Chylomicronemia from GPIHBP1 autoantibodies.

Some cases of chylomicronemia are caused by autoantibodies against glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1), an endothelial cell protein that shuttles LPL to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory findings in 22 patients. All patients had GPIHBP1 autoantibodies and chylomicronemia, but we did not find a correlation between triglyceride levels and autoantibody levels. Many of the patients had a history of pancreatitis, and most had clinical and/or serological evidence of autoimmune disease. IgA autoantibodies were present in all patients, and IgG4 autoantibodies were present in 19 of 22 patients. Patients with GPIHBP1 autoantibodies had low plasma LPL levels, consistent with impaired delivery of LPL into capillaries. Plasma levels of GPIHBP1, measured with a monoclonal antibody-based ELISA, were very low in 17 patients, reflecting the inability of the ELISA to detect GPIHBP1 in the presence of autoantibodies (immunoassay interference). However, GPIHBP1 levels were very high in five patients, indicating little capacity of their autoantibodies to interfere with the ELISA. Recently, several GPIHBP1 autoantibody syndrome patients were treated successfully with rituximab, resulting in the disappearance of GPIHBP1 autoantibodies and normalization of both plasma triglyceride and LPL levels. The GPIHBP1 autoantibody syndrome should be considered in any patient with newly acquired and unexplained chylomicronemia.

Pilot study comparing the Childhood Arthritis & Rheumatology Research Alliance (CARRA) systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans.

OBJECTIVES: To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry. METHODS: Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months. TRIAL REGISTRATION: clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled). RESULTS: Thirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (p = 0.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome. CONCLUSIONS: The CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.

Recurrent parotitis as a presentation of primary pediatric Sjögren syndrome.

Parotitis is a common condition seen in the pediatric population, usually as an isolated occurrence associated with viral or bacterial infection. The differential diagnosis expands when recurrent parotitis is encountered. One etiology is primary pediatric Sjögren syndrome (SS), an autoimmune condition typically associated with dryness of the eyes and mouth in adults. Pediatric patients often present with isolated recurrent bilateral parotitis, however, and we describe 4 such cases in children aged 9 to 17 years at presentation. Despite lack of ocular complaints, 3 of these patients had ocular findings on ophthalmologic exam. Our patients also exhibited classic laboratory abnormalities, including positive antinuclear antibody, SS A, and SS B antibodies; presence of rheumatoid factor; and hypergammaglobulinemia. Consideration of SS in the child with recurrent parotitis is important for timely and appropriate referral and treatment. We review the differential diagnosis of parotitis in children as well as the salient features of pediatric SS.

Clinical outcomes after withdrawal of anti-tumor necrosis factor α therapy in patients with juvenile idiopathic arthritis: a twelve-year experience.

OBJECTIVE: To estimate the length of time to disease flare and the likelihood of achieving clinical remission after discontinuation of treatment with tumor necrosis factor α (TNFα) blockers in patients with juvenile idiopathic arthritis (JIA). METHODS: We conducted a retrospective chart review in a cohort of patients with JIA treated with TNFα inhibitors between January 1, 1998 and November 1, 2009. Demographic information, laboratory data, and medication exposure were extracted using a standardized tool. Outcomes of interest were based on preliminary criteria for remission in JIA. RESULTS: One hundred seventy-one patients with 255 discrete episodes of anti-TNFα treatment were reviewed. The median duration of patient observation was 59.7 months (range 5.8-211.2 months). Among patients in whom disease was inactive after discontinuation of anti-TNFα therapy, 50% had persistently inactive disease at 6 months, and 33% had clinical remission at 12 months. The median duration of anti-TNFα therapy after inactive disease was obtained was 6.1 months (range 0-67.9 months). No significant association was observed between the time to disease flare after cessation of treatment with TNFα antagonists and the length of time from the diagnosis of JIA to the initiation of anti-TNFα therapy, the duration of therapy following the onset of inactive disease, or the total duration of treatment with TNFα antagonists prior to discontinuation. The category of JIA, sex, and age at diagnosis were not associated with the risk of relapse. CONCLUSION: One-third of patients with JIA can successfully undergo withdrawal of treatment with TNFα antagonists and be spared the cost and potential morbidity of treatment for at least 12 months. Further studies are needed to identify factors to accurately identify these patients.