AMJ Vol 9 No 1 March 2022-2.indd Althea Medical Journal. 2022;9(1) 49 Lung Abnormalities in Systemic Sclerosis Patients through Spirometry, Chest X-Ray, and High-Resolution Computed Tomography Scan Sumartini Dewi,1,3 Waliyyuddin Robbani,2 Iceu Dimas Kulsum1 1Department of Internal Medicine, Faculty of Medicine Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Bandung, Indonesia, 2Faculty of Medicine Universitas Padjadjaran, Indonesia, 3Immunology Study Center, Faculty of Medicine Universitas Padjadjaran, Indonesia Correspondence: Dr. Sumartini Dewi, dr., Sp.PD-KR., M.Kes, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, Jalan Pasteur No. 38, Bandung, Indonesia, E-mail: sumartini.dewi@unpad.ac.id Introduction Systemic sclerosis (SSc) is a chronic progressive multisystem autoimmune disease with heterogenous clinical manifestations.1,2 The etiologies are multifactorial, including genetic and environmental.3 The pathophysiological processes that occur are endothelial dysfunction, autoimmunity and the fibrosis process.4,5 Based on skin involvement, clinical manifestations, and laboratory examination results, SSc is divided into two subtypes: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc).1 SSc can affect all system organs in the body.6 Pulmonary organ manifestations frequently occur, but the symptoms are non-specific. Symptoms can be fatigue, dry cough, or shortness of breath.7,8 Early detection of organ involvement in SSc is essential.9 Patients diagnosed early and receiving prompt therapy can minimize the possibility of irreversible organ damage.6 In a study conducted on 953 systemic sclerosis patients, subjects with severe interstitial lung disease (ILD) have a poor prognosis.8 Another study has shown that one of two main leading causes of death in SSc patients are ILD.10 Radiological examination and pulmonary function tests (spirometry) are needed to detect lung abnormalities in SSc patients.11 Spirometry is more affordable than other modalities because the tools are widely available; however, the obtained results cannot rule out extrapulmonary abnormalities such as skin disorders.12 A tuberculosis-like appearance often appears on chest X-ray Althea Medical Journal. 2022;9(1):49–54 Abstract Background: Systemic sclerosis (SSc) is a multisystem autoimmune illness with a wide range of clinical symptoms. The pulmonary organ manifestations frequently occur, but the symptoms are non- specific. Radiological examination and pulmonary function tests (spirometry) are needed to detect lung abnormalities in SSc patients. This study aimed to obtain information about the overview of lung abnormalities in SSc patients through spirometry, chest x-ray, and high-resolution computed tomography (HRCT) scan examination. Methods: A descriptive qualitative study was conducted on 75 SSc patients registered in Dr. Hasan Sadikin General Hospital Bandung from January 2019 to December 2020. Data were collected with a total sampling method and presented in proportions and percentages. Results: The majority of subjects were affected by cutaneous 73 (97%), pulmonary 29 (39%), and musculoskeletal 17 (23%) involvement. Spirometry revealed that 43 subjects (57%) had restrictive lung disease, with one false-positive case and two false-negative cases. On a chest x-ray, 45 (60%) of subjects had abnormalities. The majority of subjects were found to have Ground-glass opacities on HRCT scans. Ground-glass opacities were discovered in 46 subjects (82%) and 27 subjects (60%) were identified as having severe fibrosis scores. Conclusion: According to spirometry results and abnormalities on chest x-ray and HRCT scans, the majority of SSc patients have restrictive lung disease. Keywords: Chest X-ray, HRCT scan, interstitial lung disease, sclerosis systemic, spirometry https://doi.org/10.15850/amj.v9n1.2509 Althea Medical Journal. 2022;9(1) 50 examination resulting in misdiagnosis.13 Chest x-rays also cannot detect early ILD.14 High- resolution computed tomography (HRCT) scan requires sophisticated equipment and is limited only to a few large hospitals; however, it should still be performed because it is the gold standard for detecting ILD disorders.15–16 Research on overview of lung abnormalities on systemic sclerosis patients through spirometry, chest X-ray, and high-resolution computed tomography scan has not been widely studied in Indonesia. This study is expected to add information about the overview of lung abnormalities in SSc patients. The study results are expected to form the basis of future studies and help clinicians be aware of ILD incidence. This study aimed to obtain information about the overview of lung abnormalities in SSc patients through spirometry, chest X-ray, and HRCT scan examination. Methods A descriptive qualitative study was conducted on 75 SSc patients obtained from the patient registry in Dr. Hasan Sadikin General Hospital Bandung from January 2019 to December 2020. Data were collected with a total sampling method; proportions and percentages were presented in tables. The inclusion criteria were spirometry examination, chest X-ray, and HRCT scan data in the systemic sclerosis patient registry. Exclusion criteria were intrapulmonary and extrapulmonary conditions that were not caused by SSc, such as pulmonary tuberculosis or lung tumors and other lung infections. Variables used in this study were clinical characteristic (age, sex, modified Rodnan skin score, SSc subtype and clinical manifestation) and examination result (spirometry, chest x-ray and HRCT scan). Age used in this study was the age of subjects when they were admitted to the Rheumatology Clinic Dr. Hasan Sadikin General Hospital, Bandung. Sex consisted of male and female. The modified Rodnan skin score (MRSS) used in this study was the MRSS of subjects when they were admitted to the Rheumatology Clinic Dr. Hasan Sadikin General Hospital, Bandung. SSc subtype consisted of a diffuse and limited type. Clinical manifestations consisted of skin, respiration, musculoskeletal, gastrointestinal, and cardiovascular. Spirometry examination results consisted of restrictive lung disease and were graded based on severity. Chest X-ray consisted of normal and abnormal based Althea Medical Journal March 2022 on radiologist expertise. Likewise, HRCT scan consisted of normal and abnormal based on radiologist expertise. This study was approved by the Ethics Committee of Universitas Padjadjaran Bandung, Indonesia (No. 928/UN6.KEP/ EC/2020) and obtained the Research Licensing Letter issued by the Research Ethics Committee of Dr. Hasan Sadikin General Hospital Bandung (No. LB.02.01/X.2.2.1/2271/2021). Results The study result showed that the majority of subjects were female (97%). The mean age of the subjects was 39.08±13.52 years. Furthermore, the median MRSS score of the subjects was 15 (0–39). Most of the subjects had a diffuse type of SSc of 63%. The most common clinical manifestations were skin disorders 97%, respiratory disorders 39%, and musculoskeletal disorders 23% (Table 1). The spirometry examination showed that most subjects had restrictive lung disease (57%) (Table 2). From chest X-ray examinations, 30 subjects (40%) had normal results and 45 (60%) had abnormal results (Table 3). There were 19 subjects (25%) of the 75 subjects who did not undergo an HRCT scan. Only 56 subjects (75%) underwent HRCT scan examination. The most common lung abnormality based on HRCT scan was Ground- glass opacities (GGO) in 46 subjects (82%) (Table 4). There were 30 subjects (40%) with fibrosis scores that were not calculated, while most of the subjects with a score that was calculated (27 subjects, 60%) had severe pulmonary fibrosis (Table 5). Discussion This study showed a significant difference in gender among all patients at the Rheumatology Clinic Dr. Hasan Sadikin General Hospital, Bandung. The ratio of male and female was 73 and 2. This is consistent with a cohort study conducted by EULAR Scleroderma Trials and Research (EUSTAR) in 2011 in Europe, where the incidence of SSc in women was greater than that of men.17 Based on the subtype, diffuse SSc is the most common, this finding is appropriate with literature that states the diffuse type of SSc is the most common subtype of SSc.5 There were 73 subjects (97%) who had skin disorders, 29 subjects (39%) with respiratory Althea Medical Journal. 2022;9(1) 51Sumartini Dewi et al.: Lung Abnormalities in Systemic Sclerosis Patients through Spirometry, Chest X-Ray, and High-Resolution Computed Tomography Scan Table 1 Clinical Characteristic of Systemic Sclerosis Patients Characteristics Total (n=75) n (%) Age on average (years) 39.08±13.52 Gender Female Male 73 (97) 2 (3) MRSS score median 15 (0–39) SSc subtype Diffuse Limited 47 (63) 28 (37) Clinical manifestation Skin Skin stiffness Raynaud’s phenomenon Sclerodactyly Fish mouth Salt and pepper appearance Digital scar Telangiectasia Sausage fingers Ulkus digity Post inflammation hyperpigmentation 73 (97) 67 (89) 62 (83) 60 (80) 44 (59) 35 (47) 33 (44) 29 (39) 25 (33) 23 (31) 6 (8) Respiration Interstitial lung disease Dyspnea Dry cough Pulmonary hypertension Pleural effusion 29 (39) 20 (27) 18 (24) 11 (15) 7 (9) 1 (1) Musculoskeletal Arthralgia Joint stiffness Myopathy 17 (23) 15 (20) 5 (7) 1 (1) Gastrointestinal Dry mouth Nausea Decreased body weight Bloating Vomiting Esophageal dysmotility 7 (9) 4 (5) 2 (3) 2 (3) 2 (3) 1 (1) 1 (1) Cardiovascular Chest pain Palpitation Constrictive pericarditis Congestive heart failure 4 (5) 1 (1) 1 (1) 1 (1) 1 (1) N/A 2 (3) Note: Most of the subjects had overlapping clinical examinations, MRSS=modified Rodnan skin score disorders, and 17 subjects (23%) with musculoskeletal disorders. This is appropriate with the literature that states skin disorders, respiratory disorders, and musculoskeletal disorders are the most common manifestations in SSc subjects.6 Based on pulmonary function tests (spirometry), 43 subjects (57%) had restrictive lung abnormalities. One subject had normal spirometry results with abnormal chest HRCT scan result, which was mild pulmonary fibrosis. Two subjects had mild restrictive spirometry examination results with normal chest scan HRCT results. Suliman et al.18 in their study at the Zürich University Hospital, state that spirometry is only able to detect 59 of 102 SSc-ILD patients. Errors in the detection of lung abnormalities in these SSc patients are partly due to the low level of sensitivity and the limitations of the spirometry device, which cannot distinguish the cause of the restriction whether it is due to lung abnormalities, or from the stiffness of the chest and abdominal skin that is common in SSc patients.18 In this study, some subjects had mild restrictive spirometry results, but their chest scan HRCT results were normal. These subjects had skin disorders in the form of diffuse cuticle sclerosis that affects the chest wall and abdomen. This suggests that spirometry has limitations and can show false positive or false negative results, and can lead to false diagnosis if used as the primary modality in SSc-ILD detection. On chest X-ray, 45 subjects (60%) had abnormal results, and 30 subjects (40%) had normal results. In the group of subjects with normal chest X-ray, 16 subjects (21%) had abnormal HRCT scan results. In the group of subjects with normal chest X-ray but abnormal HRCT scan results, 9 subjects (12%) had Table 2 Spirometry Results of Systemic Sclerosis Patients Spirometry Results Total (n=75) n (%) Normal 3 (4) Restrictive lung diseases Mild Moderate Severe Very severe 43 (57) 19 (25) 24 (32) 0 0 N/A 29 (39) Note: N/A= not available; Not all subjects undergo spirometry examination Althea Medical Journal. 2022;9(1) 52 restrictive spirometry results; restrictive mild in 4 subjects (5%) and moderate restrictive in 5 subjects (7%). A study conducted by Morales-Cárdenas et al.19 mentions that the HRCT scan can detect SSc-ILD at the disease onset. This suggests that chest X-ray examination is not accurate in detecting SSc- ILD at the onset of the disease. However, the spirometry examination as an additional modality can increase accuracy in SSc-ILD diagnosis, especially in health facilities that do not have access to HRCT chest scans or at SSc patients who cannot perform HRCT thoracic scans.20 Four subjects (5%) had a chest X-ray image of active TB in this study. According to a study conducted by Agrawal et al.13 in 2019, the radiological features of ILD are similar to pulmonary tuberculosis, so misdiagnosis often occurs. When a chest HRCT scan is performed on a subject who has a chest X-ray in the form of active TB, there is no visible Table 3 Chest X-Ray Results of Systemic Sclerosis Patients Variables Total (n=75) n (%) Proportion Chest X-ray resultsb Normal pattern 30 (40) 0.400 Abnormal Cardiomegaly Bronchopneumonia Suggestive ILD Bronchitis Pleural effusion Aortic atherosclerosis Tuberculosis Pneumonia 45 (60) 22 (29) 9 (12) 8 (10) 7 (9) 6 (8) 6 (8) 4 (5) 3 (4) 0.600 0.293 0.120 0.106 0.093 0.080 0.080 0.053 0.040 Note: Some subjects have more than one abnormality on chest X-ray, ILD=interstitial lung disease Table 4 HRCT Scan Results of the Systemic Sclerosis Patients HRCT Scan Results Total (n=56) n (%) Proportion Ground glass opacities Bronchiectasis Irregular pleural margins Honeycombing Subpleural cyst Subpleural lines 46 (82) 35 (62) 13 (23) 8 (14) 6 (11) 2 (3) 46 (82) 35 (62) 13 (23) 8 (14) 6 (11) 2 (3) Note: Not all subjects undergo HRCT scan examination and most of the subjects has more than one lung abnormality based on HRCT scan examination, HRCT=high-resolution computed tomography Table 5 Fibrosis Severity Score Based on HRCT Scan Examination of Systemic Sclerosis Patients Variables Total (n=45) n (%) Proportion Normal Mild Moderate Severe 2 (4) 7 (15) 9 (20) 27 (60) 0.044 0.155 0.200 0.600 Note: Not all HRCT scan results are calculated for the degree of pulmonary fibrosis Althea Medical Journal March 2022 Althea Medical Journal. 2022;9(1) 53 infiltrate characteristic of TB infection. This suggests that chest X-rays cannot differentiate infiltrates due to SSc fibrosis or from TB infection and may cause errors in the diagnosis of pulmonary abnormalities in SSc patients. On the chest HRCT scan, the most common type of lung lesion in SSc patients with pulmonary abnormalities was the type of GGO lesion, which were 46 subjects (82%). This is consistent with the study conducted by Sambataro et al.21 in 2020, which states that the type of GGO lesions often appears on the chest HRCT scan of SSc patients with pulmonary abnormalities. This study is a qualitative descriptive study that evaluates data from spirometry, chest X-ray, and HRCT scan recorded in the systemic sclerosis patient registry; however, not all subjects undergo chest X-ray or chest HRCT examination, so that not all results are recorded. The subject’s condition when performing spirometry examination was not recorded in the systemic sclerosis patient registry. This can lead to bias since several intrapulmonary and extrapulmonary conditions do not result from SSc, such as skin and muscle stiffness at the chest and abdominal wall, pregnancy, and spine abnormalities affecting chest expansion.12 All data taken are only based on the sclerosis systemic patient registry, which may cause errors in data input actions. Data errors have been minimized by cross-checking with data from the Respirology Division for spirometry results and Radiology Department for chest X-ray and HRCT scan results. Some subjects did not undergo supporting examinations at hospital, so the incomplete data could not be searched in the patient’s medical record. In conclusion, most SSc patients have restrictive lung disease based on spirometry examination, and abnormality based on chest X-ray and HRCT scan examination. The HRCT scan examination remains the gold standard in a suspected interstitial lung disease case. 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