Current Rheumatology Reviews - Volume 15, Issue 2, 2019

Background: Sarcoidosis is a multisystem inflammatory disease with an etiology that is not clearly understood. Amongst the different organs that may be affected, the lungs are the most common. Musculoskeletal manifestations of the disease are uncommon. Objectives: They include arthropathy, bone lesions, or myopathy, all of which may occur as initial symptoms or develop during the course of the disease. Methods: Articular involvement my present as arthralgia or arthritis. Skeletal complications usually develop in the chronic state of the disease. Muscular disease is rare and usually asymptomatic. Appropriate imaging modalities including X-ray, MRI, FDG-PET/CT assist in the diagnosis of rheumatic sarcoidosis. However, biopsy is necessary for definite diagnosis. Result and Conclusion: In most cases of musculoskeletal involvement, NSAIDs and corticosteroids are sufficient for symptomatic management. For more resistant cases immunosuppressive drugs (i.e., methotrexate) and TNF- inhibitors are used. Our aim is to review various types of musculoskeletal involvement in sarcoidosis and their existing treatment options.

Background: Depression and anxiety are common neuropsychiatric complaints in patients with Systemic Lupus Erythematosus (SLE). While numerous studies have been performed to investigate the prevalence, impact, and associated factors of depression and anxiety, current literature presents mixed results. In particular, the prevalence of anxiety and depression varies substantially between studies due to methodological limitations, and heterogeneity in defining anxiety and depression, patient selection, and metrics used. Moreover, there is a lack of studies evaluating the validity, reliability, and interpretability of commonly used screening tools for depression and anxiety in SLE patients. Result and Conclusion: Further investigations should aim to reach a consensus surrounding the role of controversial associated factors in depression and anxiety of SLE patients, while also focusing on the identification of novel factors that have not yet been highlighted in the literature.

The pathological hallmarks of Systemic Sclerosis (SSc) constitute an inter-related triad of autoimmunity, vasculopathy and tissue remodeling. Many signaling mediators have been implicated in SSc pathology; most focusing on individual components of this pathogenic triad and current treatment paradigms tend to approach management of such as distinct entities. The present review shall examine the role of Vascular Endothelial Growth Factor (VEGF) in SSc pathogenesis. We shall outline potential mechanisms whereby differential Vascular Endothelial Growth Factor-A (VEGF-A) isoform expression (through conventional and alternative VEGF-A splicing,) may influence the relevant burden of vasculopathy and fibrosis offering novel insight into clinical heterogeneity and disease progression in SSc. Emerging therapeutic approaches targeting VEGF signaling pathways might play an important role in the management of SSc, and differential VEGF-A splice isoform expression may provide a tool for personalized medicine approaches to disease management.

Background: Knee Osteoarthritis (OA) is a disabling musculoskeletal condition among the elderly. Self-reported instability is one of the impairments associated with osteoarthritis. A complete understanding of the self-reported instability in knee OA is essential, to identify the best strategies for overcoming this impairment. The focus of this scoping review is to provide an overview of evidence supported information about the prevalence and other associated features of selfreported instability in Knee OA. A broad search of the database PubMed with keywords such as knee osteoarthritis and instability resulted in 1075 articles. After title abstract and full-text screening, 19 relevant articles are described in the review. Overall, there is less amount of published literature on this topic. Studies reported prevalence rates of more than 60% for self-reported instability in knee osteoarthritis, which causes functional deterioration and high fear of falls. The most probable causative factors for self-reported instability in knee OA were altered sensory mechanisms and decreased muscle strength. Conclusion: To conclude, self-reported knee instability in knee OA requires thorough evaluation and directed treatment with further studies providing rationalistic evidence-based management strategies. The current literature regarding self-reported knee instability is summarized, highlighting the research gaps.

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-kβ 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.

Background: Selenium is an essential trace element with fundamental effects on human biology. Trace elements deficiency is not an uncommon finding in autoimmune diseases. This deficiency may be a consequence of autoimmune diseases or may contribute to their etiology. With regard to evidence showing the association between selenium deficiency and generation of reactive oxygen species and subsequent inflammation, reviewing the role of selenium in collagen vascular diseases could help researchers to devise strategies for managing these diseases. Objective: The present study aimed to evaluate the role of selenium and autoimmune rheumatic diseases. Data Sources: PubMed, Scopus, Science Direct, and Google Scholar. Study Eligibility Criteria: All the studies on the use of selenium without any limitations in terms of the preparation method, administration route, or formulation process were included in the study. The exclusion criteria were: 1) Articles published in languages other than English, 2) Administration of chemical and hormonal drugs rather than selenium, 3) Investigation of the effects of selenium on the autoimmune problems in animal models, and 4) Insufficiency of the presented data or poor description of the applied methods. Furthermore, review articles, meta-analyses, expert opinions, editorial letters, case reports, consensus statements, and qualitative studies were excluded from the study. Data Extraction: In this systematic review, articles were evaluated through searching following keywords in combination with selenium: "autoimmune rheumatic diseases "or "scleroderma" or "systemic sclerosis" or "Behcet's disease" or "Sjögren syndrome" or "systemic lupus erythematosus" or "musculoskeletal diseases" or "rheumatoid arthritis" or "vasculitis" or "seronegative arthritis" or "antiphospholipid antibody syndrome". Results: Of 312 articles, 280 were excluded and 32 articles were entered in this study. Based on the majority of studies assessing selenium level in patients with collagen vascular diseases, lower selenium levels were observed in these patients. Moreover, the majority of articles showed an improvement in clinical symptoms of collagen vascular diseases compared to controls after the treatment of patients with different dosages of L-selenomethionine. Conclusion: A decrease in the serum level of selenium was noted in patients with autoimmune diseases, which may be a risk factor for inflammation and initiation of autoimmunity in these patients. A sufficient quantity of selenium has been shown to contribute to the management of complications of autoimmune diseases and even improved survival in patients with autoimmune diseases, which may be due to the anti-inflammatory effects of selenium. Since this issue is of clinical importance, it can be considered in potential nutrition interventions and have beneficial effects on some autoimmune diseases.

Objective: The present study was conducted to evaluate the efficacy of conventional TMJ imaging in depicting osseous changes in mandibular condyle and glenoid fossa in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) by comparing the finding against CT and with an objective that if conventional TMJ imaging modality can appreciate the osseous changes in RA and OA then what is the need for CT scan. Thus further reducing the patient’s radiation dose. Materials and Methods: A total of 70 patients (40 Rheumatoid Arthritis; 30 Osteoarthritis) were taken in the study aged between 40 - 60 years and divided in to age groups. Then according to clinical history they were divided according to being symptomatic and asymptomatic. Further radiographic examination was carried out. First the trans-cranial view was obtained (conventional view left and right TMJ) and subsequently a CT scan was obtained and the interpretation was carried out to note the osseous changes like erosion, flattening, sclerosis and osteophyte formation. Results: After comparison of the two radiographic methods it was observed that both were equally efficacious in evaluating the osseous changes in arthritic patients. Conclusion: Thus, it was concluded that when both the radiographic methods (conventional and CT scan) are equally efficacious in evaluating the osseous degenerative changes of TMJ in arthritis. Thus we should prefer the conventional technique so that the patient in not exposed to unnecessary radiation dosage.

Objective: To investigate the changes of serum Uric Acid (sUA), lipids and Cystatin C (CysC) in primary gout patients, and to explore the clinical significance in gout patients. Methods: sUA, CysC, high-sensitivity C-reactive Protein (hsCRP) and other biochemical parameters were measured in 326 gout patient and 210 healthy control subjects, blood cell counts were also detected. Clinical data were collected from gout patients. Results: sUA, CysC, hsCRP, Body Mass Index (BMI), White Blood Cell (WBC) counts, neutrophil Granulocyte (GR), Monocyte (Mo), Triglycerides (TG), plasma Total Cholesterol (TC), Very Low Density Lipoprotein (VLDL), apolipoprotein B100 (apoB100), Blood Glucose (GLU), serum Creatinine (sCr) and Urea Nitrogen (BUN) were significantly increased in gout patients compared with HC subjects (P<0.01, respectively), while lymphocyte counts and High Density Lipoprotein- Cholesterol (HDL-C) were significantly decreased in gout patients compared with HC subjects (P<0.01, respectively). Positive correlations were observed between concentration of sUA and age, TG, VLDL, sCr and CysC (P<0.05, respectively). While negative correlations were observed between the concentration of sUA and HDL-C(P<0.01). Besides, Positive correlations were observed between concentration of CysC and WBC, GR, Mo, apoA1, GLU, sCr, BUN, sUA, hsCRP (P<0.05, respectively). While negative correlations were observed between the concentration of CysC and TC, LDL-C(P<0.01, respectively). Conclusions: Blood lipid profile changes in gout patients. Gout patients who suffer from lipid metabolism disorder and vascular diseases might be associated with hyperuricemia, which leads to endothelial cell damage and vascular smooth muscle cell proliferation. CysC might be a marker for renal function damage and inflammation. Hyperuricemia is the risk factor of renal disorder in gout patients.

Background: Systemic Lupus Erythematosus (SLE) involves genetic, environmental, and hormonal alterations, including Vitamin D deficiency. Objective: To evaluate the association between vitamin D levels with anti-dsDNA, complement proteins, immunoglobulins levels and disease activity scores. Methods: A cross-sectional study was performed. The levels of 25-OH vitamin D were measured in patients older than 18 years with SLE according to ACR/97 [American College of Rheumatology 1997] from 2013 to 2015. The association was assessed by Mann-Whitney U and Kruskal Wallis tests for continuous variables, and by the Chi or Fisher exact test for the nominal variables. Results: Sixty-nine patients were included; 82% were women; the mean age was 38.5 years; 36.2% had low levels of vitamin D with higher consumption [p=0.006] of C4 and C3 complement proteins, plus higher levels of anti-dsDNA. Lower values of vitamin D were observed in patients with moderate to severe activity [p=0.0001] by SLEDAI [Systemic Lupus Erythematosus Activity Index] and general domain [p=0.039] and renal domain [p=0.009] by BILAG [British Isles Lupus Assessment Group] 2004. The mean vitamin D levels were higher in the group not receiving steroids when compared to those groups with dosages of 0.5-1mg/kg/d [p=0.048]. Conclusion: Lower levels of vitamin D are associated with greater complement protein consumption and higher disease activity rates. Therefore, it is important to evaluate vitamin D supplementation in patients with SLE as part of the treatment, especially when it includes the use of steroids.

Background: The presence of neuropatic pain (NeP) is common in subjects with established Rheumatoid Arthritis (RA), and it can influence the disease remission. These aspects have not been investigated in patients with Early Rheumatoid Arthritis (ERA). Objective: To investigate the effect of NeP on the achievement of remission in patients with ERA. Method: The study involved consecutive ERA patients with moderate or high disease activity. The painDETECT Questionnaire (PDQ), the 36-item Short Form Health Survey (SF-36), and the Euro- QoL-5 Dimensions (EQ-5D) were administered to all the patients, and their co-morbidity data were used to calculate their modified Rheumatic Disease Comorbidity Index (mRDCI). After six months’ follow-up, the presence or otherwise of NeP in each individual patient was calculated, and whether or not the Boolean remission criteria were satisfied. Results: The study was completed by 115 patients (76% females) whose PDQ scores indicated that 13% had probable NeP. At the end of the follow-up period, 25 patients (21.7%) met the Boolean remission criteria. Logistic regression analysis showed that baseline PDQ scores (p=0.0023) and the mRDCI (p=0.0054) were the strongest predictors of not being in Boolean remission. Only one of the 15 patients with concomitant NeP achieved Boolean remission. Conclusion: The presence of NeP may affect the achievement of remission in ERA patients. The PDQ can be a useful tool to measure central pain sensitisation in such patients.

Background: Amyloidosis is a life-threatening complication of Rheumatoid Arthritis (RA) that should be detected as early as possible to avoid its morbidity and mortality. Objective: To detect subclinical amyloidosis in RA patients without proteinuria and a disease duration more than 5 years. Patients: Eighty-six RA patients seen between October 2013 and August 2014 were recruited for the study. Those with 5 years disease duration were included in the study but those who had proteinuria, serum creatinine > 1.5 mg/dl, disease onset before the age of 16 years or improper specimens, were excluded, leaving 30 eligible patients (23 women, 7 men). The clinical, laboratory and imaging results and treatments were maintained for each patient. Abdominal Fat Aspiration Biopsy (AFAB) was performed on all 30 patients. Amyloid deposits were spotted by polarised light microscopy following Congo red staining. Informed consent was acquired from all patients. Clinical disease activity was scored according to DAS. ELISA measured serum amyloid A protein (SAA), CRP and RF. Results: AFAB stained positive for amyloid in 4 (13.3%) patients out of 30. The amyloid deposits were (1+) in 1 patient and (2+) in 3 patients. Longer RA duration correlated positively with amyloidosis (12.50 years versus 6.15years) (P < 0.001). Extra-articular manifestations were present in 50% of the amyloid patients and in 15.3% of the non-amyloid patients. This difference was significant (P < 0.01). DAS 28 score was higher in amyloid patients (P < 0.001). No difference was found between amyloid and non-amyloid patients regarding age, sex or deformities. SAA was significantly higher in amyloid patients (P < 0.001). However, haemoglobin levels were found to be significantly lower in amyloid patients (P < 0.001). Conclusion: The prevalence of subclinical amyloidosis by AFAB was found to be (13.3%). The use of AFAB should be encouraged, particularly in patients with longer disease duration and low haemoglobin level to confirm early detection of subclinical amyloidosis.

Background: Interpreting the structure in the wrist is complicated by the existence of multiple joints as well as variability in bone shapes and anatomical patterns. Previous studies have evaluated lunate and capitate shape in an attempt to understand functional anatomical patterns. Objective: The purpose of this study was to describe anatomical shapes and wrist patterns in normal wrist radiographs. We hypothesized that there is a significant relationship in the midcarpal joint with at least one consistent pattern of wrist anatomy. Methods: Seventy plain posteroanterior (PA) and lateral wrist radiographs were evaluated. These radiographs were part of a previously established normal database, had all been read by a radiologist as normal, and had undergone further examination by 2 hand surgeons for quality. Evaluation included: lunate and capitate shape (type 1 and 2 lunate shape according to the classification system by Viegas et al.), ulnar variance, radial inclination and height, and volar tilt. Results: A significant association was found between lunate and capitate shape using a dichotomal classification system for both lunate and capitate shapes (p=0.003). Type 1 wrists were defined as lunate type1and a spherical distal capitate. Type 2 wrists had a lunate type 2 and a flat distal capitate. No statistically significant associations were detected between these wrist types and measurements of the radiocarpal joint. Conclusion: There was a significant relationship between the bone shapes within the midcarpal joint. These were not related to radiocarpal anatomical shape. Further study is necessary to better describe the two types of wrist patterns that were defined and to understand their influence on wrist biomechanics and pathology.

Background: Scleroderma or systemic sclerosis (SSc) is a rare systemic autoimmune disease. Many conditions mimic the presentation of SSc, especially skin thickening and fibrosis. One of these conditions is scleredema, a rare collagen and mucin deposition disorder which was found to be associated with diabetes mellitus, streptococcal infection or monoclonal gammopathy. Case Presentation: A 55 years old female presented with insidious onset and progressive course of diffuse skin thickening of face, neck, arms, forearms, thighs, chest, back, and excluding both hands and feet of 6 years’ duration associated with arthralgia, dysphagia and dyspnea on exertion of 1- year duration. There was no history of Raynaud’s phenomenon. Erythrocyte sedimentation rate was 100 mm/1st h, autoantibodies for SSc were negative, nail fold capillaroscopy normal, pulmonary function tests showed restrictive pattern and high-resolution computed tomography showed interstitial lung fibrosis. Patient was not fulfilling the American collage of rheumatology/European League Against Rheumatism classification criteria for SSc. Skin biopsy was done and revealed histological appearance of scleredema. Investigations were done for disease association with scleredema. The patient was not diabetic, antistreptolysin O titer was normal, serum protein electrophoresis, immunofixation and bone marrow biopsy were done, and the patient was diagnosed as scleredema associated with immunoglobulin A kappa multiple myeloma. Treatment by combination of bortezomib, cyclophosphamide, and dexamethasone was started with marked clinical and hematological improvement. Conclusion: Many conditions mimic SSc including scleredema, which may be the initial presentation of multiple myeloma. Rheumatologists and dermatologists should be able to recognize these conditions to provide the suitable management and follow-up for these patients.