|Year : 2019 | Volume
| Issue : 4 | Page : 277-282
Charlson Comorbidity Index in patients with systemic lupus erythematosus in Egypt and its relation with disease characteristics
Samah M Alian1, Sahar S Khalil2, Rabab S Zaghlol1
1 Department of Rheumatology and Rehabilitation, Faculty of Medicine, Zagazig University, Zagazig, Sharqia Governorate, Egypt
2 Department of Rheumatology and Rehabilitation, Faculty of Medicine, Zagazig University, Zagazig, Sharqia Governorate, Egypt; Department of Physical Medicine and Rehabilitation, Dubai Hospital, Dubai, United Arab Emirates
|Date of Web Publication||31-Dec-2019|
Dr. Samah M Alian
Omar Ibn El-Khattab Street, Zagazig, Sharqia Governorate
Source of Support: None, Conflict of Interest: None
Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder associated with various comorbid conditions.
Here, we assessed the burden of comorbidity in patients with SLE in Egypt using the Charlson Comorbidity Index (CCI) and determined its association with the disease characteristics.
Patients and Methods: In this retrospective study, data of patients with SLE in Egypt were collected from the medical records. This included demographic data, clinical characteristics, comorbidities, and baseline SLE disease activity index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) scores at the last visit. The CCI score was calculated for each patient. The data of deceased patients were also collected.
Results: Overall, 152 patients were included in this study. The most common comorbidities excluded from the CCI were serious infections (27%) and hypertension (23%); the most common comorbidities included in the CCI, apart from the connective tissue disease, were moderate or severe renal disease (12.5%), peptic ulcer (9.9%), and diabetes mellitus (9.9%) without end-organ damage. The mean CCI score was 1.9 and was significantly correlated with the disease duration, SLEDAI, and SDI. The death rate was 7.9%; the most common cause of death was infection (50%). Death was significantly associated with a high score of SLEDAI, SDI, and CCI. The mortality rate was higher in patients with SLE along with hypertension, renal affection, hyperlipidemia, infection, and tumors (P < 0.05).
Conclusion: Patients with SLE in Egypt experienced comorbidities and high CCI scores that affected their survival.
Keywords: Comorbidity, Egypt, mortality, systemic lupus erythematosus
|How to cite this article:|
Alian SM, Khalil SS, Zaghlol RS. Charlson Comorbidity Index in patients with systemic lupus erythematosus in Egypt and its relation with disease characteristics. Indian J Rheumatol 2019;14:277-82
|How to cite this URL:|
Alian SM, Khalil SS, Zaghlol RS. Charlson Comorbidity Index in patients with systemic lupus erythematosus in Egypt and its relation with disease characteristics. Indian J Rheumatol [serial online] 2019 [cited 2020 Aug 11];14:277-82. Available from: http://www.indianjrheumatol.com/text.asp?2019/14/4/277/270741
| Introduction|| |
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with diverse clinical features. SLE can attack any organ of the body, affect its function, and/or cause damage. The damage is not only caused by SLE itself but also by other comorbid conditions as well as the cumulative effects of therapeutic drugs, especially steroids and immunosuppressants.
Over the past few decades, the survival of SLE patients has dramatically improved, placing them at an increased risk of developing new comorbidities. Associated comorbidities usually lead to aggressive management, worse prognosis, increased health-care costs, and a negative impact on the quality of life. The European League Against Rheumatism included the importance of monitoring, prevention, and management of risk factors in its recommendations.
The Charlson Comorbidity Index (CCI) is a validated tool, which was developed for the prediction of mortality risk of comorbid diseases. It includes 19 categories. Each category has a weighted score from 1 to 6 according to its ability to predict the risk of mortality; thereafter, all scores are summated into a single score. This index was developed mainly based on the analysis of medical records; a higher score indicates a higher risk of mortality.
SLE-associated comorbidities in a large population in Egypt have not been well studied. Hence, the aim of this study was to assess the incidence of comorbidities in patients with SLE in Egypt using the CCI and to determine the relationship between CCI and the disease characteristics, disease activity, induced damage, and mortality risk.
| Patients and Methods|| |
This is a single-center retrospective cohort study. The data of patients with SLE were collected from the medical records of the Rheumatology and Rehabilitation Department, Zagazig University Hospital, which is the biggest hospital in eastern Egypt. Informed consent was obtained from all patients or their families (in case of deceased patients). The study was approved by the Ethical Committee of the institute and was conducted in accordance with the guidelines of the Declaration of Helsinki. The diagnosis of SLE was based on the updated American College of Rheumatology (ACR) revised criteria for SLE classification.
Data on demographics and clinical characteristics of the patients including age at the time of diagnosis, sex, disease duration, occupation, education, smoking status, body mass index (BMI), diagnosis of antiphospholipid syndrome (APS) using the revised APS classification criteria, SLE medication history, comorbidities, erythrocyte sediment rate, and anti-double-stranded DNA antibody laboratory test results were collected. Moreover, the baseline SLE disease activity index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores at the last visit were collected. Comorbidities present at any moment during the evolution of SLE, whether listed in CCI or not, were screened; thereafter, the CCI was calculated for each patient. Furthermore, information on the patients who discontinued follow-up was obtained. When follow-up was discontinued due to death, the cause of death was ascertained by reviewing the hospital file and death certificate. The rate of premature death (before the age of 70 years according to the World Health Organization's definition) was calculated.
Data were collected, tabulated, and then statistically analyzed using the SPSS software (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY, USA: IBM Corp.). Quantitative data were expressed as mean ± standard deviation, and qualitative data were expressed as numbers (percentages). The Student's t-test was used to analyze the difference between two independent groups and when data were parametric, while the Mann–Whitney U-test was used when the data were nonparametric. Percentages of categorical variables were compared using the Chi-square test or Fisher's exact test when appropriate. Spearman's correlation was used to assess the relationship between various study variables (nonparametric); (+) indicated a positive relationship, while (−) indicated an inverse relationship. All tests were two-sided. A value of P < 0.05 was considered statistically significant (S), while a value of P ≥ 0.05 was considered statistically nonsignificant.
| Results|| |
The demographic data, clinical characteristics, and comorbidities that are not included in the CCI and medical history of the patients are shown in [Table 1]. The distribution of CCI items in the patients is shown in [Table 2]. Apart from the connective tissue disease (100%), the most frequent comorbidities were moderate or severe renal disease (12.5%), followed by peptic ulcer (9.9%) and diabetes mellitus (9.9%) without end-organ damage. Leukemia (0.7%) and metastatic solid tumor (0.7%) were the least frequent complications. Dementia or acquired immunodeficiency syndrome was not detected in the patients.
|Table 1: Demographic and clinical characteristics of the enrolled patients|
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|Table 2: Distribution of Charlson Comorbidity Index items in enrolled patients|
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When the CCI scores in different groups of patients were assessed according to the disease characteristics, CCI scores were found to be significantly higher in male patients, smokers, and those with steroids intake >10 mg/day and lupus nephritis [Table 3]. Moreover, comparisons showed that the CCI score was positively correlated with the disease duration (r = 0.345, P = 0.000), SLEDAI score (r = 0.373, P = 0.000), and SDI score (r = 0.452, P = 0.000 [Table 4].
|Table 3: CCI score in different groups of patients according to their disease characteristics|
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|Table 4: Correlation between CCI score and SLE patient's characteristics|
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Twelve deaths occurred during the follow-up period which included 7 men and 5 women. The rate of premature death (mortality rate) defined as the ratio of the number of patients who died due to SLE to the total number of patients with SLE was 7.9%. The attributed causes of early death were infection in six patients (50%), cardiovascular events in four patients (33.3%), and tumors in two patients (16.7%) (not tabulated).
The deceased patients (n = 12) had significantly higher age at diagnosis, BMI, SLEDAI score, SDI score, and CCI score but lower disease duration than patients who were alive (n = 140). Moreover, mortality was higher in male patients. The deceased patients experienced a higher incidence of lupus nephritis, hypertension, dyslipidemia, serious infections, and tumors than those who were alive (P< 0.05) [Table 5].
| Discussion|| |
SLE is associated with various comorbidities that affect the quality of life and survival rate of the patients. Early diagnosis and recognition of high-risk patients might be useful for proper disease management and risk factors reduction. The CCI is a tool for identifying comorbidities associated with an increased risk of mortality. It has been validated in many clinical studies as a tool for predicting early mortality risk in various diseases.,
SDI and CCI are valuable tools for detecting SLE severity and associated complications. However, by definition, SDI only determines the damage induced after SLE development. In contrast, the CCI has the advantages of determining the cumulative comorbidities and assigning a specified weight to each comorbid item based on its ability to cause mortality. Despite numerous researches conducted on patients in Egypt with different rheumatic diseases, studies with a large sample size remain inadequate. With increase in the population in Egypt, it is important to raise the quality of clinical studies.
This work has demonstrated that patients with SLE in Egypt experience several comorbidities that affect their survival. Therefore, these comorbidities should be carefully screened and treated along with the usual SLE treatment. There are two fundamental findings in the current study: first, the disease duration, SLEDAI, and SDI were significantly associated with the CCI and second, the relationship between the CCI and SDI indicated that the development of organ damage was significantly related to the occurrence of comorbidities.
The most common comorbidities detected were serious infections, followed by hypertension. Multiple studies found that patients with SLE have a greater burden of comorbidities such as infection, hypertension, cardiovascular risks,, cerebrovascular accidents, dyslipidemia, osteoporosis, osteonecrosis, metabolic syndrome, and tumors.
The mean CCI score in this study was 1.9. The most frequent item in the index, apart from the connective tissue disease (100%), was moderate or severe renal disease (12.5%). The mean CCI score in the current study is relatively higher than other studies; the mean CCI score of patients with SLE has been shown to be 1.57 in Canada, 1.35 in Sweden, and 1.0 in Korea. This might indicate that the study population has a higher risk of comorbidity. Moreover, the CCI related to the renal disease is noticeably higher in our study than other studies conducted worldwide.,, This might be related to the higher rate of renal involvement in patients with SLE (46.7%). Similarly, other studies conducted in Egypt have confirmed the high incidence of renal disorder, ranging from 44.7% to 67.8% among the patients with SLE in Egypt.,,
In this study, the CCI scores were significantly higher in the male patients, smokers, those with steroid intake >10 mg/day, those with lupus nephritis, and deceased patients. The CCI score was not significantly different between juvenile-onset and adult-onset lupus and this may be due to the small number of juvenile-onset patients in our study. Moreover, the CCI score was positively correlated with the disease duration, SLEDAI score, and SDI score. This is in agreement with the study performed by Kim et al. on patients with SLE in Korea; the study confirmed the association of organ damage with higher CCI and SLEDAI scores. Moreover, they highlighted the role of cumulative therapeutic medications, disease activity, and comorbid conditions as contributing factors for the development of organ damage in patients with SLE.
We found that the deceased patients had a significantly higher age at diagnosis, BMI, SLEDAI score, SDI score, and CCI score and had lower disease duration than patients who were alive. Moreover, mortality was higher in male patients. The deceased patients had higher incidences of lupus nephritis, hypertension, dyslipidemia, serious infections, and tumors than those who were alive.
A study of 841 hospital-admitted patients with SLE in Singapore concluded that the mortality rate was associated with higher CCI scores. They confirmed the importance of using CCI to screen the high-risk patients to manage their comorbidities and thus improve the survival rates.
A multicenter population-based study conducted on 669 patients with SLE showed that the age-adjusted CCI is a valid tool to predict mortality and that it is strongly associated with decreased survival. Consistent with this study, a case–control study performed by Hernández-Cruz et al. concluded that the high SLEDAI score, multiorgan involvement, steroid usage, and infections were associated with mortality in patients with SLE in Mexico. In addition, the infection was shown to be the most common cause of mortality.
In the current study, the mortality rate was 7.9%. The most common causes of death were infections, followed by cardiovascular events. This mortality rate is comparable to other studies worldwide., In contrast, some studies also reported lower and higher death rates. The difference between these studies could be explained by the differences in genetic, cultural, and environmental backgrounds as well as the method of patient selection and the variability in the disease duration of each cohort that could potentially affect the disease progression.
Confirming the association between mortality and SLE disease characteristics, Doria et al., concluded that higher mortality rates are associated with male sex, renal disorder, APS positivity, and disease severity. Moreover, other studies also linked the high baseline disease activity with increased mortality rates, considering the disease activity as an important prognostic factor for the survival of patients with SLE., In addition, another study found an association between increased BMI and the increased incidence of lupus nephritis, hypertension, dyslipidemia, and atherosclerosis, and consequently, decreased quality of life and functional capacity. In agreement with this study, a retrospective study conducted in Turkey compared the disease characteristics in deceased patients and alive patients with SLE; the study showed that the deceased group had significantly higher age at the time of diagnosis and shorter disease duration than the alive group. The shorter time of follow-up and higher age at diagnosis were the most important predictors of mortality.
In a study where data are collected from patients' files, there are chances of missing data and difficulty of confirm some data. Moreover, some patients discontinue their follow-up program or do not attend the follow-up visits regularly. Fortunately, these limitations were not present in our study. However, a prospective multicenter study with a large sample size is required to verify the findings of our study.
| Conclusion|| |
Patients with SLE in Egypt experience a number of comorbidities and have a high CCI score that affect their survival. Appropriate screening and management of comorbidities should be considered for proper clinical care of patients with SLE.
Comorbidity and mortality continues to be associated with SLE despite the advances in SLE therapy. Further research is required to investigate the long-term complications of SLE and the optimal disease management strategy without increasing the risks of developing additional comorbidities. Multicenter studies on different ethnic populations are required to know the exact burden of comorbidity and its effect on survival.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]