Current Rheumatology Reviews - Volume 10, Issue 2, 2014

Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease affecting millions of people worldwide. It can affect any organ systems of the body. However, all systems may not be involved initially rather than they may be affected gradually, sometimes over years. Diagnosis depends on characteristic clinical features and laboratory test results. Some features such as skin rash, joint symptoms and oral ulcers are common in SLE. But initial presentation of many patients is unusual because either they do not have these common features of the disease or the presentation mimics other illnesses. As a result, delayed diagnosis and misdiagnosis are common. Therefore, high index of initial suspicion of SLE is critical. In clinical practice, SLE should be suspected in any patient presenting with an unexplained disease process involving two or more organ systems. To make a diagnosis in an unusual presentation, thorough clinical evaluation with details history of both present and past illnesses as well as laboratory tests for SLE should be performed. Usually primary-care physicians first evaluate SLE patients; but there is no single article, where all the information on when to suspect SLE in an unusual presentation, is available in an integrated form. In this article, a list of conditions, when SLE should be suspected in an unusual presentation, has been given and some relatively common areas with diagnostic challenges of SLE have been briefly described. To prepare this manuscript, most articles have been identified through ‘Pubmed’ search using keywords-atypical/ unusual presentation of SLE, case reports on SLE, gastrointestinal manifestations of SLE, neuropsychiatric SLE, diagnostic challenges with SLE, etc. Selected most articles are from currently medline-indexed journals.

Recent publications have proposed revisions to disease classification criteria, new definitions of early diagnosis and remission, as well as guidelines for implementing treat-to-target strategies for the management of patients with spondyloarthritis. Despite developments leading to this practice-changing approach, the concept of treat to target for spondyloarthritis has not yet been widely accepted or implemented in standard clinical care. By placing greater emphasis on clinical features that manifest early in the disease process, the early and aggressive treatment of the most common forms of spondyloarthritis (namely ankylosing spondylitis and psoriatic arthritis), has been shown to have favorable patient outcomes in reducing synovial inflammation, delaying joint damage, and maintaining functional status. This article discusses the recent concept of Treat to Target in spondyloarthritis and the importance of early diagnosis of both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). It also highlights the main outcome measures for spondyloarthritis patients achieving treatment goals of low levels of disease activity or clinical remission.

The term overlap syndromes (OS) is used to define a group of disorders characterized by the presence, in the same patient, of clinical features typical for more than one definite connective tissue disease (CTD). Objective: To show that patients may not only have an overlap of two or more CTDs but may also change their disease phenotype from that of a definite CTD to another. Patients and methods: Retrospective analysis of medical records of four patients with a disease duration of about thirty years and a transition from a well definite CTD into another. Results: The first patient was diagnosed, at the beginning of the 1980s, as affected by diffuse cutaneous systemic sclerosis (dcSSc) and developed systemic lupus erythematosus (SLE) twenty-five years later. The second and the third patients were diagnosed with SLE at the beginning of their disease: the second patient developed, in the course of her disease, an overlap syndrome (OS) SSc/rheumatoid arthritis (RA) and the third SSc and finally microscopic polyangiitis (MPA). The fourth patient was diagnosed as primary Sjogren’s syndrome (SS) then as rheumatoid arthritis (RA) and finally developed SLE. Conclusions: Patients may not only show an overlap of two or more CTDs but also a transition from a well definite CTD into another. We propose the term “transitional connective tissue diseases” (TCTDs) to define their disease. A higher number of patients may allow us to better identify this new subgroup of CTDs and probably, also, predictors of evolution.

Monitoring treatment effects can inform both the physician and patient whether the medication has achieved its anticipated targets. There are several variances between patients cohorts included in clinical trials and subjects managed in standard clinical setting. Therefore, defining a patient as a “responder” or “non-responder” to management might not be applicable in day to day care, in particular in patients suffering from chronic diseases. So far, in patients receiving treatment for osteoporosis, there is no clear guidance on when the fracture risk has been reduced to an acceptable low level. As a consequence, some patients at low risk for fracture may have continued their treatment for longer periods than necessary, whereas others at high risk for fracture may have their treatment stopped whilst the continuation of the same medication or a change to a more potent therapy might be of value. In many specialties, goal-directed treating to target is already the standard and the time has come for goal-directed management of osteoporosis. Adopting treat-to-target approach in osteoporosis has the prospective of developing the patients’ care, plummeting the osteoporotic fractures burden, in addition to having a positive cost-effectiveness impact. This article aims at discussing the potential utility of “treat-totarget” approach for osteoporotic patients management in standard clinical practice. It also includes a suggested algorithm for long term osteoporosis treatment as well as post-drug holiday management based on “treat to target” strategy.

The human wrist is a composite joint which incorporates multiple smaller joints. The biomechanics of the wrist are dependent on its bony structure but also on the ligamentous constitution of its joints. This increases the complexity of the joint and reduces our ability to understand its anatomy, mechanics and pathology. Therefore, our understanding and treatment of osteoarthritis in the wrist lags behind that of other joints in the body such as the knee. We discuss some of the recent directions in the comprehension and treatment of wrist osteoarthritis.

Aim: The aim of this review is to update the knowledge about the Kawasaki disease (KD) which includes the way of early detection and latest treatment plan for the disease. Method: A number of literatures were reviewed and latest information about the etiology, diagnosis, laboratory investigation, treatment and outcome of the disease was collected and depicted in the review article. Result: Kawasaki disease is a multisystem vasculitis mainly affecting medium sized blood vessels. It is the second most common cause of vasculitis after Henoch Scholein Purpura (HSP) in children. Etiology of the disease is still unknown. Auto-immunity with genetic influence is thought to associate with the disease. Many physicians are ignorant of the disease. The pediatrician must be aware of the disease and suspect this condition in less than 5 year old children presenting with more than 5 days fever. the number of methods on the basis of criteria is set for the diagnosis of the disease. Latest treatment plan is set up for the disease which reduces the morbidity and mortality to a great extent. Conclusion: Physicians must have consciousness and comprehensive knowledge for the early suspicion of this disease. Any child presenting with fever for more than 5 days should not be ignored and other criteria of KD have to be evaluated by the physician. Early diagnosis and updated treatment are imperative for the prevention of morbidity and mortality for the disease.

Background: Generalized Joint Hypermobility (GJH) is regarded as the main diagnostic criterion for Hypermobility Syndrome and is assumed to be of importance for the development of musculoskeletal complaints and functional decline. However GJH is also highly prevalent amongst healthy individuals whereas its consequences for physical functioning are unclear. Therefore the objective of the study was to determine the association of GJH with physical functioning in healthy adolescents and young adults. Methods: 328 participants (mean age (sd): 20.2 (1.8), gender (male/female): 134/194) were included. In order to establish the effect of GJH, subjects with symptomatic forms of GJH were excluded, as were subjects with other conditions that could influence physical functioning. Age, gender, BMI, GJH, muscle strength and physical activity level (PAL) in METS were collected. Results: GJH was associated with reduced muscle strength for all muscle groups (p=<.05), controlled for age and BMI. Ranging from -0.7 to -1.0SD in females and -.3 to -1.3SD in males. GJH was found to be significantly associated with higher amounts of METS spent on cycling, ranging from +0.2 to +0.9SD in females (p=.002) and +0.3 to +0.9SD in males (p=.041), where lower amounts of METS spent on sports activities was observed, ranging from -0.4 to -1.2SD in females (p=.002) and -0.2 to -1.9SD in males (p=.004). Conclusion: Individuals with GJH have reduced muscle strength and tend to avoid dynamic activities and prefer more stable activities, like cycling. This may indicate that individuals with GJH adapt their behaviour to prevent musculoskeletal complaints and functional decline.

Aim of the work: The aim of the present work was to study the role of vascular surgery in the management of primary vasculitis patients with peripheral ischemic manifestations. Patients and methods: Ten primary vasculitis patients with peripheral ischemic manifestations were studied and reviewed for the diagnosis, clinical manifestations, investigations, treatment options and role of vascular surgery. The Birmingham Vasculitis Activity Score (BVAS) was recorded. Results: Giant cell arteritis was present in one patient; granulomatosis with polyangiitis in 5, essential cryoglobulinemic vasculitis in 3 and 1 (child) had Henoch–Schönlein purpura. They showed the following peripheral vascular manifestations: intermittent claudications, Raynauds, deep venous thrombosis and thrombophelebitis in 10% each; digital ulceration and trophic changes in 20% while acrocyanosis and dry gangrene were present in 30%. Renal involvement was present in 60% of patients. The mean BVAS was 11.5±6.57 at initial presentation. The disease activity remarkably improved over the disease course in all patients to be at their last visit (2.6±2.22) (p=0.002). Regarding the vascular surgery role in their management, in addition to their medical treatment, 40% required an additional surgical intervention. Two had a minor amputation of the toes; one performed thoracoscopic cervical sympathectomy and another needed tibial angioplasty. Conclusion: Primary vasculitis patients presenting with peripheral ischemic manifestations require surgical attention. Their management is essentially medical and individualized to the diagnosis and presenting symptoms. Endovascular treatment may offer a safe and less invasive approach in high surgical risk patients. Sympathectomy is of high therapeutic potential in those with severe pain and trophic changes.

Serum cartilage oligomeric matrix protein (COMP) level is a new marker of joint destruction in patients with rheumatoid arthritis (RA), and a new means of identifying patients with progressive joint damage. To evaluate the effect of tocilizumab (TCZ) on serum COMP levels, and whether there is any difference in this effect between patients failing on anti-TNF treatment and those failing on disease-modifying anti-rheumatic drugs (DMARDs). Fifty-one patients with long-standing RA (42 F, 9 M; mean age 62±14 years; disease duration 4.5±1.2 years) unresponsive to DMARDs and anti-TNF drugs were treated with TCZ 8 mg/kg/month. Serum COMP levels were measured by means of an ELISA at baseline and after six months of TCZ treatment; the patents’ DAS28 scores and levels of RF (IgM, IgG, IgA), anti-CCP autoantibodies, ESR, CRP and IL-6 were evaluated at the same times. After six months of TCZ treatment, there was a significant decrease from baseline in ESR (46.1 [28.7-68.9] vs 34.3 [4.1- 58.8] mm/h, P <0.0001), CRP (2.2 [0.8-4.4] vs 1.3 [0.7-3.8] mg/dL, P <0.0001), TNF-α (21.3 [7.6-29.8] vs 17.4 [3.4-28.6] pg/mL, P=0.0408), IL-6 (6.9 [3.5-9.6] vs 3.4 [3.0-9.6] pg/mL, p<0.0001); anti-CCP (55.1 [30.2-273.0] vs 54.7 [30.1- 269.8] IU/mL, P=0.9683), RF-IgM (142.0 [48.0-260.0] vs 138.0 [42.0-243.0] IU/mL, P=0.4828), RF-IgA (81.0 [20-140] vs 108.0 [20-175] U/mL, P=0.0003), and RF-IgG (65.2 [30-158] vs 58.3 [38.0-158.0] U/mL, P=0.2671). There was also a significant decrease in DAS28 scores (4.3 [3.2-5.9] vs 3.7 [2.3-5.4], P <0.0001), and a non-significant decrease in serum COMP levels (0.95 [0.04-2.90] vs 0.98 [0.05-2.36] μg/mL; P = 0.9856). A decrease in serum COMP levels was observed in the patients failing on anti-TNF treatment or anti-DMARDs without any difference. TCZ therapy in patients with long-standing RA is associated with a significant decrease in ESR, CRP, IL-6, TNF and DAS28 values, and a decrease in serum COMP levels, particularly in patients failing on previous anti-TNF therapy. These findings suggest that TCZ has an effect on cartilage joint destruction after only six months of treatment.

Objective: This study assessed an association of anti-cyclic citrullinated peptide antibodies (ACPA) with clinical and radiological disease severity in patients with rheumatoid arthritis (RA). Materials and Methods: Fifty patients diagnosed with RA as per 2010 revised American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria were included in this cross-sectional study. Serum levels of ACPA, C-reactive protein (CRP) and rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), disease activity score with 28-joint counts and ESR (DAS28-ESR), patient’s global assessment of disease activity using visual analogue scale (PtGA-VAS), modified health assessment questionnaire score (M-HAQ) and radiological damage in hands and feet (modified Larsen score) were determined. Results: ACPA were positive in 48 (96%) and RF in 44 (88%) patients. Mean Larsen score was 19.82 ± 17.11 and mean DAS28-ESR 6.39 ± 1.59. A significant correlation of ACPA levels was seen with RF (p=0.03) and Larsen score (p=0.02) but not with DAS28-ESR (p=0.17) and M-HAQ (p=0.81). A significant correlation was seen between Larsen score and disease duration (p<0.0001), age (p=0.04), DAS28-ESR (p=0.001) and M-HAQ (p<0.0001). Multivariate analysis showed that painful joint count (p=0.003), ESR (p<0.001) and PtGA-VAS (p=0.009) were independently associated with clinical disease activity severity. Disease duration (p=0.01), ACPA levels (p=0.004) and DAS28-ESR (p=0.03) were independently associated with radiological joint damage. Conclusion: Serum ACPA levels correlate significantly with radiological severity of RA but not with clinical disease severity and are independently associated with radiological outcome.