A histologic evaluation of mixed connective tissue disease in childhood

Abstract

Mixed connective tissue disease (MCTD) includes features of scleroderma, dermatomyositis and systemic lupus erythematosus (SLE), and has speckled antinuclear antibodies (ANA) and high titers of anti-RNP antibodies. There are no comprehensive investigations of its histopathology. We have followed 15 children with MCTD, of whom four have died (mean disease duration prior to death 5.4 years). The immediate causes of death were pneumococcal sepsis (two patients), meningococcal sepsis (one patient) and uncontrollable thrombocytopenia (one patient). Material from the three available autopsies and five renal biopsies was reviewed. The most prominent histopathologic feature was widespread proliferative vascular lesions including intimai vascular change in 31 of 58 organs (53 per cent) and medial vessel wall thickening in nine organs (16 per cent). Systemic hypertension was absent; the normal vascular responses to aging could be excluded. Inflammatory infiltrates, often with prominent plasmacytosis, were present in 26 of 58 organs (45 per cent), but fibrinoid vascular change (9 per cent) and fibrosis (14 per cent) were rare. Eight renal specimens all showed some degree of glomerulonephritis; membranous change was present in three, and six showed significant vascular sclerosis. The histopathology of MCTD is superficially similar to systemic sclerosis, but it may be distinguished by less frequent fibrosis, the frequency of organs with intimal vascular change, and a predilection for intimai thickening of large arteries including coronary, pulmonary, renal and aortic. A distinctive replacement of muscle layers by hyaline in the gastrointestinal tract, and an unusual nodular hyperplasia of the thymic medulla were also observed and may be unique features of MCTD. The findings from this study suggest an immunologic basis for MCTD different from those postulated for other rheumatic diseases, and strongly suggest that adjustment of morbidity and mortality expectations for MCTD are necessary.