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

Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults

OBJECTIVE: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histologic LN activity. METHODS: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n = 47) at the time of kidney biopsy. Histologic LN activity was measured by the National Institutes of Health activity index (NIH-AI) and the tubulointerstitial activity index (TIAI). High LN-activity status (versus moderate/low) was defined as NIH-AI scores >10 (versus ≤10) or TIAI scores >5 (versus ≤5). RAIL algorithms that predicted LN-activity status for both NIH-AI and TIAI were derived by stepwise multivariate logistic regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined. RESULTS: The differential excretion of 6 UBMs (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin, and kidney injury molecule 1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activity (NIH-AI) status with >92% accuracy and LN-activity (TIAI) status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71% and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses. CONCLUSION: The RAIL is a robust and highly accurate noninvasive measure of LN activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation

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

Validation of the lupus nephritis clinical indices in childhood-onset systemic lupus erythematosus.

OBJECTIVE: To validate clinical indices of lupus nephritis (LN) activity and damage when used in children against the criterion standard of kidney biopsy findings. METHODS: In 83 children requiring kidney biopsy the SLE Disease Activity Index Renal Domain (SLEDAI-R); British Isles Lupus Assessment Group index Renal Domain (BILAG-R), Systemic Lupus International Collaborating Clinics Renal Activity (SLICC-RAS) and Damage Index Renal Domain (SDI-R) were measured. Fixed effect and logistic models were done to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low/moderate vs. high LN-activity [NIH Activity Index (NIH-AI) score: ≤ 10 vs. > 10; Tubulointerstitial Activity Index (TIAI) score: ≤ 5 vs. > 5) or the absence vs. presence of LN chronicity [NIH Chronicity Index (NIH-CI) score: 0 vs. ≥ 1]. RESULTS: There were 10, 50 and 23 patients with class I/II, III/IV and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with LN-activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between LN-activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture LN chronicity was 23.5% and 91.7%, respectively. Despite designed to measure LN-activity, SLICC-RAS and SLEDAI-R scores significantly differed with LN chronicity status. CONCLUSION: Current clinical indices of LN fail to discriminate ISN/RPS Class in children. Despite its shortcomings, the SLEDAI-R appears to best for measuring LN activity in a clinical setting. The SDI-R is a poor correlate of LN chronicity