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Dermatology > DISEASES OF THE VESSELS
Blue Rubber Bleb Nevus Syndrome
Article Last Updated: Oct 2, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Basil S Cherpelis, MD, Chief, Dermatologic Surgery, Assistant Professor, Department of Dermatology, University of South Florida
Basil S Cherpelis is a member of the following medical societies: American Academy of Dermatology
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
Editors: Bernice R Krafchik, MBChB, FRCPC, Professor Emeritus, Department of Pediatrics, Section of Dermatology, University of Toronto; Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA; Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
bean syndrome
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.
Race
The syndrome has been reported in persons of all races, 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.
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.
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.
- 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 manifestations 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. 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.
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.
Kaposi Sarcoma
Klippel-Trenaunay-Weber Syndrome
Maffucci Syndrome
Venous Lakes
Other Problems to be Considered
Arteriovenous malformation
Capillary-lymphatic malformation
Lab Studies
- Fecal occult blood test: Screen for occult blood loss from GI BRBNS lesions.
- CBC count: Screen for iron deficiency anemia.
- Urinalysis: Hematuria may be caused by lesions in the bladder.
Imaging Studies
- Radiographs: Radiographic images may be useful in suspected bone or joint involvement to detect fractures, bony overgrowth, and articular derangement. Radiographic contrast techniques may detect GI lesions, but endoscopy is considered to be superior.
- MRI: This recently has been described as a useful tool for detecting extracutaneous lesions and for screening asymptomatic family members.
Procedures
- Endoscopy
- GI lesions may be demonstrated by endoscopic examination or by radiographic contrast techniques.
- Upper GI endoscopy is more sensitive than an upper GI series and colonoscopy more useful than a barium enema.
- Endoscopy also provides the opportunity to treat and diagnose the lesions.
Histologic Findings
Histopathologic examination of skin lesions reveals vascular tissue with tortuous, blood-filled ectatic vessels, lined by a single layer of endothelium, with surrounding thin connective tissue. Dystrophic calcification may be present.
Medical Care
No systemic therapy is currently considered a standard of care. One report indicated the successful use of interferon-beta to treat the manifestations of disseminated intravascular coagulation in one patient with disseminated skin and GI venous malformations.
Surgical Care
- Cutaneous lesions
- Cutaneous lesions do not need to be treated, unless they are cosmetically unacceptable or functionally troublesome. Malignant transformation of BRBNS lesions has not been reported.
- Methods to remove lesions include electrodesiccation and curettage, liquid nitrogen, and excision. These modalities often lead to recurrence or healing with a hypertrophic scar. Successful treatment without scarring has been reported with the use of the carbon dioxide laser. Treatment of 225 lesions without recurrence was reported with the use of the carbon dioxide laser.
- Extracutaneous lesions
- Bleeding from GI lesions usually is managed conservatively with iron supplementation and blood transfusions when necessary. Endoscopic coagulation or removal is an effective modality for repeated bleeding. Experience with endoscopic sclerotherapy suggests that it is ineffective and complicated by the development of ulcerations and strictures. Endoscopic laser (Nd:YAG) photocoagulation has been used successfully for lesions in the alimentary tract. When traditional methods fail and the vascular lesions are confined to a segment of the GI tract, resection of the involved segment of gut may be indicated. This approach should be used with caution because recurrences may occur after excision. Diffuse and scattered lesions or those where operation is not feasible should be treated conservatively.
- Orthopedic lesions are managed with orthotics and supportive measures, unless impaired function necessitates surgery.
- An 8-month old infant with bleeding hemangiomas of the rectum and colon was successfully treated with argon plasma coagulation. This treatment resulted in long-term success.
- In one report, an aggressive surgical approach to treatment was attempted in 10 patients. GI venous malformations were identified endoscopically and then treated by wedge resection, polypectomy, suture ligation, segmental bowel resection, or band ligation. Only one patient developed recurrent GI bleeding.
Consultations
- Patients should be referred to a gastroenterologist for management of GI manifestations as needed.
- Referral to an orthopedist can assist in the care of patients with bone or joint involvement.
- Symptomatic patients should be referred to the appropriate specialist depending on the organ system involved.
- In cases with familial occurrence, patients should be referred for genetic counseling.
Further Outpatient Care
- New GI lesions may continue to occur, so patients need periodic GI and hematologic surveillance studies.
Complications
- Rarely, acute GI hemorrhage or CNS involvement may result in death.
Prognosis
- The prognosis depends on the extent of visceral organ involvement. Most patients have a normal life span.
Medical/Legal Pitfalls
- Skin examinations should be performed on patients who present with abdominal pain or GI bleeding. Recognizing typical blue rubber bleb skin lesions would provide a potential diagnosis and could prevent unnecessary diagnostic procedures or invasive surgery.
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Blue Rubber Bleb Nevus Syndrome excerpt Article Last Updated: Oct 2, 2006
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