Caplans syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S Javaria Anwer M.D.[2]

Caplan syndrome is known as Rheumatoid pneumoconiosis. This is a combination of Rheumatoid Arthritis and pneumoconiosis. It is a rare syndrome occurring mostly in miners exposed to silica, coal and asbestos. For the first time, Caplan, a British physician in 1953 first described this syndrome. It is hypothesized that silica get ingested by macrophages. Silica destroys the macrophages and again engulfed by another macrophage. This repeating process leads to chronic inflammation and fibrosis. Due to having the capability to move around, silica can travel to other organs away from lung and can induce autoantigens. Silica has an adjuvant effect on antibody production. In patients with silicosis , increased rheumatoid factor and antinuclear antibodies has been found. By producing TNF-α and Interleukin 1 , silica induces joint destruction. Silica also plays a role in inducing both innate and adaptive immunity. Patients with Caplan syndrome are mostly asymptomatic but in advanced stages dyspnea and cough might occur. In Caplan syndrome, increased inflammatory markers are found in serum study though there is no arthritis. Caplan syndrome with polyarthritis mostly positive for Anti citrullinated Peptide Antibodies (ACPA). Caplan nodules can appear with or before the onset of arthritis. In many cases miners have typical radiographic pictures of Caplan syndrome without any features of Rheumatoid Arthritis. Chest X ray findings of Caplan syndrome is characterized by well defined lung nodules of 0.5-5 cm throughout the lungs but predominantly in the peripheral areas. These nodules might appear as crops and later coalesce into a larger one. The onset of nodules are sudden, rapidly growing and can remain in the lungs for years longer. They might regress spontaneously unless get cavitated or calcified. Pleural effusion and pneumothorax are rare complications. CT scan findings are similar to chest x ray but provides more specific information such as mixed nodular infiltrative changes in lungs. But chest x ray or CT scan are not capable of differentiate between Caplan nodules and ordinary silicotic nodules. Biopsy is required to confirm the diagnosis. On histopathology, Caplan nodules show central necrosis similar to rheumatoid nodules except the presence of dust particles. Surrounding the dust ring there is a zone of inflammation consisting of granulocytes, macrophages and giant cells. This inflammatory zone is the distinguishable criteria of Caplan nodules from rheumatoid nodules. There is no definitive treatment for Caplan syndrome. Lung nodules in Caplan syndrome usually do not require any treatment until any complication develop. Disease modifying anti rheumatic drugs (DMARDs) can be used to treat Rheumatoid arthritis. But DMARDs have no role in treatment of pulmonary nodules. In some cases, corticosteroid found to be helpful to stop the progression of pulmonary nodules. Anti TNF therapy are commonly used in treatment of RA but recent study showed that Anti TNF therapy may induce pulmonary nodules. Anti TNF therapy play role in activating latent tuberculosis and silicosis increase the risk of tuberculosis infection . So, it is strongly recommended to screen for latent TB in the patients with Rheumatoid Pneumoconiosis. In irreversible pulmonary fibrosis lung transplant can be the ultimate choice.

In 1953, the chest x ray findings of multiple pulmonary nodules, in the coal miners with Rheumatoid Arthritis(RA) of Welsh, was described by Caplan. In 1940 and 1955, rheumatoid nodules were described in autopsy study of heart and lungs. An epidemiological study was conducted by Miall and associates in 1955 to determine the validity of Caplan syndrome. J. Gough reported the histological diagnostic findings for Caplan Syndrome in 1958.

Caplan Syndrome is known as Rheumatoid pneumoconiosis. In patients with rheumatoid arthritis, lungs show increased immune response to the foreign materials. In coal miners with RA, exposure to silica causes the release of different cytokines as interleukin-1,granulocyte colony stimulating factor and tumor necrosis factor-alpha by monocytes and macrophages. Lymphocytes get activated by the cytokines and leading to hyperactive autoimmune response.

Caplan syndrome is caused by breathing in coal mining dust. This causes inflammation and can lead to the development of many small lung lumps (nodules) and mild asthma-like airway disease. The condition occurs in miners (especially those working in anthracite coal-mines), asbestosis, silicosis and other pneumoconioses. There is probably also a genetic predisposition and smoking is thought to be an aggravating factor.

Caplan syndrome must be differentiated from Asbestosis, Silicosis, and Tuberculsosis.

The incidence of Caplan syndrome is 1 in 100,000 people but it is decreasing due to the reduction of exposure to coal, silica, and asbestos. Silica exposure has the most prevalence of Caplan syndrome.

Common risk factors in the development of Caplan syndrome include pneumoconiosis, rheumatoid arthritis.

The patients with Caplan syndrome are mostly asymptomatic initially. Lung nodules in Caplan syndrome are rapidly growing; gain final size within weeks to month and then remain unchanged for years long. If left untreated, patients with Caplan syndrome may progress to develop wheeze in the chest which doesn’t change with cough suggestive of irreversible pulmonary fibrosis

Caplan Syndrome is mostly common in coal miners with Rheumatoid Arthritis. Presenting symptoms could be shortness of breath, cough, wheezing.

Common physical examination findings of Caplan Syndrome include typical Rheumatoid arthritis features as swollen, tender metacarpophalangeal and proximal interphalangeal joints. Pulmonary findings might include wheeze, crackles not improving with coughing.

No definitive laboratory findings are related to Caplan syndrome. But serum study might show positive findings of Rheumatoid factor, antinuclear antibodies.

An x-ray may be helpful in the diagnosis of Caplan Syndrome. Findings on an x-ray suggestive of Caplan Syndrome include well defined round , cavitating nodules with the diameter of 0.5-5cm.

There are no certain chest CT scan findings than the chest x-ray associated with Caplan Syndrome.

There are no MRI findings associated with Caplan Syndrome.

There are some imaging findings of hands and feet such as bilateral erosion of bones and joint space narrowing which are associated with Caplan Syndrome.

Serum study may be helpful in the diagnosis of Caplan Syndrome. Serum study may found positive for rheumatoid factor, antinuclear antibodies, elevated ESR, and CRP.

There is no treatment for Caplan Syndrome; the mainstay of therapy is supportive care. Supportive therapy for Caplan Syndrome includes treatment of Rheumatoid arthritis, Steroid. Lung transplant for irreversible pulmonary fibrosis..

No definitive surgery is helpful in Caplan Syndrome except in massive pulmonary fibrosis, lung transplant is required.

The primary preventive measure for Caplan syndrome is reducing exposure to inorganic dust as silica, asbestos.

Effective measures for the secondary prevention of Caplan’s syndrome include limited exposure to respirable mine dust, personal respirable dust monitor can be used by the miners to monitor dust in their breathing zones, a regular medical screening to detect pneumoconiosis in the early stages, smoking cessation, and medical counseling.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

In 1953, the chest x ray findings of multiple pulmonary nodules, in the coal miners with Rheumatoid Arthritis(RA) of Welsh, was described by Caplan. In 13 coal miners with RA, along with the small silicotic nodules, well-defined, larger lung nodules were found. Caplan identified that miners with pulmonary nodules on chest x-ray eventually developed arthritis though they have not diagnosed cases of RA. Though Caplan’s initial idea was of infectious etiology, two years later several cases of ‘ rheumatoid pneumoconiosis‘ with tuberculosis were reported. But the theory of rheumatoid pneumoconiosis and tuberculous pneumoconiosis got rejected by time. Caplan’s syndrome concept was expanded to cover the exposure to all inorganic dust from different sources. In 1940 and 1950, rheumatoid nodules were identified by several authors in autopsy studies of different organs as heart and lungs. But the relation to silica exposure was not discussed. Years later after Caplan’s publication, multiple cases with pulmonary nodules in miners with RA were reported. But 20 cases with lung nodules were reported without any dust exposure.

• Caplan Syndrome was first discovered by Dr. Anthony Caplan, a British physician, in 1953.
• In 1955, theory of tuberculous rheumatism and tuberculous pneumoconiosis were developed which got abandoned later.
• In 1940 and 1955, rheumatoid nodules were described in autopsy study of heart and lungs.
• In 1948, Ellman and Ball reported the pulmonary nodules found in coal miners were prevalent only in men with dust exposures and not related to ordinary silicosis or rheumatoid arthritis.
• An epidemiological study was conducted by Miall and associates in 1955 to determine the validity of Caplan syndrome.
• In 1958, J. Gough described the histological criterias to diagnose Caplan syndrome.^{[1] [2] [3]}

• Caplan’s syndrome was originally described in coal miners with progressive massive fibrosis by Caplan in 1953.^[2]

• In 1955, the first epidemiological study was conducted to validate the criteria of Caplan syndrome.
• J. Gough reported the histological diagnostic findings for Caplan Syndrome in 1958.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

There is no established system for the classification of Caplan Syndrome.

There is no established system for the classification of Caplan’s Syndrome.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

Caplan Syndrome is known as Rheumatoid pneumoconiosis. In patients with rheumatoid arthritis, lungs show increased immune response to the foreign materials. In coal miners with RA, exposure to silica causes the release of different cytokines as interleukin-1,granulocyte colony stimulating factor and tumor necrosis factor-alpha by monocytes and macrophages. Lymphocytes get activated by the cytokines and leading to hyperactive autoimmune response.

• It is understood that syndrome is the result of alteration of immune response in the patients with Rheumatoid arthritis.^[1]
• There is an increased immune response to foreign materials in the lungs.Silica initiates hyperactive immune responses in the coal miners with Rheumatoid arthritis
• Macrophages engulf silica particles, causing inflammation which eventually activate the firbroblasts.
• Due to having apoptotic capacity, engulfed silica destroy the macrophages and again get taken up by another macrophage. This continued process activates chronic immune response and fibrosis.

• No genetic association is found in Caplan Syndrome.

Conditions associated with [disease name] include:

• Rheumatoid Arthritis ^[1]
• Silicosis
• Asbestosis

Some people who have been exposed to the dust have severe lung scarring that makes it difficult for their lungs to carry oxygen to the bloodstream (called progressive massive fibrosis). People with rheumatoid arthritis do not seem more likely to have this complication of scarring.

Persons with rheumatoid arthritis are more likely to develop larger areas of inflammation and scarring in response to coal dust.

Microscopic features of Caplan syndrome are

• Central necrotic area with various amounts of collagen tissue. ^{[2] [3]}
• Few nuclei might be found in the central necrotic area.
• Outside of the necrotic area there are alternate layers of black coal dust and necrotic tissue.
• Surrounding the dust ring, there is a zone of inflammation containing granulocytes, macrophages, and giant cells. Macrophages might contain some dust particles.
• Outside of the inflammatory zone, there are some palisading cells.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

Caplan syndrome is caused by breathing in coal mining dust. This causes inflammation and can lead to the development of many small lung lumps (nodules) and mild asthma-like airway disease. The condition occurs in miners (especially those working in anthracite coal-mines), asbestosis, silicosis and other pneumoconioses. There is probably also a genetic predisposition and smoking is thought to be an aggravating factor.

Common causes of Caplan Syndrome may include:^[1]

• Rheumatoid arthritis
• Silicosis, asbestosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

Caplan syndrome must be differentiated from asbestosis, silicosis, and tuberculosis.

Caplan syndrome must be differentiated from asbestosis, silicosis and other respiratory diseases with lung lesions.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

The incidence of Caplan syndrome is 1 in 100,000 people but it is decreasing due to the reduction of exposure to coal, silica, and asbestos. Silica exposure has the most prevalence of Caplan syndrome.

• Caplan syndrome is very rare in the United States. Incidence is currently 1 in 100,000 people but is likely to fall as the coal mining industry declines.^[1]

• The prevalence of Caplan syndrome is estimated to be very low.^[1]
• Most recent study showed the prevalence of Caplan syndrome n Japan is 0.75% and in the USA it is 0.89%. No recent study on the prevalence in Europe.^[2]

• Mortality rate in Caplan syndrome is very low except in association with black lung caused by coal worker pneumoconiosis.^[3]

• Aveerage age of first radiographic appearance of Caplan syndrome is 54 years. The age range is 41 to 64 years of age. ^[4][5]

• There is no racial predilection to Caplan syndrome.

• There is no study available on gender.

• The majority of Caplan syndrome cases are reported 0.75% in Japan and 1.5% in the United States.^[6]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

Common risk factors in the development of Caplan syndrome include pneumoconiosis, rheumatoid arthritis.

The most potent risk factor in the development of Caplan syndrome is Pneumoconiosis. Other risk factors include Rheumatoid arthritis, smoking.^{[1] [2]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Sharmi Biswas, M.B.B.S

If left untreated, some patients might develop irreversible pulmonary fibrosis.

• The patients with Caplan syndrome are mostly asymptomatic initially. ^{[1] [2]}
• Caplan nodules appear with or later than the onset of Rheumatoid arthritis.^[3]
• Caplan nodules may lead to cavitation or calcification with pleural effusion or in rare cases pneumothorax.
• Lung nodules in Caplan syndrome are rapidly growing; gain final size within weeks to month and then remain unchanged for years long.
• Most of the lung nodules resolve spontaneously while some leave behind asteroid scarring. In 10% cases, cavitation and calcification happen.
• There are cases of Caplan syndrome with radiologic findings of Caplan nodules but no rheumatoid factor.
• The symptoms of dyspnea and cough typically develop with the progression of the disease.
• If left untreated, patients with Caplan syndrome may progress to develop wheeze in the chest which doesn’t change with cough suggestive of irreversible pulmonary fibrosis.

Possible complications include^{[3] [4]}:

• Increased risk for tuberculosis and aspergillosis
• Hemoptysis
• Pleural effusion
• Pneumothorax
• Progressive massive fibrosis (scarring)
• Side effects of medications

Caplan syndrome rarely causes serious breathing trouble or disability due to lung problems.^[4]

The nodules may pre-date the appearance of rheumatoid arthritis by several years. Otherwise, prognosis is as for RA; lung disease may remit spontaneously, but pulmonary fibrosis may also progress.