Bean syndrome is also known as Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital blood vessel (vascular) anomaly in various organ systems including the liver, spleen, heart, eye, and central nervous system disorder that affects the skin and internal organs of the body and consists of multifocal venous malformations (VM) with the presence of fluid-filled blisters (blebs) as visible, circumscribed, chronic lesions (nevus). Multiple distinctive skin lesions are usually characteristic of this disorder and are often present at birth or present during early childhood. Lesions in the gastrointestinal tract frequently become apparent during childhood or early adulthood. The lesions are multifocal venous malformations, resulting from abnormal embryonic blood vessel development. Patients with blue rubber bleb nevus syndrome are at increased risk for gastrointestinal hemorrhage and severe iron deficiency anemia
Symptoms
BRBNS is characterized by soft, elevated lesions on the skin or just under the skin that is dark blue, red, purple-red, or black. The venous malformations may be tender, contain blood, and be easily compressed, and are usually located on the upper limbs, trunk, and soles of the feet but can occur anywhere. The lesions increase in size and become more apparent over time but have not been reported to become cancerous. The organ system most commonly affected by BRBNS is the gastrointestinal (GI) tract, particularly the small intestine. The lesions in the GI tract often bleed and can lead to mild or severe anemia. Iron replacement and/or frequent blood transfusions may be required. The GI lesions can also cause an obstruction or blockage (intussusception) of part of the bowel. Skeletal abnormalities and venous malformations in muscles are sometimes associated with BRBNS.
Causes
Blue rubber bleb nevus syndrome is sporadic. Although families have been described in which the condition follows autosomal dominant inheritance, these families have other multifocal venous malformations.
Blue rubber bleb nevus syndrome is usually a sporadic disorder; however, autosomal dominant modes of inheritance are reported, specifically with a locus found on chromosome 9p.[rx][rx][rx] Recently, somatic mutations in TIE2, an endothelial cell tyrosine kinase receptor for angiopoietins, have been discovered to cause the disorder. Soblet et al. studied 17 patients with blue rubber bleb nevus syndrome and six individuals with multifocal vascular malformations. The majority of patients with blue rubber bleb nevus syndrome were associated with mutations in TEK (also known as TIE2), which encodes TEK receptor tyrosine kinase. In contrast to common unifocal venous malformation, multifocal malformations are associated with two somatic activating mutations on the same allele (double [cis] mutations).[8]
Diagnosis
BRBNS is diagnosed by physical examination and a procedure in which the GI tract is illuminated and visualized (endoscopy). Genetic testing for BRBNS is available on a research basis only. Endoscopy has been the leading diagnostic tool for diagnosing BRBNS for those who have lesions in the gastrointestinal tract. The GI tract is illuminated and visualized in endoscopy. [rx] Endoscopy also allows immediate therapeutic measures like argon plasma, coagulation, laser photocoagulation, sclerotherapy, or band ligation.[rx] Besides physical examination and endoscopy, ultrasonography, radiographic images, CT, and magnetic resonance imaging are helpful for the detection of affected visceral organs.[rx]
Aside from clinical diagnosis, other diagnostic modalities include imaging studies. Ultrasound is the initial diagnostic study of choice as it is the least invasive. Ultrasound may be performed endoscopically if gastrointestinal venous malformations are suspected. Ultrasound should be performed by a radiologist or ultrasound technician who is experienced in vascular anomalies. Since the radiologist reading the study may not have the clinical history or benefit of seeing the patient in real-time, it is recommended by some sources to send the patient for an ultrasound at the vascular anomalies center. If ultrasound is inconclusive or not possible, then magnetic resonance imaging (MRI) with intravenous contrast, arterial and venous phases, and fat suppression is indicated. Other diagnostic modalities include computed tomography (CT), barium studies, and skin biopsy. Technetium Tc-99m-labeled red blood cell imaging may help localize the source and extent of blood loss.[rx]
Blue rubber bleb nevi can be examined under dermoscopy with features of superficial, light red arborizing veins, maculae with undefined borders on the palms and soles, and blue-purple nodules with lacunae divided by white linear structures.[rx] Patients underwent endoscopic evaluation including flexible fiberoptic esophagogastroduodenoscopy, colonoscopy, and intraoperative flexible or rigid enteroscopy. An attempt was made to eradicate every identifiable vascular malformation from the stomach to the anus
Other laboratory studies that may be helpful in evaluation and management include fecal occult blood tests, complete blood counts, iron panels, and urinalysis to screen for hematuria and bladder involvement.[rx]
Treatment
Iron therapy and blood transfusions are used to conservatively manage BRBNS. The skin lesions associated with BRBNS can be treated with laser therapy, injection of chemicals that collapse the lesion (sclerotherapy), or surgical removal. The cutaneous lesions can be effectively treated by laser, surgical removal, electrodesiccation, cryotherapy, and sclerotherapy.[rx] In other cases, iron therapy (such as iron supplementation) and blood transfusions are used to conservatively manage BRBNS because of the amount of blood that is lost from the GI bleeding.[rx] It is not necessary to remove the lesions in the gastrointestinal system unless the bleeding leads to anemia and repeatedly has blood transfusionsLesions in the gastrointestinal system are usually not removed unless bleeding leads to anemia and necessitates repeated blood transfusions. If there is a recurrence with new angioma in the gastrointestinal tract, laser-steroid therapy is needed.[rx] Gastrointestinal lesions can be safely removed surgically, but one or several lengthy operations may be required.
Pharmacologic agents have been tried with variable responses.[rx] Somatostatin analogs like subcutaneous octreotide can be used to decrease splanchnic blood flow in patients with gastrointestinal hemorrhage. This may help decrease the need for blood transfusions in these patients. Other pharmacologic agents reported efficacious include corticosteroids, interferon-alpha, IVIG, and vincristine.[rx] Sirolimus was recently reported in the literature as a successful treatment option for this condition; however, the dose and treatment duration remains uncertain. Sirolimus is an angiogenesis inhibitor that has been used to avoid blood transfusions in these patients, who often require multiple in their lifetime.[rx][rx][rx][rx]
Resection techniques included full-thickness wedge excision, polypectomy via enterotomy, suture ligation via enterotomy, segmental bowel resection, and endoscopic band ligation. Some gastric, duodenal, and colonic lesions examined endoscopically were band-ligated if operative evaluation of the viscera confirmed the absence of transmural involvement of the lesions.
Investigational Therapies
Argon plasma coagulation and octreotide acetate have been described in individual cases to reduce GI bleeding, but there are no cases of prolonged durable eradication of bleeding.
References
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