BRBNS 1_0713 Derm Clinic 2
BRBNS 2_0713 Derm Clinic 2
A 25-year-old woman complained of painful and enlarging lesions on her feet that had been present for most of her life. The woman also had been born with a large vascular malformation on the left elbow that was treated with excision.
At age 2 years, she had developed profound anemia, and workup showed multiple vascular lesions of the GI tract. She required iron supplementation and transfusions but ultimately underwent GI resection. Skin examination showed noncompressible, blue-black, vascular, and slightly verrucal papules on the feet, buttocks, and extremities. Family history was unremarkable.
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This patient had been diagnosed in her childhood with blue rubber bleb nevus syndrome (BRBNS), a rare congenital condition in which patients develop both cutaneous and visceral venous malformations, with the GI tract being the most common extracutaneous site of involvement.1
BRBNS was first described by Gascoyen in 1860 in a patient with vascular hamartomas of the skin and GI tract. The clinical findings were further delineated in 1958 by Bean, who used the term blue rubber bleb nevus syndrome to describe the appearance and texture of the cutaneous vascular lesions, which he likened to rubber nipples. The condition is also called Bean syndrome.2
As illustrated by the patient in this case, most reported cases of BRBNS are of sporadic inheritance, but reports of autosomal dominant transmission exist.3 The gene defect has yet to be identified,3 but some studies have localized a possible mutation to chromosome 9p.2 There is no gender or race predilection.4
Given the rarity of the condition, the initial diagnosis may be delayed or incorrect. Patients usually present with vascular skin lesions within the first few years of life (often at birth), but the diagnosis of BRBNS is not generally rendered until childhood, when the complications of GI hemorrhage become apparent.1 The pathogenesis of BRBNS is poorly understood, but some have proposed that disordered angiogenesis or enlargement of dormant vessels may be causative.4
Cutaneous examination in patients with BRBNS can reveal three types of vascular lesions, which are generally present at birth and become larger (1 mm to 10 cm) and more numerous (up to hundreds) over time.2 Type I lesions are sizable and disfiguring venous malformations that can progressively enlarge and compress surrounding tissues. Surgical intervention is often required to preserve vital structures.2,3 The patient in this case had a type I lesion of the left elbow.
Type II lesions are the classic blebs as described by Bean. These lesions are blue in color because of the underlying blood-filled sac, and they protrude from the skin like rubber nipples. On palpation, type II lesions are rubbery and compressible and may be associated with pain and hyperhidrosis.
Type III lesions (as seen on the feet of the patient in this case) are nonblanchable, blue-black papules.2 Biopsy reveals dilated and blood-filled capillary spaces lined by endothelial cells residing in the dermis or the subcutis.2 These findings most closely resemble venous malformations.
Based on histology, cutaneous lesions in BRBNS have been incorrectly labeled as hemangiomas, but the microscopic features of hemangiomas often show increased mast cells in the dermis with vascular channels demonstrating a prominent basement membrane, findings not seen in the classic venous malformations of BRBNS.2
The dermatoscopic features of these vascular lesions have also been described.5 These lesions can occur anywhere on the skin surface, but they are most commonly located on the upper extremities, trunk, and perineum.3 There have been no reports of malignant transformation of these lesions, but they tend not to involute.2,3 Unlike the GI lesions described below, it is unusual for patients to experience spontaneous bleeding of the skin lesions.1
Although cutaneous lesions are clinically apparent early in life and rarely require medical intervention (with the exception of the type I lesions), GI vascular malformations are not usually apparent until later in childhood, when hemorrhagic complications ensue.1 The lesions of the GI tract are more friable than those of the skin, resulting most often in chronic occult bleeding that presents with melena and anemia.3 Rarely, more brisk hemorrhage can occur. Lesions are most often found in the small bowel but can be present anywhere along the GI tract from the mouth to the anus.4
In addition to GI involvement, extracutaneous lesions have been reported in the central nervous system, genitourinary tract, spleen, liver, eye, adrenal glands, and thyroid.1,2 Skeletal problems can occur as a result of pressure from an adjacent vascular malformation, either in the joint space or along the bone.2
Patients in whom the diagnosis of BRBNS is suspected based on typical cutaneous findings should undergo a complete history and physical examination, complete blood count, and stool guaiac test. Positive guaiac test and anemia necessitate a full investigation of the GI tract to identify bleeding sites.2 Endoscopy, CT scan, MRI, angiography, or barium studies can be used.1,2
In the absence of significant GI bleeding, conservative management with iron supplementation and transfusions may be sufficient. Use of interferon and corticosteroids has been reported, but these measures have not been as efficacious in treating bleeding complications from BRBNS as they have been in treating infantile hemangiomas.2,4
Surgical management is reserved for cases in which the lesions are localized to a limited segment of the bowel that is amenable to resection.4 Otherwise, endoscopic management by means of sclerotherapy, band ligation, laser coagulation, or polypectomy is preferred due to the high rate of recurrence of the vascular lesions.4
Cutaneous lesions are only treated if they are symptomatic or cosmetically troubling; laser therapy, curettage, excision, and sclerotherapy have been reported as helpful.2
Differential diagnosis includes other genodermatoses with vascular lesions of both the skin and the viscera. Osler-Weber-Rendu (hereditary hemorrhagic telangiectasia) syndrome presents with punctate vascular lesions of the skin, lungs, and GI tract.
Maffucci syndrome is distinguished by prominent bony abnormalities and malignant transformation of the skeletal lesions. Klippel-Trenaunay-Weber is characterized by unilateral soft tissue and bony hypertrophy with overlying venous malformation and rare hematochezia from gut or rectal involvement.2
Prognosis for individuals diagnosed with BRBNS is generally good, and only patients with extensive internal involvement may have shortening of their lifespan.3 Patient monitoring depends on the individual presentation, according to organ-system involvement and severity of manifestations.4
The patient in this case had several symptomatic skin lesions that were successfully excised. She has no current complaints of GI bleeding but is seen regularly by hematology for monitoring of iron-deficiency anemia, which is well-controlled with oral supplementation.
Kaitlyn Stortz is a third-year medical student at Virginia Commonwealth University in Richmond, where Erin Reese, MD, is an assistant professor of dermatology.
- Deng ZH, Xu CD, Chen SN. Diagnosis and treatment of blue rubber bleb nevus syndrome in children. World J Pediatr. 2008;4:70-73.
- Nahm WK, Moise S, Eichenfield LF, et al. Venous malformations in blue rubber bleb nevus syndrome: variable onset of presentation. J Am Acad Dermatol. 2004;50(5 Suppl):S101-S106.
- Thrash B, Patel M, Shah KR, et al. Cutaneous manifestations of gastrointestinal disease: part II. J Am Acad Dermatol. 2013;68: 211.e1-211.e33.
- Ertem D, Acar Y, Kotiloglu E, et al. Blue rubber bleb nevus syndrome. Pediatrics. 2001;107:418-420.
- Mejia-Rodriguez S, Valencia-Herrera A, Escobar-Sanchez A, Mena-Cedillos C. Dermoscopic features in bean (blue rubber bleb nevus) syndrome. Pediatr Dermatol. 2008;25:270-272.