- Email: [email protected]
A Man in His Early 70s With Progressive Dyspnea and Abnormal Fundoscopic Examination
CHEST
Postgraduate Education Corner PULMONARY, CRITICAL CARE, AND SLEEP PEARLS
A Man in His Early 70s With Progressive Dyspnea and Abnormal Fundoscopic Examination Sarah Bastawrous, DO; and Jan V. Hirschmann, MD
CHEST 2014; 145(1):178–181
man in his early 70s complained of progresAblack sive dyspnea on exertion for 15 years. He had occa-
sional cough productive of clear sputum, but no chest pain. He had a 60-pack-year smoking history and previous illicit drug use, including IV injection of heroin and methylphenidate, complicated by tricuspid valve endocarditis nearly 30 years ago. He had no significant travel or occupational history. He had no visual complaints. He did not drink alcohol and had no pets or exposure to birds. He had no known previous TB, and his tuberculin test was negative. Physical Examination Findings BP, temperature, and heart rate were normal. Oxygen saturation was 95% on 2 L of supplemental oxygen. Chest auscultation indicated decreased breath sounds without wheezing. Fundoscopic examination of the eyes revealed numerous irregular, bright, yellowishwhite dots within the retinal vessels with no evidence of surrounding inflammation (Fig 1). The remainder of his examination was unremarkable. Diagnostic Studies
Figure 1. Fundoscopic image of the retina.
laboratory findings were normal. A chest radiograph showed diffuse emphysema with dense perihilar masslike lesions and reticular opacities extending to the upper and middle lung zones. There was distortion of the normal lung architecture with apical scarring and pleural thickening (Fig 2).
The patient’s metabolic panel was normal. CBC count revealed a hematocrit level of 37%. Other Manuscript received May 31, 2013; revision accepted June 21, 2013. Affiliations: From the Department of Radiology (Dr Bastawrous) and Department of Medicine (Dr Hirschmann), VA Puget Sound Health Care System; and Department of Radiology (Dr Bastawrous) and Department of Medicine (Dr Hirschmann), UW Medicine, University of Washington, Seattle, WA. Correspondence to: Sarah Bastawrous, DO, Department of Radiology, VA Puget Sound Health Care System, Mail Box 358280, S-114, 1660 S Columbian Way, Seattle WA 98108-1597; e-mail: [email protected] © 2014 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1277 178
Postgraduate Education Corner
Figure 2. Chest radiographs show marked emphysema, upward elevation of both hila with dense perihilar, mass-like lesions, and reticular opacities extending to the upper and middle lung zones. Distortion of the normal lung architecture with apical scarring and pleural thickening is also present. A, Posteroanterior view. B, Left lateral view.
What is the diagnosis?
journal.publications.chestnet.org
CHEST / 145 / 1 / JANUARY 2014
179
Diagnosis: Pulmonary talcosis and talc retinopathy Discussion Pulmonary disease caused by talc (hydrous magnesium silicate) may occur from inhaling it, as in mining or industrial exposure, but may also develop from the IV injection of medications, such as methadone or methylphenidate, intended for oral use. These pills contain talc, whose purposes are to hold the components of the medication together and to prevent the tablets from adhering to the equipment used in their production. Drug abusers crush the oral medications, mix the pulverized material with water, heat it, sometimes sieve the mixture through cotton or cigarette filters, and then inject the product intravenously. The insoluble talc particles lodge within the pulmonary arterial circulation, sometimes provoking the formation of foreign-body granulomas, which can narrow or occlude the vessels. When extensive, these vascular abnormalities, often accompanied by medial hypertrophy of the muscular pulmonary arteries, may lead to pulmonary arterial hypertension. Visible microscopically as birefringent, needle-shaped particles, the talc can also erode through the pulmonary vessel walls to produce perivascular and interstitial granulomas. With time, the individual granulomas may expand and coalesce, producing larger nodules and masses, usually perihilar, which consist of talccontaining foreign-body giant cells, sometimes accompanied by lymphocytes, plasma cells, eosinophils, and fibrous tissue. Substantial fibrosis may cause contraction and retraction of involved lung tissue and distortion of the pulmonary architecture. Pulmonary vascular disease and interstitial disease may coexist or one type may predominate in talcosis. In any of these situations, a frequent, but unexplained, finding is emphysema. Usually, panacinar emphysema is present in the lower lobes, especially with methylphenidate injections, but in some patients it is centrilobular and typically located in the upper lobes. Often, talc is found outside the lung, in mediastinal lymph nodes, liver, spleen, muscle, heart, kidney, skin, pancreas, bone marrow, and retinal vessels, but usually no symptoms arise from this extrapulmonary involvement. The talc may reach the systemic circulation by successfully traversing the normal pulmonary vessels or via arteriovenous shunts in the vasculature of the lung or, elsewhere, such as through a patent foramen ovale. Talc particles presumably arrive at the mediastinal lymph nodes by migrating from the lung granulomas into the lymphatic channels and then lodging in the regional lymph nodes. Individuals with talcosis may be asymptomatic and have typically injected thousands of tablets (as many as an estimated 280,000), usually from an average daily 180
use of about 15 to 40 pills over several years. When pulmonary talcosis produces symptoms, the most common complaints are exertional dyspnea and a dry or productive cough. Some patients have substantial weight loss, and fever is occasionally present. Spontaneous pneumothorax may occur, especially as the disease progresses, when chronic respiratory failure, pulmonary hypertension, and cor pulmonale can also develop. Physical examination of the thorax is usually normal, but crackles may be audible, and breath sounds often diminish as emphysema supervenes. Pulmonary function tests show obstruction, restriction, or both, and a reduced diffusing capacity is common. When emphysema is present, airflow obstruction is frequently pronounced, causing air trapping and hyperinflation. Commonly present on physical examination, but usually asymptomatic, is retinal involvement. Talc retinopathy is characterized by tiny yellowish-white glistening particles in both the arteries and veins of the posterior pole, concentrated around the macula, where the vasculature is densest and the blood flow greatest. The presence of talc in the retinal veins indicates that these particles can pass through the fine ophthalmic arterial system in the absence of arteriovenous shunts; presumably, they can do the same in the pulmonary circulation. Occasionally, talc causes retinal ischemia, leading to such complications as visual loss, new vessel formation, vitreous hemorrhage, and retinal detachment from traction or from a rent in the retina (a rhegmatogenous detachment). Talc retinopathy seems related to the total amount of material injected; in one study, for example, it was present only in those who had injected at least an estimated 9,000 tablets. Once present, it tends to remain unchanged over years. The earliest findings on chest imaging are small nodules, generally , 1 mm in diameter, and usually evenly distributed throughout all lung fields. CT scanning demonstrates that the nodules are centrilobular. Sometimes, diffuse ground-glass opacities are visible, presumably representing granulomas too small to be detectable as individual nodules. The granulomas can enlarge and coalesce to produce bilateral conglomerate masses in the perihilar regions, which may contain high-attenuation areas, representing the dense concentration of talc. These aggregates of granulomatous and fibrous tissue, whose radiographic appearance resembles that of progressive massive fibrosis in silicosis, are commonly accompanied by lower-lobe panacinar emphysema and bullae. However, these emphysematous changes can also develop in the absence of any masses. Pulmonary talcosis tends to cause worsening respiratory compromise, usually from pulmonary artery hypertension and/or emphysema, even in those who have discontinued their IV injections. Sometimes, the onset and progression of severe airflow obstruction Postgraduate Education Corner
are rapid. Occasionally, patients may respond to systemic corticosteroids, but typically the disease is progressive. Clinical Course The patient underwent a pulmonary wedge resection for a 2.5 cm 3 1.5 cm left upper lobe nodule 17 years previously, which demonstrated fibrosis and foreign-body reaction to crystalline material, confirming the diagnosis of pulmonary talcosis. Despite discontinuing IV injection of methylphenidate many years ago, he has had progressive respiratory insufficiency, requiring supplemental oxygen, and his chest imaging has shown enlarging perihilar masses and worsening emphysema. The fundoscopic exam showed bilateral, irregularly shaped crystalline deposits within the retinal vessels, especially those surrounding the fovea, characteristic of talc emboli. Clinical Pearls 1. IV injection of pulverized tablets intended for oral use can cause formation of talc-containing foreignbody granulomas in the pulmonary vessels and/or interstitium, leading to progressive respiratory disease due to pulmonary hypertension, lung fibrosis, or emphysema. 2. Although pulmonary function tests can reveal either restrictive or obstructive abnormalities, most patients with significant symptoms have severe airflow obstruction, typically associated with lower-lobe panacinar emphysema. 3. An important finding on physical examination in many patients with pulmonary talcosis is the pres-
journal.publications.chestnet.org
ence on fundoscopy of whitish-yellow particles in the retinal arteries and veins, representing aggregates of talc particles and granulomas. Most patients with talc retinopathy, however, have no visual symptoms. 4. The major imaging features are diffuse micronodules throughout all lung fields, bilateral perihilar conglomerate masses, and emphysema, which is usually panacinar and in the lower lobes, but is occasionally in the upper lobes and centrilobular. Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Suggested Readings AtLee WE Jr. Talc and cornstarch emboli in eyes of drug abusers. JAMA. 1972;219(1):49-51. Paré JA, Fraser RG, Hogg JC, Howlett JG, Murphy SB. Pulmonary ‘mainline’ granulomatosis: talcosis of intravenous methadone abuse. Medicine (Baltimore). 1979;58(3):229-239. Tse DT, Ober RR. Talc retinopathy. Am J Ophthalmol. 1980;90(5): 624-640. McLane NJ, Carroll DM. Ocular manifestations of drug abuse. Surv Ophthalmol. 1986;30(5):298-313. Paré JP, Cote G, Fraser RS. Long-term follow-up of drug abusers with intravenous talcosis. Am Rev Respir Dis. 1989;139(1): 233-241. Strack LK, Aberegg SK. A 53-year-old woman with chronic pain and progressive dyspnea and cough. Chest. 2009;135(5):1380-1383. Marchiori E, Lourenço S, Gasparetto TD, Zanetti G, Mano CM, Nobre LF. Pulmonary talcosis: imaging findings. Lung. 2010; 188(2):165-171.
CHEST / 145 / 1 / JANUARY 2014
181
Postgraduate Education Corner PULMONARY, CRITICAL CARE, AND SLEEP PEARLS
A Man in His Early 70s With Progressive Dyspnea and Abnormal Fundoscopic Examination Sarah Bastawrous, DO; and Jan V. Hirschmann, MD
CHEST 2014; 145(1):178–181
man in his early 70s complained of progresAblack sive dyspnea on exertion for 15 years. He had occa-
sional cough productive of clear sputum, but no chest pain. He had a 60-pack-year smoking history and previous illicit drug use, including IV injection of heroin and methylphenidate, complicated by tricuspid valve endocarditis nearly 30 years ago. He had no significant travel or occupational history. He had no visual complaints. He did not drink alcohol and had no pets or exposure to birds. He had no known previous TB, and his tuberculin test was negative. Physical Examination Findings BP, temperature, and heart rate were normal. Oxygen saturation was 95% on 2 L of supplemental oxygen. Chest auscultation indicated decreased breath sounds without wheezing. Fundoscopic examination of the eyes revealed numerous irregular, bright, yellowishwhite dots within the retinal vessels with no evidence of surrounding inflammation (Fig 1). The remainder of his examination was unremarkable. Diagnostic Studies
Figure 1. Fundoscopic image of the retina.
laboratory findings were normal. A chest radiograph showed diffuse emphysema with dense perihilar masslike lesions and reticular opacities extending to the upper and middle lung zones. There was distortion of the normal lung architecture with apical scarring and pleural thickening (Fig 2).
The patient’s metabolic panel was normal. CBC count revealed a hematocrit level of 37%. Other Manuscript received May 31, 2013; revision accepted June 21, 2013. Affiliations: From the Department of Radiology (Dr Bastawrous) and Department of Medicine (Dr Hirschmann), VA Puget Sound Health Care System; and Department of Radiology (Dr Bastawrous) and Department of Medicine (Dr Hirschmann), UW Medicine, University of Washington, Seattle, WA. Correspondence to: Sarah Bastawrous, DO, Department of Radiology, VA Puget Sound Health Care System, Mail Box 358280, S-114, 1660 S Columbian Way, Seattle WA 98108-1597; e-mail: [email protected] © 2014 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-1277 178
Postgraduate Education Corner
Figure 2. Chest radiographs show marked emphysema, upward elevation of both hila with dense perihilar, mass-like lesions, and reticular opacities extending to the upper and middle lung zones. Distortion of the normal lung architecture with apical scarring and pleural thickening is also present. A, Posteroanterior view. B, Left lateral view.
What is the diagnosis?
journal.publications.chestnet.org
CHEST / 145 / 1 / JANUARY 2014
179
Diagnosis: Pulmonary talcosis and talc retinopathy Discussion Pulmonary disease caused by talc (hydrous magnesium silicate) may occur from inhaling it, as in mining or industrial exposure, but may also develop from the IV injection of medications, such as methadone or methylphenidate, intended for oral use. These pills contain talc, whose purposes are to hold the components of the medication together and to prevent the tablets from adhering to the equipment used in their production. Drug abusers crush the oral medications, mix the pulverized material with water, heat it, sometimes sieve the mixture through cotton or cigarette filters, and then inject the product intravenously. The insoluble talc particles lodge within the pulmonary arterial circulation, sometimes provoking the formation of foreign-body granulomas, which can narrow or occlude the vessels. When extensive, these vascular abnormalities, often accompanied by medial hypertrophy of the muscular pulmonary arteries, may lead to pulmonary arterial hypertension. Visible microscopically as birefringent, needle-shaped particles, the talc can also erode through the pulmonary vessel walls to produce perivascular and interstitial granulomas. With time, the individual granulomas may expand and coalesce, producing larger nodules and masses, usually perihilar, which consist of talccontaining foreign-body giant cells, sometimes accompanied by lymphocytes, plasma cells, eosinophils, and fibrous tissue. Substantial fibrosis may cause contraction and retraction of involved lung tissue and distortion of the pulmonary architecture. Pulmonary vascular disease and interstitial disease may coexist or one type may predominate in talcosis. In any of these situations, a frequent, but unexplained, finding is emphysema. Usually, panacinar emphysema is present in the lower lobes, especially with methylphenidate injections, but in some patients it is centrilobular and typically located in the upper lobes. Often, talc is found outside the lung, in mediastinal lymph nodes, liver, spleen, muscle, heart, kidney, skin, pancreas, bone marrow, and retinal vessels, but usually no symptoms arise from this extrapulmonary involvement. The talc may reach the systemic circulation by successfully traversing the normal pulmonary vessels or via arteriovenous shunts in the vasculature of the lung or, elsewhere, such as through a patent foramen ovale. Talc particles presumably arrive at the mediastinal lymph nodes by migrating from the lung granulomas into the lymphatic channels and then lodging in the regional lymph nodes. Individuals with talcosis may be asymptomatic and have typically injected thousands of tablets (as many as an estimated 280,000), usually from an average daily 180
use of about 15 to 40 pills over several years. When pulmonary talcosis produces symptoms, the most common complaints are exertional dyspnea and a dry or productive cough. Some patients have substantial weight loss, and fever is occasionally present. Spontaneous pneumothorax may occur, especially as the disease progresses, when chronic respiratory failure, pulmonary hypertension, and cor pulmonale can also develop. Physical examination of the thorax is usually normal, but crackles may be audible, and breath sounds often diminish as emphysema supervenes. Pulmonary function tests show obstruction, restriction, or both, and a reduced diffusing capacity is common. When emphysema is present, airflow obstruction is frequently pronounced, causing air trapping and hyperinflation. Commonly present on physical examination, but usually asymptomatic, is retinal involvement. Talc retinopathy is characterized by tiny yellowish-white glistening particles in both the arteries and veins of the posterior pole, concentrated around the macula, where the vasculature is densest and the blood flow greatest. The presence of talc in the retinal veins indicates that these particles can pass through the fine ophthalmic arterial system in the absence of arteriovenous shunts; presumably, they can do the same in the pulmonary circulation. Occasionally, talc causes retinal ischemia, leading to such complications as visual loss, new vessel formation, vitreous hemorrhage, and retinal detachment from traction or from a rent in the retina (a rhegmatogenous detachment). Talc retinopathy seems related to the total amount of material injected; in one study, for example, it was present only in those who had injected at least an estimated 9,000 tablets. Once present, it tends to remain unchanged over years. The earliest findings on chest imaging are small nodules, generally , 1 mm in diameter, and usually evenly distributed throughout all lung fields. CT scanning demonstrates that the nodules are centrilobular. Sometimes, diffuse ground-glass opacities are visible, presumably representing granulomas too small to be detectable as individual nodules. The granulomas can enlarge and coalesce to produce bilateral conglomerate masses in the perihilar regions, which may contain high-attenuation areas, representing the dense concentration of talc. These aggregates of granulomatous and fibrous tissue, whose radiographic appearance resembles that of progressive massive fibrosis in silicosis, are commonly accompanied by lower-lobe panacinar emphysema and bullae. However, these emphysematous changes can also develop in the absence of any masses. Pulmonary talcosis tends to cause worsening respiratory compromise, usually from pulmonary artery hypertension and/or emphysema, even in those who have discontinued their IV injections. Sometimes, the onset and progression of severe airflow obstruction Postgraduate Education Corner
are rapid. Occasionally, patients may respond to systemic corticosteroids, but typically the disease is progressive. Clinical Course The patient underwent a pulmonary wedge resection for a 2.5 cm 3 1.5 cm left upper lobe nodule 17 years previously, which demonstrated fibrosis and foreign-body reaction to crystalline material, confirming the diagnosis of pulmonary talcosis. Despite discontinuing IV injection of methylphenidate many years ago, he has had progressive respiratory insufficiency, requiring supplemental oxygen, and his chest imaging has shown enlarging perihilar masses and worsening emphysema. The fundoscopic exam showed bilateral, irregularly shaped crystalline deposits within the retinal vessels, especially those surrounding the fovea, characteristic of talc emboli. Clinical Pearls 1. IV injection of pulverized tablets intended for oral use can cause formation of talc-containing foreignbody granulomas in the pulmonary vessels and/or interstitium, leading to progressive respiratory disease due to pulmonary hypertension, lung fibrosis, or emphysema. 2. Although pulmonary function tests can reveal either restrictive or obstructive abnormalities, most patients with significant symptoms have severe airflow obstruction, typically associated with lower-lobe panacinar emphysema. 3. An important finding on physical examination in many patients with pulmonary talcosis is the pres-
journal.publications.chestnet.org
ence on fundoscopy of whitish-yellow particles in the retinal arteries and veins, representing aggregates of talc particles and granulomas. Most patients with talc retinopathy, however, have no visual symptoms. 4. The major imaging features are diffuse micronodules throughout all lung fields, bilateral perihilar conglomerate masses, and emphysema, which is usually panacinar and in the lower lobes, but is occasionally in the upper lobes and centrilobular. Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Suggested Readings AtLee WE Jr. Talc and cornstarch emboli in eyes of drug abusers. JAMA. 1972;219(1):49-51. Paré JA, Fraser RG, Hogg JC, Howlett JG, Murphy SB. Pulmonary ‘mainline’ granulomatosis: talcosis of intravenous methadone abuse. Medicine (Baltimore). 1979;58(3):229-239. Tse DT, Ober RR. Talc retinopathy. Am J Ophthalmol. 1980;90(5): 624-640. McLane NJ, Carroll DM. Ocular manifestations of drug abuse. Surv Ophthalmol. 1986;30(5):298-313. Paré JP, Cote G, Fraser RS. Long-term follow-up of drug abusers with intravenous talcosis. Am Rev Respir Dis. 1989;139(1): 233-241. Strack LK, Aberegg SK. A 53-year-old woman with chronic pain and progressive dyspnea and cough. Chest. 2009;135(5):1380-1383. Marchiori E, Lourenço S, Gasparetto TD, Zanetti G, Mano CM, Nobre LF. Pulmonary talcosis: imaging findings. Lung. 2010; 188(2):165-171.
CHEST / 145 / 1 / JANUARY 2014
181