Hallmark trials in ANCA-associated vasculitis (AAV) for the pediatric rheumatologist.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to a complex group of systemic vasculitides that are characterized by primary small-to-medium sized blood vessel inflammation with the presence of autoantibodies known as ANCA. AAV diseases include Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA), and Microscopic Polyangiitis (MPA). AAVs are challenging conditions associated with high cumulative disease and treatment related morbidity and mortality. Given its rarity and the resulting paucity of pediatric-specific clinical trial evidence, pediatric rheumatologists have had to often extrapolate from adult literature for management and therapeutic decisions. The aim of this review is to provide a comprehensive overview of the important findings and overall conclusions of critical landmark clinical trials in the induction and maintenance treatments in adult AAV for the pediatric rheumatologist. This review also highlights the outcomes of recent pediatric AAV observational studies and discusses the future research priorities in pediatric AAV management.

Monogenic interferonopathies: Phenotypic and genotypic findings of CANDLE syndrome and its overlap with C1q deficient SLE.

OBJECTIVE: To report the clinical and genetic features of the first cases of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome in an Arab population and to compare them with patients of C1q deficient systemic lupus erythematosus (SLE). MATERIALS AND METHODS: This is a retrospective case series of patients with CANDLE syndrome and C1q deficient SLE seen at a single tertiary hospital. Medical records were reviewed for demographic data, clinical and laboratory features, histopathology and imaging findings, and response to therapeutic intervention. Descriptive data were summarized. RESULTS: Three patients from unrelated families fulfilled the clinical manifestations of CANDLE syndrome. The disease onset was within the first 4 months of age. Two patients had uncommon features including uveitis, pulmonary involvement, aseptic meningitis and global delay. Skin biopsy showed heterogeneous findings. Genomic DNA screening was homozygous for mutation in PSMB8, (NM_004159.4:c.212C>T, p.T71M) in one patient and inconclusive for the other two patients. The comparison group was three patients with familial C1q deficient SLE from three unrelated families, who were born to consanguineous parents with at least one affected sibling. They presented with extensive mucocutaneous lesions, discoid rash and scarring alopecia. They required frequent admissions due to infections. CONCLUSION: This is the first report of CANDLE syndrome in an Arab population; our patients had heterogeneous phenotypic and genetic features with overlap manifestations with C1q deficient SLE. Both are monogenic interferonopathies. However, C1q deficient SLE had more systemic inflammatory disease.

The impact of antiphospholipid antibodies in children with lupus nephritis.

BACKGROUND AND OBJECTIVES: To evaluate the frequency of antiphospholipid antibodies (APLa) among patients with childhood lupus nephritis (cLN) and to assess their impact on long-term renal outcomes. DESIGN AND SETTING: This is an observational hospital based study. PATIENTS AND METHODS: Patients with cLN diagnosed by renal biopsy seen between January 2002 and June 2014 were included. APLa positivity was defined if detection was positive on 2 occasions 6-12 weeks apart during their follow up. Demographic features, age at disease onset, disease duration, follow-up duration and clinical and laboratory variables at the time of renal biopsy were collected. The renal biopsy was reviewed for the nephritis class, microthrombi, activity and chronicity indices. Renal outcome measures included the serum creatinine levels, protein/creatinine ratio and end stage renal disease (ESRD). RESULTS: Fifty-nine, (49 female) patients with a mean age of 19.8 years and mean disease duration of 6.8 years were involved. APLa were detected in 46 (78%) patients. Twenty-two patients had class IV nephritis, which was more prevalent in APLa positive patients. The frequencies of class III and V nephritis was similar in 10 patients in each class (7 patients in each class with APLa). The presence of APLa did not correlate with nephritis activity or the chronicity indices. Microthrombosis was found in 10 patients, and 8 of them had APLa. Patients with APLa had a higher frequency of elevated serum creatinine and hypertension, 9 developed ESRD, and 7 had APLa. There was no statistically significant association between the presence of APLa and the accrual damage index and clinical manifestations. Furthermore, there was no association between APLa and other autoantibodies. CONCLUSION: The frequency of APLa in cLN was high. While the association is not statistically significant, APLa positive patients tend to develop renal microthrombi and are probably at higher risk of ESRD.