0
Selected Reports |

Blue Rubber Bleb Nevus Syndrome*: Endobronchial Involvement Presenting as Chronic Cough FREE TO VIEW

Laura K. Gilbey; Carlos E. Girod
Author and Funding Information

*From the Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX.

Correspondence to: Carlos E. Girod, MD, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9034; e-mail: carlos.girod@utsouthwestern.edu



Chest. 2003;124(2):760-763. doi:10.1378/chest.124.2.760
Text Size: A A A
Published online

This case report describes a rare presentation of chronic cough secondary to endobronchial involvement with blue rubber bleb nevus syndrome (BRBNS) lesions. BRNBS is a rare syndrome characterized with cavernous hemangiomas involving the skin and GI tract. We report the case of a 37-year-old woman, with known BRBNS, who acquired an intractable cough with a radiograph revealing multiple pulmonary nodules. A bronchoscopy demonstrated various bluish, raised, and hypervascular lesions characteristic for BRBNS involving the right mainstem bronchus and segmental bronchi. To our knowledge, this is the first report of endobronchial involvement with BRBNS.

Figures in this Article

The blue rubber bleb nevus syndrome (BRBNS), previously known as Gascoyen syndrome, is a rare syndrome characterized by cavernous hemangiomas involving primarily the cutaneous tissues and GI tract.1 Pulmonary involvement has been described in rare cases with involvement of the pleura and subpleural parenchyma.24 We describe a patient with BRBNS presenting with a chronic cough and bronchoscopic and radiologic findings of hemangiomas of the endobronchial mucosa.

A 37-year-old nonsmoking woman with a history of BRBNS was referred for a chronic cough. During early childhood, she was found to have multiple skin nevi and recurrent GI bleeds requiring a partial gastrectomy and ileostomy. She has had many hemangiomatous GI lesions that have subsequently been treated with endoscopic electrocautery and iron therapy. In addition, she has involvement of the skin, genitalia, oral mucosa, and joints. The majority of these lesions have been successfully treated with sclerotherapy.

Three months prior to presentation, a harsh, nonproductive cough developed. The cough progressed to recurrent paroxysms averaging four spells a day in association with a choking sensation and nocturnal awakenings. She denied chest pain, fevers, shortness of breath, wheezing, sputum production, or hemoptysis.

On examination, she had multiple bluish, well-marginated, and partially compressible skin lesions, most prominent over the upper and lower extremities. The largest hemangioma was along the left mandible, measuring approximately 4 × 4 cm with a rubbery consistency. The oropharynx demonstrated multiple lesions consistent with blue nevi. The lungs were clear to auscultation, and the remainder of her examination was unremarkable.

The chest radiograph revealed multiple small nodules at the lung bases and right hilar fullness. Chest CT showed bilateral axillary soft-tissue masses with a lobulated, “frond-like” appearance. There were similar soft-tissue densities in the aortopulmonary window and left paratracheal region measuring 2 cm and 2.5 × 1.5 cm, respectively. Multiple small pulmonary nodules (2 to 15 mm in size) were detected in association with distal pulmonary vessels or abutting the pleura (Fig 1 ).

Fiberoptic bronchoscopy revealed a normal larynx and hypopharynx. A raised, bluish submucosal lesion consistent with a cavernous hemangioma was detected at the junction of the main carina and right mainstem bronchus (Fig 2 ). Similar lesions were also present at the right lower lobe bronchus.

A chest MRI with gadolinium revealed lobulated soft-tissue masses and pulmonary nodules. On immediate post-contrast imaging, there was no enhancement of these lesions. However, on delayed post-contrast imaging, these lesions showed moderate enhancement consistent with low-pressure vascular pathology (Fig 3 ). There was also delayed enhancement at the takeoff of the right mainstem bronchus correlating with the hemangiomas seen by bronchoscopy. These features are consistent with involvement of the bronchial mucosa, mediastinum, and lung parenchyma with BRBNS.

The chronic cough was treated with nonspecific antitussive therapy. Endobronchial laser treatment of the endobronchial lesions was considered. Surprisingly, the cough resolved with the administration of benzonatate pearls. The patient has been closely followed up for a year with stability of the pulmonary lesions and no recurrence of cough.

Since Gascoyen’s original description in 1860 of cutaneous and bleeding GI lesions, < 150 cases of the BRBNS have been reported. A century later, Bean1 coined the term blue rubber bleb nevus syndrome for this rare disorder characterized by vascular malformations of the skin and viscera, especially in the GI tract. The hemangiomas are usually evident at birth and appear as multiple bluish vascular lesions on the arms and trunk. These skin lesions usually increase in size and number with age. Patients are most often brought to medical attention because of chronic iron-deficiency anemia as a result of bleeding GI lesions.,57

Other tissues and organs affected in BRBNS include the liver, spleen, heart, CNS, skeletal muscle, pharynx, adrenal glands, kidneys, thyroid, eyes, and genital organs.36,813 The typical histologic feature of BRBNS is the presence of cavernous hemangiomas formed by dilated capillaries with flat endothelial cells and connective tissue stroma.14 Although most cases of BRBNS are sporadic, an autosomal dominant inheritance has been described.15

Descriptions of lung involvement have been limited to postmortem studies with angiomatous BRBNS lesions in the subpleural parenchyma and pleura.24 The only report of symptomatic pulmonary involvement involved a patient with spontaneous hemothorax. At thoracotomy, this patient was found to have angiomas of the visceral pleura.2 In our patient, we describe involvement of the mediastinum and bronchial mucosa leading to refractory chronic cough. To our knowledge, this is the first report of symptomatic endobronchial involvement in BRBNS.

Involuntary cough is stimulated by the vagus nerve with irritant receptors located in the lower oropharynx, esophagus, larynx, lower respiratory tract, tympanic membrane, and external auditory meatus. The reflex usually arises from stimulation of the bronchial mucosa between the larynx and second order bronchi.16 This patient’s chronic cough is suspected to be due to proliferating hemangiomas in the large airways with irritation of cough receptors.

The management of skin lesions in the BRBNS is limited to surgical excision or laser ablation. For patients with visceral involvement, case reports have documented the utility of surgery and/or sclerotherapy especially in bleeding GI lesions. In our patient, the possibility of utilizing endoscopic laser therapy was considered but not utilized since the endobronchial lesions were small and nonocclusive. Nonspecific antitussive therapy was initiated with benzonatate perles, a nonnarcotic oral antitussive with main mechanism of action being cough suppression by anesthetizing the stretch receptors in the airways involved in the cough reflex.17 This patient reported immediate improvement in the cough and has continued to be asymptomatic from a pulmonary standpoint at 1 year of follow-up. The exact mechanism for this improvement with benzonatate remains unexplained.

Abbreviation: BRBNS = blue rubber bleb nevus syndrome

This work was supported by the Ben R. Briggs Fund for Pulmonary Research.

Figure Jump LinkFigure 1. Top, A: chest CT scan without contrast reveals multiple nodular opacities in the lung parenchyma. Some of these nodules abut the pleura and are associated with pulmonary vessels. Bottom, B: right upper lobe nodule and an irregular, soft-tissue mass at the periaortic space (arrow).Grahic Jump Location
Figure Jump LinkFigure 2. Bronchoscopy revealed a bluish-colored vascular lesion at the proximal, anterior take-off of the right mainstem (MS) bronchus (arrow). Similar lesions were seen in the right lower lobe segmental bronchi (not shown). Endobronchial biopsies were not performed because bleeding risk and similarity of these lesions by visual inspection to the visceral and cutaneous BRBNS lesions.Grahic Jump Location
Figure Jump LinkFigure 3. MRI of the chest before and after the administration of gadolinium revealed multiple frond-like masses in the subcutaneous tissue and IM soft tissue (not shown). Multiple pulmonary and subpleural nodules are again demonstrated. On the early post-contrast gradient echo sequences, no significant enhancement was seen in any of the lesions. On the delayed-contrast images, there was a moderate amount of contrast enhancement of the right pulmonary nodule and the irregular, soft-tissue mass located in the periaortic region (arrow). This contrast enhancement is consistent with low-pressure vascular pathology as expected for venous hemangiomas. This MRI section corresponds to the CT image in Figure 1 , bottom, B.Grahic Jump Location

The authors thank the Ben R. Briggs Fund for Pulmonary Research.

Bean, WB (1958)Vascular spiders and related lesions of the skin.,178-185 Charles C. Thomas, Publisher. Springfield, IL:
 
Langleben, D, Wolkove, N, Srolovitz, H, et al Hemothorax and hemopericardium in a patient with Bean’s blue rubber bleb nevus syndrome.Chest1989;95,1352-1353. [PubMed] [CrossRef]
 
Rice, JS, Fischer, DS Blue rubber bleb nevus syndrome.Arch Dermatol1962;86,503-511. [PubMed]
 
Waybright, EA, Selhorst, JB, Rosenblum, WI, et al Blue rubber bleb nevus syndrome with CNS involvement and thrombosis of a vein of Galen malformation.Ann Neurol1978;3,464-467. [PubMed]
 
Moodley, M, Randial, P Blue rubber bleb nevus syndrome: case report and review of the literature.Pediatrics1993;92,160-162. [PubMed]
 
Wong, SH, Lau, WY Blue rubber bleb nevus syndrome.Dis Colon Rectum1982;25,371-374. [PubMed]
 
Tyrrel, RT, Baumgartner, BR, Montemayor, KA Blue rubber bleb nevus syndrome: CT diagnosis of intussusception.Am J Radiol1990;154,105-106
 
Belsheim, MR, Sullivan, SN Blue rubber bleb nevus syndrome.Can J Surg1980;23,274-275. [PubMed]
 
Baiocco, FA, Gamoletti, R, Negri, A, et al Blue rubber bleb nevus syndrome: a case with predominantly ENT localization.J Laryngol Otol1984;98,317-319. [PubMed]
 
Busund, B, Stray-Pedersen, S, Iversen, O, et al Blue rubber bleb nevus syndrome with manifestations in the vulva.Acta Obstet Gynecol Scand1993;72,310-313. [PubMed]
 
Smart, RH, Newton, DE Hemangioma of the penis with blue rubber bleb nevus syndrome.J Urology1975;113,570-571
 
McCarthy, JC, Goldberg, MJ, Zimbler, S Orthopaedic dysfunction in the blue rubber bleb nevus syndrome.J Bone Joint Surg1982;64A,280-283
 
Crompton, JL, Taylor, D Ocular lesions in the blue rubber bleb naevus syndrome.Br J Ophthalmol1981;65,133-137. [PubMed]
 
McCauley, RGK, Leonidas, JC, Bartoshesky, LE Blue rubber bleb nevus syndrome.Radiology1979;133,375-377. [PubMed]
 
Kisu, T, Yamaoka, K, Uchida, Y A case of blue rubber bleb nevus syndrome with familial onset.Gastroenterol Jpn1986;21,262-266. [PubMed]
 
Patrick, H, Patrick, F Chronic cough.Med Clin North Am1995;79,361-372. [PubMed]
 
Schrefer, J, Nissen, D Mosby’s GenRx: a comprehensive reference for generic and brand prescription drugs. 11th ed.2001 Mosby. St. Louis, MO:
 

Figures

Figure Jump LinkFigure 1. Top, A: chest CT scan without contrast reveals multiple nodular opacities in the lung parenchyma. Some of these nodules abut the pleura and are associated with pulmonary vessels. Bottom, B: right upper lobe nodule and an irregular, soft-tissue mass at the periaortic space (arrow).Grahic Jump Location
Figure Jump LinkFigure 2. Bronchoscopy revealed a bluish-colored vascular lesion at the proximal, anterior take-off of the right mainstem (MS) bronchus (arrow). Similar lesions were seen in the right lower lobe segmental bronchi (not shown). Endobronchial biopsies were not performed because bleeding risk and similarity of these lesions by visual inspection to the visceral and cutaneous BRBNS lesions.Grahic Jump Location
Figure Jump LinkFigure 3. MRI of the chest before and after the administration of gadolinium revealed multiple frond-like masses in the subcutaneous tissue and IM soft tissue (not shown). Multiple pulmonary and subpleural nodules are again demonstrated. On the early post-contrast gradient echo sequences, no significant enhancement was seen in any of the lesions. On the delayed-contrast images, there was a moderate amount of contrast enhancement of the right pulmonary nodule and the irregular, soft-tissue mass located in the periaortic region (arrow). This contrast enhancement is consistent with low-pressure vascular pathology as expected for venous hemangiomas. This MRI section corresponds to the CT image in Figure 1 , bottom, B.Grahic Jump Location

Tables

References

Bean, WB (1958)Vascular spiders and related lesions of the skin.,178-185 Charles C. Thomas, Publisher. Springfield, IL:
 
Langleben, D, Wolkove, N, Srolovitz, H, et al Hemothorax and hemopericardium in a patient with Bean’s blue rubber bleb nevus syndrome.Chest1989;95,1352-1353. [PubMed] [CrossRef]
 
Rice, JS, Fischer, DS Blue rubber bleb nevus syndrome.Arch Dermatol1962;86,503-511. [PubMed]
 
Waybright, EA, Selhorst, JB, Rosenblum, WI, et al Blue rubber bleb nevus syndrome with CNS involvement and thrombosis of a vein of Galen malformation.Ann Neurol1978;3,464-467. [PubMed]
 
Moodley, M, Randial, P Blue rubber bleb nevus syndrome: case report and review of the literature.Pediatrics1993;92,160-162. [PubMed]
 
Wong, SH, Lau, WY Blue rubber bleb nevus syndrome.Dis Colon Rectum1982;25,371-374. [PubMed]
 
Tyrrel, RT, Baumgartner, BR, Montemayor, KA Blue rubber bleb nevus syndrome: CT diagnosis of intussusception.Am J Radiol1990;154,105-106
 
Belsheim, MR, Sullivan, SN Blue rubber bleb nevus syndrome.Can J Surg1980;23,274-275. [PubMed]
 
Baiocco, FA, Gamoletti, R, Negri, A, et al Blue rubber bleb nevus syndrome: a case with predominantly ENT localization.J Laryngol Otol1984;98,317-319. [PubMed]
 
Busund, B, Stray-Pedersen, S, Iversen, O, et al Blue rubber bleb nevus syndrome with manifestations in the vulva.Acta Obstet Gynecol Scand1993;72,310-313. [PubMed]
 
Smart, RH, Newton, DE Hemangioma of the penis with blue rubber bleb nevus syndrome.J Urology1975;113,570-571
 
McCarthy, JC, Goldberg, MJ, Zimbler, S Orthopaedic dysfunction in the blue rubber bleb nevus syndrome.J Bone Joint Surg1982;64A,280-283
 
Crompton, JL, Taylor, D Ocular lesions in the blue rubber bleb naevus syndrome.Br J Ophthalmol1981;65,133-137. [PubMed]
 
McCauley, RGK, Leonidas, JC, Bartoshesky, LE Blue rubber bleb nevus syndrome.Radiology1979;133,375-377. [PubMed]
 
Kisu, T, Yamaoka, K, Uchida, Y A case of blue rubber bleb nevus syndrome with familial onset.Gastroenterol Jpn1986;21,262-266. [PubMed]
 
Patrick, H, Patrick, F Chronic cough.Med Clin North Am1995;79,361-372. [PubMed]
 
Schrefer, J, Nissen, D Mosby’s GenRx: a comprehensive reference for generic and brand prescription drugs. 11th ed.2001 Mosby. St. Louis, MO:
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
CHEST Collections
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543