Current Rheumatology Reviews - Volume 15, Issue 1, 2019

The Treat-to-Target (T2T) principle has been advocated in a number of inflammatory and non-inflammatory medical illnesses. Tight control of disease activity has been shown to improve the outcome of rheumatoid arthritis and psoriatic arthritis as compared to the conventional approach. However, whether T2T can be applied to patients with lupus nephritis is still under emerging discussion. Treatment of lupus nephritis should target at inducing and maintaining remission of the kidney inflammation so as to preserve renal function and improve survival in the longterm. However, there is no universal agreement on the definition of remission or low disease activity state of nephritis, as well as the time points for switching of therapies. Moreover, despite the availability of objective parameters for monitoring such as proteinuria and urinary sediments, differentiation between ongoing activity and damage in some patients with persistent urinary abnormalities remains difficult without a renal biopsy. A large number of serum and urinary biomarkers have been tested in lupus nephritis but none of them have been validated for routine clinical use. In real life practice, therapeutic options for lupus nephritis are limited. As patients with lupus nephritis are more prone to infective complications, tight disease control with aggressive immunosuppressive therapies may have safety concern. Not until the feasibility, efficacy, safety and cost-effectiveness of T2T in lupus nephritis is confirmed by comparative trials, this approach should not be routinely recommended with the current treatment armamentarium and monitoring regimes.

Background: Behçet's Disease (BD) is characterized by numerous systemic manifestations and is known for its ability to affect both, arteries and the veins. However, the etiology of BD is only partially understood, and previous studies have demonstrated a role for genetic and epigenetic factors that contribute to disease pathophysiology. Several studies have implicated T cells and monocytes in the pathogenesis of BD especially when these cells are stimulated by heat shock proteins and streptococcal antigen. Furthermore, during disease exacerbations adenosine deaminase has an important role in activating lymphocyte proliferation, maturation, and differentiation in BD. This article presents a review of the published literature mainly from the last 20 years. The topics of main concern were the role of genetic and epigenetic factors as contributing factors in disease pathophysiology. Result and Conclusion: The authors used MeSH terms “Behçet's disease” with “pathophysiology,” “pathogenesis,” “genetic” or “epigenetic” to search the PubMed database. All the relevant studies identified were included and are described according to the aforementioned subheadings.

Background: In the last decade, we have come to better understand and manage the vasculitides. The classification of vasculitides has been revised. Genome- wide association studies and linkage analyses have been undertaken in hope of better understanding the pathogenesis of vasculitides. Comprehensive genetic studies have highlighted new pathways that may guide us in more targeted therapies. Description of the monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2), Haploinsufficiency of A20 (HA20), have introduced a new perspective to vasculopathies, and introduced alternative treatments for these diseases. Conclusion: In this review, the important discoveries in pathogenesis and consensus treatment recommendations from the past decade will be summarized.

Immune-mediated necrotizing myopathies (IMNMs) are a group of acquired autoimmune muscle disorders which are characterized by proximal muscle weakness, high levels of creatinine kinase, and myopathic findings on electromyogram (EMG). Muscle biopsy in IMNM differentiates it from the other subgroups of Idiopathic Inflammatory Myositis (IIM) by the presence of myofibre necrosis and prominent regeneration without substantial lymphocytic inflammatory infiltrates. Anti-signal recognition particle (SRP) and anti-3hydroxy-3 methylglutarylcoenzyme A reductase (HMGCR) autoantibodies were found in two-thirds of IMNM patients. In terms of treatment, IMNM is more resistant to conventional immunosuppressive treatment, therefore, other modalities of treatment such as Intravenous Immunoglobulin (IVIG) and rituximab are often required.

Current patient care in rheumatology relies primarily on a combination of traditional clinical assessment and standard laboratory tests. Investigators seek to discover new biomarkers and novel technologies to boost the research in this field. Mechanistic biomarkers such as cytokines, cell types, antibodies, signaling molecules, are rooted in the mechanism underlying the disease and can guide the clinical management of the disease. Conversely, descriptive biomarkers are byproducts of the disease process, depict the state of a disease but are not involved in its pathogenesis. In this article, we reviewed the field of common laboratory biomarkers in rheumatology, highlighting both their descriptive or mechanistic value as well as their role in clinical practice.

Background: Rheumatoid Arthritis (RA) is a chronic multi systemic disorder with the unclarified ethiopathology. Although several markers have been presented for recognition of RA, but none of them has been specific. New markers such as HLA typing and activity of Adenosine Deaminase (ADA) isoenzymes could be useful and specific. Objective: The aim of this study is to evaluate the pattern of ADA isoenzymes activity and HLA typing in both RA patients and healthy cases. Methods: Blood samples were collected from 55 RA patients and 60 healthy subjects, over a period of 6 months. Levels of C-reactive Protein (CRP), Rheumatoid Factor (RF) and ADA (ADA1, ADA2, total ADA) were measured using AVITEX kit and HITACHI Auto Analyzer. In addition, HLA-DRB1*01,*04 and *10 was detected using PCR-SSP. Results: ADA activity, particularly ADA2 level, was significantly higher among RA group (Pv <0.05). The concentrations of tADA in patients with RF and CRP positive were significantly higher (Pv <0.05). The allele prevalence of DRB1*01 was significantly higher in RA patients (13.1%) compared with control group (5.5%, respectively) (P <0.05, Bonferroni adjustment P<0.003). Calculated sensitivity and specificity for diagnostic tests in this study are listed as: CRP (75%), RF (80%), ADA (84%) and RF (90%), ADA (83%), CRP (72%), respectively. Conclusion: Increased tADA level and the frequency of DRB1*10 and *01 caused susceptibility to RA.

Background: Musculoskeletal Injury (MSKI), a common problem in both military and physically active civilian populations, has been suggested to result from both extrinsic and intrinsic factors. Objective: To investigate prospectively whether gait biomechanics, aerobic fitness levels and smoking status as well as entry military selection test variables can be used to predict MSKI development during recruit training. Methods: British infantry male recruits (n = 562) were selected for the study. Plantar pressure variables, smoking habit, aerobic fitness as measured by a 1.5 mile run time and initial military selection test (combination of fitness, Trainability score) were collected prior to commencement of infantry recruit training. Injury data were collected during the 26 week training period. Results: Incidence rate of MSKI over a 26 week training period was 41.28% (95 % CI: 37.28 - 45.40%). The injured group had a higher medial plantar pressure (p < 0.03), shorter time to peak heel rotation (p < 0.02), current smoking status (p < 0.001) and a slower 1.5 mile run time (p < 0.03). In contrast, there were no significant differences (p > 0.23) in lateral heel pressure, age, weight, height, BMI and military selection test. A logistic regression model predicted MSKI significantly (p= 0.03) with an accuracy of 34.50% of all MSK injury and 76.70% of the non-injured group with an overall accuracy of 69.50%. Conclusion: The logistic regression model combining the three risk factors was capable of predicting 34.5% of all MSKI. A specific biomechanical profile, slow 1.5 mile run time and current smoking status were identified as predictors of subsequent MSKI development. The proposed model could include evaluation of other potential risk factors and if validated then further enhance the specificity, sensitivity and applicability.

Background and Objectives: Concomitant neurologic manifestations and positive antiphospholipid antibodies (APAs) have been investigated in different manners. The present study aimed to investigate the association between neurologic manifestations and APAs. Materials and Methods: This cross-sectional descriptive study was conducted on 100 consecutive patients with selected neurological manifestations and at least one positive APAs within the age range of 20-50 years, referred to the Rheumatic Diseases Research Center from the Northeast Central Neurology Department of Iran during August 2012 to March 2014. Results: According to the results, 89% of the participants were persistently positive for APAs, including lupus anticoagulant, IgG anticardiolipin (aCL), IgM aCL, IgG β-2 glycoprotein 1 (β2- GP1), and IgM β2-GP1, observed in 16%, 41%, 42%, 17%, and 15% of the patients, respectively. Furthermore, 10% of the patients had concomitant lupus manifestations, and 37% of them showed anti-DNA. The IgG and IgM aCL were the most prevalent antibodies. Cerebral vascular accident (33%), retinal artery/vein occlusion (21%), and seizure (20%) were the most frequent presentations among the patients. In addition, the patients with multiple sclerosis (composing 3% of the subjects) were 100% positive for IgG and IgM aCL, as well as lupus anticoagulant. In addition, IgM anti-β2- GP1 was 100% positive in optic neuritis patients (composing 5% of the subjects) and was significantly associated with this neurologic disorder. IgM anti-β2-GP1 was also prevalent in the cases with Guillain-Barré syndrome. The most prevalent persistently positive antibody in the patients with cerebrovascular accident was IgM aCL. Conclusion: The findings of this study revealed some associations between the subtypes of APAs and incidence of neurologic disorders. However, the exact correlation between those symptoms and APAs needs further investigations.

Objective: To 1. implement flipped classroom rheumatology teaching for undergraduate education. 2. Evaluate outcomes of teaching using OSCE assessment and student perceived effectiveness and satisfaction survey. Methods: The flipped classroom education, 55-students, was conducted in 3 phases. Phase 1: Carried out in the students’ own time. Web links were emailed to assist exposure of the instructional part of the lesson online. Phase 2: Interactive in-class activity to share personal reflection and reinforce the key aspects. Phase 3: A simulated OSCE assessment. A cohort of 56-students, who were taught in the last educational year on the same topics according to standard teaching protocols, were included as control group. The clinical Outcomes were assessed using the scores of the OSCE examination model. Academic outcomes included the engagement measure as well as the students’ answers to perceived effectiveness and satisfaction survey. Results: There was no significant difference regarding demographics between the 2 students’ groups. There was a significant improvement (p< 0.05) in the flipped learning, in contrast to the control group, in terms of clinical (OSCE score) as well as communication skills. Student perceived effectiveness and satisfaction was significantly higher among the flipped learning (p< 0.05). Scores from the flipped learning cohort showed a state of engagement significantly higher than the control group (p< 0.01). Conclusion: Flipped learning implementation musculoskeletal learning successfully demonstrated a promising platform for using technology to make better use of the students' time, and for increasing their satisfaction. Active learning increases student engagement and can lead to improved retention of knowledge.

Background: Systemic sclerosis is a disorder of connective tissue with unknown cause, affecting the skin and internal organs, characterized by fibrotic changes. Objective: To determine the correlation between serum homocysteine level and interstitial lung involvement in systemic sclerosis. Materials and Methods: In this case – control study, 59 patients who fulfilled the ACR/EULAR classification criteria for systemic sclerosis and were referred to Hafez Hospital of Shiraz, Iran, were included as the case group. Fifty nine healthy subjects were involved as the control group. Patients were divided into two groups based on interstitial lung involvement and two subtypes, diffuse and limited type. Serum homocysteine, vitamin B12, and folate levels compared between the controls, and cases groups. Results: Of 59 case and control group, 53 (%89.8) were female and the mean age did not differ in both groups (P=0.929). Thirty five (%59.3) patients had interstitial lung involvement and 38(%64.4) had diffuse cutaneous systemic sclerosis. The mean serum homocysteine level was 13.9±6.3 μmol/L in the case and 13.7±9.2 μmol/L in the control group (P=0.86). The mean serum homocysteine level did not differ between the patients with and without interstitial lung involvement (P=0.52). The patients with lung involvement was older than those without lung involvement (P=0.004). Lung disease was more common in diffuse type (P=0.014). Conclusion: In our study, serum homocysteine level did not differ between the patients and healthy subjects. Also, there was no correlation between serum homocysteine level and lung involvement, but lung involvement was more common in older patients and also diffuse subtype.

Introduction: Gauzoma is an iatrogenic complication which occurs rarely due to surgical team negligence. Depending on the sterility of the retained tissue, it can lead to life threatening surgical complications or may remain asymptomatic for many years and be detected incidentally in imaging studies. It may be mistaken as tumors or aneurysms. Thus, high clinical suspicion is needed to diagnose them in patients with past history of operation. Reporting Case: A 35 years old woman, a known case of scleroderma underwent open-heart surgery 20 years before being diagnosed as scleroderma, presented by dyspnea especially on activity. The High Resolution CT (HRCT) for evaluating the interestial lung disease was done which detected a 7 cm (in greatest diameter) inflammatory mass in posterior aspect of left hemi thorax with a radiopaque thread in its center. True cut biopsy was done and sent for pathology, which revealed fragments of foreign body materials probably gauze pad fibers with cell debris and blood. Conclusion: Here, we highlighted the details in clinical history, CT findings, and pathology report of gauzoma in thorax of a scleroderma patient following previous open-heart surgery. It can be guidance for clinician to consider this diagnosis in patients with past history of operation.