An investigation of the relationship between Behçet's disease and tenascin-C.

Objectives: The study aimed to investigate serum tenascin-C levels and its relationship with pathogenesis of Behçet's disease (BD) with inflammatory processes. Patients and methods: This prospective and analytical study included 34 BD patients (19 males, 15 females; mean age: 31.5±8.2 years; range, 18 to 48 years) who met the 2014 International Criteria for Behçet's Disease and had no comorbidities and 37 healthy volunteers (21 females, 16 males; mean age: 29.6±5.3 years; range, 21 to 45 years). Sex, age, age at diagnosis, clinical and laboratory data, medication use, and smoking history of the participants were recorded. Serum tenascin-C levels were measured using a commercially available tenascin-C enzyme-linked immunosorbent assay kit. Results: There was no significant difference between the groups in terms of age (p=0.262) and sex (p=0.287). Serum tenascin-C levels were significantly lower in the BD group (10,824±7,612 pg/mL) compared to the control group (27,574±14,533 pg/mL, p<0.001). In the receiver operating characteristic analysis performed for the diagnostic value of tenascin-C level in BD, the sensitivity was determined as 79.4% and the specificity as 82.5% (p<0.001). No statistically significant difference was observed in tenascin-C levels in correlation with clinical characteristics, laboratory values, medication use, and smoking in the BD group. Conclusion: In contrast to other chronic inflammatory diseases, lower levels of tenascin-C were observed in patients with BD than in the healthy individuals, which can be attributed to the absence of prolonged chronic inflammatory course in BD. The fact that tenascin-C levels are high in other rheumatic inflammatory diseases but low in BD may be useful in the differential diagnosis of BD.

Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

A national, multicenter, retrospective study evaluating retention rate and efficacy of tocilizumab treatment in patients with active rheumatoid arthritis who had an inadequate response to csDMARDs and/or TNF inhibitors.

BACKGROUND: To describe the disease activity and retention rate in rheumatoid arthritis (RA) patients with inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or tumor necrosis factor inhibitors (TNFis) who were prescribed tocilizumab (TCZ) as first-line or second-line biologic treatment in real-world setting. METHODS: Data gathered from patients' files was used in a multicenter and retrospective context. Retention rates and the Disease Activity Score in 28 joints with CRP (DAS28-CRP) were evaluated at time points. The relationship of drug efficacy with factors such as smoking, obesity, and previous use of TNFis was also examined. RESULTS: One hundred and twenty-four patients with a median (IQR) RA duration of 3.7 (7.4) years were included. Mean (SD) age was52.9 (12.9) and 75% of the patients were female. TCZ retention rates in the 6th and 12th months were 94.1% and 86.6%, respectively. In all patients, DAS28-CRP level decreased significantly from baseline to Months 3 and 6. There was an increase in patients with remission and/or low disease activity and a decrease in patients with high disease activity at Month 3 and Month 6 (p < 0.001 for both). Disease activity was similar between subgroups based on body mass index, smoking status, and previous use of TNFis at any time point. Regression analysis showed that absence of concomitant corticosteroid treatment independently was associated with remission/LDA achievement at Month 6 [OR = 0.31, 95% CI (0.14- 0.72), p = 0.006], and Month 12 [OR = 0.35, 95% CI (0.13-0.94), p = 0.037]. Overall, 25 mild adverse events were reported. DISCUSSION: TCZ was found to be effective and safe in RA patients with IR to csDMARDs and/or TNFis. The drug retention rate was considered satisfactory with more than half of the patients continuing TCZ treatment at Month 12.

EGFR blocker lapatinib inhibits the synthesis of matrix metalloproteinases from synovial fibroblasts.

BACKGROUND: Epidermal growth factor receptor (EGFR) family members and their associated ligands may be related to bone and joint destruction in rheumatoid arthritis. Matrix metalloproteinases are responsible for joint and bone tissue degradation. This study is intended to investigate the effect of epidermal growth factor receptor inhibition by lapatinib on the synthesis of matrix metalloproteinases in in vitro. METHODS: Synovial fibroblast cell culture was obtained from a patient with rheumatoid arthritis who underwent knee arthroplasty. Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were added to the cell culture to stimulate synovial fibroblast cells and create an inflammatory character. Understimulated and nonstimulated conditions, lapatinib was applied to the culture in four different concentrations of 25, 50, 100, and 200 µmol. Then, matrix metalloproteinase -1, -3, and, -13 levels were assessed. RESULTS: When stimulated with IL-1ß and TNF-α, the synthesis of matrix metalloproteinases from synovial fibroblast was increased significantly. When lapatinib is added to the stimulated synovial fibroblasts, matrix metalloproteinases synthesis is significantly suppressed. DISCUSSION: Inhibition of the EGFR pathway with lapatinib suppresses matrix metalloproteinases synthesis. Our results suggest EGFR pathway inhibition may be a promising option to prevent joint destruction in the treatment of rheumatoid arthritis.

The Relationship Between COVID-19 Disease Severity and Zonulin Levels.

Introduction Zonulin is a protein that plays a role in the reversible regulation of epithelial permeability. As zonulin is released in large amounts into the intestinal lumen, it disrupts the integrity of the tight junctions and causes continuous migration of antigens to the submucosa. Consequently, it can trigger inflammatory processes and severe immune reactions. In severe cases, SARS-CoV-2 may have a major impact on the clinical manifestations of the disease by directly or indirectly affecting intestinal cells and triggering systemic inflammation. Therefore, our study aimed to investigate the role of one of the possible mediators, zonulin, in the severity of the COVID-19 infection. Methods  Thirty COVID-19 patients and 35 healthy controls were included in the study. Blood samples were taken from the patients on the 1st, 4th, and 8th days of hospitalization. Serum zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Complete blood count (white blood cell [WBC], neutrophil, lymphocyte, and platelet), biochemical parameters (serum lactic acid dehydrogenase [LDH], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], D-dimer, ferritin, fibrinogen levels) were determined and chronic systemic disease states of the patients were assessed. Results  Serum zonulin levels were notably higher in the healthy control group compared to the patient group (p=0.003). Although there was an increase in the zonulin values by time in hospitalization, this rising was not significant. Conversely, ESR and CRP levels were significantly higher in the patient group (p<0.001). There was no significant difference between the two groups regarding gender, age, and WBC counts. Conclusion  The serum zonulin levels of COVID-19 patients with the mild clinical course were lower than the healthy control group. Moreover, serum zonulin levels were not correlated with ESR, CRP, and other inflammation markers. Our results suggest that low serum zonulin levels in COVID-19 patients might represent a mild disease course.

Ovarian Reserve and Pelvic Ultrasound Assessment in Familial Mediterranean Fever.

Introduction Familial Mediterranean fever (FMF) is an inflammatory rheumatic disease that affects people in their reproductive period. The aim of this study was to investigate the number of gravida, ovarian reserve, and ovarian doppler characteristics in FMF patients. Methods The study design is cross-sectional. Between November 1, 2018, and October 31, 2019, 40 FMF patients, and 40 age-matched volunteers were included in the study. Early follicular phase follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), progesterone, and anti-Mullerian hormone (AMH) levels, as well as ovarian volume, antral follicle count (AFC), ovarian stromal artery doppler findings, and pelvic pathologies, were evaluated. Results The number of gravida, and the AFC was significantly higher in the control group (16.00 ± 5.22) compared to the patients with FMF (13.00 ± 4.09) (p = 0.026). LH values were significantly higher in the FMF group. Thirteen patients (32.5%) received anakinra and colchicine, and 27 patients (67.5%) received only colchicine. There was no significant difference between the patients receiving anakinra, and the patients receiving colchicine in terms of AMH, FSH, AFC, and E2 values. Conclusion FMF patients were found to have low gravida and AFC, and a significant portion was observed to have pelvic fluid and hydrosalpinx. In conclusion, the presence of pelvic fluid, hydrosalpinx, and low AFC persist in FMF patients despite colchicine and/or anti-interleukin-1 treatments. The low gravida may be related to these pathologies detected in patients with FMF.

Budd-Chiari syndrome in Behçet's disease: a retrospective multicenter study.

OBJECTIVE: To compare the clinical features, laboratory findings, and prognosis of Behçet's disease (BD) patients with and without Budd-Chiari syndrome (BCS). METHODS: This multicenter retrospective study investigated 61 (M/F: 41/20) patients with BD, having coexistent BCS, and 169 (M/F:100/69) BD patients as the control group without BCS from 22 different centers of Turkey diagnosed between 1990 and 2017. RESULTS: Of the total 61 BD patients with BCS, the onset of the first symptom and the median age of diagnosis were earlier in contrast to BD patients without BCS (p = 0.005 and p = 0.007). Lower extremity deep vein and inferior vena cava (IVC) thrombosis were more common in patients with BCS (all; p < 0.01) compared to the control group. Mortality was significantly higher in BD-BCS patients with IVC thrombosis than in the controls (p = 0.004). Since most of the cases in our cohort had chronic and silent form of BCS, mortality rate was 14.8%, which was on the lower range of mortality rate reported in literature (14-47%). While all BD-BCS patients received immunosuppressive (IS) agents, only half of them received additional anticoagulant treatments. Among IS agents, interferon treatment was more frequently used in this cohort (19%), compared to other series reported in literature (2.3%). CONCLUSION: To our knowledge, this is the largest series of BD patients with BCS. Our patients had earlier disease onset and diagnosis, higher frequency of IVC thrombosis, and higher mortality rate, compared to BD patients without BCS. Mortality was significantly higher in BD-BCS patients with IVC thrombosis compared to controls. Key Points • Mortality rate is higher in BD-associated BCS patients with IVC involvement. • Chronic and silent form of BD-associated BCS has a better prognosis. • The main treatment options are corticosteroids and immunosuppressive agents, whereas anticoagulant treatment remains controversial.

Assessment of pulmonary arterial stiffness in patients with systemic sclerosis without overt pulmonary hypertension.

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and complicate most systemic diseases. Systemic sclerosis (SSc), represents the leading cause of connective tissue disease (CTD) associated with PAH. Although SSc is a rare disease, it is associated with higher morbidity and early mortality than other rheumatological diseases due to developing SSc-associated interstitial pulmonary disease (ILD) and/or pulmonary arterial hypertension (PAH). The impact of the early diagnosis on the prognosis is evident. In this context, in our study, we aimed to investigate the early changes in pulmonary vascular bed by measuring pulmonary arterial stiffness (PAS) in SSc patients without overt PAH. Sixty-two SSc patients and fifty-eight gender and age-matched, healthy subjects enrolled in this cross-sectional observational study. SSc patients were evaluated in terms of disease duration and severity. Modified rodnan skin score (mRSS) was calculated as disease severity index. Echocardiographic parameters were assessed and compared to the control group. Right ventricular (RV) diameters, systolic pulmonary artery pressure (sPAP), and right ventricle myocardial performance index (RV-MPI) were significantly higher in the SSc group compared to the control group (p < 0.05). Tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC) were significantly lower in the SSc group compared to the control group (p < 0.05). PAS value (25.5 ± 9.2 kHz/ms vs. 18.1 ± 7.4 kHz/ms, p < 0.001) was significantly higher in the SSc group than in the control group. A statistically significant positive correlation relationship was detected between the PAS value and CRP, ESR, disease duration, mRSS. According to these results, in SSc patients, PAS as an inexpensive and easily applicable echocardiographic method might serve as a marker of early detection of PAH.

Infliximab therapy in parenchymal neuro-Behçet's disease: A single-center experience.

BACKGROUND: Parenchymal neuro-Behçet's disease involvement is the most serious complication of Behçet's disease, and no sufficient data on its treatment exists. This study aims to investigate the efficacy and safety of infliximab treatment in neuro-Behçet's disease patients with parenchymal involvement. MATERIALS AND METHODS: Patients who were diagnosed with Behçet's disease with parenchymal neurological involvement and underwent infliximab treatment for at least 12 months were included in the study. Demographic, clinical, and radiological data of the patients were accessed through the electronic database of our hospital. RESULTS: This study comprises 19 patients who were diagnosed with neuro-Behçet's disease and used infliximab: 12 male and 7 female patients. The mean age of the patients was 36.5 ± 11.7 years, and the diagnostic age was 26.3 ± 10.8 years. The duration of treatment with infliximab was 32.3 months (minimum 11, max 79). In the 19 patients receiving infliximab treatment, 11 (58%) patients achieved remission (complete disappearance of neurological symptoms) and 7 (37%) patients achieved disease stability (no new neurological findings); steroid treatments were discontinued for these 18 patients. In addition, only 5 patients were concomitantly taking immunosuppressive drugs with the infliximab. Infliximab was discontinued after the development of a new parenchymal attack in the 9th month of infliximab treatment. CONCLUSION: In conclusion, parenchymal neurological involvement in Behçet's disease is an important cause of disability, and no sufficient data exists in literature on its treatment. The results of our study suggest that infliximab treatment was effective and safe in neuro-Behçet's disease parenchymal involvement for preventing long-term neurological attacks and discontinuing corticosteroid treatment.

The inhibition of Src kinase suppresses the production of matrix metalloproteinases in from synovial fibroblasts and inhibits MAPK and STATs pathways

Background/aim: The purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings. Materials and methods: Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP ­1, ­3, and ­13 levels in FLSs culture were determined by ELISA. Results: The tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP ­1, ­3, and ­13 expressions from FLSs induced by IL-1ß and TNF-α were increased, while dasatinib suppressed their productions from FLSs. Conclusion: The present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA.

Adult-onset still's disease and treatment results with tocilizumab.

AIMS: Adult-onset Still's disease (AOSD) is a rare and non-familial auto-inflammatory disorder. Increased levels of IL-6 and other pro-inflammatory cytokines have been shown in AOSD. To evaluate the efficacy and safety profile of tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody, in AOSD. METHODS: Thirty-nine patients followed up with the diagnosis of AOSD between 2013 and 2019 were retrospectively evaluated and the 16 patients (10 Female/6 Male) treated with TCZ for refractory AOSD were included in the study group. Among the remaining 23 patients 16 had non-biological treatments and had no important complications at the presentation. TCZ was given to patients at a dose of 4-8 mg/kg every 4 weeks. Patients were evaluated after 3-6 months of TCZ treatment for side effects, inflammatory and clinical response and concomitant treatments. RESULTS: In TCZ (+) patients, the majority were female (62.5%), the mean age at disease onset was 38.5 ± 17.9 (20-81) years, and the most common symptoms and signs were myalgia (81.3%), fever (81.3%) and skin eruptions (75%). There was no difference between TCZ (+) and TCZ (-) groups for age, sex and clinical presentations. There was a significant decrease in dose of prednisolone, sedimentation rate, leucocyte count, C-reactive protein and ferritin levels and improvement in all clinical complaints after TCZ treatment. There were no relapses during the treatment. Three patients are in remission and under follow-up without any treatment after cessation of TCZ (4 months-3 years). No exacerbation of disease yet seen in those patients. CONCLUSIONS: TCZ is an effective and well-tolerated treatment option for treatment resistant AOSD and contributes to the glucocorticoid-sparing. Since TCZ is a new drug in the treatment of AOSD, further studies are needed to assess whether the complications reported during the treatment are because of TCZ or natural course of the disease or coincidental findings.

Efficacy of anti-interleukin-1 treatment in colchicine-resistant arthritis in patients with familial Mediterranean fever.

OBJECTIVE: In the familial Mediterranean fever (FMF) clinic, arthritis is among the most common symptoms, and it generally responds well to colchicine treatment. However, cases of patients with chronic prolonged colchicine-resistant arthritis have been reported, and there are inadequate studies on the treatments to be used for such patients. METHODS: This study included 18 patients diagnosed with FMF who had colchicine-resistant chronic arthritis and received anti-interleukin (IL)-1 treatment for at least 1 year. The clinical and laboratory data of the patients were retrospectively retrieved from the database of our hospital. RESULTS: Remission was achieved in arthritis attacks in 16 of 18 patients who started anti-IL-1 therapy because of colchicine-resistant chronic arthritis. The clinical and laboratory values of the other 2 patients improved, but complete remission could not be achieved. The treatment dose of colchicine was reduced with anti-IL-1 therapy. In addition to the improvement in arthritis symptoms, remission was achieved in other clinical findings of FMF by anti-IL-1 therapy. In this study, with an average follow-up time of 33 months, no adverse effects requiring discontinuation were observed in any patient. CONCLUSION: Anti-IL-1 therapy is effective and reliable in the treatment of colchicine-resistant chronic FMF arthritis. The efficacy of anti-IL-1 therapy was realized without concomitant disease-modifying antirheumatic drug therapy, despite the reduction in colchicine dose.

Clinical manifestations of Behçet's syndrome: A single-center cohort of 777 patients.

OBJECTIVE: Behçet's syndrome (BS) is a multisystem variable vessel vasculitis characterized by skin-mucosal lesions. It can also involve the eyes, blood vessels, joints, gastrointestinal system, urogenital system, and central nervous system. BS starts in the third or fourth decade and affects both genders equally. The disease is more severe in young men. Although the sensitivity of the pathergy test (PT) is decreasing today, it is still an important clue in the diagnosis of BS. We describe the characteristics of BS in our region, retrospectively. We also analyzed the effect of gender, age, family history, and skin PT positivity status on the difference of clinical involvement. METHODS: A total of 777 BS patients (391 women and 386 men; 40.0 ± 11.6 years old) who applied to our Rheumatology Department between January 2010 and June 2020 were included in the study. RESULTS: Of the 777 patients, 391 were female (50.3%) and 386 were male (49.7%). The mean age at diagnosis was 30.3 ± 9.8 years. The proportion of patients with BS in their family was 10.2%. Of the 777 patients, 310 (39.9%) had only mucocutaneous symptoms. Other 467 patients (60.1%) had at least one of the ocular, musculoskeletal, vascular, neurologic, intestinal, or genitourinary involvement. Serious involvements such as eye, cardiovascular, and neurologic involvement were more common in male patients. CONCLUSION: BS has the different clinical phenotypes according to gender, age of onset, and skin PT positivity status. Gender influences on the major organ involvements such as eye, neurologic, and vascular.

The receptor for advanced glycation end product (RAGE) pathway in COVID-19.

INTRODUCTION: Coronavirus disease-2019 (COVID-19) with lung involvement frequently causes morbidity and mortality. Advanced age appears to be the most important risk factor. The receptor for advanced glycation end-product (RAGE) pathway is considered to play important roles in the physiological aging and pathogenesis of lung diseases. This study aimed to investigate the possible relationship between COVID-19 and RAGE pathway. MATERIALS AND METHODS: This study included 23 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed tomography. Serum soluble-RAGE (sRAGE) levels were determined using enzyme-linked immunosorbent assay. RESULTS: The sRAGE levels were significantly higher in the asymptomatic group than in the control group. Age, fibrinogen, C-reactive protein, and ferritin levels were higher and the sRAGE level was lower in the patients with lung involvement than in the asymptomatic patients. CONCLUSIONS: In this study, patients with high sRAGE levels were younger and had asymptomatic COVID-19. Patients with low sRAGE levels were elderly patients with lung involvement, which indicates that the RAGE pathway plays an important role in the aggravation of COVID-19.

The assessment of the serum levels of TWEAK and prostaglandin F2α in COVID ­ 19

Background/aim: It is claimed that aberrant immune response has a more important role than the cytopathic effect of the virus in the morbidity and mortality of the coronavirus disease 2019 (COVID-19). We aimed to investigate the possible roles of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 pathway and leukotrienes (LT) in uncontrolled immune response that occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Materials and methods: This study included 25 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed-tomography. Serum TWEAK, LTE4, and prostaglandin F2α (PGF2α) levels were determined. Results: Compared with the healthy control group, TWEAK, LTE4, and PGF2α levels were higher in the group of SARS-CoV-2 infection without lung involvement. In the group of SARS-CoV-2 infection with lung involvement, age, fibrinogen, sedimentation, C-reactive protein and ferritin, TWEAK, LTE4, and PGF2α levels were higher, and lymphocyte levels were lower compared with the asymptomatic group. Conclusions: In the study, TWEAK and LTE4 levels increased in cases with COVID-19. These results support that TWEAK/Fn14 pathway and LT may involved in the pathology of aberrant immune response against SARS-CoV-2. Inhibition of each of these pathways may be a potential target in the treatment of COVID-19.

Two cases of calcium pyrophosphate deposition disease (CPPD) presented with spondylodiscitis.

Calcium pyrophosphate deposition disease (CPPD) is a crystal arthropathy, and may present with various clinical manifestations such as asymptomatic CPPD, osteoarthritis with CPPD, acute CPPD crystal arthritis (formerly pseudogout), and chronic CPPD crystal inflammatory arthritis. It is known that aging, trauma and osteoarthritis are major risk factors for CPPD. Acute CPP arthritis may occur as monoarticular or oligoarticular and usually involves large peripheral joints such as the knees, wrists and ankles. CPPD is characterized by sudden onset of severe pain, swelling and periarticular erythema, and systemic symptoms such as fever, chills, and weakness may occur. On the other hand, axial CPPD has been reported rarely and most cases appear with symptoms related to a mass effect such as foramen magnum syndrome, spinal stenosis, radiculopathy, myelopathy, synovial cyst or cauda equina syndrome. In addition, there are fewer reported cases of spinal CPPD that cause neck and back pain. This clinical condition should be considered in the differential diagnosis of acute neck and back pain.

The importance of Mediterranean fever gene in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease characterized by recurrent serositis attacks and fever. The discovery of the Mediterranean fever (MEFV) gene has been a milestone in FMF etiopathogenesis. Our knowledge about the relationship between the MEFV gene and FMF phenotype increases each day. This study aims to investigate the relationship between MEFV gene mutations and the FMF clinical findings of a single-center FMF cohort. METHODS: Gender, age, age at symptom onset, age at diagnosis, clinical characteristics, and MEFV gene analysis of the patients were recorded. RESULTS: A total of 837 FMF patients were included in this study. There were 515 females and 322 males. The age at symptom onset was 18.3±10.9 years, while the age at diagnosis was 24.4±10.9 years. The most common symptom that accompanied fever was peritonitis (91.1%), while the other common clinical findings were pleuritis (45%), myalgia (44%), and arthritis (36%). A total of 47 patients developed amyloidosis. A total of 553 (66%) FMF patients had M694V mutation, 221 (26%) of which were homozygous, while 332 (40%) were heterozygous. Exon 10 mutation frequency was 759 (91%), while the non-exon 10 mutation frequency was 78 (9%). There was no wild type among the patients. CONCLUSION: In conclusion, the fact that a vast majority of the disease burden was constituted by the exon 10, especially M694V mutations and that none of the 837 patients from our cohort had a wild-type FMF proved the significance of MEFV gene mutation analysis. Therefore, we speculate that it is necessary to examine the MEFV gene mutations in each FMF suspected case. It seems plausible to re-evaluate the FMF diagnosis for cases in which a wild type MEFV gene mutation occurs.

Effectiveness of Methotrexate in Idiopathic Granulomatous Mastitis Treatment.

BACKGROUND: Idiopathic granulomatous mastitis is a rare inflammatory disease of the breast, for which there is a lack of consensus on the treatment protocol; it requires long-term follow-up and is associated with a high rate of relapse after surgical treatment. In this study, we report on the largest single-center cohort of idiopathic granulomatous mastitis treated with steroids + methotrexate. METHODS: We retrospectively examined the data of 33 patients histopathologically diagnosed with idiopathic granulomatous mastitis who were evaluated by our Rheumatology or General Surgery Clinics between 2013 and 2016. RESULTS: Of the 33 female patients (age: 38.64 ± 6.9 years), 24 were admitted with an initial diagnosis of idiopathic granulomatous mastitis, whereas 9 were admitted after surgical treatment. Remission was achieved in 87.9% of patients with steroid + methotrexate treatment, and there were no relapses during the 24-months follow-up period. CONCLUSIONS: Steroid + methotrexate treatment is an effective and reliable method for ensuring long-term remission in patients with idiopathic granulomatous mastitis diagnosis.

Infliximab treatment in refractory vascular Behcet's disease: A single-center experience.

OBJECTIVE: This study aims to investigate the efficacy and reliability of infliximab treatment in Behcet's disease with vascular involvement. METHODS: This single-center retrospective study included a total of 18 patients diagnosed with Behcet's disease with vascular involvement who were initiated infliximab treatment after exhibiting resistance to conventional immunosuppressive treatments. RESULTS: Seventeen patients achieved remission with infliximab treatment. While 18 patients were receiving a median of 50 (IQR: 20-61) mg/day equivalent of methylprednisolone before infliximab treatment, after infliximab treatment, only four patients were receiving 4 mg/day equivalent of methylprednisolone (p < 0.001). Only 4 patients were receiving oral anticoagulant treatment during infliximab treatment, and compared to the patients who were not receiving oral anticoagulants, there was no significant difference between the two groups according to occurrence of new vascular events. CONCLUSION: Infliximab seems to be an effective and reliable treatment in Behcet's disease with vascular involvement and may also allow reduced dosage or even the discontinuation of corticosteroids. The results of our study suggest that oral anticoagulant use is unnecessary in Behcet's disease with vascular involvement. However, further long-term randomized controlled studies are needed to investigate the length of infliximab regimen, whether or not it should be discontinued, and if so, whether or not immunosuppressants should be given as maintenance after discontinuation.