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Silicosis associated with systemic lupus erythematosus

Abstract

The hypothesis that exposure to silica might be associated with a wide range of autoimmune diseases including SLE (Systemic Lupus Erythematosus) has been discussed over the last decade, but only few cases of silicosis and SLE were described in the literature. We report the case of a male patient in his fifth decade of life, with previous exposure to silica, who worked as a well digger for ten years. The patient’s clinical picture started with articular symptoms, sporadic peaks of fever, anemia, positive anti-nuclear factor, peripheral (1/10) and homogeneous (1/500) standard, and productive cough. Computed tomography of the chest showed a diffuse interstitial process, bilateral nodules, para-aortic and para-tracheal hilar calcifications, compatible with pulmonary and ganglial silicosis. He developed acute respiratory distress syndrome (ARDS) and died.

Systemic lupus erythematosus; Silicosis; Pneumoconiosis; Autoimmune diseases


CASE REPORT

Silicosis associated with systemic lupus erythematosus* * Study performed at Getulio Vargas Hospital, Universidade Federal do Piauí – UFPI.

Shirley Castro HolandaI; Maria do Socorro T.M. AlmeidaII; Antônio de Deus FilhoIII

IGeneral Medicine Resident Physician, 2nd year

IIRheumatology Associate Professor, General Medicine Department

IIIPneumology Associate Professor, General Medicine Department. Specialist by The Brazilian Society for Pneumology and Tysiology.

Correspondence Correspondence to Shirley Castro Holanda Rua Miguel Arcoverde, 191, Bl. D, apto. 102 64046-170 – Teresina, PI Tel. (86) 233-9401 e-mail: shirleyh@uol.com.br

ABSTRACT

The hypothesis that exposure to silica might be associated with a wide range of autoimmune diseases including SLE (Systemic Lupus Erythematosus) has been discussed over the last decade, but only few cases of silicosis and SLE were described in the literature. We report the case of a male patient in his fifth decade of life, with previous exposure to silica, who worked as a well digger for ten years. The patient’s clinical picture started with articular symptoms, sporadic peaks of fever, anemia, positive anti-nuclear factor, peripheral (1/10) and homogeneous (1/500) standard, and productive cough. Computed tomography of the chest showed a diffuse interstitial process, bilateral nodules, para-aortic and para-tracheal hilar calcifications, compatible with pulmonary and ganglial silicosis. He developed acute respiratory distress syndrome (ARDS) and died.

Key words: Systemic lupus erythematosus. Silicosis. Pneumoconiosis. Autoimmune diseases

Acronyms and abbreviations used in this paper

SLE – Systemic lupus erythematosus

RA – Rheumatoid arthritis

PSS – Progressive Systemic Sclerosis

ACR – American College of Rheumatism

SiO2 – Silicium dioxide

ANF – Anti-nuclear factor

IL-1 – Interleukin 1

a-TNF –Alfa tumor necrosis factor

b-TGF –Beta Tumor growing factor

ILO – International Labor Office

ARDS – Acute respiratory distress syndrome

Introduction

Silicosis is a chronic interstitial pulmonary disease resulting from inhalation of free silica (SiO2) particles. Several recent studies have suggested a possible relationship between occupational exposure to crystalline silica dust and some autoimmune diseases. These include rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), vasculitis with renal impairment (Wegener’s granulomatosis), haemolytic anemia, dermatomiositis, Sjögren syndrome, Graves’ disease, and systemic lupus erythematosus (SLE).(1-3) Silicosis is sometimes associated to peripheral (humoral and cellular) blood abnormalities, including a positive antinuclear factor (ANF) and rheumatoid factor (RF), serum hyper gamma globulin (particularly IgA and IgG), and T-lymphocyte changes (T helper and T suppressor).(4)

Mechanisms responsible for the association of occupational exposure to silica and autoimmune diseases are not yet well established.(5) Some studies show that SLE is more frequently diagnosed in silicosis patients than in those hospitalized with other disorders (2,3) but few reports are available about this association.

It is possible that certain autoimmune diseases may predispose some individuals exposed to silica to the development of silicosis. However, it is difficult to establish a relationship in view of the chronic nature of both diseases.(3)

This report describes a case of SLE associated to pulmonary silicosis in a male patient who developed SLE at about 40 years of age.

Case report

This is the case of a male, mulatto, 40 year old patient. He was a bricklayer’s assistant, born and resident in Teresina-PI, with a history of previous silica exposure for a 10 year period during which he was intermittently a well digger. Since it was not a full time occupation, real exposure time was approximately 900 days (number of wells dug x average digging time). He presented with a clinical picture of inflammatory signs and functional limitation of the right knee in addition to sporadic fever. Joint involvement increased with the left knee and metacarpophalangeal and interphalangeal joints also being affected. At physical examination the patient was pale (++/+4), eupneic, (RR = 18) BP = 140 x 90 mmHg. Pulmonary auscultation disclosed rude vesicular murmur with fine crackles in the pulmonary lower lobes, abdomen was normal. On the third day in-hospital he developed tachydyspnea (RR = 34), and hypotension BP = 90 x 60 mmHg. Pulmonary auscultation showed a rude vesicular murmur with fine crackles mainly in the right pulmonary lower lobe. Lab tests: Ht = 33%; Hb = 10.8 g/dL; white blood cells = 2,300/mm3 (band forms – 64%; segmented – 32%; eosinophils – 0%; lymphocites – 4%; monocites – 0%); normal platelet count; HSV at the 1st hour: 120 mm; positive antinuclear factor (ANF), with peripheral (1/10) and homogenous (1/500) pattern; X-ray of joints involved: normal; O2Sat = 88.9%. CT scan of the chest (Figures 1 and 2) showed diffuse interstitial fibrosis, bilaterally calcified nodes in the hilar, para-aortic, and para-tracheal regions, compatible with chronic pulmonary and nodal silicosis. The patient remained at the intensive care unit for seven days due to pneumonia associated with respiratory failure and ceftriaxone was administered. Upon return to the ward he was given corticosteroids and discharged in an improved condition for out-patient follow-up.



Eight months after discharge, he was readmitted to the hospital with dry cough, fever, ventilation-dependent chest pain and anorexia. At physical examination he was pale (++/+4), dehydrated (+/+4), tachydyspneic (RR = 38 ), BP = 120 x 80mmHg. At pulmonary auscultation: fine crackles in the lower third of the right lung, with bilateral decreased pulmonary expansibility. Lab tests: Ht: = 46%; Hb = 15g/dL; white blood cells: 10,000mm3 (band forms – 2%; segmented – 69%; lymphocytes – 23%; monocytes – 6%; eosinophils – 0%); KB test in sputum (three samples) – negative; respiratory function test: highly restrictive disorder, with above normal flows; chest CT scan suggested a diffuse reticular-nodal interstitial infiltrate, bilateral parenchymal consolidation (Figure 3). Diagnosis of respiratory infection was reached and the patient developed an acute respiratory distress syndrome. He was submitted to mechanical ventilation, received antibiotic therapy (ceftriaxone and cyprofloxacin), but eventually died.


Discussion

Recent studies suggest a connection between prolonged exposure to silica and some connective tissue disorders.(1-3) In 1953, Caplan showed the relation between pulmonary disease in silicosis patients and rheumatoid arthritis (Caplan’s syndrome).(6) Erasmus, in 1957, described the association between silicosis and systemic progressive sclerosis, also known as Erasmus’ syndrome.(7) However, there are still few reports of SLE cases in patients with pulmonary silicosis.(5,8-10) A series of silicosis cases in association with connective tissue disease was described by Koeger et al (four patients with SLE and one patient with discoid lupus).(2) Sanchez-Roman et al described seven patients with SLE and one with cutaneous lupus.(1) A study of 300 workers at a company that used sand blasting identified 50 cases of silicosis, three were associated to SLE and five to mixed connective tissue disease. The three SLE cases had concurrent PSS.(1) In a study by Mehlhrn et al of 37 subjects who had been exposed to silica for many years, 30 were found to have silicosis. These authors suggest that silicosis may be associated with SLE due to a pathogenesis common to both diseases.(11) There are also some isolated reports in literature about the association of silicosis with SLE.(5,8-10)

The pathophysiology of pulmonary silicosis is well known. After being inhaled, silica particles may be found in the alveolar space, pulmonary tissue and lymphatic vessels. The alveolar and interstitial macrophages trap these particles and are thereafter activated, producing lisossomal agents, pro-inflammatory and pro-fibrotic cytokines such as interleukin 1 (IL-1), alpha tumor necrosis factor (a-TNF), beta tumor growth factor (b-TGF) and arachidonic acid metabolites.(12) Attempt of silica particles’ phagocytosis by the macrophages, the recruiting of various inflammatory cells and the development of fibrosis and granulomas may bring about a change in the pulmonary parenchymal structure which then progresses to fibrous pulmonary disease.(2,13) Different from the macrophage’s function in the course of the disease, little is known about the role of lymphocytes in silicosis and about the precise mechanism inducing development of autoimmune diseases.(14)

In our patient, the diagnosis of pulmonary silicosis was established because of the history of exposure to silica dust while digging wells and also to the changes in radiographs and CT scans compatible with pulmonary silicosis in accordance with the International Labor Office (ILO) guidelines.(15) Diagnosis of SLE was based upon clinical and laboratory findings according to criteria of the American College of Rheumatism (ACR).(16)

Presence of bilateral nodes and of para-aortic, para-tracheal and hilar calcifications observed at chest CT scan (Figures 1 and 2) are characteristic of pulmonary silicosis.

The systemic involvement by lupus was evident because of arthritis symptoms, haematology changes (anemia), fever, serositis (pleural effusion) and changes in laboratory results changes such as the positive ANF. Finding of a positive ANF in our patient suggests the presence of a lupus-like disease, since it meets the ACR criteria for SLE .It is estimated that prevalence of a positive ANF in silicosis patients ranges from 26 to 44%, even without clinical findings of SLE.(17)

Several occupational activities, such as well digging have been related to the occurrence of silicosis. The first cases of silicosis among well diggers were described in Piauí in 1984.(18) An aggravating aspect of this case is that in Piauí, 87% of the soil has a high free silica concentration and silica may be responsible for more than 96% of its mineral composition. Another difficulty is the digging process itself, in which the worker remains within a small area of 1.5 meter of diameter, therefore being exposed to a massive dust inhalation inside a limited and poorly ventilated space. In a study conducted in Piauí in 1999 with 103 well diggers, the authors found an incidence of pulmonary silicosis of 18.4%.(19) We conclude by highlighting the importance of the occupational history when treating patients with SLE or other autoimmune diseases, especially in males with associated pulmonary symptoms, since both diseases may be related. We also call attention to the need for adequate protection measures for workers such as well diggers exposed to silica dust. Further controlled studies are required for a better evaluation of an eventual interaction in the pathophysiology of silicosis and SLE.

Received for publication on 24/Feb/2003

Approved, after review on 26/May/2003

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  • 19. Deus Filho A, Lages JN, Gonçalves MER, Viana VPV, Mangueira RC. Silicose em cavadores de poços em tręs municípios da microrregiăo do Médio-Parnaíba-PI. Rev Assoc Saúde Públ Piauí 1999;2:194-9.
  • Correspondence to
    Shirley Castro Holanda
    Rua Miguel Arcoverde, 191, Bl. D, apto. 102
    64046-170 – Teresina, PI
    Tel. (86) 233-9401
    e-mail:
  • *
    Study performed at Getulio Vargas Hospital, Universidade Federal do Piauí – UFPI.
  • Publication Dates

    • Publication in this collection
      02 Dec 2003
    • Date of issue
      Aug 2003

    History

    • Received
      24 Feb 2003
    • Accepted
      26 Mar 2003
    Sociedade Brasileira de Pneumologia e Tisiologia Faculdade de Medicina da Universidade de São Paulo, Departamento de Patologia, Laboratório de Poluição Atmosférica, Av. Dr. Arnaldo, 455, 01246-903 São Paulo SP Brazil, Tel: +55 11 3060-9281 - São Paulo - SP - Brazil
    E-mail: jpneumo@terra.com.br