Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10-5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.

De novo manifestations during adalimumab treatment in Behçet's syndrome.

OBJECTIVES: Treatment response may be variable across organ manifestations of Behçet syndrome (BS). We aimed to determine the frequency of de novo manifestations during adalimumab treatment. METHODS: We conducted a chart review of all BS patients who received adalimumab in our center between 2008 and 2023. Demographic data, reasons for initiating adalimumab, concurrent medications, previous treatments, and outcomes were recorded. We defined de novo manifestations as new BS manifestations that occurred for the first time during treatment with adalimumab. For patients with vascular involvement, a new vascular event at another vessel was also considered as a de novo manifestation. RESULTS: Among the 335 patients, a de novo manifestation developed in 14 (4%) patients. De novo manifestations were vascular involvement in 5 patients, arthritis in 3, anterior uveitis in 2, nervous system involvement in 2, gastrointestinal involvement in 1, and epididymitis in 1 patient. The primary reasons for adalimumab treatment were vascular involvement in 5 patients, uveitis in 4, arthritis in 3, mucocutaneous involvement in 1, and epididymitis in 1 patient. Upon the development of de novo manifestation, adalimumab was switched to another biologic in 4 patients, dose was intensified in 3, colchicine, conventional immunosuppressives, and/or glucocorticoids were added in 5, and topical eye drops were added in 2 patients, leading to remission of de novo manifestations in all patients. CONCLUSION: De novo manifestations were infrequent (4%) among BS patients treated with adalimumab. Of these, 57% were major organ involvement, mainly vascular involvement. None of the patients developed posterior uveitis.

Atrial myxoma as a mimicker of intracardiac thrombus in Behçet's syndrome: a case study with histopathological confirmation.

Cardiomyopathies cause most intracardiac thrombosis (ICT), and Behçet's syndrome (BS) is a rare inflammatory disease that can be responsible for a proportion of ICT. Other inflammatory disorders involved in the aetiology of ICT include antiphospholipid syndrome, Henoch-Schonlein purpura, COVID-19, and Loeffler endocarditis. ICT usually occur during the active phase of BS, and they have a close relationship with vascular involvement. Atrial myxomas are benign cardiac tumours arising from the interatrial septum. They can lead to a substantial acute phase response, making them difficult to distinguish from inflammatory diseases. In this case study, we present a 46-year-old female BS patient who presented with constitutional symptoms mimicking BS flare in a routine follow-up visit and was diagnosed with left atrial myxoma after administration of several lines of immunosuppressives. Then, she underwent surgical tumour excision, and a histopathological examination confirmed the diagnosis.In conclusion, atrial myxoma should be kept in mind first of all when suspecting ICT, and advanced imaging methods such as cardiac magnetic resonance imaging (MRI) should be used if necessary.

Pulmonary artery involvement due to Behçet's syndrome and Hughes Stovin syndrome: a comparative study.

OBJECTIVES: Hughes-Stovin syndrome (HSS) is a rare inflammatory condition defined as pulmonary artery aneurysms (PAA) associated with deep vein thrombosis. It is similar to vascular involvement of Behçet's syndrome (BS), but differs in the absence of typical skin-mucosal findings. Whether HSS is a distinct entity or a form fruste of BS is debated. We formally compared HSS cases retrieved from the literature to BS patients with PAI followed by a tertiary centre. METHODS: A systemic literature search using 'Hughes Stovin syndrome' as the key word covering the period between 2000 and 2023 revealed 58 (43 M/15 F) case reports (PROSPERO: CRD42023413537). We identified 74 (62M/12 F) BS patients with PAI followed up in a tertiary centre in Turkey from 2000 until 2020. We evaluated two cohorts head-to-head in terms of demographic and clinical features. RESULTS: BS and HSS patients were found to be comparable with regard to several demographic, clinical and histopathological features. However, PAA were significantly more frequent and isolated pulmonary artery thrombosis (PAT) less common in HSS than that found in BS. Moreover, patients with HSS were more likely to be treated with anti-coagulants and vascular or surgical interventions, whereas less likely to receive immunosuppressive treatment. CONCLUSIONS: Our study indicates that HSS is indeed an 'incomplete form of BS'. It can be considered as evidence supporting the notion that the vascular phenotype develops independently from skin-mucosa lesions and uveitis in BS. However, HSS has been described mainly focusing on aneurysms, overlooking the aspect of in-situ thrombosis.

Tocilizumab may not be a good option for vascular involvement due to Behçet's syndrome.

OBJECTIVES: Tocilizumab has been increasingly reported as an alternative therapeutic agent in the management of Behçet's syndrome (BS) and it has been mostly tried in BS patients with neurological and eye involvement. As therapeutic responses to each drug may vary across different types of BS involvement, we aimed to report seven patients with large vessel involvement treated with tocilizumab. METHODS: We enrolled seven BS patients with vascular involvement who were given tocilizumab at the Behçet's Disease Research Centre in Istanbul University-Cerrahpasa between 2000 and 2022. Demographic information, BS features, types of vascular involvement, previous and concomitant medications, C-reactive protein (CRP) levels, imaging modality results, and outcomes were documented from the patients' medical records. RESULTS: Within a median of 6 months after the initiation of tocilizumab, 5 patients experienced vascular relapses. These relapses included the emergence of new bilateral pulmonary artery aneurysms, a new pulmonary artery thrombus, parenchymal lung involvement, deep vein thrombosis in the lower extremity, and pseudotumor cerebri in one patient each. CRP levels were normal in 4 of the 5 patients at the time of vascular relapse. One of these 5 patients and another patient with aortitis had an exacerbation of mucocutaneous symptoms. In the last patient, venous ulcers did not respond to tocilizumab and were complicated with infection. CONCLUSIONS: Tocilizumab could potentially exacerbate vascular manifestations, similar to what is observed with mucocutaneous lesions in BS patients. Furthermore, CRP levels appear to be ineffective in monitoring these patients.

HLA-B gene methylation and expression in Behçet's syndrome: a potential role of epigenetics in the pathogenesis.

OBJECTIVES: The HLA-B51 locus has the strongest association with Behçet's syndrome (BS). The presence of a CpG island in the HLA-B gene led us to examine the role of epigenetic regulation in BS. METHODS: HLA-B51 genotyping was performed via sequence-specific PCR in 15 index familial BS cases, 17 affected relatives, 26 unaffected relatives, 46 sporadic BS cases, and 41 healthy controls. HLA-B methylation level was determined using the Zymo OneStep qMethyl kit, and HLA-B51 mRNA level was assessed by quantitative real-time PCR in 14 index familial BS cases, 15 affected relatives, 15 unaffected relatives, 11 sporadic BS cases, and 10 healthy controls. RESULTS: HLA-B51 carrier ratio was 13/15 in index familial cases, 13/17 in affected relatives, 22/26 in unaffected relatives, 8/25 in healthy controls, and 35/47 in sporadic BS cases. HLA-B51 expression level in HLA-B51+ BS cases was 2.2-fold higher than in their unaffected relatives (p=0.0149) and 1.3-fold higher than in healthy controls (p=0.0188), while sporadic BS cases had a 2.7-fold higher level than healthy controls (p=0.0487). HLA-B promoter methylation was significantly lower in HLA-B51+ familial BS cases than in unaffected relatives (0.4-fold, p=0.01), affected relatives (0.36-fold, p=0.0219), and healthy controls (0.34-fold, p=0.0371) and slightly lower in HLA-B51+ sporadic BS cases than in healthy controls (0.71-fold, p=0.2347). There was an inverse correlation between HLA-B promoter methylation and HLA-B51 expression in HLA-B51+ sporadic BS cases (p=0.0164). CONCLUSIONS: This study indicates epigenetic involvement associated with the HLA-B51 locus in BS, both in familial and sporadic cases. Further studies with larger sample sizes are needed to confirm our results.

Carotid artery ultrasonography and shear wave elastography in Takayasu's arteritis: a comparative analysis with diabetes mellitus.

OBJECTIVES: Takayasu's arteritis (TAK) is a chronic inflammatory large vessel vasculitis with a grim prognosis due to the excessive risk for cardiovascular (CV) diseases. Its diagnosis relies on radiographic imaging and its differentiation particularly from atherosclerosis could be challenging. Hypothesising that vascular morphology observed in TAK would be comparable to that found in type 2 diabetes mellitus (T2DM), a prototype for advanced atherosclerosis, we compared two disease groups using carotid artery B mode US and shear wave elastography (SWE). METHODS: A total of 72 patients with TAK (63F/9M; mean age: 42.7± 10.0 years) and 74 patients with T2DM (65F/9M; mean age: 50.2± 7.1 years) were studied. Intima-media thickness (IMT), outer diameter and arterial stiffness as assessed by SWE values were measured on the common carotid artery (CCA) and atherosclerotic plaques were recorded. Clinical characteristics, CV risk factors and previous history of CV diseases were determined. Framingham risk score was calculated. RESUULTS: Patients with TAK exhibited significantly lower atherosclerotic risk but higher systolic blood pressure (BP) levels compared to those with T2DM. The mean values of CCA IMT, outer diameter, and stiffness were significantly elevated among patients with TAK compared to those with T2DM. Carotid artery plaques were evenly distributed between the study groups, but their anatomical localisation and composition differed significantly. While coronary artery disease (CAD) was more prevalent among T2DM patients, cerebrovascular diseases were more frequent among TAK patients. CONCLUSIONS: Our study revealed distinctive vascular alterations and atherosclerotic changes when compared to advanced atherosclerosis associated with T2DM. Apart from these, higher levels of systolic BP and significantly different distribution of CV diseases between TAK and T2DM also suggest that TAK should be handled with distinct assessment strategies than that employed in conventional atherosclerotic conditions.

Hearing loss in Takayasu's arteritis.

OBJECTIVES: Neurosensory hearing loss is well-documented in chronic autoimmune conditions such as systemic lupus erythematosus (SLE). However, the literature lacks data on the prevalence and characteristics of hearing impairment in Takayasu's arteritis (TAK). In this cross-sectional study, our principal objective was to systematically assess the auditory function of individuals diagnosed with TAK, against SLE patients and healthy controls (HC). METHODS: Age and gender matched TAK and SLE patients followed up in a tertiary centre along with healthy controls were included in a two-phase study. In the first phase, a questionnaire on ENT symptoms was administered to the patient (TAK: n=104 and SLE: n= 151) and HC (n=174) groups. In the second phase, patients (TAK: n=53 and SLE: n=33) and HC (n=45) underwent audiometric tests. RESULTS: The questionnaire survey revealed that both TAK and SLE patients reported hearing loss (27.9%, 25.8%, 7.4%, p<0.001), tinnitus (49%, 35.8%, 13.8%, p<0.001) and vertigo (46.2%, 33.8%, 16.7%, p<0.001) at significantly higher rates than HC. Audiometry results indicated that both TAK (30.2%) and SLE patients (18.2%) had increased hearing loss compared to HC (8.9%), however, only TAK patients were found to have significantly increased risk in age adjusted logistic regression analysis (OR= 3.915, 95%CI: 1.179-12.998, p=0.026). Hearing loss was mainly neurosensory in all groups. TAK patients were affected at both low (<6000 Hz) and high (>6000 Hz) frequencies, whereas SLE patients were affected only at high frequencies. Hearing loss was significantly associated only with older age. No association was observed with the anatomical location of vascular involvement or history of stroke. CONCLUSIONS: Our study reveals an increased prevalence of hearing loss in TAK. Further research is crucial to uncover the underlying causes.

Role of Optical Coherence Tomography in Vasculitis-Associated Pulmonary Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Identifying and understanding the microstructural changes within the wall of the pulmonary artery (PA) is crucial for elucidating disease mechanisms and guiding treatment strategies. We assessed the utility of optical coherence tomography (OCT) in identifying such changes within segmental/subsegmental PAs and compared the morphological variations in WHO group 4 pulmonary hypertension associated with Behcet Disease (BD), Takayasu arteritis (TA) and chronic thromboembolic pulmonary hypertension (CTEPH). Idiopathic pulmonary arterial hypertension (IPAH) patients served as controls.Methods and Results: A total of 197 cross-sectional images were analyzed from 20 consecutive patients. BD patients exhibited lower %wall area and mean wall thickness (MWT) compared with CTEPH, TA and, IPAH patients. TA patients showed a notably higher %wall area, which was significant in IPAH and BD patients. Variations in %wall area measurements were observed across distinct cross-sectional segments of the PA within individual patients (22% in CTEPH, 19% in BD, 16% in TA, 23% in IPAH patients). Intravascular webs, bands, and thrombi were observed in BD and CTEPH patients. OCT provided clear delineation of vascular wall calcifications and adventitial vasa vasorum. No procedure-related complications were observed. CONCLUSIONS: PA involvement differs among the various etiologies of PH, with the PA being heterogeneously affected. OCT offers promise in elucidating microstructural vascular wall changes and providing insights into disease mechanisms and treatment effects.

Targeting complement dysregulation: eculizumab in scleroderma renal crisis management-a case-based review.

Systemic sclerosis (SSc) poses significant challenges in clinical management, especially when complicated by scleroderma renal crisis (SRC), a rare but life-threatening manifestation. Here, we report a 41-year-old female patient with SSc who presented with SRC and concurrent thrombotic microangiopathy. Her condition persisted despite conventional treatments such as plasma exchange and renin-angiotensin-aldosterone system blockade. In particular, treatment with eculizumab, a C5 complement inhibitor, led to a rapid improvement in platelet count, reduction in lactate dehydrogenase levels, and complete recovery of renal function. Genetic testing revealed a variant of unknown significance in the thrombomodulin (THBD) gene, which is associated with the complement system. This case highlights the complex interplay between complement dysregulation and SRC, and highlights the promising role of eculizumab in refractory cases. Further investigation of complement involvement and the efficacy of eculizumab in SRC warrants attention to improving therapeutic outcomes in this challenging condition.

Sexual dysfunction among female patients with rheumatic diseases.

To demonstrate the burden of sexual dysfunction (SD) among females with rheumatic diseases, we conducted a cross-sectional comparative study in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Behçet's syndrome (BS) along with suitable healthy controls (HCs). Age-matched female patients with SSc (n = 50), SLE (n = 49), and BS (n = 54), along with 52 female HCs were included in this study between April and October, 2021. Sociodemographic features were recorded, and psychometric tests, i.e., female sexual function index (FSFI), Beck depression inventory (BDI), body cathexis scale, and marital adjustment test (MAT) were performed. Scale scores were compared, and binary logistic regression was used to identify predictors for SD in the whole group. The total FSFI and body cathexis scores among the patient groups were significantly lower than those of the HCs (p < 0.001). Depression was significantly more frequent in the patient groups. MAT scores did not differ significantly between the study groups. Patients with SSc had the worst scores in each psychometric index, including MAT. Decreased body cathexis score [OR 0.974, 95% CI (0.957-0.991), p = 0.003] and low MAT score [OR 0.937, 95% CI (0.896-0.980), p = 0.005], and being diagnosed with SSc [OR 6.6, 95% CI (1.975-22.498), p = 0.002], SLE [OR 2.7, 95% CI (0.998-7.753), p = 0.050], and BS [OR 2.8, 95% CI (1.100-7.359), p = 0.031], were identified as independent predictors for SD. Body cathexis seems to be the most important independent predictor for SD, and the burden of SD appears heavier in patients with SSc, probably due to poor body image satisfaction.

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.

Behçet's syndrome: one year in review 2023.

This critical review of studies on Behçet's syndrome published during 2022 includes studies on epidemiology, patients' perspective, pathogenesis, diagnosis, clinical features and management. Studies on pathogenesis included potential biomarkers mostly related to macrophages, neutrophil and cytokine balance, new GWAS and polymorphism studies, and studies on miRNAs and long non-coding RNAs. Clinical studies showed that application of pneumococcal vaccine to the prick site increased the sensitivity and specificity of the pathergy test and the prevalence of AA amyloidosis had decreased over the years. Studies on management indicated that more data are needed to understand the effect of apremilast on BS manifestations other than oral ulcers, and new BS manifestations may develop during treatment with infliximab. Other biologics and Jak inhibitors might be an option for patients who are refractory to TNF-α inhibitors. Moreover, endovascular repair of arterial aneurysms might be an alternative to open surgery.

Mycophenolate mofetil may be an alternative for maintenance therapy of Behçet syndrome uveitis: a single-center retrospective analysis.

Experience with mycophenolate in uveitis due to Behçet syndrome (BS) is limited. Twelve patients with panuveitis or posterior uveitis who were started mycophenolate were included. Data on demographic characteristics, therapies, ocular attacks, and adverse events were extracted from patient charts. Seven patients with BS uveitis were prescribed mycophenolate for remission induction, of which 6 were refractory/intolerant to conventional immunosuppressives. Mycophenolate was combined with anti-TNFs in 3 patients, resulting in no further ocular attacks. Mycophenolate had to be stopped in the fourth patient due to adverse events. The remaining 3 patients continued to have ocular attacks and were switched to other agents without any drop in visual acuity. Among the 5 patients who were prescribed mycophenolate for maintenance, 2 were relapse free, but 3 experienced ocular attacks. One patient had an exacerbation of mucocutaneous lesions, and 2 experienced adverse events. Mycophenolate monotherapy may not be adequate for remission induction of refractory BS uveitis, but it can be a safe and effective alternative when combined with a biologic agent. It may also be an option for maintenance therapy.

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.

Behçet's syndrome: one year in review 2022.

This review highlights publications on different aspects of Behçet's syndrome (BS) that appeared in 2021 and provides a critical view. These publications include works on the epidemiology of BS across different continents, newly developed instruments to assess damage in BS, studies highlighting the immunopathogenesis, genetics and epigenetic factors, histopathology of the pathergy lesion, clinical and imaging aspects of vascular involvement, and safety and efficacy of therapeutic agents including tocilizumab, apremilast and direct oral anticoagulants.

Higher antibody responses after mRNA-based vaccine compared to inactivated vaccine against SARS-CoV-2 in Behcet's syndrome.

There are limited data about humoral response to vaccine in Behçet's syndrome (BS). We compared SARS-CoV-2 antibody response after two doses of inactivated (Sinovac/CoronaVac) or mRNA (Pfizer/BioNTech) vaccines in patients with BS and healthy controls (HCs). We studied 166 (92M/74F) patients with BS (mean age: 42.9 ± 9.6 years) and 165 (75M/90F) healthy controls (mean age: 42.4 ± 10.4 years), in a single-center cross-sectional design between April 2021 and October 2021. A total of 80 patients with BS and 89 HCs received two doses of CoronaVac, while 86 patients with BS and 76 HCs were vaccinated with BioNTech. All study subjects had a negative history for COVID-19. Serum samples were collected at least 21 days after the second dose of the vaccine. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. We found that the great majority in both patient and HC groups had detectable antibodies after either CoronaVac (96.3% vs 100%) or BioNTech (98.8% vs 100%). Among those vaccinated with CoronaVac, BS patients had significantly lower median (IQR) titers compared to HCs [36.5 (12.5-128.5) vs 102 (59-180), p < 0.001]. On the other hand, antibody titers did not differ among patients with BS and HCs who were vaccinated with BioNTech [1648.5 (527.0-3693.8) vs 1516.0 (836.3-2599.5), p = 0.512). Among different treatment regimen subgroups in both vaccine groups, those who were using anti-TNF-based treatment had the lowest antibody titers. However, the difference was statistically significant only among those vaccinated with CoronaVac. Among patients vaccinated with BioNTech, there was no statistically significant difference between different treatment regimen groups. Compared to inactivated COVID-19 vaccine, mRNA-based vaccine elicited higher antibody titers among BS patients. Only in the CoronaVac group, patients especially those using anti-TNF agents were found to have low titers compared to healthy subjects. BS patients vaccinated with BioNTech were found to have similar seroconversion rates and antibody levels compared to healthy controls. Further studies should assess whether the low antibody titers are associated with diminished protection against COVID-19 in both vaccine groups.

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.