Caplan Syndrome

Article Author:
Divyesh Nemakayala
Article Editor:
Kamleshun Ramphul
Updated:
3/14/2019 4:51:05 PM
PubMed Link:
Caplan Syndrome

Introduction

Caplan syndrome was first described in 1953 by Dr. Anthony Caplan, a physician on the Cardiff Pneumoconiosis Panel, as radiologic evidence of intrapulmonary nodules in coal miners with a diagnosis of rheumatoid arthritis (RA).[1]

Etiology

Caplan syndrome is caused by work exposure to coal, asbestos, and/or silica which causes pneumoconiosis, an inflammatory reactive lung condition to the dust, in a patient with a rheumatoid arthritis diagnosis. Smoking is believed to aggravate these lung findings.[2][3]

Epidemiology

The reported incidence of Caplan syndrome is 1 in every 100,000 people. This has been a declining number due to lower exposure to coal, asbestos, and silica. Prevalence of Caplan syndrome is higher in patients with silica exposure compared to the other causes. The first epidemiologic study undertaken by the Pneumoconiosis Research Unit observed an increased prevalence of RA amongst 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 amongst 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 which 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, 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 which are swollen, tender metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, along with possible pulmonary findings such as rales, wheezes, and crackles. It is defined as lung nodules in work-exposed personnel, with nodules varying in size from 0.5 to 5 centimeters. The nodules may grow, remain unchanged, disappear, and then reappear.

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 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 the 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 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. Infection with bacterial granulomatous such as fungi, mycobacterial, Nocardia, parasitic
  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 condition 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 condition 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

Practitioners are advised to consult pulmonology for further assistance in patient care. 

Deterrence and Patient Education

People should avoid exposure to inorganic dust, risk factors such as sandblasting, or exposure to asbestos. 

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 is best done with an interprofessional team that includes the primary care physician, nurse practitioner, pulmonologist, radiologist and pathologist. The majority of patients first come to attention at outpatient clinics where they may complain of dyspnea and/or joint pain. 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 the 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)


References

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[2] Sharma RK,Sharma AK,Sharma A, Erasmus Syndrome: Association of Silicosis and Systemic Sclerosis. Indian dermatology online journal. 2018 May-Jun;     [PubMed PMID: 29854640]
[3] Rozenberg D,Shapera S, What to do with all of these lung nodules? Canadian respiratory journal. 2014 May-Jun;     [PubMed PMID: 24914609]
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[8] Otsuki T,Maeda M,Murakami S,Hayashi H,Miura Y,Kusaka M,Nakano T,Fukuoka K,Kishimoto T,Hyodoh F,Ueki A,Nishimura Y, Immunological effects of silica and asbestos. Cellular     [PubMed PMID: 17764616]
[9] Arakawa H,Honma K,Shida H,Saito Y,Morikubo H, Computed tomography findings of Caplan syndrome. Journal of computer assisted tomography. 2003 Sep-Oct;     [PubMed PMID: 14501367]
[10] Bankier AA,Fleischmann D,Kiener HP,Wiesmayr MN,Herold CJ, [Pleural and pulmonary changes within the scope of rheumatoid arthritis]. Der Radiologe. 1996 Aug;     [PubMed PMID: 8975281]