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BackgroundFamilial Mediterranean fever (FMF) is an inherited autoinflammatory disease characterized by recurrent episodes of fever and serositis. Arthritis is one of the most common attack manifestations. Arthritis in FMF is usually in the form of acute mono- or oligoarthritis of the large joints of the lower extremities. While acute attacks of arthritis usually heal without causing permanent deformity, the severe, long-lasting form of chronic arthritis can last for months or even years and result in permanent deformity.ObjectivesIn this study, we described the characteristics of joint involvement in FMF in a single cohort.MethodsThe medical records of patients with joint involvement from our cohort of 2350 patients who were diagnosed with familial Mediterranean fever were retrospectively scanned through the files and hospital database. The prevalence, demographic information, genetic test results, clinical features, features of joint involvement, treatments and responses, acute phase values in the attack and remission periods, and family history of patients with joint involvement were recorded.Results953 patients (n=953) from a total of 2350 patients had arthralgia or arthritis (40%). In our study, the male/female ratio was found to be 0.49 (male n=316, female n=637). The number of patients who underwent genetic testing was 787 (82%), and 702 (89%) of these patients had mutations in the MEFV gene. The most common pathogenic mutation is the M694V mutation with a rate of 43%. Concomitant diseases and their frequencies are shown in Table 1, the most common accompanying disease was spondylarthritis at a rate of 27%. Arthritis was present in the first attack in 55% (n=531), while arthritis was found in the ongoing attacks in 45%. The duration of the attack was between 24-96 hours in 77% (n=837) of the patients, and the duration was longer than 96 hours in 23% (n=116). The most common finding accompanying the attacks was exercise-related leg pain. Family history was present in 61% (n=580). 73% of the patients (n=696) were involved in the ankle and 51% were involved in the knee (n=492). The incidence of sacroiliitis was 14% (n=142). As for the number of joints, 91% of the patients had mono- and oligoarthritis. Asymmetric involvement was detected in 77% of the patients. Red arthritis was present in %73 of our study group. HLA-B27 was examined in 185 patients, 24 of them were positive (12%). It was found that 43% of the patients had treatment changes due to arthritis. Colchicine dose increases and changes were performed in 32% of these patients. NSAIDs were started in 21%, corticosteroids in 15%, DMARDs in 12%, anti-TNF in 10%, and anti-IL-1 in 8%. The mean dose of colchicine was as 1.56 ± 0.5 mg. Unresponsiveness to colchicine was found in 21% (n=122).Table 1.Concomitant diseases of our FMF cohortConclusionFMF diagnosis should definitely be considered in people with red mono-oligoarthritis in the large joints of the lower extremities. One of the most important features of joint involvement in FMF patients is the short duration of arthritis. The accompanying effort-related leg pain is an important symptom that should suggest FMF. In patients with a diagnosis of FMF and arthritis, the required colchicine dose in the treatment and the rate of colchicine unresponsiveness are higher than in other attack types. The incidence of sacroiliitis and spondyloarthropathy increases in patients with FMF, and joint involvement features are similar. FMF should be considered in the differential diagnosis of patients with inflammatory low back pain.Disclosure of InterestsNone declared

BackgroundFamilial Mediterranean Fever(FMF) is an autoinflammatory disease characterized by recurrent polyserositis attacks. Attacks typically consist of fever and/or abdominal pain and/or chest pain and/or arthritis. The disease is caused by mutations in the MEFV gene. Abdominal pain during the attacks is frequently misdiagnosed as acute abdomen and these patients go undersurgical intervention is not uncommon [1].ObjectivesSevere abdominal pain during FMF attacks is frequently misdiagnosed as acute abdomen and patients receive surgical intervention. In this study, we aim to compare the clinical and genetic characteristics of FMF patients with appendectomies to those without appendectomies.MethodsWe reviewed 176 patients with FMF who went under appendectomy. We randomly matched these patients with 176 FMF patients without appendectomy for comparison. We compared clinical manifestations, MEFV mutations, and treatment modalities.ResultsIn this study, 176 patients with FMF went under appendectomy. Only 2 of these appendectomies were performed after FMF diagnosis. In the appendectomy group fever(84% vs 68%), abdominal pain(91% vs 79%), pathogenic exon 10 mutations(65% vs 59%), lower leg pain(0.5% vs 0%) and orchitis(0.5% vs 0%) were more common but only the abdominal pain and fever was statistically significant. In the control group chest pain(18% vs 19%), arthralgia(46% vs 53%), arthritis(29% vs 37%), anti IL-1 usage(3% vs 5%), amyloidosis (0% vs 3%) and erysipelas(1% vs 3%) were more common but none of them were statistically significant. Myalgia(3%) was the same in both groups[Table 1]. Median diagnostic delay was 8(IQR 2-15) years in the appendectomy group and 3.5(IQR1-10) years in the control group.Table 1.Characteristics of the patientsNo Of Patients(%)AppendicitisNo Of Patients(%)P valueControl GroupPatients176(100)176(100)Fever148(84)120(68)0.0007Abdominal Pain160(91)139(79)0.0029Chest Pain32(18)33(19)1Arthralgia81(46)94(53)0.20Arthritis51(29)65(37)0.12Myalgia5(3)5(3)1Erysipelas2(1)5(3)0.45Lower Leg Pain1(0.5)0(0)-Orchitis1(0.5)0(0)-Anti IL-1 usage6(3)9(5)0.6Amyloidosis0(0)6(3)-Diagnostic Delay8.5(IQR2-15) years3.5(IQR1-10) years0.0002Pathogenic Exon 10 Mutations114(65)103(59)0.27Appendectomy Before FMF diagnosis174(99)0(0)ConclusionEven after the discovery of colchicine and identification of the MEFV gene diagnosis of FMF remains a challenge. Previous studies reported a median diagnostic delay of 8.2-11 years. In these studies, 28%-32% of the patients went under abdominal surgical intervention before the diagnosis of the FMF[2,3]. The most common symptoms of FMF(fever and abdominal pain) are also the most common symptoms of acute abdomen. Thus distinguishing between FMF and acute abdomen in undiagnosed FMF patients represents an understated problem. These patients have a longer diagnostic delay[8(IQR 2-15) vs 3.5(IQR1-10) years], worse control of attacks, poorer quality of life. In our study, most of the appendectomies were unnecessary in the FMF patients. Thus we recommend investigating the patient for FMF if the evidence of the acute abdomen does not expand beyond the symptoms.References[1]Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. 2019 Feb;48(1 Pt 2):e61-e76.[2]Erdogan M, Ugurlu S, Ozdogan H, Seyahi E. Familial Mediterranean fever: misdiagnosis and diagnostic delay in Turkey. Clin Exp Rheumatol. 2019 Nov-Dec;37 Suppl 121(6):119-124.[3]Hageman IMG, Visser H, Veenstra J, Baas F, Siegert CEH. Familial Mediterranean Fever (FMF): a single centre retrospective study in Amsterdam.Disclosure of InterestsNone declared

BackgroundFamilial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever and serositis. Although it is known that the attack frequency differs among patients carrying different mutant genotypes [1], whether physical and environmental factors play a role in triggering attacks or whether they have an influence on timing of attacks remains to be elucidated.ObjectivesWe aimed to identify different conditions causing flare-ups in FMF course and to investigate if there is a significant difference between patients carrying distinct mutations, regarding the distribution of the factors mentioned.MethodsTwo hundred patients were randomly selected among individuals who were routinely followed-up with FMF diagnosis in our centre. Individuals carrying only a variant of unknown significance or polymorphism such as R202Q, according to Infevers database, were excluded in order to gather a cohort consisting of patients with definite FMF. An inquiry was made based upon triggering factors determined by the patients themselves. The patients were classified into subgroups by their sex and mutation genotype. Since M694V variant is responsible for pronounced FMF course [2], we sorted the patients according to their status for M694V mutant allele. Group A included patients carrying M694V homozygously. Group B included patients carrying at least one M694V mutant allele whereas Group C consisted of patients who were non-M694V carriers. Chi-square test was performed to assess distribution of the trigger factors in terms of establishing its significance.ResultsDetailed distribution of trigger factors is shown in Table 1. 144 out of 200 patients described a culprit condition. Patients usually stated more than one factor, however some patients reported only one. The most-reported trigger factors by the cohort are summarized as following: 76 emotional stress (38%), 60 menstruation (30%), 40 cold exposure (20%), 34 fatigue (17%), 13 seasonal changes (6.5%). The distribution of trigger factors between Group A, B, and C were non-significant (p=0.88).Table 1.The distribution of triggering factors in subgroups.GroupTotal(%)Reported trigger factor (%)Mens- truation(%)Emotionalstress(%)Cold exposure(%)Fatigue(%)Seasonalchanges(%)Others(%)Female12397 (78.8)60 (48.8)47 (38.2)24 (19.5)19 (15.4)7 (5.7)6 (4.9)Male7747 (61)-29 (37.7)16 (20.8)15 (19.5)6 (7.8)7 (9.1)Group A6144 (72.1)14 (23)24 (39.3)13 (21.3)12 (19.7)4 (6.6)6 (9.8)Group B165120 (72.7)49 (29.7)66 (40)34 (20.6)29 (17.6)13 (7.9)11 (6.6)Group C3524 (68.6)11 (31.4)10 (28.6)6 (17.1)5 (14.3)01 (2.8)Group A: M694V homozygous patients, Group B: patients with at least one M694V allele, Group C: non-M694V carriersConclusionWe concluded that trigger factors did not vary between distinct mutant genotypes. Although emotional stress is the most reported trigger factor by the participants, one should bear in mind that emotional stress influences most chronic diseases negatively. We also observed that menstruation overtly triggers an FMF attack. Additionally, cold exposure should be considered as a notable trigger factor. It is still unclear what triggers an FMF attack in 28% of the patients, remains a mystery.References[1]Grossman C, Kassel Y, Livneh A, Ben-Zvi I. Familial Mediterranean fever (FMF) phenotype in patients homozygous to the MEFV M694V mutation. Eur J Med Genet. 2019 Jun;62(6):103532. doi: 10.1016/j.ejmg.2018.08.013.[2]Egeli BH, Ugurlu S. Familial Mediterranean Fever: Clinical State Of The Art. QJM. 2020 Oct 20:hcaa291. doi: 10.1093/qjmed/hcaa291.Disclosure of InterestsNone declared

BackgroundFamilial Mediterranean fever (FMF) is a rare hereditary autoinflammatory disease with disease onset in childhood in most cases. Although autoinflammatory disease awareness is increasing among physicians, delayed diagnosis is still prevalent as a cause of greater morbidity[1].ObjectivesWe aimed to study the characteristics of FMF patients diagnosed between 2000-2010 and 2011-2021 and to see if there was a difference in diagnostic delay.MethodsWe retrospectively evaluated the medical records of the FMF patients followed up in our rheumatology clinic that were diagnosed between 2000-2021 and split them into two groups according to the year they received their diagnosis. There were 1151 patients diagnosed between 2000-2010 (Group 1) and 821 patients diagnosed between 2011-2021 (Group 2). The data studied included gender, age of onset, diagnostic delay, attack characteristics, MEFV mutation, and family history.ResultsThe median current age of patients in Group 1 is 37 years (IQR:30-46) and the median current age of the patients in Group 2 is 36 years (IQR:29-44). The female to male ratio was 1.57 in Group 1 and 1.75 in Group 2, with no significant difference between the groups. Group 2 had later disease onset (p<0.001) and later diagnosis (p<0.001) than Group 1 as shown in the Table 1. The proportion of patients with at least one M694V mutation was higher in Group 2 (p<0.001). The attack durations did not vary between the groups. There was no significant difference in the prevalence of abdominal pain, fever, arthritis, and arthralgia between Group 1 and Group 2. Chest pain (p=0.005), myalgia (p<0.001), and erysipelas-like erythema (p=0.041) were more common in Group 2 than Group 1. Patients with positive family history were more frequent in Group 2 than Group 1 (p=0.046).Table 1.Group 1 (2000-2010, n=1151)Group 2 (2011-2021, n=821)pFemale/Male, n704/447522/2990.275Age at onset, median (IQR) years13 (7-21)18 (12-26)<0.001Delay in diagnosis, median (IQR) years4 (1-11)5,5(2-15)<0.001Attack duration, median (IQR) years3(2-4)3(2-4)0.325Presence of at least one M694V mutation (%)526(46%)390(60%)<0.001Presence of abdominal pain in the initial attack (%)936(81%)669(81%)0.926Presence of fever in the initial attack (%)855(74%)592(72%)0.281Presence of chest pain in the initial attack (%)218(19%)199(24%)0.005Presence of arthritis in the initial attack (%)330(29%)215(26%)0.224Presence of arthralgia in the initial attack (%)213(19%)170(21%)0.223Presence of myalgia in the initial attack (%)45(4%)65(8%)<0.001Presence of erysipelas like erythema in the initial attack (%)31(3%)36(4%)0.041Presence of positive family history (%)652(57%)502(61%)0.046ConclusionThere was some increase in the diagnostic delay in 2011-2021 compared to 2000-2010. This may be partly due to the later onset of symptoms in patients diagnosed in 2011-2021, which could have led the physicians to consider other differential diagnoses. Nevertheless, diagnostic delay in FMF still seems a prevalent problem that should be addressed to prevent excess morbidity and mortality.References[1]Erdogan M, Ugurlu S, Ozdogan H, Seyahi E. Familial Mediterranean fever: misdiagnosis and diagnostic delay in Turkey. Clin Exp Rheumatol. 2019;37 Suppl 121(6):119-124.Disclosure of InterestsNone declared