Exploring S100A8/A9, Neopterin, and MMP3 in Familial Mediterranean Fever.

Familial mediterranean fever (FMF) is characterized by inflammatory attacks due to overactivation of pyrin inflammasome. This study aimed to investigate the reliability of S100A8/A9, neopterin, and matrix metalloproteinase 3 (MMP3) at monitoring subclinical inflammation and disease activity, and at differentiating FMF attacks from appendicitis, the most common misdiagnosis among FMF patients. Blood samples (n=75), comprising from FMF patients during an attack (n=20), the same FMF patients during the attack-free period (n=14), patients with appendicitis (n=24), and healthy volunteers (n=17) were obtained. Duplicate determinations of S100A8/A9, neopterin, and MMP-3 levels were conducted using the enzyme-linked immunosorbent assay (ELISA). FMF patients with and without attack and patients with appendicitis had significantly elevated S100A8/A9 levels compared to healthy volunteers (p-values: <0.001, 0.036, 0.002, respectively). Patients with appendicitis and FMF patients with and without attack had significantly increased serum neopterin levels compared to healthy volunteers (p-value: <0.001). MMP3 levels were significantly higher among patients with appendicitis and FMF patients during attack compared to healthy controls (p-values: <0.001, 0.001). Serum levels of S100A8/A9, neopterin, and MMP3 were increased significantly during attacks compared to attack-free periods among FMF patients (p-values: 0.03, 0.047, 0.007). S100A8/A9 emerges as a valuable marker for monitoring disease activity. Neopterin and S100A8/A9 might help physicians to monitor subclinical inflammation during the attack-free periods of FMF patients. MMP3 might aid in diagnosing FMF attacks when distinguishing between attack and attack-free periods is challenging.

Efficacy and safety of anti-interleukin-1 treatment in familial Mediterranean fever patients: a systematic review and meta-analysis.

OBJECTIVES: FMF is the most common hereditary monogenic fever syndrome marked by recurrent attacks of fever and polyserositis. Colchicine is the current recommended first-line treatment for FMF. However, a small portion of FMF patients are unresponsive or intolerant to colchicine. Anti-IL-1 agents are alternative treatment options for colchicine-resistant or -intolerant FMF patients. This systematic review and meta-analysis aimed to provide qualitative and quantitative evidence for the efficacy and safety of anti-IL-1 agents in adult and paediatric FMF patients. METHODS: MEDLINE, EMBASE, CENTRAL and Web of Science were screened from inception to May 2023. We included adult and paediatric FMF patients who received continuous treatment with at least one of the anti-IL-1 drugs: anakinra, canakinumab and rilonacept. The primary efficacy outcome was the proportion of patients who achieved complete remission of attacks and the primary safety outcome was the proportion of patients who experienced at least one adverse event during treatment. A random-effects meta-analysis was performed for the quantitative synthesis. RESULTS: Fourty-four reports consisting of 1399 FMF patients were included. Sixty percent (95% CI 49%, 72%) of the adult patients and 81% (95% CI 72%, 89%) of the paediatric patients achieved complete remission. Anti-IL-1 agents significantly decreased levels of inflammatory markers. At least one adverse event was observed in 25% (95% CI 13%, 37%) of the adult patients and 12% (95% CI 3%, 21%) of the paediatric patients. CONCLUSION: Anti-IL-1 agents were effective and demonstrated a low adverse event profile in paediatric and adult FMF patients.

Efficacy and Safety of Biological Drugs in Still's Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Still's disease is a rare autoinflammatory disorder characterized by systemic inflammation, fever, rash, and arthritis. The term "Still's disease" covers the pediatric subtype systemic Juvenile Idiopathic Arthritis (sJIA) and adult-onset Still's disease (AOSD), which affects adults. Biological drugs, including anti-interleukin-1 agents anakinra, canakinumab, rilonacept, and the interleukin-6 antagonist tocilizumab, are used in the management of Still's disease. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials, and the study protocol was registered in PROSPERO (CRD42023450442). MEDLINE, EMBASE, and CENTRAL were screened from inception until September 17, 2023. We included patients with Still's disease who received placebo or biological drugs: anakinra, canakinumab, rilonacept, or tocilizumab. The primary efficacy and safety outcomes were achievement of ACR50 response and occurrence of serious adverse events, respectively. The interventions were ranked using rankograms and SUCRA values. RESULTS: Nine trials with 430 patients were included. All biological drugs were associated with greater odds of ACR50 response compared with placebo. There was no statistically significant association between biological drugs and serious adverse events. The multivariate meta-analysis found no difference between biological drugs. As per SUCRA rankings, anakinra was the most effective and safe option with respect to ACR50 response and occurrence of serious adverse events. CONCLUSION: This is the first systematic review and meta-analysis to assess the efficacy and safety of biological drugs in pediatric and adult patients with Still's disease. Biological drugs were effective in achieving ACR response and demonstrated a low adverse event profile in the management of Still's disease.

A rare case of uncharacterized autoinflammatory disease: Patient carrying variations in NLRP3 and TNFRSF1A genes.

Tumor necrosis factor type 1A receptor-associated periodic syndrome (TRAPS) and cryopyrin-associated autoinflammatory syndrome (CAPS) are rare monogenic autoinflammatory diseases (AIDs) mainly caused by pathogenic variations in the TNFRSF1A and NLRP3 genes, respectively. Here, we describe a unique patient presenting with symptoms overlapping both TRAPS and CAPS, without known pathogenic variants in the respective genes. The patient harbored the p.Val200Met variation in NLRP3 and the p.Ser226Cys variation in TNFRSF1A, prompting us to delve deeper into the functional analysis due to conflicting or inconclusive pathogenicity interpretations of the variants across various databases. Molecular dynamics analysis of the p.Val200Met variation in NLRP3 revealed a rigid conformation in the helical domain 2 subdomain of the NACHT domain. This increased rigidity suggests a potential mechanism by which this variation supports the assembly of the NLRP3 inflammasome. Notably, the patient's peripheral mononuclear blood cells demonstrated an elevated IL-1ß response upon lipopolysaccharides (LPS) induction. Subsequent initiation of anti-IL-1ß therapy resulted in a significant alleviation of the patient's symptoms, further supporting our hypothesis. We interpret these findings as suggestive of a potential pathophysiological role for the NLPR3 p.Val200Met variation in shaping the patient's clinical phenotype, which was also supported by clinical and genetic analysis of the family. This case underscores the complexity of the genetic landscape in AIDs and highlights the value of combining family genetic and functional data to refine the understanding and management of such challenging cases.

Anxiety and depression among patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is a systemic autoinflammatory disease that requires lifelong treatment and is associated with several comorbidities, including mental health disorders such as anxiety and depression. FMF and mental health necessitate further research; hence, this study aims to observe anxiety and depression and their relationship with several variables in patients with FMF. METHODS: As the study population, 360 FMF patients were surveyed between June and October 2022. Surveys included inventories assessing anxiety and depression, i.e., the Beck's Depression Inventory (BDI), the Beck's Anxiety Inventory (BAI), and the State-Trait Anxiety Inventory (STAI). RESULTS: Mean scores for STAI-Y1 (state), STAI-Y2 (trait), BAI, and BDI were 42.2 ± 12.0, 45.9 ± 10.6, 24.0 ± 13.9, and 13.1 ± 8.99, respectively. Medication-adherent patients had significantly lower scores on STAI-Y1 (41.5 ± 11.4 vs. 45.2 ± 14.0; p-value: 0.04). M694V homozygous patients exhibited significantly lower scores in the BDI (12.4 ± 9.37 vs. 13.2 ± 8.93; p-value: < 0.001) and BAI (17.0 ± 12.1 vs. 25.1 ± 13.9; p-value: 0.001). The patients with an exon-10 mutation demonstrated significantly lower scores compared to patients with an exon­2 mutation (17.9 ± 12.3, 29.6 ± 13.3; p-value: < 0.001). CONCLUSION: The patients with FMF had mild depression and moderate anxiety scores. A higher level of education and medication adherence were associated with lower levels of anxiety. Likewise, the patients with genotypes associated with severe disease courses had lower levels of anxiety. We suggest that physicians should be more attentive to patients with a milder disease course and ensure that these patients are provided with sufficient treatment and knowledge about their disease.

Anakinra in idiopathic recurrent pericarditis: a comprehensive case series and literature review.

OBJECTIVE: Idiopathic recurrent pericarditis (IRP) is defined by recurring episodes of pericardial inflammation without a known cause. This study investigates the safety and efficacy of anakinra, an interleukin­1 inhibitor, as a successful therapy for IRP in cases resistant to conventional treatment. METHODS: A retrospective evaluation of patients treated at our autoinflammatory center between 2011 and 2023 was conducted. Patient files were examined for demographic, clinical, and treatment response data, including nonsteroid anti-inflammatory drugs (NSAIDs), corticosteroids, and colchicine. Monogenic autoinflammatory disease screening was performed for Mediterranean Fever (MEFV), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase (MVK), nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), and nucleotide-binding oligomerization domain-containing protein 2 (NOD2). Patients who experienced multiple episodes of pericarditis were diagnosed with recurrent pericarditis. The study evaluated anakinra treatment in IRP patients unresponsive to conventional therapy. RESULTS: The study included 21 participants, 9 (42.9%) female and 12 (57.1%) male. The average age of the participants was 43.1 ± 16.5 years. The MEFV mutation analysis revealed that 2 (9.5%) had a mutation in exon 10 and 4 (19.0%) had one in exon 2. Out of the 16 cases, 15 successfully discontinued steroid treatment. Four patients (19.0%) experienced injection site reactions. C­reactive protein (CRP) levels were measured at an average of 196 ± 67.8 mg/l before and 2.6 ± 3.15 mg/l after anakinra treatment. CONCLUSION: In conclusion, the study adds to the growing evidence for the efficacy of interleukin-1 inhibitors, such as anakinra, as a promising treatment modality for IRP in cases resistant to conventional treatment.

Fertilization, reproductive system, and pregnancy in familial Mediterranean fever: Clinical state of art.

Systemic autoinflammatory diseases have always been one of the most striking and challenging aspects of the art of medicine. Among this fascinating constellation of diseases, familial Mediterranean fever (FMF) is the most common. FMF involves the reproductive system and may cause fertility problems. With the start of the interleukin (IL)-1 inhibitors era, there is a need to reorganize our knowledge on FMF management, particularly in pregnant patients and those experiencing fertilization problems. The primary aim of this review is to gather recent information on the effects of FMF on fertilization and the reproductive system, as well as to shed light on the management of pregnancy in FMF patients.

Behçet disease, familial Mediterranean fever and MEFV variations: More than just an association.

Behçet disease (BD) and familial Mediterranean fever (FMF) are two inflammatory disorders that share many features including historical background, ethnical distribution and inflammatory characteristics. Several studies suggested that BD and FMF might occur in the same individual more commonly than expected. Additionally, the pathogenic MEFV gene variants, especially p.Met694Val, activating the inflammasome complex have been shown to increase the risk for BD in regions where both FMF and BD are prevalent. Whether these variants are associated with certain disease subtypes and whether they may help in the planning of treatment need to be explored. This review provides a recent overview of the plausible association between FMF and BD and the role of MEFV variants in the pathogenesis of BD.

Infliximab for vascular involvement in Behçet's syndrome.

OBJECTIVE: Vascular involvement is an important cause of morbidity and mortality in patients with Behçet's syndrome (BS). We aimed to survey the efficacy and safety of infliximab (IFX) in BS patients with vascular involvement followed in a dedicated tertiary center. METHODS: Charts of all BS patients who used IFX for vascular involvement between 2004 and 2022 were reviewed. Primary endpoint was remission at Month 6, defined as lack of new clinical symptoms and findings associated with vascular lesion, lack of worsening of the primary vascular lesion and a new vascular lesion on imaging, and CRP < 10 mg/L. Relapse was defined as development of a new vascular lesion or recurrence of the preexisting vascular lesion. RESULTS: Among the 127 patients (102 men, mean age at IFX initiation: 35.8 ± 9.0 years) treated with IFX, 110 (87%) had received IFX for remission induction and 87 of these (79%) were already on immunosuppressives when the vascular lesion requiring IFX developed. The remission rate was 73% (93/127) at Month 6 and 63% (80/127) at Month 12. Seventeen patients experienced relapses. Remission rates were better among patients with pulmonary artery involvement and venous thrombosis compared to patients with non-pulmonary artery involvement and venous ulcers. Fourteen patients had adverse events leading to IFX discontinuation and 4 had died due to lung adenocarcinoma, sepsis, and pulmonary hypertension-related right heart failure due to pulmonary artery thrombosis (n = 2). CONCLUSION: Infliximab seems to be effective in majority of BS patients with vascular involvement, even in those who are refractory to immunosuppressives and glucocorticoids.

Detection of a rare variant in PSTPIP1 through three generations in a family with an initial diagnosis of FMF/MKD-overlapping phenotype.

OBJECTIVE: The presence of FMF cases without MEFV (MEFV innate immunity regulator, pyrin) pathogenic variants led us to search for other genes' involvement in the disease development. Here, we describe the presence of genetic heterogeneity in a three-generation family with an FMF/mevalonate kinase deficiency (MKD)-overlapping phenotype without MEFV/MVK (mevalonate kinase) pathogenic variants. METHOD: Targeted sequencing revealed a rare, fully penetrant variant in PSTPIP1 (p.Arg228Cys, rs781341816). Computational stability analyses of PSTPIP1 protein were performed. PSTPIP1-pyrin protein interaction was examined by immunoprecipitation and immunoblotting in peripheral blood mononuclear cells (PBMCs) of patients and healthy controls. PBMCs were cultured, and inflammation was induced by LPS+ATP treatment, followed by protein level measurements of caspase-1, IL1ß, pyrin and PSTPIP1 in cell lysates and mature caspase-1 and mature IL1ß in supernatants. RESULTS: The conserved, rare (GnomAD, 0.000028) PSTPIP1 p.Arg228Cys variant, previously reported in ClinVar as a variant with uncertain significance, showed complete penetrance in the family presenting an autosomal dominant pattern. Computational analyses showed a potentially destabilizing effect of the variant on PSTPIP1 protein. Accordingly, PSTPIP1-pyrin interaction was increased in patients harboring the variant, which resulted in elevated levels of mature caspase-1 and IL1ß in the inflammation-induced patient samples. CONCLUSIONS: Unlike previously described cases with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA)-associated PSTPIP1 variants, our patients with the p.Arg228Cys variant presented with an FMF/MKD-overlapping phenotype. As additional data on the genetic heterogeneity in the variable clinical spectrum of autoinflammatory syndromes, we suggest that the p.Arg228Cys variant in PSTPIP1 is related to inflammation responses through strong PSTPIP1-pyrin interaction and pyrin inflammasome activation.

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.

Comparison of telerehabilitation methods for patients with systemic sclerosis in the COVID-19 Era: A randomized controlled study.

STUDY DESIGN: This was a single-blinded randomized clinical trial. INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune connective tissue disease that progresses with fibrosis. Patients with SSc need to be protected against epidemic diseases and provided for in terms of rehabilitation needs. PURPOSE OF THE STUDY: To compare the effects of real-time telerehabilitation (RTT) and asynchronous telerehabilitation (AT) on individuals with SSc. METHODS: Forty-two participants with SSc with a mean age of 44.17 ±â€¯11.05 years were included in the study. The patients were randomly divided into three groups, RTT (n = 16), AT (n = 16), and control (n = 16) groups. A structured rehabilitation program was performed in real-time (RTT group) and asynchronously (AT group) for 40 minutes per day, in three sessions per week for 8 weeks. The participants' finger and wrist joint range of motion (ROM), upper extremity functions, grip strength, superficial sense of touch, activities of daily living (ADL), and general health status were assessed at baseline and after treatment. RESULTS: After 8 weeks, there were improvements in finger ROM (effect size [ES] = 0.23 to 0.60), wrist ROM (ES = 0.45 to 0.83), upper extremity functions (ES = 0.61 to 1.00), and ADL parameters (ES = 0.74) in the RTT group (p < 0.05). Also, there were improvements in finger ROM (ES = 0.16 to 0.45) and hand functions (ES = 0.54 to 0.55) in the AT group (p < 0.05). The RTT and AT groups had better hand functions and finger ROM than the control group in (p < 0.05). In addition, the RTT group had better wrist ROM than the control group (p = 0.008). RTT was superior to AT only in lateral pinch strength (p = 0.025). DISCUSSION: Experimental groups achieved a statistically significant change in ROM, upper extremity functions and ADL over time in concordance with prior investigations. Changes in grip strength, superficial sense of touch, and general health status scores differed from previous investigations and the between-group comparison was not statistically significant. CONCLUSIONS: Both RTT and AT may be effective in individuals with SSc, and RTT has additional benefits.

Screening of antigliadin and antitissue transglutaminase antibodies in patients with chronic plaque psoriasis: a case-control study.

BACKGROUND: In this study, we aimed to investigate different types of celiac antibodies in psoriasis patients and to see if the presenceof the antibodies was associated with other variables. METHODS: We included patients with plaque psoriasis who were followed up in our dermatology clinic between February 2019 and February 2021 and added a healthy control group for comparison. The antibodies studied were serum antitissue transglutaminase (tTG)-IgA, tTG-IgG, antigliadin antibody (AGA)-IgA, and AGA-IgG. The patients' records were used to note age, sex, the pattern of psoriasis involvement, psoriasis area and severity index (PASI), presence of hypertension, presence of type 2 diabetes mellitus, use of methotrexate, and use of biologic agents. RESULTS: Sixty-five psoriasis patients (31 F, 34 M, mean age: 38.9 ± 15.2) and 65 controls (42 F, 23 M, mean age: 40.7 ± 13.2) wereincluded in the study. There was no significant difference in antibody levels between the groups: tTG-IgA (2.4 U/mL vs 3.2 U/mL, p = 0.11), tTG-IgG (2.2 U/mL vs 3.2 U/mL, p = 0.74), AGA-IgA (2.4 U/mL vs 3.5 U/mL, p = 0.068), and AGA-IgG (3.2 U/mL vs 4.2 U/mL, p = 0.15). One patient from the psoriasis group only had borderline positive antibody levels whereas the rest of the psoriasis and control group had negative levels. Hypertensive psoriasis patients had significantly higher AGA-IgA titers compared to normotensive psoriasis patients (4.2 U/mL vs 2.3 U/mL, p = 0.005). DISCUSSION: There was no increase in the AGA-IgA/IgG and tTG-IgA/IgG levels in psoriasis patients compared to the healthy population. However, hypertensive psoriasis patients had higher AGA-IgA levels compared to normotensive ones.

Frequency and severity of COVID-19 in patients with various rheumatic diseases treated regularly with colchicine or hydroxychloroquine.

This study aimed to investigate whether patients regularly using colchicine or hydroxychloroquine (HCQ) have an advantage of protection from coronavirus disease 2019 (COVID-19) or developing less severe disease. Patients who were taking colchicine or HCQ regularly for a rheumatic disease including Familial Mediterranean Fever, Behçet's syndrome, Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Sjogren's syndrome, as well as their healthy household contacts as the control group, were included in the study. The clinical data regarding COVID-19 were collected using a standard form, and serum samples were analyzed for anti-severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) nucleocapsid immunoglobulin G (IgG). A total of 635 regular colchicine users with their 643 household contacts and 317 regular HCQ users with their 333 household contacts were analyzed. Anti-SARS-COV-2 IgG was positive in 43 (6.8%) regular colchicine users and 35 (5.4%) household contacts (odds ratio [OR] = 1.3; 95% confidence interval [CI]:0.8-2; p = 0.3). COVID-19-related symptoms were described by 29 (67.4%) of the patients and 17 (48.6%) household contacts (OR = 2.2; 95% CI :0.9-5.5; p = 0.09), and hospital admission was observed in five (11.6%) and one (2.9%) of these subjects (OR = 4.5; 95% CI: 0.5-40.2; p = 0.1), respectively. Seropositive subjects were observed in 22 (6.9%) regular HCQ users and 24 (7.2%) household contacts (OR = 1.1; 95% CI: 0.6-1.9; p = 0.8). COVID-19-related symptoms occurred in 16 (72.7%) of the 22 patients and 12 (50%) of 24 household contacts (OR = 2.7; 95% CI: 0.8-9.1; p = 0.1). Three patients (13.6%) were admitted to hospital, while one household contact (4.2%) was hospitalized (OR = 3.6; 95% CI: 0.3-37.8; p = 0.2). Being on a regular treatment of colchicine or HCQ did not result in the prevention of COVID-19 or amelioration of its manifestations.

Frequency of AA amyloidosis has decreased in Behçet's syndrome: a retrospective study with long-term follow-up and a systematic review.

OBJECTIVE: A decline in the frequency of AA amyloidosis secondary to RA and infectious diseases has been reported. We aimed to determine the change in the frequency of AA amyloidosis in our Behçet's syndrome (BS) patients and to summarize the clinical characteristics of and outcomes for our patients, and also those identified by a systematic review. METHODS: We identified patients with amyloidosis in our BS cohort (as well as their clinical and laboratory features, treatment, and outcome) through a chart review. The primary end points were end-stage renal disease and death. The prevalence of AA amyloidosis was estimated separately for patients registered during 1976-2000 and those registered during 2001-2017, in order to determine whether there was any change in the frequency. We searched PubMed and EMBASE for reports on BS patients with AA amyloidosis. Risk of bias was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. RESULTS: The prevalence of AA amyloidosis was 0.62% (24/3820) in the earlier cohort and declined to 0.054% (3/5590) in the recent cohort. The systematic review revealed 82 cases in 42 publications. The main features of patients were male predominance and a high frequency of vascular involvement. One-third of patients died within 6 months after diagnosis of amyloidosis. CONCLUSION: The frequency of AA amyloidosis has decreased in patients with BS, which is similar to the decrease observed for AA amyloidosis due to other inflammatory and infectious causes. However, AA amyloidosis is a rare, but potentially fatal complication of BS.

Emergence of new manifestations during infliximab treatment in Behçet's syndrome.

OBJECTIVES: Infliximab (IFX) is increasingly being used for the treatment of severe manifestations of Behçet's syndrome (BS). However, emergence of new manifestations has also been occasionally reported during IFX treatment. We aimed to assess the frequency of new manifestations in our BS patients treated with IFX. METHODS: A chart review was conducted to identify all BS patients treated with IFX in our clinic between 2004 and 2020. Demographic data, indications for IFX initiation, concomitant treatments and outcomes were recorded. A new manifestation was defined as the emergence of a new organ involvement or mucocutaneous manifestation developing for the first time during IFX treatment or within 12 weeks after the last infusion of IFX. RESULTS: Among our 282 patients who used IFX, 19 (7%) patients had developed a total of 23 new manifestations during a mean follow-up of 20.0 (15.3) months. Patients with vascular involvement were more likely to develop a new manifestation (12/19, 63%). Initial manifestations that required IFX were in remission at the time of new manifestation in 14/19 patients. IFX treatment was intensified (n = 6) and/or glucocorticoids, immunosuppressives or colchicine was added to IFX (n = 21). IFX was switched to another agent for the remaining manifestations (n = 8). These treatment modifications led to remission in 17/19 patients. CONCLUSION: New manifestations developed during IFX treatment in 7% of our patients with BS. They could be managed by intensifying IFX treatment or adding other agents in the majority of these manifestations.

The frequency of obstructive sleep apnea in patients with primary Sjogren's syndrome.

INTRODUCTION: There is a lack of information about the frequency of obstructive sleep apnea (OSA) in primary Sjogren's syndrome (pSS). Using all-night polysomnography (PSG), this study aimed to investigate the frequency of OSA in pSS and the factors affecting the frequency of OSA in this condition.  METHODS: Consecutive patients with pSS who presented to the Collagen Tissue Diseases follow-up polyclinic of the Department of Chest Diseases between 1 April 2019 and 31 December, 2020, were included in the study. Demographic characteristics, chronic diseases, smoking history in pack-years, anthropometric data, Epworth Sleepiness Scale score, pulmonary function test parameters, current thorax computed tomography findings, and PSG data were recorded. The control group was created by the retrospective screening of patients admitted to the sleep polyclinic and who underwent PSG but did not have pSS. RESULTS: OSA was detected in 37 (84%) of 44 patients with pSS who underwent PSG. Of 37 patients with OSA, 25 (68%) had moderate or severe OSA. Snoring and witnessed apneas, REM%, snoring index, and maximum apnea and maximum hypopnea duration were statistically significantly lower in the pSS group compared with the control group (p < 0.001, p = 0.003, p = 0.025, p = 0.001, p = 0.028, and p = 0.035, respectively). CONCLUSION: The frequency of OSA in patients with pSS was 84%, with a decrease in REM%. Although a correlation between symptoms suggesting OSA and the presence of radiological lung involvement, spirometry, and DLCO values with OSA could not be demonstrated, physicians are recommended to be attentive for the presence of OSA in all patients with pSS and to investigate OSA using PSG.

Safety of SARS-CoV-2 vaccination in patients with Behcet's syndrome and familial Mediterranean fever: a cross-sectional comparative study on the effects of M-RNA based and inactivated vaccine.

Most of the published data relate to classical forms of rheumatic diseases (RD) and information on rare inflammatory disorders such as Behçet's syndrome (BS) and familial Mediterranean fever (FMF) is limited. We studied the frequency of side effects and disease flares after COVID-19 vaccination with either Pfizer/BioNTech or Sinovac/CoronaVac in 256 patients with BS, 247 with FMF, and 601 with RD. Telephone interviews were conducted using a questionnaire survey in a cross-sectional design in patients with BS, FMF, and RD followed by a single university hospital. Study participants were vaccinated either with CoronaVac (BS:109, FMF: 90, and RD: 343,) or BioNTech (BS: 147, FMF: 157 and RD: 258). The majority have received double dose (BS: 94.9%, FMF 92.3% and RD: 86.2%). BioNTech ensured a significantly better efficacy than CoronaVac against COVID-19 in all patient groups (BS: 1.4% vs 10.1%; FMF: 3.2% vs 12.2%, RD:2.7% vs 6.4%). Those with at least one adverse event (AE) were significantly more frequent among those vaccinated with BioNTech than those with CoronaVac (BS: 86.4% vs 45%; FMF: 83.4% vs 53.3%; and RD: 83.3% vs 45.5%). The majority of AEs were mild to moderate and transient and this was true for either vaccine. There were also AEs that required medical attention in all study groups following CoronaVac (BS: 5.5%, FMF: 3.3%, and RD:2.9%) or BioNTech (BS: 5.4%, FMF: 1.9%, and RD: 4.7%). The main causes for medical assistance were disease flare and cardiovascular events. Patients with BS (16.0%) and FMF (17.4%) were found to flare significantly more frequently when compared to those with RD (6.0%) (p < 0.001). This was true for either vaccine. BS patients reported mainly skin-mucosa lesions; there were however, 11 (4.3%) who developed major organ attack such as uveitis, thrombosis or stroke. Flare in FMF patients were associated mainly with acute serositis with or without fever. Arthralgia/arthritis or inflammatory back pain were observed mainly in the RD group. Our study demonstrates that BS and FMF patients vaccinated with either CoronaVac or BioNTech demonstrated similar AE profile and frequency compared to RD patients. AEs that required physician consultation or hospitalization occurred in all study groups after either CoronaVac or BioNTech. Increased frequency of flares in BS and FMF compared to that seen in RD might reflect defects in innate immunity and deserves further investigation. Caution should be required when monitoring these patients after vaccination.

Screening for latent tuberculosis before starting TNF-alpha inhibitors in a population with high BCG vaccination rates.

It is assumed that in candidates for TNF-alpha inhibitor (TNFi) treatment, tuberculin skin test (TST) may be unreliable, since BCG vaccination causes false positive and drugs cause false negative results, favoring the use of Quantiferon or T-spot assays. However, these tests may not be readily available in all parts of the world. We aimed to determine the reliability of TST with respect to BCG vaccination and drugs in candidates for TNFi treatment, and how isoniazid is tolerated, assuming that the use of TST would result in increased isoniazid use. We included 1031 adult patients who were prescribed a TNFi for the first time. We analysed the association of BCG and drugs with TST and Quantiferon results, the determinants of a positive TST, and evaluated the tolerability of isoniazid. BCG vaccination and male sex were associated with positive TST (OR 3.56, 95% CI 1.98-6.41 and OR 2.54, 95% CI 1.75-3.68, respectively), while prednisolone and azathioprine were associated with negative TST (OR 0.63, 95% CI 0.43-0.91 and OR 0.40, 95% CI 0.11-0.76). Isoniazid was prescribed to 684 (66.3%) patients and had to be discontinued in 12.2% of these before 9 months, most commonly due to hepatotoxicity (44%). One patient developed tuberculosis despite isoniazid use. BCG vaccination may be associated with false positive TST, despite a long time since vaccination in candidates for TNFi treatment. Prednisolone and azathioprine use were associated with negative TST. Despite the high frequency of isoniazid use associated with using TST instead of QTF, isoniazid was generally well tolerated.

The incidence, clinical characteristics, and outcome of COVID-19 in a prospectively followed cohort of patients with Behçet's syndrome.

Initial case series of small number of patients at the beginning of the pandemic reported a rather guarded prognosis for Behçet's syndrome (BS) patients infected with SARS-CoV-2. In this prospective study, we describe the incidence, clinical characteristics, disease course, management, and outcome in a large cohort of BS patients with laboratory-confirmed infection of SARS-CoV-2. We defined a cohort of 1047 registered BS patients who were aged between 16 and 60 years and seen routinely before the pandemic at the multidisciplinary outpatient clinic. We followed prospectively this cohort from beginning of April 2020 until the end of April 2021. During 13 months of follow-up, of the 1047 (599 M/448 F) patients, 592 (56.5%) were tested for SARS-CoV-2 PCR at least once and 215 (20.5%; 95% CI 0.18-0.23) were tested positive. We observed 2 peaks which took place in December 2020 and April 2021. Of the 215 PCR positive patients, complete information was available in 214. Of these 214, 14 (6.5%) were asymptomatic for COVID-19. In the remaining, the most common symptoms were anosmia, fatigue, fever, arthralgia, and headache. A total of 40 (18.7%) had lung involvement, 25 (11.7%) were hospitalized, 1 was admitted to the intensive care unit while none died. Favipiravir was the most prescribed drug (74.3%), followed by colchicine (40.2%), and hydroxychloroquine (20.1%) in the treatment of COVID-19. After COVID-19, 5 patients (2.3%) were given supplemental O2 and 31 (14.5%) antiaggregant or anticoagulants. During COVID-19, of the 214 PCR positive patients, 116 (54.2%) decreased the dose of their immunosuppressives or stopped taking completely; 36 (16.8%) experienced a BS flare which was mostly oral ulcers (10.3%). None of the patients reported a thrombotic event. A total of 93 (43.5%) patients reported BS flares after a median 45 days of COVID-19 infection and this was found to be significantly associated with immunosuppressive drug discontinuation. Multiple regression analysis adjusted for age and gender indicated that smoking and using interferon-alpha decreased the likelihood of getting COVID-19. The incidence and severity of COVID-19 did not differ between those who were using colchicine or not. The cumulative incidence of COVID-19 in this prospectively followed cohort of BS patients was almost two folds of that estimated for the general population living in Istanbul, Turkey, however, the clinical outcome of COVID-19 was not severe and there was no mortality. The protective effect of smoking and interferon deserves further investigation. On the other hand, colchicine did not have any positive or negative effect against COVID-19. Significant number of patients flared after COVID-19, however, this was significantly associated with immunosuppressive discontinuation during the infection. Contrary to our previous observations, COVID-19 did not seem to exacerbate thrombotic events during or after the infection.