Blue rubber bleb nevus syndrome is an uncommon condition manifested by gastrointestinal and skin hemangiomas that lead to gastrointestinal bleeding and anemia. The purpose of this report is to present a case with long-term follow-up. The patient is a 37-year-old female with a life-long history of blue rubber bleb nevus syndrome. She underwent multiple resectional operations that combined to give her a partial gastrectomy, partial small bowel resection, total abdominal colectomy, and end ileostomy. She continues to need endoscopy with sclerotherapy. In addition, she has iron-deficiency anemia, nephrolithiasis, major depression, and malnutrition despite vitamin and caloric supplements. There are no other reports showing these complications of blue rubber bleb nevus syndrome or with this length of follow-up. Therapy for blue rubber bleb nevus syndrome should be conservative if possible, because operative therapy may lead to significant longterm complications.
lue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by cutaneous and intestinal hemangiomas associated with gastrointestinal bleeding and anemia. Bean first described the syndrome in 1958.1 There have been fewer than 150 cases reported in the literature,2 and none have long-term follow-up. This report demonstrates a case of BRBNS with longterm follow-up.
The patient is a 37-year-old female diagnosed with BRBNS as an infant. Her first operation as an infant was a right colectomy for gastrointestinal bleeding. During the next 6 years, she underwent a partial gastrectomy, right hemicolectomy with ileostomy, ileostomy takedown with ileocolostomy, small bowel resection, and finally a completion colectomy with ileostomy and Hartmann's procedure, all performed at another institution. Since that time, she has had multiple admissions for continued bleeding with the need for transfusions. The interim between transfusions has ranged from 3 months to 2 years. In the last 3 years, she has undergone eight enteroscopies with sclerotherapy. Sclerotherapy in her rectal stump has resulted in severe scarring and a loss of rectal pliability, making it impossible to take down her ileostomy. The absorptive capability of the small bowel is reduced from a combination of the resections and sclerotherapy. Although not requiring parenteral nutrition, she depends on vitamin and caloric supplements to sustain her weight and maintain adequate nutritional parameters. She continues to take iron supplements to combat iron-deficiency anemia. Cosmetic sclerotherapy has been performed for a large hemangioma on her face and neck. She has required lithotripsy for renal stones. Finally, she takes antidepressants and is in counseling for a suicide attempt secondary to her medical condition.
BRBNS is characterized by cutaneous cavernous hemangiomas associated with hemangiomas of the gastrointestinal tract. Bean first described the syndrome in 1958 with blue vascular nevi of the skin, hemangiomas of the gastrointestinal tract, and gastrointestinal hemorrhage.1 This bleeding often leads to irondeficiency anemia. The bleeding is usually occult and less often melena or hematochezia.3 This may be because the visceral hemangiomas are fragile and bleed easily.2 The cutaneous lesions are soft, rubbery, and compressible. Although most hemangiomas involute, these nevi show no evidence of regression. In fact, follow-up shows progression and recurrence.4-7 Most cases of BRBNS present in children, with a female-tomale ratio of 2:1.8
The cause of BRBNS is unknown. Most cases are sporadic.9 Other investigators have shown six families with up to five generations affected in an autosomal dominant pattern. 10-14 Recently, a gene for venous malformations was mapped to chromosome 9p from an extended family in which several members had BRBNS-like cutaneous, mucocutaneous, and visceral lesions,15 but this did not definitively map BRBNS.16
The nevi show a predilection for the trunk and upper extremities, but they can be located anywhere. They vary in size from a few millimeters to up to 10 cm.17 Patients may have several hundred skin and intestinal hemangiomas.18-20 They are frequently painful at night and often interfere with sleep.21 Excessive sweating in the overlying skin has been accounted for by the close anatomical association between the nevi and sweat glands.22-24 Histologically, they are venous malformations with a cluster of dilated irregular spaces lined by a thin layer of endothelium with a varied amount of fibrous connective tissue at the walls.9
The most common location for gastrointestinal lesions is the small bowel, but they can be anywhere from the tongue to the anus. In the colon, they are usually on the left side and in the rectum.25 Thrombocytopenia and chronic consumptive coagulopathy have been reported in association with the syndrome.26,27 Other intestinal complications include intussusception, volvulus, infection, and secondary complications from massive bleeding and transfusions.23,28,29 Gastrointestinal hemorrhage is the most common cause of death.30 Malignant transformation has never been reported.8
The diagnosis is usually made on clinical grounds. Upper endoscopy, colonoscopy, computed tomography barium studies, and angiography have all been used as diagnostic tools. Angiography has not always been successful in detecting BRBNS.31 Computed tomography will show lesions that enhance with contrast and are usually calcified.32 Magnetic resonance imaging (MRI) has recently been shown to be an excellent method for identifying the presence and extent of lesions in BRBNS.17 T2-weighted images are bright from slow flow or thrombosis within the nevi. MRI may be useful for screening family members.
The differential diagnosis includes glomangiomatosis and Osler-Weber-Rendu syndrome (OWRS).8 Histologically, BRBNS is easily distinguished from glomangiomatosis. OWRS is excluded by the typical appearance of its skin lesions, which are in a nevus flammeus (port-wine-stain) pattern.6,22 Histologically, OWRS is characterized by capillary hemangiomas, whereas BRBNS is distinguished by venous cavernous angiomas. In addition, OWRS nevi are frequently subungual and on the nasal mucosa commonly associated with epistaxis. 11,30,33
All patients should be treated with oral iron supplements and transfusions when needed. Oral prednisone, aspirin, and interferon alpha-2a have not proven to be successful.8,26,34 Neonates diagnosed with BRBNS may have a more virulent expression of the disease. Some have recommended an aggressive combination of endoscopic excision and bowel resection.5,35 Others have advocated endoscopic hemangioectomy or ligation, endoscopic laser coagulation, and endoscopic sclerosants.2-4,36,37 No long-term follow-up is listed with any of these case reports. Bowel resection is recommended for intussusception.6
Based on the long-term follow-up of this patient, the treatment for BRBNS should be conservative. Because there is no "cure" and progression of the disease is likely, a conservative surgical approach to minimize intestinal loss seems preferable. Endoscopic control of the nevi using sclerosants is a reasonable first-line therapy. If operations are performed, assisted enteroscopic sclerotherapy or hemangioectomy and repair rather than resection should be favored in most instances to reduce the risk of malnutrition. Eliminating the bleeding hemangioma with long-term preservation of functioning bowel should be the ultimate goal.
Therapy for BRBNS may lead to long-term complications. Conservative treatment and bowel preservation should be the management goal. Surgical resection should be reserved for those patients with uncontrolled bleeding, localized lesions, and intussusception. MRI seems to be a reasonable screening tool for first-degree relatives with cutaneous lesions.
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Guarantor: LTC Ronald J. Place, MC USA
Contributor: LTC Ronald J. Place, MC USA
Section of Colon and Rectal Surgery, Department of Surgery, Madigan Army Medical Center, Fort Lewis, WA 98431.
This manuscript was received for review in August 2000. The revised manuscript was accepted for publication in December 2000.
Copyright Association of Military Surgeons of the United States Aug 2001
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