Current Rheumatology Reviews - Volume 15, Issue 4, 2019

Giant Cell Arteritis (GCA), or Horton’s Arteritis, is a chronic form of vasculitis of the large and medium vessels, especially involving the extracranial branches of the carotid arteries, in particular, the temporal artery, with the involvement of the axillary, femoral and iliac arteries too. Arterial wall inflammation leads to luminal occlusion and tissue ischemia, which is responsible for the clinical manifestations of the disease. A substantial number of patients affected by GCA present head and neck symptoms, including ocular, neurological and otorhinolaryngological manifestations. The aim of this article is to present pathogenesis, clinical aspects and treatment approaches of GCA manifestations.

Background: The process of antigen presentation to immune cells is an undeniable contributor to the pathogenesis of autoimmune diseases. Different studies have indicated several factors that are related to autoimmunity. Human Leukocyte Antigens (HLAs) are among such factors, which have a key role in autoimmunity because of their involvement in antigen presentation process. Methods: Relevant English language literature was searched and retrieved from Google Scholar search engine and PubMed database (1996-2018). The following keywords were used: "Human leukocyte antigen", "Behcet’s syndrome", "Rheumatoid arthritis", "Systemic lupus erythematosus", "Type 1 diabetes", "Celiac Disease" and "Autoimmunity". Results: There is a strong association between HLA alleles and autoimmune diseases. For instance, HLA-B alleles and Behcet’s syndrome are strongly correlated, and systemic lupus erythematosus and Type 1 diabetes are related to HLA-DQA1 and HLA-DQB1, respectively. Conclusion: Association between numerous HLA alleles and autoimmune diseases may justify and rationalize their use as biomarkers as well as possible diagnostic laboratory parameters.

Interstitial Lung Disease (ILD) is a well-known complication of rheumatoid arthritis (RA) which often results in significant morbidity and mortality. It is often diagnosed late in the disease process via descriptive criteria. Multiple subtypes of RA-ILD exist as defined by chest CT and histopathology. In the absence of formal natural history studies and definitive diagnostics, a conventional dogma has emerged that there are two major subtypes of RA-ILD (nonspecific interstitial pneumonia (NSIP) and Usual Interstitial Pneumonia (UIP)). These subtypes are based on clinical experience and correlation studies. However, recent animal model data are incongruous with established paradigms of RA-ILD and beg reassessment of the clinical evidence in order to better understand etiology, pathogenesis, prognosis, and response to therapy. To this end, here we: 1) review the literature on epidemiology, radiology, histopathology and clinical outcomes of the various RAILD subtypes, existing animal models, and current theories on RA-ILD pathogenesis; 2) highlight the major gaps in our knowledge; and 3) propose future research to test an emerging theory of RAILD that posits initial rheumatic lung inflammation in the form of NSIP-like pathology transforms mesenchymal cells to derive chimeric disease, and subsequently develops into frank UIP-like fibrosis in some RA patients. Elucidation of the pathogenesis of RA-ILD is critical for the development of effective interventions for RA-ILD.

Background: Osteoarthritis (OA) is a type of progressive rheumatoid disease, which leads to the degeneration of the articular cartilage, synovium, subchondral bone, tendons, and the surrounding ligaments.There are various treatments for knee OA, including pharmaceutical, nonpharmaceutical, and surgical treatments. Considering the chronic nature of the disease as well as the necessity for the long-term use of chemical medications, various side effects could occur that include gastrointestinal bleeding, hypertension, congestive heart failure, hyperkalemia, and kidney failure. Therefore, suitable treatments with fewer side effects should be recommended. Recent investigations suggest increased tendency in people to use Complementary and Alternative Medicine (CAM) for knee OA treatment. Objective: This systematic review aimed to assess the effectiveness and safety of herbal preparations for the treatment of OA. Methods: The searched databases were Cochrane, Scopus, and PubMed. All the selected papers pertained to randomized controlled trials until August 8, 2017 in English in which one or several specific herbs had been used in knee OA treatment. Results: We included 24 randomized trials (involving 2399 women and men). There were several different herbal medicines used within the included trials. Conclusion: The results show that the methods used in these trials may reduce symptoms and the extent of NSAID consumption and enhance the quality of life. Additional trials are suggested to investigate the safety and efficacy of herbs for the treatment of patients with OA.

Systemic Lupus Erythematosus (SLE) has a profound impact on quality of life. Objective: The objective of this study was to explore the quality of life among Egyptian SLE patients and to assess its relationships with demographic and clinical features. Methods: One hundred sixty-four SLE patients were recruited for this study. Demographic information; clinical parameters; disease activity, as evaluated by the systemic lupus erythematosus Disease Activity Index; and organ damage, as assessed by the systemic lupus international Collaborative Clinics/American College of Rheumatology Damage Index, were reported. Quality of life was assessed with a quality of life questionnaire specifically designed for patients with systemic lupus erythematosus; the questions are grouped in the following six domains: physical function, sociooccupational activities, symptoms, treatment, mood, and self-image. Higher values indicate poorer quality of life. Results: Of the 164 Egyptian SLE patients who completed the survey, 142 (86.6%) were women. The mean age of the participants was 31± 8 years, the mean systemic lupus erythematosus disease activity index score was 17 ± 11, the mean systemic lupus international collaborative clinics/ American College of Rheumatology Damage Index score was 0.9 ± 1.2, and the mean quality of life score was 18.23± 6.89. Strong correlations were found between the total quality of life score and the scores for each domain of the questionnaire separately and disease activity, neurological manifestations, renal manifestations and musculoskeletal manifestations (p<0.0001); moreover, there was a significant positive correlation between the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index score and the total quality of life score (p=0.005). Conclusion: Poor quality of life among Egyptian SLE patients and disease activity are strongly related to impaired lifestyles in these patients.

Introduction: The definition of remission in Rheumatoid Arthritis (RA) is still difficult to determine. An ultrasound of the hands may be important in helping confirm clinical remission. Objective: This study’s aim was to evaluate the interest in using an ultrasound of the hands to confirm clinical remission, as well as comparing the various remission scores (DAS 28 VS, DAS 28 CRP, and SDAI) and the ultrasound data, in order to deduce the most accurate score to confirm this remission. Methods: In this prospective monocentric study, we studied patients with rheumatoid arthritis in clinical remission, according to DAS 28 VS, for at least 3 months without corticosteroid therapy. An ultrasound mode B / Doppler of the hands was taken by an experienced rheumatologist, involving 22 joints: wrists, Metacarpophalangeal (MCP) joints and proximal interphalangeal joints (PPI) bilaterally. Results: Fifty-one patients were included. They were classified in remission according to DAS 28 VS as well as DAS 28 CRP, whereas the remission according to SDAI was achieved in 66.7% of our patients. Synovial hypertrophy and power Doppler were present in respectively 65% and 25% of the patients. SDAI was the most accurate score to confirm RA remission (p < 0.003). Conclusion: SDAI appears to be the most appropriate score for the definition of remission in rheumatoid arthritis, but despite the use of the latter, ultrasound synovitis may still be present. Further work deserves to be done to clarify the value of ultrasound evaluation in the definition of RA remission.

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objectives: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

Background: As a multisystem autoimmune disease, Systemic Lupus Erythematosus (SLE) mainly affects women during reproductive age. This retrospective study was designed to investigate the fetal and maternal outcomes of Iranian women with SLE. Methods: Clinical and laboratory records of 60 pregnancies in 55 SLE patients who attended Hafez hospital, a tertiary referral center for high risk pregnancies and SLE patients affiliated with Shiraz University of Medical Science, were reviewed during April 2012 and March 2016. Results: The mean age of the patients was 29.28±4.6 years and mean disease duration was 5.09±4.2 years. Live birth rate was 83.3% after exclusion of elective abortions. There were 50 live births, 3 neonatal deaths, 3 spontaneous abortions and 7 stillbirths. 9 (15%) women developed preeclampsia and there was 1 (1.6%) case of HELLP syndrome. Lupus flares occurred in 27 (45%) patients during pregnancy. Preterm delivery occurred in 11.6% of pregnancies. Skin and joints were the most frequently affected organs. Patients with previous lupus nephritis (n=18) were associated with a higher risk of maternal complication, but fetal outcomes were similar in both groups. Cesarean rate was about 66%, mostly related to fetal indications (50%). Conclusion: Pregnancies in most women with pre-existing SLE can now be managed with successful results although presence of previous lupus nephritis is still a major risk factor for adverse maternal outcomes. In our study, fetal outcome was not different between patients with lupus nephritis compared with the patients without nephritis who were under treatments. Hence, to achieve favorable long-term results, we recommend regular multispecialty treatment approaches and progestational counseling for women with SLE.

Background: Many patients may have resistance to TNF-blockers. These drugs may induce neutralizing antibodies. The determination of the drug levels of TNF-blockers and Anti-Drug Antibodies (ADAs) against TNF-blockers may help to make clinical decisions. Objectives: The objective of this study was to associate and predict the drug levels of TNFblockers and ADAs in relation to disease activity in patients with Spondyloarthritis (SpA) and Rheumatoid Arthritis (RA). Methods: Cross-sectional study including patients fulfilling ASAS classification criteria for SpA and 2010 ACR-EULAR classification criteria for RA. These patients were treated with Adalimumab (ADA), Infliximab (IFX), and Etanercept (ETN). A bivariate analysis and the chi-square test were performed to evaluate the association of ADAs and drug levels with activity measures for SpA and RA. Five regression models analyzing drug levels, ADAs and disease activity measures using a multiple linear regression were performed in order to evaluate the prediction of ADAs and drug levels in relation to disease activity. Results: In SpA, IFX levels were associated with BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) (p=0.034). In RA, total drug levels were associated with DAS28-ESR (28 joint Disease activity Score-erythrocyte sedimentation rate), (p=0.008), DAS28-CRP (p=0.042), CDAI (Clinical Disease Activity Index) (p=0.047) and SDAI (Simple Disease activity index), (p=0.017). ADA levels had association with CDAI (p=0.002) and SDAI (p=0.002). IFX levels were associated with a DAS28-ESR (p=0.044), DAS28-CRP (p=0.022) and SDAI (p=0.022). ADAs were associated in SpA with BASDAI (p=0.027). Drug levels and ADAs did not predict disease activity in patients with SpA or RA. Conclusion: ADAs and drug levels of anti-TNF are associated with disease activity measures in patients with SpA and RA. However, they cannot predict clinical activity in these conditions.