Angioendotheliomatosis

Updated: Jun 07, 2017
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

Angioendotheliomatosis is a histopathological term characterized by proliferation of cells within vascular lumina with secondary intravascular thrombi and obliteration of the vessels. While angioendotheliomatosis was initially thought to be a single disease entity, recent studies showed that it may be divided into two or maybe more variants.

A benign reactive variant (reactive angioendotheliomatosis [RAE]) is a rare and poorly defined disorder characterized by intravascular proliferation of cells expressing endothelial cell markers.

A malignant variant (malignant angioendotheliomatosis [MAE]) is an angiotropic lymphoma mostly of the B-cell phenotype.

Previously, angioendotheliomatosis with cells of histiocytic differentiation have also been described; however, currently this entity is called intralymphatic histiocytosis. This differentiation could possibly be due to the development of more specific immunohistochemical markers. [1, 2, 3]

Intravascular histiocytic cell proliferation may be a neoplastic proliferation of histiocytes (intralymphatic histiocytosis) or an early stage of classic reactive angioendotheliomatosis. The latter represents residual cells associated with the organization of microthrombi, which are later followed by endothelial cell proliferation.

A local variant of reactive angioendotheliomatosis associated with ischemia resulting from arterial occlusion and atherosclerosis has also been described and is called diffuse dermal angiomatosis (DDA). [4, 5, 6, 7] This variant is confined to the ischemic area.

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Pathophysiology

The pathogenesis of reactive angioendotheliomatosis is still not fully elucidated. Although the exact stimulus for the proliferation of endothelial cells is not known, occlusion of vascular lumina of different causes seems to be the common feature of this disease. [8, 9] In reactive angioendotheliomatosis, frequent association with systemic infection, subacute bacterial endocarditis, acute otitis media, pulmonary tuberculosis, allergic response to cow's milk protein, arthritis, [10, 11] cryoproteinemias, monoclonal gammopathies, iatrogenic arteriovenous fistulas, antiphospholipid syndrome, [12, 13] severe peripheral vascular atherosclerotic disease, or chronic venous insufficiency, [14] has been reported.

These findings suggest that reactive angioendotheliomatosis represents a hypersensitivity reaction. Probably different stimuli (eg, bacteria, viruses, cryptoproteins) can lead to the vessels occlusion, hypoxemia, and subsequently endothelial cell proliferation. Some authors suggest that reactive angioendotheliomatosis is an unusual residuum of leukocytoclastic vasculitis.

The lesions of malignant angioendotheliomatosis are thought to result from a sludging effect of the circulating malignant lymphoid cells. Fibrin deposits seem to play a role in this process, thus explaining the infarctive symptoms patients may experience. [15]

In diffuse dermal angiomatosis, in which the vessels are partially occluded by atherosclerotic plaques, a local increase of vascular endothelial growth factor (VEGF) caused by hypoxia that can subsequently lead to endothelial cell proliferation is a possible cause. [16] A history of heavy smoking could be regarded as an important factor in diffuse dermal angiomatosis pathogenesis.

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Epidemiology

Frequency

About 100 cases of malignant angioendotheliomatosis and about 40 cases of the reactive form have been described worldwide. The first case of RAE was described by Gottron and Nikolowski in 1958. [17]

Sex

Men and women are equally affected by both forms of angioendotheliomatosis.

Age

Most patients presenting with the malignant form are 40-80 years. The average age at onset of the malignant form is about 60 years.

The reactive form has been described in all age groups, from infancy to old age [18] ; however, reactive angioendotheliomatosis is most common in adulthood.

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Prognosis

Malignant angioendotheliomatosis is a multisystem disorder that is usually fatal. It has a poor prognosis, with an average survival time of 13 months. In about 80% of patients, a fatal outcome is observed within a year of diagnosis.

In diffuse dermal angiomatosis, after bypass surgery, skin lesions (even ulcerative) demonstrate rapid improvement, with subsequent total healing sometimes leaving residual scarring, usually in 6 weeks maximum.

Reactive angioendotheliomatosis has a good prognosis and usually regresses when the underlying disease, if discovered, is successfully treated. The disease sometimes regresses spontaneously. The prognosis depends on the underlying cause.

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