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Background:Familial Mediterranean Fever (FMF) is a condition marked by recurring episodes of polyserositis, and some patients may experience joint involvement either during attacks or in a chronic form. The presence of Spondyloarthropathy (SpA) and its common features alongside FMF is often observed study. In certain instances, chronic arthritis or other SpA findings does not show a response to colchicine treatment.Objectives:In this study, we explored the connection between SpA, its musculoskeletal features, chronic arthritis, and resistance to colchicine in our FMF patient group.Methods:We enrolled 243 adult patients with Familial Mediterranean Fever (FMF) in our study, all of whom met the Tel-Hashomer Criteria. Various data, including demographic information, disease-related features, smoking habits, and comorbidities, were collected. Additionally, we utilized The International Severity Scoring System for FMF (ISSF) scores to assess the severity of the disease. Colchicine resistance was identified in patients who continued to experience one or more attacks per month despite receiving the maximum tolerated dose for at least 6 months and/or ongoing subclinical inflammation. In our research, we categorized patients into two groups based on whether they exhibited resistance to colchicine. We initially compared FMF-related features between these groups. Next, we examined the variables that showed significance in the initial analysis using a more comprehensive multivariate approach to understand their relationship with colchicine resistance.Results:Colchicine resistance was present in 54 (%22.2) of 243 patients included in the study. There was no difference between patients with and without colchicine resistance in terms of age (p=0.36), gender (p=0.94), disease duration (p=0.76), frequency of SpA (p=0.37), Charston comorbidity score (p=0.22), smoking (p=0.87), presence of musculoskeletal system findings (p=0.11), erysipelas-like rash (p=0.32), sacroiliitis (p=0.34), enthesitis (p=0.56) and presence of exon 10 MEFV mutation (p=0.05). However, the frequency of attacks (p<0.001), ISSF score (p<0.001), amyloidosis (p<0.001) and chronic arthritis (p=0.001) were more frequent in the colchicine resistant group. Mean colchicine dose was found to be higher in the resistant group (p=0.001). In multivariate analysis, ISSF score (p=0.003), attack frequency (p=0.03), resistant arthritis (p=0.002) and amyloidosis (p<0.001) were found to be associated with colchicine resistance (Table 1).Table 1.FMF features related to colchicine resistanceOR%95 CIPAmyloidosis7.72.6-22.8<0.001ISSF score3.51.5-8.00.003Attack frequency1.11.0-1.40.03Chronic arthritis6.01.8-19.30.002ISSF: The International Severity Scoring System for FMFConclusion:The study revealed that the occurrence of colchicine resistance is linked to the presence of chronic arthritis, along with amyloidosis,attack frequency and ISSF score, while no such association was identified with SpA or all other SpA features.REFERENCES:NIL.Acknowledgements:NIL. NoneDisclosure of Interests:None declared.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by self-limited inflammatory attacks of fever and polyserositis along with elevated acute phase reactants. FMF is inherited autosomal recessively; however, a significant proportion of heterozygotes also express the phenotype. FMF is caused by mutations in the gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response and production of interleukin-1β (IL-1β). Recent studies have shown that pyrin recognizes bacterial modifications in Rho GTPases, which results in inflammasome activation and increase in IL-1β. Pyrin does not directly recognize Rho modification but probably affected by Rho effector kinase, which is a downstream event in the actin cytoskeleton pathway. Recently, an international group of experts has published the recommendations for the management of FMF. Colchicine is the mainstay of FMF treatment, and its regular use prevents attacks and controls subclinical inflammation in the majority of patients. Furthermore, it decreases the long-term risk of amyloidosis. However, a minority of FMF patients fail to response or tolerate colchicine treatment. Anti-interleukin-1 drugs could be considered in these patients. One should keep in mind the possibility of non-compliance in colchicine-non-responders. Although FMF is a relatively well-described AID and almost 20 years has passed since the discovery of the gene, there are still a number of unsolved problems about it such as the exact mechanism of the disease, symptomatic heterozygotes and their treatment, and the optimal management of colchicine resistance.

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In this retrospective cohort study, we aimed to assess the effects of various MEFV genotypes on the clinical characteristics of the patients, with a special focus on the joint involvement. In total, 782 patients with FMF were categorized into 3 groups according to the MEFV mutation; Group 1: Patients homozygous for M694V; Group 2: Patients carrying other pathogenic  MEFV  variants in exon 10 in homozygous or compound heterozygous states; and Group 3: FMF patients with other variants or without mutations. Clinical and demographic findings were compared between groups. Among the 782 FMF patients, total frequency of arthritis was 237 (30.3%): 207 (26.4%) were acute monoarthritis and 67 (8.5%) were chronic arthritis. Both the frequency of arthritis (acute and/or chronic) (40.4% vs. 24.8% vs. 26.7%; p:0.001) and acute monoarthritis (35.4% vs. 20% vs. 23.7%; p:0.001) were significantly higher in Group 1 than in the other groups. FMF patients with chronic arthritis showed a distinct juvenile idiopathic arthritis (JIA) distribution pattern with a more frequent enthesitis-related arthritis (ERA) subtype (43.2%). HLA-B27 was positive in 24% of the ERA patients. Conclusion : Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritis comparing to other MEFV genotypes. In addition, the risk of chronic arthritis seems not related to the MEFV mutations. However, FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA and undifferentiated arthritis subtype. What is known: • Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritis What is new: • FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA subtype • ERA patients with negative HLA-B27 antigen should also be assessed for polyserositis episodes of FMF, especially in countries with high FMF carrier frequency

Mycoplasma hyorhinis is one of the causative agents of polyserositis and arthritis in postweaning pigs. Knowledge regarding colonisation frequency and age distribution in modern pig production is lacking. The objective of this study was to estimate the prevalence of M hyorhinis colonisation in different age groups across three commercial pig populations. Nasal swabs were collected from sows, piglets and nursery pigs of different ages. Oral fluids were collected from nursery pigs. Necropsies were performed to assess the presence of M hyorhinis‐associated disease. M hyorhinis was detected in 5/60 sows in herd A, 3/60 in herd B and none in herd C. In herd A and B, the prevalence was low in preweaning piglets (∼8 per cent) and high in postweaning pigs (∼98 per cent). A total of 7/8 oral fluids tested PCR positive in herds A and B, while 1/8 tested positive in herd C. In herd C, the preweaning and postweaning prevalence was low. In herds A and B, necropsied pigs had polyserositis lesions where M hyorhinis was detected by PCR. This study showed that prevalence of M hyorhinis colonisation varies with pig age and across farms. Information generated will aid in the design and implementation of control and prevention strategies.

BackgroundFamilial Mediterranean Fever (FMF) is the most common hereditary monogenic fever syndrome characterized by recurrent attacks of fever and polyserositis. Types and frquencies of attacks can change throughout the life of patients. The course of disease is affected by pathophysiological changes due to aging, increased comorbid diseases and multiple drug use.ObjectivesThe objective of this study was to understand the effect of aging on clinical features and disease course in patients with Familial Mediterranean Fever.Methods343 patients who were followed up with the diagnosis of FMF between 2005 to 2020 and were over 50 years old as of 2022 were included. The demographic characteristics of the patients, MEFV mutations, attack characteristics and the treatments they received were analyzed retrospectively. Attack characteristics, frequency of attacks and VAS scores of the patients were also analyzed and compared as pre-treatment, post-treatment, and most recent attacks.ResultsFemale to male ratio was 1.8:1. The mean age of patients was 57.6±6.5 (50-84) years. Age of symptoms started, age at diagnosis and delay at diagnosis were compared between the female and male patients. At the age of symptoms started, no significant difference was detected between the two groups, while the age at diagnosis was later and the time of delay at diagnosis was longer in female patients (p=0.006 and p=0.001).Number and frequencies of attacks and VAS scores were compared as attacks before treatment, attacks after treatment and attacks in the last year, a significant decrease was found in the last attacks (p<0.001). The frequency of fever, abdominal pain, arthritis and chest pain was significantly lower in the most recent attacks when compared to pre-treatment and post-treatment (p<0.001). The last attacks of the patients were mostly in the form of abdominal pain. Patients were compared as those who did not have an attack in the last year and who had an attack, it was seen that the mean age was lower in the group that had an attack (p<0.005). The mean of current colchicine dose was 1.29±0.43 mg, the mean dose of colchicine at diagnosis was 1.37±0.36 mg and the mean of maximum colchicine dose was 1.6±0.43 mg.Conclusion:Demographic Status, Patients (n:343)Male/female, n 119/224Age of onset, mean (S.D.), years 57.6 (6.5)Age at diagnosis, mean (S.D.), years 40.8 (10.8)Age of symptoms started, mean (S.D), years 24 (14.4)Delay at diagnosis, mean (S.D.), years 16.8 (14.5)Clinical features, n (%)Pre-Treatmentn (%)Post-Treatmentn (%)Recent Attacksn (%)p valueFeverAbdominal Pain266 (77.6)253 (73.8)52 (15)<0.001Arthralgia293 (85.4)299 (87.2)223 (65)<0.001Arthritis56 (16.3)82 (23.9)33 (9.6)<0.001Chest pain87 (25.4)100 (29.2)32 (9.3)<0.001Myalgia71 (20)79 (23)24 (7)<0.001Erysipelas-like23 (6.7)34 (9.9)46 (13.5)0.14erythema11 (3.2)12 (3.5)7 (2)0.487Number of attacks, mean (S.D.), years15.0 (11.9)3.04 (6.46)2 (3.67)<0.001VAS ScoresPre-treatment, mean (S.D.)8.05 (1.78)<0.001Post-treatment, mean (S.D.)2.91 (2.53)Recent, mean (S.D.)1.75 (2.38)It has been shown that there is a decrease in disease activity, frequency of attacks and the dose of colchicine used in FMF with aging.References[1] Ozen S, Bilginer Y (2014) A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin. Nat Rev Rheumatol 10:135-147[2] van der Hilst J, Moutschen M, Messiaen PE, Lauwerys BR, Vanderschueren S (2016) Efficacy of anti-IL-1 treatment in familial Mediterranean fever: a systematic review of the literature. Biologics 10:75-80[3]Siegal S (1949) Benign paroxysmal peritonitis. Gastroenterology 12:234-247[4]Reimann HA (1951) Periodic disease. Medicine (Baltimore) 30:219-245[5]Heller H, Sohar E, Sherf L (1958) Familial Mediterranean fever. AMA Arch Intern Med 102:50-71Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Mycoplasma hyorhinis is an emerging swine pathogen bacterium causing polyserositis and polyarthritis in weaners and finishers. The pathogen is distributed world-wide, generating significant economic losses. No commercially available vaccine is available in Europe. Therefore, besides improving the housing conditions for prevention, antimicrobial therapy of the diseased animals is the only option to control the infection. Our aim was to determine the minimal inhibitory concentrations (MIC) of ten antimicrobials potentially used against M . hyorhinis infection. The antibiotic susceptibility of 76 M . hyorhinis isolates from Belgium, Germany, Hungary, Italy and Poland collected between 2019 and 2021 was determined by broth micro-dilution method and mismatch amplification mutation assay (MAMA). Low concentrations of tiamulin (MIC 90 0.312 μg/ml), doxycycline (MIC 90 0.078 μg/ml), oxytetracycline (MIC 90 0.25 μg/ml), florfenicol (MIC 90 2 μg/ml) and moderate concentrations of enrofloxacin (MIC 90 1.25 μg/ml) inhibited the growth of the isolates. For the tested macrolides and lincomycin, a bimodal MIC pattern was observed (MIC 90 >64 μg/ml for lincomycin, tulathromycin, tylosin and tilmicosin and 5 μg/ml for tylvalosin). The results of the MAMA assay were in line with the conventional method with three exceptions. Based on our statistical analyses, significant differences in MIC values of tiamulin and doxycycline were observed between certain countries. Our results show various levels of antimicrobial susceptibility among M . hyorhinis isolates to the tested antibiotics. The data underline the importance of susceptibility monitoring on pan-European level and provides essential information for proper antibiotic choice in therapy.

Background Familial Mediterranean Fever (FMF), an autoinflammatory disease, is characterized by self-limited inflammatory attacks of fever and polyserositis along with high acute phase response. Although colchicine remains the mainstay in treatment, intolerance and resistance in a certain portion of patients have been posing a problem for physicians. Main body Like many autoimmune and autoinflammatory diseases, many colchicine-resistant or intolerant FMF cases have been successfully treated with biologics. In addition, many studies have tested the efficacy of biologics in treating FMF manifestations. Conclusion Since carriers of FMF show significantly elevated levels of serum TNF alpha, IL-1, and IL-6, FMF patients who failed colchicine were successfully treated with anti IL-1, anti IL-6, or TNF inhibitors drugs. It is best to use colchicine in combination with biologics.

Kabuki syndrome (KS) is a well-recognized disorder characterized by postnatal growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability. The syndrome is caused by KMT2D gene mutations or less frequently KDM6A gene mutations or deletions. We report a systematic evaluation of KS patients from Campania region of Italy; data were also compared with literature ones. We collected data of 15 subjects (8 males and 7 females with age range 10–26 years; mean age 16.9 years) with confirmed diagnosis of KS, representing the entire cohort of patients from Campania Region. Each patient performed biochemical testing and instrumental investigation. Neuro-intellectual development, cranio-facial dysmorphisms, and multisystem involvement data were collected retrospectively. For each category, type of defects and frequency of the anomalies were analyzed. Our observation shows that KS patients from Campania region have some particular and previously underscored, neurological and immunological findings. We found high prevalence of EEG’s abnormalities (43%) and MRI brain abnormalities (60%). Microcephaly resulted more common in our series (33%), if compared with major cohorts described in literature. Biochemical features of immunodeficiency and autoimmune diseases including thyroid autoimmunity, polyserositis, and vitiligo were observed with high prevalence (54.5%). Low immunoglobulins levels were a frequent finding. Lymphocyte class investigation showed significantly reduced CD8 levels in one patient. Conclusions : These data confirm great heterogeneity of clinical manifestations in KS and suggest to introduce further clinical diagnostic criteria in order to perform a correct and precocious diagnosis. What is Known • Kabuki syndrome is characterized by growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability • Immune dysfunction is a common finding but autoimmune diseases are rarely seen • Neurological features are common What is New • Some particular facial features could help gestalt diagnosis (hypertelorism, broad nasal bridge, micrognathia, tooth agenesis, cutaneous haemangiomas and strabismus) • Higher prevalence of autoimmune disorders than previously reported • Particular neurological features are present in this cohort (EEG and MRI brain abnormalities)

Fibrinous polyserositis in swine farming is a common pathological finding in nursery animals. The differential diagnosis of this finding should include Glaesserella parasuis (aetiological agent of Glässer's disease) and Mycoplasma hyorhinis, among others. These microorganisms are early colonizers of the upper respiratory tract of piglets. The composition of the nasal microbiota at weaning was shown to constitute a predisposing factor for the development of Glässer's disease. Here, we unravel the role of the nasal microbiota in the subsequent systemic infection by M. hyorhinis, and the similarities and differences with Glässer's disease. Nasal samples from farms with recurrent problems with polyserositis associated with M. hyorhinis (MH) or Glässer's disease (GD) were included in this study, together with healthy control farms (HC). Nasal swabs were taken from piglets in MH farms at weaning, before the onset of the clinical outbreaks, and were submitted to 16S rRNA gene amplicon sequencing (V3-V4 region). These sequences were analyzed together with sequences from similar samples previously obtained in GD and HC farms. Animals from farms with disease (MH and GD) had a nasal microbiota with lower diversity than those from the HC farms. However, the composition of the nasal microbiota of the piglets from these disease farms was different, suggesting that divergent microbiota imbalances may predispose the animals to the two systemic infections. We also found variants of the pathogens that were associated with the farms with the corresponding disease, highlighting the importance of studying the microbiome at strain-level resolution

BackgroundFamilial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterised with fever, recurrent episodes of self-limiting polyserositis and arthritis. FMF arthritis is generally acute monoarthritis especially in the larger joints of the lower extremities, healing without a sequelae. However some of the patients develop different type of chronic arthritis, predominantly oligoarticular juvenile idiopathic arthritis (JIA) and juvenile pondyloarthropathies (JSpA). Studies on JSpA among childhood FMF patients are spare.ObjectivesTo evaluate frequency of JSpA in a large childhood FMF cohort. Furthermore, we aimed to define main characteristics of JSpA among childhood FMF patients.MethodsA total of 320 juvenile FMF patients were blindly questioned according to recently proposed criteria for JSpA by 3 researchers (EO, DS, ET) that were previously educated for FMF and JSpA. A standardised case report form was prepared and completed for each patient. This form was including demographic data, clinical features, MEFV mutation and treatment. Patients fulfilled the JSpA criteria and were classified as probable JSpA. Afterwards, an expert in paediatric rheumatology (OK) reevaluated the classified patients and some of them were confirmed to be a definite while some of them were accepted as potential JSpA patients.ResultsAs a result, 37 patients (11.5%) were initially classified as potential JSpA. Furthermore, 32 (10%) of them were accepted as definite and 5 (1.5%) patients as probable JSpA in childhood FMF. Demographic, clinical and treatment data of definitive JSPA patients are shown in Table I. The most frequent MEFV mutation among JSPA patients was M694V (63.33%).Table I. Demographic, clinical and genetic features of childhood FMF patients.FMF +Definite JSPAFMF +Probable JSPAFMF patients without JIA and JSpAFMF+JIA (except ERA or JSpA) Patients, n32526815Female, n (%)10 (31.25%)1 (20%)148 (55.22%)10 (66.66%)Age of disease onset, mean±SD years7.19±3.685.60±4.934.91±3.404.93±3.32Age at study, mean±SD years14.84±3.7013.40±1.6712.51±4.4310.73±3.57Family History of FMF, n (%)15 (46.87%)1 (20%)132 (49.25%)6 (40%)Colchicine resistance in FMF patients, n(%)2 (6.25%)014 (5.22%)1 (6.66%)M694V mutation n(%)Homozygote, n(%)Heterozygote, n(%)Compound heterozygote, n(%)NA, n(%)19/30 (63.33%)7 (36.84%)5 (26.31%)7 (36.84%)2 (6.25%)3 (60%)2 (66.66%)1 (33.33%)00148/245 (60.40%)51 (34.45%)54 (36.48%)43 (29.05%)23 (8.58%)11 (73.33%)8 (72.72%)2 (18.18%)1 (9.09%)0Disease onset over 6 years,n (%) years26 (81.25%)5 (100%)6 (40%)Oligorthritis, n(%)21 (65.62%)1 (20%)14 (93.33%)Inflammatory back pain, n(%)17/32 (53.12%)3/5 (60%)0Enthesopathy22/32 (68.75%)3/5 (60%)0Sacroiliitis14/21 (66.66%)0/1 (0)0/5 (0)ConclusionsArticular involvement compatible with JSpA could be seen in childhood FMF patients. Spondyloarthropathy was detected in 10% of childhood FMF cases. The M694V mutation is the most common MEFV mutation among JSpA patients with FMF. JSpA should be considered in childhood FMF patients, especially in those chronic arthritis, axial involvement and enthesopathy.Reference[1] Adrovic A, Sezen M, Barut K, et al. The performance of classification criteria for juvenile spondyloarthropathies. Rheumatol Int2017;37:2013–2018.Disclosure of InterestNone declared