF. Liver impairment was explored with FibroMax (a non-invasive method to estimate hepatic steatosis, necrosis, inflammation and fibrosis) and liver ultrasound. Among 520 FMF adult patients, 43 had persistent hepatic cytolysis and 20 patients were included (11 women, median age at inclusion: 49.5 years). According to the FibroMax results, patients were classified as having steatosis, fibrosis, and possible or definite nonalcoholic steato-hepatitis in 10 (50%), 9 (45%) and 7 (35%) of cases, respectively. The score of steatosis did not seem associated with the usual metabolic risk factors. No significant association was found between the cumulated dose of colchicine and any of the scores included in FibroMax. In adult FMF patients with persistent hepatic cytolysis, steatosis is the first cause to consider even in the absence of usual metabolic risk factors, suggesting other mechanisms. Colchicine did not seem to be involved in this toxicity.