Blue rubber bleb nevus syndrome

Overview

Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder characterized by the presence of multiple venous malformations, primarily affecting the skin and gastrointestinal (GI) tract. These lesions, also called venous blebs, appear as soft, blue to purple nodules that can range in size and number. While the skin lesions are typically benign and painless, those in the GI tract can cause chronic bleeding, leading to iron-deficiency anemia. BRBNS can vary widely in severity, from mild cutaneous involvement to life-threatening internal hemorrhages.

Causes

The exact cause of BRBNS is not fully understood, but most cases occur sporadically with no family history. In rare cases, the condition has been reported as inherited in an autosomal dominant pattern, meaning a mutation in one copy of the gene can lead to the syndrome. Recent research has suggested that somatic mutations in the TEK (TIE2) gene, which plays a role in blood vessel development, may be associated with BRBNS. However, more studies are needed to confirm the genetic mechanisms involved.

Symptoms

Symptoms of blue rubber bleb nevus syndrome typically appear at birth or in early childhood and may include:

• Blue to purple compressible skin nodules – often rubbery and painless, commonly found on the trunk, limbs, and face

• Gastrointestinal bleeding – leading to black, tarry stools (melena) or visible blood in stool

• Iron-deficiency anemia – due to chronic internal bleeding

• Fatigue and weakness – associated with anemia

• Pain or discomfort – if vascular malformations occur in internal organs such as the muscles, joints, or brain

• Rare complications – such as intestinal obstruction, intussusception, or hemorrhage

Diagnosis

Diagnosis of BRBNS is based on clinical findings and imaging studies. Diagnostic steps include:

• Physical examination – identification of characteristic skin lesions

• Endoscopy or colonoscopy – to detect vascular malformations in the GI tract and evaluate bleeding sources

• Magnetic resonance imaging (MRI) or CT scans – to assess internal organ involvement

• Capsule endoscopy – a swallowable camera to examine the small intestine

• Blood tests – to check for anemia and monitor iron levels

• Genetic testing – may be considered in suspected familial cases or for research purposes

Treatment

There is no cure for BRBNS, so treatment focuses on symptom management and preventing complications. Options include:

• Iron supplementation – orally or intravenously to manage chronic anemia

• Blood transfusions – in cases of significant blood loss or severe anemia

• Endoscopic interventions – such as cauterization, sclerotherapy, or laser ablation of GI lesions

• Surgical removal – of problematic lesions that cause obstruction or uncontrollable bleeding

• Pharmacologic therapy – including sirolimus (an mTOR inhibitor) which has shown promise in reducing lesion size and bleeding

• Dermatologic procedures – for cosmetic removal or treatment of painful skin lesions

Prognosis

The prognosis for individuals with BRBNS varies depending on the severity and extent of internal involvement. Most patients live normal lifespans with appropriate treatment and monitoring, although chronic anemia and recurrent bleeding can impact quality of life. Regular follow-up with gastroenterologists, hematologists, and dermatologists is important for managing the condition. Advances in targeted therapies, such as sirolimus, offer hope for improved outcomes in moderate to severe cases.