Jason A. Dare

Juvenile dermatomyositis as a paraneoplastic phenomenon: an update.

Approximately 33% of adult patients with dermatomyositis develop malignancy with up to 42% presenting after the diagnosis has been made; careful evaluation for malignancy is often undertaken at the time of dermatomyositis diagnosis. This phenomenon has rarely been noted in pediatric patients and extensive workup for malignancy is not indicated in pediatric patients. In 1993, 6 cases were reported in which juvenile dermatomyositis/polymyositis (JDM/PM) appeared to be part of a paraneoplastic phenomenon. Our objective was to update the literature for reported cases of malignancy associated with JDM/PM; we reviewed the literature over the last 15 years and located 6 additional cases. In 9 of 12 reported patients an unusual physical finding such as splenomegaly or lymphadenopathy was noted at the time of diagnosis, and in the entire group, the malignancy occurred within a mean of 12 months. It is less likely that JDM/PM in pediatric patients is a paraneoplastic phenomenon as it is in adult patients. However, if the physical examination at the time of diagnosis of JDM/PM is atypical the presence of malignancy must be considered and a more in-depth evaluation to rule out malignancy should be performed prior to the initiation of treatment.

Preliminary response to Janus kinase inhibition with baricitinib in chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE)

Preliminary response to Janus kinase inhibition with baricitinib in chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) G Montealegre, A Reinhardt, P Brogan, Y Berkun, A Zlotogorski, D Brown, P Chira, L Gao, J Dare, S Schalm, R Merino, D Chapelle, H Kim, S Judd, M O’Brien, A Almeida De Jesus, Y Kim, B Kost, Y Huang, S Paul, A Brofferio, C-C Lee, C Hadigan, T Heller, C Minniti, K Rother, R Goldbach-Mansky

Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease

To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti–tumor necrosis factor (anti‐TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease.

Transcriptional profiles of JIA patient blood with subsequent poor response to methotrexate

Objective The mechanisms that determine the efficacy or inefficacy of MTX in JIA are ill-defined. The objective of this study was to identify a gene expression transcriptional signature associated with poor response to MTX in patients with JIA. Methods RNA sequencing was used to measure gene expression in peripheral blood mononuclear cells collected from 47 patients with JIA prior to MTX treatment and 14 age-matched controls. Differentially expressed baseline genes between responders and non-responders were evaluated. Biological differences between all JIA patients and controls were explored by constructing a signature of differentially expressed genes. Unsupervised clustering and pathway analysis was performed. Results A signature of 99 differentially expressed genes (Bonferroni-corrected P < 0.05) capturing the biological differences between all JIA patients and controls was identified. Unsupervised clustering of samples based on this list of 99 genes produced subgroups enriched for MTX response status. Comparing this gene signature with reference signatures from sorted cell populations revealed high concordance between the expression signatures of monocytes and of MTX non-responders. CXCL8 (IL-8) was the most significantly differentially expressed gene transcript comparing all JIA patients with controls (Bonferroni-corrected P = 4.12 × 10-10). Conclusion Variability in clinical response to MTX in JIA patients is associated with differences in gene transcripts modulated in monocytes. These gene expression profiles may provide a basis for biomarkers predictive of treatment response.

Serum S100A8/A9 and S100A12 Levels in Children with Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinical Inactive Disease During and Flare after Discontinuation of Anti‐TNF Therapy

To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti–tumor necrosis factor (anti‐TNF) therapy and the occurrence of disease flare following withdrawal of anti‐TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA).