 Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 - 1 - Sleep disorders and other medical and socio-demographic factors in systemic scleroderma Leyla Bagheri (1), Hoda Kavosi (2), Nasim Shokouhi (3), Shila Aghayani (4), Khosro Sadeghniiat Haghighi (5), Seyed Reza Najafizadeh (6) (1) Department of Internal Medicine, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; (2) Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran; (3) Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran; (4) Department of Rheumatology, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; (5) Sleep Breathing Disorders Research Center, Tehran University of Medical Sciences, Tehran, Iran; (6) Rheumatology Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Abstract We aimed to investigate sleep disorders in patients with systemic scleroderma (SSc) and its relationship with socio-demographic and medical factors and to provide a suitable solution to better control the disease and improve the quality of life in these patients. This cross-sectional study evaluated SSc patients seen at a rheumatology clinic from September 1, 2022, through April 1, 2023.The patients were examined by the main investigator of the project and entered the study after taking the medical history and meeting the criteria of ACR 2013 Classification Criteria. Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and STOP-Bang Questionnaire were employed to investigate sleep disorders. A total of 103 patients were included in the study. The average age of the patients was 48.42 ± 12.4 years. PSQI showed lower quality of sleep scores among SSc (68% of patients), which was significantly related to the degree of skin stiffness in patients, telangiectasia, interstitial lung disease (ILD) in computed tomography (CT) scan, patient age, duration of the disease, and pulmonary artery pressure (PAP). STOP-Bang Questionnaire revealed that obstructive sleep apnea (OSA) was significantly associated with telangiectasia, ILD, patient age, disease onset age, disease duration, body mass index and PAP. Insomnia had a statistically significant relationship with telangiectasia, ILD and patient age. Drowsiness during daily activities was not significantly related to any of the individual variables and disease-related variables. Sleep disorders are common in patients with systemic scleroderma. Telangiectasia, ILD and patient age were related to all sleep quality disorders and respiratory apnea and insomnia. Furthermore, the amount of skin involvement significantly causes disturbances in the quality of sleep of patients, where in the group with diffuse skin stiffness, 80% of patients exhibited disturbances in the quality of sleep. Therefore, paying attention to sleep health can be an effective factor in improving the quality of life of patients with SSc. Key Words: systemic scleroderma; sleep disorders; telangiectasia; quality of life. Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 Scleroderma or systemic sclerosis (SSc) is a condition accompanied by restricted dermatological condition (e.g., abnormal skin thickening, and systemic involvement of internal organs (pulmonary hypertension (PH), interstitial lung disease (ILD), esophageal motility disorders, oropharyngeal dysfunction, etc.). This disease is characterized by immune dysfunction, vasculopathy and excessive collagen fibrosis.1-6 The wide array of cardiopulmonary phenotypes in SSc has raised the hypothesis that scleroderma may be linked to sleep- disordered breathing (SDB).5 This immune dysfunction has been previously described to be associated with difficulty sleeping and increased risk for sleep.4,8-10 Few studies are available regarding potential factors associated with sleep problems in SSc. The findings of Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 - 2 - existing studies have shown its correlation with esophageal dysmotility, dyspnea and restless leg syndrome, and fatigue as well as pain, the severity of reflux symptoms, worsening dyspnea, Gastrointestinal symptoms, and pruritus.8,9,11-13 Therefore, the current study aimed at assessing the association of sleep disturbance with socio-demographic and medical factors among patients with SSc. Understanding the factors potentially related to sleep problems in SSc is important to guide clinicians in the management of patients and improving overall quality of life and well-being. Materials and Methods Patients We cross-sectionally evaluated patients seen at the rheumatology clinic, two tertiary referral centers of Iran, from September 1, 2022, through April 1, 2023, for scleroderma evaluation. Sufficient sample size was determined as 41 using G-power tool, considering a Type I error as low as 0.05, a power as high as 0.95, an effect size of 0.2 and a P of 0.7. All experimental procedures were ethically approved by the ethics board of Vice-Chancellor of Research and Technology of Tehran University of Medical Sciences Research. All methods in our study were carried out in accordance with the Declaration of Helsinki. Informed consent was obtained from all subjects The inclusion criteria were: SSc confirmed by 2 rheumatology specialists based on American College of Rheumatology (ACR) 2013 Classification criteria, Age 18 and above, and the ability to fill out questionnaires. Exclusion criteria included: Psychological disorders such as major depression and psychosis (based on the patient's history and medical records), Primary cognitive impairment, Pregnancy, History of using sleeping pills, BMI > 35, and Patient's lack of consent to participate in the research. we excluded patients who received more or equal 5 milligrams of prednisolone. Data Collection Demographic data of the patients (age, gender, BMI, disease duration) and data related to the major symptoms and organ involvement of the disease including Raynaud’s phenomenon, digital ulcers, skin stiffness, telangiectasia, ILD based on chest CT scan, forced vital capacity(FVC) percent predicted in spirometry, left ventricle ejection fraction percentage (EF%) by echocardiography ,pulmonary arterial pressure(PAP) measurement by right heart catheterization, gastroesophageal reflux, arthritis and/or arthralgia and renal crisis were collected by prepared questionnaires based on interview and registered patients files. Then the information was matched with the patient's medical records. In order to investigate sleep disorders in these patients, The Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and STOP-Bang Questionnaire are used in the present study. PSQI questionnaire was used to check sleep quality during the last month. This questionnaire contains 8 items, based on which a score higher than 5 indicates poor sleep quality. STOP-Bang questionnaire was employed to assess respiratory apnea and based on 5 questions, patients were divided into two groups with respiratory apnea and without it. The ESS questionnaire was used to check the amount of daily sleepiness, which includes 8 questions and is divided based on whether the patient falls asleep or not in different situations. The ISI Table 1. Frequency of sleep disorders based on standard questionnaires in patients with systemic scleroderma participating in the study. Variable Condition Frequency in systemic scleroderma patients Percent (%) Number Sleep quality based on the Pittsburgh Questionnaire (PSQI) ≥ 5 is not a problem )32 ( 33 5 < Disturbance in sleep quality )68 ( 70 Insomnia(ISI) 7-0 lack of sleep )46.6 ( 48 14-8 mild insomnia )24.3 ( 25 15-21 moderate insomnia )25.2 ( 26 22-28 severe insomnia )3.9 ( 4 sleepiness (ESS) ≥ 10 without drowsiness )93.2 ( 96 < 10 severe drowsiness )6.8 ( 7 Respiratory disorder and apnea while sleeping (Stop Bang) <3 No risk of breathing apnea )68.9 ( 71 ≥3 At risk of breathing apnea )31.1 ( 32 Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 - 3 - questionnaire also examines insomnia, which includes 7 questions, and based on scoring, patients are divided into no insomnia (scale 0-7), mild insomnia (scale14-8), moderate insomnia (scale15-21) and severe insomnia (scale 22-28). The datasets used or analyzed during the current study are available from the corresponding author on reasonable request. Statistical analysis We analyzed data with IBM SPSS version 20.0 (Chicago, IL, USA). The extracted information is analyzed with independent t test, chi square and regression analysis. Independent two-sample t-tests and Mann-Whitney were used for normally and no normally distributed variables. The level of statistical significance was set at p<0.05. Results Descriptive findings Demographic information is shown in Table 1. Among 103 patients participating in the research, 86% of the patients were women and 14% of the patients were men. Based on the body mass index (BMI), 52% of the patients were within the normal weight range. This is while 35% of the patients were overweight and 13% of them were underweight. As shown in Table 1, the most common co- morbidities in SSc patients referring to the clinic were related to Raynaud's phenomenon (99%), skin stiffness (diffuse: 40.8%; limited: 58.3%), (Table 1). Furthermore, gastroesophageal reflux (76.7%), ILD (67%) and arthralgia/arthritis (65%) had a high prevalence among patients. Telangiectasia and digital ulcers had a prevalence of 38.8% and 30.1% among patients, respectively. The renal crisis was not observed in any of the patients referred to the clinic. Inappropriate sleep quality was the most common sleep disorder (68% prevalence) among the studied patients, followed by insomnia, severe insomnia: 3.9%, moderate insomnia: 26%; mild insomnia: 25%). 32% of patients were at risk of sleep apnea and 7% of patients had severe sleepiness during daily activities (Table 1). Analytical findings Fisher's and chi-square tests were employed to investigate the relationship between sleep quality and qualitative findings based on the PSQI questionnaire. Disturbance in sleep quality was significantly related to skin stiffness, telangiectasia and ILD, (p<0.5). The results of logistic regression showed that the chance of sleep quality disorder in people with ILD CT complication is 4.97 times higher than in people without this complication. The chance of sleep quality disorder in people with diffuse skin stiffness was 2.83 times higher than in people with limited skin stiffness. The chance of having a disorder in the quality of sleep in those with telangiectasia was 7.67 times that of patients who did not have this complication (Supplementary materials Table 1). In order to investigate the relationship between sleep quality and patients' condition based on the PSQI questionnaire, for quantitative findings, independent two-sample t-tests and Mann-Whitney tests were used for normal and non-normal data, respectively. Disturbance in sleep quality was significantly related to patients' age, duration of disease and pulmonary artery pressure (PAP) (p<0.5) (Table 2). Based on the Stop-Bang questionaire, the level of sleep apnea was found to be significantly associated with telangiectasia and ILD (Supplementary materials: Table 2). The results of logistic regression showed that the chance of having sleep apnea in individuals with ILD CT complications was found to be 2.82 times higher than those without complications. The chance of having sleep apnea in people with telangiectasia was 3.47 times higher than those without this complication. Table 2. The results of the relationship between sleep quality and quantitative variables in patients with SSc. Two-sample independent t-test Disturbance in sleep quality No disturbance in sleep quality P-value Age of the patient 51.17 ± 11.32 42.58 ± 12.75 0.001 Age of disease onset 38.37 ± 10.51 34.98 ± 12.46 0.154 FVC% predicted 70.86 ± 15.39 76.82 ± 16.34 0.075 Mann-Whitney test duration of illness 12.0 (6.0, 18.0) 6.0 (4.0, 10.0) 0.001 BMI 23.5 (20.6, 29.0) 21.08 (20.3, 25.2) 0.101 EF % 55.0 (55.0, 55.0) 55.0 (55.0, 55.0) 0.524 PAP mmHg <<<< 30.0 (27.0, 37.3) 27.08 (20.0, 30.0) 0.004 Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 - 4 - In order to investigate the association of sleep apnea with the condition of patients based on the Stop-Bang questionnaire, sleep apnea was significantly related to the age of the patients, the age of onset of the disease, the duration of the disease, BMI and PAP (Table 3). Based on the ESS questionnaire, no significant relationship was found between sleepiness and any of the investigated variables in patients as revealed by Fisher's and chi-square tests (Supplementary materials: Table 3). Based on the ESS questionnaire, no significant relationship was found between sleepiness and any of the investigated variables as revealed by independent two- sample t-tests and Mann-Whitney (Table 4). Based on the ISI questionnaire and qualitative findings, a significant relationship was found between insomnia and telangiectasia and ILD (Supplementary materials: Table 4). The one-way analysis of variance (ANOVA) showed that insomnia has a significant relationship only with the age of the patients (Table 5). Post hoc Tukey test demonstrated that the average age of the normal insomnia group was significantly different from the subclinical insomnia and moderate insomnia groups (p<.05). As a matter of fact, the average age of individuals in the group with normal insomnia was 10.3 Table 3. The results of the relationship between sleep apnea and quantitative variables in patients with SSc. Two-sample independent t-test At risk of sleep apnea No risk of apnea p-value Age of the patient 57.41 ± 9.42 44.37 ± 11.46 <.001 Age of disease onset 42.63 ± 9.61 34.88 ± 11.12 0.001 FVC % predicted 70.91 ± 16.43 73.61 ± 15.66 0.427 Mann-Whitney test duration of illness 13.0 (7.3, 21.8) 8.0 (4.0, 13.0) 0.002 BMI 24.5 (21.0, 31.9) 21.9 (20.3, 25.8) 0.013 EF % 55.0 (51.3, 55.0) 55.0 (55.0, 55.0) 0.683 PAP mmHg 31.5 (25.8, 39.5) 28.0 (25.0, 32.0) 0.024 Table 4. The results of the relationship between sleepiness during daily activities and the quantitative variables. Two-sample independent t-test With sleepiness No sleepiness p-value Patient age 53.71 ± 11.10 48.03 ± 12.46 0.244 FVC% predicted 74.00 ± 15.71 72.68 ± 15.96 0.833 Mann-Whitney test with sleepiness No sleepiness P-value Age of disease onset 45.0 (40, 49.0) 34.0 (28.0, 46.5) 0.095 duration of illness 6.0 (5, 18.0) 10.0 (5.0, 16.0) 0.670 BMI 28.7 (21, 35.5) 22.2 (20.4, 26.5) 0.086 EF % 55.0 (50, 55.0) 55.0 (55.0, 55.0) 0.662 PAP(mmHg) 30.0 (28, 37.0) 29.0 (25.0, 35.0) 0.674 Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 - 5 - years lower compared to the group with subclinical insomnia. In addition, the average age difference between the normal group and the insomnia group was 9.12 years. Table 5. The results of ANOVA test to investigate the relationship between different groups of insomnia and quantitative parametric variables Normal Subclinical insomnia Moderate insomnia severe insomnia p-value Age of the patient 43.19 ± 12.02 53.56 ± 9.84 52.31 ± 12.16 53.75 ± 11.62 0.001 Age of disease onset 35.36 ± 11.13 37.96 ± 10.80 39.19 ± 10.93 43.75 ± 16.15 0.314 BMI 23.29 ± 4.36 23.46 ± 5.23 24.99 ± 6.39 27.88 ± 4.89 0.229 FVC % (predicted) 75.25 ± 15.17 67.60 ± 17.39 72.85 ± 16.08 74.75 ± 7.63 0.276 Table 6. The results of the Kruskal-Wallis test regarding the relationship of different groups of insomnia with quantitative non-parametric variables. Normal Subclinical insomnia Moderate insomnia severe insomnia P-value Disease duration 6.0 (3.3, 10.0) 16.0 (7.5, 22.0) 13.0 (6.8, 17.3) 9.0 (4.3, 16.8) <.001 EF % 55.0 (55.0, 55.0) 55.0 (55.0, 55.0) 55.0 (50.0, 55.0) 52.5 (46.3, 55.0) 0.036 PAP mmHg 27.0 (21.3, 30.0) 30.0 (27.0, 33.5) 36.5 (26.5, 40.3) 38.0 (30.5, 40.3) 0.001 Table 7. Dunn's test. Dunn's multiple comparisons test Mean rank diff. P-value Disease duration Normal vs subclinical insomnia -30.0 <.001 Normal vs moderate insomnia -24.0 0.006 Normal vs severe insomnia -11.1 >.999 Subclinical insomnia VS moderate insomnia 6.0 >.999 Subclinical insomnia VS severe insomnia 18.8 >.999 Moderate insomnia vs severe insomnia 12.9 >.999 EF % Normal vs subclinical insomnia -6.0 0.342 Normal vs moderate insomnia 11.2 0.071 Normal vs severe insomnia 22.0 0.098 Subclinical insomnia VS moderate insomnia 17.2 0.016 Subclinical insomnia VS severe insomnia 28.0 0.042 Moderate insomnia vs severe insomnia 10.8 0.432 PAP mmHg Normal vs subclinical insomnia -14.1 0.056 Normal vs moderate insomnia -26 <.001 Normal vs severe insomnia -35.9 0.021 Subclinical insomnia VS moderate insomnia -11.9 0.154 Subclinical insomnia VS severe insomnia -21.8 0.174 Moderate insomnia vs severe insomnia -9.9 0.536 Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 - 6 - Due to the non-normality of the data in the insomnia groups, the non-parametric Kruskal-Wallis test was used, and the results showed that the studied groups have statistically significant differences in terms of the duration of the disease and the percentage of EF and PAP (Table 6). Dunn's test was used for pairwise comparisons using GraphPad Prism (Table 7). Discussion The present study was conducted with the aim of investigating sleep disorders and their relationship with socio-demographic and medical factors in patients with SSc referred to the two tertiary referral rheumatology clinics. In the current study, variables of individual characteristics such as gender of patients, age of patients, and body mass index (BMI) as well as characteristics of the disease including skin stiffness type, age of disease onset and duration of disease, telangiectasia, ILD and other organ involvement were separately analyzed for their relationship with various common types of sleep disorders. The results of the present study demonstrated that patients with SSc suffer from many sleep disorders. Our findings demonstrated a statistically significant relationship between skin stiffness, telangiectasia, ILD observation in CT scan, patient age, duration of illness and pulmonary artery pressure with sleep quality (p<0.05). Furthermore, patients who had lower pulmonary artery pressure had better sleep quality, less risk of sleep apnea, and less insomnia. In other words, the majority of patients with blood pressure higher than 27 mmHg suffered from one of the types of sleep disorders. It was also found that the presence of gastroesophageal reflux, forced vital capacity (FVC) percent predicted measures and having arthritis or arthralgia were not predictors of poor sleep. SBD increases with increasing age, likely owing to the physiological and physical changes. Additionally, increased comorbidity and its subsequent polypharmacy are linked to SDB with increasing age.14 Nokes et al. (2019) reported that the only predictive variables for abnormal oximetry were age as revealed by regression analysis, which is considered to be associated with an increased risk of SDB, regardless of the presence of underlying lung disease.5 Minic et al. (2014) revealed that older age and increased Epworth Sleepiness Scale were linked to an increased risk of SDB.15 Obstructive sleep apnea is associated with an increased risk of pulmonary hypertension regardless of the presence of interstitial lung disease, so detection and treatment of sleep apnea in SSc patients is an important measure to prevent or postpone pulmonary hypertension and help to decrease morbidity and mortality in this group.19 SSc has been described to be linked to lung complications including ILD, pulmonary hypertension, restrictive-ventilatory limitation and fibrosis associated with anatomic changes in the upper airways,5 affecting sleep quality and sleep breathing movements. In clinical studies, it is also believed that SSc patients with polysomnography findings are at increased risk of sleep disorders. Prado et al. (2002) evaluated sleep disorders in SSc patients and found that SSc patients had decreased sleep efficiency, rapid-eye movement sleep, increased arousal index and slow-wave sleep, but not sleep apnea seemed to have an increased risk for sleep-disordered breathing in SSc.10 This immune dysfunction has been previously described to be associated with difficulty sleeping and increased risk for sleep disturbance.7-10 Sleep disturbances have been found to be related to worsening dyspnea, depressed mood and severity of reflux symptoms in SSc patients.9 Another study by Milette et al. (2013) reported that sleep disturbance in SSc was correlated with gastrointestinal symptoms, pain and pruritus.7 Researchers have also shown that lower quality of sleep was found to be linked to pain, fatigue, depressive symptoms, and functional status among SSc patients.16 In the same context, it has been shown that higher depression, fatigue and pain scores in patients with SSc were associated with functional disability.17,18 Poor sleep quality not only can be associated with a functional disability but also is an important problem in childbearing women which can related to the incidence of diabetes during pregnancy.20 The strong point of our study is the assessment of one the most important missed compliant of the SSc patients by nonaggressive and simple validated methods like questionnaires, of course, there are limitations to our study. it's more exact to do other procedures like polysomnography or measure inflammatory and fibrotic serum biomarkers in future studies. the impact of drugs like steroids and substances or smoking and alcohol consumption could be evaluated in other studies in the future. In conclusion, it was found that low quality of sleep is a very common symptom in patients with SSc. Interestingly, the presence of gastroesophageal reflux, forced vital capacity (FVC) percent predicted measures and having arthritis or arthralgia were not predictors of poor sleep. Our findings revealed a statistically significant relationship between skin stiffness, telangiectasia, ILD observation in CT scan, patient age, duration of illness and pulmonary artery pressure values with sleep quality. Sleep disorders in patients with SSc occur due to multifactorial origin and multidirectional disease-related variables such as degree of skin stiffness and respiratory involvement. List of acronyms ACR- American College of Rheumatology BMI- body mass index ESS -Epworth Sleepiness Scale FVC- forced vital capacity ILD- interstitial lung disease ISI -Insomnia Severity Index PH- pulmonary hypertension PSQI -Pittsburgh Sleep Quality Index SDB- sleep-disordered breathing SSc -systemic scleroderma Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 - 7 - Contributions of Authors Study conception, design, methodology, data collection, formal analysis, writing original draft, review and editing done by LB, HK, SA, KSH and SRN. All authors read and approved the final edited manuscript. Acknowledgments The authors are grateful to the partecipants for their kind cooperation. Funding None. Conflict of Interest The authors declare they have no financial, personal, or other conflicts of interest. Ethical Publication Statement We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Corresponding Author Seyed Reza Najafizadeh, Rheumatology Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. ORCID iD: 0000-0002-1860-9450 Email: najafisr@tums.ac.ir E-mails and ORCID iD of co-authors Leyla Bagheri : Leylabagheri90@gmail.com ORCID iD: 0000-0002-7496-5417 Hoda Kavosi: h-kavosi@sina.tums.ac.ir ORCID iD: 0000-0003-4762-6943 Nasim Shokouhi: shokouhinasim@ymail.com ORCID iD :0000-0002-4746-8087 Shila Aghayani: shila.aghayani@yahoo.com ORCID iD: 0000-0001-6002-079X Khosro Sadeghniiat Haghighi: Sadeghniiat@yahoo.com ORCID iD: 0000-0001-5242-5113 References 1. Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009 May 7;360(19):1989-2003. doi: 10.1056/NEJMra 0806188. PMID: 19420368. 2. 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Submission: December 12, 2023 Revision received: December 24, 2023 Accepted for publication: December 27, 2023 Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 9 Supplementary materials: Table 1. The results regarding the relationship between sleep quality and patients' condition. Sleep quality Total p-value No disturbance disturbance Gender Female 27 62 89 0.368 81.80% 88.60% 86.40% Male 6 8 14 18.20% 11.40% 13.60% Weight range Underweight 5 8 13 0.519 15.20% 11.40% 12.60% Normal weight 19 35 54 57.60% 50.00% 52.40% Overweight 9 27 36 27.30% 38.60% 35.00% Skin stiffness does not have 1 0 1 0.017 3.00% 0.00% 1.00% Limited 24 36 60 72.70% 51.40% 58.30% Diffuse 8 34 42 24.20% 48.60% 40.80% Raynaud’s phenomenon Does not have 0 1 1 1 0.00% 1.40% 1.00% Has it 33 69 102 100.00% 98.60% 99.00% Digital ulcers does not have 23 49 72 0.975 69.70% 70.00% 69.90% Has it 10 21 31 30.30% 30.00% 30.10% Telangiectasia does not have 29 34 63 <.001 87.90% 48.60% 61.20% Has it 4 36 40 12.10% 51.40% 38.80% ILD CT does not have 19 15 34 <.001 57.60% 21.40% 33.00% Has it 14 55 69 42.40% 78.60% 67.00% Reflux does not have 7 17 24 0.731 21.20% 24.30% 23.30% Has it 26 53 79 78.80% 75.70% 76.70% Arthralgia and/or arthritis does not have 14 22 36 0.275 42.40% 31.40% 35.00% Has it 19 48 67 57.60% 68.60% 65.00% Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 10 Supplementary materials: Table 2. The results of the relationship between the risk of sleep apnea and the condition of patients. category Groups Total p-value No risk of sleep apnea risk of sleep apnea Gender Female 64 25 89 0.124 90.10% 78.10% 86.40% Man 7 7 14 9.90% 21.90% 13.60% Weight range Underweight 10 3 13 0.230 14.10% 9.40% 12.60% Normal weight 40 14 54 56.30% 43.80% 52.40% Overweight 21 15 36 29.60% 46.90% 35.00% Skin stiffness does not have 1 0 1 0.174 1.40% 0.00% 1.00% limited 45 15 60 63.40% 46.90% 58.30% diffuse 25 17 42 35.20% 53.10% 40.80% Raynaud’s phenomenon does not have 0 1 1 0.311 0.00% 3.10% 1.00% has it 71 31 102 100.00% 96.90% 99.00% Digital ulcers does not have 49 23 72 0.820 69.00% 71.90% 69.90% has it 22 9 31 31.00% 28.10% 30.10% Telangiectasia does not have 50 13 63 0.004 70.40% 40.60% 61.20% has it 21 19 40 29.60% 59.40% 38.80% ILD CT does not have 28 6 34 0.039 39.40% 18.80% 33.00% has it 43 26 69 60.60% 81.30% 67.00% Reflux does not have 15 9 24 0.458 21.10% 28.10% 23.30% has it 56 23 79 78.90% 71.90% 76.70% Arthralgia and/or arthritis does not have 29 7 36 0.062 40.80% 21.90% 35.00% has it 42 25 67 59.20% 78.10% 65.00% Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 11 Supplementary materials: Table 3. The results of the relationship between sleepiness during daily activities and the qualitative variables. Category Groups Total p-value No sleepiness With sleepiness Gender Female 82 7 89 0.589 85.40% 100.00% 86.40% Man 14 0 14 14.60% 0.00% 13.60% Weight range Underweight 13 0 13 0.463 13.50% 0.00% 12.60% Normal weight 51 3 54 53.10% 42.90% 52.40% Overweight 32 4 36 33.30% 57.10% 35.00% Skin stiffness does not have 1 0 1 1.000 1.00% 0.00% 1.00% limited 56 4 60 58.30% 57.10% 58.30% diffuse 39 3 42 40.60% 42.90% 40.80% Raynaud’s phenomenon does not have 1 0 1 1.000 1.00% 0.00% 1.00% has it 95 7 102 99.00% 100.00% 99.00% Digital ulcers does not have 68 4 72 0.427 70.80% 57.10% 69.90% has it 28 3 31 29.20% 42.90% 30.10% Telangiectasia does not have 57 6 63 0.243 59.40% 85.70% 61.20% has it 39 1 40 40.60% 14.30% 38.80% ILD CT does not have 32 2 34 1.000 33.30% 28.60% 33.00% has it 64 5 69 66.70% 71.40% 67.00% Reflux does not have 22 2 24 0.663 22.90% 28.60% 23.30% has it 74 5 79 77.10% 71.40% 76.70% Arthralgia and/or arthritis does not have 35 1 36 0.417 36.50% 14.30% 35.00% has it 61 6 67 63.50% 85.70% 65.00% Sleep disorders in systemic scleroderma Eur J Transl Myol 34 (1) 12183, 2024 doi: 10.4081/ejtm.2024.12183 12 Supplementary materials: Table 4. The relationship of types of insomnia with patients' condition base on the Fisher's and Chi-2 tests. Normal )n=48( Subclinical insomnia (n=25) moderate insomnia (n=26) severe insomnia (n=4) Total p-value Gender Female 41 22 22 4 89 1 85.40% 88.00% 84.60% 100.00% 86.40% Man 7 3 4 0 14 14.60% 12.00% 15.40% 0.00% 13.60% Weight range Underweight 7 2 4 0 13 0.717 14.60% 8.00% 15.40% 0.00% 12.60% Normal weight 26 15 12 1 54 54.20% 60.00% 46.20% 25.00% 52.40% Overweight 15 8 10 3 36 31.30% 32.00% 38.50% 75.00% 35.00% Skin stiffness does not have 1 0 0 0 1 0.11 2.10% 0.00% 0.00% 0.00% 1.00% limited 34 11 13 2 60 70.80% 44.00% 50.00% 50.00% 58.30% diffuse 13 14 13 2 42 27.10% 56.00% 50.00% 50.00% 40.80% Raynaud’s phenomenon does not have 0 1 0 0 1 0.28 0.00% 4.00% 0.00% 0.00% 1.00% has it 48 24 26 4 102 100.00% 96.00% 100.00% 100.00% 99.00% Digital ulcers does not have 33 20 15 4 72 0.222 68.80% 80.00% 57.70% 100.00% 69.90% has it 15 5 11 0 31 31.30% 20.00% 42.30% 0.00% 30.10% Telangiectasia does not have 37 13 12 1 63 0.011 77.10% 52.00% 46.20% 25.00% 61.20% has it 11 12 14 3 40 22.90% 48.00% 53.80% 75.00% 38.80% ILD CT does not have 24 3 6 1 34 0.003 50.00% 12.00% 23.10% 25.00% 33.00% has it 24 22 20 3 69 50.00% 88.00% 76.90% 75.00% 67.00% Reflux does not have 10 6 8 0 24 0.649 20.80% 24.00% 30.80% 0.00% 23.30% has it 38 19 18 4 79 79.20% 76.00% 69.20% 100.00% 76.70% Arthralgia and/or arthritis does not have 23 6 6 1 36 0.086 47.90% 24.00% 23.10% 25.00% 35.00% has it 25 19 20 3 67 52.10% 76.00% 76.90% 75.00% 65.00% Patients Results