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
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]
- Soft Tissue Mass
He presented with a rubber-like soft-tissue mass in the left knee and the right side of the neck, recurrent pain, and fixed flexion contracture of the knee. [ncbi.nlm.nih.gov]
Soft tissue masses not specific for hemangiomas can be revealed by CT scans. Selective arteriography and scintillography are useful in cases of active bleeding. In our case, the massive bleeding indicated surgical treatment. [scielo.br]
Physical examination indicated that the blue-black rubber-like soft-tissue masses ranging from 5 mm to 5 cm were on the neck, upper and lower limbs, chest walls, and back (Fig. 1 a). [karger.com]
On the contrast-enhanced CT images, the lesions were demonstrated by the thickening of bowel wall, nodular or irregular elevated lesions, soft-tissue masses, and enhancement in venous phase. [journals.lww.com]
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]
The management of ophthalmic involvement in blue rubber bleb nevus syndrome Case Report Abstract Objective: Blue rubber bleb nevus syndrome is a rare vascular disease most commonly associated with venous malformations of the skin and the gastrointestinal [egms.de]
A 27-year-old white woman presented with enophthalmos in the right eye. The visual acuity was 20/20 in both eyes. External examination showed 7 mm of enophthalmos of the right eye with deepened superior palpebral sulcus compared with the left eye. [ncbi.nlm.nih.gov]
Multiple orbital venous malformations presenting with enophthalmos in a patient with presumed blue rubber bleb nevus syndrome. Ophthal Plast Reconstr Surg. 2008 Jul-Aug;24(4):331-4. DOI: 10.1097/IOP.0b013e31817d027a 11. [egms.de]
Multiple orbital venous malformations presenting with enophthalmos in a patient with presumed blue rubber bleb nevus syndrome. [eyewiki.aao.org]
Neurologic examination showed right enophthalmos and ptosis, which had been present from early childhood. Motor and sensory findings were normal. [ajnr.org]
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.
- Microcytic Anemia
Blue Rubber Bleb Nevus Syndrome: Laser Photocoagulation of Colonic Hemangiomas in a Child with Microcytic Anemia. Pediatric Dermatology, Vol. 9, Issue. 2, p. 91. CrossRef Google Scholar Oranje, Arnold P. 1986. Blue Rubber Bleb Nevus Syndrome. [cambridge.org]
Morris L, Lynch PM, Gleason WA Jr, et al: Blue rubber bleb nevus syndrome: laser photocoagulation of colonic hemangiomas in a child with microcytic anemia. Pediatr Dermatol. 1992;9(2): 91-4. INTERNET Cherpelis BS. [rarediseases.org]
Blue rubber bleb nevus syndrome: laser photocoagulation of colonic hemangiomas in a child with microcytic anemia. Pediatr Dermatol 1992;9:91–94. PubMed CrossRef Google Scholar 31. [doi.org]
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]
Some patients also receive treatment due to cosmetic problems[ 10, 13, 14, 33 ]. The treatment of GI BRBNS is determined by the extent of intestinal involvement and severity of the disease. [doi.org]
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]
Etiology Underlying etiology is not known. BRBNS appears to be a sporadic event (although a small number of autosomal dominant cases has been reported). [clinicaladvisor.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]
Summary Epidemiology More than 200 cases have been published so far, but prevalence is unknown. [orpha.net]
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 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]
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- 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.
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- 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.