The Evolution in the Cutaneous and Gastrointestinal Pathology of Pediatric Kohlmeier-Degos Disease Under Combined...

Kohlmeier-Degos disease is a potentially severe multiorgan thrombotic vascular injury syndrome with characteristic cutaneous lesions characterized by depressed porcelain white plaques with telangiectatic rims. This occlusive vasculopathy involves the microvasculature but also extends to affect arterioles and small arteries where a peculiar intravascular and intimal fibrosing reaction occurs. We discovered in earlier studies that complement pathway activation and enhanced type I interferon signaling are held to be a critical impetus for the endothelial cell injury. Significant upregulation of type I interferon signaling is also responsible for the neointimal expansion and fibrosis. We had the opportunity of examining before and after treatment biopsies in a pediatric patient receiving the 3-drug protocol for the treatment of Kohlmeier-Degos disease.

The patient was a 13-year-old girl who presented with a few months history of depressed white macular skin lesions and abdominal pain. A laparotomy revealed multiple serosal porcelain plaques and evidence of acute severe intestinal ischemia. The patient's pretreatment skin and intestinal resection samples showed a striking pauci-inflammatory microangiopathy associated with endothelial cell necrosis and microvascular thrombosis and arteriolar and arterial neointimal hyperplasia with intimal fibrosis, extensive vascular C5b-9 deposition and enhanced type I interferon signaling in the skin and intestine. Extravascular fibrosis with a loss in the expression of CD34 amid fibroblasts was observed. A diagnosis was made of Kohlmeier-Degos disease. The post-treatment biopsies of the skin and intestine demonstrated complete abrogation of both endothelial cell injury and intravascular fibrin thrombi. There was no evidence of neointimal fibrosis. The CD34 negative procollagen scleroderma phenotype was not observed in fibroblasts. A discernible but less intense type I interferon signal was present while the C5b-9 studies were negative in the post-treatment skin biopsy. The intestinal resection specimen obtained several months later had a negative interferon signature. Fibrous intravascular occlusion was limited to rare vessels in the intestinal resection specimen.

The cutaneous and extracutaneous lesions of Kohlmeier-Degos disease are potentially reversible. The combination of therapeutic complement inhibition, downregulation of type I interferon expression, and the promotion of vascular patency and reduced platelet activation through prostacyclin administration define the cornerstone of treatment.