Inflammatory rheumatic diseases developed after COVID-19 vaccination: presentation of a case series and review of the literature.

OBJECTIVE: An increasing number of new on-set autoimmune-inflammatory rheumatic diseases (AIRD) after COVID-19 vaccination has begun to be reported in the literature. In this article, we present our patients with new-onset AIRD after vaccination for COVID-19 and review the literature on the subject. PATIENTS AND METHODS: We investigated the clinical characteristics and laboratory parameters of previously described "newly developed AIRD in individuals recently vaccinated for COVID-19", in 22 cases vaccinated with one of the COVID-19 vaccines (BNT162b2 or CoronaVac) approved in our country. RESULTS: We collected 22 cases (14 female, 63.6%) that developed an AIRD after COVID-19 vaccination. Mean age was 53±14.4 (24-87) years. The interval between the last dose of vaccination and the development of the first complaint was 23.9±19.5 (4-90) days. CoronaVac was administered to four patients, and the BNT162b2 to 18 patients. AIRD-related symptoms developed in 12 patients after the first dose, in 8 patients after the second dose, and in two patients after the third dose. Twelve out of the 22 (54.5%) cases were diagnosed with rheumatoid arthritis, two with SLE, and the remaining eight patients each with leukocytoclastic vasculitis, Sjogren's syndrome, psoriatic arthritis, ankylosing spondylitis, systemic sclerosis, mixed connective tissue disease, eosinophilic granulomatosis with polyangiitis, and inflammatory myositis, respectively. Six patients had a history of documented antecedent COVID-19 infection. CONCLUSIONS: Autoimmune/inflammatory rheumatic diseases may develop after COVID-19 vaccinations. In the era of the COVID-19 pandemic, vaccination should be questioned carefully in newly diagnosed AIRD patients.

The validity and reliability of Systemic Lupus Erythematosus Quality of Life Questionnaire (L-QoL) in a Turkish population.

Background Systemic lupus erythematosus (SLE) may have a profound impact on quality of life. There is increasing interest in measuring quality of life in lupus patients. The purpose of this study was to investigate the validity and reliability of SLE Quality of Life Questionnaire (L-QoL) in Turkish SLE patients. Methods SLE according to 2012 Systemic Lupus International Collaborating Clinics Classification Criteria were recruited into the study. Demographic data, clinical parameters and disease activity measured with the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K); were noted. Nottingham Health Profile and Health Assessment Questionnaire were filled out in addition to the Turkish L-QoL (LQoL-TR). Internal consistency, test-retest reliability, and convergent and discriminant validity were evaluated. Results The mean age of participants was 43.55 ± 14.33 years and the mean disease duration was 89.8 ± 92.1 months. The patients filled out LQoL-TR in 2.5 min. Strong correlation of LQoL-TR with all subgroups of the Nottingham Health Profile and the Health Assessment Questionnaire were established showing the convergent validity. The highest correlation was demonstrated with emotional reactions (rho = 0.72) and sleep component (rho = 0.65) of the Nottingham Health Profile scale ( p < 0.0001). Its poor and not significant correlation with nonfunctional parameters (age, disease duration, perceived general health, SLEDAI-2K) showed its discriminative properties. LQoL-TR demonstrated good internal reliability with a Cronbach's α of 0.93 and test-retest reliability with intraclass correlation coefficient of 0.87. Conclusion The LQoL-TR is a practical and useful tool which demonstrates good validity and reliability.

Familial Mediterranean fever gene (MEFV) mutations and disease severity in systemic lupus erythematosus (SLE): implications for the role of the E148Q MEFV allele in inflammation.

OBJECTIVE: Observed low prevalence of SLE among familial Mediterranean fever (FMF) patients in several large cohorts suggests a possible protective effect of the MEFV mutations from SLE. In contrast, SLE patient carriers for the common MEFV mutations had rather complex disease expression with an increased frequency of febrile episodes and pleurisy and a decreased renal complication rate. Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of biopsy-proven SLE nephritis patients. MATERIAL AND METHOD: The prevalence of four MEFV gene mutations (M694V, M680I, V726A and E148Q) was investigated in 114 SLE patients and effect on disease severity was analyzed in patients with biopsy-proven SLE nephritis. RESULTS: None of the SLE patients fulfilled the revised Tel-Hashomer criteria. Fourteen of 114 SLE patients (12.2%) were found to carry at least one MEFV mutation. A single patient in the SLE-Nephritis group was compound heterozygous for M694V/M680I mutations and only one patient in the SLE-Mild group was homozygous for E148Q mutation. Carrier frequency was similar to controls in SLE patients (12.2 vs 18.8%, p = 0.34). After the exclusion of the less penetrant E148Q mutation, re-analysis revealed an association between exon 10 mutations and SLE nephritis (p = 0.050, odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.04-16.6). Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE = 20/186 vs. 3/114, p = 0.08) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis = 20/186 vs. 0/47, p = 0.016, OR = 11.69, 95% CI = 0.69-197.13). CONCLUSIONS: Carrier rate for the studied MEFV mutations was slightly lower in the SLE group, which is in agreement with previous observations that FMF may confer some protection from SLE. Exon 10 mutations were associated with SLE nephritis after the exclusion of the E148Q mutation. The significance of the E148Q as a disease-causing mutation is controversial, and whether E148Q substitution is a polymorphism generally affecting inflammatory pathways is not addressed in the current literature. In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation into its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.

Ankylosing spondylitis and a diagnostic dilemma: coccydynia.

OBJECTIVES: Coccydynia is defined as pain in or around the tail bone area. The most common cause of coccydynia is either a trauma such as a fall directly on to the coccyx or repetitive minor trauma. The etiology remains obscure in up to 30% of patients. The literature on the contribution of rheumatic diseases to coccydynia is scarce. Our objective was to investigate the prevalence of coccydynia in ankylosing spondylitis (AS) patients. METHODS: One hundred and seven consecutive patients with AS were evaluated for coccydynia were enrolled between January and November 2012 for a cross-sectional analysis. Seventy-four consecutive patients were followed for mechanical back pain as controls and the AS patients were interviewed for the presence of coccydynia. The data collected was evaluated on SPSS® version 11.5 and Microsoft Excel® Programmes. RESULTS: Prevalence of coccydynia in AS (38.3%) was significantly higher than the control group (p<0.0001) in both female and male AS patients (female AS vs. control=40.9% vs. 18.4%, p=0.015 and male AS vs. control=36.5% vs. 8.0%, p=0.005). Both genders were affected equally in the AS group whereas coccydynia was slightly more frequent in female patients in the control group. CONCLUSIONS: Coccydynia is a previously neglected symptom of AS and it is almost three times more common in AS than in non-specific chronic low back pain. Our observation may implicate that inflammatory diseases have a role in the etiology of coccydynia, especially in those without a history of recent or past trauma and coccydynia may be a factor associated with the severity of AS as well.

Active disease requiring TNF-alpha-antagonist therapy can be well discriminated with different ASDAS sets: a prospective, follow-up of disease activity assessment in ankylosing spondylitis.

OBJECTIVES: To evaluate the validity of different ASDAS sets to assess disease activity in ankylosing spondylitis (AS) in comparison to standard activity assessment tools in routine clinical setting and to determine the best cut-off values for deciding active disease requiring TNF-α antagonist therapy. METHODS: Two hundred consecutive AS patients (M/F:104/96) were enrolled. Mean (SD) age was 40.3 (11.7) and disease duration was 11 (8.5) years. Disease activity was assessed by four different ASDAS sets, BASDAI, patient and physicians' global assessments, ESR and CRP. The correlation between different parameters and ASDAS scores of patients requiring TNF-α antagonist therapy were determined. RESULTS: At the time of the assessment 18.5% of the patients were only having NSAIDs, 43% were receiving sulphasalazine and/or methotrexate and 38.5% were under TNF-α antagonists. After the evaluation, 36 (18%) patients were decided to require TNF-α antagonist therapy, 33 (16.5%) patients were started sulphasalazine or methotrexate or their dose increased and 131 (65.5%) patients were decided to be stable without any requirement for a change in therapy. The patients requiring new-TNFα antagonist therapy had significantly higher ASDAS values. The ROC curve analysis revealed best-cut off values for ASDAS sets (ASDAS A: 3.28, ASDAS B: 3.07, ASDAS C: 2.38 and ASDAS D: 3.1) When standardised mean differences were compared, ASDAS B was the best set within the others, but not significantly different from other ASDAS sets and standard assessment tools except acute-phase reactants. CONCLUSIONS: ASDAS sets perform well to discriminate TNF-α antagonist requirement in advanced AS patients. However BASDAI and patient's or physician's global assessments also had acceptable performances in our clinical setting.

Anti-Saccharomyces cerevisiae antibodies (ASCA) in spondyloarthropathies: a reassessment.

OBJECTIVES: Seronegative spondyloarthropathies, especially ankylosing spondylitis (AS), is shown to be associated with inflammatory bowel disease. Anti-Saccharomyces cerevisiae antibodies (ASCA) is a valid serological marker for Crohn's disease. Presence of ASCA is controversial in AS. In this study, we aimed to investigate the prevalence of ASCA in spondyloarthropathies and its relationship with disease activity and severity. METHODS: One hundred and seventy-five patients with AS, 47 patients with undifferentiated spondyloarthropathy (uSpA) and 103 healthy controls (HCs) were studied. All patients were questioned for demographic features and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores. Radiological damage is assessed by Bath Ankylosing Spondylitis Radiology Index (BASRI) and modified Stroke Ankylosing Spondylitis Spinal Score (mSASSS). ASCA levels were measured with standard ELISA kits. RESULTS: There was an overall increased prevalence of ASCA IgA in AS and uSpA compared with HCs (20.6 and 19.1% vs 5.8%, P = 0.0008 and P = 0.02, respectively). No association was observed between ASCA positivity and erythrocyte sedimentation rate, C-reactive protein levels and BASDAI scores. However, ASCA-positive patients had higher BASRI scores [median BASRI: 7 (2-12) vs 6 (2-12); P = 0.037]. Although not reaching significance, they also had reduced chest expansion and higher Bath Ankylosing Spondylitis Functional Index (BASFI) scores. ASCA-positive AS patients also required anti-tumour necrosis factor therapy more frequently (P = 0.006). CONCLUSIONS: ASCA IgA seems to be more prevalent in AS and uSpA. ASCA can also be a marker of radiological damage and a more severe course in AS.

PTPN22 gene polymorphism in Behçet's disease.

A functional single nucleotide polymorphism (SNP) of PTPN22 gene encoding the protein tyrosine phosphatase has been reported to be associated with autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus and type I diabetes. PTPN22 R620W polymorphism has a wide variation of allelic frequencies among different populations. This polymorphism is investigated in Turkish patients with Behçet's disease (BD), a systemic vasculitis with immune activation. DNA samples from 134 patients with BD and 177 healthy controls are genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism method for the SNP (rs2476601, A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with XcmI enzyme. The frequency of heterozygous genotype (AG) was 5.1% (9/177) in control group, whereas polymorphic allele was not present in the whole BD group (P = 0.012, OR 0.65, 95% confidence interval 0.0-1.1). Both the lower prevalence in the general population and the absence in BD show the limited role of PTPN22 polymorphism in the pathogenesis of autoimmunity in Turkey.

The investigation of sacroiliitis with different imaging techniques in spondyloarthropathies.

PURPOSE: The aim of this study was to compare the value of different imaging techniques in spondyloarthropathy (SpA) patients with inflammatory low back pain. PATIENTS AND METHODS: We evaluated 54 patients who fulfilled the European spondyloarthropathy classification criteria and had inflammatory low back pain. They were subdivided into two groups according to changes on plain radiography rated on a 0-4 scale according to modified New York criteria. Group A patients had at least grade-2 unilateral or bilateral changes in the sacroiliac (SI) joints, whereas group B included patients with radiologic changes not exceeding grade 0-1. Quantitative SI scintigraphy and magnetic resonance imaging (MRI) were performed to investigate the value of these techniques to the diagnosis of sacroiliitis, and the sacroiliac joint:sacrum uptake ratios were calculated. Scintiscanning was done in 80 healthy subjects to define the normal range. RESULTS: The sensitivities of plain radiography, quantitative SI scintigraphy, and MRI were 61%, 55%, and 89%, respectively, among the patients with SpA. MRI and quantitative SI scintigraphy detected sacroiliitis in 97% and 49% of group A, respectively. In group B, these results were 76% and 66%, respectively. CONCLUSION: Magnetic resonance imaging is the most sensitive method for detecting acute or chronic changes in SpA patients with histories of inflammatory low back pain and normal or indeterminate findings on plain radiographs.

MEFV mutations are increased in Behçet's disease (BD) and are associated with vascular involvement.

OBJECTIVE: A high prevalence of Behçet's disease (BD) among familial Mediterranean fever (FMF) patients has been described recently and a weak association of BD and certain MEFV gene mutations, originally linked to FMF, has been reported in an ethnically mixed population from France. We further investigated the presence of MEFV mutations in BD patients from Turkey, a country with a high prevalence of both disorders. METHODS: The frequencies of three FMF-related MEFV mutations (M694V, M680I and V726A) were investigated in BD patients (n = 57) by molecular genetic studies using a polymerase chain reaction with the ARMS method. All patients fulfilled the International Study Group Criteria for the diagnosis of BD and patients with FMF-like symptoms or a chronic inflammatory disease were excluded. RESULTS: Fifteen BD patients were found to carry one single MEFV mutation (26%), compared to 9.1% in the control group (p = 0.003, OR: 3.5, 95% CI: 1.6-7.6). Among 20 BD patients with vascular involvement, 11 (55%) had MEFV mutations compared to 4 patients (11%) in the non-vascular group (p = 0.001, OR: 10, 95% CI: 2.5-39.3). M694V was the dominant mutation in our study group (11 out of 15 patients with mutated alleles). Six out of 7 female patients with vascular involvement carried MEFV mutations in contrast to 5 out of 13 male patients (85.7% versus 38.4%, p = 0.07, OR: 0.1, 95% CI: 0.009-1.14). No association with other clinical manifestations was observed. CONCLUSION: MEFV mutations, originally linked to FMF, may act as a genetic susceptibility factor for other inflammatory disorders such as vascular BD.

Effects of simvastatin only or in combination with continuous combined hormone replacement therapy on serum lipid levels in hypercholesterolaemic post-menopausal women.

AIMS: To evaluate the effects of simvastatin only or combined with continuous hormone replacement therapy on the serum lipid profile in hypercholesterolaemic post-menopausal women. METHODS AND RESULTS: One hundred hypercholesterolaemic post-menopausal women were given either simvastatin 10 mg daily together with oestrogen 0.625 mg and medroxyprogesterone 2.5 mg daily (HRT+simvastatin group) (n:50) or simvastatin 10 mg daily (simvastatin only group) (n:50) in a prospective manner. Serum total, low density lipoprotein, and high density lipoprotein cholesterol and triglyceride levels were measured at baseline, at 3 and 6 months. The initial mean (+/-SD) cholesterol values were as follows for the HRT+simvastatin group and the simvastatin only group, respectively: total cholesterol 240. 0+/-28.0 and 248.9+/-28.2 mg x dl(-1); low density lipoprotein cholesterol 174.7+/-25.6 and 175.1+/-25.9 mg x dl(-1); high density lipoprotein cholesterol 37.2+/-5.0 and 39.9+/-7.3 mg x dl(-1). Compared with the baseline, total and low density lipoprotein cholesterol levels decreased; and high density lipoprotein cholesterol levels increased significantly at 3 and 6 months in both groups. However, the mean percent reduction in total cholesterol and low density lipoprotein cholesterol was significantly greater in the HRT+ simvastatin group compared with the simvastatin only group both at 3 months (12.3+/-7.0% vs 8.9+/-6.2%;P<0.01; and 19.0+/-10.6% vs 13.2+/-10.4%;P< 0.005, respectively) and at 6 months (14.6+/-7.7% vs 11.3+/-7.4%;P<0.05 and 23.3+/-9.7% vs 15.8+/-12.3%;P<0.005, respectively). The mean percent increase in serum high density lipoprotein cholesterol concentrations was also significantly greater in the HRT+simvastatin group compared with the simvastatin only group at both times (14.6+/-11.8% vs 9.8+/-11.8%;P<0.005, at 3 months, and 21.3+/-15.2% vs 11.1+/-12.5;P<0.005, at 6 months, respectively). Furthermore, significantly more patients in the HRT+simvastatin group than in the simvastatin only group attained their target treatment goals dictated by the National Cholesterol Education Program Adult Treatment Panel II Guidelines. Although the mean percent decrease in triglyceride levels was significantly greater in the HRT+simvastatin group at 3 months, the significance disappeared at 6 months. CONCLUSION: The combination of simvastatin and continuous combined hormone replacement therapy seems to be more effective than simvastatin only in the treatment of hypercholesterolaemia in post-menopausal women.

Elevated hepatic lipase activity and low levels of high density lipoprotein in a normotriglyceridemic, nonobese Turkish population.

Low levels of high density lipoprotein cholesterol (HDL-C) are associated with increased risk of coronary heart disease and, in the United States, are often associated with hypertriglyceridemia and obesity. In Turkey, low HDL-C levels are highly prevalent, 53% of men and 26% of women having HDL-C levels <35 mg/dl, in the absence of hypertriglyceridemia and obesity. In this study to investigate the cause of low HDL-C levels in Turks, various factors affecting HDL metabolism were assessed in normotriglyceridemic Turkish men and women living in Istanbul and in non-Turkish men and women living in San Francisco. Turkish men and women had significantly lower HDL-C levels than the San Francisco men and women, as well as markedly lower apolipoprotein A-I levels (25 and 39 mg/dl lower, respectively). In both Turkish and non-Turkish subjects, the mean body mass index was <27 kg/m2, the mean triglyceride level was <120 mg/dl, and the mean total cholesterol was 170-180 mg/dl. The mean hepatic triglyceride lipase activity was 21% and 31% higher in Turkish men and women, respectively, than in non-Turkish men and women, and remained higher even after subjects with a body mass index >50th percentile for men and women in the United States were excluded from the analysis. As no dietary or behavioral factors have been identified in the Turkish population that account for increased hepatic triglyceride lipase activity, the elevation most likely has a genetic basis. high density lipoprotein in a normotriglyceridemic, nonobese Turkish population.

Volatile anesthetics and agonist-induced contractions in porcine coronary artery smooth muscle and Ca2+ mobilization in cultured immortalized vascular smooth muscle cells.

BACKGROUND: These experiments addressed four specific questions. Do isoflurane and halothane (0.5-3.0% in the gas phase) inhibit contractions evoked in isolated porcine coronary artery rings (without endothelium) by the specific Ca2+ mobilizing agonists serotonin, endothelin-1, and F-? Are contractions evoked by phorbol-activated protein kinase C inhibited by the anesthetics? In a well-characterized vascular smooth muscle cell culture model (A7r5 and A10), do the anesthetics attenuate serotonin- and endothelin-induced Ca2+ mobilization? Do the anesthetics inhibit intracellular Ca2+ mobilization via facilitated cAMP formation? METHODS: Tension was measured in rings suspended in organ chambers. Apparent intracellular Ca2+ was estimated in cells using indo-1 and flow cytometry. Cyclic AMP was measured by radioimmunoassay. RESULTS: At the anesthetic concentrations examined, isoflurane attenuated contractions evoked by serotonin and F- but not those induced by endothelin-1 or phorbol dibutyrate. In cells, isoflurane 2% attenuated 3 x 10(-5) M serotonin-induced Ca2+ mobilization by about 26%, whereas Ca2+ responses evoked by endothelin 10(-8) M were more resistant to anesthetic inhibitory effect. Halothane attenuated contractions in rings evoked by serotonin, endothelin, and F- but lacked effect on phorbol-induced responses. In cells, halothane 2% inhibited Ca2+ mobilization induced by serotonin by about 43% and that induced by endothelin by about 31%. Neither anesthetic facilitated cAMP formation. CONCLUSIONS: Isoflurane and halothane variably attenuated contractions evoked by Ca2+ mobilizing agonists--by a cellular action beyond the receptor level--but did not inhibit phorbol activated protein kinase C. Serotonin- and endothelin-induced Ca2+ mobilization was inhibited by isoflurane and halothane--but the mechanism does not depend upon increased cAMP.