Occupational Medicine 2007;57:221–224 Published online 22 January 2007 doi:10.1093/occmed/kql162
CASE REPORT
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Pulmonary alveolar proteinosis induced by silica dust? Riitta Sauni1, R. Ja¨rvenpa¨a¨2, E. Iivonen3, S. Nevalainen4 and J. Uitti1 ...................................................................................................................................................................................
Abstract
Pulmonary alveolar proteinosis (PAP) is a rare disease, with several aetiologies. This study reports the first Finnish case of PAP with possible induction by silica dust. A 58-year-old male patient had a documented history of heavy exposure to silica dust over a long period, although he himself considered the exposure to be low. The patient’s cumulative exposure to silica dust was 10 mg mÿ3 years according to the workplace measurements. The patient developed classical symptoms and signs of PAP that closely mimicked those of acute silicosis, but he did not have any signs of classic silicosis. We conclude that significant chronic exposure to silica favours the diagnosis of PAP rather than acute silicosis in this case. PAP should be taken into account when patients exposed to silica dust complain of respiratory symptoms. A patient’s assessment of his/her exposure to silica may not always be reliable.
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Key words
Acute silicosis; exposure; lung disease; occupational disease; pulmonary alveolar proteinosis; silica.
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Introduction Pulmonary alveolar proteinosis (PAP) is an uncommon disease that was first described in 1958 [1]. Typical symptoms are shortness of breath and dry cough. Histologically, there is granular eosinophilic material in the alveoli that stains intensively with periodic acid Schiff. A primary (idiopathic) PAP can be distinguished from a secondary PAP. The latter has been related to infections [2], malignant haematological diseases [3], immunodeficiency disorders [4,5] and exposure to chemicals and inorganic dusts like silica or cement dust, cellulose fibres, combustion products of plastics [6], aluminium and titanium oxide [7–10]. The rareness of PAP makes it impossible to study it in depth with epidemiologic methods, and no dose–response estimates are available in relation to, for example, silica exposure. The clinical picture of PAP closely resembles that of acute silicosis, but so far the two have been considered separate diseases [11,12]. Acute silicosis develops after exposure to high 1
Finnish Institute of Occupational Health, Tampere, Finland and Clinic of Occupational Medicine, Tampere University Hospital, Tampere, Finland.
2
Department of Diagnostic Radiology, Tampere University Hospital, Tampere, Finland.
3
Department of Pulmonary Diseases, Tampere University Hospital, Tampere, Finland.
4
Suomen Terveystalo Group, Lahti, Finland.
Correspondence to: Riitta Sauni, Finnish Institute of Occupational Health, PO Box 486, 33101 Tampere, Finland. Tel: 1358 30 474 8650; fax: 1358 30 474 8605; e-mail:
[email protected]
concentrations of respirable crystalline silica within 5 years. It seems that, in the scientific literature, the distinction between PAP and acute silicosis has not always been clear. Previous cases of PAP in association with silica exposure have been described as silicoproteinosis, a feature that has also been shown to be related to acute silicosis [13–15]. This study reports a case of a drilling machine technician whose unusually long-lasting exposure to silica dust without peaks of exposure supports the diagnosis of PAP rather than acute silicosis, and it also presents estimations of the exposure.
Clinical history The patient was a 58-year-old man who had suffered from arterial hypertension and ulcerative colitis. He neither had previous history of any lung disease nor had ever smoked. He had worked as a drilling machine technician in mines for 35 years. In the spring of 2005, he started to experience shortness of breath on exertion. The chest radiograph was abnormal and suggestive of lung fibrosis (Figure 1). High-resolution computed tomography (HRCT) showed both ground-glass opacification and abundant reticular interstitial infiltrate (Figure 2). The lung function measurements indicated mild restriction: forced vital capacity (FVC) 3.40 l (72% of predicted), forced expiratory volume in 1 s (FEV1) 2.89 l (76% of predicted) and FEV% 80 (85% of predicted). The diffusing capacity of the lungs was significantly reduced, diffusing capacity (DL, CO) being 31% and transfer coefficient
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formed for both lungs. Thereafter, the symptoms improved to some extent, and the patient could manage without oxygen therapy. No other predisposing factors for PAP than silica dust exposure could be determined.
Occupational history and exposure
Figure 1. A chest radiograph of the patient at the time of diagnosis showing bilateral reticular pulmonary infiltrates.
Exposure to fine silica dust is difficult to evaluate without quantitative measurements at the worksite. Such measurements had been conducted over the years in the mines where our patient worked. The patient had worked for 70% of his working time in mines in which the concentration of silica dust had been 0.13–0.18 mg mÿ3 depending on the working site. The other 30% of his working time had been spent doing test drillings either in underground (one-third of the time) or in open air (two-thirds of the time). The silica dust concentration during the underground drilling had been 0.21 mg mÿ3, and in open air it had been 1.04 mg mÿ3. The silica measurements are static samples that reflect the minimum exposure level of all the workers in that site. The exposure of those workers who take part in, for example, drilling is probably remarkably higher. On the basis of the static samples, the cumulative exposure to silica dust can be approximated to be 10 mg mÿ3 years, indicating heavy exposure. According to the patient himself, the silica exposure was relatively low.
Discussion
Figure 2. A HRCT image of the patient showing ground-glass opacification and abundant reticular interstitial infiltrate.
of the lung (KCO) being 50% of the predicted value. The blood gas analysis showed hypoxia (PaO2 6.9, PaCO2 3.9, pH 7.44). The haemoglobin concentration was 20.3 g dlÿ1, but the infection parameters were normal. The antibodies to HIV were negative. The general status of the patient was good. Inspiratory crackles were heard in both lungs. Bronchoalveolar lavage (BAL) was performed through bronchoscopy. The macroscopic appearance of the lavage fluid was milk-like. The microscopic analysis revealed abundant amorphous material with crystalline structures. The total cell count was elevated, as was the lymphocyte count. Among the amorphous material were rounded particles that stained positively with periodic acid Schiff. A therapeutic lavage was per-
The gold standard for the diagnosis of PAP has been open-lung biopsy. However, nowadays, BAL alone is sufficient to diagnose most cases of PAP [16]. The BAL findings of our patient were typical of PAP, as were the radiographic findings (Figures 1 and 2). We found no other known aetiological reason for PAP than occupational exposure, primarily to silica dust. However, the possibility of idiopathic PAP and concomitant exposure to silica dust cannot be ruled out in a study of a single case such as this. The clinical picture of PAP resembles closely that of acute silicosis [11,12,17]. Acute silicosis develops after exposure to high concentrations of respirable crystalline silica within a period ranging from a few weeks to 5 years after the initial exposure and in its classical form it is fatal [18–20]. In our case, the exposure to silica dust had continued much longer, for 35 years before the first respiratory symptoms. Although the exposure levels of silica were considered high, to our knowledge, there were no extraordinary high peak exposures. This opinion is based on the statements of the patient and the management of the mine. There are no continuous monitoring results of silica dust levels available. The unusually long time and the even level of exposure to silica do not support the diagnosis of acute silicosis.
R. SAUNI ET AL.: PULMONARY ALVEOLAR PROTEINOSIS 223
However, this case raises an interesting question, whether acute silicosis and silica-induced PAP can be variants of the same disease. The common symptoms of both PAP and acute silicosis include progressive dyspnoea, cough, crackles, weight loss, fever, clubbing, cyanosis and chest pain [1,11,16]. The histopathology, including the filling of alveoli with phospholipids and proteins, and radiological findings are very similar in both diseases. In chest radiographs, bilateral, symmetric alveolar filling patterns with perihilar infiltrates are commonly seen [21,22]. HRCT shows reticular, reticonodular and ground-glass opacities [22–24]. The relationship between silica dust exposure and a PAP-like disease has been documented in several studies. Exposure to silica dust has induced changes in the lungs of rats and mice that resemble the histological features of PAP in humans [25,26]. As early as the 1930s, an acute type of silicosis was described [13] that resembled PAP histologically. It was related to heavy exposure to silica over a relatively short period of time, and it was called silicoproteinosis [8,9,14]. We have found three publications about PAP due to occupational silica exposure. One of these concerned a US cement truck driver [27], one involved a US sandblaster [7] and the third discussed a French ceramics worker [28]. It is hard to deduce the model of silica exposure needed for PAP from these cases. There is conflicting evidence as to whether silicotic nodules are present in patients with silica-induced PAP [9,14,15,28]. In a study of 13 PAP cases [29], two showed both silicosis and PAP radiologically. The chest radiograph or HRCT of our patient did not show any signs of chronic silicosis, although there was a long history of extensive silica dust exposure. It is possible that chronic silicosis and PAP have different pathogenetic mechanisms. It has been suggested that silica dust may mechanically irritate Type II pneumocytes and provoke an excessive discharge of surfactant and associated lipids without the fibrogenic effect that is essential in chronic silicosis [30]. The National Institute for Occupational Safety and Health (NIOSH) in the USA recommends an exposure limit of 0.05 mg mÿ3 for respirable crystalline silica as a time-weighted average for up to a 10-h workday during a 40-h workweek to reduce the health risks of silica [31]. The NIOSH hazard review of silica also mentions PAP as one possible adverse health effect of silica in addition to silicosis and lung cancer. In Finland, the exposure limit for respirable crystalline silica is 0.2 mg mÿ3 although this limit is under discussion. Studies show that the risk of silicosis and lung cancer is increased when the concentration of silica dust increases. The silica dust concentration of our patient’s worksite varied from 0.13 mg mÿ3 to 1.04 mg mÿ3. However, the patient himself evaluated the amount of dust as being relatively low. It is possible that respirable crystalline silica, which includes particles with aerodynamic diameters of less than 10 mm, is partly invisible and may lead to an underestimation of the health
risks and to a worker neglecting the use of respiratory protection. Although PAP is a rare pulmonary disease, it should be taken into account when patients exposed to silica dust complain of chest tightness and cough and when there are typical signs of PAP radiologically. It is also noteworthy that the self-estimation of silica dust exposure of patients may not always be reliable. Exposure to silica should be controlled with industrial hygiene measures and kept as low as possible, respiratory protection being used when necessary.
Conflicts of interest None declared.
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