Anti-interleukin-1 treatment among patients with familial Mediterranean fever resistant to colchicine treatment. Retrospective analysis.

BACKGROUND: Up to 5% of familial Mediterranean fever (FMF) cases are unresponsive to colchicine, through resistance, side effects and toxicity. Anakinra is an alternative treatment for FMF patients whose disease remains uncontrolled with colchicine. We aimed to evaluate anti-interleukin-1 treatment regarding clinical findings, laboratory parameters and quality of life (QoL) among FMF patients presenting resistance and toxicity towards colchicine. DESIGN AND SETTING: Descriptive observational study at the rheumatology clinic, Adnan Menderes University Medical School, Aydin, Turkey. METHODS: Among the patients included, age, sex, MEFV genotypes, acute-phase reactants, hepatic/renal function tests, average colchicine dose, disease duration, attack frequency, attack duration, disease severity, proteinuria, amyloidosis and QoL were evaluated. Colchicine resistance was defined as > 6 typical episodes/year or > 3 per 4-6 months. Kolmogorov-Smirnov, Friedman and two-way analysis of variance tests were used for statistical analyses. RESULTS: Between 2015 and 2017, 14 FMF patients receiving anakinra were enrolled. The mean colchicine dose was 1.7 ± 0.3 mg/day before use of anakinra. Ten patients were attack-free after treatment, while three showed reductions of at least 50% in attack frequency, attack duration and disease severity. Proteinuria levels in all patients with renal amyloidosis decreased after treatment. QoL among patients with renal amyloidosis differed significantly from QoL among non-amyloidosis patients. Mean visual analogue scale scores significantly improved in both groups after use of anakinra. CONCLUSIONS: Use of anakinra reduced attack frequency and proteinuria and acute-phase reactant levels, and improved QoL, with only a few uncomplicated side effects among colchicine-resistant or intolerant FMF patients. Injection-site reactions of severity insufficient to require discontinuation of treatment were seen.

Relationship between bone mineral density and anti-citrullinated protein antibody and rheumatoid factor in patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is one of the causes of osteoporosis, and it leads to systemic bone loss. The anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) are associated with local and systemic low bone mineral density and osteoclast-mediated bone resorption independently of inflammation in patients with RA. In this article, we aimed to evaluate the relationship between the ACPA, RF, and systemic bone mineral density in patients with RA. METHODS: Ninety-three patients (6 male, 87 female) with RA were included in the study. The disease activity score 28-erythrocyte sedimentation rate and titers of RF, ACPA, and bone mineral density of the total hip, femoral neck, and lumbar areas were evaluated. The independent samples t-test, Mann-Whitney U-test, Spearman's correlation, and multivariable regression analysis were used for the statistical analysis. RESULTS: The RF and ACPA were positive in 40.9% and 48.4% of patients with RA, respectively. Disease activity was negatively correlated with the T- and Z-scores. The T- and Z-scores were lower in the seropositive group than in the seronegative group. The ACPA was negatively correlated with the T- and Z-scores of the femoral neck. There was a significant difference for the Z-score of the femoral neck in patients with ACPA and RF-positive patients compared to seronegative patients with RA. CONCLUSION: A low bone mineral density, especially in the femoral neck, is associated with the presence of ACPA and RF. It would be a more appropriate approach to carefully monitor osteoporosis in seropositive RA patients.

Anti-interleukin-1 treatment among patients with familial Mediterranean fever resistant to colchicine treatment. Retrospective analysis

ABSTRACT BACKGROUND: Up to 5% of familial Mediterranean fever (FMF) cases are unresponsive to colchicine, through resistance, side effects and toxicity. Anakinra is an alternative treatment for FMF patients whose disease remains uncontrolled with colchicine. We aimed to evaluate anti-interleukin-1 treatment regarding clinical findings, laboratory parameters and quality of life (QoL) among FMF patients presenting resistance and toxicity towards colchicine. DESIGN AND SETTING: Descriptive observational study at the rheumatology clinic, Adnan Menderes University Medical School, Aydın, Turkey. METHODS: Among the patients included, age, sex, MEFV genotypes, acute-phase reactants, hepatic/renal function tests, average colchicine dose, disease duration, attack frequency, attack duration, disease severity, proteinuria, amyloidosis and QoL were evaluated. Colchicine resistance was defined as > 6 typical episodes/year or > 3 per 4-6 months. Kolmogorov-Smirnov, Friedman and two-way analysis of variance tests were used for statistical analyses. RESULTS: Between 2015 and 2017, 14 FMF patients receiving anakinra were enrolled. The mean colchicine dose was 1.7 ± 0.3 mg/day before use of anakinra. Ten patients were attack-free after treatment, while three showed reductions of at least 50% in attack frequency, attack duration and disease severity. Proteinuria levels in all patients with renal amyloidosis decreased after treatment. QoL among patients with renal amyloidosis differed significantly from QoL among non-amyloidosis patients. Mean visual analogue scale scores significantly improved in both groups after use of anakinra. CONCLUSIONS: Use of anakinra reduced attack frequency and proteinuria and acute-phase reactant levels, and improved QoL, with only a few uncomplicated side effects among colchicine-resistant or intolerant FMF patients. Injection-site reactions of severity insufficient to require discontinuation of treatment were seen.

Relationship between neutrophil-lymphocyte, platelet-lymphocyte ratio and disease activity in rheumatoid arthritis treated with rituximab.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may be used as indicators of inflammatory markers and disease activity due to inflammatory changes in neutrophils, platelets and lymphocytes. Our aim is to investigate the relationship between NLR, PLR ratio and disease activity in RA patients treated with rituximab. METHODS: Thirty-eight patients (8 male, 30 female, mean age 56.8 ± 11.8 years) diagnosed with RA and 30 healthy controls were included in the study. Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR), lymphocyte, neutrophil, platelet counts, ESR, C-reactive protein (CRP), PLR, and NLR were evaluated before and after rituximab in RA patients. The relationship between all parameters was assessed by Pearson's correlation, Wilcoxon signed-rank, Mann-Whitney U and paired t tests. RESULTS: The levels of CRP, ESR, and DAS28-ESR decreased significantly at 6 months of rituximab treatment compared to pre-treatment. NLR and PLR ratios were higher in patients with RA than the control group. The median levels were 33.5 mm/hour, 5.7 mg/dL, and 3.7 respectively after 6 months of rituximab treatment. And, the levels were lower than baseline treatment. There was a significant correlation between the levels of DAS28-ESR and NLR, DAS28-ESR and PLR before and after treatment. CONCLUSIONS: The NLR and PLR were higher than healthy controls and correlated with DAS28-ESR in patients with RA. These parameters which are indicative of disease activity decrease with rituximab and correlate with disease activity at 6 months. The NLR and PLR may be useful indices to evaluate RA disease activity treated with rituximab.

Pustulotic Arthro-Osteitis (Sonozaki Syndrome): A Case Report and Review of Literature.

Pustulotic arthro-osteitis (PAO) is a rare chronic inflammatory disease, which has now been classified as a seronegative spondyloarthritis. The sternoclavicular and sternocostal joints, pelvis, vertebra, hip, and long bones are affected. Skin findings of the disease are accepted as a variant of pustular psoriasis, but some authors have suggested that palmoplantar pustulosis (PPP) is a different entity. The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome should be considered in the differential diagnosis. PAO differs from SAPHO by the absence of hyperostosis and the difference in skin manifestations. Here, we aimed to present a 34-year-old female patient with a diagnosis of PAO with typical skin findings and joint involvement.

The association between clinically suspect arthralgia and adipokines in obese patients.

OBJECTIVE: Obesity is a moderate low-grade chronic inflammatory condition. The cause of low-grade inflammation in obese patients who have clinically suspect arthralgia (CSA) may be the subject of debate in clinical practice. Our aim is to determine whether inflammation is associated with obesity or rheumatic disease, and the association between leptin, chemerin, visfatin and inflammatory markers in obese patients with/without musculoskeletal symptoms. METHODS: Seventy-four obese patients who admitted to our rheumatology clinic with CSA were enrolled. The control group consisted of 40 obese patients who have no rheumatic symptoms. Body mass index (BMI) was calculated in kg/m2 with body weight ratio to height squared, and obesity was defined as BMI 30 or above. Age, gender, BMI, waist and hip circumferences, waist-to-hip ratio (WHR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), leptin, chemerin, and visfatin were evaluated. The relationship between all parameters was assessed by Spearman correlation, Wilcoxon Signed-rank, and paired t-tests. RESULTS: There were no significant differences for age, gender, ESR and CRP between obese patients with CSA and control group. The mean TNF-α, IL-1ß, IL-6 concentrations were 60.8 pg/mL, 39.9 pg/ml, and 26.2% in obese patients with CSA, respectively. ESR, CRP, TNF-α, IL-6, and IL-1ß concentrations were higher in these patients compared to obese patients without any rheumatic symptoms. The mean WHR and waist circumference were 0.8±0.1 and 107.1±13.4 cm, respectively in patients with CSA. IL-6 correlated with WHR and waist circumference, positively. There were significant differences for adipokines such as chemerin, visfatin, but not for leptin between both group. Moreover, a significant correlation was found between pro-inflammatory cytokines and visfatin, chemerin. CONCLUSION: Visfatin and chemerin correlated with inflammation and may be useful indicators of undifferentiated inflammatory arthritis in obese patients with CSA.

Tumor-Associated Antigens in Rheumatoid Arthritis Interstitial Lung Disease or Malignancy?

OBJECTIVES: This study aims to evaluate the serum tumor-associated antigen levels and the possible association between these markers and interstitial lung disease (ILD) or malignancy in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: The study included 83 RA patients (20 males, 63 females; mean age 59.3±12.1 years; range 25 to 83 years), 43 with ILD (13 males, 30 females; mean age 60.1±11.5 years; range 25 to 83 years) and 40 without ILD (7 males, 33 females; mean age 58.5±12.7 years; range 28 to 78 years). Clinical symptoms, pulmonary function test, chest X-ray, and high-resolution computed tomography were used for the diagnosis of ILD. Age, sex, history of smoking, acute-phase reactants, rheumatoid factor, anti-cyclic citrullinated peptide, carcinoembryonic antigen, cancer antigen (CA) 15-3, CA 125, and CA 19-9 were evaluated. The relationship between parameters in RA patients with/without ILD was assessed by t-test and Mann-Whitney U test. RESULTS: Five RA patients (11.6%) with ILD had carcinoembryonic antigen levels above the upper limit. The numbers of RA-ILD patients with above the upper limit of CA 19-9, CA 15-3, and CA 125 levels were 10 (23.2%), 13 (30.2%), and five (11.6%), respectively. Rates of RA patients without ILD with tumor-associated antigens exceeding the upper limit were 15% for carcinoembryonic antigen, 2.5% for CA 19-9, 7.5% for CA 15-3, and 7.5% for CA 125. No evidence of any malignancy was detected by medical history, physical examination, and laboratory and imaging methods in patients who had high levels of serum tumor-associated antigen. CA 15-3 (p=0.001), CA 125 (p=0.040), and CA 19-9 (p=0.018) levels were statistically significantly different in RA patients with ILD compared to those without ILD. Rheumatoid factor, anti-cyclic citrullinated peptide, and tumor-associated antigens were higher in RA patients with ILD than those without ILD. CONCLUSION: There is a relationship between ILD and tumor marker levels in connective tissue diseases. Elevated tumor markers may not be associated with hidden tumor or malignancy in RA patients. These antigens may be used as predictive biomarkers particularly in RA patients with ILD.