British Journal of Industrial Medicine 1984;41:84-87

Pulmonary granulomatous reaction: talcpneumoconiosis or chronic sarcoidosis?P TUKIAINEN,' J NICKELS,2 E TASKINEN,3 AND M NYBERG4

From the Department ofPulmonary Diseases,' Helsinki University Central Hospital, the Institute ofOccupational Health,2 the Transplantation Laboratory,3 University ofHelsinki, and Aurora Hospital,4Helsinki, Finland

ABSTRACT A chronic pulmonary granulomatous reaction was associated with an almost identicalclinical picture in two patients exposed to talc. In both patients lung biopsy showed the depositionof talc particles and a heavy granulomatous reaction. At the time of diagnosis the Kveim testresult was negative in both patients, urinary calcium excretion was normal, and there were noextrapulmonary manifestations and no response to steroid treatment. These findings pointagainst sarcoidosis. The serum angiotensin-converting enzyme level, however, was raised in bothpatients. It was concluded that the patient who was exposed to talc in the rubber industry had atrue talc pneumoconiosis. The other patient, who was exposed to cosmetic talcum powder,suffered from chronic sarcoidosis with talc deposition in the lungs, since an enlarged axillar lymphnode containing granulomatous inflammation was discovered after two years' follow up. Thesecases show that it may be extremely difficult to differentiate between chronic sarcoidosis and talcpneumoconiosis even after careful clinical and histological analysis.

True talc is a hydrous magnesium silicate. Depen-ding on where it is mined, commercially availabletalc also contains varying amounts of asbestosminerals which form chains or fibres and may there-fore have an asbestos like effect on the lungs. Owingto the widespread industrial and private use of talcand talcum powder much interest has been directedto the biological effects of this mineral, which havebeen reported to cause pneumoconiosis in peopleemployed in talc mills and talc mines, and in workersusing talc in production processes-for example, inthe rubber industry.'Although widely used as a dusting powder, talc is

not generally considered a health hazard whenexposure is limited to cosmetic application at home.A search has found four reports of chronicgranulomatous pulmonary disease referable toexcessive use of cosmetic talc in adults.2-5 In allthese cases the question arises whether it was a truetalc pneumoconiosis or talc deposition and coinci-dental sarcoidosis.We report a case of chronic pulmonary

granulomatous reaction in a patient who had usedcosmetic talcum powder for several years. As a

Received 5 November 1982Accepted 10 January 1983

comparison we describe a patient who was exposedto talc in the rubber industry and who showed achronic granulomatous lung reaction which webelieve represents true talc pneumoconiosis.

Case 1

A 58 year old woman had a history of myomectomyin 1952, cholecystectomy in 1968, and hysterectomyin 1977. She had been a smoker for 20 years. InApril 1977 she was operated on because of atraumatic leg fracture. As a complication she hadthrombosis in the left femoral vein and pulmonaryembolism. The symptoms and signs of embolismdisappeared during treatment with anticoagulants.Chest radiography was normal at that time. Thepatient was in good condition until summer 1980when she began to suffer from dry cough, dyspnoea,tachycardia, and low grade fever. In November1980 crepitant rales were heard at the bases of thelungs. Chest radiography showed fine diffuseopacities. Spirometry showed normal lung volumes.Diffusing capacity was lowered (DLCo 64% of pre-dicted). The sedimentation rate was 38 mm/h. Thefollowing variables were within normal limits:haemoglobin, white cell count, differential andthrombocyte counts, creatinine, transaminases,

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Pulmonary granulomatous reaction: talc pneumoconiosis or chronic sarcoidosis?

alkaline phosphatase, serum calcium, urinary cal-cium excretion, and urine analysis. Serum lysozymewas slightly raised (27 mg/l (normal 20 mg/l)) andserum angiotensin converting enzyme (ACE) wasnormal (38 U/l). Mantoux 10 TU was negative.The concentration of serum immunoglobulins, C3

and C4, and the titres of cryoprecipitins, directCoombs-test, Latex-fixation test, Waaler-Rose, andantinuclear antibodies were normal. The Kveim testresult was negative.Three months later, in February 1981, laboratory

results were the same as before, except that theserum ACE was raised (70 U/l). For diagnostic pur-poses an anterolateral thoracotomy was performed.The lung showed a diffuse nodular consistency. Abiopsy specimen was taken from the lingula. Cul-tures for tuberculosis, bacteria, and fungi were nega-tive. Histological examination showed a heavyintra-alveolar and interstitial granulomatousinflammation (fig 1) consisting of epitheloid andgiant cells forming granules, macrophages, lym-phocytes, plasma cells, some eosinophils, andfibrosis. Numerous birefringent particles were dis-covered inside the giant cells (fig 1). For elementalelectron probe microanalysis 5 ,tm thick tissue sec-tions of the lung were deparaffinised in xylene,mounted on carbon coated nylon grids by conduc-tive carbon cement, and examined by scanning elec-tron microscopy (SEM) in a graphite holder (JEM-100 CX electron microscope fitted with a PrincetonGamma-Tech PGT System III energy dispersive xray microanalyser). The foreign body material insidethe granulomas contained magnesium and silicon incombination with chlorine, calcium, iron, and zinc(fig 2), characteristic of talc.Because the examinations pointed to the possibil-

ity of talcosis a careful inquiry was undertaken intothe dust exposure of the patient. She had appliednon-powdering talc on her face for 20 years and

after that, talcum powder two to three times a dayduring a 10 year period, usually in an unventilatedroom. The total amount of powder used was twoboxes a year. In the patient's own opinion theamount of powder used was not excessive enough tocause any disease. Elemental analysis of two differ-ent commercially available talcum powder pre-parations was also carried out. Electron probemicroanalysis of these preparations showed mag-nesium, aluminium, silicon, potassium, iron, andzinc (fig 3).

In March 1981, treatment with prednisolone wasstarted with an initial dose of 40 mg. The dose wasgradually lowered to 10 mg a day over a period offour months. When the treatment was discontinuedafter nine months no improvement of pulmonaryfunction or radiographs was observed. The serumangiotensin values fell to normal during the steroidtreatment (26 U/1) but rose again after treatmentceased (77 U/l).

After two years' follow up an enlarged axillarlymph node was noticed. A biopsy specimen showedgranulomatous inflammation.

Case 2

A 55 year old woman had smoked 10 cigarettes aday for 30 years. From 1958 to 1968 she had packedrubber balls and was exposed to the talc used as adusting agent to prevent adhesion of the balls.During the first five years after exposure she beganto suffer insidiously from dyspnoea. In April 1973 achest radiograph showed diffuse nodular opacities;lung auscultation was normal. All the following var-iables were within normal limits: sedimentation rate,haemoglobin, white cell count, differential andthrombocyte counts, creatinine, transaminases,alkaline phosphatase, serum calcium, daily urinarycalcium excretion, urine analysis, titres of latex

Fig 1 Open lung biopsy specimen of case I showing heavy granulomatous inflammation (a) with strongly birefringentcrystal inside a giant cell (b) van Gieson, x 230 (a), x 1200 (b).

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Tukiainen, Nickels, Taskinen, and Nyberg

Counts

00 Energy ( kev 100

Fig 2 Electron probe microanalysis from a pulmonarybirefringent crystal showing magnesium (Mg), silicon (Si),chlorine (Cl), calcium (Ca), iron (Fe), and zinc (Zn)characteristic of talc. Copper (Cu) is derived fromsupporting material.

fixation test, Waaler-Rose, cryoprecipitins, andantinuclear antibodies. Mantoux 10 tuberculin unit(TU) was positive. Spirometry showed normal lungvolumes (FVC 107% of predicted), but diffusingcapacity was lowered (DLco 60% of predicted). TheKveim test result was negative.A lung biopsy was performed with a transthoracic

TruCut needle in the right lower lobe. The biopsyspecimen showed numerous small interstitialgranulomas (fig 4a). Within these granulomasnumerous particles were found, most of themdouble-refractile and resembling talc particles (fig4b). Some ferruginous bodies were also seen. Thealveolar spaces were patent.

In July 1973 treatment with prednisolone wasstarted with an initial dose of 40 mg. The dose wasgradually lowered and the treatment was terminatedafter two months because no objective improvement

Fig 3 Electron probe microanalysis from a commerciallyavailable talcum powder preparation showing magnesium(Mg), aluminium (Al), silicon (Si), potassium (K), iron(Fe), and zinc (Zn). Copper (Cu) is derived fromsupporting material.

Fig 4 TruCut needle biopsy specimen ofcase 2. (a) Aperivascular granulomatous inflammation. Haematoxylin &eosin, original magnification x 150. (b) Numerousbirefringent particles in polarised light in areas ofinflammation.

was observed in the chest radiograph or in pulmo-nary function.

In April 1980 spirometry showed normal lungvolumes (FVC 84% of predicted) and diffusing

I capacity was lowered (DLco 51% of predicted). Atthat time serum ACE was slightly raised at 49,u mol/l (normal 40 ,u mol1).

Discussion

Talc used in the manufacture of cosmetic talcumpowder is normally of high purity. Nevertheless, xray diffraction analysis of 21 powders obtainedthrough retail channels in the United States showedthat few of them consisted of pure talc. Quartz, ran-ging from 2% to 5% was found in eight, while onesample contained 35%. Detectable amounts offibrous tremolite and anthophyllite were reported tobe present in 10, and chrysotile in two.6Epidemiological studies indicate that prolongedexposure to cosmetic grade talc is not associatedwith the development of pneumoconiosis, thoughexposure to industrial grade talc may result in thiscondition.78

Exposure to talc causes three distinct types of

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Pulmonary granulomatous reaction: talc pneumoconiosis or chronic sarcoidosis?

lesion depending on the composition of the "talc." 'Ill defined nodular lesions are associated with arelatively high quartz content in the lungs. Diffuseinterstitial fibrosis is associated with exposure to talccontaining significant amounts of tremolite,anthophyllite, or other fibrous minerals. Foreignbody granulomas are obviously caused by pure talc.An extensive use of talcum powder was reported

in association with pure talc pneumoconioses.2-5The histological changes were identical in all thesecases-foreign body granulomas and varyingamounts of interstitial fibrosis.Although one of our patients (case 1) had used

talcum powder for 10 years, usually in a smallunventilated room, the amount of talc was obviouslynot as excessive as in the patient previously repor-ted. Therefore, the question arises whether our caseis an example of talc pneumoconiosis or of talcdeposition in the lungs with coincidental sarcoidosis.

Neither of our patients showed extrapulmonarymanifestations compatible with sarcoidosis. TheKveim test result was negative and urinary calciumexcretion was normal. No improvement was obser-ved during treatment with steroids even though thehistological alterations were mainly inflammatory.On the other hand, both patients had raised valuesfor serum ACE, which is known to be raised inabout 75% of patients with active sarcoidosis.9Other diseases with raised ACE levels are Gauher'sdisease, leprosy, berylliosis, Lennert's lymphoma,lymphangioleiomytomatosls, Mycobacterium intra-cellulare infection, osteoarthritis, plasmo-cytoma with lung involvement, and Q fever. Farberet al reported raised levels of ACE in a case of talcpneumoconosis in a pentazocine abuser (drug con-taining talc as filler).'0 Thus the possibility of talcpneumoconiosis cannot be excluded on the bases ofraised ACE alone. Epitheloid cells are known toexcrete ACE,9 thus this might be an unspecificphenomenon independent of the aetiology of thegranulomatous reaction. In the present casesgranulomas seemed to be able to produce ACE.

In both our patients histological examinationshowed excessive amounts of birefringent dust par-ticles in the lung tissue and foreign body granulomasand talc particles in the cytoplasm of giant cells.Except, perhaps, for the talc containing giant cells,'

these findings do not establish any causal relation-ship between talc and the disease.

In our patients the quantity of dust exposureseemed to be important in the differential diagnosisof sarcoidosis and talc pneumoconiosis before thedetection of granulomatous inflammation of an axil-lar node in case 1. The patient who handled talcpowdered rubber balls had an exposure that may beclassified as typical, and therefore we believe thepatient had a true talc pneumoconiosis. The patientwho used talcum powder at home had an exposurethat was not unusual. Therefore the quantity of dustexposure seems to be insufficient, even though thequantity of dust in the lung tissue was excessive. Webelieve that this patient represents a case of chronicsarcoidosis and coincidental talc deposition in thelungs.Our report shows that even after careful clinical

and laboratory examination together with analysisof lung biopsy specimens it may be extremelydifficult to differentiate between chronic sarcoidosisand talc pneumoconiosis.

References'Parkes WR. "Talc" pneumoconiosis. In: Parkes WR, ed. Occu-

patonal lung disorders. London: Butterworths, 1981:296-310.

2Fraser RG, Pare JAP. Diagnosis of diseases of the chest.Philadelphia: WB Saunders, 1970:937-8.

Moskowitz RL. Talc pneumoconiosis, a treated case. Chest1970;58:37-41.

4Nam K, Gracey DR. Pulmonary talcosis from cosmetic talcumpowder. JAMA 1972;221:492-3.

5Wells IP, Dubbins PA, Whimster WF. Pulmonary disease causedby inhalation of cosmetic talcum powder. Br J Radiol1979;52:586-8.

6Rohl AN, Langer AM, Selikoff IJ, et al. Consumer talcums andpowders: mineral and chemical characterization. J ToxicolEnviron Health 1976;2:255-84.

7Kleinfeld M, Messite J, Zaki MH. Mortality experiences amongtalc workers: a follow-up study. JOM 1974;16:345-9.

Rubino GF, Scansetti G, Piolatto G, Gay G. Mortalityand mor-bidity among talc miners and millers in Italy. In: Lemen R,Dement JM, eds. Dusts and disease. Illinois: Pathotoxic Pub-lishers, 1979;357-63.

9Lieberman J, Nosal A, Schlessner LA, et al. Serum angiotensinconverting enzyme for diagnosis and therapeutic evaluation ofsarcoidosis. Am Rev Respir Dis 1979;120:.329-35.

Farber HW, Mathers JAL Jr, Glauser FL. Gallium scans andserum angiotensin converting enzyme levels in talcgranulomatosis and lymphocytic interstitial pneumonitis.South Med J 1980:73:1663-6.

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