Tracheobronchial Obstruction due to Silicosis 1•2
BARBARA C. CAHILL, KEITH R. HARMON, SARA J. SHUMWAY, JAMES K. MICKMAN, and MARSHALL I. HERTZ
Introduction Broncholithiasis, the erosion of chronically inflamed calcified perihilar and mediastinal lymph nodes into the tracheobronchial tree, can result in cough, hemoptysis, lithoptysis, airway obstruction, pneumonia, and fistula formation. Although previous infection with tuberculosis and histoplasmosis account for the majority of cases of broncholith formation, silicosis is the only known noninfectious cause (1). We report an unusual case of broncholithiasis in a patient with silicosis who developed airway obstruction from endobronchial polypoid masses of granulation tissue adjacent to eggshell calcifications in the mediastinum.
SUMMARY Bronchollthlasls can result In airway obstruction through the erosion of calcified lymph nodes Into the bronchial lumen or by extrinsic compression of the tracheobronchial tree. We report an unusual case of bronchollthlasls In a patient with silicosis who developed airway obstruction from endobronchial polypoid masses of granulation tissue adjacent to calcified mediastinal lymph nodes. The production of granulation tissue may have been the result of bronchollths In the early stages of erosion Into the tracheobronchial tree. Efforts to ablate the endobronchial polyps using VAGlaser phototherapy were only temporarily successful and surgical removal of the calcified madl· astlnallymph nodes was reqUired to halt further polyp growth. Surgical specimens grew Mycobac· terium a"ium·intracellu/are (MAl), a common pathogen In patients with silicosis. MAl may have contributed to the local Inflammatory milieu provoking the exuberant tissue response. AM REV RESPIR DIS 1992; 145:719-721
Case Report A 72-yr-old woman presented with complaints of "purring" in her chest, accompanied by progressive disabling dyspnea and worsening of a chronic nonproductive cough. Her past medical history included a diagnosis of Sjogren's syndrome. She had undergone neck irradiation in childhood for thyroiditis, and required thyroid hormone replacement. The patient was a lifelong nonsmoker. She had worked for 24 yr in a factory using aerosolized silica dust to coat circuit boards. On physical examination, the patient was dyspneic at rest. Inspiratory and expiratory rhonchi were noted over the central airways. The cardiac examination was normal. There was no clubbing, peripheral edema, or joint deformity. The chest roentgenogram demonstrated diffuse nodular infiltrates as well as eggshell calcifications of the hilar and paratracheallymph nodes (figure I). Tomograms (figure 2) showed narrowing of the tracheal lumen and left main bronchus, adjacent to calcified lymph nodes. Spirometry demonstrated severeairflow obstruction with an FEV. of 0.92 L (48070 of predicted) and an FVC of 2.79 L (114070 of predicted). The flow volume loop was consistent with variable intrathoracic airflow obstruction. Flexible bronchoscopic examination revealed two large endobronchial polypoid lesions with nearcomplete obstruction of the trachea and left main bronchus (figure 3). No intraluminal calcifications were visualized. Biopsies of the lesions revealed only granulation tissue with acute and chronic inflammation. Special stains for mycobacteria, fungus, and amyloid were negative. Cultures of bronchial brushings, washings, and biopsy specimens were negative. The endobronchial granulation tissue was ablated with 7,600 joules of YAG laser energy. Despite initial clinical improvement, the patient's symptoms recurred within 3 wk and bronchoscopy demonstrated regrowth of the granulation tissue. When repeat YAG laser failed to effect longterm relief of her airway obstruction, the patient
Fig. 1. Chest roentgenogram showing bilateral hilar and paratracheal eggshell calcifications and reticulonodular infiltrates.
was taken to thoracotomy for surgical removal of calcified lymph nodes. At operation, densely adherent calcified lymph nodes encased the distal trachea and the right and left main bronchi. The lymph nodes along the most proximal left main bronchus created an obvious deformity in the bronchial wall. These nodes were incised longitudinally and their contents evacuated by curettage. Histologic examination of surgical specimens revealed caseating granulomas that contained acidfast bacilli. Also present were fibroelastotic nodules containing refractile silica crystals. No granulation tissue was found in resected specimens. Cultures grew Mycobacterium avium intrace//ulare (MAl). Isoniazid, rifampin, pyrazinamide, and streptomycin were instituted, but the patient stopped all drugs when intolerable vertigo developed and persisted despite the discontinuation of streptomycin. Her postoperative spirometry showed an improvement in FEV. to 2.17 L and the flow-volume loop normalized. The patient was followed clini-
cally for signs of active disease and remained symptom free for 6 months without therapy.
Discussion This case demonstrates one of the unusual complications of silicosis. Chronic exposure to aerosolized silica particles in the workplace
(Received in original form March 25,1991 and in revised form July 8, 1991) t From the University of Minnesota, the University of Minnesota Heart and Lung Institute, and Group Health, Inc., Minneapolis, Minnesota. 2 Correspondence and requests for reprints should be addressed to Barbara C. Cahill, M.D., University of Minnesota, Box 276 UMHC, 420 Delaware Street SE, Minneapolis, MN 55455.
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CASE REPORT
Fig. 2. Tomogramshowing narrowing of the tracheal lumen by soft-tissue density adjacent to calcified lymph node (arrow). Additional tomographic images demonstrated obstruction of the left mainstem bronchus adjacent to matted calcified lymph nodes.
ultimately led to this patient's large airway obstruction. Pathologically, inhaled silica particles < 10 urn in diameter deposit in the lower respiratory tract where they are scavenged by macrophages. Once ingested, these silica particles destabilize lysosomal membranes, resulting in autolysis of the macrophage and spillage of cellular contents as well as free silica particles back into the lower airway. Repetition of this cycle over time destroys delicate lung architecture, culminating in the formation of bullae and fibrotic silicotic nodules. Passage of silica-laden macrophages into 10cal lymphatics concentrates free silica particles in the hilar and mediastinal lymph nodes. Chronic inflammation and fibrosis in these nodes leads to the adenopathy commonly seen on chest roentgenograms of silicotic patients (2). In approximately 50/0 of cases, these nodes calcify in an eggshell pattern. Although once thought pathognomic of silicosis, eggshell calcifications have been seen in other disease processes including tuberculosis and sarcoidosis (3). On rare occasions, inflammation of affected lymph nodes involves the adjacent bronchial wall, leading to distortion of the bronchiallumen. Cough, hemoptysis, lithoptysis, airway obstruction, pneumonia, and fistula formation can result from extrinsic compression of the tracheobronchial tree or the erosion of calcified material into the bronchial lumen (1). Broncholithiasis, the erosion of calcified lymph nodes into the airway, is most often caused by previous infection with tuberculosis or histoplasmosis; silicosis is the only documented noninfectious cause of broncholithiasis (1). This patient developed large airway obstruction from the exuberant growth
Fig. 3. (Left) Endobronchial mass of granulation tissue obstructing tracheal lumen (arrow). (Right) Tracheal lumen after ablation of polyp with VAG laser phototherapy.
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CASE REPORT
of granulation tissue, presumably stimulated by broncholiths in the early stages of erosion into the tracheobronchial tree. MAl may have contributed to the local inflammatory milieu, provoking overproduction of granulation tissue in the airway. YAG laser phototherapy afforded transient relief of airway obstruction, but continued stimulation from eroding lymph nodes resulted in rapid regrowth of polypoid tissue. After surgical removal of the offending nodes, airway obstruction did not recur. Despite a lack of systemic symptoms, stable serial chest roentgenograms, and multiple negative endobronchial cultures, MAl was easily isolated from surgical specimens, raising the question of this patient's need for antituberculous therapy. The increased incidence of tuberculous and nontuberculous mycobacterial disease in patients with silicosis is well documented. Scavenged silica particles impair normal macrophage function, the first line of defense in mycobacterial infection. In vitro studies have also demonstrated accelerated growth of mycobacteria in macrophages exposed to sublethal doses of silica{2, 4). Despite the increased incidence of mycobacterial disease in these patients, cultures are often
negative and extrapulmonary disease rare because infectious foci are walled off in silicotic nodules, lacking access to the airway, vascular, and lymphatic channels (4). The initial decision to treat this patient was based on the fact that MAl was isolated from an area of active inflammation, as well as the possibility that the organism may have been spilled into the mediastinum at the time of surgery. When side effects of antituberculous medications led the patient to discontinue all drugs, a decision was made to follow her clinical course and chest roentgenogram rather than reinstitute therapy. It is interesting to note that this patient developed Sjogren's syndrome in the course of her lung disease, but it is unclear whether the two events are related. Silicotic patients are known to have an increased prevalence of autoimmune disease, notably rheumatoid arthritis, systemic lupus erythematosis, and systemic sclerosis. They typically display hypergammaglobulinemia and have increased numbers of autoantibodies compared with patients without silicosis (2). The strong clinical association between progressive massive fibrosis and autoimmune disease in some patients with silicosis may reflect a genetically encod-
ed fibroproliferative response to inflammatory stimuli (5, 6). In addition, although silica exerts a direct cytotoxic effect on the lower airway, plasma cells and immunoglobulins can be demonstrated in pathologic specimens of silicotic nodules, suggesting a potential role for the immune system in the progression of silica-induced fibrosis (2). References 1. Dixon GF, Donnerberg RL, Schonfeld SA, Whitcomb ME. Advances in the diagnosis and treatment of broncholithiasis, Am Rev Respir Dis 1984; 129:1028-30. 2. Ziskind M, Jones RN, Weill H. State of the art. Silicosis. Am Rev Respir Dis 1976; 113:643-65. 3. Jacobson G, Felson B, Pendergrass EP, Flinn RH, Lainhart WS. Eggshell calcifications in coal and metal miners. Sem Roentgenol1967; 2:276-82. 4. Snider DE. The relationship between tuberculosis and silicosis. Am Rev Respir Dis 1978; 118:455-60. 5. Sluis-Cremer GK, Hessel PA, Hnizdo E, Churchill AR. Relationship between silicosis and rheumatoid arthritis. Thorax 1986; 41:596-601. 6. Koskinin H, Tiilikainen A, Nordman H. Increased prevalence of HLA-AwI9 and of the phenogroup Aw19, B18in advanced silicosis. Chest 1983; 83:848-52.
BARBARA C. CAHILL, KEITH R. HARMON, SARA J. SHUMWAY, JAMES K. MICKMAN, and MARSHALL I. HERTZ
Introduction Broncholithiasis, the erosion of chronically inflamed calcified perihilar and mediastinal lymph nodes into the tracheobronchial tree, can result in cough, hemoptysis, lithoptysis, airway obstruction, pneumonia, and fistula formation. Although previous infection with tuberculosis and histoplasmosis account for the majority of cases of broncholith formation, silicosis is the only known noninfectious cause (1). We report an unusual case of broncholithiasis in a patient with silicosis who developed airway obstruction from endobronchial polypoid masses of granulation tissue adjacent to eggshell calcifications in the mediastinum.
SUMMARY Bronchollthlasls can result In airway obstruction through the erosion of calcified lymph nodes Into the bronchial lumen or by extrinsic compression of the tracheobronchial tree. We report an unusual case of bronchollthlasls In a patient with silicosis who developed airway obstruction from endobronchial polypoid masses of granulation tissue adjacent to calcified mediastinal lymph nodes. The production of granulation tissue may have been the result of bronchollths In the early stages of erosion Into the tracheobronchial tree. Efforts to ablate the endobronchial polyps using VAGlaser phototherapy were only temporarily successful and surgical removal of the calcified madl· astlnallymph nodes was reqUired to halt further polyp growth. Surgical specimens grew Mycobac· terium a"ium·intracellu/are (MAl), a common pathogen In patients with silicosis. MAl may have contributed to the local Inflammatory milieu provoking the exuberant tissue response. AM REV RESPIR DIS 1992; 145:719-721
Case Report A 72-yr-old woman presented with complaints of "purring" in her chest, accompanied by progressive disabling dyspnea and worsening of a chronic nonproductive cough. Her past medical history included a diagnosis of Sjogren's syndrome. She had undergone neck irradiation in childhood for thyroiditis, and required thyroid hormone replacement. The patient was a lifelong nonsmoker. She had worked for 24 yr in a factory using aerosolized silica dust to coat circuit boards. On physical examination, the patient was dyspneic at rest. Inspiratory and expiratory rhonchi were noted over the central airways. The cardiac examination was normal. There was no clubbing, peripheral edema, or joint deformity. The chest roentgenogram demonstrated diffuse nodular infiltrates as well as eggshell calcifications of the hilar and paratracheallymph nodes (figure I). Tomograms (figure 2) showed narrowing of the tracheal lumen and left main bronchus, adjacent to calcified lymph nodes. Spirometry demonstrated severeairflow obstruction with an FEV. of 0.92 L (48070 of predicted) and an FVC of 2.79 L (114070 of predicted). The flow volume loop was consistent with variable intrathoracic airflow obstruction. Flexible bronchoscopic examination revealed two large endobronchial polypoid lesions with nearcomplete obstruction of the trachea and left main bronchus (figure 3). No intraluminal calcifications were visualized. Biopsies of the lesions revealed only granulation tissue with acute and chronic inflammation. Special stains for mycobacteria, fungus, and amyloid were negative. Cultures of bronchial brushings, washings, and biopsy specimens were negative. The endobronchial granulation tissue was ablated with 7,600 joules of YAG laser energy. Despite initial clinical improvement, the patient's symptoms recurred within 3 wk and bronchoscopy demonstrated regrowth of the granulation tissue. When repeat YAG laser failed to effect longterm relief of her airway obstruction, the patient
Fig. 1. Chest roentgenogram showing bilateral hilar and paratracheal eggshell calcifications and reticulonodular infiltrates.
was taken to thoracotomy for surgical removal of calcified lymph nodes. At operation, densely adherent calcified lymph nodes encased the distal trachea and the right and left main bronchi. The lymph nodes along the most proximal left main bronchus created an obvious deformity in the bronchial wall. These nodes were incised longitudinally and their contents evacuated by curettage. Histologic examination of surgical specimens revealed caseating granulomas that contained acidfast bacilli. Also present were fibroelastotic nodules containing refractile silica crystals. No granulation tissue was found in resected specimens. Cultures grew Mycobacterium avium intrace//ulare (MAl). Isoniazid, rifampin, pyrazinamide, and streptomycin were instituted, but the patient stopped all drugs when intolerable vertigo developed and persisted despite the discontinuation of streptomycin. Her postoperative spirometry showed an improvement in FEV. to 2.17 L and the flow-volume loop normalized. The patient was followed clini-
cally for signs of active disease and remained symptom free for 6 months without therapy.
Discussion This case demonstrates one of the unusual complications of silicosis. Chronic exposure to aerosolized silica particles in the workplace
(Received in original form March 25,1991 and in revised form July 8, 1991) t From the University of Minnesota, the University of Minnesota Heart and Lung Institute, and Group Health, Inc., Minneapolis, Minnesota. 2 Correspondence and requests for reprints should be addressed to Barbara C. Cahill, M.D., University of Minnesota, Box 276 UMHC, 420 Delaware Street SE, Minneapolis, MN 55455.
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CASE REPORT
Fig. 2. Tomogramshowing narrowing of the tracheal lumen by soft-tissue density adjacent to calcified lymph node (arrow). Additional tomographic images demonstrated obstruction of the left mainstem bronchus adjacent to matted calcified lymph nodes.
ultimately led to this patient's large airway obstruction. Pathologically, inhaled silica particles < 10 urn in diameter deposit in the lower respiratory tract where they are scavenged by macrophages. Once ingested, these silica particles destabilize lysosomal membranes, resulting in autolysis of the macrophage and spillage of cellular contents as well as free silica particles back into the lower airway. Repetition of this cycle over time destroys delicate lung architecture, culminating in the formation of bullae and fibrotic silicotic nodules. Passage of silica-laden macrophages into 10cal lymphatics concentrates free silica particles in the hilar and mediastinal lymph nodes. Chronic inflammation and fibrosis in these nodes leads to the adenopathy commonly seen on chest roentgenograms of silicotic patients (2). In approximately 50/0 of cases, these nodes calcify in an eggshell pattern. Although once thought pathognomic of silicosis, eggshell calcifications have been seen in other disease processes including tuberculosis and sarcoidosis (3). On rare occasions, inflammation of affected lymph nodes involves the adjacent bronchial wall, leading to distortion of the bronchiallumen. Cough, hemoptysis, lithoptysis, airway obstruction, pneumonia, and fistula formation can result from extrinsic compression of the tracheobronchial tree or the erosion of calcified material into the bronchial lumen (1). Broncholithiasis, the erosion of calcified lymph nodes into the airway, is most often caused by previous infection with tuberculosis or histoplasmosis; silicosis is the only documented noninfectious cause of broncholithiasis (1). This patient developed large airway obstruction from the exuberant growth
Fig. 3. (Left) Endobronchial mass of granulation tissue obstructing tracheal lumen (arrow). (Right) Tracheal lumen after ablation of polyp with VAG laser phototherapy.
721
CASE REPORT
of granulation tissue, presumably stimulated by broncholiths in the early stages of erosion into the tracheobronchial tree. MAl may have contributed to the local inflammatory milieu, provoking overproduction of granulation tissue in the airway. YAG laser phototherapy afforded transient relief of airway obstruction, but continued stimulation from eroding lymph nodes resulted in rapid regrowth of polypoid tissue. After surgical removal of the offending nodes, airway obstruction did not recur. Despite a lack of systemic symptoms, stable serial chest roentgenograms, and multiple negative endobronchial cultures, MAl was easily isolated from surgical specimens, raising the question of this patient's need for antituberculous therapy. The increased incidence of tuberculous and nontuberculous mycobacterial disease in patients with silicosis is well documented. Scavenged silica particles impair normal macrophage function, the first line of defense in mycobacterial infection. In vitro studies have also demonstrated accelerated growth of mycobacteria in macrophages exposed to sublethal doses of silica{2, 4). Despite the increased incidence of mycobacterial disease in these patients, cultures are often
negative and extrapulmonary disease rare because infectious foci are walled off in silicotic nodules, lacking access to the airway, vascular, and lymphatic channels (4). The initial decision to treat this patient was based on the fact that MAl was isolated from an area of active inflammation, as well as the possibility that the organism may have been spilled into the mediastinum at the time of surgery. When side effects of antituberculous medications led the patient to discontinue all drugs, a decision was made to follow her clinical course and chest roentgenogram rather than reinstitute therapy. It is interesting to note that this patient developed Sjogren's syndrome in the course of her lung disease, but it is unclear whether the two events are related. Silicotic patients are known to have an increased prevalence of autoimmune disease, notably rheumatoid arthritis, systemic lupus erythematosis, and systemic sclerosis. They typically display hypergammaglobulinemia and have increased numbers of autoantibodies compared with patients without silicosis (2). The strong clinical association between progressive massive fibrosis and autoimmune disease in some patients with silicosis may reflect a genetically encod-
ed fibroproliferative response to inflammatory stimuli (5, 6). In addition, although silica exerts a direct cytotoxic effect on the lower airway, plasma cells and immunoglobulins can be demonstrated in pathologic specimens of silicotic nodules, suggesting a potential role for the immune system in the progression of silica-induced fibrosis (2). References 1. Dixon GF, Donnerberg RL, Schonfeld SA, Whitcomb ME. Advances in the diagnosis and treatment of broncholithiasis, Am Rev Respir Dis 1984; 129:1028-30. 2. Ziskind M, Jones RN, Weill H. State of the art. Silicosis. Am Rev Respir Dis 1976; 113:643-65. 3. Jacobson G, Felson B, Pendergrass EP, Flinn RH, Lainhart WS. Eggshell calcifications in coal and metal miners. Sem Roentgenol1967; 2:276-82. 4. Snider DE. The relationship between tuberculosis and silicosis. Am Rev Respir Dis 1978; 118:455-60. 5. Sluis-Cremer GK, Hessel PA, Hnizdo E, Churchill AR. Relationship between silicosis and rheumatoid arthritis. Thorax 1986; 41:596-601. 6. Koskinin H, Tiilikainen A, Nordman H. Increased prevalence of HLA-AwI9 and of the phenogroup Aw19, B18in advanced silicosis. Chest 1983; 83:848-52.
