Nonsteroidal Anti-Inflammatory Drugs: A survey of practices and concerns of pediatric medical and surgical specialists and a summary of available safety data

<p>Abstract</p> <p>Objectives</p> <p>To examine the prescribing habits of NSAIDs among pediatric medical and surgical practitioners, and to examine concerns and barriers to their use.</p> <p>Methods</p> <p>A sample of 1289 pediatricians, pediatric rheumatologists, sports medicine physicians, pediatric surgeons and pediatric orthopedic surgeons in the United States and Canada were sent an email link to a 22-question web-based survey.</p> <p>Results</p> <p>338 surveys (28%) were completed, 84 were undeliverable. Of all respondents, 164 (50%) had never prescribed a selective cyclooxygenase-2 (COX-2) NSAID. The most common reasons for ever prescribing an NSAID were musculoskeletal pain, soft-tissue injury, fever, arthritis, fracture, and headache. Compared to traditional NSAIDs, selective COX-2 NSAIDs were believed to be as safe (42%) or safer (24%); have equal (52%) to greater efficacy (20%) for pain; have equal (59%) to greater efficacy (15%) for inflammation; and have equal (39%) to improved (44%) tolerability. Pediatric rheumatologists reported significantly more frequent abdominal pain (81% vs. 23%), epistaxis (13% vs. 2%), easy bruising (64% vs. 8%), headaches (21% vs. 1%) and fatigue (12% vs. 1%) for traditional NSAIDs than for selective COX-2 NSAIDs. Prescribing habits of NSAIDs have changed since the voluntary withdrawal of rofecoxib and valdecoxib; 3% of pediatric rheumatologists reported giving fewer traditional NSAID prescriptions, and while 57% reported giving fewer selective COX-2 NSAIDs, 26% reported that they no longer prescribed these medications.</p> <p>Conclusions</p> <p>Traditional and selective COX-2 NSAIDs were perceived as safe by pediatric specialists. The data were compared to the published pediatric safety literature.</p

Favorable outcome of juvenile dermatomyositis treated without systemic corticosteroids.

OBJECTIVE: To describe the course of patients with juvenile dermatomyositis (JDM) treated effectively without systemic corticosteroids. STUDY DESIGN: A retrospective study of 38 patients with JDM treated at a tertiary care children\u27s hospital identified 8 patients who had never received corticosteroids. Disease presentation and course, pharmacologic, and ancillary treatments were recorded. RESULTS: Patients in the no corticosteroid group were followed for a median of 2.8 years (range, 2.1 to 9.5 years). Treatment was primarily with intravenous immunoglobulin (IVIG) (75%) and methotrexate (50%), with favorable response in all. No serious treatment complications were observed; headaches were reported by 3 patients receiving IVIG. Two patients had a myositis flare after discontinuing all medications for more than 1 year; complete resolution of symptoms was observed after either 1 or 2 further doses of IVIG. Two patients had calcinosis (at 1 and 9 years of disease); however, no patient had joint contractures, muscle atrophy, lipodystrophy, or functional limitations. CONCLUSIONS: Systemic corticosteroids can be avoided in a select group of patients with JDM. Alternative agents such as methotrexate and IVIG may be prescribed to effectively treat JDM and prevent complications

H syndrome: 5 new cases from the United States with novel features and responses to therapy

Abstract Background H Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). Less than 100 patients with H syndrome have been described in the literature, with the majority being of Arab descent, and only a few from North America. Case presentation Here we report five pediatric patients from three medical centers in the United States who were identified to have H syndrome by whole exome sequencing. These five patients, all of whom presented to pediatric rheumatologists prior to diagnosis, include two of Northern European descent, bringing the total number of Caucasian patients described to three. The patients share many of the characteristics previously reported with H syndrome, including hyperpigmentation, hypertrichosis, short stature, insulin-dependent diabetes, arthritis and systemic inflammation, as well as some novel features, including selective IgG subclass deficiency and autoimmune hepatitis. They share genetic mutations previously described in patients of the same ethnic background, as well as a novel mutation. In two patients, treatment with prednisone improved inflammation, however both patients flared once prednisone was tapered. In one of these patients, treatment with tocilizumab alone resulted in marked improvement in systemic inflammation and growth. The other had partial response to prednisone, azathioprine, and TNF inhibition; thus, his anti-TNF biologic was recently switched to tocilizumab due to persistent polyarthritis. Another patient improved on Methotrexate, with further improvement after the addition of tocilizumab. Conclusion H syndrome is a rare autoinflammatory syndrome with pleiotropic manifestations that affect multiple organ systems and is often mistaken for other conditions. Rheumatologists should be aware of this syndrome and its association with arthritis. It should be considered in patients with short stature and systemic inflammation, particularly with cutaneous findings. Some patients respond to treatment with biologics alone or in combination with other immune suppressants; in particular, treatment of systemic inflammation with IL-6 blockade appears to be promising. Overall, better identification and understanding of the pathophysiology may help devise earlier diagnosis and better treatment strategies

Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein

ObjectiveParticipants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy.MethodsSubgroups were prespecified and defined by age (&gt; or ≤15.5 years), systemic lupus erythematosus (SLE) duration (&gt; or ≤24 months), pubertal status (Tanner score≥4 as post-pubertal or &lt;4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or &lt;110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or &lt;1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models.ResultsSignificant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures.ConclusionsPubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy.Trial registrationClinical Trials.gov Identifier: NCT00065806

2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases

ObjectiveTo provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).MethodsThis guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation.ResultsThis guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence.ConclusionApplication of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings