Blue rubber bleb nevus syndrome is a rare disorder consisting of multiple venous system malformations predominantly involving the skin, musculoskeletal system, and gastrointestinal tract. Lesions may involve any tissue and have a potential for severe bleeding and death.
The name blue rubber bleb nevus syndrome is derived from the rubber-like consistency on palpation of the cutaneous lesions. They present as dark blue compressible papules that may or may not be painful  and measure from millimeters to centimeters in diameter. These cutaneous nevi do not bleed spontaneously but are fragile and may be flat, elevated or pedunculated.
Patients have nonspecific complaints like asthenia caused by chronic hemorrhage due to acute blood loss following hematemesis, rectal bleeding or melena, hemoptysis, hematuria, epistaxis or nasal bleeding  or signs of hemothorax or hemopericardium. Occipital lobe bleeding associated with blue rubber nevus syndrome has been described, leading to blindness . Similar lesions may be encountered in any  type of tissue: glandular, muscular, genital, bone, heart, lung, renal, pericardium and peritoneum  .
Nevi are usually present and diagnosed at birth and have a natural tendency to grow and multiply or even invade neighboring structures as the child grows older, but malignant transformation has not been reported yet. Nevi located close to bones may cause bowing deformity, while those in the neighborhood of joints may lead to hemarthrosis and affect joint mechanics. Their histological nature, consisting of dysplastic veins with abnormal walls may cause consumption coagulopathy that exacerbates blood loss.
Entire Body System
Oral iron replacement was begun and her anemia was corrected. The patient is presently in stable condition. [revistagastroenterologiamexico.org]
BRBNS is associated with anemia and occasionally involves orthopedic manifestations. A 6-year-old boy was referred to hospital for evaluation of anemia. [ncbi.nlm.nih.gov]
He had severe anemia and a venous swelling on the trunk. Similar lesions were found in the stomach, bowel, and on his foot. [scielo.br]
Jaw & Teeth
- Vascular Disease
Abstract Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital vascular disease associated with important morbidity and non-insignificant risk of mortality in cases of severe gastrointestinal or neurological involvement. [ncbi.nlm.nih.gov]
主要主题词： Esophagus; Gastrointestinal Neoplasms; Nevus, Blue; Skin Neoplasms; Vascular Diseases [paper.medlive.cn]
[…] was described by Gascoyen in 1860. , In 1958, Bean differentiated this type of angiomatosis from other cutaneous vascular diseases. , BRBNS can affect many organs and there are only fewer than 200 cases published. ,, This disease [jiaomr.in]
Clinical examination may reveal signs of chronic or acute posthemorrhagic anemia or of other complications like volvulus, bowel infarction or intussusception. Mobility may be impaired due to the extension of the lesion inside the joint  or due to spinal cord compression . Patients may exhibit dyspnea caused by severe anemia or recurrent thromboembolism and pulmonary hypertension  or cyanosis induced by pulmonary stenosis .
Workup should include a complete blood count, serum iron levels, a stool sample for occult blood and a urine sample that may detect hematuria.
Skeletal and articular involvement is diagnosed using simple X-rays and may include focal lytic defects or cortical remodeling . The extent of gastrointestinal lesions is best evaluated using superior digestive endoscopy or colonoscopy, while magnetic resonance imaging , computer tomography  and Technetium-99 scintigraphy  detect extracutaneous lesions and bleeding. Magnetic resonance imaging is especially useful in diagnosing liver, spleen and pancreatic lesions, while capsule endoscopy is emerging as an alternative to evaluate gastrointestinal nevi . This is particularly useful since barium studies, the cheaper and more widely accessible alternative only shows polypoid structures and is unable to differentiate between polyps and nevi, creating confusion.
Visceral angiography is not usually indicated, unless performed for other reasons in the same area, despite the fact that it might offer valuable information during the venous phase.
If the extent of the disease is not easily appreciated using noninvasive measures, an exploratory laparoscopy should be performed, especially since this could limit the area of the small bowel to be resected.
- Pericardial Effusion
A chest x-ray showed an enlarged cardiac silhouette suggestive of pericardial effusion (Figure B). This was confirmed by transthoracic echocardiography. Therapeutic pericardiocentesis showed haemopericardium. [mja.com.au]
- Multiple Pulmonary Nodules
We report the case of a 37-year-old woman, with known BRBNS, who acquired an intractable cough with a radiograph revealing multiple pulmonary nodules. [ncbi.nlm.nih.gov]
The dose and length of treatment with these agents has not been well defined and lesions may return to their pretreatment size after discontinuation of treatment. In the absence of GI bleeding, conservative treatment should suffice. [dermatologyadvisor.com]
There are currently no effective treatments for BRBNS. Here, we report a case of successful treatment with a small dose of sirolimus of a BRBN patient with a de novo gene mutation. [ncbi.nlm.nih.gov]
Rarely, CNS involvement can be fatal.  The prognosis for blue rubber bleb nevus syndrome (BRBNS) depends on the extent of visceral organ involvement and complications related to the degree of symptoms. [emedicine.com]
Etiology Underlying etiology is not known. BRBNS appears to be a sporadic event (although a small number of autosomal dominant cases has been reported). [dermatologyadvisor.com]
The etiology of blue rubber bleb nevus syndrome (BRBNS) remains unknown.  The literature suggests that this condition occurs sporadically. [5, 6] A few reported cases have been associated with an autosomal dominant inheritance pattern, for which a [emedicine.com]
In addition, we review the available literature on the epidemiology, clinical features, associated conditions, diagnosis and treatment. [ncbi.nlm.nih.gov]
A world wide website was established to determine the epidemiology, natural history, and clinical aspects of BRBNS. Results : 35 individuals with the diagnosis of BRBNS responded to the website. Only 20 fulfilled the definition of BRBNS. [nature.com]
Even though the disease appears sporadically in the majority of reported cases, some have a dominant autosomal component related to a mutation of chromosome 9p.3 The epidemiology and natural history of BRBNS is not well known. [revistagastroenterologiamexico.org]
Summary Epidemiology More than 200 cases have been published so far, but prevalence is unknown. [orpha.net]
The detailed clinical, endoscopical and histopathological description is given as a wide range of differential diagnosis of vascular lesions based on pathophysiology and updated classification of vascular lesions. [termedia.pl]
The disease shows no predilection for gender. Etiology and Pathophysiology The etiology and pathophysiology of BRBNS is unknown, however activating mutations in the angiopoietin receptor TIE2/TEK have been determined as a potential cause for BRBNS. [eyewiki.aao.org]
Goodpasture syndrome: pathophysiology, diagnosis, and management. Nephrol Nurs J 2001;28(3):305-12. Jóźwiak L, Orłowska-Kowalik G, Książek A. Zespół Goodpasture’a współ- istniejący z nieswoistym zapaleniem jelit u 28-letniej kobiety. [ojs.pum.edu.pl]
Pathophysiology It is not known whether BRBNS occurs secondary to angiogenesis, vasculogenesis, or enlargement of dormant vessels. Systemic Implications and Complications The biggest concern in BRBNS is GI involvement. [dermatologyadvisor.com]
Pathophysiology Skin manifestations can typically be found at birth, whereas, organ system involvement tends to appear later in life.  The internal organ system most frequently involved is the GI system, for which GI bleeding is a common symptom. [ [emedicine.com]
The patient was treated with octreotide to prevent rebleeding. During the 12 months of treatment he had no gastrointestinal bleeding episodes or anaemia. Then repeat capsule endoscopy showed that the small bowel vascular lesions were unchanged. [ncbi.nlm.nih.gov]
Current medical research has not established a way of preventing Blue Rubber Bleb Nevus Syndrome If there is a family history of BRBNS, then genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing [dovemed.com]
- Yuksekkaya H, Ozbek O, Keser M, et al. Blue rubber bleb nevus syndrome: successful treatment with sirolimus. Pediatrics. 2012;129(4):e1080-1084.
- Esposito C, Giurin I, Farina A, et al. Blue rubber bleb nevus: an uncommon cause of intestinal intussusception. Eur J Pediatr. 2012;171(7):1139-1140.
- Huang W, Rhodes A. A Case of Blue Rubber Bleb Nevus Syndrome with Gastrointestinal and Central Nervous System Involvement. Pediatr Dermatol. 2012;29(4):524-525.
- Starr BM, Katzenmeyer WK, Guinto F, et al. The blue rubber bleb nevus syndrome: a case with prominent head and neck findings. Am J Otolaryngol. 2005;26(4):282-284.
- Boente MD, Cordisco MR, Frontini MD, et al. Blue rubber bleb nevus (Bean syndrome): evolution of four cases and clinical response to pharmacological agents. Pediatr Dermatol 1999; 16:222 –227.
- Moodley M, Ramdial P. Blue rubber bleb nevus syndrome: case report and review of the literature. Pediatrics. 1993; 92:160 –162.
- Doi T, Masumoto N, Sonoda M, et al. Blue rubber bleb nevus syndrome with knee joint disorder. Pediatr Int. 2016;58(8):740-743
- Garen PD, Sahn EE. Spinal cord compression in blue rubber bleb nevus syndrome. Arch Dermatol. 1994;130(7):934-935.
- Giordano C, Battagliese A, di Gioia CR, et al. Blue rubber bleb nevus syndrome and pulmonary hypertension: an unusual association. Cardiovasc Pathol. 2004;13(6):317-322.
- Singal A, Vohra S, Sharma R, et al. Blue Rubber Bleb Nevus Syndrome with Musculo-skeletal Involvement and Pulmonary Stenosis. Indian Pediatr. 2016; 53(6):525-7.
- McCarthy JC, Goldberg MJ, Zimbler S. Orthopaedic dysfunction in the blue rubber bleb nevus syndrome. J Bone Joint Surg Am 1982;64:280 –283.
- Shannon J, Auld J. Blue rubber bleb naevus syndrome associated with cortical blindness. Australas J Dermatol. 2005;46 (3):192-5.
- Senturk S, Bilici A, Miroglu TC, Bilek SU. Blue rubber bleb nevus syndrome: imaging of small bowel lesions with peroral CT enterography. Abdom Imaging. 2011;36(5):520-523.
- Yarlagadda R, Menda Y, Graham MM. Tc-99m red blood cell imaging in a patient with blue rubber bleb nevus syndrome. Clin Nucl Med. 2008;33(5):374-376.
- Lewis BS, Swain P. Capsule endoscopy in the evaluation of patients with suspected small intestinal bleeding: results of a pilot study. Gastrointest Endosc 2002; 56:349 –353.