Continuing Education Activity

Caplan syndrome was first described in 1953 by Dr. Anthony Caplan, a provider on the Cardiff pneumoconiosis panel, as radiologic evidence of intrapulmonary nodules in coal miners with a diagnosis of rheumatoid arthritis (RA). It is also called rheumatoid pneumoconiosis. This activity reviews the evaluation and management of Caplan syndrome and highlights the role of the interprofessional team in evaluating and improving care for patients with this condition.

Objectives:

• Describe the pathophysiology of Caplan syndrome.
• Review the presentation of Caplan syndrome.
• Summarize the treatment options for Caplan syndrome.
• Explain modalities to improve care coordination among interprofessional team members in order to improve outcomes for patients affected by Caplan syndrome.

Introduction

Caplan syndrome was first described in 1953 by Dr. Anthony Caplan, a provider on the Cardiff pneumoconiosis panel, as radiologic evidence of intrapulmonary nodules in coal miners with a diagnosis of rheumatoid arthritis (RA).[1] It is also called rheumatoid pneumoconiosis. It is a combination of rheumatoid arthritis and pneumoconiosis that manifests as intrapulmonary nodules, which appear well-defined and homogenous on chest x-ray. It is defined as lung nodules in dust-exposed personnel, either with a history of rheumatoid arthritis or develops RA after 5-10 years. There are multiple nodules varying in size from 0.5 to 5 centimeters. The nodules may grow, remain unchanged, disappear, and then reappear. These nodules can cavitate, calcify or develop air-fluid levels.

Etiology

Caplan syndrome is caused by work exposure to coal, asbestos, or silica which causes pneumoconiosis, an inflammatory reactive lung condition to dust particles, in patients with a rheumatoid arthritis diagnosis. There is probably a genetic predisposition as well and smoking is believed to aggravate these lung findings.[2][3]

Epidemiology

The reported incidence of Caplan syndrome is 1 in every 100,000 people, with a decline in incidence due to a decrease in exposure to coal, asbestos, and silica material. Silica exposure in particular is related to higher prevalence. The first epidemiologic study undertaken by the pneumoconiosis research unit observed an increased prevalence of rheumatoid arthritis (RA) among men with progressive massive fibrosis (PMF). Miall et al. found no increased prevalence of rheumatoid arthritis in miners when compared to a community where PMF and rheumatoid arthritis were prevalent and therefore concluded that the etiology of RA was not associated with exposure to dust or lung changes of complicated pneumoconiosis. There was a high prevalence rate of PMF and tuberculosis among miners and ex-miners with rheumatoid arthritis.[4][5]

Pathophysiology

An autoimmune condition is a phenomenon where one's body has inflammatory cells which attack its own tissue and, in the case of RA, the synovium. It is believed that in these patients, there is an alteration that causes the increased immune response to foreign materials in the lungs. There is immune hyperactivity that is sparked by silica in which monocytes and macrophages release cytokines such as interleukin-1 and granulocyte-macrophage-colony-stimulating factor and tumor necrosis factor-alpha. The sharp edges of the silica also cause lysis of lysosomal proteases in macrophages. Lymphocytes are activated by the cytokines released by macrophages. This all leads to an autoimmune phenomenon through exposure to silica which is triggered in genetically predisposed individuals who have RA.

Histopathology

Gough et al. made the first pathological study of the syndrome in 1955. He described it microscopically as a concentric arrangement of lighter and darker layers of the classical silicotic nodule with areas of grey and yellow. Gough suggested that the histological criteria for diagnosis are a central area of necrotic collagen, outside which a zone of active inflammation, consisting of a cellular array of macrophages and neutrophils present.

History and Physical

Caplan syndrome presents with cough and shortness of breath, along with symptoms of rheumatoid arthritis such as prolonged morning stiffness, with symmetric arthritis in a systemic fashion. Physical examination typically shows rheumatoid arthritis findings for joints that are swollen, tender metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, along with possible pulmonary findings such as wheeze, and crackles that do not change the character on coughing signifying fibrosis.

Evaluation

The findings of this syndrome consist of rheumatoid nodules in the lungs noted as rounded opacities 0.5 to 5 centimeters which may cavitate and resemble tuberculosis on chest radiology. The opacities can differ in size, varying from small opacities which appear as simple pneumoconiosis, and very large opacities which can appear as progressive massive fibrosis. There may be accompanying pleural effusion. Usually, the opacities coincide with the onset of arthritis, but there are reported cases where arthritis developed about 6 to 10 years before the lung lesions. Lung function tests may reveal a mixed restrictive and obstructive picture with a total loss of lung volume along with the reduced diffusing capacity of the lungs for carbon monoxide. Complete serum studies for rheumatoid factor; antinuclear antibodies may be present. Silicosis, asbestosis, and tuberculosis should always be in the differential.[6][7][8][9]

Treatment / Management

Caplan syndrome does not require treatment, and management should be focused on treating the extrapulmonary manifestations of rheumatoid arthritis. Previous studies involving the treatment of lung lesions from this condition were disappointing as the assumption was made that the tubercle bacillus was a possible etiological factor in the causation of the lung lesions, and anti-tuberculous medications were given. In such cases, there is no obvious benefit. Once tuberculosis is excluded, treatment with steroids can be started. Exposure to coal dust must be stopped along with other lung toxin exposures such as smoking. The RA should be treated per guidelines with disease-modifying antirheumatic drugs.

Differential Diagnosis

Asbestosis and silicosis are the two major differentials for Caplan syndrome. An asbestosis is a form of pneumoconiosis that presents in patients with chronic inhalation of a cumulative dose of inhaled asbestos fibers. The asbestos fibers are fibrogenic to the lungs, causing lung nodules that may appear similar to the radiologic imaging for Caplan syndrome. The difference is these patients have known exposure to asbestos inhalation such as with products containing asbestos cement-like pipes, shingles, clapboard, sheets, vinyl-asbestos floor tiles, asbestos paper in filtering and insulating products, brake linings, clutch facings, textile products such as yarn, felt tape, cord, rope, and spray products used for acoustic, thermal, and fireproofing purposes. Silicosis is similar to the pathogenesis of asbestos and is usually associated with workers in the sandblasting industry.

Other Differentials for Multiple Cavitary Pulmonary Nodules

1. Neoplasm
2. Granulomatous infection with bacteria, fungi, mycobacteria, Nocardia, or parasite
3. Inflammatory such as granulomatosis with polyangiitis, Langerhans cell histiocytosis, sarcoidosis
4. Vascular such as pulmonary embolism with infarction
5. Developmental such as congenital pulmonary airway malformation, pulmonary sequestration
6. Drug toxicities with amiodarone, infliximab, bleomycin, carbamazepine
7. Amyloidosis

Prognosis

The prognosis of this Caplan syndrome depends on risk exposure and is similar to rheumatoid arthritis, except when the lung disease has progressed to an irreversible fibrosis stage. For the most part, the prognosis rarely causes disability due to lung problems because of standardized guidelines and treatments available to rheumatoid arthritis patients.

Complications

In some severe cases, the Caplan syndrome can progress to a more severe stage involving irreversible fibrosis stage. The patients typically will present with restrictive lung disease and symptoms of chronic shortness of breath and cough. More intensive treatment options should be considered in such severe cases along with transplant options.

Consultations

Management of Caplan syndrome requires teamwork between different specialties. Following consultations are needed to improve outcomes.

• Pulmonologist
• Radiologist
• Rheumatologist
• Pathologist

Deterrence and Patient Education

Patients who are diagnosed with pneumoconiosis should be advised to change their profession and move to a dust-free profession. While people who are working in coal mines, stone crushing, sandblaster, or such industries in which they are exposed to inorganic dust, should get regular check-ups, lung function testing, and chest X-rays every 1-3 years. Encourage smoking cessation to all miners who smoke.

Pearls and Other Issues

Several case reports for Caplan syndrome, pulmonary function tests typically have shown mild airway obstruction. Constantinides et al. had a retrospective study and compared 24 patients with Caplan syndrome and 36 patients with progressive massive fibrosis, suggesting an overlap in pulmonary function tests. Caplan syndrome had less airflow obstruction compared to progressive massive fibrosis patients, without differences with respect to lung volumes and diffusion capacity. This study was adjusted for age, mining exposure, and smoking.

Enhancing Healthcare Team Outcomes

The diagnosis and management of Caplan syndrome are best done with an interprofessional team that includes the primary care provider, nurse practitioner, pulmonologist, radiologist, and pathologist. The majority of patients first come to attention at outpatient clinics where they may complain of dyspnea or joint pains. The diagnosis can be difficult but the condition does not require any specific treatment. The treatment is focused on treating the extrapulmonary manifestations of rheumatoid arthritis.

Exposure to coal dust must be stopped along with other lung toxin exposures such as smoking. The RA should be treated per guidelines with disease-modifying antirheumatic drugs.

The prognosis for patients with Caplan syndrome is guarded; those with mild disease do not have reduced life expectancy, but those with severe disease may develop lung fibrosis which can be debilitating.[10] (Level V)