Blue Rubber Bleb Nevus Syndrome Presenting as Severe Transfusion‐Dependent Anemia in an Elderly Patient: An Unusual Cause of Lower Gastrointestinal Bleeding

ABSTRACT

Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder characterized by venous malformations involving the skin and gastrointestinal (GI) tract. GI involvement may lead to chronic bleeding and iron deficiency anemia, most commonly presenting in younger individuals. We report the case of an 83‐year‐old male presenting with progressive fatigue and severe anemia (hemoglobin 5 g/dL), requiring multiple blood transfusions. His medical history was significant for recurrent anemia and prior gastrointestinal bleeding. Upper endoscopy was unremarkable; however, colonoscopy revealed multiple bluish, compressible venous malformations scattered throughout the ascending and transverse colon, consistent with BRBNS. Capsule endoscopy excluded small bowel involvement. Given the diffuse distribution and number of lesions, endoscopic or surgical intervention was not feasible. The patient was managed conservatively with blood transfusions and close outpatient follow‐up. BRBNS is typically diagnosed in childhood, and adult presentation, particularly in the elderly, is uncommon. Gastrointestinal lesions are more prone to bleeding than cutaneous lesions and may lead to chronic transfusion‐dependent anemia. Diagnosis requires a high index of suspicion, especially in patients with recurrent unexplained anemia and negative initial investigations. Management remains challenging and depends on disease extent, ranging from conservative measures to endoscopic, surgical, or pharmacologic therapies. This case highlights an unusual late presentation of BRBNS with isolated colonic involvement and emphasizes the importance of considering vascular malformations in the differential diagnosis of obscure gastrointestinal bleeding in elderly patients.

Key Clinical Message

Unexplained, recurrent anemia in the elderly is not always due to common causes. Rare entities like Blue rubber bleb nevus syndrome should be considered, especially when standard investigations are unrevealing.

1. Introduction

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by cutaneous vascular malformations commonly associated with gastrointestinal tract involvement [1]. More recently, Rudolf Happle suggested the designation “blue rubber bleb angiomatosis” in 2010 to better reflect its vascular nature [2]. BRBNS affects both pediatric and adult populations without sex predilection, though it appears to be less frequently reported among Black individuals [3]. Most cases are sporadic, with no identifiable family history; however, an autosomal dominant inheritance pattern has been described in some patients [3].

2. Case History/Examination

An 83‐year‐old male presented to the emergency department with a 4‐day history of progressive fatigue, lethargy, and generalized pallor. His past medical history was significant for chronic anemia requiring multiple prior hospitalizations and repeated blood transfusions. Previous evaluations had suggested a hemolytic component; however, no definitive underlying etiology had been established despite prior investigations, with the most recent admission occurring 2 weeks prior to presentation. His comorbidities included hypertension, diabetes mellitus, coronary artery disease, chronic kidney disease, congenital blindness, psoriasis, and second‐degree atrioventricular block status post permanent pacemaker insertion. His home medications included antihypertensive agents, antidiabetic medications, and antiplatelet therapy (aspirin) for coronary artery disease and previous carotid artery stenting. The use of antiplatelet agents may have contributed to the severity of gastrointestinal blood loss and worsening anemia.

His surgical history was notable for carotid artery stenting performed for carotid artery stenosis, as well as prior arteriography and embolization for a massive upper gastrointestinal bleed secondary to a large (2 cm) duodenal bulb ulcer. He reported no known drug or food allergies. On admission, the patient appeared pale but was hemodynamically stable. A comprehensive physical examination, including a detailed dermatologic assessment, revealed no cutaneous venous malformations or other vascular lesions suggestive of BRBNS. No clinically evident extracutaneous vascular malformations were identified.

3. Investigations and Treatment

Laboratory investigations were unremarkable except for severe anemia, with a hemoglobin level of 5 g/dL. Additional laboratory investigations demonstrated findings consistent with chronic blood loss anemia, including a serum ferritin level of 9 ng/mL (reference range: 30–400 ng/mL), serum iron of 24 μg/dL (reference range: 60–170 μg/dL), and transferrin saturation of 8% (reference range: 20%–50%). Markers of hemolysis revealed a mildly elevated lactate dehydrogenase (LDH) level of 320 U/L (reference range: 140–280 U/L), reduced haptoglobin level of 18 mg/dL (reference range: 30–200 mg/dL), and an increased reticulocyte count of 3.8% (reference range: 0.5%–2.5%). He was admitted for transfusion and received a total of four units of packed red blood cells, resulting in an increase in hemoglobin to 10.7 g/dL over 4 days. Following stabilization, a gastroenterology consultation was obtained to investigate a potential source of recurrent anemia, given his prior history of gastrointestinal bleeding. Esophagogastroduodenoscopy revealed no evidence of active upper gastrointestinal bleeding, with normal findings in the esophagus (without varices), duodenal bulb, and the remaining portions of the duodenum. Subsequently, colonoscopy demonstrated multiple (approximately 15–20) bluish, compressible venous malformations ranging from approximately 5 to 25 mm in diameter scattered throughout the ascending and transverse colon. No active bleeding or stigmata of recent hemorrhage were identified at the time of endoscopy (Figures 1 and 2). Endoscopic biopsy was considered but ultimately deferred because of the highly vascular nature of the lesions and the substantial risk of procedure‐related bleeding. Given the characteristic endoscopic appearance, tissue confirmation was not considered essential for establishing the diagnosis. These findings were consistent with a diagnosis of BRBNS, which likely accounted for the patient's chronic anemia. Although histologic confirmation was not obtained, the diagnosis was considered highly probable based on the characteristic endoscopic appearance of multiple bluish, compressible venous malformations in the setting of recurrent transfusion‐dependent gastrointestinal blood loss and the absence of alternative bleeding sources despite extensive evaluation. The distinctive morphology of the lesions, together with the clinical presentation, strongly supported the diagnosis of BRBNS. Given the number and size of the lesions, endoscopic intervention was deemed not feasible. To complete the evaluation, video capsule endoscopy was performed to assess the small bowel, which revealed no additional abnormalities.

FIGURE 1.

Venous malformations of varying sizes, appearing as bluish, compressible blebs scattered throughout the ascending colon.

FIGURE 2.

Venous malformations of varying sizes, appearing as bluish, compressible blebs scattered throughout the transverse colon.

4. Outcome and Follow‐Up

The patient was managed conservatively with blood transfusions and supportive care. Conservative management was favored because of the patient's advanced age, significant comorbidity burden, diffuse distribution of lesions, absence of active bleeding during endoscopic evaluation, and the potentially high risk associated with invasive therapeutic interventions. He was discharged in stable condition with close outpatient follow‐up and regular monitoring of his hemoglobin levels.

Endoscopic therapeutic modalities including band ligation, sclerotherapy, and argon plasma coagulation were considered during multidisciplinary discussions. However, these options were not pursued because of the diffuse and multifocal nature of the lesions, lack of active bleeding, and concerns regarding procedural risks in the setting of advanced age and multiple comorbidities.

5. Discussion

BRBNS was likely first described by Camilleri et al. in 1948 [4]. A century later, Bean [5] formally introduced the term to characterize this rare congenital disorder marked by vascular malformations involving the skin and gastrointestinal (GI) tract. In his original description, three types of cutaneous lesions were identified: (1) soft, compressible, bluish bleb‐like lesions that refill rapidly after pressure; (2) large, disfiguring cavernous malformations capable of compressing adjacent structures; and (3) irregular macular blue lesions scattered across the body [3].

BRBNS shows no sex predilection and may present at any age. Cutaneous lesions typically appear early in life, increasing in size and number over time, often influenced by local trauma. These lesions are usually asymptomatic, rarely bleed spontaneously, and have no malignant potential [1, 6]. While most are painless, some may become tender upon compression [3, 7].

Gastrointestinal involvement generally becomes evident in adulthood, often presenting with anemia, occult blood loss, or overt bleeding. Venous malformations may affect any segment of the GI tract, although they are most frequently located in the small intestine and colon [3, 8]. Unlike cutaneous lesions, GI malformations bleed more readily, leading to manifestations such as hematemesis, melena, or rectal bleeding. Chronic blood loss may result in iron deficiency anemia requiring ongoing supplementation or transfusion [3]. In the present case, anemia was likely multifactorial. Although chronic gastrointestinal blood loss from BRBNS was considered the principal contributor, additional factors may have exacerbated the severity of anemia, including chronic kidney disease, a previously suspected hemolytic component, prior severe upper gastrointestinal bleeding due to a duodenal ulcer, and the use of antiplatelet therapy for underlying cardiovascular disease. Such coexistence of multiple etiologies may further complicate the diagnostic evaluation of anemia in elderly patients and potentially delay recognition of uncommon causes such as BRBNS. Lesions may appear polylobulated, nodular, sessile, pedunculated, or ulcerated, and complications include intussusception, volvulus, intestinal infarction, and, in severe cases, hypovolemic shock [1, 9].

Early diagnosis is essential to prevent severe bleeding complications. Colonoscopy remains the preferred modality for detecting colonic lesions, whereas small bowel involvement may require CT enterography, magnetic resonance imaging, capsule endoscopy, or double‐balloon enteroscopy [10]. In cases of active bleeding, selective arteriography and scintigraphy can aid in localization [3].

Management depends on lesion distribution, size, and clinical progression. Conservative treatment is appropriate for patients with limited or asymptomatic lesions. In cases of significant bleeding or anemia, less invasive options include endoscopic sclerotherapy, band ligation, laser therapy, and selective surgical excision [3]. Extensive surgical approaches, such as segmental resection or colectomy, are reserved for localized or refractory disease, although success is often limited due to the diffuse nature of lesions [3].

A systematic review of 106 cases from 76 reports demonstrated a clinical success rate of 92.4%. Three main therapeutic strategies were identified: systemic pharmacologic therapy, endoscopic intervention, and surgery. Systemic therapy was more commonly used as a second‐line option following recurrence or endoscopic failure but was associated with higher rates of adverse events. Recently, sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR) pathway, has emerged as a promising therapeutic option for patients with extensive, refractory, or surgically inaccessible BRBNS lesions [11]. Several case reports and small case series have demonstrated reductions in gastrointestinal bleeding, transfusion requirements, and lesion size following sirolimus therapy. Nevertheless, the optimal dose, treatment duration, and long‐term safety profile remain incompletely defined, particularly in elderly patients with multiple comorbidities. Consequently, treatment decisions should be individualized and carefully balanced against potential adverse effects [11]. Endoscopic treatment required more sessions compared with surgery, while no significant differences were observed in recurrence rates or follow‐up duration among the approaches [12].

Few cases of BRBNS presenting in elderly individuals have been reported in the literature (Table 1). Similar to the case described by Goud et al. [18], our patient presented in advanced age with severe anemia and without cutaneous manifestations, highlighting the diagnostic challenge posed by isolated gastrointestinal disease. However, unlike most reported elderly cases in which the small intestine was predominantly involved [14, 16], our patient exhibited isolated colonic involvement without evidence of small bowel lesions on capsule endoscopy. Furthermore, the diagnosis was established at 83 years of age, making this among the oldest reported patients with newly diagnosed BRBNS. These findings underscore the marked clinical heterogeneity of BRBNS and emphasize that the syndrome should remain a diagnostic consideration even in elderly patients presenting with obscure gastrointestinal bleeding or transfusion‐dependent anemia.

TABLE 1.

Summary table of adult BRBNS case reports with lower GI bleeding.

Author (year)	Age/sex	Presentation	GI location	Cutaneous lesions	Intervention	Outcome
Martinez et al. (2014) [3]	41/M	Recurrent hematochezia, anemia	Colon (right colon vascular lesion)	Present	Endoscopic + local excision and sclerosis	No recurrence at 2 years
Goud et al. (2016) [12]	76/M	Hematochezia, severe anemia	Colon + esophagus	Absent	Supportive + endoscopic evaluation	Stabilization after transfusion
Deshpande et al. (2014) [13]	40/M	Chronic melena, anemia	Small bowel (jejunojejunal intussusception)	Present	Surgical resection	Uneventful recovery
Jin (2014) [9]	45/F	Severe anemia, GI bleeding	Colon + multiple GI sites	Present (extensive)	Supportive ± interventional	Clinical improvement
Reddy et al. (2022) [14]	Adult/M	GI bleeding (occult/overt)	Jejunum (isolated GI BRBNS)	Absent	Endoscopic/conservative	Stable after management
Zhai et al. (2022) [15]	56/F	Melena, chronic anemia	Small bowel	Present	Argon plasma coagulation + sirolimus	No recurrence at 12 months
Romanello et al. (2025) [16]	Adult	GI bleeding, anemia	Small bowel	Not specified	Supportive/interventional	Improved
Rashid et al. (2019) [17]	Adult	Chronic GI bleeding, transfusion‐dependent anemia	GI tract (multiple)	Present	Supportive ± interventional	Variable

This case is particularly noteworthy due to several uncommon features. First, BRBNS typically manifests in childhood or early adulthood, whereas our patient presented at an advanced age of 83 years, making this an exceptionally rare late diagnosis [13, 14, 16, 18]. Second, the disease in this case was confined to the colon without evidence of small bowel involvement, which contrasts with the more commonly reported predominance of small intestinal lesions. Furthermore, the absence of characteristic cutaneous findings, often considered a hallmark of BRBNS, added to the diagnostic challenge and may have contributed to delayed recognition [14, 18]. Finally, the patient's presentation with severe transfusion‐dependent anemia in the setting of multiple comorbidities underscores the importance of considering BRBNS as a differential diagnosis even in elderly patients with obscure gastrointestinal bleeding. Collectively, these features highlight the heterogeneity of BRBNS and reinforce the need for individualized diagnostic and therapeutic approaches.

The absence of cutaneous manifestations and lack of histopathological confirmation represented diagnostic challenges in this case. Nevertheless, the typical endoscopic appearance of the lesions combined with the patient's clinical course and exclusion of other potential sources of bleeding made BRBNS the most likely diagnosis.

BRBNS is a rare but important cause of gastrointestinal bleeding that may present atypically in adulthood. This case illustrates an unusual late presentation with isolated colonic involvement and severe transfusion‐dependent anemia in the absence of cutaneous manifestations. Diagnosis requires a high index of suspicion, particularly in patients with recurrent unexplained anemia. Management remains individualized, with conservative treatment being a reasonable option in diffuse disease not amenable to intervention. Awareness of such atypical presentations is essential to avoid diagnostic delays and to optimize patient outcomes through appropriate monitoring and tailored therapeutic strategies.

Author Contributions

Philippe Attieh: conceptualization, data curation, writing – original draft. Rim Moubayed: conceptualization, writing – original draft, data curation. Karam Karam: conceptualization, writing – original draft, data curation. Ihab l El Hajj: conceptualization, writing – original draft, data curation. Mahmoud Harb: conceptualization, writing – original draft, data curation.

Funding

The authors have nothing to report.

Disclosure

Our research was conducted in accordance to the declaration of Helsinki.

Ethics Statement

Ethics committee at Clemenceau Medical Center approved this study.

Consent

Patients in this manuscript have given written informed consent to publication of this case report details.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.