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Talcosis Associated with IV Abuse of Oral Medications

CT Findings

¹ Department of Radiology, Vancouver General Hospital and University of British Columbia, 855 W. 12th Ave., Vancouver, B. C., V5Z 1M9, Canada.
² Department of Radiology, University of Michigan Hospitals, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0326.
³ Department of Radiology, University of Washington, 1959 N.E. Pacific St., Seattle, WA 98195.

Received June 18, 1999; accepted after revision August 11, 1999.

 
Address correspondence to N. L. Müller.

Abstract

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OBJECTIVE. Our objective was to evaluate the CT appearance of talcosis associated with IV abuse of oral medications and to compare the findings of talcosis related to methylphenidate with those findings seen with other drugs.

MATERIALS AND METHODS. The CT scans of 12 patients with talcosis (seven men, five women), 33-54 years old (mean age, 44 years), were analyzed retrospectively. Seven patients had abused methylphenidate; five patients had no history of abuse. The diagnosis of talcosis was made histologically in 11 patients and at funduscopy in one patient. CT was performed with 1 - to 1.5-mm collimation (n = 10 patients) or 5- to 10-mm collimation (n = 2).

RESULTS. The predominant abnormalities seen on CT consisted of a diffuse fine nodular pattern (n = 2), a combination of nodules and lower lobe panacinar emphysema (n = 3), and ground-glass attenuation (n = 2). Emphysema was the only abnormality seen in the remaining five patients (lower lobe panacinar, n = 4; upper lobe centrilobular, n = 1). No significant difference in the prevalence of nodules and ground-glass attenuation was seen between the methylphenidate and non-methylphenidate groups. Lower lobe panacinar emphysema was more common in methylphenidate abusers (six [86%] of seven patients) than in non-methylphenidate drug abusers (one [20%] of five, p < 0.05, Fisher's exact test).

CONCLUSION. The CT manifestations of talcosis consist of a fine micronodular pattern, ground-glass attenuation, and emphysema. A significantly increased prevalence of lower lobe panacinar emphysema is seen in IV drug addicts who abuse methylphenidate.

Introduction

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The IV abuse of oral medication can cause pulmonary talcosis [1]. In oral medications, talc (magnesium silicate) acts as a filler and lubricant. When the drug is crushed, melted, dissolved in water, and IV-injected, numerous tiny particles of talc become lodged in the pulmonary vessels. These particles migrate to the pulmonary interstitium, where they cause a foreign body granulomatous reaction. The foreign body reaction can be confirmed by identifying birefringent talc crystals in the granulomas under polarized light.

IV drug abusers who develop talcosis experience progressive dyspnea and symptoms resembling chronic obstructive pulmonary disease. The chest radiographic manifestations of talcosis have been previously described [2, 3]. To our knowledge, only two studies describing the CT features of talcosis exist; each examines only three patients with CT [3, 4]. In addition, IV abuse of methylphenidate (Ritalin; Novartis Pharmaceuticals, Dorval, Quebec, Canada) has a tendency to cause severe panacinar emphysema, predominantly in the lower lobes [3]. This pattern resembles the emphysema described in patients with alpha₁-antiprotease deficiency.

The aim of this study was to assess the CT appearance of talcosis associated with IV abuse of oral medication in a relatively large number of patients and to compare the findings in talcosis associated with Ritalin with those seen with other drugs.

Materials and Methods

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Subjects
We retrospectively analyzed the CT scans of 12 patients with talcosis associated with IV drug abuse. These patients had been investigated at one of five centers over the previous 10 years for progressive dyspnea. The clinical details were obtained from a review of the patients' charts. The study group comprised five women and seven men, 33-54 years old (mean age, 44 years). Seven patients had injected IV Ritalin, either alone or in combination with heroin, cocaine, or pentazocine. Five patients gave a history of IV injection of various oral drugs, but not Ritalin. The various drugs included heroin, cocaine, diazepam, acetaminophen, meperidine, pentazocine, and methadone, frequently in combination. All patients were cigarette smokers (15-60 pack-years). The CT findings of three of the 12 patients were previously reported [4].

The diagnosis of pulmonary talcosis was made histologically in 11 patients by either autopsy (n = 2), lung volume reduction surgery for treatment of emphysema (n = 2), lung transplantation for endstage respiratory failure (n = 3), transbronchial biopsy (n = 3), or open lung biopsy (n = 1). In one patient, the diagnosis of talcosis was made on the basis of an appropriate clinical history and chest radiographic findings and was confirmed at fundus-copy, which revealed birefringent particles consistent with talc emboli in the retinal vessels. This patient was a 54-year-old woman who gave a 12-year history of IV abuse of heroin and methadone. Chest radiographs 7 years apart showed progression of a fine nodular pattern and perihilar conglomerate masses.

CT Scans
The patients were examined with either a 9800 (n = 6) or HiSpeed Advantage scanner (n = 6) (both by General Electric Medical Systems, Milwaukee, WI). All scans were performed at end-inspiration. Ten patients had thin-section CT with 1- to 1.5-mm collimation at 10-mm intervals. Two patients had conventional CT with a slice thickness of 10 (n = 1) or 5 mm (n = 1).

All thin-section CT images were reconstructed with a high-spatial-frequency algorithm (high-resolution CT). The lung windows were photographed at a window level of -450 to -700 H and a window width of 1000-2000 H. The mediastinal windows were imaged at a window level of 20-40 H, and a window width of 350-500 H.

Radiologic Evaluation
The CT scans were assessed randomly and independently by two observers for nodularity, conglomerate masses, ground-glass attenuation, and emphysema. In cases of discrepancy between the observers, the final imaging features were determined by consensus.

The lungs were assessed for the presence, size, number, and distribution of nodules. Conglomerate masses were defined as focal parahilar opacities, measuring greater than 1 cm, associated with loss of lung volume and architectural parenchymal distortion [4, 5]. The presence or absence of high attenuation equivalent to that of calcium in areas of conglomeration was recorded. Ground-glass attenuation was defined as a hazy increase in lung opacity that was not associated with obscuration of underlying vessels [5].

Emphysema was defined as an area of low attenuation with associated arterial deficiency [6, 7]. The emphysema was further described as either centri-lobular or panacinar. Centrilobular emphysema was identified by the presence of localized areas of low attenuation near the center of secondary pulmonary lobules and interspersed with regions of healthy lung [6, 7]. Panacinar emphysema was defined by the presence of widespread areas of low attenuation without small focal areas of lucency [6, 7]. The distribution of the emphysema was assessed for lobar predominance and the severity was indicated subjectively as involving less than 25%, 25-50%, or greater than 50% of the lung volume.

Statistical Analysis
Interobserver agreement was assessed with the kappa statistic [8]. Comparison between the prevalence of abnormal CT findings in the patients with known IV Ritalin abuse and in patients without a history of Ritalin abuse was performed with the Fisher's exact test [8].

Results

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Five (42%) of the 12 patients had innumerable small lung nodules (Fig. 1). In all five patients the nodules were 1 mm or less in diameter. The nodules created a fine granular appearance that, in many areas, was sufficiently profuse to resemble ground-glass opacification. The fine granularity involved all three lung zones to a similar extent except for sparing of emphysematous portions of the lung. The fine granular appearance was identified in two (29%) of the seven predominantly Ritalin abusers, and three (60%) of the five of the non-Ritalin group (p = 0.53, Fisher's exact test).

View larger version (133K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1. —36-year-old woman with talcosis related to IV abuse of methylphenidate and pentazocine. High-resolution CT scan (1-mm collimation) reveals diffuse fine granular pattern. In some areas profusion of micronodules creates ground-glass appearance (arrows).

Conglomerate masses were seen in three (25%) patients, two Ritalin abusers and one non-Ritalin abuser (Fig. 2A,2B,2C). The conglomerate masses were located in a perihilar distribution. Areas of high attenuation equivalent to that of calcium were present in two of the three patients with conglomerate masses. All three patients with conglomerate masses also had a diffuse fine-nodular pattern. Two of the three patients, both Ritalin abusers, had lower lobe panacinar emphysema.

View larger version (134K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —36-year-old woman with talcosis related to IV abuse of methylphenidate. High-resolution CT scan (1-mm collimation), photographed at lung windows, shows conglomerated masses (arrows) in left lower lobe, lingula, and superior segment of right lower lobe. Note panacinar emphysema in both lower lobes and lingula.

View larger version (100K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —36-year-old woman with talcosis related to IV abuse of methylphenidate. High-resolution CT scan (1-mm collimation) at same level as A, but photographed at mediastinal settings, shows highly attenuated material and conglomerated masses.

View larger version (104K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C. —36-year-old woman with talcosis related to IV abuse of methylphenidate. High-resolution CT scan (1-mm collimation) through lung bases shows lower lobe panacinar emphysema.

Ground-glass attenuation was identified in seven patients although it was a major finding in only two of these patients (Fig. 3). In the remaining patients, the attenuation resulted from a confluence of micronodules.

View larger version (75K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3. —46-year-old man with talcosis associated with IV abuse of meperidine. High-resolution CT scan (1.5-mm collimation) shows areas of ground-glass attenuation in both upper lobes.

Emphysema was identified in 10 (83%) of 12 patients. Six patients had CT findings characteristic of panacinar emphysema, two had centrilobular emphysema, and two had both centrilobular emphysema in the upper lobes and panacinar emphysema in the lower lobes. Centrilobular emphysema involved mainly the upper lobes in all patients, whereas the panacinar emphysema involved mainly the lower lobes in seven (88%) of the eight patients. In one patient, severe emphysema was present in the upper but not in the lower lobes. The appearance on CT was considered most consistent with panacinar emphysema. However, this patient had a 60-pack-year history of smoking, and the upper lobe emphysema presumably was centrilobular rather than panacinar. The proportion of lung volume affected by emphysema was less than 25% in three patients, between 25% and 50% in three, and greater than 50% in four.

Six (86%) of the seven patients who predominantly abused IV Ritalin had emphysema (Fig. 4A,4B). Five of these patients had CT findings suggestive of panacinar emphysema affecting the lower lobes, one patient had both panacinar emphysema in the lower lobes and centrilobular emphysema in the upper lobes, and one had only centrilobular emphysema in the upper lobes. Four (67%) of six patients in the non-Ritalin group had evidence of emphysema on CT. One had centrilobular emphysema in the upper lobes, one had panacinar emphysema in the upper lobes, and one had both centrilobular emphysema in the upper lobes and panacinar emphysema in the lower lobes. A significant difference was seen in the prevalence of lower lobe panacinar emphysema in patients with Ritalin abuse (6/7 patients) compared with that of the other patients (1/5, Fisher's exact test, p < 0.05).

View larger version (88K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A. —51-year-old man with talcosis related to IV abuse of methylphenidate. CT scan (5-mm collimation) through upper lobes shows no definite evidence of emphysema.

View larger version (73K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B. —51-year-old man with talcosis related to IV abuse of methylphenidate. CT scan (5-mm collimation) through lower lobes shows diffuse panacinar emphysema. Note blood flow redistribution to upper lobes.

In summary, the predominant abnormalities on CT consisted of a diffuse fine nodular pattern (n = 1), a combination of nodules and conglomerate masses (n = 1), lower lobe panacinar emphysema (n = 4), a combination of nodules and lower lobe panacinar emphysema (n = 3), ground-glass attenuation (n = 2), and upper lobe centrilobular emphysema (n = 1). In five patients emphysema was the only finding; four of these were Ritalin abusers.

A high degree of interobserver agreement was found in the interpretation of the images. The kappa value was 0.87 for lung nodularity and 0.62 for the diagnosis of emphysema. Both observers agreed in the interpretation of all three cases with conglomerate masses, in both cases with predominantly or exclusively ground-glass attenuation, and in the predominant lower lobe distribution of the emphysema present in six Ritalin abusers.

Discussion

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Paré et al. [2] reported the chest radiographic manifestations of 17 drug addicts, all primarily methadone addicts. Seven of the 17 patients showed a diffuse pinpoint micronodularity on the chest radiograph; in two patients this micronodularity was associated with conglomerate masses. In another study, Paré et al. [9] noted that on long-term follow-up of three patients with micronodularity, two developed conglomerate masses and lower lobe emphysema and one developed lower lobe bullae only. On long-term follow-up of three patients not described in the original study, progressive massive fibrosis was seen in two, again associated with lower lobe emphysema, and diffuse reticulonodular changes were identified in both the upper lobes and lower lobes in the third patient [9]. Because no CT was performed, the type of emphysema present was not clarified. Only one patient had panacinar emphysema in the lower lobes at autopsy but this finding was associated with bilateral upper lobe conglomerate masses. From Paré et al., it was postulated that, in talcosis associated with the IV abuse of oral medication, a progression occurred from a fine micronodular pattern to conglomerate masses in the upper lobes, similar to the progressive massive fibrosis seen with silicosis. This observation is consistent with the findings of our study, in which conglomerate-mass formation was detected only in patients with a diffuse fine granular pattern in the lung parenchyma.

In our study, the main manifestation of talcosis was the presence of innumerable nodules measuring 1 mm or less in diameter, a finding seen in five of the 12 patients. Three of these five patients also had conglomerate masses. Two of the three patients had areas of high attenuation resembling calcification in the conglomerate masses. Similar findings were described in two previous studies [3, 4]. In areas where the small nodules were most numerous, the appearance resembled ground-glass attenuation. However, two patients had ground-glass attenuation without any visible nodularity. Although most patients were smokers and had emphysema, a predominantly lower lobe distribution of panacinar emphysema was seen almost exclusively in Ritalin abusers.

Obstructive lung disease in IV drug abusers is uncommon, but precocious severe emphysema was noted in IV Ritalin abusers [10,11,12]. Schmidt et al. [10] studied seven young IV Ritalin abusers with profound obstructive lung disease and described the pathologic basis of the severe chronic airways limitation. All seven patients had severe panacinar emphysema involving mainly the lower lobes without upper lobe conglomerate masses or bulla formation. The distribution and type of emphysema resembled that of alpha₁-antiprotease deficiency although no evidence of this disease existed in any of their patients. In another study of 21 patients with obstructive pulmonary disease associated with IV Ritalin abuse, the abnormal radiographic finding consisted of basilar emphysema [3]. This finding was confirmed in three patients on CT. The pathogenesis of the lower lobe panacinar emphysema was not determined in these two studies. Cigarette smoking was considered unlikely to be the causative agent because this most frequently leads to upper lobe centrilobular emphysema. Therefore, it was postulated that the presence of panacinar emphysema may relate directly to the effects of either IV talc or IV Ritalin [10]. In the current study, panacinar emphysema in the lower lobes was detected in six (86%) of seven patients who predominantly abused IV Ritalin, and in only one (20%) of five patients who did not. This difference supports the hypothesis that Ritalin itself may be the primary causal agent.

Our study has several limitations. The patients were selected retrospectively from five centers. Therefore, different CT protocols had been used and thin-section CT was not performed in two patients, both of whom had lower lobe panacinar emphysema. IV drug users often abuse multiple drugs simultaneously and smoke heavily. Both habits could result in a mixed pattern of changes detected on CT. One patient did not have the diagnosis of talcosis confirmed pathologically. However, this patient had a significant history of IV drug abuse and had birefringent particles at funduscopy, a diagnostic finding of talc retinopathy.

In summary, we detected four main patterns of abnormality on the CT scans of patients with talcosis related to the IV abuse of oral medications. The patterns consisted of a fine micronodular pattern, conglomerate parahilar masses on a background of micronodularity, ground-glass attenuation, and emphysema. These patterns frequently appeared in combination. No significant difference in the prevalence of micronodularity or ground-glass attenuation was found between IV drug abusers who did or did not abuse Ritalin. Lower lobe panacinar emphysema was found more frequently in IV drug addicts who abused Ritalin.

References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Feigin DS. Talc: understanding its manifestations in the chest. AJR 1986; 146 :295-301[Abstract/Free Full Text]
2. Paré JP, Cote G, Fraser RS. Longterm follow-up of drug abusers with intravenous talcosis. Am Rev Respir Dis 1989; 139 :233-241[Medline]
3. Stern EJ, Frank MS, Schmutz JF, Glenny RW, Schmidt RA, Godwin JD. Panlobular pulmonary emphysema caused by IV injection of methylphenidate (Ritalin): findings on chest radiographs and CT scans. AJR 1994; 162 :555-560[Abstract/Free Full Text]
4. Padley SPG, Adler BD, Staples CA, Miller RR, Müller NL. Pulmonary talcosis: CT findings in three cases. Radiology 1993;186:125-127[Abstract/Free Full Text]
5. Webb WR, Müller NL, Naidich DP. High-resolution CT of the lung. Philadelphia: Lippincott-Raven, 1995:71-72
6. Bergin CJ, Müller NL, Miller RR. CT in the qualitative assessment of emphysema. J Thorac Imaging 1986;1:94-103[Medline]
7. Thurlbeck WM, Müller NL. Emphysema: definition, imaging and quantification. AJR 1994;163:1017-1025[Abstract/Free Full Text]
8. Dawson-Saunders B, Trapp RG. Basic and clinical biostatistics. East Norwalk, CT: Appleton and Lange, 1994:152-153
9. Paré JA, Fraser RG, Hogg JC, Howlett JG, Murphy SB. Pulmonary "mainline" granulomatosis: talcosis of intravenous methadone abuse. Medicine (Baltimore) 1979;58:229-239[Medline]
10. Schmidt RA, Glenny RW, Godwin JD, Hampson NB, Cantino ME, Reichenbach DD. Panlobular emphysema in young intravenous Ritalin abusers. Am Rev Respir Dis 1991;143:649-656[Medline]
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