Discussion
As a rare disease, the clinical manifestations of BRBNS is varied dependent on organs involvement. The lesions often occur at the cutaneous and GI tract. The typical lesions of cutaneous are only a few or quite a few scattered dark blue nevus with different size, usually asymptomatic [3]. The notable symptoms with GI tract lesions are hemorrhage and secondary anemia due to digestive tract blood loss [4]. A series of reports applause that video capsule endoscopy can provide direct and complete scanning of small-bowel lesions [2]. For this patient, she has suffered refractory IDA for 12 years, without any obvious signs of GI tract hemorrhage including hematochezia, melena, and negative FOBT many times. Misdiagnosis and delayed curation often occurs in such patients without significant cutaneous lesions or GI tract bleeding events.
The etiology of BRBNS is still unknown, and the majority of cases are sporadic without definite family history. It has been described an autosomal dominant transmission in some cases, with the responsible locus in 9p chromosome [5]. Recently, Soblet et al. discovered that somatic mutations in TEK (the gene encoding TIE2) could result in ligand-independent activation of TIE2 and lead to BRBNS[6]. The treatment of BRBNS includes supportive therapy [2], pharmacological interventions[7], and endoscopic treatments[8]. Surgery is reserved for patients with significant hemorrhage or other complications [9]. Nowadays, some researchers also propose that sirolimus is useful for the patients with BRBNS. However, there are no clear guidelines regarding dosing regimen, and the long-term safety [10].
Until now, there is no available guidelines for diagnosis and management for BRBNS. The management of BRBNS generally depends on the extent of intestinal involvement and presence of other organ involvement, we just simply outline the management and treatment of BRBNS (Fig. 3). If patients only exhibit intermittent occult bleeding or mild anemia, palliative options such as iron supplementation and blood transfusion are usually chosen [2]. When patients have massive hemorrhage, refractory severe anemia, or related GI complications such as intussusception, rupture, gangrene, volvulus, and infarction, surgery or endoscopic treatment are recommended [11]. The successful use of sirolimus was recently reported in the treatment of BRBNS [12]. However, sirolimus has potential side effects on renal function, bone marrow, and cholesterol metabolism. In consideration of the patient’s young age, we did not adopt this method. In this patient, we first deliver conservative therapies to improve the severity of anemia, and then we perform surgical resection successfully. She is in the remission condition but further follow-up is still needed.
Refractory IDA and chronic occult bleeding from GI tract could happen due to BRBNS. Clinicians should keep in mind to detect the underlying diseases from GI tract by endoscopy. Precision diagnosis and appropriate intervention could booster to upgrade the quality of life for patients.