Letter to the Editor Mixed pneumoconiosis due to silicates and hard metals associated with primary Sjögren’s syndrome due to silica Pneumoconiose mista por silicatos e metais duros associada à síndrome de Sjögren primária por silicatos Pedro Gonçalo de Silva Ferreira, António Jorge Correia Gouveia Ferreira, Lina Maria Rodrigues de Carvalho, António Segorbe Luís To the Editor: Here, we describe the case of a 75-year-old showed high levels of silica, copper, cobalt, man who presented with a 3-year history of chromium, rubidium, molybdenum, and zinc. progressive dyspnea on exertion (classified as grade Laboratory testing revealed that the patient II/III on the modified Medical Research Council had a hemoglobin level of 11.6 g/dL, normal scale) and persistent dry cough. He had worked inflammatory markers, a creatinine level of 1.0 as a professional welder for 35 years, welding mg/dL, and an inactive urinary sediment, as well alloys, polishing weldments by sandblasting and as having a beta-2 microglobulin level of 6.56 steel blasting, and regularly performing isolation mg/L and a serum angiotensin-converting enzyme of fixed appliances with asbestos fibers. level of 127 U/L. In addition, he had polyclonal Treated in the primary care setting in the first hypergammaglobulinemia (IgG and IgA) and year, the patient developed recurrent scaly skin positive antinuclear antibodies (anti-SSA60 and lesions (exhibiting a lichenified/desquamative anti-SSB antibodies) at high titers. Schirmer’s pattern) on the limbs, Raynaud’s phenomenon, test confirmed xerophthalmia (right eye, 9 mm; sicca syndrome, and weight loss (5 kg). Physical left eye, 7 mm). examination revealed that he was breathing Functionally, the patient had a moderate normally, with an SpO of 95% and auscultatory restrictive pattern (Tiffeneau index, 80; FEV , 2 1 findings of basal inspiratory crackles, and that 70.9%; FVC, 66.8%; TLC, 64.6%; and RV, there was no digital clubbing. 68.4%), moderately reduced DLCO (51.2% of A chest X-ray showed reticular interstitial predicted), and a short six-minute walk distance changes. A CT scan of the chest showed with desaturation of 5%. calcified mediastinal adenopathy exhibiting A surgical lung biopsy showed foci of fibroblast an “eggshell” pattern, interlobular reticulation, proliferation, macrophages with anthracotic traction bronchiectasis, and septal thickening, pigmentation and birefringent particles suggestive as well as areas of ground-glass opacity, alveolar of silicates, multinucleated giant cells along the consolidation with a peribronchovascular bronchoalveolar axes and interlobular septa, as distribution, and areas of pleural thickening well as alveolar macrophage desquamation and (Figure 1). diffuse pleural fibrosis (Figure 2). The patient underwent a skin biopsy, which A diagnosis of mixed pneumoconiosis due showed non-specific lichenoid changes. A BAL, to silica, hard metals, and asbestos, associated performed at the level of the middle lobe (right with primary Sjögren’s syndrome (SS) with bronchus, 4a), revealed a total cell count of possible pulmonary parenchymal involvement, 130,000 cells/mL, with 40% lymphocytes and 16% was established. The patient was started on a neutrophils, as well as negative microbiological four-month course of 0.5 mg/kg prednisolone, and cytological findings. Immunophenotyping which resulted in decreased dyspnea on exertion showed a predominance of CD8 T lymphocytes and complete resolution of the skin lesions, (CD4/CD8 ratio = 0.68) and B lymphocytes (20%). although there was only slight improvement in The inorganic fraction showed no asbestos bodies radiological findings and in DLCO. and was sent for determination of the levels of The concomitant diagnosis of late-onset hard metals and silicates by inductively coupled primary SS, established in accordance with the plasma-atomic emission spectrometry. This study criteria proposed by the European American J Bras Pneumol. 2014;40(1):92-95 Mixed pneumoconiosis due to silicates and hard metals associated 93 with primary Sjögren’s syndrome due to silica A B C D E Figure 1 - Initial radiological findings. In A, chest X-ray showing a reticular interstitial pattern predominantly in the lower lung fields, already denoting some loss of volume. In B-E, CT scan showing septal thickening patterns, traction bronchiectasis, small areas of ground-glass opacity, and consolidation with a peribronchovascular distribution. Consensus Group, may be related to the long- Lung mineralogical analysis is useful in the term exposure to silica, which is in agreement etiological detection of particles in pneumoconiosis.(7) with the few existing reports in the literature. In the present case, the BAL fluid levels of silicates (1-3) In fact, it has been shown that intense and hard metals were determined by inductively exposure to silica can lead to the development coupled plasma-atomic emission spectrometry. of autoimmune processes, namely systemic This type of information makes it possible to sclerosis,(4) rheumatoid arthritis,(4) and primary document occupational exposure, which is often SS,(1-4) in a proportion of exposed workers. In mixed in nature, several decades after exposure was this context, alveolar lymphocytosis has been discontinued, assisting in the etiological identification correlated with pulmonary involvement in SS and of some occupational respiratory diseases.(9) Although with unfavorable prognosis.(5) In the present case, direct analysis of lung biopsy/autopsy specimens the finding of peribronchovascular lymphocytic is the most direct marker to determine particle infiltration with a significant proportion of B accumulation, BAL fluid analysis is simpler and lymphocytes may be related to parenchymal yields results that show good agreement with those infiltration attributable to SS. The correct exclusion obtained from tissue specimens.(9) However, biopsy is of lymphoma was essential. essential in cases in which the differential diagnosis The pneumoconiotic component, radiologically with sarcoidosis is required. expressed by inflammatory changes and fibrotic The hard metals most widely used in industry involvement, manifests histologically as a periseptal are tungsten carbide, molybdenum carbide, and and peribronchovascular fibroblastic reaction, as chromium carbide—cobalt and nickel being well as by the presence of macrophages with alloying elements—and they can induce antigen- anthracotic pigmentation and birefringent particles. specific immune responses in the lung as well The observed patterns of alveolar desquamation as innate immune responses characterized by and giant cell reaction are the ones that are inflammation and triggered by oxidative injury. typically seen in hard metal lung disease.(6-8) The (8) Of the elements detected in patient BAL fluid areas of diffuse pleural fibrosis are relatable to samples, silica, chromium, molybdenum, cobalt, exposure to asbestos. and zinc have all been associated with lung fibrosis Typical histology of parenchymal disease due or pneumoconiosis.(10) It is known, however, that to hard metals corresponds to the pattern of high concentrations of particles in tissues or interstitial fibrosis with giant cell reaction and body fluids indicate significant exposure but not foci of desquamative interstitial pneumonia with necessarily disease. Nevertheless, when used in or without bronchiolitis obliterans.(6-8) In some cases of heavy exposure and suggestive clinical, cases, there can be sarcoid features or only a radiological, and histological findings, such as the mixed-dust pneumoconiosis pattern. present case, determination of the levels of hard J Bras Pneumol. 2014;40(1):92-95 94 Ferreira PG, Ferreira AJ, Carvalho LM, Segorbe-Luís A A HE X 40 B HHF35 X 100 C HE X 400 D CD3 X 100 E CD 20 X 40 F CDS X 200 Figure 2 - Photomicrographs of histological sections of surgical lung biopsy specimens. In A, chronic inflammatory infiltrate and septal fibrosing reaction (H&E; magnification, ×40). In B, active fibroblastic foci (HHF35; magnification, ×100). In C, macrophages with anthracotic pigmentation and birefringent silica particles, as well as multinucleated giant cells along the bronchoalveolar axes and interlobular septa (HPX; magnification, ×400). In D, lymphocytic inflammatory infiltrate with T cells (CD3; magnification, ×100). In E, foci of B cells (CD20+) in the chronic inflammatory infiltrate (CD20; magnification, ×40). In F, predominance of T cells with a CD8 immunophenotype (CD8; magnification, ×200). metals is a valuable element in the diagnosis of Given the large number of workers involved, a less common types of pneumoconiosis, as well better understanding of the impacts of exposure as in the understanding of their pathogenesis.(7) to welding fumes on pulmonary function will J Bras Pneumol. 2014;40(1):92-95 Mixed pneumoconiosis due to silicates and hard metals associated 95 with primary Sjögren’s syndrome due to silica be important for the development of better syndrome in a dental technician. Rheumatology (Oxford). prevention strategies. 2003;42(10):1268-9. http://dx.doi.org/10.1093/ rheumatology/keg334 PMid:14508049 3. Kirwan JR. Out-patient workload. Rheumatology (Oxford). 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Scanning Microsc. 1989;3(4):1207-16; discussion 1. Puisieux F, Hachulla E, Brouillard M, Hatron PY, Devulder 1217-8. PMid:2561220 B. Silicosis and primary Gougerot-Sjögren syndrome 10. Selden A, Sahle W, Johansson L, Sorenson S, Persson [Article in French]. Rev Med Interne. 1994;15(9):575-9. B. Three cases of dental technician’s pneumoconiosis http://dx.doi.org/10.1016/S0248-8663(05)82502-0 related to cobalt-chromium-molybdenum dust exposure. 2. Astudillo L, Sailler L, Ecoiffier M, Giron J, Couret B, Chest. 1996;109(3):837-42. http://dx.doi.org/10.1378/ Arlet-Suau E. Exposure to silica and primary Sjögren’s chest.109.3.837 PMid:8617099 Submitted: 10 July 2013. Accepted, after review: 12 July 2013. J Bras Pneumol. 2014;40(1):92-95