Dermatology

Cutaneous Reactive Angiomatoses (Angioendotheliomatosis, Diffuse Dermal Angiomatosis, Acroangiodermatitis)

Cutaneous Reactive Angiomatoses (Angioendotheliomatosis, Diffuse Dermal Angiomatosis, Acroangiodermatitis)

Are You Confident of the Diagnosis?

Diagnosis confirmation

Angioendotheliomatosis is part of a spectrum of reactive vascular proliferations in the skin that are best referred to as "cutaneous reactive angiomatoses."Erythematous or purpuric patches and plaques are the most common presentation. They may become necrotic and ulcerate. Some cases have been mistaken for cellulitis or vascular tumors such as angiosarcomas or Kaposi's sarcoma. The lower extremities are the most commonly affected site.

A wide range of clinical and histopathologic findings have been documented, leading to the use of multiple different terms for what is essentially the same condition. Reactive angioendotheliomatosis, diffuse dermal angiomatosis, acroangiodermatitis, and numerous other labels have been applied. Some variants may be more likely to be associated with particular underlying causes (see Who is at Risk below). An increased number of endothelial cells is common to all types, however, and there is usually also at least some increase in the number of blood vessels with discernible lumens {Figure 1, Figure 2, Figure 3, Figure 4).

Figure 1.

Acroangiodermatitis, a vascular proliferation presumably related to venous stasis. The dermis contains a marked increase in the number of capillary-sized blood vessels. Hemorrhage and /or hemosiderin deposition is common.

Figure 2.

Reactive angioendotheliomatosis. There is a marked proliferation of dermal vessels with conspicuous lumens, but solid-appearing clusters of endothelial cells are also evident. Many of the endothelial cells are large, and mitotic figure may be evident, causing concern for angiosarcoma.

Figure 3.

Diffuse dermal angiomatosis. Most of the dermis is occupied by a proliferation of endothelial cells and small, irregularly shaped vascular spaces. (X100)

Figure 4.

Diffuse dermal angiomatosis. The proliferation of endothelial cells is often very cellular, and mitotic figures may be evident. The features may resemble Kaposi's sarcoma to some extent. (X400)

Reactive cutaneous angiomatoses have been mistaken for cellulitis and vascular tumors clinically, and histopathologic features may closely mimic vascular neoplasms. Angiosarcoma, Kaposi sarcoma, glomeruloid hemangioma, epithelioid hemangioendothelioma, Dabska tumor, acquired tufted angioma, Masson's tumor, and intravascular B-cell lymphoma may be differential diagnostic considerations depending on the features of a given case.

Who is at Risk for Developing this Disease?

The disease is rare but can occur in any age group and either gender. It is almost always associated with underlying vascular occlusion. The source of the occlusion may be localized or systemic.

Associated conditions are numerous and varied. They include but are not limited to:

  • Peripheral vascular disease / atherosclerosis

  • Calciphylaxis

  • Systemic infections (eg, subacute bacterial endocarditis)

  • Rheumatoid arthritis and other autoimmune diseases

  • Antiphospholipid antibody syndrome

  • Viral hepatitis

  • Cholesterol emboli

  • Arteriovenous shunts

  • Chronic lymphatic leukemia

  • Monoclonal gammopathy

  • Angiosarcoma

The "diffuse dermal angiomatosis" variant of cutaneous reactive angiomatosis is usually associated with peripheral vascular disease / atherosclerosis. The "acroangiodermatitis" variant seems to be most common with AV malformations, iatrogenic AV fistulas, or venous hypertension.

What is the Cause of the Disease?

Pathophysiology

The pathophysiology is not fully understood, but occlusion of blood vessel lumens appears to be common to all variants of the disease. The occlusion leads to vascular destruction, the recruitment of inflammatory cells and the subsequent reactive proliferation of pericytes and endothelial cells.

Systemic Implications and Complications

The condition manifests within the skin but is actually almost always a harbinger of underlying local or systemic disease. A prompt and thorough evaluation for an underlying cause of vascular occlusion is necessary.

Treatment Options

The optimal approach is to quickly identify and treat the underlying cause of the vascular occlusion. Resolution of skin lesions with antibiotic therapy should occur in cases associated with systemic infection. Vascular bypass surgery has successfully treated lesions caused by atherosclerosis.

Compression garments and pressure pumps have been recommended for the "acroangiodermatitis" variant, but surgical treatment of small fistula, embolization, or laser ablation have also been used. Cases caused by cold agglutinins may respond to avoidance of cold.

Therapy targeted at the lesions themselves may include local or systemic corticosteroids. Isotretinoin has also been used Table I summarizes therapies that have been reported for some of the different variants.

Table I.

Treatment options for cutaneous reactive angiomatoses
Type Topical Systemic Surgical
Reactive angioendotheliomatosis Treatment of underlying systemic disorder with antibiotics
Attenuation of neoangiogenesis with corticosteroids
Diffuse dermal angiomatosis Isotretinoin for localized disease of the breast (2 months of 1mg/kg) Early vascular bypass surgery of affected area
Corticosteroids
Acroangiodermatitis Compression garments and pressure pumps Surgical elimination of small fistulae
Embolization
Laser ablation
Prednisone 5mg per day
Sulphasalazine 5mg per day
Reactive intravascular histiocytosis Compression garments and pressure pumps Hydroxychloroquine 200mg per day Cyclophosphamide 200mg per day intravenously x3 days, 150mg per day orally x 5 days, 100mg per day orally x 7 days
Reactive glomeruloid angioendotheliomatosis Avoidance of exposure to cold
Angiopericytomatosis Treatment of underlying multiple myeloma with corticosteroids and immunosuppression

Optimal Therapeutic Approach for this Disease

The optimal approach is to quickly identify and treat the underlying cause of the vascular occlusion.

Patient Management

Management will depend upon the underlying cause.

Unusual Clinical Scenarios to Consider in Patient Management

As noted above, virtually any cause of vascular occlusion may result in reactive angioendoetheliomatosis, but it should be remembered that malignancies (including underlying angiosarcomas) are rare associations, as are hematolymphoid neoplasms. In addition, it is now clear that cases erroneously referred to in the past as "malignant angioendotheliomatosis" actually represent an intravascular variant of large B-cell lymphoma.

What is the Evidence?

Rongioletti, F, Rebora, A. "Cutaneous reactive angiomatoses: patterns and classification of reactive vascular proliferation". J Am Acad Dermatol. vol. 49. 2003 Nov. pp. 887-96.

(This article is a detailed review of all subtypes of cutaenous reactive angiomatoses and provides useful clinical and histopathologic images.)

McMenamin, ME, Fletcher, CD. "Reactive angioendotheliomatosis: a study of 15 cases demonstrating a wide clinicopathologic spectrum". Am J Surg Pathol. vol. 26. 2002 Jun. pp. 685-97.

(The wide variability in presentation, clinical course, and associations with numerous systemic diseases are documented in this case series of 15 patients with reactive cutaneous angiomatoses.)

Kim, S, Elenitsas, R, James, WD. "Diffuse dermal angiomatosis: a variant of reactive angioendotheliomatosis associated with peripheral vascular atherosclerosis". Arch Dermatol. vol. 138. 2002 Apr. pp. 456-8.

(This case report is a good illustration of the "diffuse dermal angiomatosis" variant of reactive angiomatosis.)

Utermann, S, Kahle, B, Petzoldt, D. "[Successful long-term therapy of Stewart-Bluefarb syndrome]". Hautarzt. vol. 51. 2000 May. pp. 336-9.

(This case study describes a 32-year-old female with Stewart-Bluefarb syndrome, a subtype of acroangiodermatitis, who was successfully treated multiple times with embolization of effected vessels.)

Rieger, E, Soyer, HP, Leboit, PE, Metze, D, Slovak, R, Kerl, H. "Reactive angioendotheliomatosis or intravascular histiocytosis? An immunohistochemical and ultrastructural study in two cases of intravascular histiocytic cell proliferation". Br J Dermatol. vol. 140. 1999 Mar. pp. 497-504.

(This manuscript describes the clinical course of two female patients and provides a discussion of the underlying pathogenesis.)

Rongioletti, F, Gambinil, C, Smollerl, BR, Parodi, A, Rebora, A. "Angiopericytomatosis and subcutaneus thrombophlebitis in multiple myeloma". Br J Dermatol. vol. 147. 2002 Nov. pp. 1037-40.

This case report describes a 70-year-old man with B-cell non-Hodgkin’s lymphoma with episodes of cutaneous reactive angiomatosis due to cold agglutinins.)

Mariñas, EA, Vidaurrazaga, N, Burgos-Bretones, JJ, Eizagirre, X, de Lagrán, ZM, Izu, R, Díaz-Pérez, JL. "Cutaneous reactive angiomatosis associated with chronic lymphoid leukemia". Am J Dermatopathol. vol. 30. 2008 Dec. pp. 604-7.

(This case report describes a 59-year-old man with B-chronic lymphocytic leukemia found to have lesions consistent with cutaneous reactive angiomatosis. This is the first case to describe complete involution of cutaneous reactive angiomatosis without treatment.)

Prinz Vavricka, BM, Barry, C, Victor, T, Guitart, J. "Diffuse dermal angiomatosis associated with calciphylaxis". Am J Dermatopathol. vol. 31. 2009 Oct. pp. 653-7.

(This retrospective study looked at 11 cases of skin biopsies taken of patients with calciphylaxis. Upon histologic examination all cases had some degree of diffuse dermal proliferation suggesting that diffuse dermal angiomatosis is a common finding in patients with necrotizing ulcers due to calciphylaxis.)

(Draper, BK, Boyd, AS. "Diffuse dermal angiomatosis". J Cutan Pathol. vol. 33. 2006 Sep. pp. 646-8.

(This is another report of diffuse dermal angiomatosis secondary to peripheral atherosclerosis. The cutaneous lesions resolved after revascularization of the diseased vessels.)

10. Clarke, LE, Julian, KG, Clarke, JT, Ioffreda, MD. "Reactive angioendotheliomatosis in association with a well differentiated angiosarcoma". Am J Dermatopathol. vol. 27. 2005 Oct. pp. 422-7.

(This report describes the unusual occurence of reactive angioendotheliomatosis overlying a well-differentiated angiosarcoma.)
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