Rituximab treatment for chronic steroid-dependent Henoch-Schonlein purpura: 8 cases and a review of the literature.

BACKGROUND: Henoch-Schonlein purpura (HSP) is a small vessel vasculitis that is characterized by non-thrombocytopenic purpura, abdominal pain, arthritis, and glomerulonephritis. Typically, HSP is self-limited requiring only supportive care, but more severe cases may require corticosteroid (CS) treatment. Rarely, a subset of these patients has persistent rash, arthritis, abdominal involvement, or renal disease despite treatment with CS, or has disease recurrence on CS tapering. Refractory HSP has been effectively treated with a variety of CS sparing therapies. For life-threatening refractory HSP, the B cell depleting agent, rituximab (RTX), has been reported as beneficial for children with substantial renal or central nervous system involvement. However, RTX use for children with less severe HSP, but chronic CS dependent disease refractory to CS sparing immunomodulatory agents, has been less well explored. Herein, we describe 8 children treated with RTX for chronic refractory HSP and report a reduction in recurrent hospitalizations and eventual CS discontinuation. METHODS: This is a retrospective analysis of eight children who were treated with RTX for chronic CS dependent HSP during the years 2006-2014 at a single institution. A chart review of the electronic medical record was performed to determine the presenting symptoms, the type and duration of treatment received, and the number of hospitalizations prior to and after RTX. The number of hospitalizations and oral corticosteroid burden were analyzed using the Wilcoxon signed rank test. RESULTS: Prior to receiving RTX, seven patients had at least one hospitalization for HSP (median 1.5, range 0-3). Following RTX, only two patients were hospitalized, each a single time for recurrent abdominal pain. The median oral CS burden was 0.345 mg/kg/day before RTX and 0 mg/kg/day at 6 months (p = 0.078), 1 year (p = 0.0625), and 2 years (p = 0.03) following RTX infusion. Seven out of eight children met remission criteria, defined as no active rash, arthritis, nephritis (hematuria and proteinuria), or gastrointestinal distress following RTX. No serious adverse events were noted. CONCLUSION: Overall, RTX effectively reduced the number of hospital admissions and oral CS burden. RTX also helped most all children achieve clinical remission. RTX appears to be an effective and safe alternative for chronic CS dependent and immunomodulatory refractory childhood HSP.

Magnetic Resonance Imaging Findings following Intraarticular Infliximab Therapy for Refractory Temporomandibular Joint Arthritis among Children with Juvenile Idiopathic Arthritis.

OBJECTIVE: To evaluate the involvement of intraarticular (IA) infliximab (IFX) in the management of temporomandibular joint (TMJ) arthritis associated with juvenile idiopathic arthritis (JIA) that is refractory to systemic treatment and IA corticosteroid therapy. METHODS: Ours was a retrospective study of children with JIA who received IA IFX into the TMJ. The effectiveness of treatment on the progression of acute and chronic changes was assessed by a quantitative magnetic resonance imaging scoring system. RESULTS: Median acute and chronic scores worsened by 0.25 and 0.75, respectively. In multivariate analysis, worsening acute scores and passage of time predicted worsening of the chronic scores. CONCLUSION: IA IFX allowed for progression of refractory TMJ arthritis in most but not all children with JIA.

Safety and efficacy of rituximab in childhood-onset systemic lupus erythematosus and other rheumatic diseases.

OBJECTIVE: Rituximab (RTX) has been used to treat many pediatric autoimmune conditions. We investigated the safety and efficacy of RTX in a variety of pediatric autoimmune diseases, especially systemic lupus erythematosus (SLE). METHODS: Retrospective study of children treated with RTX. Effectiveness data was recorded for patients with at least 12 months of followup; safety data was recorded for all subjects. RESULTS: The study included 104 children; 50 had SLE. Improvements in corticosteroid dosage, physician's global assessment of disease activity, and SLE-associated markers of disease activity were seen. The incidence of hospitalized infections was similar to previous studies of patients with childhood-onset SLE. CONCLUSION: RTX can be safely administered to children and appears to contribute to decreased disease activity and steroid burden.

High doses of infliximab in the management of juvenile idiopathic arthritis.

OBJECTIVE: To review our experiences with high-dose infliximab (IFX) to treat juvenile idiopathic arthritis (JIA). We routinely use high doses of IFX (10-20 mg/kg) in children with recalcitrant or highly active JIA. Although biologics have revolutionized treatment of JIA, many patients have active disease despite therapy. Studies have shown benefits of high-dose IFX in several conditions, including inflammatory bowel disease, psoriasis, and idiopathic uveitis. The safety and effectiveness of high-dose IFX have not been evaluated in JIA. METHODS: We performed a retrospective review of children with JIA who received IFX ≥ 10 mg/kg. We recorded all serious adverse events (SAE), medically important infections, and infusion reactions. We also recorded the physician global assessment of disease activity (MD global) and active joint count (AJC) at initiation of high-dose IFX and 3, 6, and 12 months thereafter. RESULTS: Fifty-eight subjects received a total of 1064 infusions over 95 person-years. There were a total of 9 SAE (9.5/100 person-yrs), 7 of which were potentially related to therapy, and 6 infusion reactions (0.5%), none constituting anaphylaxis. Statistically significant improvements were observed in the AJC (median 0, range 0-31, vs 2, 0-39) and MD global (12, 2-31, vs 22, 5-80) over the first year. CONCLUSION: High-dose IFX appears safe in the management of JIA. Future prospective controlled studies are necessary to evaluate its safety and efficacy.