A four-year follow-up of Caplan’s syndrome: A case report

Abstract

Caplan’s syndrome, also known as rheumatoid pneumoconiosis, is characterized by pulmonary nodules and rheumatoid arthritis in patients with pneumoconiosis. Owing to its low incidence rate and the presence of multiple nodules on lung computed tomography, it is often mistaken for other pulmonary diseases. Herein, we report the case of a 60-year-old man who presented to the hospital with joint edema and recurrent polyarthralgia. Laboratory studies revealed higher levels of rheumatoid factor and anti-citrullinated peptide antibodies, together with an enhanced erythrocyte sedimentation rate. Chest high-resolution computed tomography revealed multiple bilateral nodules during the evaluation for treatment contraindications. Based on the patient’s occupational background and findings from multidisciplinary consultations, a definitive diagnosis of Caplan syndrome was made. Maintenance therapy included low-dose methylprednisolone (gradually tapered and discontinued over 3 months), methotrexate, and hydroxychloroquine. The patient’s arthralgia and pulmonary nodules demonstrated stability over a follow-up period of up to 4 years, thereby indicating the success of this treatment.

Introduction

Caplan’s syndrome, sometimes known as rheumatoid pneumoconiosis (RP), is a rare silicosis complication with an incidence of 0.75%–0.89%. ¹ It is characterized by independent specific lesions in the respiratory system and joints. Caplan’s syndrome was first identified and documented by the British physician Dr. Caplan among coal miners in South Wales, and it subsequently gained recognition over time. ² Caplan’s syndrome, which appears as multiple scattered round nodules in lung fields (with diameters ranging from 0.5 to 5 cm) upon pulmonary imaging, is easily confused with pulmonary tuberculosis and metastatic lung tumors during diagnosis. Currently, no consensus exists on the treatment of Caplan’s syndrome. This report describes the case of a patient with joint pain who was later diagnosed with Caplan’s syndrome based on occupational history, clinical symptoms, and diagnostic test results. He was treated with short-term low-dose hormone therapy and long-term methotrexate (MTX) and hydroxychloroquine (HCQ) maintenance, resulting in a favorable outcome.

Case presentation

In March 2021, a 60-year-old man was admitted to the Internal Medicine Clinic of the Third People’s Hospital of Yuhang District, Hangzhou City, China, presenting with recurrent polyarticular pain persisting for 2 years and worsening over the past week. He had been taking diclofenac sodium intermittently for pain relief during this period. Outpatient test results revealed an erythrocyte sedimentation rate (ESR) of 50 mm/h (reference range: 0–15 mm/h), rheumatoid factor titer of 85.2 IU/mL (reference range: 0–18 IU/L), and anti-citrullinated peptide antibody (ACPA) level of 150 U/mL (reference range: 0–35 U/mL). Thus, he was referred to the Rheumatology Department for further assessment and treatment.

Physical examination revealed bilateral wrist swelling, pronounced tenderness on the left side, tenderness on both metacarpophalangeal joints and multiple proximal interphalangeal joints, and tenderness on the right elbow joint. The Disease Activity Score 28 (DAS28) was 6.09.

Subsequent thorough examinations revealed an elevated level of high-sensitivity C-reactive protein (CRP) at 20.4 mg/L (reference range: 0–6 mg/L), an antinuclear antibody titer of 1:100, and a negative result on the T-SPOT test. X-ray imaging of both hands displayed minor subchondral bone erosion in the interphalangeal joints (Figure 1). High-resolution computed tomography (HRCT) revealed multiple small round nodules in both lungs, some of which showed calcification, with the most prominent nodules located in the upper lobe of the right lung (Figure 2(a)).

Figure 1.

X-Ray of both hands. The 2–5 interphalangeal joint space of the right hand exhibited narrowing, with hyperplastic changes observed in the corresponding articular surface, particularly in the middle finger (red marker). The 3–4 proximal interphalangeal joint of the left hand displayed slight narrowing, while the distal ends of the left ulna and radius were irregular, accompanied by localized bone hyperplasia (red marker).

Figure 2.

A 4-year follow-up of high-resolution computed tomography (HRCT). (a) Initial HRCT demonstrated numerous well-defined pulmonary nodules bilaterally, primarily located in the apical and peripheral areas of both lungs, with a lower quantity noted in the basal regions. The nodules varied in diameter from several millimeters to approximately one centimeter, with the largest nodule situated in the right upper lobe (red arrow). The lesion displayed an irregular morphology, with its peripheral margin revealing a fibrous strand shadow adjacent to the chest wall with clear boundaries. (b) No significant alteration was observed compared with the initial HRCT and (c–e) compared with initial HRCT, the pulmonary nodules remained stable. Several nodules in the upper lobes of both lungs progressively exhibited a tendency to merge without any discernible cavitation (red arrow).

The patient had a medical history of gout and no familial predisposition to rheumatism. Notably, he had engaged in gold mining for 4 years, involving activities such as drilling holes in rock formations and veins as well as crushing large rocks. These tasks resulted in significant dust exposure.

Considering the patient’s professional background and the HRCT results, we planned a multidisciplinary consultation involving the departments of respiratory medicine and radiology. Differential diagnoses included tuberculosis and pulmonary metastases. Owing to the patient’s reluctance to undergo lung puncture or bronchoscopy, alternative investigations were pursued, including sputum smear analysis for acid-fast bacilli, tuberculosis genetic assays, tumor marker assessments, thyroid ultrasonography, and comprehensive abdominal computed tomography (CT). All findings yielded negative results, thereby ruling out pulmonary tuberculosis and pulmonary neoplasms. After a thorough review of the literature and an assessment of the patient’s occupational background and advice from respiratory and radiology specialists, a diagnosis of Caplan’s syndrome was considered, which is a form of rheumatoid arthritis (RA)–related lung disease.

Before treatment, we assessed the patient’s pulmonary function, revealing mild restrictive ventilatory dysfunction and a slight reduction in diffusing capacity (forced vital capacity: 79%, forced expiratory volume in 1 s: 86%, total lung capacity measured with helium dilution: 71%, and transfer factor for carbon monoxide: 78%). Owing to the absence of respiratory symptoms, he was treated with the standard RA treatment regimen, which included oral HCQ (0.2 g twice daily), oral MTX (10 mg weekly, with 10 mg of folic acid administered the day after MTX), and daily intravenous methylprednisolone (20 mg).

Three days later, the patient’s joint pain symptoms demonstrated significant improvement. He was subsequently discharged from the hospital. The treatment plan was modified to include oral administration of methylprednisolone at a dose of 8 mg once daily (tapered and discontinued over a 3-month follow-up period), while MTX and HCQ were continued as previously prescribed.

During the 4-year follow-up period, the patient did not report any significant recurrence of joint pain or swelling. Additionally, he did not present with any severe respiratory symptoms, except for intermittent upper respiratory tract infections, which were managed with symptomatic treatment. Throughout this period, we conducted regular monitoring of his ESR and CRP levels, which consistently fell within normal ranges. However, his ACPA titers were consistently elevated above the normal range (86.3 U/mL in May 2022 and 91.8 U/mL in December 2024). Although the patient’s lack of significant pulmonary symptoms, we continuously monitored changes in his HRCT over 4 years, observing that pulmonary nodules remained largely stable. Notably, some nodules in the upper lobes of both lungs revealed signs of fusion, without obvious cavitation (Figure 2(b–e)). These imaging findings align with previous descriptions of Caplan’s syndrome progression, where nodular lesions may fuse, remain unchanged, recur, or exhibit cavitation and calcification. ³

We have de-identified the patient’s details and obtained approval from the Ethics Committee of The Third People’s Hospital of YuHang District, Hangzhou city (202503181600000454250) for publication. The reporting of this study conforms to the Case Report (CARE) guidelines. ⁴ We obtained informed consent from the patients for treatment and publication.

Discussion

Caplan’s syndrome, also known as RP, was initially identified among coal miners in South Wales in 1953 and is believed to be associated with exposure to coal dust. Early investigations indicated a prevalence of approximately 0.4% among patients with pneumoconiosis; however, recent studies suggest that the incidence of Caplan’s syndrome may be higher among coal miners, ranging between 0.74% and 0.89%. ¹ Nevertheless, the incidence of pneumoconiosis has declined significantly owing to advancements in industrial technology, decreased dust exposure in the workplace, and improved protective measures, making Caplan’s syndrome a rare occurrence in clinical practice and less understood by clinicians. The etiology of this condition remains unclear. Past studies have proposed a clear causal link between silica inhalation and autoimmune diseases. Silica particles, when inhaled, can be engulfed by alveolar macrophages, triggering immune hyperactivity. This process leads to the production of various cytokines, such as interleukin-1 and tumor necrosis factor-α, by activating macrophages and perpetuating chronic immune activity and fibrosis through antigen presentation to CD4 T lymphocytes by dendritic cells. This cycle results in sustained immune activity and fibrosis, leading to autoantigen production. ³ Therefore, the presence of ACPAs is commonly observed in patients with Caplan’s syndrome, with high ACPA titers indicating a connection between silica dust exposure and ACPA-positive RA. RA in individuals exposed to dust may show varied manifestations, with onset occurring between 1 and 10 years postexposure. ⁵ Caplan’s syndrome represents a combination of RA and pneumoconiosis. Histologically, typical Caplan’s nodules comprise necrotic rheumatoid nodules containing dust, with a central necrotic region composed of coal dust and necrotic tissues. Polymorphonuclear granulocytes, macrophages, and giant cells infiltrate this area, with coal dust deposits occasionally found within macrophages. This inflammatory milieu aids in distinguishing Caplan’s nodules from pneumoconiosis nodules. ³

Imaging manifestations of Caplan’s syndrome vary from those of typical pneumoconiosis. Pulmonary nodules in patients with Caplan’s syndrome are predominantly located peripherally, appearing as round nodules ranging in size from 0.5 to 5 cm. Nodule formation does not follow a typical pattern, with some patients experiencing rapid nodule appearance, expansion, stabilization, and progression to progressive massive fibrosis (PMF). Cavities and calcifications are common features during the disease course.^5,6 Similar to the patient in this case, pulmonary nodules are primarily found in the lung apex and periphery, with sporadic calcifications. Follow-up revealed a trend of fusion in the upper right lung nodules. Typical pneumoconiosis presents an angel-wing-like distribution on chest X-ray, progressing toward the hilum from the lung’s outer two-thirds. On CT scans, it typically shows circular or irregular small shadows ≤10 mm in diameter around bronchovascular bundles, with advanced stages displaying larger shadows and PMF.^7,8

It is challenging to distinguish Caplan’s syndrome from pulmonary tuberculosis, pulmonary malignancies, and rheumatoid pulmonary nodules using imaging owing to their common association. Miliary tuberculosis can manifest as diffuse, miliary-sized nodules in both lungs on CT scans, resembling Caplan’s nodules. ⁹ Metastatic lung tumors, another diagnostic challenge, may exhibit multiple nodules of varying sizes in both lungs on CT scans. These nodules typically appear round or oval, with uniform density and clear outlines, predominantly in the middle and lower lung fields as well as the outer lung fields, with some possibly containing cavities.^10,11 Identifying primary lesions and obtaining histological evidence are crucial for definitive diagnosis. In addition, differentiating Caplan’s nodules from rheumatoid pulmonary nodules on imaging poses a significant challenge. Rheumatoid pulmonary nodules are specific pulmonary manifestations of RA and can be clinically asymptomatic. Rheumatoid pulmonary nodules typically appear as single or multiple round or irregular solid nodules on imaging, often situated subpleurally or adjacent to the interlobular septa. Approximately 50% of these nodules are thick-walled cavities.^12,13 While the definitive diagnosis of Caplan’s syndrome relies on histopathology, biopsy is not always necessary. A comprehensive assessment considering the patient’s occupational background, characteristic lung imaging findings, and confirmed presence of RA collectively aid in the precise identification of Caplan’s syndrome.^5,14

Currently, Caplan’s syndrome lacks targeted drug therapy. Treatment for pulmonary nodules associated with this syndrome is typically unnecessary unless complications arise, such as nodule cavity rupture resulting in pleural effusion, pneumothorax, pyopneumothorax, bronchopleural fistula, hemoptysis, and infection. In the event of complications, symptomatic management is crucial. RA is managed with antirheumatic drugs following clinical guidelines. Initially, the patient received low doses of methylprednisolone, MTX, and HCQ, leading to stabilization of joint pain and lung nodules over a 4-year follow-up period. He was satisfied with this treatment, thereby precluding the exploration of alternative treatments. Nevertheless, recent reports have documented the successful use of rituximab in managing Caplan’s syndrome, effectively alleviating joint symptoms while maintaining stability in lung nodules.^1,15 Rituximab, a monoclonal antibody targeting CD20 for B cell depletion, is recommended for patients with moderately to severely active RA unresponsive to conventional synthetic disease-modifying antirheumatic drugs or tumor necrosis factor inhibitors. Recent studies have demonstrated its efficacy in treating RA-associated interstitial lung disease and preserving lung function stability. ¹⁶

While most individuals with Caplan’s syndrome exhibit a favorable prognosis, a subset may progress to advanced pulmonary fibrosis. Notably, those with severe RA are at an increased risk of developing interstitial lung disease, which can result in subsequent deterioration of pulmonary function. Consequently, individuals diagnosed with Caplan’s syndrome should be advised on occupational modifications, routine medical assessments, and tailored management strategies for their primary condition.

Conclusions

Caplan’s syndrome, while uncommon, warrants consideration in individuals with a background of dust exposure and joint manifestations. Currently, there are no specific pharmacological interventions tailored for Caplan’s syndrome. Our case report demonstrates that initiating low-dose corticosteroids (gradually tapered and discontinued over 3 months) alongside ongoing therapy with MTX and HCQ can ameliorate joint symptoms and maintain stability of pulmonary nodules. A study limitation was not exploring alternative treatments. Further clinical perspectives and investigations are warranted to define uniform therapeutic approaches.