eMedicine Specialties > Dermatology > Diseases of the Vessels

Blue Rubber Bleb Nevus Syndrome

Author: Basil S Cherpelis, MD, Assistant Professor, Chief of Dermatologic Surgery, Department of Dermatology and Cutaneous Surgery, Assistant Professor, Department of Oncologic Sciences, University of South Florida; Consulting Staff, Moffitt Cancer Center, Tampa General Hospital and James A Haley Veterans Affairs Medical Center
Coauthor(s): Neil A Fenske, MD, Director of Dermatology and Cutaneous Surgery, Professor, Departments of Internal Medicine and Pathology, University of South Florida College of Medicine
Contributor Information and Disclosures

Updated: Oct 23, 2008

Introduction

Background

Blue rubber bleb nevus syndrome (BRBNS) is a syndrome characterized by multiple cutaneous venous malformations in association with visceral lesions, most commonly affecting the GI tract. In 1860, Gascoyen first described an association between cavernous hemangiomas of the skin and similar lesions in the GI tract. In 1958, Bean further described these lesions and coined the term blue rubber bleb nevus syndrome. BRBNS is an important syndrome because of its potential for serious or fatal bleeding.

Pathophysiology

The cutaneous and GI systems most frequently are involved with multiple vascular blebs or nodules. However, case reports have demonstrated that the central nervous system, thyroid, parotid, eyes, oral cavity, musculoskeletal, oral cavity, lungs, kidney, liver, spleen, and bladder also may be affected.

Histopathologic examination of lesions reveals blood-filled ectatic vessels, lined by a single layer of endothelial cells, with surrounding thin connective tissue.

Frequency

International

BRBNS is a rare disorder with only approximately 150 cases reported in the world's literature. Most cases are sporadic, but autosomal dominant inheritance has been reported.

Mortality/Morbidity

The mortality and morbidity associated with BRBNS depends on the extent of visceral organ involvement. Most patients have a normal life span with cosmesis being the major concern. No malignant transformation of cutaneous or visceral lesions has been reported. Some patients may have severe hemorrhage from the GI tract, which can be fatal. Serial transfusions and periodic surveillance can modify the morbidity of the disease. Lesions involving bones and joints can cause profound discomfort and loss of function, requiring amputations in some cases. Rarely, central nervous system involvement can be fatal.¹

Race

The syndrome has been reported in persons of all races,² although whites appear to be most frequently affected.

Sex

The disease affects males and females equally.

Age

Cutaneous lesions are often apparent at birth or manifest in early childhood, but late onset, beyond midlife, has been reported. GI involvement usually becomes evident during early adulthood.

Clinical

History

Affected patients may present to the dermatologist because of cosmetic concerns.

• Most lesions are asymptomatic but some may be spontaneously painful or tender to palpation.
• Patients may note increased sweating on the skin overlying the lesion.
• Physical complaints or symptoms vary depending on the organ system involved.
  • Patients may report fatigue from occult blood loss. Hematemesis, melena or frank rectal bleeding may prompt emergent presentations.
  • When bone is involved, there may be complaints of joint pain or impaired ambulation. Extracutaneous lesions also may result in epistaxis, hemoptysis, hematuria, or menorrhagia.
  • Patients may present with blindness due to cerebral or cerebellar cavernomas that may hemorrhage into the occipital lobes.³

Physical

Physical findings are divided into cutaneous and extracutaneous manifestations.

• Cutaneous manifestations
  • Skin lesions are usually highly characteristic, as multiple, protuberant, dark blue, compressible blebs, a few millimeters to several centimeters in diameter and varied in hue and shape. They have the look and feel of a rubber nipple. Lesions may be few in number or range into the hundreds.
  • Three types of cutaneous lesions have been described: (1) blue, rubbery, blood-filled sacs with a smooth or wrinkled surface that are easily compressible and promptly refill when pressure is released; (2) large, disfiguring, cavernous lesions that may compress vital structures; and (3) blue, irregular macules.
  • The color of cavernous lesions may appear red, purple-red, blue, or black, and morphology varies from flat to elevated, occasionally pedunculated, nodules.
  • Lesions may be tender to palpation, and overlying hyperhidrosis may be noted.
  • Skin lesions rarely bleed unless traumatized.
  • Progression in size and number of blebs may occur with advancing age.
  • The lesions are principally located on the upper limbs, trunk, and perineum, but they may occur anywhere.⁴
• Dermoscopic features: Described in a 2008 report,⁵ dermoscopic features include a superficial, light-red arborizing venous pattern or vessel dilations; maculae with nondefined borders predominantly on the palms and soles; red-purple nodules with lacunas separated by a white linear structure, corresponding to fibrous demarcations; and lesions with an exophytic, verrucous surface.
• Extracutaneous manifestations
  • The visceral organ system most commonly affected is the GI tract. Vascular malformations may occur anywhere from oral to anal mucosa but predominantly occur in the small bowel. In contrast to the skin lesions, the GI lesions often bleed. They may spontaneously rupture causing acute hemorrhage and death. However, most bleeding from the GI tract is slow, minor, chronic, and occult, resulting in iron deficiency anemia from ongoing loss. A case of thrombocytopenia and disseminated intravascular coagulation has been reported in association with BRBNS. Other complications include intussusception, volvulus, and bowel infarction. These diagnoses should be considered in patients with BRBNS and abdominal pain.
  • Orthopedic manifestations⁶ include skeletal bowing, pathologic fractures, bony overgrowth, and articular derangement. Bone deformities may arise as a result of pressure effects from adjacent vascular lesions. Vertebral lesions have caused spinal cord compression and vertebral collapse, and the lesions may extend into joint spaces affecting range of motion.⁷ Extensive lesions also have been reported on the feet, impairing ambulation. Debilitating enlargement occasionally requires amputation of the affected limb.
  • Blue rubber bleb nevi have been reported in the skull, central nervous system, thyroid, parotid, eyes, oral cavity, lungs, pleura, pericardium, musculoskeletal system, peritoneal cavity, mesentery, kidney, liver, spleen, penis, vulva, and bladder.
  • Recurrent thromboembolic events from shunts in visceral lesions led to the development of pulmonary hypertension in one case.⁸

Causes

The cause of BRBNS is unknown. Most cases are sporadic, but autosomal dominance has been reported. The disorder has not been localized to a specific chromosome or gene defect.

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