Talc induced granulomatosis is rare and is mainly caused by injection of tablets intended for oral consumption.1,2 We report a case of talc associated perivascular granulomatosis in the lung in an individual with no known history of intravenous drug use.
An obese 33 year old housewife was found dead in bed. She had a long, complex history of illness, with diagnoses of hypothyroidism and depression, and was treated privately for colitis, for which she underwent multiple surgical procedures. She was taking methadone tablets orally for chronic abdominal and back pain, in addition to venlafaxine, azathioprine, diazepam, temazepam, dosulepin (dothiepin), and frusemide. In the weeks before her death she had found it difficult to get about and spent most of her time at home.
A complete necropsy was carried out revealing multiple small intestinal adhesions and an enlarged fatty liver. The rest of the organs were unremarkable. To elucidate the cause of death, blocks of the heart, lung, and liver were taken, together with blood and urine samples for laboratory analysis.
Histologically, the congested lung showed patchy interstitial fibrosis with a mild alveolitis. Thrombus formation was seen within the pulmonary arteries. Foreign body granulomata with a perivascular distribution (fig 1) were noted. With polarised light, some of these granulomata were seen to contain needle shaped particles. These particles were also present within a pulmonary artery and within the interstitium of the lung focally. The liver showed macrovesicular steatosis, interphase hepatitis, and foci of perivenular and pericellular fibrosis. On birefringence, occasional aggregates of needle shaped particles were seen in macrophages in the portal triads of the liver. Maltese cross shaped particles (fig 2) were found within some hepatic veins.
Figure 1 A foreign body granuloma with a perivascular location within the lung. Needle shaped particles were seen in the granuloma under polarised light.
Figure 2 A rounded cornstarch particle showing Maltese cross birefringence within a hepatic vein.
Drugs intended for oral use can be injected intravenously by grinding the tablets to a powder and dissolving them in water before injection. Tablets and capsules prepared for oral administration frequently contain insoluble fillers such as cornstarch, talc, and microcrystalline cellulose,1,3,4,5 with the last two most frequently encountered in the lungs of intravenous drug abusers.3 Cornstarch particles are uncommon and are usually associated with talc.3,6 Under polarised light, talc particles have a needle‐like structure. Cornstarch particles are round and have a distinctive Maltese cross birefringence.
These filler particles are mainly entrapped within the pulmonary vasculature and can cause thrombosis and the formation of intravascular granulomata. Systemic spread may occur as small particles escape filtration by the lung and can be seen within the microcirculation of the retina on ophthalmoscopy.2 A postmortem study of 33 intravenous drug addicts demonstrated birefringent material mainly within lung tissue (94%), followed by the spleen (76%), liver (55%), lymph nodes (39%), and bone marrow (24%).7 Starch is considered a marker of recent drug injection because it is metabolised and disappears with time.4,5
Perivascular and interstitial granulomatous lesions form when the particles erode through the pulmonary arterial wall. This means that longstanding intravenous users of dissolved tablets tend to have granulomata located primarily in the pulmonary interstitium. Those with shorter durations of addiction have granulomata in the vascular lumina.8
The causes of granulomata are endless, but finding pulmonary granulomata in an intravascular or perivascular location should alert one to the possible abuse of oral drugs intravenously and a search for insoluble filler particles instituted. In our case, the perivascular granulomata indicate a long duration of drug injection and the cornstarch particles indicate recent abuse of drugs intravenously. Blood investigations showed correspondingly high and fatal levels of methadone and dothiepin.
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References
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