Degos Disease

A C5b-9/Interferon-α–Mediated Endotheliopathy Syndrome

Cynthia M. Magro, MD; Jonathan C. Poe, PhD; Connie Kim; Lee Shapiro, MD; Gerard Nuovo, MD; Mary K. Crow, MD; Yanick J. Crow, MedSci, MBBS, MRCP, PhD

Disclosures

Am J Clin Pathol. 2011;135(4):599-610. 

In This Article

Abstract and Introduction

Abstract

Degos disease is a lethal small vessel angiopathy targeting the skin, gastrointestinal tract, and central nervous system, potentially developing in the setting of known autoimmune disease, although forme fruste primary variants exist. Its pathogenetic basis is unknown.
Four cases of Degos disease were encountered in archival material, representing 2 men, ages 38 and 43 years, and 2 females, ages 48 and 2 years; 3 patients died of disease. All had characteristic skin lesions with gastrointestinal involvement; other affected organs included brain in one and pericardium and pleura in another. Skin biopsies showed pauci-inflammatory thrombogenic microangiopathy with endothelial cell injury. Extracutaneous organs demonstrated fibromucinous occlusive arteriopathy. Prominent vascular C5b-9 was seen in the skin, gastrointestinal tract, and brain. All cases had evidence of high expression of interferon-α (based on tissue expression of MXA, a type I interferon-inducible protein), endothelial tubuloreticular inclusions, and an interferon gene signature in peripheral blood mononuclear cells. The MXA expression paralleled the pattern of C5b-9 deposition.
Degos disease is a distinct vascular injury syndrome whereby a dysregulated interferon-α response in concert with membranolytic attack complex deposition may contribute to the unique vascular changes. Understanding the pathophysiology of the disease process could lead to more directed therapies, including terminal complement inhibition with agents such as eculizumab.

Introduction

Degos disease falls under the alternative appellation of malignant atrophic papulosis based on the fatal outcome that frequently characterizes its clinical course.[1–7] Morphologic features of Degos disease include a pauci-inflammatory thrombotic microangiopathy syndrome with characteristic clinical features, including porcelain-like depressed infarcts of the skin concurrent with similar lesions involving the gastrointestinal tract.[7] The 3 main targeted organ systems are skin, gastrointestinal tract, and central nervous system (CNS).[7] The gut infarcts may lead to perforation and death, typically of sepsis. There is a growing list of underlying predisposing conditions associated with Degos disease, including lupus erythematosus, dermatomyositis, scleroderma, and certain thrombophilic tendency states such as factor V Leiden mutation and antiphospholipid antibody syndrome.[3,5,8–11] Hereditary forms have been described.[1] The frequent catastrophic outcome is characteristically attributable to the local effects of severe tissue ischemia.

We describe 4 cases of Degos disease, exploring its pathophysiologic basis, a critical step in the establishment of novel therapeutic options to treat this frequently fatal condition. Three of the cases have been previously reported.[12–14] A unifying pathophysiologic basis for the vascular changes is proposed.

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