Review article
Rheumatoid pneumoconiosis (Caplan's syndrome)

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Abstract

In 1953, Caplan described a characteristic radiographic pattern in coal miners with rheumatoid arthritis (RA) that was distinct from the typical progressive massive fibrosis pattern of coalworkers' pneumoconiosis. It consists of multiple well-defined rounded nodules on chest X-ray, from about 0.5 to about several centimetres in diameter, distributed throughout the lungs but predominantly at the lung periphery. Lesions appear often in crops, may coalesce and form a larger confluent nodule. Nodules often cavitate or calcify. They typically occur in the setting of pre-existing mild pneumoconiosis, but pneumoconiosis is not a prerequisite. The onset of the nodules is typically sudden, and their course varies thereafter, ranging from regression to progression. Histologically, the nodules have a characteristic appearance and are distinguishable from silicotic nodules or progressive massive fibrosis. Individual susceptibility is considered to play a role in the development of the disease. However, the pathogenetic link between exposure to silica, pneumoconiosis and RA has not been clarified conclusively. This review summarizes history, definition and current knowledge on epidemiology, pathology, pathophysiology, clinical presentation and treatment of Caplan's syndrome.

Introduction

Extra-articular manifestations of rheumatoid arthritis (RA) are of outstanding clinical significance and have a negative impact on the quality of life and the life expectancy of patients with RA [1], [2]. RA has a wide spectrum of pleuropulmonary manifestations: necrobiotic pulmonary nodules, pulmonary fibrosis, bronchiolitis obliterans and pleural abnormalities [3], [4]. This review summarizes the medical literature with respect to pulmonary nodules, dust exposure and RA. We performed a Medline-based search of the medical literature using the search terms “Caplan/Kaplan [and] syndrome”, “rheumatoid [and] pneumoconiosis”, “rheumatoid [and] pulmonary/lung”, and “rheumatoid [and] silica”. Furthermore we screened the reference lists of old publications for qualified references. We analyzed these publications chronologically and omitted those which did not add information to current knowledge. Thus it is not a systematic review because many of the previous data do not add to current knowledge and thus have been omitted. Overall, 38 references were detected by the systemic Medline research and 24 references by the reference lists, among them 10 references which are not listed in Medline.

Section snippets

History

In 1953, Caplan described the occurrence of multiple peripheral lung nodules in chest X-rays of Welsh coal miners with RA. Fifty-one out of 14,000 coal miners suffered from RA, in 13 of whom he observed larger, well-defined pulmonary nodules additionally to scant typical small silicotic nodules [5]. Caplan pointed out that not all miners with characteristic nodules on chest X-ray had RA, but many of them developed arthritis as long as ten years after the occurrence of the lung lesions. He

Definition

Caplan's syndrome, also referred to as RP, is defined as the combination of multiple well-defined pulmonary nodules predominantly in the lung periphery and inorganic dust exposure in patients with RA. Although radiologically documented silicosis or coal workers pneumoconiosis is not a prerequisite for a diagnosis of Caplan's syndrome, most patients with RP show at least slight pneumoconiosis at the time of diagnosis [23], [26], [54]. As arthritis may be absent [13] or develop later in the

Epidemiology

As pulmonary nodules have been described in RA patients with and without dust exposure, the proof of an association between dust exposure and nodules can only be established by epidemiologic data that show an increased prevalence of pulmonary nodules in dust-exposed subjects compared to a non-exposed control group. As the radiographic appearance of Caplan's syndrome is typical, but not pathognomonic, an overlap between Caplan nodules and progressive massive fibrosis (PMF) in epidemiologic

Pathology

The classification of RP into two subtypes has been proposed: the classic (Caplan) type is characterized by larger nodules with uniform necrosis which is associated with mild pneumoconiosis and the silicotic type, which is characterized by smaller nodules in which the necrotic area retains some characteristics of a silicotic nodule. The background disease of this type is silicosis with or without massive fibrosis [24], [37].

The histopathological pattern of the “Caplan nodules” has been

Pathophysiology

Despite the description and the well-defined clinical presentation, pathogenesis and causality between pneumoconiosis, RA and the pulmonary changes in RP are still inconclusive and the pathophysiology of the processes involved remains undefined. It is still not clear whether silicosis predisposes some individuals to develop autoimmune disease or whether the autoimmune disease may predispose some individuals to develop silicosis [41]. The question of individual susceptibility remains unanswered.

Symptoms, lung function and laboratory findings

In most patients the Caplan nodules are asymptomatic and without adverse effects on lung function tests. A comparison between patients with Caplan's syndrome and patients with non-rheumatoid PMF showed less obstruction in the former [52]. As most studies about Caplan's syndrome are older, laboratory tests were performed with a limited spectrum of methods (reviewed by [25]). The patients with RP may show signs of inflammation in laboratory tests, even in the absence of active arthritis. Elevated

Therapy

The pulmonary nodules in Caplan's syndrome are asymptomatic and do not require treatment unless a complication develops, e.g. following rupture of a cavitating lesion into the pleural space [4]. Treatment of RA should be performed according to current rheumatological guidelines, irrespective of Caplan's syndrome. Treatment of articular disease by disease-modifying drugs does not necessarily alter the evolution of pulmonary nodules, but corticosteroids have been reported useful in some patients

Learning points

  • Caplan's syndrome is a characteristic radiographic pattern in patients with rheumatoid arthritis and coalworkers' pneumoconiosis. It consists of multiple well-defined rounded nodules on chest X-ray.

  • They typically occur in the setting of pre-existing mild pneumoconiosis, but pneumoconiosis is not a prerequisite.

  • Histologically, the nodules have a characteristic appearance and are distinguishable from silicotic nodules, progressive massive fibrosis and rheumatoid nodules. Differential diagnosis

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