Current Rheumatology Reviews - Volume 16, Issue 1, 2020

Introduction: Post-Streptococcal Reactive Arthritis (PSRA) is defined as inflammatory arthritis of ≥1 joint associated with a recent group A streptococcal infection in a patient who does not fulfill the Jones criteria for the diagnosis of Acute Rheumatic Fever (ARF). Methods: In this narrative review, we conducted a systematic search on MEDLINE, EMBASE, Cochrane Library and Google Scholar using the words poststreptococcal reactive arthritis. The search covered the time period between 1982 and 2016. The purpose of this review is to summarize the current state of knowledge of PSRA with respect to the definition, epidemiology, clinical presentation and treatment. We also summarize the key differences between PSRA, reactive arthritis (ReA) and ARF. Results: PSRA has a bimodal age distribution at ages 8-14 and 21-37 years with an almost equal male to female ratio. Clinically, it causes acute asymmetrical non-migratory polyarthritis, however, tenosynovitis and small joint arthritis may occur. This disease entity can be associated with extraarticular manifestations, including erythema nodosum, uveitis and glomerulonephritis. The frequency of HLA-B27 in PSRA does not differ from that of the normal population, which suggests that it is a separate entity from ReA. Involvement of the axial skeleton, including sacroiliitis, is uncommon in PSRA. PSRA tends to occur within 10 days of a group A streptococcal infection, as opposed to the 2 to 3 weeks delay for ARF. PSRA can be associated with prolonged or recurrent arthritis, in contrast to ARF, in which arthritis usually lasts a few days to 3 weeks. Treatment usually involves NSAIDs or corticosteroids. Conclusion: We summarize clinical features that help differentiate PSRA from ARF and ReA. First-line treatment options include NSAIDs and corticosteroids. Most cases resolve spontaneously within a few weeks, but some cases are recurrent or prolonged. There are no published randomized controlled trials of PSRA.

Synovial plicae are thickenings of the synovial knee membrane; they are very frequent and often asymptomatic. However, they can become symptomatic due to idiopathic or secondary causes, like trauma and inflammation of the synovial tissue. Currently, synovial plicae are classified as infrapatellar, mediopatellar and suprapatellar. The prevalence of the mediopatellar plica over the other forms of plicae varies between 18% and 60%. The most reported symptom of the mediopatellar plica is pain located medial to the patella above the joint line. Magnetic Resonance Imaging (MRI) is the most useful examination to highlight the presence of the plica, its measurement and exact location. The treatment is initially conservative, i.e. medical treatment and physiotherapy, however when these fail, the plica should be removed surgically via arthroscopy. In the current paper, we aim to report our clinical experience in the management of medial patellar plica syndrome by describing the clinical presentation and diagnosis of this condition as well as its treatment.

Background: Behçet’s Disease (BD, OMIM 109650) is a chronic relapsing inflammatory disease of unknown etiology with unpredictable exacerbations and remissions. First described in 1937 by the Turkish dermatologist HulusiBehçet, as a trisympton complex (oral and genital ulcers and uveitis), it is now recognized as a multisystemic disease. The syndrome can manifest in diverse ways and can involve nearly every organ system. 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. This article presents a review of the relevant published literature about the immunopathogenesis of BD. Result: The authors used MeSH terms “Behçet’s disease” with “pathophysiology,” “pathogenesis,” “genetic”, “epigenetic”, “immunogenetic” or “immune response” to search the PubMed database. All the relevant studies identified were included.

Primary Systemic Vasculitides (PSV) are a heterogeneous group of diseases. Outcome scores are important to evaluate vasculitis patients in a more structured and standard way and these help physicians to predict patients with poor prognosis or high risk of relapse. Furthermore, we need reliable outcome measures for clinical trials. There are a number of vasculitis outcome scores available in the clinical practice with different strengths and limitations. These are mainly measures of disease activity, disease damage, response to treatment and quality of life. Birmingham Vasculitis Activity Score (BVAS) and its pediatric version aim to evaluate a wide scope of PSV. On the other hand, some outcome studies have focused on a single vasculitis type since the whole group includes different diseases with heterogeneous clinical features. The aim of this review is to provide an overview on outcome measures currently being used in the evaluation of patients with PSV. We mainly focus on immunoglobulin A vasculitis/Henochschönlein purpura, Kawasaki disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, polyarteritis nodosa, Takayasu arteritis and Behçet’s disease.

Aim: The primary objective was to assess the risk of fractures in adults with RA compared with controls from the general population. The review also assessed an increased risk of fractures in RA patients when accounting for steroid use, RA disease severity or functional impairment. Methods: Citations were screened from MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and CINAHL. Included citations were written in English, including adult patients at least 18 years of age and compared fracture incidence or prevalence between RA patients and a control group. Case-control, cohort and cross-sectional studies were included. Results: There were a total of 3451 citations; after application of the inclusion criteria, 17 studies were selected. In 14 of the 17 studies, there was an increase in the risk of fracture in RA patients compared to controls. In studies that evaluated for glucocorticoid use, four of 13 demonstrated an increased risk of fracture with glucocorticoid use, however, only two of these four studies specifically assessed glucocorticoid use amongst patients with RA. In studies that analyzed RA severity or functional impairment, two of seven demonstrated disease severity or impairment as a risk factor for fracture. There was marked study heterogeneity in terms of patient and fracture characteristics, which was a limitation of the analysis that impeded the ability to make direct comparisons. Conclusion: The risk of fracture in RA patients is elevated when compared to the general population, although the etiology of the increased risk remains to be elucidated.

Background: A hot, swollen joint is a common clinical condition encountered in the ED and elective orthopaedic and rheumatology clinics. These patients can be difficult to manage and properly treat. Aims and Objectives: The aim of this study was to report a single centre retrospective analysis of patients presenting to our institution for a hot, swollen joint over a three-month period. Methods: The study included patients presenting with a hot, swollen joint to ED or electively to clinics. The synovial fluid was aspirated and sent for microbiological and cytological investigation. P value was set to < 0.001. 36 patients (22 M, 14 F) with a mean age of 72.8 ± 17.4 years met our criteria. 20 cases (55.6 %) involved the knee joint, the wrist in 10 cases (27.8%), the elbow in 3 cases (8.3%) and the shoulder in 3 cases (8.3%). Results: Of the 36 synovial fluid samples collected, only 7 (19.4%) reported evidence of infection. On cytological examination of the synovial fluid, 21 (58.3%) reported presence of calcium pyrophosphates crystals (Pseudogout), 4 (11.1 %) reported presence of uric acid crystals (Gout) and 11 (30.5%) reported absence of crystals. We found a significant correlation between age and the diagnosis of pseudogout and between previous antibiotic treatment and ED presentation. Our study sheds light on the high incidence of crystal-related pathologies. Conclusion: In order to improve our management of this common condition and enhance our understanding of the clinical diagnosis in certain patient population, further high-profile clinical studies are needed.

Background: Osteoarthritis (OA) ranks fifth among all forms of disability affecting 10% of the world population. Current treatments available are associated with multiple side effects and do not slow down the progression of the disease. Moreover, no such effective treatment is available to date in various systems of medicine to treat osteoarthritis. Curcumin and Arnica have shown evident clinical advances in the treatment of osteoarthritis. Objective: The aim of the present study was to design, optimize and characterize novel herbal transdermal patches of curcumin and Arnica montana using factorial design. Methods: A multiple factorial design was employed to investigate the effect of hydroxypropyl methyl cellulose, ethyl cellulose and jojoba oil on elongation and drug release. Transdermal patches were evaluated by FTIR, DSC, FESEM, ex vivo drug permeation, anti osteoarthritic activity and analgesic activity. Results: Independent variables exhibited a significant effect on the physicochemical properties of the prepared formulations. The higher values of drug release and elongation were observed with the higher concentration of hydroxypropyl methylcellulose and jojoba oil. Anti osteoarthritic activity was assessed by complete Freund's adjuvant arthritis model; using rats and analgesic activity by Eddy's hot plate method, using mice. Combination patch exhibited good anti osteoarthritic and analgesic activity as compare to individual drug patches. Conclusion: The design results revealed that the combination patch exhibited good physicochemical, anti osteoarthritic and analgesic activity for the treatment of osteoarthritis in animals. More plants and their combinations should be explored to get reliable, safe and effective formulations that can compete with synthetic drugs.

Background: Up to 44% of patients treated with infliximab and 7% of patients treated with etanercept reported to have anti-drug antibodies within the first 6 months of treatment. Recently, anti-TNF-α therapies have been reported to be employed in the induction of the druginduced lupus erythematous. Objective: The aim of the present study was to investigate the relationship between anti-TNFα antibodies and various manifestations of lupus erythematous. Methods: We enrolled a total of 56 cases divided into 28 known cases of rheumatoid arthritis and 28 cases of ankylosing spondylitis patients and 56 controls. The case group was divided into 4 groups according to the underlying disease (RA or AS) and treatment regimen (infliximab or etanercept). ANA and anti-dsDNA levels and lupus criteria were assessed at the beginning of the study and 4 months after the initiation of anti-TNFα. Results: 36% and 21% of RA patients treated with infliximab, were ANA and anti-dsDNA positive after 4 months (P=0.003, P=0.025). 28% and 7% of RA patients treated with etanercept, were ANA and anti-dsDNA positive after 4 months (P=0.009, P=0.15). 21% and 7% of AS patients treated with infliximab, were ANA and anti-dsDNA positive, respectively (P=0.025, P=0.15). 14% and 7% of AS patients treated with etanercept, were ANA and anti-dsDNA positive, respectively (P=0.63, P=0.15). Three patients who were positive for auto-antibodies developed three criteria for SLE. Conclusion: Infliximab potentially may increase both ANA and anti-dsDNA levels in rheumatoid arthritis, but only ANA in ankylosing spondylitis patients. In general, clinicians should consider different clinical symptoms of ATIL, which may be present as a lupus-like syndrome similar to idiopathic SLE or classical DIL.

Background: Methotrexate hepatotoxicity could be a reason for the discontinuation or dose reduction in patients with Rheumatoid Arthritis (RA); however, the consequence of different policies in this situation is unclear and the physicians need to know what would happen after their decision. Objective: To demonstrate the consequence of multiple approaches towards transaminitis management in patients with RA receiving Methotrexate (MTX). Methods: Data were obtained from the previous work (2006) on 295 patients with RA undergoing MTX treatment. Those who developed transaminitis at least one time were selected for this study. Then, the physicians’ decisions regarding discontinuing, decreasing, or prescribing a fixed dose of MTX along with the effect of each decision on the next liver enzyme were evaluated. Results: Strategies of decreasing dose or discontinuing MTX were adopted in 31.4% of patients and prescribing fixed dose was done in 53.9% of patients, leading to 93% and 65% next enzyme normalization, respectively. Thirty-four patients had definite MTX induced transaminitis and 55.9% of the physicians decided to decrease MTX dose for them, causing normalization of the next enzyme in 83% of these patients. In contrast, continuing MTX, even with the same dose, in definite MTX induced transaminitis cases led to consecutive enzyme elevations in 88.9% of these patients (p=0.001). Conclusion: Normalization of liver enzymes was observed after decreasing dose or discontinuing MTX, suggesting this policy as the best practice for the management of MTX induced transaminitis. However, the trend to improvement, despite the type of physicians’ decision, was observed. This trend was not found in definite MTX induced transaminitis, revealing the prominence of the physician’s policy in this situation.

Introduction: Osteoporosis is a common comorbidity in Rheumatoid Arthritis (RA) patients and can result in estimated double risk of pathological fractures. Bone Mineral Density (BMD) is known to decrease with RA because of mechanisms incorporating traditional as well as disease-specific causes. With the advent of newer disease-modifying antirheumatic agents and bone protection medications, it is becoming important to identify those individuals who are at increased risk of developing osteoporosis among RA patients. Aim: In the current study, we aim to evaluate a multitude of factors including focal erosions on radiographs of hands or feet that can predict osteoporosis in RA patients. Methods: After obtaining IRB approval, 26 patients (20 females & 6 males) with a median age of 62 years (95% CI: 57.4 - 66.0) were retrospectively identified from a Rheumatology clinic database with an established diagnosis of RA but not taking osteoporosis medications. A detailed assessment was accomplished including evaluating a number of disease-specific variables, hands/feet radiographs and Dual-energy X-ray Absorptiometry (DXA). Results: The total hip BMD was lower in RA patients with radiographic erosions (0.862 g/cm2 ± 0.17) compared to those patients without erosions (1.011 g/cm2 ± 0.13). On univariate logistic regression, the presence of radiographic erosions predicted osteoporosis of the hip (p = 0.04). ROC curve demonstrated satisfactory performance of erosions in predicting WHO-defined osteoporosis or osteopenia at the hip (AUC = 0.732). Conclusion: RA patients who show radiographic erosions are more likely to develop hip osteoporosis that may require further intervention.