Diagnosis of perinuclear anti-neutrophil cytoplasmic antibody-associated microscopic polyangiitis in silicotics: case report
© Lee et al. 2016
Received: 7 October 2015
Accepted: 26 April 2016
Published: 14 May 2016
An association between silica exposure and autoimmune diseases including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis has been made.
A 56-year-old male presented with silicosis and had an occupational history of precious metal processing for 30 years and a 30 pack-year smoking history. The patient was diagnosed with pneumoconiosis and received compensation. No other complications were reported for pneumoconiosis. The patient suddenly presented with a non-specific headache for several days and microscopic hematuria was identified upon examination in the outpatient clinic. Following several weeks, the patient presented with aggravated dyspnea and hemoptysis, and his Modification of Diet in Renal Disease estimated glomerular filtration rate indicated acute kidney injury. Diagnostic analysis revealed perinuclear ANCA-associated microscopic polyangiitis (p-ANCA-associated MPA).
Exposure to silica dust was likely one of the cause of p-ANCA-associated MPA. Possible pathogenic mechanisms of autoimmune diseases in silicotics and emphasis of the necessity for early diagnosis are discussed.
KeywordsOccupational exposure Silicon dioxide Silicosis Autoimmune disease
Silica dust exposure and silicosis have been hypothesized to be associated with autoimmune diseases . Although a complete pathogenic mechanism is yet unknown, the increasing number of cases linking silica exposure and autoimmune diseases and the dose-dependent relationship between silica exposure and risk of autoimmune diseases  support the aforementioned hypothesis.
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis in silicotics is difficult to diagnose due to its non-specific clinical findings and need for pathological confirmation. Hemoptysis is a common clinical manifestation in both ANCA-associated vasculitis and simple or complicated pneumoconiosis with comorbid fungal ball infection. Furthermore, in such patients, hemoptysis may mimic pneumonia on a chest radiograph. Apart from these clinical similarities, there are several distinctions between the treatment of ANCA-associated vasculitis and pneumonia. ANCA-associated vasculitis requires immunosuppressive therapy, whereas pneumonia may be treated with antibiotics. Therefore, differential diagnosis is necessary.
Few cases of silicosis with ANCA-associated vasculitis, which is involved in both the lung and kidney, have been described. We report the case of a 56-year-old male with silicosis and perinuclear ANCA-associated microscopic polyangiitis (p-ANCA-associated MPA).
A 56-year-old male had a prior history of pneumoconiosis and an occupation history of precious metal processing for the previous 30 years. The patient had received Special Examinations for Pneumoconiosis in 2005. Pneumoconiosis was compensated by the Ministry of Employment and Labor and the Korea Workers’ Compensation and Welfare Service (COMWEL); however, the official complication for pneumoconiosis was not reported. A chest radiograph showed calcified pneumoconiotic nodules and bilateral nodular type q/q opacities and profusions of 3/3 in both lung fields, and was consistent with the diagnosis of pneumoconiosis in accordance with the International Labour Office (ILO) classification . The patient had a 30 pack-year history of smoking and had been treated for hypertension with nifedipine (120 mg).
The patient presented with a non-specific headache lasting for several days to the outpatient clinic of the Department of Occupational and Environmental Medicine. Blood urea nitrogen (BUN) and serum creatinine levels were 52.5 mg/dl and 4.69 mg/dl, respectively, and were elevated compared with previous values of 20.4 mg/dl for BUN and 1.16 mg/dl for serum creatinine. Microscopic hematuria was detected on urinalysis. The patient was referred to a nephrologist and a kidney sonogram was performed. Renal parenchymal disease affecting both kidneys and a left simple renal cyst of 1.2 cm in size were detected. A kidney biopsy was recommended by the nephrologist but was not undertaken due to the high medical cost.
Approximately 2 weeks following the last visit at the outpatient clinic, the patient was admitted to emergency complaining of aggravated dyspnea and massive hemoptysis. There was no history of fever, joint pain, or skin rashes.
Vital signs revealed an elevated systolic blood pressure of 230 mmHg, increased diastolic blood pressure of 160 mmHg, and a respiratory rate of 30–36 breaths per min. Initially, percutaneous oxygen saturation checked by a rescue worker was 44 %. Auscultation revealed coarse breathing sounds without wheezing throughout both lung fields. Analysis of arterial blood gases on room air showed a pH of 7.179, a PaCO2 of 36.0 mmHg, a PaO2 of 82.0 mmHg, a HCO3 of 12.9 mmol/l, and an O2 saturation of 92.9 %.
Laboratory findings revealed normocytic-normochromic anemia. The erythrocyte sedimentation rate (ESR) was found to be increased at 58 mm/h. Serum levels of high-sensitivity C-reactive protein (hs-CRP) and potassium were elevated (3.32 mg/dl and 7.2 mEq/l, respectively). A BUN level of 101 mg/dl and a serum creatinine level of 10.63 mg/dl were found. The Modification of Diet in Renal Disease estimated glomerular filtration rate (MDRD estimated GFR) was calculated to be 5.07 ml/min/1.73 m2 indicating acute kidney injury. Normal serum protein levels were detected. A routine urinalysis revealed a glucose level of 1+, more than 100 red blood cells per high power field, and proteinuria (3+).
We reported a case of p-ANCA-associated MPA that was diagnosed by renal biopsy in a patient with silicosis presenting with hemoptysis, hematuria, and acute kidney injury.
Silica dust exposure may be associated with an increased risk of autoimmune diseases including ANCA-associated vasculitis. Exposure to silica dust may contribute to some possible mechanisms of autoimmunity . First, silica dust may play a role in the production of autoantibodies. Second, silica induces anti-Fas autoantibody production that inhibits apoptosis of responder T cells in CD4 positive peripheral blood T cells. Third, increasing Fas expression in regulatory T cells (Treg), which regulate the activation of responder T cells, leads to apoptosis of Treg. The aforementioned possible mechanisms may induce an imbalance of T cells (responder T cells > Treg cells). Finally, dysregulation of autoimmunity results in complications of autoimmune disorders .
In cases with multiorgan involvement of the respiratory and renal systems, infectious, malignant, and autoimmune diseases should be considered in the differential diagnosis. In the present case, both infectious and malignant conditions were excluded; therefore, autoimmune diseases such as Wegener’s granulomatosis, Goodpasture syndrome, and systemic vasculitis were considered as a possible cause . Laboratory results showed increased p-ANCA levels, and pathological analysis suggested an ANCA-associated MPA. Finally, the patient was diagnosed with ANCA-associated MPA involving both the lung and kidney. As the treatment of ANCA-associated MPA involves immunosuppressive therapy and differs from that of infectious (antibiotics including anti-fungal or anti-bacterial agents) or malignant conditions (chemotherapy) , early diagnosis remains crucial. Fortunately, the patient presented here was discharged with a successful outcome.
ANCA-associated MPA, which is one of the most common ANCA-associated vasculitides involving both the lung and kidney, was previously diagnosed in a patient with silicosis . Therefore, in cases of silicosis with presenting symptoms of hemoptysis, hematuria, proteinuria, or renal failure, an early assessment for autoimmune disease, including ANCA-associated MPA, should be carefully considered to prevent end organ damage.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
blood urea nitrogen
Ministry of Employment and Labor and the Korea Workers’ Compensation and Welfare Service
erythrocyte sedimentation rate
glomerular filtration rate
high-sensitivity C-reactive protein
International Labour Office
low-dose chest computed tomography
Modification of Diet in Renal Disease
perinuclear anti-neutrophil cytoplasmic autoantibody
periodic acid-Schiff stain
regulatory T cells.
This study was supported by medical library of the Catholic university of Korea.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Hogan SL, Satterly KK, Dooley MA, Nachman PH, Jennette JC, Falk RJ. Silica exposure in anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and lupus nephritis. J Am Soc Nephrol. 2001;12:134–42.PubMedGoogle Scholar
- Hogan SL, Cooper GS, Savitz DA, Nylander-French LA, Parks CG, Chin H, et al. Association of silica exposure with anti-neutrophil cytoplasmic autoantibody small-vessel vasculitis: a population-based, case–control study. Clin J Am Soc Nephrol. 2007;2:290–9.View ArticlePubMedPubMed CentralGoogle Scholar
- International Labour Office. Guidelines for the Use of the ILO International Classification of Radiographs of Pneumoconioses, Revised edition 2011. Geneva: International Labour Office; 2011.Google Scholar
- Lee S, Matsuzaki H, Kumagai-Takei N, Yoshitome K, Maeda M, Chen Y, et al. Silica exposure and altered regulation of autoimmunity. Environ Health Prev Med. 2014;19:322–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Miller A, Chan M, Wiik A, Misbah SA, Luqmani RA. An approach to the diagnosis and management of systemic vasculitis. Clin Exp Immunol. 2010;160:143–60.View ArticlePubMedPubMed CentralGoogle Scholar
- Mansi IA, Opran A, Rosner F. ANCA-associated small-vessel vasculitis. Am Fam Physician. 2002;65:1615–20.PubMedGoogle Scholar