Rheumatoid Arthritis Related Interstitial Lung Disease: Patterns of High-resolution Computed Tomography

Background and aim Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease characterized by bilateral involvement of mostly small joints of hands and feet. There can be various extra-articular manifestations of the disease including lung parenchymal disease. Pulmonary involvement in RA patients leads to increased morbidity and mortality. The overall burden of RA related pulmonary disease is underestimated due to the limitation of resources in underdeveloped countries. High-resolution computed tomography (HRCT) is an important tool used to diagnose different abnormalities in RA related interstitial lung disease (ILD). The objective of the study was to evaluate HRCT findings in patients of RA related ILD and categorize the radiological findings according to clinical findings. Method This descriptive prospective observational study was conducted at Mayo Hospital, Lahore from June 2014 to June 2015. Patients of RA suspected of lung disease after selection underwent HRCT chest on 128-slice Hitachi CT scanner (Hitachi Global, Tokyo, Japan) in the radiology department. Images were reconstructed and evaluated by experienced radiologists. Findings were recorded on a questionnaire. Data was analyzed on SPSS version 21 (IBM Corp, Armonk, US). Results Out of the 54 patients scanned, interlobular septal thickening was the most common finding found in 22 of the patients. Ground-glass opacification was recognized in 21 patients, honeycombing in nine and bronchiectasis in two patients. Regarding zonal predilection of disease pattern, lower zones of lungs were found involved in most of the cases. The disease was found to be bilateral in 15 patients. Based on these findings, usual interstitial pneumonitis (UIP) was diagnosed in six patients and non-specific interstitial pneumonitis (NSIP) in 14 others. Conclusion This study concluded that HRCT images are very useful in diagnosing interstitial lung disease related to rheumatoid arthritis.


Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease exhibiting clinical signs and symptoms of predominantly joint disease [1][2][3]. This disease is characterized by symmetrical bilateral involvement of mostly small joints of hand and feet; however as it leads to chronic synovitis, all joints may be involved [4][5]. There can be various extra-articular manifestations (EAM) of the disease e.g. upper airway, lower airway, pleural, vascular and lung parenchymal disease, etc. [6][7][8]. The overall burden of RA related pulmonary disease is underestimated due to the limitation of resources in underdeveloped countries [9]. Prevalence of interstitial lung disease (ILD) was found to be 97.9% per 100000 with more of the secondary ILDs than primary ILD. is around 19-44% [10]. Pulmonary involvement seen in RA patients has high clinical significance as it leads to increased morbidity and mortality [11]. The most important characteristic of RA related pulmonary disease is that almost all anatomical parts of the lung are prone to RA related tissue injury [12]. The overall risk of having ILD in RA patients is 19.2% as compared to the risk of having ILD in the common population [13]. ILD is a spectrum of pulmonary diseases that involve all parts of pulmonary bronchovascular units, including alveolar epithelium, capillary endothelium, alveoli, perivascular connective tissue, and perilymphatic tissues. RA is only second to systemic sclerosis as far as the incidence of ILD in connective tissue disorders is concerned [14]. The natural history of ILD is not very well defined in patients. Complications may arise themself or secondary to immunosuppressive drug treatment. High-resolution computed tomography (HRCT), that emerged during the past decade, is an important tool to diagnose the different abnormalities in RA related ILD.

Materials And Methods
From June 2014 to June 2015, 54 patients were selected from the outpatient department of Mayo Hospital, Lahore, with RA related pulmonary disease, according to American College of Radiology (ACR) criteria 2010 [15]. The complete history was taken, and patients with comorbidities like pulmonary tuberculosis, chronic obstructive pulmonary disease (COPD), and lung masses were excluded after evaluating chest X-rays. HRCT chest was performed using a multislice multidetector scanner. Axial images were acquired in a supine position, taking complete deep inspiration. Images were taken using a 0.5 m slice thickness with at least 1 cm slice interval. Image reconstruction was done using a bone algorithm.

Results
Altogether 54 cases were studied to complete the sample size of the project. Out of the 54 patients, 18 (33.33%) were male, while 36 (66.67%) were female. The mean age of the patient was 44.17± 11.315 years, with the minimum age being 15 years and the maximum age being 65 years. Patients had a variable presentation, and the commonest presentation to the hospital was exertional dyspnea ( Table 1).    (Table 3). Similarly, one (1.9%) had unilateral bronchiectasis involving the right lung, and one (1.9%) patient had bronchiectasis involving the left lung.

Findings Unilateral right lung involvement Unilateral left lung involvement Bilateral involvement
Ground  Regarding the zone involvement, the lower zone was found to be more frequently involved (   Based on these patterns of involvement of the lung, usual interstitial pneumonia (UIP) was diagnosed in six (11.1%) patients (Table 5). Similarly, non-specific interstitial pneumonia (NSIP) was diagnosed in 14 (25.9%) of the patients. Findings of HRCT that did not fall under any defined category were labeled as others, as were present in five (9.3%) patients.    Similarly, GGO was present in 21 (38.9%) patients (Figure 2), nine (16.7%) patients had honeycombing. Bronchiectasis was present in two (3.7%), whereas traction bronchiectasis was present in 17 (31.5%) such as shown in Figure 3. Air trapping was present in one (1.9%), two (3.7%) patients had mosaic perfusion, and three (5.6%) patients had architectural distortion.

FIGURE 3: Axial section showing bronchiectasis
Blue arrowhead indicates bronchiectasis.
Metafratzi ZM et al. .used normal healthy individuals as control against known patients of RA [19]. They used a semi-quantitative grading system, which has also been described in the past. The presence and extent of findings on HRCT chest were coded according to lung zones bilaterally, making a total of six zones. Only air trapping was given a score of eight on its presence on paired inspiratory and expiratory images. The control subjects showed minimal findings with scores of less than 3.6. The most common findings were air trapping and bronchiectasis. The abnormalities noticed in patients were equal to a score of 5.2 (moderate in severity) with only air trapping having a score of 14 (maximum severity). Other findings were bronchiectasis, bronchial wall thickening, macro nodules, and GGO.
Chansakul TN, in their study, concluded that traction bronchiectasis and the extent of honeycombing (as our earlier findings illustrated in Figures 4-6) were strongly associated with morbidity and mortality [20]. RA related ILD carried a bad prognosis when they compared HRCT findings to pulmonary function tests. They also completely evaluated patients' intrathoracic noncardiac findings on CT scans in terms of pleural, parenchymal, vascular disease as well as drug-related complications and opportunistic infections. They found that UIP (illustrated in Figure 5) was commoner than NSIP. There was more overlap between NSIP and UIP patterns.