Caplan's Syndrome - Rheumatoid Pneumoconiosis

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Rheumatoid pneumoconiosis (Caplan's syndrome) with a classical presentation.

[Article in English, Portuguese]
De Capitani EM1, Schweller M, Silva CM, Metze K, Cerqueira EM, Bértolo MB.

Abstract

Although rare, rheumatoid pneumoconiosis, also known as Caplan's syndrome, can occur in workers exposed to silica, as well as in patients with silicosis, coal workers' pneumoconiosis or asbestosis. Prevalence is higher among patients with silicosis, despite the fact that it was originally described in coal workers with pneumoconiosis. The classical finding that defines this syndrome is that of rheumatoid nodules in the lungs, regardless of whether there are small rounded opacities suggestive of pneumoconiosis or large opacities consistent with massive pulmonary fibrosis, with or without clinical rheumatoid arthritis.
We describe the case of a female patient with rheumatoid arthritis, diagnosed 34 years after 7 years of occupational exposure to silica at a porcelain plant. A chest X-ray showed circular opacities of 1-5 cm in diameter, bilaterally distributed at the periphery of the lungs. A CT-guided thoracic punch biopsy of one of those nodules revealed that it was rheumatoid nodule surrounded by a palisade of macrophages, which is typical of Caplan's syndrome. Aspects of diagnosis, classification and occurrence of this syndrome are discussed, emphasizing the importance of the occupational anamnesis of patients with rheumatoid arthritis and lung opacities on chest X-rays.
PMID:
 
19820822
[PubMed - indexed for MEDLINE] 
Free full text
https://www.ncbi.nlm.nih.gov/pubmed/19820822



[Caplan's syndrome: rarely presenting as <<pulmorenal>> syndrome].

[Article in German]
Nowak A1, Göhner K2, Cohen CD3.

Abstract

in English, German

HISTORY AND ADMISSION FINDINGS:

A 59-year-old man complained about having dry cough for months and a recent sudden onset of minor hemoptoe, asymmetric arthritis, myalgia as well as lack of appetite. He presented an occupational history of 12-year exposure to an organic dust as uranium miner in German Democratic Republic followed by 21 years as heavy construction worker in Germany and in Switzerland. Laboratory work-up tested positive for microhematuria and anti-neutrophilic cytoplasmic antibodies (ANCA). Chest X-rays and CT scan showed bilaterally scattered nodules. Thoracoscopic wedge resection was performed, histopathological analysis revealed granuloma with central necrotic area containing black coal dust and silica depositions surrounded by histiocytes. The pulmonary opacities on X-ray and the typical histology in the light of significant dust exposure allow the diagnosis of a Caplan's syndrome.

TREATMENT AND COURSE:

The symptoms improved rapidly under steroid therapy. Further investigations revealed a clear renal cell carcinoma as a cause for the persistent microhematuria.

CONCLUSION:

Rheumatoid arthritis, pulmonary nodules and history of prolonged dust exposure are classical findings that define Caplan's syndrome. These patients present with different immunological phenomena - in our case ANCA-positivity without vasculitis. Interestingly, the renal cell carcinoma which led to the "pulmorenal" syndrome in our patient is another health problem overrepresented in uranium mine workers.

KEYWORDS:

Caplan's syndrome; Caplan-Syndrom; anti-neutrophile zytoplasmatische Antikörper; anti-neutrophilic cytoplasmic antibodies; rheumatoid pneumoconiosis; rheumatoide Pneumokoniose
PMID:
 
24568764
 
DOI:
 
10.1024/1661-8157/a001573
[PubMed - indexed for MEDLINE]                https://www.ncbi.nlm.nih.gov/pubmed/24568764









What to do with all of these lung nodules?

Dmitry Rozenberg, MD1,2 and Shane Shapera, MD1,2
Author information ► Copyright and License information ►

Abstract

Caplan syndrome is a rare entity that is specific to rheumatoid arthritis and presents with multiple, well-defined necrotic nodules in patients with occupational dust exposure. The present report describes a case of Caplan syndrome involving a 71-year-old man with a known diagnosis of seropositive rheumatoid arthritis who presented to the authors’ centre with a five-year history of multiple, bilateral cavitary lung nodules with mild dyspnea on exertion. He was an ex-smoker (30 pack-years) and had previously worked with silica. The case highlights the clinical, radiological and pathological features of this syndrome and outlines the importance of considering a broad differential in the management of pulmonary nodules, especially in patients with rheumatoid arthritis.
Keywords: Lung diseases, Nodules, Pneumoconiosis, Rheumatoid arthritis

Learning objectives

  • To recognize that Caplan syndrome is a rare pulmonary manifestation of rheumatoid arthritis (RA) found in patients with occupational dust exposure.
  • To be aware of the differential diagnosis and management of cavitary pulmonary nodules in Caplan syndrome.

CAN MEDS Competency: Medical Expert

Pretest

  • What is the classic clinical and radiological presentation of Caplan syndrome?
  • What is the differential diagnosis of cavitary pulmonary nodules in RA?
  • How do you treat Caplan syndrome?

CASE PRESENTATION

A 71-year-old man was referred to the authors’ facility with a five-year history of multiple, bilateral cavitary lung nodules. He was asymptomatic from a respiratory standpoint, with only mild dyspnea on exertion over the past six months, with no weight loss, cough or hemoptysis. The patient described a 10-year history of polyarthritis consistent with his known diagnosis of seropositive rheumatoid arthritis (RA). His RA was previously well controlled with methotrexate and leflunomide for several years. Four years before presenting to the authors’ centre, his medications were changed to azathioprine and prednisone, given the concern of multiple lung nodules (Figure 1A). He also had ischemic cardiomyopathy, atrial fibrillation, type 2 diabetes and gastroesophageal reflux disease.
Figure 1)
A Computed tomography scan (coronal view) demonstrating bilateral nodules in the upper lung zones (blue arrows) and calcified hilar lymphadenopathy (white arrows) five years before presentation. BComputed tomography scan (axial images) illustrating calcified ...
He was a retired construction worker who had significant exposure to rock dust as a result of rock drilling for 10 years and rock mining in graphite mines in the latter part of his career. He had no asbestos or sandblasting exposure. He was an ex-smoker (30 pack-year history) with no alcohol or recreational drug use. He described no tuberculosis exposures. His family history was noncontributory.
On examination, the patient appeared comfortable and in no respiratory distress. His cardiorespiratory examination was unremarkable aside from an oxygen saturation of 92% on room air. He had hand changes consistent with a diagnosis of RA with no digital clubbing. He had no subcutaneous nodules, rashes or joint swelling.
His pulmonary function tests demonstrated a mixed pattern with mild restriction (total lung capacity 5.0 L [70% predicted]) and post-bronchodilator obstruction (forced expiratory volume in 1 s [FEV1]/ forced vital capacity [FVC] ratio 0.67; FEV1 1.46L [45% of predicted]) with a moderate reduction in his diffusing capacity for carbon monoxide (DLCO) (47%). His vital capacity (VC) was 2.2 L (49%) and his residual volume 2.8 L (110%). His rheumatoid factor (>650 kIU/L) and anticitrullinated protein antibody (500 mg/L) were strongly positive; antinuclear antibody, extranuclear antigen panel and antinuclear cytoplasmic antibodies were negative; and erythrocyte sedimentation rate (73 mm/h) and C-reactive protein (77 mg/L) were moderately elevated. His echocardiogram had shown a left ventricular ejection fraction of 40%, with no evidence of pulmonary hypertension.
Chest imaging demonstrated stable calcified mediastinal and hilar lymphadenopathy with numerous parenchymal nodules and cavities, which had waxed and waned over the past five years (Figures 1A to 1C). Cultures from a spontaneous sputum sample (culture and sensitivity, acid-fast bacilli and fungal) were negative six months before presentation at the authors’ centre. Subsequently, bronchoscopy demonstrated normal anatomy, cytology and a second set of negative cultures (culture and sensitivity, acid-fast bacilli and fungal). A left-sided video-assisted thoracic surgical biopsy revealed multiple nodules with necrosis surrounded by dust, with areas of surrounding inflammation and fibroblastic response (Figures 2A and 2B). A diagnosis of Caplan syndrome was made.
Figure 2)
A High magnification (×100) view of a necrotic nodule (star marks area of necrosis) containing abundant dust particles (arrow). Hematoxylin and eosin stain. B High magnification (×100) view of mixed dust nodule, with abundant silicotic ...
His referring physicians were advised to continue with the current extrapulmonary RA management. Tiotropium was started for his concomitant airflow obstruction with improvement in his pulmonary function tests (total lung capacity 5.4 L [78% of predicted]; FEV1/FVC ratio 0.90; FEV1 2.2 L [70%]). His VC was 2.5 L (56%), residual volume 2.9 L (116%) and DLCO (58%). The nodules remain unchanged over one year of follow-up.

DISCUSSION

With a prevalence of approximately 1% in Canada (), RA has many pulmonary manifestations: necrobiotic nodules, interstitial disease, pleural abnormalities, bronchiolitis obliterans, vasculitis, drug-induced lung disease, upper airway disease, organizing pneumonia and Caplan syndrome (,).
The prevalence of nodules in RA is difficult to estimate. In two older case series of RA patients with 253 and 702 patients screened using chest x-ray, no nodules were identified (,). However, one study demonstrated pulmonary nodules to be quite common, found in 13 of 40 (32%) patients who underwent biopsy for suspected lung involvement (). Multiple cavitary pulmonary nodules can have malignant and benign etiologies, as outlined in Table 1.
TABLE 1
Differential for multiple cavitary pulmonary nodules
In the present case, malignancy and infection (including mycobacterium) was believed to be unlikely given the indolent course, normal sputum cultures, negative bronchoscopy and video-assisted thoracic surgical biopsy. A diagnosis of Caplan syndrome was made based on the diagnostic criteria of multiple, well-defined pulmonary nodules and inorganic dust exposure in a patient with RA (). An open-lung biopsy was not absolutely necessary, but was helpful to confirm this rare entity and exclude alternative diagnoses. Histopathology can be useful in patients without a diagnosis of RA because the nodules can precede the onset of RA symptoms.
Caplan () originally described this entity in 1953, having observed an increased prevalence of pulmonary manifestations in coal miners with RA who were exposed to mineral coal or silica dust. He observed well-defined rounded opacities 0.5 cm to 5 cm in size that were bilateral and predominantly peripheral on chest x-ray, a pattern different from progressive massive fibrosis (PMF), associated with coal worker’s pneumoconiosis. Although most cases of Caplan syndrome have been reported in coal workers, some have been in patients exposed to asbestos or free silica (,), as in our case.
The majority of the literature regarding Caplan syndrome was published before the advent of chest computed tomography (CT), with reliance entirely on chest x-rays. Although a few case reports have described using chest CT, it has not been helpful in distinguishing Caplan syndrome from simple silicotic nodules (,). However, CT imaging can be useful in recognizing other forms of RA-associated lung disease. Typically, radiological findings of Caplan syndrome include benign-appearing nodules that can coalesce, cavitate or calcify in the periphery of the lung (). Although uncommon, pulmonary complications can include pneumothorax, pleural effusions, hemoptysis and, most importantly, an increased prevalence of tuberculosis compared with other pneumoconioses (). A more comprehensive overview of the clinical and radiological presentations can be found in a review article by Schreiber et al ().
A few case reports have described pulmonary function tests in Caplan syndrome, which typically have shown mild airway obstruction (,). In the largest study to date, however, Constantinidis et al () retrospectively compared 24 patients with Caplan syndrome and 36 patients with PMF suggesting overlap in pulmonary function tests. When adjusted for age, smoking and mining exposure, patients with Caplan syndrome had less airflow obstruction than patients with PMF, but no other differences with respect to lung volumes and diffusion capacity were identified. In the present case, we speculate the reduced VC and DLCO could be due to the patient’s upper lobe cavitary fibrotic changes producing a physiological pattern of lung restriction that resembles mild PMF. There were no signs of diffuse interstitial lung disease, pulmonary vascular disease or history of diaphragmatic dysfunction.
There have been two pathologies described in Caplan syndrome, both illustrated in our case. The classic pattern initially described in 1955 has an area of central necrosis of the RA nodules surrounded by dust particles. This area is further surrounded by multiple inflammatory cells: neutrophils, macrophages and several giant cells (Figure 2A) (). The second pattern is the silicotic type, in which the nodules are smaller and contain the same features of a silicotic nodule, but maintain an outer ring of inflammatory cells that is different from a simple silicotic nodule (Figure 2B) (). The differential for these pathological findings includes RA nodules, silicotic nodules and coal worker’s pneumoconiosis ().
Despite numerous descriptions of the clinical features of Caplan syndrome, the pathogenesis and detailed understanding of the interactions between inhaled inorganic dusts and the immune response in patients with RA have not been defined. There is increasing evidence that silica inhalation can be associated with the development of auto-immune diseases such as RA, systemic sclerosis, systemic lupus erythematosus and antineutrophil cytoplasmic antibody vasculitis but its pathogenesis requires further study ().
The pulmonary manifestations of Caplan syndrome do not require any specific therapy unless rare complications develop such as infection or bronchopleural fistula (). In a few cases, the use of corticosteroids has been described in slowing the progression of rapidly growing nodules (). The role of tumour necrosis factor inhibitors in the treatment of Caplan syndrome is unknown, but worsening of RA nodules has been reported with tumour necrosis factor use (). Treatment should be focused on smoking cessation, limiting occupational exposure and controlling the extrapulmonary manifestations of the underlying RA.

SUMMARY

The present case demonstrates the classic historical, radiological and pathological features of Caplan syndrome, a rare entity. The case outlines the importance of considering a broad differential in the management of cavitary pulmonary nodules, especially in patients with RA. Given there is no specific therapy for Caplan syndrome, the focus should be on management of extrapulmonary RA.

Post-test:

  • What is the classic clinical and radiological presentation of Caplan syndrome?
  • Caplan syndrome can present in patients with RA and occupational dust exposure (usually coal) with minimal respiratory symptoms. Radiology demonstrates well-defined rounded opacities that are 0.5 cm to 5 cm in size that are bilateral and predominantly peripheral, and can cavitate and fluctuate over the years.
  • What is the differential diagnosis of cavitary pulmonary nodules in RA?
  • It is important to consider a broad differential in the work-up of cavitary pulmonary nodules (see Table 1) ensuring that malignancy and tuberculosis are excluded.
  • How do you treat Caplan syndrome?
  • Caplan syndrome does not require any particular treatment. The management should be focused on treating the extrapulmonary manifestations of RA.

Footnotes

DISCLOSURES: The authors have no financial disclosures or conflicts of interest to declare.

REFERENCES

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Articles from Canadian Respiratory Journal are provided here courtesy of Hindawi Publishing Corporation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128467/



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