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Angioendotheliomatosis

  • Author: Anna Zalewska, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Oct 10, 2014
 

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]

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).[3, 4, 5, 6] 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.[7] In reactive angioendotheliomatosis, frequent association with systemic infection, subacute bacterial endocarditis, acute otitis media, pulmonary tuberculosis, allergic response to cow's milk protein, arthritis,[8, 9] cryoproteinemias, monoclonal gammopathies, iatrogenic arteriovenous fistulas, antiphospholipid syndrome,[10, 11] severe peripheral vascular atherosclerotic disease, or chronic venous insufficiency,[12] 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.

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.[13] A history of heavy smoking could be regarded as an important factor in diffuse dermal angiomatosis pathogenesis.

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Epidemiology

Frequency

International

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.[14]

Mortality/Morbidity

The malignant form 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.

Reactive angioendotheliomatosis is a self-limited entity; however, recurrences may be observed. The prognosis depends on the underlying cause.

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[15] ; however, reactive angioendotheliomatosis is most common in adulthood.

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Contributor Information and Disclosures
Author

Anna Zalewska, MD, PhD Professor of Dermatology and Venereology, Psychodermatology Department, Chair of Clinical Immunology and Microbiology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Arash Taheri, MD Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Nothing to disclose.

References
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