Intra-articular steroid injection for temporomandibular joint arthritis in juvenile idiopathic arthritis: A systematic review on efficacy and safety

Objective

To determine the current level of evidence for the use of intra-articular corticosteroid injections (IACI) against temporomandibular joint (TMJ) arthritis in patients with juvenile idiopathic arthritis (JIA) with a particular focus on clinical and radiological improvements and safety profile.

Methods

A comprehensive electronic search strategy was performed in all major medical databases in February 2012. Studies were selected independently by two reviewers in accordance with a pre-specified protocol and a risk of bias assessment for all included studies.

Results

Ninety-four unique citations were identified of which seven remained after the inclusion criteria were applied and all of these were assessed to have a high risk of bias. The current limited level of evidence suggests potential beneficial properties of IACI in patients with TMJ arthritis-related symptoms and/or MRI-verified signs of TMJ inflammation. Currently, no scientific evidence substantiates the effect of IACI in terms of (I) improving maximal mouth opening capacity significantly, (II) reducing radiological disease progression, (III) normalising/improving mandibular growth, and (IV) increasing efficacy upon repeated injections.

Conclusion

The current level of evidence allows only very limited conclusions on the effect of IACI therapy in patients with TMJ arthritis. Knowledge on the long-term impact of IACI on mandibular growth is not available. Future studies designed in accordance with evidence-based standards are needed to allow a more general conclusion on efficacy and safety of this treatment modality in patients with TMJ arthritis.     

Réactions cutanées paradoxales sous traitement par tocilizumab

Introduction

Tocilizumab (TCZ) is a humanized antihuman interleukin (IL)-6 receptor antibody recommended for the treatment of moderate to severe active rheumatoid arthritis, adult-onset Still disease, Castleman disease and more recently, systemic juvenile idiopathic arthritis. Like anti-TNFα, rituximab and less frequently abatacept, TCZ can induce paradoxical cutaneous eruption like psoriasis with predominantly palmoplantar presentation.

Case report

We report a 47-year-old woman with psoriastic arthritis who developed under anti-TNFα therapy and later under tocilizumab a paradoxical palmoplantar eruption.

Conclusion

The specific underlying mechanisms of this side effect are unclear but relapse of these lesions seems to be observed with certain biological agents.     

Inflammatory,immune-mediated adverse reactions related to soft tissue dermal fillers

Background

An increasing number of persons seek medical solutions for esthetic indications and for diverse pathological conditions, such as malformations, trauma, or cancer. Despite manufacturers' and different authors' claims that fillers are non-immunogenic or that complications are uncommon, unwanted adverse reactions do occur.

Objectives

To review the literature regarding the multiple types of immune-mediated adverse reactions related to medical dermal filler injections/prosthesis.

Methods

A comprehensive MEDLINE, PubMed, and Google Scholar electronic database search was performed (2000–January 2012). Selected articles published before 2000 referring to general concerns regarding the studied topic were also included. The search provided almost 300 articles. Finally, 235 studies were selected and included.

Results

All known fillers present in the market have been shown to be able to provoke early- and late-onset inflammatory adverse reactions. Their true prevalence is unknown but appears to be significant. The majority of the late-onset adverse effects are inflammatory and immune-mediated in nature. Edema, granulomas, sarcoid-like disorders, and panniculitis are the findings most commonly seen. Rarely, systemic granulomatous and autoimmune diseases, and to lesser extent acute hypersensitivity reactions can be seen.

Conclusions

All implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions that may appear early or late and range from local to systemic. Most fillers act more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies. Management of both acute and systemic reactions is often difficult and requires anti-inflammatory and occasionally immunosuppressive therapy.     

Estado actual del tratamiento con infiltraciones intraarticulares en la artritis idiopática juvenil

Objective

Intra-articular corticosteroid injections (IACI) are a fundamental part in the treatment of juvenile idiopathic arthritis. The current situation of IACI is reviewed in a population of children.

Features of portal hypertension are associated with major adverse events in Fontan patients: The VAST study

Background

Chronic congestive hepatopathy is known to cause hepatic fibrosis and portal hypertension in patients post-Fontan operation for single ventricle palliation. The clinical significance of these findings is not clear. We hypothesized that features of portal hypertension would be significantly related to major adverse events.

Methods

A retrospective review of 73 adult and pediatric post-Fontan patients referred for a liver evaluation from 2001 to 2011 was performed. The relationship between features of portal hypertension (VAST score ≥ 2, 1 point each for Varices, Ascites, Splenomegaly or Thrombocytopenia) and a major adverse event (death, need for transplant, or hepatocellular carcinoma) was examined using logistic regression.

Results

73 post-Fontan patients (30% female, 73% Caucasian, 66% systemic left ventricle (SLV), mean age 24 ± 11 years, mean interval from Fontan 17 ± 6 years) were included in analysis. Features of portal hypertension (VAST score ≥ 2) were present in 26 (36%), and there were 19 major adverse events: death (n = 12), transplant (n = 6), and HCC (n = 1). A significant relationship was found between VAST score ≥ 2 and major adverse events (OR = 9.8, 95% CI [2.9–32.7]). After adjusting for time since Fontan, SLV, age, hemoglobin and type of failure, VAST score ≥ 2 remained significant (OR = 9.1, 95% CI [1.4–57.6]).

Conclusion

Fontan patients with features of portal hypertension have a 9-fold increased risk for a major adverse event. Therapies targeted to manage clinical manifestations of portal hypertension, and early referral to heart transplant may help delay major adverse events. Future prospective studies are needed to confirm these findings.     

Anakinra as first‐line disease‐modifying therapy in systemic juvenile idiopathic arthritis: Report of forty‐six patients from an international multicenter series

Objective

To examine the safety and efficacy of the interleukin‐1 (IL‐1) receptor antagonist anakinra as first‐line therapy for systemic juvenile idiopathic arthritis (JIA).

Methods

Patients with systemic JIA receiving anakinra as part of initial disease‐modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome.

Results

Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C‐reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed.

Conclusion

Anakinra as first‐line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL‐1 inhibition as first‐line, rather than rescue, therapy in systemic JIA.

     

Corticosteroid Therapy for Cardiac Sarcoidosis: A Systematic Review

Background

There are no published clinical consensus guidelines or systematic evaluation supporting the use of corticosteroids for the treatment of cardiac sarcoidosis. The purpose of this study was to systematically review the published data on corticosteroid treatment of cardiac sarcoidosis.

Methods

Studies were identified from MEDLINE, EMBASE, Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and National Institutes of Health Clinical Trials.gov database. The quality of included articles was rated using Scottish Intercollegiate Guidelines Network 50. Outcomes examined were atrioventricular (AV) conduction, left ventricular function, ventricular arrhythmias, and mortality.

Results

A total of 1491 references were retrieved and 10 publications met the inclusion criteria. There were no randomized trials and all publications were of poor to fair quality. In the 10 reports, 257 patients received corticosteroids and 42 patients did not. There were 57 patients with AV conduction disease treated with corticosteroids, with 27/57 (47.4%) improving. In contrast, 16 patients were not treated with corticosteroids and 0/16 improved. Four publications reported on left ventricular function recovery, 2 reported on ventricular arrhythmia burden, and 9 reported on mortality. However, the data quality were too limited to draw conclusions for any of these outcomes.

Conclusions

Our systematic review identified 10 publications reporting outcomes after corticosteroid therapy. The best data relates to AV conduction recovery and corticosteroids appeared to be beneficial. It is not possible to draw clear conclusions about the utility of corticosteroids for the other outcomes. There is a clear need for large multicentre prospective registries and trials in this patient population.     

Therapeutic efficacy of humanized recombinant anti–interleukin‐6 receptor antibody in children with systemic‐onset juvenile idiopathic arthritis

Objective

To investigate the safety and efficacy of a recombinant human anti–interleukin‐6 (anti–IL‐6) receptor monoclonal antibody (MRA) that indirectly inhibits the effects of IL‐6 in children with systemic‐onset juvenile idiopathic arthritis (JIA) refractory to high‐dose, long‐term corticosteroids.

Methods

An individual escalating‐dose trial was conducted in 11 children with active systemic‐onset JIA who met the inclusion criteria. All were first administered an intravenous dose of 2 mg/kg MRA. Each child without active inflammation was given a second identical dose 2 weeks later and a third identical dose 2 weeks after the second dose. Children with disease flares according to laboratory marker values received a 4‐mg/kg dose. Those without disease flares at this dose received a second 4‐mg/kg dose 2 weeks later and a third 4‐mg/kg dose 2 weeks after the second dose, while those with active inflammation received an additional 3 doses of 8 mg/kg MRA. Efficacy was evaluated every 2 weeks according to responses on the JIA core set of improvement criteria and the results of laboratory tests.

Results

MRA abruptly reduced disease activity in 10 of the 11 children, as assessed by the occurrence of febrile episodes, active arthritis, scores on the Childhood Health Assessment Questionnaire, and levels of acute‐phase reactants. However, levels of inflammatory reactants fluctuated until the proper MRA dose for each child was reached. Two weeks after the third fixed dose of MRA, 90.9% of all patients had a 30% improvement response, 90.9% had a 50% improvement response, and 63.6% had a 70% improvement response.

Conclusion

MRA treatment of children with active systemic disease results in clinical improvement and in normalized levels of acute‐phase reactants. MRA was safe and well tolerated and provided greater clinical benefit than conventional corticosteroids, considering the ill effects of IL‐6 and adverse events.

     

Spondyloarthropathies tardives se présentant sous le masque d’une pseudopolyarthrite rhizomélique

Purpose

Polymyalgia rheumatica (PMR) is a frequent cause for long-term corticosteroid therapy. Management of PMR is difficult and recommendations (regarding diagnosis and treatment) from the British Society of Rheumatology have been recently published in order to avoid false diagnosis and unnecessary corticosteroid therapy. On the other hand, late onset spondyloarthropathies are difficult to diagnose due to their various presentation (peripheral and axial manifestations, usually associated with severe systemic manifestations) and the absence of validated diagnosis criteria in the elderly.

Methods

We report on eight patients, who all of them initially responding to Bird's criteria for PMR, and whose outcome was refractory PMR with multiple flares, poor therapeutic response, with inability to taper steroids.

Results

After a mean follow-up of 25 months, a diagnosis of late onset spondyloarthropathy was done in all theses patients based on clinical history, physical examination, and spine MRI. In four of the cases the use of TNFα blockers allowed to taper corticosteroid and to control the disease. Retrospectively, the diagnosis at presentation was difficult.

Conclusion

Among PMR patients with poor response to corticosteroids and multiple flares, the possibility of a late onset spondyloarthropathy should be discussed. There is an unmet need for validated diagnosis criteria in such patients.     

Polyradiculonévrite aiguë révélant un lupus érythémateux systémique : une présentation inhabituelle d’évolution fatale

Introduction

Neurological manifestations of systemic lupus erythematosus are common and numerous. They mainly involve the central nervous system, peripheral involvement being rare. Acute polyradiculoneuropathy is very uncommon.

Case report

We report a 44-year-old man, who presented with acute polyradiculoneuropathy revealing systemic lupus erythematosus. Outcome was fatal despite treatment with corticosteroids and immunoglobulin.

Conclusion

Acute polyradiculoneuropathy is a very rare manifestation of systemic lupus erythematosus and can compromise functional and life prognosis. Early diagnosis and management are crucial.     

Efficacité clinique et biologique du tocilizumab au cours de la maladie de Horton : à propos de trois observations et revue de la littérature

Introduction

Treatment of giant cell arteritis is based on prolonged corticosteroid therapy but adverse side effects are common especially in the elderly.

Case reports

We report three patients with giant cell vasculitis treated by tocilizumab, an interleukin-6 receptor antibody, owing to resistance or intolerance to corticosteroid therapy. A favorable outcome was rapidly observed both on clinical and biological data allowing a corticoid therapy sparing.

Conclusion

Tocilizumab is a promising treatment of giant cell arteritis but controlled trials are needed to confirm its efficacy.     

Treatment of acute gout: A systematic review

Objective

Acute gout is traditionally treated with NSAIDs, corticosteroids, and colchicine; however, subjects have multiple comorbidities that limit the use of some conventional therapies. We systematically reviewed the published data on the pharmacologic and non-pharmacologic agents used for the treatment of acute gouty arthritis.

Methods

A systematic search was performed using PubMed and Cochrane database through May 2013. We included only randomized controlled trials (RCTs) that included NSAIDs, corticosteroids, colchicine, adrenocorticotropic hormone (ACTH), interleukin-1 (IL-1) inhibitors, topical ice, or herbal supplements.

Results

Thirty articles were selected for systematic review. The results show that NSAIDs and COX-2 inhibitors are effective agents for the treatment of acute gout attacks. Systemic corticosteroids have similar efficacy to therapeutic doses of NSAIDs, with studies supporting oral and intramuscular use. ACTH is suggested to be efficacious in acute gout. Oral colchicine demonstrated to be effective, with low-dose colchicine demonstrating a comparable tolerability profile as placebo and a significantly lower side effect profile to high-dose colchicine. The IL-1β inhibitory antibody, canakinumab, was effective for the treatment of acute attacks in subjects refractory to and in those with contraindications to NSAIDs and/or colchicine. However, rilonacept was demonstrated to be not as effective, and there are no RCTs for the use of anakinra.

Conclusion

NSAIDs, COX-2 selective inhibitors, corticosteroids, colchicine, ACTH, and canakinumab have evidence to suggest efficacy in treatment of acute gout.     

Association of cardiac events with coronary artery disease detected by 64-slice or greater coronary CT angiography: A systematic review and meta-analysis

Background

The value of ≥ 64-slice coronary CT angiography (CCTA) to determine odds of cardiac death or non-fatal myocardial infarction (MI) needs further clarification.

Methods

We performed a systematic review and meta-analysis using publications reporting events/severity of coronary artery disease (CAD) in patients with suspected CAD undergoing CCTA. Patients were divided into: no CAD, non-obstructive CAD (maximal stenosis < 50%), and obstructive CAD (≥ 50% stenosis). Odds ratios with 95% confidence intervals were calculated using a fixed or random effects model. Heterogeneity was assessed using the I² index.

Results

We included thirty-two studies comprising 41,960 patients with 363 all-cause deaths (15.0%), 114 cardiac deaths (4.7%), 342 MI (14.2%), 69 unstable angina (2.8%), and 1527 late revascularizations (63.2%) over 1.96 (SD 0.77) years of follow-up. Cardiac death or MI occurred in 0.04% without, 1.29% with non-obstructive, and 6.53% with obstructive CAD. OR for cardiac death or MI was: 14.92 (95% CI, 6.78 to 32.85) for obstructive CAD, 6.41 (95% CI, 2.44 to 16.84) for non-obstructive CAD versus no CAD, and 3.19 (95% CI, 2.29 to 4.45) for non-obstructive versus obstructive CAD and 6.56 (95% CI, 3.07 to 14.02) for no versus any CAD. Similar trends were noted for all-cause mortality and composite major adverse cardiovascular events.

Conclusions

Increasing CAD severity detected by CCTA is associated with cardiac death or MI, all-cause mortality, and composite major adverse cardiovascular events. Absence of CAD is associated with very low odds of major adverse events, but non-obstructive disease significantly increases odds of cardiac adverse events in this follow-up period.     

Incidence and pattern of 12 years of reported transfusion adverse events in Zimbabwe: a retrospective analysis

Background

Haemovigilance hinges on a systematically structured reporting system, which unfortunately does not always exist in resource-limited settings. We determined the incidence and pattern of transfusion-related adverse events reported to the National Blood Service Zimbabwe.

Materials and methods

A retrospective review of the transfusion-event records of the National Blood Service Zimbabwe was conducted covering the period from 1 January 1999 to 31 December 2011. All transfusion-related event reports received during the period were analysed.

Results

A total of 308 transfusion adverse events (0.046%) were reported for 670,625 blood components distributed. The majority (61.6%) of the patients who experienced an adverse event were female. The median age was 36 years (range, 1–89 years). The majority (68.8%) of the adverse events were acute transfusion reactions consisting of febrile non-haemolytic transfusion reactions (58.5%), minor allergies (31.6%), haemolytic reactions (5.2%), severe allergic reactions (2.4%), anaphylaxis (1.4%) and hypotension (0.9%). Two-thirds (66.6%) of the adverse events occurred following administration of whole blood, although only 10.6% of the blood was distributed as whole blood. Packed cells, which accounted for 75% of blood components distributed, were associated with 20.1% of the events.

Discussion

The incidence of suspected transfusion adverse events was generally lower than the incidences reported globally in countries with well-established haemovigilance systems. The administration of whole blood was disproportionately associated with transfusion adverse events. The pattern of the transfusion adverse events reported here highlights the probable differences in practice between different settings. Under-reporting of transfusion events is rife in passive reporting systems.     

Fasciite avec éosinophilie (syndrome de Shulman) : à propos de 11 patients

Purpose

Eosinophilic fasciitis or Shulman's disease is a rare condition of unknown etiology.

Methods

We report a retrospective case series of 11 patients with eosinophilic fasciitis (seven men and four women, including a single pediatric case) and perform a systematic literature review to determine the main features of this disease.

Results

Mean age of the patients was 46 years. Subcutaneous induration of limbs observed in all the patients was the major presenting symptom. The induration was atypically located in the chest area in two patients. Blood eosinophilia was absent in five cases. Histological fasciitis was demonstrated in all patients and eosinophilic infiltration was present in seven patients. Relapse of subcutaneous induration was observed in only one patient who gradually developed systemic sclerosis.

Conclusion

Diagnosis of eosinophilic fasciitis should be considered in the presence myalgia and subcutaneous induration of limbs, blood eosinophilia and hypergammaglobulinemia. Treatment is based on systemic corticosteroids.     

Left atrial volume index is an independent predictor of major adverse cardiovascular events in acute coronary syndrome

Background

Left atrial volume index (LAVI) is well proven to be a reliable method of determining left atrial size, which has prognostic implications in cardiovascular diseases. Studies demonstrate that increased LAVI is a predictor of mortality in myocardial infarction, but its association with other major adverse cardiovascular events (MACEs) among patients post acute coronary syndrome (ACS) has not been adequately evaluated.

Methods

We calculated the baseline LAVI for all patients who were admitted with ACS between December 2010 and August 2011. The patients were stratified into 2 arms: normal LAVI and increased LAVI, with a cutoff value of 28 mL/m². All patients were prospectively followed up during 6 months for development of MACEs.

Results

Of the 75 patients who completed the study, 32 had increased LAVI, and 43 had normal LAVI. More than half (55%) of the patients were diagnosed with unstable angina. During the follow-up period of 6 months, 30 patients (93.8%) in the increased-LAVI arm and 23 patients (53.5%) in the normal-LAVI arm developed at least a single MACE. Patients with increased LAVI had significantly more MACEs (P = 0.021). The occurrence of MACE remained significantly higher in the increased-LAVI group even when atrial fibrillation was excluded (P = 0.016). After adjusting for confounding variables by multivariate analysis, LAVI was found to have a significant association with MACEs (P = 0.030, odds ratio = 1.229 (95% confidence interval, 1.020-1.481).

Conclusion

LAVI is a useful tool for prognostication and an independent predictor of MACEs post ACS.     

Anti–tumor necrosis factor α blockade in the treatment of juvenile spondylarthropathy

Objective

Persistent inflammation refractory to standard antirheumatic therapy in children with juvenile spondylarthropathy (SpA) leads to morbidity and reduced quality of life. Tumor necrosis factor α (TNFα) plays an important role in the pathogenesis of synovitis and enthesitis. This study was undertaken to examine the impact of anti‐TNFα agents on juvenile SpA that is refractory to nonsteroidal antiinflammatory drugs (NSAIDs), disease‐modifying antirheumatic drugs, and corticosteroids.

Methods

Ten juvenile SpA patients with a mean ± SEM age of 15.0 ± 0.7 years and disease duration of 4.4 ± 0.8 years, all of whom were HLA–B27 positive, were followed up for 1 year after initiation of either infliximab (n = 8) or etanercept (n = 2). Outcomes examined were within‐subject differences in the tender entheseal count (TEC) and active joint count (AJC), markers of inflammation, functional assessments (Childhood Health Assessment Questionnaire [C‐HAQ] score), and requirements for antirheumatic drugs.

Results

At baseline, all patients exhibited active arthritis and enthesitis that were resistant to NSAIDs (n = 10), methotrexate (n = 6), sulfasalazine (n = 8), corticosteroids (oral n = 6, intravenous pulse n = 3, and intraarticular n = 6), and bisphosphonates (n = 2). In 2 patients, sulfasalazine (n = 2), corticosteroids (n = 1), and bisphosphonates (n = 1) were stopped after initiation of the anti‐TNFα agent. In all patients, the arthritis and enthesitis significantly improved as evidenced by remission of the TEC and AJC by 6 months that was sustained during the 1‐year followup, markers of inflammation and C‐HAQ scores normalized, and there was a reduction in requirements for antirheumatic drugs (reduced dosage or discontinuation of NSAIDs n = 10, methotrexate n = 5, sulfasalazine n = 6, corticosteroids n = 4, and bisphosphonates n = 1).

Conclusion

Anti‐TNFα therapy is a potential novel treatment for refractory juvenile SpA. Further prospective studies are required to examine the effectiveness and long‐term outcomes of anti‐TNFα therapy in this cohort.

     

Experience with etanercept in an academic medical center: Are infection rates increased?

Objectives

There is little established information regarding the safety of antitumor necrosis factor therapies used outside the setting of clinical trials. This study evaluated the long‐term safety and tolerability of open‐label use of etanercept when used to treat patients with a variety of systemic rheumatic diseases. Reduction of concomitant corticosteroid and disease‐modifying antirheumatic drug was also assessed.

Methods

Retrospective medical record review of 180 patients who were started on etanercept between December 1998 and April 2000 at an academic medical center.

Results

Most patients (81%) remained on therapy for longer than 6 months, and a significant number (43%) of patients for longer than 12 months. Etanercept was prescribed for rheumatoid arthritis (RA) in 144 patients and for diseases other than RA, including ankylosing spondylitis, psoriatic arthritis, and polymyositis, in 36 patients. Fifty‐six percent of patients taking corticosteroids were able to reduce their dose and 51% of patients were able to taper their methotrexate dosages. Forty‐three patients (26%) discontinued etanercept. Reasons for discontinuing therapy included serious adverse events (2.9%), of which infection was most common. These included a psoas abscess secondary to Mycobacterium avium‐intracellulare, septic wrist, bacteremia, and septic total hip replacement. Two deaths associated with infection were seen.

Conclusions

The majority of the studied patients tolerated etanercept for longer than 6 months. Many of these patients were able to subsequently taper or even discontinue corticosteroid and methotrexate therapy. Serious infections occurred in this patient population. Our results underscore the value of long‐term observation under the conditions of clinical practice beyond controlled clinical trials.