Deficiency of adenosine deaminase 2: a challenging differential diagnosis of polyarteritis nodosa.

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disorder that was first described in 2014. It is a monogenic disease that is caused by loss-of-function variants in the ADA2 gene. Deficiency of adenosine deaminase 2 involves small- and medium-sized vessels and its clinical presentations include polyarteritis nodosa (PAN)-like features such as livedoid rash, early-onset stroke, hypogammaglobulinemia, hematological abnormalities, and systemic inflammation. Early diagnosis and treatment of DADA2 are crucial as the clinical features could be potentially life-threatening but might be treatable. The first-line treatment of choice in DADA2 is tumor necrosis factor α inhibitors. We aimed to provide an overview of the known pathophysiology, clinical presentations, diagnosis, and treatment of DADA2. A clearer knowledge of DADA2 may help to better diagnose, manage, and improve the clinical outcome of DADA2 patients. However, further studies are required to investigate the genotype-phenotype associations and exact pathophysiology of DADA2.

The impact of intra-sacroiliac joint methylprednisolone injection in the recovery of patients with spondyloarthropathy: a randomized controlled trial.

Introduction: Spondyloarthropathies are a group of chronic inflammatory diseases with specific clinical symptoms in rheumatic diseases. These patients suffer from pain in the joints. Physicians have tried several ways to decrease the pain in these patients. This study aimed to evaluate the effect of intra-sacroiliac joint methylprednisolone injection under the guidance of ultrasonography in spondyloarthropathy patients. Material and methods: In this randomized control trial we studied 60 patients with spondyloarthropathy (30 patients in the intervention group and 30 patients in the control group) from January 2020 to December 2020. The intervention group patients received 40 mg of intra-sacroiliac joint (SIJ) methylprednisolone injection at the beginning in addition to treatment with nonsteroidal anti-inflammatory drugs (inflammatory dose) and sulfasalazine (2 to 3 g/day). Patients' pain intensity and symptoms were assessed in the 2nd, 4th, 6th, and 8th weeks after glucocorticosteroid injection. Quantitative factors were compared by independent Student's t-test. Data analysis was performed using SPSS version 22.0 software. A p-value < 0.005 was considered significant. Results: There were no statistically significant differences in Visual Analogue Scale (VAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) criteria and finger-to-floor (FTF) levels in the intervention and control groups. There were significant differences in VAS and BASDAI criteria and FTF levels 2 weeks after the injection, and this difference remained the same until the end of the 8th week. The p-value was significant (p-value < 0.0001). Conclusions: The sacroiliac joint methylprednisolone injection approach with ultrasound guidance seems to be effective in pain relief and function, and patient satisfaction scores. Additionally using the guidance of ultrasonography in this approach is without the risk of radiation exposure.

Evaluation of CD4+/CD25+/high/CD127low/- Regulatory T Cells in Rheumatoid Arthritis Patients.

BACKGROUND: Rheumatoid arthritis (RA) is the most common rheumatoid disease of unknown etiology, determined by the articular cartilage destruction and bone loss. The hallmark of RA is the defect in immune tolerance. Regulatory T cells (Treg) play a critical role in the protection of peripheral tolerance. OBJECTIVE: To assess the percentage of CD4+/CD25+/high/CD127low/- Treg cells in peripheral blood of RA patients as compared with the healthy individuals. METHODS: The number of CD4+/CD25+/high/CD127low/- Treg cells was assessed by multicolor flow cytometry. The clinical disease activity of RA patients was determined by disease activity score 28 (DAS-28). The correlations of DAS-28 and erythrocyte sedimentation rate (ESR) with Treg cells were evaluated. RESULTS: The percentage of CD4+/CD25+/high/CD127low/- Treg cells in peripheral blood of RA patients significantly decreased as compared with the healthy individuals (P= 0.0002). The percentage of CD4+/CD25+/high/CD127low/- Treg cells negatively correlated with DAS-28 and ESR. CONCLUSION: This study concludes that the defect of Treg cells plays a vital role in the pathogenesis of this disease. Further studies are necessary to determine the role of Treg cells in the clinical course of rheumatoid arthritis.

Assessment of Treatment Safety and Quality of Life in Patients Receiving Etanercept Biosimilar for Autoimmune Arthritis (ASQA): A Multicenter Post-marketing Surveillance Study.

INTRODUCTION: Phase IV post-marketing surveillance studies are needed to evaluate the real-world safety and effectiveness of drug products. This study aimed to evaluate the safety and effectiveness of biosimilar etanercept (Altebrel, AryoGen Co., Iran) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). METHODS: In this open-label, multicenter, prospective, observational, post-marketing surveillance study, 583 patients received biosimilar etanercept 25 mg twice weekly or 50 mg once weekly and were followed up to 12 months. The primary objective was to evaluate the safety of biosimilar etanercept by documenting all the adverse events in the case report forms throughout the study period. The secondary objective was to evaluate the effectiveness of biosimilar etanercept in study patients, where longitudinal changes in health assessment questionnaire (HAQ), pain, and disease activity scores were assessed. RESULTS: A total of 583 patients (44.80 ± 13.09 years of age) were included and followed for an average of 8.12 ± 3.96 months. Among all patients, 172 (29.50%) experienced at least one adverse event, and injection site reaction, abdominal pain, and upper respiratory tract infection were the most common. HAQ scores decreased from 1.32 ± 0.77 at baseline to 0.81 ± 0.61 at 12 months in patients with RA/PsA (p < 0.01) and from 0.82 ± 0.58 at baseline to 0.66 ± 0.63 at 12 months in patients with AS (p = 0.18). Pain scores decreased from 6.49 ± 2.41 at baseline to 3.51 ± 2.39 at 12 months (p < 0.01). CONCLUSION: The results demonstrated the real-world safety and effectiveness of biosimilar etanercept in patients with RA, PsA, and AS. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04582084.

Prevalence of Toxoplasma gondii and Toxocara canis Among Myositis Patients in the Southwest of Iran.

INTRODUCTION: Parasitic myositis is caused by some parasites, such as Toxoplasma gondii) T. gondii (and Toxocara canis (T. canis). So, the aim of the study was to evaluate the prevalence T. gondii and T. canis in patients with myositis and healthy individuals. METHODS: A total of 108 samples were randomly selected as the control (54 healthy individuals) and test (54 myositis patients) groups. IgG and IgM antibodies (Ab) against T. gondii and IgG Ab against T. canis were measured by the enzyme-linked immunosorbent assay (ELISA). The detection of chronic and acute toxoplasmosis was performed by the ELISA IgG avidity. The presence of T. gondii in the blood was evaluated using the nested polymerase chain reaction (nested-PCR). RESULTS: Of 108, 33 (30.6%) cases were positive for IgG against T. gondii that 19 (35.2%) and 14 (25.9%) were observed in myositis patients and healthy individuals, respectively (P=0.296). Of 19 positive cases, 12 (63.2%) and 7 (36.8%) cases were detected as chronic and acute toxoplasmosis, respectively, while, all positive cases in the control group had chronic toxoplasmosis (P=0.013). One (1.9%) sample was positive for anti- T. gondii IgM and two (3.7%) samples were positive for IgG against T. canis by the ELISA that these positive cases were observed only in myositis patients (P=1.000 P=0.495, respectively). B1 T. gondii gene was amplified in 12 (63.2%) and 1 (7.1%) in myositis patients and healthy subjects (P=0.001). CONCLUSION: Our findings showed that there was a relatively high prevalence of acute toxoplasmosis in myositis patients in comparison with the control subjects in the Southwest of Iran.

Evaluating the Relationship Between Serum Level of Interleukin-6 and Rheumatoid Arthritis Severity and Disease Activity.

AIM: The aim of this study was to evaluate the relationship between Interleukin-6 (IL-6) serum level and the severity and activity of Rheumatoid Arthritis (RA). METHODS: In this cross-sectional study, 120 RA patients referred to the rheumatology clinic, the patients were diagnosed by rheumatologists according to ACR / EULAR 2010 criteria. Based on DAS28 score the patients were divided into 4 groups: Remission, Mild, Moderate and Severe. Each group contained 30 patients. Serum levels of Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), anti-Cyclic Citrullinated Peptide (anti-CCP) and Rheumatoid Factor (RF) and serum levels of IL-6, were measured. The relationship between these factors was measured and compared to the relationship between IL-6 and these factors, and the activity of the disease was evaluated based on DAS-28. RESULTS: This study showed that the serum level of IL-6 has a significant relationship with RA activity according to DAS-28 (P value <0.001). There is also a significant relationship between the ESR level, the number of painful joints, and the number of swollen joints, and the severity of the disease based on VAS. CONCLUSION: Generally the findings of this study indicate that serum level of IL-6 plays an important role in the severity and activity of RA disease and can be considered as a determining factor in evaluating the severity of RA in RA patients and it is a good guide for a step up or down of treatment.

Sensitivity and specificity assessment of DWI and ADC for the diagnosis of osteoporosis in postmenopausal patients.

OBJECTIVE: In this study, we prospectively investigated the diagnostic capability of diffusion-weighted magnetic resonance imaging (DWI) in assessing vertebral marrow changes in postmenopausal women with osteoporosis. MATERIALS AND METHODS: Sixty postmenopausal women (mean age 60.2 ± 6.11 years) underwent both dual-energy X-ray absorptiometry (DEXA) of the spine and MRI. Results were acquired from each patient's L2 to L4, for a total of 180 lumbar vertebrae. Based on bone mineral density (BMD) measurements obtained from DEXA, the vertebrae were divided into three groups as follows: normal (n = 52), osteopenic (n = 92), and osteoporotic (n = 36). DWI of the vertebral body was performed to assess the apparent diffusion coefficient (ADC). The ADC outcomes were compared among the three groups and correlated with BMD. RESULTS: ADC values (× 10-6 mm2/s) were significantly lower in the osteoporotic group (135.67 ± 44.10) in comparison to the normal group (561.85 ± 190.37) (P = 0.0001). The results showed a positive correlation between ADC and BMD values (r = 0.748, P = 0.0001). In receiver operating characteristic (ROC) analysis, the area under the curve for DWI was 0.912 (P = 0.001). A cut-off value of 400 mm2/s for the diagnosis of osteoporosis; had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 90.90%, 83.34%, 88.89%, 93.75%, and 76.93%, respectively. CONCLUSION: ADC values correlated positively with BMD in women. DWI can allow quantitative evaluation of bone marrow changes and osteoporosis in postmenopausal women.

A randomized, triple-blind, placebo-controlled clinical trial, evaluating the sesamin supplement effects on proteolytic enzymes, inflammatory markers, and clinical indices in women with rheumatoid arthritis.

Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200-mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases-3) and inflammatory biomarkers (hs-CRP, IL-1ß, IL-6, TNF-α, and cyclooxygenase-2) were measured with enzyme-linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases-3 decreased significantly in sesamin group. Also, serum levels of hs-CRP, TNF-α, and cyclooxygenase-2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.

Metformin one in a Million Efficient Medicines for Rheumatoid Arthritis Complications: Inflammation, Osteoblastogenesis, Cardiovascular Disease, Malignancies.

BACKGROUND: Rheumatoid arthritis is a widespread autoimmune disease and inflammation and bone destruction are two main issues in rheumatoid arthritis. OBJECTIVE: To discussing metformin effects on rheumatoid arthritis complications. METHODS: We conducted a narrative literature search including clinical trials, experimental studies on laboratory animals and cell lines. Our search covered Medline, PubMed and Google Scholar databases from 1999 until 2018. We used the terms" Metformin; Rheumatoid arthritis; Cardiovascular disease; Cancer; Osteoblastogenesis. DISCUSSION: Inflammatory pro-cytokines such as Interlukin-6 play important roles in T. helper 17 cell lineage differentiation. Interlukin-6 and Tumor Necrosis Factor-α activate Janus kinase receptors signal through signaling transducer and activator of transcription signaling pathway which plays important role in inflammation, bone destruction and cancer in rheumatoid arthritis patients. Interlukin-6 and Tumor Necrosis Factor-α synergistically activate signaling transducer and activator of transcription and Nuclear Factor-kß pathways and both cytokines increase the chance of cancer development in rheumatoid arthritis patients. Metformin is AMPK activators that can suppress mTOR, STAT3 and HIF-1 so AMPK activation plays important role in suppressing inflammation and osteoclastogenesis and decreasing cancer. CONCLUSION: Metformin effect on AMPK and mTOR pathways gives the capability to change Treg/Th17 balance and decrease Th17 differentiation and inflammation, osteoclastogenesis and cancers in RA patients. Metformin can be useful in protecting bones especially in first stages of RA and it can decrease inflammation, CVD and cancer in RA patients so Metformin beside DAMARs can be useful in increasing RA patients' life quality with less harm and cost.

The Relationship between Serum Level of Vitamin D3 and the Severity of New Onset Rheumatoid Arthritis Activity.

INTRODUCTION: Rheumatoid Arthritis (RA) is a systemic inflammatory disease which typically involves wrists, ankles, and finally every joint. Some of studies have reported a reverse relationship between the level of vitamin D and RA severity. AIM: The present study was carried out in order to check the potential relationship between the level of vitamin D and RA severity. MATERIALS AND METHODS: Ninety-three patients with RA with onset in recent three months (new onset RA), and 31 patients without RA were chosen as the control group. The patients all aged under 75 years and were diagnosed by a rheumatologist. The serum level of vitamin D was measured through blood test by chemiluminescence method by taking a blood sample of 5 cc. The relationship between the average level of vitamin D and disease severity was analyzed based on scoring scale of DAS28 in different groups with RA. The significant level of the above mentioned tests was set at p<0.05. Data analysis was carried out using SPSS 20.0. RESULTS: The results of the present study indicated that there was no significant relationship between the two groups in terms of the serum level of vitamin D. Since the subgroups of the patients are not homogenous in terms of age and based on disease severity, ANOVA and chi-square were used to modify this heterogeneity and compare vitamin D levels in patients based on disease severity. The results indicated that there was a significant difference between the three groups of patients in terms of disease severity, such that disease severity rose with a decrease in the serum level of vitamin D, (p-value <0.001). CONCLUSION: There was a significant reverse relationship between the serum level of vitamin D and RA severity based on Das Score 28. Therefore, it is recommended that if there is a lack of or insufficient amounts of this vitamin in the body, vitamin D supply needs to be optimized along with other standard medications in order to reduce the RA severity.

Effect of Atorvastatin on the Disease Activity and Severity of Rheumatoid Arthritis: Double-Blind Randomized Controlled Trial.

INTRODUCTION: HMG-CoA (3-hydroxy-3- methylglutary lcoenzyme A) reductase inhibitors (statins) have anti-inflammatory properties which may be particularly useful in rheumatoid arthritis to suppress disease activity and inflammatory factors. AIM: The purpose of this clinical trial was to determine anti-inflammatory properties of statins in rheumatoid arthritis. MATERIALS AND METHODS: Eighty Iranian patients with rheumatoid arthritis, aged between 19 to 75 years were recruited to take part in this randomized, double-blind placebo-controlled trial. Subjects were randomly allocated to two groups to take atorvastatin or placebo 40 mg daily as an adjunct to current disease-modifying anti-rheumatic drugs (DMARDs) treatment. Disease Activity Score-28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) & tender joint count (TJC) were assessed before and after three months intervention. RESULTS: Analysis was based on intention to treat. DAS28 significantly declined in the atorvastatin group in comparison with placebo (p< 0.001). SJC, TJC, CRP and ESR also were significantly dropped in the atorvastatin group in comparison with placebo. CONCLUSION: It can be concluded that atorvastatin can suppress RA activity and inflmmatory factors in RA patients for high to moderate grade of inflmmation.

The effect of pomegranate juice on clinical signs, matrix metalloproteinases and antioxidant status in patients with knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is one of the commonest forms of musculoskeletal disorders that leads to joint degeneration and has a major impact on patients' quality of life. Experimental and in vitro studies have suggested the protective roles of pomegranate juice (PJ) as a rich antioxidant source for mitigating cartilage inflammation. In this interventional study, 38 patients with knee OA were randomly divided into two groups: PJ or control for 6 weeks to evaluate the effect of this intervention on clinical signs, inflammation and antioxidant status. RESULTS: Significant decreases in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) total score (P = 0.01), stiffness score (P = 0.00) and physical function score (P = 0.01) were observed in PJ group after the intervention. The means of serum levels of matrix metalloproteinase (MMP)-13 was significantly decreased (P = 0.02) and glutathione peroxidase was increased in the intervention group compared with the control group after the study period (P = 0.02). CONCLUSIONS: According to the findings of this clinical trial, PJ consumption can improve physical function and stiffness, decrease breakdown cartilage enzymes and increase antioxidant status in patients with knee OA. © 2016 Society of Chemical Industry.

The Effect of Omega-3 Fatty Acids in Patients With Active Rheumatoid Arthritis Receiving DMARDs Therapy: Double-Blind Randomized Controlled Trial.

BACKGROUND: Rheumatoid arthritis is a symmetric peripheral polyarthritis of unknown etiology that, untreated or if unresponsive the therapy, typically leads to deformity and destruction of joints due to erosion of cartilage and bone. Omega-3 fatty acids have been shown to reduce morning stiffness, the number of tender joints and swollen joints in patients with rheumatoid arthritis. This study is designed for evaluation of omega-3 effects on disease activity and remission of rheumatoid arthritis in DMARDs treated patients and on weight changes and reduction of analgesic drugs consumption versus placebo. METHODS: Sixty patients with active rheumatoid arthritis (49 female and 11 male) underwent rheumatologist examination and disease activity score were calculated. Then patients were enrolled in this 12 week, double blind, randomized, placebo- controlled study. The patients in both groups continued their pre study standard treatment. The patients were visited every 4 weeks, 4 times and data were recorded. RESULTS: Significant improvement in the patient's global evaluation and in the physician's assessment of disease was observed in those taking omega-3. The proportions of patients who improved and of those who were able to reduce their concomitant analgesic medication were significantly greater with omega-3 consumption. There were no weight changes. CONCLUSION: Daily supplementation with omega-3 results has significant clinical benefit and may reduce the need for concomitant analgesic consumption without weight changes.