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.
Key words: bronchial diseases: cough, chronic; hemangioma, venous; nevus, blue rubber bleb; pulmonary nodules
Abbreviation: BRBNS = blue rubber bleb nevus syndrome
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. (2-4) 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, levers, 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 x 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, "found-like" appearance. There were similar soft-tissue densities in the, aortopulmonary window and left paratracheal region measuring 2 cm and 2.5 X 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).
[FIGURE 1 OMITTED]
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.
[FIGURE 2 OMITTED]
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.
[FIGURE 3 OMITTED]
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, Bean (1) 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. (5-7)
Other tissues and organs affected in BRBNS include the liver, spleen, heart, CNS, skeletal muscle, pharynx, adrenal glands, kidneys, thyroid, eyes, and genital organs. (3,4-6,8-13) 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 antosomal dominant inheritance has been described. (15)
Descriptions of lung involvement have been limited to postmortem studies with angiomalous BRBNS lesions in the subpleural parenchyma and pleura. (2-4) 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 or 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 or 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.
ACKNOWLEDGMENT: The author's thank the Ben R. Briggs Fund for Pulmonary Research.
* From the Division of Pulmonary and Critical Care Medicine. University of Texas Southwestern Medical Center, Dallas, TX, This work was supported by the Ben R. Briggs Fund for Pulmonary Research.
Manuscript received November 22, 2002: revision accepted February 18, 2003.
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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. email@example.com
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