Exploring the pathophysiologic basis of constrictive pericarditis of Kohlmeier Degos disease: A case series and review of the literature.

Kohlmeier-Degos Disease is a unique thrombotic microvascular and arteriopathic vasculopathy that is highly selective in the organs it targets. It invariably involves the skin and can be a purely cutaneous process. It affects both the microvasculature and the arterial system ranging from a thrombogenic microangiopathy to a fibrointimal obliterative arteriopathy with an accompanying background of extravascular fibrosis. A potentially lethal complication of Kohlmeier-Degos disease is constrictive pericarditis and pleuritis. We present three male patients, ages 26 years, 46 years and 58 years of age with established cutaneous and gastrointestinal Kohlmeier-Degos disease who developed progressive pericarditis which in two necessitated a pericardiectomy. There are 6 other reported cases, 5 in men, with restrictive symptoms developing on average 6 years following the onset of skin disease and all with gastrointestinal involvement. Half of the patients died within one year following the diagnosis of cardiopulmonary restrictive disease. The restrictive symptoms developed within 12 months, 2 years and 11 years following the initial skin presentation. In one patient this complication developed despite receiving eculizumab, indicative that this extravascular fibrosing reaction was not complement mediated as opposed to the thrombotic microvascular component of the disease which is C5b-9 mediated. Two of the three patients had evidence of right ventricular dysfunction. Two of our patients died within 1 year of developing constrictive pericarditis due to progressive cardiopulmonary failure. A profibrogenic process resembling scleroderma was seen given the degree of smooth muscle actin staining along with a mirror image reduction in CD34 expression within the fibrotic pleura and pericardium. There was significant upregulation in type I interferon signaling in cases tested as revealed by the degree of staining for MXA, the surrogate type I interferon marker. We propose that excessive type I interferon signaling results in the influx of monocyte derived dendritic cells with subsequent transdifferentiation into potent collagen producing myofibroblasts. We believe that targeting and suppressing type I interferon signaling should be a cornerstone of early therapy in patients with Kohlmeier- Degos disease to prevent pleural and pericardial fibrosis.