Pulmonary changes on high-resolution computed tomography of patients with rheumatoid arthritis and their association with clinical, demographic, serological and therapeutic variables

Abstracts

JUSTIFICATIVA: Pacientes com artrite reumatoide (AR) têm manifestações extra-articulares em até 50% dos casos OBJETIVO: Estudar a prevalência das alterações pulmonares à tomografia computadorizada de alta resolução em pacientes com AR e sua associação com variáveis demográficas, clinicas, sorológicas e terapêuticas. MÉTODO: Estudaram-se 71 pacientes com AR para idade de início da doença, tempo de doença, sexo, tabagismo, presença de nódulos reumatoides, síndrome de Sjögren secundária, fator reumatoide, presença de anti-CCP e fator antinuclear, queixas respiratórias, uso de medicamentos e achados pulmonares à tomografia de alta resolução. RESULTADOS: Existiam alterações tomográficas em 55% dos pacientes, sendo as mais comuns as presenças de vidro fosco, bandas parenquimatosas, bronquiectasias de tração e faveolamento. Nenhuma das variáveis clínicas estudadas se associou aos achados tomográficos, exceto a duração de doença que foi maior em pacientes com nódulos pulmonares e lesões reticulares (vidro fosco). CONCLUSÕES: Existe uma alta prevalência de alterações tomográficas na população de AR, as quais não se associam com variáveis clínicas, sorológicas, terapêuticas e demográficas salvo tempo de duração da doença

artrite reumatoide; lesão pulmonar; tomografia

ORIGINAL ARTICLE

^IPh.D. by the Instituto de Pesquisas Médicas, HUEC-PR; Full Professor of the Discipline of Rheumatology of the Faculdade Evangélica de Medicina do Paraná

^IIM.Sc. Radiologist of the Imaging Service of the Hospital Universitário Evangélico de Curitiba

^IIISpecialist; Radiologist of the Clínica de Diagnóstico Avançado por Imagem

^IVMedical student of the Faculdade Evangélica de Medicina do Paraná

^VSpecialist in Rheumatology; M.Sc. by the Universidade Federal do Paraná

Correspondence to

ABSTRACT

BACKGROUND: Extra-articular manifestations are found in up to 50% of the patients with rheumatoid arthritis (RA).

OBJECTIVE: To assess the prevalence of pulmonary changes on high-resolution computed tomography (HRCT) in patients with RA and their association with demographic, clinical, serological and therapeutic variables.

METHOD: Seventy-one patients with RA were assessed regarding their age at RA onset, duration of disease, gender, tobacco use, presence of rheumatoid nodules, secondary Sjögren's syndrome, rheumatoid factor, presence of anti-CCP and antinuclear factor, respiratory complaints, use of medications, and pulmonary changes on HRCT.

RESULTS: HRCT changes were identified in 55% of the patients, the most common being the presence of ground glass opacities, parenchymal bands, traction bronchiectasis, and honeycombing. None of the clinical variables studied associated with the HRCT findings, except for duration of the disease, which was longer in patients with pulmonary nodules and reticular lesions (ground-glass opacity).

CONCLUSIONS: There is a high prevalence of HRCT changes in patients with RA, which do not associate with clinical, serological, therapeutic and demographic variables, except for duration of disease.

Keywords: rheumatoid arthritis; pulmonary lesion; tomography.

INTRODUCTION

Rheumatoid arthritis (RA) is a relatively common disease that affects approximately 1% of the population, mainly women.¹ Characterized by the presence of an additive polyarthritis with a high deforming potential, RA is a systemic disease that, among other organs, affects the lungs.²

The spectrum of the pulmonary manifestations of RA is wide, ranging from pleuritis and nodules to interstitial lesions.² The prevalence of pulmonary changes in RA patients varies in the literature. Part of that variability can be explained by the genetic background of the population studied, due to the influence of genes, such as those of HLA DR4 and HLA DR1,^2,3 on the phenotype of the disease. Genetic polymorphisms of the HLA-B40 and B54 are associated with the presence of pulmonary changes, especially fibrosis and bronchiolitis.^4,5 In addition, some medications used in the treatment of that entity can be partially responsible for the pulmonary findings in RA patients. Leflunomide, methotrexate, and sulfasalazine have been involved in interstitial pulmonary diseases.² Methotrexate⁶ and leflunomide⁷ are considered possible inducers of peripheral and visceral nodules. Tobacco, a potentially harmful agent to the lungs, is also an aggravating factor of RA, causing not only a more aggressive disease, but also the appearance of more extra-articular manifestations.³

The present study aimed at assessing the tomographic findings of RA patients of a single rheumatology center in southern Brazil, and their possible correlation with the clinical and serological findings of the disease.

MATERIAL AND METHODS

This study has been approved by the local Committee on Ethics in Research, and written informed consent has been provided by all participants. The study assessed 71 patients meeting at least four of the American College of Rheumatology classification criteria for RA.⁸ Their ages ranged from 31 to 84 years (mean, 58.7 ± 10.4 years), ten were men and 61 women, and their mean duration of disease was 11.8 ± 6.9 years. Patients were chosen according to the scheduled visit order and decision to participate in the study. Patients with the following characteristics were excluded from the study: pregnant patients; chronic pulmonary obstructive disease; previous history of tuberculosis; history of chest surgery and irradiation.

The data obtained through analysis of the medical records were as follows: age at RA onset; presence of nodules; associated Sjögren's syndrome;⁹ presence of autoantibodies, such as rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), and antinuclear antibody (ANA); use of medications; and tobacco exposure (current smokers and ex-smokers). Then, through structured interview, data about the current presence of respiratory complaints (cough, chest pain, and dyspnea) and functional index were obtained.¹⁰

All patients underwent high-resolution computed tomography (HRCT), in the dorsal decubitus position, by using the Siemens Somatom SpiritT CT scanner, two channels, and the GE Healthcare LightSpeed Pro 16 CT scanner. The technique was as follows: axial slices were obtained during maximum inspiration, with 1- to 2-mm thickness, time interval of 500 ms-1.5 second, 10-mm increment; image reconstruction with high-resolution matrix (512 x 512); and mean level of the window ranging from -700 to -1.000 HU to assess pulmonary parenchyma, with window width of 1,000 HU. The mediastinum was assessed with a window of approximately 30-50 HU, width of 400 HU, 120 Kvp, and automatically modulated amperage (120 to 250 mA). No intravenous iodinated contrast medium was administered in any phase of the exam. Some exams had multiplanar reformatting. The CT scans were read by two radiologists, one of whom (DLE) exclusively dedicated to chest radiology, and they had no access to the patients' other data. For the purpose of statistical analysis, the findings were classified into three major groups:

a) Pulmonary lesions with increased pulmonary density: posterior and peripheral typical ground-glass opacity; atypical ground-glass opacity; focal typical groundglass opacity; focal non-segmentary consolidation; multifocal non-segmentary consolidation; focal segmentary consolidation.

b) Pulmonary lesions with nodular pattern: perilymphatic nodules, centrilobular nodules, random nodules, tree-in-bud opacities, cavitary nodules, and masses.

c) Pulmonary lesions with reticular pattern: peribronchial thickening, septal thickening, intralobular interstitial thickening, parenchymal bands, architectural distortion, traction bronchiectasis, honeycombing.

The data obtained were collected in frequency and contingency tables. The Fisher and chi-square tests were used to assess the association of nominal variables, and the Mann-Whitney and non-paired Student t tests for the numerical variables with the aid of the Graph Pad Prism software. The significance level of 5% was adopted.

RESULTS

Analysis of the population studied

In the sample studied, the age of RA onset ranged from 22 to 73 years (mean, 43.9 ± 11.0 years), 24/67 (35.8%) patients were smokers and ex-smokers, and 43/67 (64.1%) had no tobacco exposure. Rheumatoid nodules were observed in 11/68 (16.1%) patients, and secondary Sjögren's syndrome in 9/61 (14.7%). The RF was identified in 51/71 (71.8%) patients, the anti-CCP antibody was positive in 24/32 (75%) patients, and positivity for ANA was observed in 19/69 (27.5%) patients. Regarding the functional class, 27/66 (40.9%) patients were class 1, 29/66 (43.9%) were class 2, 3/66 (4.5%) were class 3, and 7/66 (10.6%) were class 4. The treatment included azathioprine for 4/71 (5.6%) patients, leflunomide for 24/71 (33.8%), methotrexate for 45/71 (63.3%), anti-TNF-α for 7/71 (9.8%), sulfasalazine for 11/71 (15.4%), and antimalarials for 43/71 (60.5%) patients.

The respiratory complaints reported were as follows: dyspnea, 12/65 (18.4%) patients; cough, 6/66 (9.0%); and chest pain, 29/66 (43.9%). No respiratory complaints were reported by 30/67 (44.7%) patients.

The CT findings of that population are shown in Table 1 and illustrated in Figure 1.

Analysis of the association of the CT findings of increased parenchymal density

The analysis of the patients with increased parenchymal density on CT (23/71 patients, 32.3%) is shown in Table 2. None of the variables studied showed an association with the CT changes in question, except for the presence of chest pain, whose association was negative.

Analysis of the association of the nodular pattern pulmonary lesions

The analysis of the patients with nodules (7/71 patients, 9.8%) is shown in Table 3, evidencing the higher presence of nodules in patients with longer lasting disease.

Analysis of the association of the reticular pattern pulmonary lesions

The analysis of the association of reticular pattern lesions (27/71 patients, 38%) with the variables studied is shown in Table 4. Once again, the only positive association was that of reticular lesions in patients with longer lasting disease.

DISCUSSION

Rheumatoid arthritis is traditionally considered a disease that involves the joints. Nevertheless, up to 50% of the patients have some type of extra-articular manifestations, such as serositis, pneumonitis, peripheral neuritis, nodules, and scleritis.² This study reviewed the prevalence of the pulmonary manifestations seen on HRCT in a group of patients of southern Brazil, aiming at correlating such findings with clinical, serological and treatment variables. The analysis of the data of the present study shows that most patients with RA (55%) have some type of CT changes. That high prevalence of findings has been confirmed by other authors, such as Zrour et al.,¹¹ who have reported changes in 49.3% of 75 patients from Tunisia, and Bilgicki et al.,³ who have reported them in 67.3% of 52 patients in Turkey. In addition, Teraski et al.,¹² studying patients with RA and respiratory symptoms, have reported CT changes in 90% of them.

The most prevalent changes were those of the reticular pattern, followed by increased parenchymal density. Positive associations with the demographic and clinical findings were scarce. Interstitial pulmonary disease has been reported as tending to be more common in male patients, those with high RF titers, and those with more severe and deforming joint disease.^13,14 However, such findings could not be confirmed in our sample, which showed an equal distribution in both genders, in the different functional classes, and in those with and without RF, anti-CCP, and ANA, although an analysis of the titers of those autoantibodies has not been performed. Similarly, the series studied by Bilgicki et al.³ has shown no association between pulmonary lesion and the male gender. However, our study showed that nodular and reticular lesions are more common in patients with longer lasting RA.

The association between the pulmonary disease of RA and tobacco use is controversial. Tobacco use has been identified as a predisposing factor to pulmonary disease in RA by several authors,^15,16 but others have already shown a lack of association between those two variables,³ such as observed in the present data.

It is worth noting that no association between the HRCT findings and the respiratory complaints of pain, cough, and dyspnea could be found. Some possible explanations for those findings are as follows: 1) patients with RA, suffering from several musculoskeletal changes, can have chest pain not related to pulmonary causes; 2) difficulty in moving around, generated by the disability secondary to RA, does not allow the perception of dyspnea unless when more advanced.

Lastly, in the present series, none of the medications studied showed any association with the CT changes. Methotrexate is currently the disease-modifying anti-rheumatic drug most commonly used in the treatment of RA and has been associated with pulmonary toxicity. There is no data about the pulmonary involvement by methotrexate in our population. Cotin et al.¹⁷have shown a deterioration of the pulmonary function in patients on methotrexate, but such findings were not clinically significant. Other authors have found no changes in neither function nor CT findings in patients with RA undergoing different types of treatment.³

The limitations of the present study were the size of the sample (n = 71) and the retrospective analysis of laboratory data (ANA, RF, and anti-CCP). The former can be responsible for type 2 statistical errors, hindering the appearance of some associations with the variables studied.

In conclusion, our RA population has a high prevalence of CT abnormalities, the most common being pulmonary lesions with reticular pattern and increased pulmonary parenchymal density. Such changes showed no association with gender, presence of auto-antibodies, functional class, and tobacco use. The pulmonary lesions of reticular and nodular patterns are more common in long-lasting disease. Finally, no association was found between HRCT changes and the use of different types of medications for treating RA.

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Pulmonary changes on high-resolution computed tomography of patients with rheumatoid arthritis and their association with clinical, demographic, serological and therapeutic variables

Thelma Larocca Skare^I; Irene Nakano^II; Dante Luiz Escuissiato^III; Renato Batistetti^IV; Tales de Oliveira Rodrigues^IV; Marília Barreto Silva^V

Publication Dates

• Publication in this collection
  11 July 2011
• Date of issue
  Aug 2011

History

• Received
  18 Jan 2011
• Accepted
  30 Apr 2011