Epidemiology of systemic vasculitis.

PURPOSE OF REVIEW: Epidemiology of vasculitides exhibit geographic variation and data from some parts of the world are still scarce. Increased recognition of these rare diseases and improvement in diagnosis and patient care may lead to changes in their epidemiology. In this review, we aimed to highlight the most recent work on the epidemiology of systemic vasculitis. RECENT FINDINGS: New data from countries where information on the epidemiology of giant cell arteritis, Takayasu arteritis and Behçet syndrome were limited have revealed that these conditions are not as rare as previously believed. The incidence rates during the coronavirus disease 2019 pandemic highlight the link between Kawasaki disease and respiratory pathogens. The use of different classification criteria hampers the comparison of true incidence and prevalence rates in antineutophil cytoplasmic antibody (ANCA)-associated vasculitis and its subtypes between geographies and over time. SUMMARY: Recent studies have highlighted the epidemiology of vasculitides in different parts of the world and changing trends. Standardization of study design and disease definitions is needed to improve the reliability and comparability of the results.

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.

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.

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.

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.

Disease and Treatment-Specific Complications of Behçet Syndrome.

PURPOSE OF REVIEW: We aimed to highlight disease-related and treatment-related complications of Behçet syndrome (BS) based on previous and recent studies and our own experience. RECENT FINDINGS: The Behçet's Disease Overall Damage Index is a newly developed instrument to assess damage in BS. Validation studies showed that damage is already present in some patients at diagnosis and continues to progress during the follow-up, mainly related to treatment complications. Nervous system and eye involvement are important causes of long-term disability. Cyclophosphamide seems to be associated with infertility and an increased risk of malignancies among BS patients, prompting the consideration of shortening the treatment duration. Flares in mucocutaneous manifestations have been reported with tocilizumab, and de novo BS manifestations with secukinumab therapy. Earlier diagnosis and treatment are essential to prevent disease-related damage in BS. Treatment-related complications seem to be the leading cause of damage during the disease course.

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.

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.

Takayasu arteritis.

PURPOSE OF REVIEW: The purpose of this review is to summarize the recent advances in Takayasu arteritis (TAK), mainly focusing on pathogenesis, imaging modalities, and management. RECENT FINDINGS: Three novel clusters based on angiographic findings were identified in the Indian cohort and replicated in the North American cohorts. Different new imaging modalities have been tried in the assessment of arterial inflammation with promising results. There is more evidence on the long-term use of tocilizumab, but relapses are common. In light of the recent findings on the pathogenesis of TAK, Janus kinase inhibitors seem to be promising. SUMMARY: Improvement in imaging modalities and in our understanding of the disease pathogenesis will allow us to better assess the disease activity and identify effective therapeutic agents.

Comparison of demographic and clinical characteristics of hospitalized COVID-19 patients with severe/critical illness in the first wave versus the second wave.

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65-157) vs. 87 mg/L (IQR: 39-140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.

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.

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.

Aortic involvement in relapsing polychondritis: case-based review.

Relapsing polychondritis is a systemic inflammatory disease that mainly affects ears, nose, eyes, joints, and large airway. Relapsing polychondritis may also affect cardiac valves and large vessels with the aorta being most frequently involved. We conducted a systematic literature review to delineate the clinical characteristics, treatment, and outcome of relapsing polychondritis patients with aortic involvement including thoracic and abdominal aorta, aortic valve, and coronary arteries. 113 patients reported in 85 manuscripts were retrieved through the systematic literature search and references of the selected manuscripts. With the addition of a patient from our center, a total of 114 patients were included in the analyses. Aortic vessel involvement was the predominant type of involvement that was identified in 93 (82%) patients, while aortic valve involvement was identified in 41 patients (36%). The median age at aortic involvement was 37 years [IQR: 30-53] with a delay of 5 years [IQR: 1-8] between first relapsing polychondritis symptom and aortic involvement. Nineteen percent of the patients were asymptomatic at the time of aortic involvement diagnosis. The initial treatment was immunosuppressives in 41 patients (56%) and surgery in 28 patients (38%). The mortality ratio was 27% in a 24 month follow-up [IQR: 7.5-54 months]. Aortic dissection or rupture was the most frequent causes of mortality. Concomitant coronary artery involvement suggested a worse outcome. Aortic involvement in relapsing polychondritis is a mortal complication despite medical and surgical treatments. It may be asymptomatic in 19% of the patients which warrants the importance of screening.

The prognostic value of serum levels of a proliferation-inducing ligand (APRIL) in treatment-naïve patients with chronic lymphocytic leukemia

Background/aim: A proliferation-inducing ligand (APRIL) has been investigated as a prognostic marker in chronic lymphocytic leukemia (CLL) patients. However, there is no cut-off level for serum APRIL (sAPRIL) levels that predict time to treatment in CLL patients. Materials and methods: Between May and December 2012, 94 consecutive CLL patients and 25 healthy controls were assessed. sAPRIL levels were measured by ELISA. Demographic data and prognostic markers were obtained from the patients' files. Treatment-naïve patients were followed up for 6.5 years for any treatment need. Results: Patients were divided into 3 groups: Treatment-naïve (n = 47), chemotherapy receiving (n = 25), and those who had received chemotherapy previously (n = 22). There was no difference in median sAPRIL levels of patients who were receiving chemotherapy at the sampling time and the healthy controls, which indicates that sAPRIL levels might be influenced by treatment. For treatment-naïve patients, the best cut-off in predicting time to treatment was found at the sAPRIL level of 2.04 ng/mL, with 78% sensitivity and 63% specificity. Time to treatment was significantly earlier in the APRIL high group (n = 27) than in the APRIL low group (n = 20) (P = 0.010, log-rank test). Conclusion: sAPRIL, a simple, promising blood test which can be measured by ELISA, will likely obtain a place in the wide range of prognostic markers in CLL. Prospective large-scale studies are required to validate and confirm the feasibility of the proposed cut-off level of 2.04 ng/mL as a predictor of time to treatment in treatment-naïve CLL patients.

Long term follow-up of Behçet's syndrome patients treated with cyclophosphamide.

OBJECTIVES: CYC remains an important treatment option for Behçet's syndrome (BS) patients with life-threatening manifestations. However, adverse events may occur with CYC and this has led to increased use of biologic agents in other vasculitides. We investigated short and long term adverse events associated with CYC use in BS patients. METHODS: We conducted a retrospective chart review of all BS patients treated with CYC between 1972 and 2006. Patients were called in and a standard form was used for collecting demographic characteristics, indication for CYC, its cumulative dose and short term adverse events, defined as those causing discontinuation of CYC, hospitalization and/or death, long term adverse events, including infertility and malignancy, and outcome. RESULTS: Of 5790 BS patients, 198 (3.4%) had used at least one dose of CYC. Main indications were vascular or neurological involvement. After a median follow-up of 17 years, 52 (26%) patients had died, 113 (57%) could be contacted, and 33 (17%) were lost to follow-up. Vascular involvement was the leading cause of death (n = 27). Seventeen (9%) patients experienced short term adverse events with haemorrhagic cystitis being the most common. After a median follow-up of 25 years (interquartile range: 15-26 years), 17 malignancies occurred in 15 (8%) patients. Infertility was experienced by 26 (30%) patients. CONCLUSION: Long term adverse events such as malignancy and infertility were major problems in our BS patients treated with CYC. These results underline the need for safer treatment modalities that are at least as effective as CYC.

How to treat myelodysplastic syndrome with clinical features resembling Behçet syndrome: a case-based systematic review.

The association between myelodysplastic syndrome (MDS) and Behçet syndrome (BS) is recognized for over 25 years. High frequency of trisomy 8 and intestinal ulcers are striking features of this association. There are no recommendations for how these patients should be treated. A systematic literature review was performed in PubMed using the keyword combination "(((((intestinal) OR gastrointestinal) OR ulcer) OR Behcet*)) AND ((myelodysplastic syndrome) OR MDS)" in March 2019. Our aim was to gain insight regarding clinical responses to individual treatment modalities. A recent case was also presented and included in the analysis. Data from 41 articles reporting on a total of 53 patients carried adequate information to assess treatment responses. Glucocorticoids provided benefit in 23 of 43 patients. Azacitidine, decitabine, thalidomide, and cyclosporine contributed to a clinical improvement in 4/6, 2/3, 3/4, and 5/8 patients respectively. Hematopoietic stem cell transplantation was successful in 9 of 13 patients. With the use of TNF inhibitors, azathioprine, and mesalamine derivatives, clinical improvement was observed in 3/11, 0/4, and 6/18 patients respectively. Patients with MDS and BS-like features who are resistant to glucocorticoids have so far benefited more from treatment approaches directed at MDS, rather than the immunosuppressive agents used for BS.

Current surgical approaches in Takayasu's arteritis: a single-centre experience.

OBJECTIVES: We investigated cardiovascular surgical interventions in a group of patients with Takayasu's arteritis (TAK) diagnosed and followed by a single centre. METHODS: . Twenty patients with TAK (5 males, 15 females, mean current age: 38.1±10.7) who were operated for a broad spectrum of cardiovascular diseases ranging from coronary heart disease to coeliac stenosis or aneurysm between July 2008 and April 2016 were studied. One patient underwent operation related to aneurysm of ascending aorta and aortic insufficiency, 2 patients had operations for both coronary arteries originating from aortic arch, 6 patients for only arteries originating from aortic arch, 1 patient for both carotid and infra-inguinal artery, 5 patients for aorta-iliac or femoral revascularisation, 5 patients for renal artery and/or coeliac or superior mesenteric artery revascularisations. Three of these interventions were endarterectomy and patch plasty. RESULTS: The mean time between diagnosis and surgical intervention was 6.1±3.1 years (range: 3 months-12 years). A total of 4/32 (12.5%) grafts were occluded during the follow up period of mean 39.2±24.6 months. Secondary interventions like cross-femoral, or graft to superficial femoral artery bypasses were needed in 2 patients who underwent aorta-bifemoral bypasses to keep patency. There was no operative mortality. We did not observe any anastomotic aneurysm. One patient died due to graft infection 3 months after the operation. Stroke occurred in 2 patients who underwent re-vascularisations of the arteries originating from aortic arch. CONCLUSIONS: In our series, we have a relatively good midterm patency rates in patients with TAK and did not observe any anastomotic pseudoaneurysm. Stroke developed in 2 patients and mortality occurred in one patient due to the graft infection 3 months after the operation. In patients with limited carotid or aorta-iliac stenosis, chance for endarterectomy should be evaluated. Well-controlled disease activity with intensive medical treatment and multi-disciplinary approach could be associated with a favourable long-term outcome.

Takayasu's arteritis: associated inflammatory diseases.

OBJECTIVES: Case reports and series suggest that Takayasu's arteritis (TAK) can co-exist with other inflammatory disorders. We conducted a formal study to look specifically at the frequency of such inflammatory disorders in a large cohort of TAK followed by a single tertiary centre. METHODS: There were 238 patients registered with a diagnosis of TAK. Of these, 19 died, 18 were lost to follow-up and 3 did not wish to respond to our questionnaire. The remaining 198 (175 F/23 M) patients were called back at the outpatient clinic. A standardised form sought whether the patient was also diagnosed with inflammatory bowel disease (IBD), ankylosing spondylitis (AS), Behçet's syndrome (BS), autoimmune or any other inflammatory disorder. The presence of skin-mucosa lesions, inflammatory eye disease and inflammatory back pain were also specifically sought for. RESULTS: We identified 37 (19%) patients with inflammatory bowel disease (n=12, 6%), ankylosing spondylitis (n=15, 8%) or Behçet's syndrome (n=10, 5%). Thirteen (6.5%) patients had systemic or localised autoimmune disease and 9 (4.5%) miscellaneous inflammatory diseases. Among the 139 patients without any concomitant disease, inflammatory back pain (n=49, 35%) was the most common feature, followed by recurrent oral ulcer (n=20, 14%) erythema nodosum (n=17, 12%), arthritis (n=12, 9%) papulopustular lesions (n=8, 6%) and uveitis/scleritis (n=6, 4%). Only 64 patients (32%) did not have any concomitant disease/condition or specific clinical feature. CONCLUSIONS: TAK does co-occur with IBD, AS and less frequently with BS in about 1/5 of the patients, at least in a hospital setting. There is no clear temporal pattern. The high prevalence of inflammatory back pain in the dorsal spine in TAK needs further scrutiny.

Disease course and healthcare costs of a cohort of rheumatoid arthritis patients from Turkey.

The objective of the study is to assess the disease course and associated healthcare costs in a cohort of established rheumatoid arthritis (RA) patients in Turkey. The study cohort consisted of 75 RA patients from our outpatient clinic who took part in a previous multicenter study assessing RA-related healthcare costs 6 years ago. In March 2018, we attempted to re-evaluate these patients with the same questionnaire of the previous study enabling us to get information on medication use, comorbidities, and RA-related healthcare costs. We used RAPID-3 for assessing disease activity, HAQ-DI for functional status and EQ-5D for quality of life. Sixty-two (83%) patients were re-evaluated, seven (9.3%) had died and three (4%) were receiving palliative care following major cardiovascular events. Forty-seven (76%) patients had used at least one biologic agent during 79.1 ± 3.3 months after the previous study. At the last evaluation, 34 patients (55%) were on biologics, 22 (35%) were on csDMARDs and 6 (9.6%) were off RA treatment. The mean RAPID3 score (4.3 ± 1.6 SD) was similar to that of the previous study. HAQ-DI (0.69 ± 0.57 SD) and EQ-5D (0.68 ± 0.21 SD) scores showed significant improvement over time. Median direct costs (€2998) were higher than indirect costs (€304). Medication costs were high (€2958). Disease activity remained stable, while functional status and QoL had improved over time. Serious infections and cardiovascular disability are a concern. Medication costs are still the main determinant of RA-related healthcare costs.