Serum biomarkers of glucocorticoid response and safety in anti-neutrophil cytoplasmic antibody-associated vasculitis and juvenile dermatomyositis.

Glucocorticoids are standard of care for many chronic inflammatory conditions, including juvenile dermatomyositis (JDM) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We sought to define pharmacodynamic biomarkers of therapeutic efficacy and safety concerns of glucocorticoid treatment for these two disorders. Previous proteomic profiling of patients with Duchenne muscular dystrophy (DMD) and inflammatory bowel disease (IBD) treated with glucocorticoids identified candidate biomarkers for efficacy and safety concerns of glucocorticoids. Serial serum samples from patients with AAV (n = 30) and JDM (n = 12) were obtained during active disease, and after treatment with glucocorticoids. For AAV, 8 of 11 biomarkers of the anti-inflammatory response to glucocorticoids were validated (P-value ≤0.05; CD23, macrophage-derived cytokine, interleukin-22 binding protein, matrix metalloproteinase-12, T lymphocyte surface antigen Ly9, fibrinogen gamma chain, angiopoietin-2 [all decreased], and protein C [increased]), as were 5 of 7 safety biomarkers (P-value ≤0.05; afamin, matrix metalloproteinase-3, insulin growth factor binding protein-5, angiotensinogen, leptin [all increased]). For JDM, 10 of 11 efficacy biomarkers were validated (P-value ≤0.05; all proteins except fibrinogen gamma chain) and 6 of 7 safety biomarkers (P-value ≤0.05; AAV proteins plus growth hormone binding protein). The identified efficacy biomarkers may be useful as objective outcome measures for early phase proof-of-concept studies when assessing novel anti-inflammatory drugs in JDM and AAV, and likely in other inflammatory disorders. Similarly, safety biomarkers may also be helpful assessing toxicity of alternatives to glucocorticoids.

Double trouble: therapeutic challenges in patients with both juvenile dermatomyositis and psoriasis.

BACKGROUND: Juvenile dermatomyositis (JDM) and psoriasis are inflammatory disorders that share interferon-α induced responses and dysregulation of cytokines, including tumor necrosis factor alpha. Although 13% of patients with JDM have a family history of psoriasis there is little information concerning children with JDM and psoriasis. OBSERVATIONS: We identified 3 children with both JDM and psoriasis. In 2 cases, psoriatic lesions occurred after the child's JDM symptoms had diminished following effective immunosuppressive therapy (high-dose intermittent intravenous methylprednisolone, methotrexate, and low dose oral corticosteroids). Patient 2, initially diagnosed as having psoriasis, was treated with prednisone and methotrexate but then developed classic JDM, which worsened following use of tumor necrosis factor alpha inhibitor and reduction of prednisone and methotrexate dosage. For each child, their history of JDM complicated the choice of therapy for psoriasis. CONCLUSIONS: Two therapies commonly used to treat psoriasis-phototherapy and tumor necrosis factor-alpha antagonists-must be used with caution in patients with both JDM and psoriasis owing to their potential to exacerbate clinical manifestations of JDM. We discuss the implications affecting treatment of children with these dual diagnoses and consider the pathophysiology linking these 2 conditions.