An unusual case of Goodpasture's syndrome in a 26-year-old man with occupational exposure to hard metal dust is described. The patient developed a life-threatening interstitial lung disease that was followed by a rapidly progressive glomerulonephritis two months later. To our knowledge, association of Goodpasture's syndrome and hard metal exposure has not been reported previously.
Goodpasture's syndrome is characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis. It has been observed after exposure to various inhalants, mostly hydrocarbons.
We describe the case of a patient exposed to hard metal dust, in whom antiglomerular basement membrane antibody-mediated Goodpasture's syndrome developed. Hard metal is an alloy of inert tungsten carbide and cobalt, which is considered the causative agent in hard metal lung disease.
A 26-year-old man of previous good health was referred to our hospital because of fever and increasing dyspnea. The last three years before hospital admission, he had been working in a metallurgical plant processing high-melting alloys, mostly hard metal. Laboratory tests showed a marked leukocytosis of 27.500/[mu]l, mild elevation of liver enzyme values, and a microhematuria. The complement fraction C4 was significantly lowered to 0.06 g/L, C3 was in the normal range. The patient's chest roentgenogram showed a barely visible bilateral micronodular pattern that contrasted with the massive compromise of respiratory function.
Treatment with high-dose steroids, imipenem, and erythromycin led to quick improvement of respiratory function. Bronchoalveolar lavage (BAL) was performed and revealed a massive increase in neutrophils, but no pathogenic microorganisms were identified, and cultures from BAL fluid remained sterile. Repeated BAL 12 days later revealed an unremarkable cell pattern and normal lymphocyte subpopulations. Many alveolar macrophages contained both iron-positive and iron-negative, coarse granular inclusions. Scanning electron microscopy, including energy dispersive x-ray spectroscopy, showed high amounts of tungsten in these dust granules, whereas cobalt could not be identified (Fig. 1). BAL fluid examined by atomic absorption spectroscopy was negative for cobalt. A transbronchial biopsy specimen showed a slightly increased desquamation of pigment-laden alveolar macrophages in otherwise normal lung parenchyma.
The patient continued receiving low-dose steroid therapy and remained in stable health for the next two months and did not return to his workplace. Macrohematuria preceded by occasional hemoptyses prompted readmission to the hospital. The chest roentgenogram was unremarkable, and laboratory tests revealed a creatinine concentration of 262.5 [mu]mol.L (2.97 mg/dl). A kidney biopsy was performed and showed extracapillary and intracapillary glomerulonephritis with linear deposits of IgG and complement C3 along the glomerular basement membrane (GBM). A diagnosis of rapidly progressive glomerulonephritis was made and confirmed by the detection of anti-GBM antibodies of the IgG subclass. C4 was markedly reduced to 0.054 g/L (control value, 0.095 g/L). The phenotyping of complement fraction C4 revealed a heterozygous C4A deficiency (C4A3, C4AQ0, C4B1, C4B2). Plasmapheresis and immunosuppressive therapy with cyclophosphamide and steroids led to prompt recovery, and the patient's renal and pulmonary function remained stable during the following 12 months.
Occupational exposure to hard metal can lead to a wide spectrum of pulmonary diseases, including occupational asthma, desquamative or giant cell interstitial pneumonitis, and diffuse interstitial fibrosis. The demonstration of tungsten particles in the lung can be taken as evidence for exposure to hard metal dust. Tungsten carbide itself is probably inert, and cobalt is regarded as the causative agent in hard metal lung disease. Due to its high solubility in body fluids, it is found only infrequently in clinical specimens. In our patient's disease, cobalt might have played a pathogenetic role through various mechanisms of action. On one hand, it might interfere with normal immunoregulation. The induction of a polyclonal B-cell activation has been demonstrated for the metal salt mercuric chloride, causing anti-GBM disease in rats. Alternatively, hard metal dust-induced tissue damage might expose pulmonary basement membrane antigens, with subsequent antibody formation, or allow the binding of otherwise sequestered anti-GBM antibodies in the lung. This mode of action has been demonstrated for hydrocarbons in experimental anti-basement membrane disease of the lung.
Although serologic and immunohistologic findings were clearly diagnostic of Goodpasture's syndrome, the clinical presentation in our patient was atypical. A reason for this might have been the patient's heterozygous C4A deficiency with very low C4 levels not expected in a patient with this phenotype. The binding of complement along the basement membrane and its activation via the classic pathway probably is of importance for the development of parenchymal damage in Goodpasture's syndrome. In contrast to C4B, which preferentially binds to cell surfaces, C4A has higher affinities for immune complexes and antibodies. Thus, the C4A deficiency, resulting in reduced C4 binding along the GBM, might have attenuated the course of glomerulonephritis.
Although the causative role of hard metal exposure for the development of Goodpasture's syndrome in our patient cannot be proved conclusively, the case illustrates the potential complex interrelations among autoimmune disease, immune defects, and exposure to substances with possible antigenic properties.
 Beirne GJ, Brennan JT. Glomerulonephritis associated with exposure to hydrocarbons mediated by antibodies to glomerular basement membrane. Arch Environ Health 1972; 25:365-69
 Sjogren I, Hillerdal G, Anderson A, Zetterstrom O. Hard metal lung disease: importance of cobalt in coolants. Thorax 1980; 35:653-59
 Davidson AG, Haslam PL, Corrin B, Coutts II, Dewar A, Riding WD, et al. Interstitial lung disease and asthma in hard-metal workers: bronchoalveolar lavage, ultrastructural, and analytical findings and results of bronchial provocation tests. Thorax 1983; 38:119-28
 Sapin C, Druet E, Druet P. Induction of anti-glomerular basement membrane antibodies in the Brown-Norway rat by mercuric chloride. Clin Exp Immunol 1977; 28:173-79
 Yamamoto T, Wilson CB. Binding of anti-basement membrane antibody to alveolar basement membrane after intratracheal gasoline installation in rabbits. Am J Pathol 1987; 126:497-505
 Law SKA, Dodds AW, Porter RR. A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. EMBO J 1984; 3:1819-23
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