Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder with multiple haemangiomas in the skin, gastrointestinal tract and other visceral organs often associated with fatal bleeding and anaemia. We report a 13-year-old female child with multiple haemangiomas on skin and gastrointestinal tract with refractory anaemia. Awareness of this entity is necessary to prevent complications.
Case Report
A 13-year-old female, child born of non consanguineous marriage was referred to Department of Pediatric Dermatology for multiple nevi on trunk and extremities from birth. It was slowly progressive with occasional bleeding from these lesions. She had generalized weakness, fatigue and anaemia from past three years. She was evaluated at various hospitals for anaemia but the cause was not known. There was no history of fever, nausea, vomiting, pain abdomen, melena, haematemesis, epistaxis or recurrent infections. She had received multiple blood transfusions but had recurrent anaemia. Her developmental milestones were normal. Family history was non contributory.
On examination, the child had pallor. Vital parameters were normal. Cutaneous examination showed multiple well defined soft compressible bluish-black, verrucous, protuberant bleb like nevi on the dorsum of left hand, left palm, chest, thighs, both soles and medial aspect of left lower leg [Table/Fig-1,2]. Oral mucosa was normal. Laboratory investigations revealed severe anaemia (haemoglobin-3.7gm/dl), thrombocytopenia (platelet count - 89000/mm3), peripheral smear showed microcytic hypochromic anaemia, with anisopikilocytosis and few target cells. Serum ferritin levels were very low (2.22ng/ml). Stool for occult blood was negative. Ultrasound showed mild hepatosplenomegaly with no focal lesions. Upper GI endoscopy was normal. Colonoscopy showed multiple nodular bluish nevi measuring 3x2 cm in the sigmoid colon. Other investigations like chest X-ray, liver functions test, haemoglobin electrophoresis and bone marrow examination was normal. Skin biopsy revealed epidermis with papillomatosis and orthohyperkeratosis, papillary dermis and reticular dermis showed large ectatic spaces lined by endothelial cells filled with blood [Table/Fig-3a,b]. Based on clinical examination and investigation diagnosis of blue rubber bleb nevus syndrome (BRBNS) was considered. The child was given blood transfusion with long term iron supplements. The child could be followed up for three months and after that did not turn up.
Discussion
BRBNS or Bean syndrome is a rare congenital disorder characterized by multiple venous malformations in skin, gastrointestinal tract and other organs. BRBNS has the potential for fatal bleeding [1]. Although sporadic, autosomal dominant inheritance has been reported. Recently it has been linked to mutation in chromosome 9p responsible for venous malformation [2]. Most cases reported from India are sporadic in nature [3,4]. The pathogenesis of the condition is still not clear.
Around 200 cases have been reported in literature. Majority of the cases reported have cutaneous and gastrointestinal involvement [5,6]. Cutaneous lesions are present from birth, but may increase in number with age. They are characterized by soft compressible bluish-black, verrucous, protuberant blebs of varying size [4]. They are often non tender, but occasionally painful. Three types of skin lesions have been described, large disfiguring lesions obstructing vital tissues, purple-black compressible rubbery nipple like angiomas and irregular blue black macules [7]. They are discrete, multifocal mainly distributed on trunk, extremities, palms and soles but can be seen anywhere in the body. Rarely these nevi can be situated in subcutaneous fat not appearing as blue blebs. Recently unilateral linearly distributed, along the lines of Blaschko has been reported [8]. Oral lesions occur in 59-64% cases, most common sites being buccal mucosa, retromolar trigone and ventrolateral tongue [9].
Visceral malformation mainly affects the gastrointestinal tract. They may occur anywhere from oral to anal mucosa but more commonly occur in the small bowel. They are sessile or polypoid and visualized by endoscopy. Gastrointestinal lesions frequently bleed as compared to skin lesions which rarely bleed. Chronic bleeding may lead to iron deficiency anaemia, bloody stool and thrombocytopenia. Rarely massive haemorrhage, bowel infarction, intussusceptions and volvulus may occur [10]. The lesions may also occur in nasal cavity, nasopharynx, eyes, thyroid, parotids, central nervous system, skeletal muscles, pleura, peritoneum, pericardium, mesentery, synovium, lungs, kidneys, liver, spleen, penis, vulva and bladder [9,10]. Other complications include skeletal bowing, pathological fracture, bony overgrowth, articular derangement and pain due to phleboliths. Rarely it is been associated with ventricular hypertrophy and atrial septal defect [7,9].
As compared to the cases reported in literature our case also had similar features of cutaneous and gastrointestinal nevi. In 30-40% cases the onset of disease is from birth [5]. Our case also presented with symptoms from birth. Rare complications reported in literature include thrombocytopenia which was seen in our case [5]. The cause of this complication is not clearly understood.
Differential diagnosis includes Maffucci syndrome, venous lakes, Osler Weber Rendu syndrome (hereditary haemorrhagic telangiectasia), Klippel-Trenauay/Parker-Weber syndrome, and disseminated haemangiomatosis and Kaposi sarcoma [11]. Histopathological examination of skin and gastrointestinal lesions shows vascular tissues with tortuous, blood filled ectatic vessels, lined by a single layer of endothelium, with surrounding thin connective tissue [2]. Gastrointestinal tract lesions can be evaluated by endoscopy, barium studies and nuclear imaging. Capsule endoscopy can detect lesions in small intestine. Sonography, MRI and doppler can confirm the nature of lesions [9,10].
Several modalities of therapy have been tried. Blood transfusion and iron tablets are given for iron deficiency anaemia. Cryotherapy, sclerotherapy, excision and long pulsed Nd: YAG 1064nm laser has been used for cutaneous lesions. Gastrointestinal lesions can be treated with excision, cauterization, endoscopic laser photocoagulation, sclerosis, band ligation or polpectomy [12]. If there is a life threatening haemorrhage, segmental resection of the involved gastrointestinal tract can be performed.
Multiple well defined soft bluish-black, verrucous, protuberant bleb like nevi on the dorsum of left hand (a), left palm (b), chest (c) and back (d)
Bluish-black, verrucous nevi present on both soles (a,b) and medial aspect of left lower leg©
(a) Epidermis shows papillomatosis and hyperkeratosis, papillary and reticular dermis shows large ectatic spaces lined by endothelial cells filled with blood (H and E x 40). (b) Papillary dermis showing large vascular spaces filled with blood (H and E x 40)
Conclusion
BRBNS is a rare but important condition as it can give rise to fatal bleeding and complications. Child presenting with anaemia of unknown origin with multiple haemangiomas of skin poses a great diagnostic challenge that requires an open mind so as not to miss any rare cause. Parents should be counseled in detail about the nature of the condition and follow up regularly. This case is presented for its rarity, as early diagnosis of this condition will prevent complications.
[1]. M Dwivedi, EBCTCG (Early Breast Cancer Trialists' Collaborative Group), SP Misra, Blue rubber bleb nevus syndrome causing upper GI haemorrhage: a novel management approach and review Gastrointest Endosc 2002 55:943-46. [Google Scholar]
[2]. Q Liu, YP Chen, YM Li, Blue rubber bleb nevus syndrome: a report of one case associated with recurrent epistaxis Chin Med J 2007 120:731-33. [Google Scholar]
[3]. A Kumar, SR Negi, K Vaishnav, K Jain, Blue rubber bleb nevus syndrome: a rare case report Indian J Pathol Microbiol 2015 58:258-59. [Google Scholar]
[4]. MK Sahu, EG Simon, JA Joseph, A Chacko, Blue rubber bleb nevus syndrome: case report and review of the literature Journal of Digestive Endoscopy 2010 1:183-85. [Google Scholar]
[5]. XL Jin, ZH Wang, XB Xiao, LS Huang, XY Zhao, Blue rubber bleb nevus syndrome: a case report and literature review World J Gastroenterol 2014 20:17254-59. [Google Scholar]
[6]. MJ Zahedi, S Darvish Moghadam, SM Seyed Mirzaei, M Dehghani, S Shaflei Pour, A Rasti, Blue rubber bleb nevus syndrome as a rare cause of iron deficiency anemia: a case report and review of literature Middle East J Dig Dis 2013 5:235-39. [Google Scholar]
[7]. S Aroor, C Varma, SC Mundkur, Blue rubber-bleb nevus syndrome which was associated with an atrial septal defect: a case report Journal of Clinical and Diagnostic Research 2012 9:1566-67. [Google Scholar]
[8]. Y Xu, B Zhou, M Zhang, D Luo, An unusual case of blue rubber bleb nevus syndrome with unilateral linear distribution Indian J Dermatol Venereol Leprol 2013 79:269-70. [Google Scholar]
[9]. GN Suma, SM Ravi Prakash, D Rao, S Goel, Blue rubber bleb nevus syndrome: prominent oral findings Indian J Dermatol Venereol Leprol 2010 76:168-71. [Google Scholar]
[10]. I Maisnam, T Das, AK Kundu, A Ghosh, Blue rubber bleb nevus syndrome causing refractory anaemia J Assoc Physicians India 2010 58:246-49. [Google Scholar]
[11]. T Kaur, S Singh, Blue rubber bleb nevus syndrome: a case report Indian J Dermatol 2014 59:98-99. [Google Scholar]
[12]. SH Shin, HS Chae, JS Ji, HK Kim, YS Cho, ED Chang, A case of blue rubber bleb nevus syndrome Korean J Inter Med 2008 23:208-12. [Google Scholar]