ABSTRACT
Background: Cytokine storm syndromes (CSS) are life-threatening systemic inflammatory disorders caused by immune system dysregulation. They can lead to organ failure and are triggered by various factors, including infections, malignancy, inborn errors of immunity, and autoimmune conditions. Trisomy 21 (TS21), also known as Down syndrome, is a genetic disorder associated with immune dysfunction, increased infection susceptibility, and inflammation. While TS21 has been linked to infectious-triggered hyperinflammation, its role as a primary cause of CSS has not been confirmed. Case Presentation. We present a case of a 16-year-old male with TS21 with fever, rash, joint pain, and abdominal symptoms. Extensive investigations ruled out infections, autoimmune conditions, malignancies, and inborn errors of immunity as triggers for a CSS. The patient's symptoms improved with treatment using IL-1 inhibition and corticosteroids. Conclusions: This case reinforces that TS21 is an immune dysregulation disorder and highlights the importance of considering CSS in TS21 patients, even when triggers are unclear. The positive response to IL-1 inhibition in this patient suggests that dysregulation of the IL-1 superfamily and the NLRP3 inflammasome may contribute to CSS in TS21. This finding raises the possibility of using IL-1 inhibition as a treatment approach for CSS in TS21 patients.
ABSTRACT
OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.
Subject(s)
Lupus Nephritis , United States , Child , Humans , Lupus Nephritis/drug therapy , Immunosuppressive Agents , Retrospective Studies , Cyclophosphamide/therapeutic use , KidneyABSTRACT
OBJECTIVE: To determine factors associated with diagnostic delays and outcomes in juvenile dermatomyositis (JDM) in the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry (CLR). METHODS: This was a cross-sectional study of subjects aged 0 to 17 years with JDM enrolled to the CLR from 2010 to 2015. Access to care was measured by calculating the distance from the subject zip code of residence to the treating pediatric rheumatology center and determining the state density of pediatric rheumatologists based on the 2015 American College of Rheumatology Workforce Study. Delay was categorized as early (<30 days), typical (1-3 months), moderate (3-12 months), and severe (>12 months). Ordered generalized additive models were used to determine the association between these measures and diagnostic delays. RESULTS: The median time to diagnosis was 3.1 months; 37.2% of patients experienced moderate delays, and 14.6% experienced severe delays. In a univariate analysis, younger age of disease onset and male sex were associated with delays. Using a generalized additive model accounting for age, sex, race, and ethnicity, increasing distance from treating pediatric rheumatologist and younger age at disease onset were associated with diagnostic delay. There was no association between the state density of rheumatologists and diagnostic delays in this model. CONCLUSION: In the CLR, we found moderate to severe diagnostic delays in the majority of subjects with JDM. Our data suggest that access to care, measured as the distance traveled to treating rheumatologist, is an important factor associated with delays in care but also highlight age as a contributing factor, suggesting that JDM may be less recognizable in young children.
