What more can we learn from muscle histopathology in children with dermatomyositis/polymyositis?

OBJECTIVE To correlate disease course and complications in children with juvenile dermatomyositis (JDM) and polymyositis (JPM) with specific features of muscle pathology on biopsy. METHODS This is a retrospective cohort analysis of 59 children diagnosed with JDM or JPM between 1965 and 1998 and followed at the Cincinnati Children's Hospital Medical Center (CCHMC) for a mean duration of 7.3 years (range 1.1-24.5 years). Disease course was characterized as limited, chronic non-ulcerative or chronic ulcerative, similar to previously defined disease course subtypes reported by Crowe et al.(1). All subjects had diagnostic muscle biopsies performed at CCHMC and had disease for at least two years' duration in order to classify their disease course as either limited or chronic. Features of muscle histopathology that were evaluated included loss of the intramuscular capillary bed, infarct, perifascicular myopathy, direct immunofluorescence (DIF) staining of the intramuscular vasculature and specifically, the locale of DIF staining, i.e., small arteries or capillaries. Disease complications that were assessed included calcinosis, contractures, muscle atrophy, lipodystrophy, gastrointestinal ulceration, cutaneous ulceration and death. Data analysis was completed using Chi-square or Fisher's exact tests and logistic regression modeling. RESULTS Twenty-two children (37%) had limited disease, 24 (41%) had chronic non-ulcerative disease and 13 (22%) had chronic ulcerative disease. Neither loss of the intramuscular capillary bed nor perifascicular myopathy on muscle biopsy significantly correlated with disease course or the various complications evaluated in this study. DIF staining of intramuscular vessels overall was not significantly associated with clinical disease course, but the localization of DIF staining to intramuscular arteries (rather than to capillaries) was significantly associated with the outcome of chronic ulcerative disease. Nine of the 13 children with chronic ulcerative disease had DIF-arterial staining on muscle biopsy (69%), significantly greater than DIF-arterial staining in children with limited disease (32% had DIF-arterial staining) (p = 0.04), chronic non-ulcerative disease (8% had DIF-arterial staining) (p = 0.0002), and non-ulcerative disease overall (limited + chronic non-ulcerative disease groups combined) (20% had DIF-arterial staining), with p = 0.001. Additionally, lack of DIF-arterial staining on biopsy was significantly correlated with patients not having gastrointestinal ulceration (p = 0.002), cutaneous ulceration (p = 0.004) and/or death (p = 0.02) as disease-related complications. Infarct on muscle biopsy was significantly associated with the development of chronic ulcerative disease (p = 0.02), being present on biopsy in 23% of children with chronic ulcerative disease compared with none of the patients with chronic non-ulcerative disease and 4% of those with limited disease. Infarct on muscle biopsy correlated with the outcomes of death (p = 0.01) and gastrointestinal ulceration (p = 0.03), but not with the development of cutaneous ulceration (p = 0.18). CONCLUSION DIF-arterial staining and infarct on muscle biopsy are significantly associated with the development of chronic ulcerative disease in JDM and JPM, while perifascicular myopathy and loss of the intramuscular capillary network are not associated with disease course. The presence of DIF-arterial staining and infarct on biopsy should suggest early use of second-line therapeutic agents to more quickly bring disease activity under control.