Case report
Blue rubber bleb nevus syndrome: late onset in a patient with cutaneous, neurological, and gastrointestinal involvement Amanda Regio Pereira1, MD, Mariana Cabral Nunes1, MD, Lilia Ramos dos Santos Guadanhim1, MD, Milvia Maria Simo˜es e Silva Enokihara2, PhD, Maria Helena Valle de Queiroz Padilha1, MS, Adriana Maria Porro1, PhD, Giuseppe D’Ippolito3, PhD, and Marcos César Floriano1, MS
1 Department of Dermatology, 2Department of Dermatology and Pathology, and 3 Department of Radiology, Universidade ~o Paulo, Sa ~o Paulo, Brazil Federal de Sa
Correspondence Amanda Regio Pereira, MD Rua Borges Lagoa, 508, Vl. Clementino ~o Paulo-SP, Brazil Sa E-mail: [email protected] Funding sources: None. Conflicts of interest: None declared. Ethics: The patient has given written informed consent for publication of this case report and all images included. The study was approved by the institutional Ethics Committee.
Introduction Blue rubber bleb nevus syndrome (BRBNS), also known as Bean’s syndrome, is an uncommon disorder characterized by multiple venous malformations affecting more frequently the skin and gastrointestinal tract, with possible involvement of any organ.1–4 There are only about 200 cases reported in the literature. Diagnosis is usually at birth or in early childhood, but late onset, despite being rare, has been previously reported.4–6 Typical skin lesions are blue or purple nodules, papules, or plaques, with a rubbery feel, that may coalesce into large masses, mostly located in the upper limbs and trunk.2 Cutaneous disease does not change the prognosis but should alert to possible and frequent internal lesions. Morbidity and mortality are determined by the extension of visceral involvement and are usually associated with intestinal bleeding.1–4 Case report
1420
A 65-year-old female patient presented to the dermatology clinic with a 7-year history of multiple asymptomatic bluish-purple papules, nodules, and tumors over the face, International Journal of Dermatology 2015, 54, 1420–1422
lips, neck, trunk, and upper limbs. The greatest lesion was an 11-cm-diameter dorsal tumor, resembling a cyst on palpation (Fig. 1a–c). Past medical history revealed two episodes of gastrointestinal hemorrhage – the first occurred seven years earlier, demanding transfusion of 13 units of packed red blood cells, and the latter required partial gastrectomy to control the bleeding. No similar cases were observed in the patient’s family. Histopathology revealed intense vascular ectasia in the papillary dermis, which was considered a venous malformation in the lip (Fig. 2), a macrocystic lymphatic malformation in the dorsal tumor and another dorsal lesion also compatible with a venous malformation. Digestive endoscopy detected two violaceous multilobulated masses, located in the esophagus and pyriform sinus (Fig. 3), whereas colonoscopy was normal. Calcified hepatic nodules, suggestive of venous malformations, were shown by abdominal computed tomography. Hypointense circumscribed lesions in the brain, compatible with cavernomas, were found using magnetic resonance imaging. The patient was treated with propranolol at a daily dose of 1 mg/kg. No adverse effects and no other hemorrhagic ª 2014 The International Society of Dermatology
Pereira et al.
Blue rubber bleb nevus syndrome
(a)
(b)
Case report
(c)
Figure 1 (a) Dorsal view of the patient: 11-cm-diameter cystic tumor and purple color nodule in the midline. (b) Limb tumor, with fibroelastic consistency and violaceous areas, suggesting vascular nature. (c) Purple papules on the lips (resembling venous lakes), bluish soft malar nodule and a fibroelastic tumor on the neck
Discussion
Figure 2 Histopathological analysis of the lip: intense vascular ectasia in the papillary dermis, with congestion of the lumen (hematoxylin-eosin, 409)
complications have occurred so far. However, after a 6-month follow-up, a reduction in the size of the lesions was not observed.
Clinical, histopathological, and imaging findings of this case are compatible with the diagnosis of BRBNS. The condition is rare and even more uncommon when it initiates in adulthood.4–6 The long gap between disease onset and diagnosis suggests that this syndrome is poorly recognized. Early diagnosis, though, is extremely important as visceral involvement can lead to severe hemorrhagic complications.5,7 The cutaneous findings may be the only clue and should alert to potential internal malformations.5,8 Lymphatic malformations are not usual in BRBNS, although previously reported, and illustrate the possibility that different types of vascular malformations (venous, arterial, lymphatic, and capillary) might coexist.3,9 Many different treatment options are mentioned in the literature, for example, surgical or endoscopic resection of symptomatic gastrointestinal lesions,10 Nd:YAG laser or surgery for cutaneous involvement,11 and systemic drugs such as corticosteroids, a-interferon, sirolimus, and propranolol.12,13
Figure 3 Endoscopic view of the esophagus and pyriform sinus: elevated violaceous multi-lobulated masses, up to 1.5 cm in
diameter ª 2014 The International Society of Dermatology
International Journal of Dermatology 2015, 54, 1420–1422
1421
1422
Case report
Blue rubber bleb nevus syndrome
In this case, the vascular malformations were stable in size, there was no functional impairment, and no relapse of gastrointestinal bleeding had been reported in the last two years. Considering the risks and benefits and the patient’s preference not to perform invasive procedures, the proposed treatment was conservative. The use of beta-blockers in vascular malformations is not scientifically grounded. In some cases, though, an empirical attempt can be made based on the wellestablished response observed in infantile hemangiomas. In conclusion, the best outcome for patients with BRBNS comes from early diagnosis and multidisciplinary followup. The dermatologist plays a key role in recognizing the syndrome and alerting other specialties to the potential involvement of any other organ and complications.
References 1 Bean WB. Vascular spiders and related lesions of the skin. Springfield, IL: Thomas, 1958. 2 Moss C, Shahidullah H. Naevi and other developmental defects. In: Burns T, Breathnach S, Cox N, Griffiths C, eds. Rook’s: textbook of dermatology, 8th edn. Oxford: Blackwell Publishing, 2010: 18.72–18.73. 3 Agnese M, Cipolletta L, Bianco MA, et al. Blue rubber bleb nevus syndrome. Acta Paediatr 2010; 99: 632–635. 4 Nahm WK, Moise S, Eichenfield LF, et al. Venous malformations in blue rubber bleb nevus syndrome: variable onset of presentation. J Am Acad Dermatol 2004; 50(5 Suppl): S101–S106.
International Journal of Dermatology 2015, 54, 1420–1422
Pereira et al.
5 Torchia D, Schincaglia E, Palleschi GM. Blue rubber-bleb naevus syndrome arising in the middle age. Int J Clin Pract 2010; 64: 115–117. 6 Mu~ noz-Navas M, Fern andez-Urien I, Espinet E, et al. Blue rubber bled nevus syndrome: three cases. Rev Esp Enferm Dig 2004; 96: 344–345. 7 Tomelleri G, Cappellari M, Di Matteo A, et al. Blue rubber bleb nevus syndrome with late onset of central nervous symptomatic involvement. Neurol Sci 2010; 31: 501–504. 8 Huang W, Rhodes A. A case of blue rubber bleb nevus syndrome with gastrointestinal and central nervous system involvement. Pediatr Dermatol 2012; 29: 524–525. 9 Marˇn-Manzano E, Utrilla L opez A, Puras Magallay E, et al. Cervical cystic lymphangioma in a patient with blue rubber bleb nevus syndrome: clinical case report and review of the literature. Ann Vasc Surg 2010; 24: 1136.el–1136.e5. 10 Fishman SJ, Smithers CJ, Folkman J, et al. Blue rubber bleb nevus syndrome: surgical eradication of bleeding. Ann Surg 2005; 241: 523–528. 11 Moser CM, Hamsch C. Successful treatment of cutaneous venous malformations in a patient with blue rubber bleb naevus syndrome by Nd:YAG laser. Br J Dermatol 2012; 166: 1143–1145. 12 Boente MD, Cordisco MR, Frontini MD, et al. Blue rubber bleb nevus (Bean syndrome): evolution of four cases and clinical response to pharmacologic agents. Pediatr Dermatol 1999; 16: 222–227. 13 Yuksekkaya H, Ozbek O, Keser M, et al. Blue rubber bleb nevus syndrome: successful treatment with sirolimus. Pediatrics 2012; 129: e1080–e1084.
ª 2014 The International Society of Dermatology
Blue rubber bleb nevus syndrome: late onset in a patient with cutaneous, neurological, and gastrointestinal involvement Amanda Regio Pereira1, MD, Mariana Cabral Nunes1, MD, Lilia Ramos dos Santos Guadanhim1, MD, Milvia Maria Simo˜es e Silva Enokihara2, PhD, Maria Helena Valle de Queiroz Padilha1, MS, Adriana Maria Porro1, PhD, Giuseppe D’Ippolito3, PhD, and Marcos César Floriano1, MS
1 Department of Dermatology, 2Department of Dermatology and Pathology, and 3 Department of Radiology, Universidade ~o Paulo, Sa ~o Paulo, Brazil Federal de Sa
Correspondence Amanda Regio Pereira, MD Rua Borges Lagoa, 508, Vl. Clementino ~o Paulo-SP, Brazil Sa E-mail: [email protected] Funding sources: None. Conflicts of interest: None declared. Ethics: The patient has given written informed consent for publication of this case report and all images included. The study was approved by the institutional Ethics Committee.
Introduction Blue rubber bleb nevus syndrome (BRBNS), also known as Bean’s syndrome, is an uncommon disorder characterized by multiple venous malformations affecting more frequently the skin and gastrointestinal tract, with possible involvement of any organ.1–4 There are only about 200 cases reported in the literature. Diagnosis is usually at birth or in early childhood, but late onset, despite being rare, has been previously reported.4–6 Typical skin lesions are blue or purple nodules, papules, or plaques, with a rubbery feel, that may coalesce into large masses, mostly located in the upper limbs and trunk.2 Cutaneous disease does not change the prognosis but should alert to possible and frequent internal lesions. Morbidity and mortality are determined by the extension of visceral involvement and are usually associated with intestinal bleeding.1–4 Case report
1420
A 65-year-old female patient presented to the dermatology clinic with a 7-year history of multiple asymptomatic bluish-purple papules, nodules, and tumors over the face, International Journal of Dermatology 2015, 54, 1420–1422
lips, neck, trunk, and upper limbs. The greatest lesion was an 11-cm-diameter dorsal tumor, resembling a cyst on palpation (Fig. 1a–c). Past medical history revealed two episodes of gastrointestinal hemorrhage – the first occurred seven years earlier, demanding transfusion of 13 units of packed red blood cells, and the latter required partial gastrectomy to control the bleeding. No similar cases were observed in the patient’s family. Histopathology revealed intense vascular ectasia in the papillary dermis, which was considered a venous malformation in the lip (Fig. 2), a macrocystic lymphatic malformation in the dorsal tumor and another dorsal lesion also compatible with a venous malformation. Digestive endoscopy detected two violaceous multilobulated masses, located in the esophagus and pyriform sinus (Fig. 3), whereas colonoscopy was normal. Calcified hepatic nodules, suggestive of venous malformations, were shown by abdominal computed tomography. Hypointense circumscribed lesions in the brain, compatible with cavernomas, were found using magnetic resonance imaging. The patient was treated with propranolol at a daily dose of 1 mg/kg. No adverse effects and no other hemorrhagic ª 2014 The International Society of Dermatology
Pereira et al.
Blue rubber bleb nevus syndrome
(a)
(b)
Case report
(c)
Figure 1 (a) Dorsal view of the patient: 11-cm-diameter cystic tumor and purple color nodule in the midline. (b) Limb tumor, with fibroelastic consistency and violaceous areas, suggesting vascular nature. (c) Purple papules on the lips (resembling venous lakes), bluish soft malar nodule and a fibroelastic tumor on the neck
Discussion
Figure 2 Histopathological analysis of the lip: intense vascular ectasia in the papillary dermis, with congestion of the lumen (hematoxylin-eosin, 409)
complications have occurred so far. However, after a 6-month follow-up, a reduction in the size of the lesions was not observed.
Clinical, histopathological, and imaging findings of this case are compatible with the diagnosis of BRBNS. The condition is rare and even more uncommon when it initiates in adulthood.4–6 The long gap between disease onset and diagnosis suggests that this syndrome is poorly recognized. Early diagnosis, though, is extremely important as visceral involvement can lead to severe hemorrhagic complications.5,7 The cutaneous findings may be the only clue and should alert to potential internal malformations.5,8 Lymphatic malformations are not usual in BRBNS, although previously reported, and illustrate the possibility that different types of vascular malformations (venous, arterial, lymphatic, and capillary) might coexist.3,9 Many different treatment options are mentioned in the literature, for example, surgical or endoscopic resection of symptomatic gastrointestinal lesions,10 Nd:YAG laser or surgery for cutaneous involvement,11 and systemic drugs such as corticosteroids, a-interferon, sirolimus, and propranolol.12,13
Figure 3 Endoscopic view of the esophagus and pyriform sinus: elevated violaceous multi-lobulated masses, up to 1.5 cm in
diameter ª 2014 The International Society of Dermatology
International Journal of Dermatology 2015, 54, 1420–1422
1421
1422
Case report
Blue rubber bleb nevus syndrome
In this case, the vascular malformations were stable in size, there was no functional impairment, and no relapse of gastrointestinal bleeding had been reported in the last two years. Considering the risks and benefits and the patient’s preference not to perform invasive procedures, the proposed treatment was conservative. The use of beta-blockers in vascular malformations is not scientifically grounded. In some cases, though, an empirical attempt can be made based on the wellestablished response observed in infantile hemangiomas. In conclusion, the best outcome for patients with BRBNS comes from early diagnosis and multidisciplinary followup. The dermatologist plays a key role in recognizing the syndrome and alerting other specialties to the potential involvement of any other organ and complications.
References 1 Bean WB. Vascular spiders and related lesions of the skin. Springfield, IL: Thomas, 1958. 2 Moss C, Shahidullah H. Naevi and other developmental defects. In: Burns T, Breathnach S, Cox N, Griffiths C, eds. Rook’s: textbook of dermatology, 8th edn. Oxford: Blackwell Publishing, 2010: 18.72–18.73. 3 Agnese M, Cipolletta L, Bianco MA, et al. Blue rubber bleb nevus syndrome. Acta Paediatr 2010; 99: 632–635. 4 Nahm WK, Moise S, Eichenfield LF, et al. Venous malformations in blue rubber bleb nevus syndrome: variable onset of presentation. J Am Acad Dermatol 2004; 50(5 Suppl): S101–S106.
International Journal of Dermatology 2015, 54, 1420–1422
Pereira et al.
5 Torchia D, Schincaglia E, Palleschi GM. Blue rubber-bleb naevus syndrome arising in the middle age. Int J Clin Pract 2010; 64: 115–117. 6 Mu~ noz-Navas M, Fern andez-Urien I, Espinet E, et al. Blue rubber bled nevus syndrome: three cases. Rev Esp Enferm Dig 2004; 96: 344–345. 7 Tomelleri G, Cappellari M, Di Matteo A, et al. Blue rubber bleb nevus syndrome with late onset of central nervous symptomatic involvement. Neurol Sci 2010; 31: 501–504. 8 Huang W, Rhodes A. A case of blue rubber bleb nevus syndrome with gastrointestinal and central nervous system involvement. Pediatr Dermatol 2012; 29: 524–525. 9 Marˇn-Manzano E, Utrilla L opez A, Puras Magallay E, et al. Cervical cystic lymphangioma in a patient with blue rubber bleb nevus syndrome: clinical case report and review of the literature. Ann Vasc Surg 2010; 24: 1136.el–1136.e5. 10 Fishman SJ, Smithers CJ, Folkman J, et al. Blue rubber bleb nevus syndrome: surgical eradication of bleeding. Ann Surg 2005; 241: 523–528. 11 Moser CM, Hamsch C. Successful treatment of cutaneous venous malformations in a patient with blue rubber bleb naevus syndrome by Nd:YAG laser. Br J Dermatol 2012; 166: 1143–1145. 12 Boente MD, Cordisco MR, Frontini MD, et al. Blue rubber bleb nevus (Bean syndrome): evolution of four cases and clinical response to pharmacologic agents. Pediatr Dermatol 1999; 16: 222–227. 13 Yuksekkaya H, Ozbek O, Keser M, et al. Blue rubber bleb nevus syndrome: successful treatment with sirolimus. Pediatrics 2012; 129: e1080–e1084.
ª 2014 The International Society of Dermatology
