Am J Dermatopathol 2017 Jan;39(1):33-39

*Virginia Tech Carilion Dermatology and Mohs Surgery, Roanoke, VA; and †Cleveland Clinic, Dermatology and Plastic Surgery Institute, Cleveland, OH.

Reactive angioendotheliomatosis (REA) is a rare benign angioproliferative condition of the skin, which has been noted to occur in patients with a variety of underlying systemic diseases. Histopathologically, this condition is characterized by vascular proliferation, and endothelial cell hyperplasia within the lumina and around dermal vessels, without significant cellular atypia. Since the first case of RAE was reported in 1958, multiple histologic patterns of benign cutaneous vascular proliferations with similar clinical presentations to RAE have been described in the literature and have been proposed as subtypes of the originally described condition. Read More

J Biol Regul Homeost Agents 2016 Apr-Jun;30(2 Suppl 2):39-43

Department of Pathology, University of Virginia Health System, Charlottesville, Virginia, USA.

A 70-year-old Caucasian male presented to our clinic for a pruritic eruption progressing over several months. He complained of fatigue with a 20-pound weight loss over the past year. On presentation, the patient had browny-yellow to violaceous, purpuric, macular and papular lesions on the legs, arms, lower abdomen and back. Read More

Vet Radiol Ultrasound 2017 Mar 5;58(2):E16-E21. Epub 2016 May 5.

Department of Pathobiology, Auburn University College of Veterinary Medicine, Auburn, AL 36849.

A 10-year-old, castrated male domestic short-haired cat was presented with an acute history of seizures, lethargy, anorexia, vomiting, and dyspnea. Magnetic resonance imaging of the brain showed multifocal areas of gray matter T2-weighted hyperintensity. The lesions did not enhance with intravenous contrast. Read More

Pathol Res Pract 2016 Apr 31;212(4):258-63. Epub 2015 Dec 31.

Anatomical Pathology Department, Marqués de Valdecilla University Hospital, Medical Faculty, University of Cantabria and IDIVAL, Santander, Spain.

Intravascular histiocytosis (IVH) is a rare condition of uncertain pathogenesis often associated with rheumatoid arthritis (RA) exclusively observed in the skin. In a retrospective study of 207 consecutive cases of aortic valve disease, we observed two cases of IVH characterized by the presence of thin-walled, dilated blood vessels containing collections of CD68+ and CD163+ mononuclear histiocytes. Immunostains for CD31, CD34, and D2-40 confirmed the intravascular location of these histiocytes. Read More

Am J Dermatopathol 2015 Oct;37(10):783-9

*Department of Pathology, I.U. Cerrahpasa Medical Faculty, Istanbul, Turkey; †Department of Pathology, Istanbul Training and Research Hospital; ‡Department of Dermatology, Marmara University; §Department of Dermatology, Istanbul Training and Research Hospital; and ¶Department of Dermatology, I.U. Cerrahpasa Medical Faculty, Istanbul, Turkey.

Intravascular/intralymphatic histiocytosis (IV/ILH) is a rare, reactive cutaneous condition, with uncertain pathogenesis. It may be associated with various inflammatory and neoplastic diseases. Although the clinical presentation is various, the biopsies reveal dilated vessels, mostly lymphatics, containing aggregates of histiocytes within their lumina. Read More

Lupus 2015 Dec 31;24(14):1557-61. Epub 2015 Jul 31.

Krishna Institute of Medical Sciences, Karad, India.

Background: Antiphospholipid antibody syndrome is an autoimmune disorder associated with pregnancy complications, venous and/or arterial thrombosis and the presence of antiphospholipid antibodies. This syndrome is known to present with various cutaneous features, but association with reactive angioendotheliomatosis has been described rarely in the literature.

Results: A woman in her thirties with a past history of three consecutive abortions developed purpuric, ulcerative plaque over the plantar aspect of the foot. Read More

Int J Dermatol 2015 Nov 30;54(11):e480-2. Epub 2015 Jul 30.

Department of Pathology, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.

Int J Dermatol 2015 Sep 14;54(9):e372-3. Epub 2015 Jul 14.

Department of Dermatology, Second University of Naples, Naples, Italy.

JFMS Open Rep 2015 Jan-Jun;1(1):2055116915579684. Epub 2015 Jun 1.

Syu Syu CAT Clinic, Tokyo, Japan.

A 3-year-old domestic shorthair cat presented with lethargy and anorexia. A blood test showed regenerative anaemia and thrombocytopenia. Thoracic radiographs showed a small amount of pleural effusion. Read More

Am J Dermatopathol 2015 May;37(5):401-4

*Dermatopathology Section, Department of Dermatology, Boston University School of Medicine, Boston, MA; and †Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX. P. P. Aung is currently affiliated to the Department of Pathology and Lab Medicine, UT-MD Anderson Cancer Center, Houston, TX.

Reactive angioendotheliomatosis (RAE) is a rare cutaneous vascular disorder characterized by intravascular hyperplasia of endothelial cells, sometimes with a vascular proliferation. Intravascular histiocytosis (IH) is a similar vascular disorder characterized by the presence of dilated vessels containing aggregates of mononuclear histiocytes (macrophages) within their lumina. Although their pathogenesis remains uncertain, there has been speculation about the possible relationship between IH and RAE. Read More

Clin Exp Dermatol 2015 Jan 30;40(1):48-51. Epub 2014 Sep 30.

Bristol Dermatology Department, Bristol Royal Infirmary, Bristol University Hospitals NHS Foundation Trust, Bristol, UK.

We present the case of a 54-year-old patient with renal transplant who developed unusual vascular changes on the forearm distal to a functioning arteriovenous fistula, as well as a painful ulcerated lesion on her anterior abdominal wall. We believe that the diffuse dermal angioendotheliomatosis variant of reactive angioendotheliomatosis had a role in the pathogenesis of this patient's lesions. Read More

J Am Acad Dermatol 2014 Dec 26;71(6):1212-7. Epub 2014 Sep 26.

Department of Dermatology, Mayo Clinic, Rochester, Minnesota; Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: Diffuse dermal angiomatosis (DDA) is a rare skin condition considered to be a type of reactive angioendotheliomatosis. Histologic features are quite characteristic. It has been reported in association with vaso-occlusive disease, trauma, or underlying hypercoagulability. Read More

Am J Dermatopathol 2015 Jul;37(7):581-4

Departments of *Dermatology, and †Pathology, La Paz University Hospital, Madrid, Spain.

Diffuse dermal angiomatosis is a rare benign condition considered a variant of reactive angioendotheliomatosis, usually related to vascular disease such as arteriovenous fistula or severe peripheral vascular disease. The most frequent clinical manifestations range from a solitary erythematous patch to an indurated plaque that may ulcerate. A clinical case of a 60-year-old woman who developed generalized livedoid lesions 2 days after the administration of intravenous trabectedin and subcutaneous pegfilgrastim for a recidivant myxoid liposarcoma has been reported. Read More

J Am Acad Dermatol 2014 Oct 1;71(4):745-53. Epub 2014 Jul 1.

Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Background: Chronic graft-versus-host disease (GVHD) may present with various cutaneous manifestations. Isolated case reports describe eruptive angiomas in this setting.

Objective: We sought to provide a clinical and pathologic description of vascular proliferations in patients with GVHD. Read More

J Am Acad Dermatol 2014 May 17;70(5):927-33. Epub 2014 Jan 17.

St John's Institute of Dermatology, St Thomas' Hospital, London, United Kingdom.

Background: Intralymphatic histiocytosis (IH) is a rare condition often associated with systemic disease. A benign condition, clinical presentations can vary greatly and its cause is largely unknown. Histologically, there are macrophages within distended lymphatic vessels, although this can be an incidental finding or the primary abnormality. Read More

J Cutan Pathol 2014 Apr 24;41(4):386-93. Epub 2014 Jan 24.

Department of Pathology (Dermatopathology), St. Joseph's Healthcare and McMaster University, Hamilton, Ontario, Canada.

Cutaneous collagenous vasculopathy (CCV) is a rare cutaneous microangiopathy that clinically resembles generalized essential telangiectasia with only 12 cases reported to date. The perivascular fibrosis is thought to be due to production of abnormal collagen by veil cells in the outer vessel walls as a result of unknown factors. This report is of an 84-year-old male with progressive telangiectasia. Read More

Dermatol Online J 2013 Nov 15;19(11):20404. Epub 2013 Nov 15.

Austin Hospital.

We report a case of a 65-year-old marathon runner who presented with painful plaques, which were worse in cold weather and progressed to ulceration. A punch biopsy revealed vascular endothelial hyperplasia and an appearance consistent with reactive angioendotheliomatosis (RAE), a rare, but benign disorder of the skin. Subsequent investigations resulted in the diagnosis of type I cryoglobulinemia; the lesions resolved completely following treatment of the underlying disorder with lenalidomide. Read More

Australas J Dermatol 2015 Feb 25;56(1):e24-7. Epub 2013 Nov 25.

Skin and Cancer Foundation, Melbourne, Victoria, Australia.

We present the case of a 49-year-old man with an 18-month history of an intermittently pruritic red-brown reticulate eruption of the medial legs, with occasional blistering. There were areas of scale, crust and superficial erosions. The patient worked long overnight shifts standing in front of hot machinery wearing shorts, and spent time sitting in front of a heater at home. Read More

Int J Dermatol 2014 Apr 21;53(4):e304-5. Epub 2013 Nov 21.

Department of Dermatology, Hospital Universitario de Alava, Alava, Spain.

Dermatology 2013 1;227(3):226-30. Epub 2013 Oct 1.

Department of Dermatology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.

Cutaneous reactive angiomatoses (CRA) encompass a distinct group of rare benign reactive vascular proliferations that include reactive angioendotheliomatosis, diffuse dermal angiomatosis and reactive intralymphatic histiocytosis. The etiology of these conditions, often associated with either localized or systemic diseases, is poorly understood. We report a 72-year-old woman who presented giant diffuse cellulitis-like plaques on the right lower limb and the pelvis and a reduction of her general condition with fever. Read More

Clin Exp Dermatol 2013 Oct 15;38(7):748-50. Epub 2013 Mar 15.

Department of Dermatology, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Reactive angioendotheliomatosis (RAE) is a diagnostically challenging condition characterized by multiple possible clinical presentations, which makes diagnosis challenging. We present a rare case of RAE mimicking cellulitis in a 74-year-old woman with a valvular disease and also end-stage renal disease, for which she was being treated with haemodialysis. Read More

J Inherit Metab Dis 2013 Nov 31;36(6):1073-7. Epub 2013 Jan 31.

Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium,

Background: Cystinosis is an autosomal recessive disease caused by intralysosomal cystine accumulation, treated with cysteamine. Recently, new adverse effects of cysteamine were reported. Skin biopsies showed microvascular proliferation (angioendotheliomatosis). Read More

Gland Surg 2012 Aug;1(2)

Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, and Massey Cancer Center, Richmond, Virginia, USA.

Diffuse dermal angiomatosis is a rare disorder, considered to be a variant of reactive cutaneous angioendotheliomatosis. The patients commonly present with severe intractable breast pain and characteristic reticular violaceous erythematous plaques with central ulcerations. Histologically, there is infiltration of the recticular dermis by endothelial cells due to excess vascular proliferation. Read More

Med Microbiol Immunol 2012 Aug 27;201(3):319-26. Epub 2012 Mar 27.

Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Universitätsklinikum, Goethe-Universität, Paul Ehrlich Str. 40, 60596, Frankfurt, Germany.

Bartonella species are highly fastidious, vector borne, zoonotic bacteria that cause persistent intraerythrocytic bacteremia and endotheliotropic infection in reservoir and incidental hosts. Based upon prior in vitro research, three Bartonella sp., B. Read More

J Pediatr 2011 Dec 23;159(6):1004-11. Epub 2011 Jul 23.

Department of Pediatric Nephrology, Laboratory of Pediatrics, University Hospitals Leuven, Leuven, Belgium.

Objective: To report new adverse effects of cysteamine.

Study Design: Detailed clinical information was obtained from the patients' physicians.

Results: New adverse events were reported in 8 of 550 patients with cystinosis treated with cysteamine in Europe during the last 5 years. Read More

Ophthal Plast Reconstr Surg 2011 May-Jun;27(3):e55-7

Department of Ophthalmology, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, United Kingdom.

Intravascular papillary endothelial hyperplasia (IPEH) or Masson's tumor is an unusual variety of benign vascular tumor. Involvement of periorbital area is uncommon. We report 2 cases of periorbital IPEH and review relevant literature. Read More

Actas Dermosifiliogr 2010 Jun;101(5):464-6

J Cutan Pathol 2011 Apr;38(4):351-3

Department of Dermatology, University of Michigan, Ann Arbor, MI 48109-0602, USA.

Intralymphatic histiocytosis (IH) is a rare condition first reported in 1994 by O'Grady et al. Less than 40 cases have been reported, with the majority occurring in patients with rheumatoid arthritis. We present a case of a 72-year-old man who developed an asymptomatic rash on his left upper arm 3 years after placement of a metal implant to stabilize a fractured humerus. Read More

Actas Dermosifiliogr 2010 Apr;101(3):257-62

Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, España.

Intralymphatic histiocytosis is a condition with nonspecific clinical features but with characteristic histopathological and immunohistochemical findings. It presents as a poorly demarcated erythematous plaque or a lesion similar to livedo reticularis, usually located on the limbs. Histologically, dilated vessels containing mononuclear cells are observed in the reticular dermis. Read More

Am J Dermatopathol 2009 Apr;31(2):140-51

Department of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.

Intralymphatic histiocytosis is a rare condition characterized by the presence of dilated lymphatic vessels containing aggregates of mononuclear histiocytes (macrophages) within their lumina. The phenomenon seems to occur almost exclusively within the reticular dermis. Although its pathogenesis remains uncertain, there has been speculation about the possible relationship between intralymphatic histiocytosis and intravascular reactive angioendotheliomatosis. Read More

Eur J Dermatol 2009 Mar-Apr;19(2):182-3. Epub 2008 Dec 23.

Vet Pathol 2008 Sep;45(5):645-9

Department of Veterinary Pathobiology, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078 (USA).

Unusual proliferative intravascular lesions were seen in multiple organs of a 2-year-old Corriente steer presumed to be persistently infected with bovine viral diarrhea virus (BVDV), based on widespread immunohistochemical detection of BVDV antigen. Proliferations of spindle cells, which were immunohistochemically positive for von Willebrand factor-related antigen, partially-to-completely occluded vessel lumens and were supported by cells that were immunohistochemically positive for smooth muscle actin. Distribution and character of the intraluminal proliferations are strikingly similar to those described in feline systemic reactive angioendotheliomatosis, a rare entity of unknown cause. Read More

Acta Derm Venereol 2008 ;88(4):402-3

Am J Dermatopathol 2008 Jun;30(3):295-9

Department of Dermatology, Columbia University Medical Center, New York, NY 10032, USA.

Intravascular B-cell lymphoma is a rare aggressive systemic neoplasm with cutaneous and neurological presentations, which commonly eludes the diagnosis ante mortem. First reported in 1959 as "angioendotheliomatosis proliferans" by Pfleger and Tappeiner, it is a subtype of extranodal diffuse large-B-cell lymphoma defined by an intravascular proliferation of clonal lymphocytes. We describe a case of intravascular lymphoma in a 68-year-old female who presented with altered mental status and indurated, erythematous, ecchymotic plaques with overlying telangiectasia and ulceration. Read More

Eur J Dermatol 2008 Mar-Apr;18(2):193-4

Clin Exp Dermatol 2007 Jan 27;32(1):45-7. Epub 2006 Sep 27.

Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

We present a unique case of a woman with multiple painful dermal lesions localized to the left upper quadrant of the body. Histological investigation revealed microvascular thrombosis with capillary-wall proliferation. Further investigation revealed a very high anticardiolipin IgG titre and a left subclavian stenosis, presumably providing the reduced blood flow and relative hypoxia to allow microthromboses to occur in the presence of a thrombophilic tendency. Read More

Arch Dermatol 2006 Mar;142(3):343-7

Department of Dermatology and Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Background: Diffuse dermal angiomatosis is rare and usually considered a variant of reactive angioendotheliomatosis. It generally involves the extremities of patients with severe vascular disease and other comorbidities. Two patients with breast involvement have been described; however, neither had a relevant medical history or a vaso-occlusive disorder, but both had large pendulous breasts, and 1 was positive for IgM anticardiolipin and antinuclear antibodies. Read More

Am J Dermatopathol 2005 Oct;27(5):422-7

Department of Pathology, The Penn State College of Medicine/Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.

A 55-year-old white female with a complex medical history including mixed connective tissue disease and peripheral vascular disease developed a group of red-purple papules on her proximal medial thigh that was followed, five months later, by the development of a large violaceous patch. She reported a history of radiation to this site (for melanoma) during her childhood. She was admitted to the hospital with a presumptive diagnosis of cellulitis, but failed to respond to antibiotics. Read More

Vet Pathol 2005 Sep;42(5):608-17

College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

A rare, multisystemic intravascular proliferative disorder was identified postmortem in eight cats. The majority of these cats died or were euthanized following episodes of dyspnea, lethargy, and anorexia. Microscopic examination revealed occlusive, intraluminal proliferations of spindle cells within small vessels. Read More

Acta Derm Venereol 2005 ;85(3):269-70

Histopathology 2005 Apr;46(4):396-402

Department of Pathology, the Jikei University School of Medicine, Tokyo, Japan.

Aims: To evaluate the expression of D2-40 in normal lymphatic endothelium and vascular tumours or tumour-like lesions of the skin and soft tissue. D2-40 is a novel monoclonal antibody to a Mr 40 000 O-linked sialoglycoprotein that reacts with a fixation-resistant epitope in lymphatic endothelium.

Methods And Results: Formalin-fixed paraffin-embedded sections from 30 normal tissue samples, including skin, soft tissue, stomach, and colon, and 84 vascular tumours or vascular tumour-like lesions were immunostained with monoclonal antibodies to D2-40 and CD31. Read More

J Eur Acad Dermatol Venereol 2005 Mar;19(2):216-9

Department of Dermatology and Venereology, Medical University of Lübeck, Germany.

We report the case of a 68-year-old female with reactive angioendotheliomatosis (RAE). This case highlights the benign course of this condition and suggests that this entity might be an intravascular histiocytosis. Read More

Cesk Patol 2004 Oct;40(4):162-6

Odd. patológie FNsP J. A. Reimana, Presov, Slovenská Republika.

Reactive angioendotheliomatosis (RAE) is a rare disorder with clinical presentation of multiple cutaneous lesions. RAE mimics mainly Kaposi sarcoma (KS) and, rarely angiosarcoma, and it usually arises in association with other systemic disease. The associated disease is mostly chronic infection. Read More

Rev Neurol 2004 Apr 1-15;38(7):640-2

Hospital de Conxo, Santiago de Compostela, España.

Case Report: A 68 year old male with no relevant clinical history was admitted to hospital because of symptoms of cognitive impairment (attentional deficit, short term memory disorders and behavioural disorders), accompanied by apraxia of gait and rectal and urinary incontinence. Results of a general clinical exploration were normal. In the MRI study of the brain numerous areas of hypersignal were observed in different arterial territories, which stood out in the T2, FLAIR and, above all, in diffusion weighted sequences. Read More

Am J Surg Pathol 2004 Feb;28(2):257-61

Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

We present a case of reactive angioendotheliomatosis (RAE) of the colon, featuring intravascular proliferation of endothelial cells with histologic resemblance to glomeruloid hemangioma. A 19-year-old Japanese male with an anal fistula was diagnosed endoscopically with Crohn's disease. Six months later, he was hospitalized for fever and abdominal pain. Read More

Am J Clin Pathol 2004 Mar;121(3):335-42

Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong, SAR China.

We assessed the usefulness of a mouse monoclonal antibody (13B10) against human herpesvirus 8 (HHV-8) latent nuclear antigen-1 (LNA-1) in diagnosis of Kaposi sarcoma (KS) and for distinguishing it from various mimickers by studying 50 cases of KS and 53 mimickers (angiosarcoma, 15; kaposiform hemangioendothelioma, 6; spindle cell hemangioma, 3; reactive angioendotheliomatosis, 3; bacillary angiomatosis, 4; acroangiomatous dematitis, 2; microvenular hemangioma, 2; hobnail hemangioma, 2; pyogenic granuloma, 5; dermatofibroma, 8; arteriovenous hemangioma, 1; verrucous hemangioma, 1; nonspecific vascular proliferation, 1) from patients with or without acquired HIV infection. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections. All 50 cases of KS were positive for HHV-8 LNA-1, with immunolocalization in the nuclei of the spindle cells and cells lining the primitive and thin-walled vascular channels, whereas all 53 mimickers (including 4 lesions from HIV-positive patients) tested negative. Read More

Acta Medica (Hradec Kralove) 2003 ;46(3):121-3

Fingerland Department of Pathology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Czech Republic.

In this report the case of intravascular large B-cell lymphoma (angiotropic lymphoma, intravascular angioendotheliomatosis, malignant endotheliomatosis) with panniculitis features is present. The diagnosis was based on finding of typical CD20 positive tumorous cells within capillaries, veins, and small arteries in the biopsy of subcutaneous adipose tissue. An accurate and early diagnosis together with combined chemotherapy resulted in good response and remission of the disease. Read More

Dermatology 2003 ;207(4):398-401

Department of Dermatology, University of Cologne, Cologne, Germany.

Reactive angioendotheliomatosis (RAE) is a very rare disorder characterized by marked proliferation of endothelial cells. It is often associated with infections, such as subacute bacterial endocarditis, but has also been described as an early sign of a developing hematological malignancy. We report the case of a 71-year-old Caucasian female who developed lupus-like RAE lesions. Read More

J Am Acad Dermatol 2003 Nov;49(5):887-96

DISEM, University of Genoa.

New and relatively old types of vascular (capillary) proliferations in the skin have been described or better categorized in the last few years. They include reactive angioendotheliomatosis, acroangiodermatitis (pseudo-Kaposi sarcoma), diffuse dermal angiomatosis, intravascular histocytosis, glomeruloid angioendotheliomatosis, and angiopericytomatosis (angiomatosis with cryoproteins). Clinically, all of them present with multiple, erythematous-violaceous and purpuric patches and plaques, sometimes evolving toward necrosis and ulceration with a wide distribution but a propensity to involve limbs. Read More

Cutis 2003 Aug;72(2):137-40

Division of Dermatology, University of California at Los Angeles, USA.

Intravascular lymphoma, also known as malignant angioendotheliomatosis or angiotropic lymphoma, is a rare non-Hodgkin lymphoma that is usually fatal. It often presents with cutaneous and/or nervous system involvement, but the disease can involve any organ system. Clinical symptoms result from the occlusion of small vessels by tumor cells and fibrin. Read More