Increased Prevalence of Comorbidities in Systemic Sclerosis Patients in India

Dear Editor,

Systemic sclerosis (SSc) significantly impacts the quality of life. It also carries one of the highest mortality rates among autoimmune diseases, with an estimated standardised mortality ratio ranging from 2.5 to 4. ¹ Patients with SSc often experience a range of comorbid conditions, which may pre-exist or develop as a consequence of the disease itself. Previous studies have highlighted the prevalence of certain comorbidities among individuals diagnosed with SSc, including pulmonary arterial hypertension, interstitial lung disease, gastroesophageal reflux disease, cardiovascular conditions and secondary infections.^2,3 The burden of comorbidities in SSc complicates disease management, considerably impacts the quality of life, increases morbidity and contributes to higher mortality rates in patients. ⁴ Continuous vigilance and prompt diagnosis are essential for the effective management of these comorbidities.

This cross-sectional study aims to investigate the pattern and prevalence of comorbidities in SSc patients across India using clinical and demographic data from the Indian Rheumatology Association (IRA) database. Data were collected from patient reports and medical charts, and the comorbidities were assessed by the trained experts using ICD-10-based Charlson Comorbidity Index definitions. Conditions included cardiovascular (myocardial infarction, heart failure, congenital and rheumatic heart disease, peripheral vascular disease), neurological (stroke, transient ischemic attack, hemiplegia, dementia, Parkinson’s), respiratory (chronic pulmonary disease, asthma), rheumatologic (rheumatic diseases, psoriasis, osteoarthritis, osteoporosis, fibromyalgia, gout), gastrointestinal (peptic ulcer, inflammatory bowel disease, recurrent diarrhoea), metabolic (diabetes, hyperlipidaemia, thyroid disorders), hepatic and renal (mild to severe liver disease, hepatitis B/C, renal disease), malignancies (leukaemia, lymphoma, metastatic and non-metastatic cancers), infections (AIDS/HIV, tuberculosis), psychiatric disorders (depression, neurosis) and allergic diathesis. ⁵

For the entire IRA database registry, the minimum number of subjects needed for comparison across the six AIRDs under consideration was 6,500. ⁶ For SSc, the estimated sample size was 166, assuming a default proportion of 0.5 per 10,000 population. Statistical analyses were conducted using SPSS (IBM, version 29.0.0). Patients were grouped by comorbidities and age (<50 and ≥50 years). Descriptive statistics were applied with categorical variables presented as counts and percentages and continuous variables as mean ± SD. Fisher’s exact test and chi-square tests analysed categorical data, while continuous variables were assessed using a two-tailed t-test. A multivariate analysis was performed for common and significant comorbidities.

The study included 183 adult patients (mean age: 47.03 ± 11.94 years; range: 21-81) who fulfilled American College of Rheumatology criteria for SSc. ⁷ The participants had an average disease duration of 118.23 ± 81.78 months. The study population exhibited a pronounced female predominance, with a female-to-male ratio of 8.63:1. Of the cohort, 77 patients (42.1%) had comorbidities, with a higher prevalence observed in females (88.3%) than males.

Regional disparities in comorbidities were evident, with a higher prevalence in the southern region (61.04%) compared with the northern region (38.96%, P = .038). While previous studies have reported the clinical and autoantibody profiles of SSc patients from northern and southern India, there is a lack of research specifically examining the prevalence of comorbidities related to SSc across these regions. This underscores the significance of the present study. In a study investigating comorbidities contributing to stroke, a similar trend was observed, with higher prevalence of associated conditions such as diabetes and dyslipidaemias in South India compared with the North. ⁸ Additionally, a nationwide study reported a multi-morbidity prevalence of 7.2%, with higher rates in urban areas and southern states, including Puducherry. ⁹ Based on these findings, it may be inferred that the regional differences in the distribution of comorbidities among SSc patients in northern and southern India could reflect broader patterns seen in the general population for other non-communicable diseases.

The variation in comorbidities between these regions may be influenced by differences in healthcare access, diagnostic facilities, genetic and environmental factors, dietary habits and lifestyle. Additionally, socioeconomic status and healthcare-seeking behaviour may contribute to these disparities.

The most common conditions in the current cohort were thyroid disorders (22.4%), hypertension (12.02%) and diabetes (5.46%). Thyroid disorders were notably higher in this study (22.4%) compared with the estimated 11% prevalence in the general Indian population. ¹⁰ A nationwide study from the Mediterranean region identified a higher prevalence of hyperthyroidism among SSc patients, predominantly in females. ¹¹ Similarly, Cherim et al. concluded that SSc patients, especially females, have a higher incidence of elevated TSH levels and hypothyroidism than the general population, findings that align with the present study. ¹²

Hypertension was observed in 12.02% of the cohort, which is lower than the prevalence reported in the SPRING registry (23.7%) and the general Indian population (29.8%).^4,13 This lower prevalence may be attributed to the study’s criteria, where patients were classified as hypertensive only if they had a prior diagnosis and required treatment intervention, rather than through proactive screening, as done in the ICMR survey and SPRING registry.

Diabetes prevalence in the current study (5.46%) closely matches the 5.6% reported in a comparative study by Panopoulos et al. among SSc patients. ¹ However, the general Indian population has a higher diabetes prevalence (11.4%), as reported in the ICMR-INDIAB study, with regional variations across the country. ¹⁴ A nationwide cohort study by Tseng et al. demonstrated that patients with SSc had a lower incidence of both Type 1 and Type 2 diabetes compared with control subjects. ¹⁵ Research indicates that the lower incidence of diabetes in SSc patients may be due to increased whole-body insulin sensitivity, which could contribute to the reduced prevalence observed in this population. ¹⁶ Additionally, Abugharbyeh et al. observed a significantly lower prevalence of SSc among diabetic patients, implying a potential protective effect of diabetes against SSc development. ¹⁷

Overall, 33.88% of patients had at least one comorbidity, while 6.56% and 1.64% had two and three comorbidities, respectively. Similarly, in a cross-sectional study conducted in North India, Ghosh et al. reported that 39.6% of SSc patients had at least one comorbidity. ²

Age stratification revealed a higher prevalence of comorbidities in patients aged >50 years (52.05%) compared with those aged ≤50 years (35.45%, P < .026). Comorbid conditions such as diabetes (10.96% in older vs. 1.82% in younger, P = .015), hypertension (20.55% vs. 6.36%, P = .004) and thyroid disorders (28.77% vs. 18.18%) were also more prevalent in older patients (Table 1). Multivariate analysis indicated a strong association between age and comorbidities, with hypertension showing the strongest link, followed by diabetes. Thyroid disorders demonstrated a significant positive association with disease duration. In line with this finding, a multicentre study of 408 SSc patients with a mean age of 59 years found that older patients had higher rates of comorbidities such as hypertension and dyslipidaemia, than younger patients. ¹

Table 1.

Prevalence, Types of Comorbidities and Comparison of Comorbidities in SSc Patients Aged Below and Above 50 Years.

Comorbidities	Overall (n = 183)	≤50 Years of Age (n = 110)	>50 of Age (n = 73)	P Value
Age (years)	47.03 ± 11.94 (21–81)	39.42 ± 7.87 (21–50)	58.51 ± 6.66 (51–81)
Total probable duration of illness (in months)	118.23 ± 81.78 (6–480)	98.05 ± 54.55 (8–252)	147.17 ± 103.42 (6-480)	<.001#
Gender [M(F)]	19 (164)	14 (96)	5 (68)	.202*
Region-wise distribution
North	72	50 (45.45%)	22 (30.14%)	.038*
South	111	60 (54.55%)	51 (69.86%)
Comorbidity status
Present	77 (42.08%)	39 (35.45%)	38 (52.05%)	.026*
Comorbidities
Peripheral vascular disease	2 (1.09%)	1 (0.91%)	1 (1.37%)	1.000^
Migraine	3 (1.64%)	3 (2.73%)	0 (0%)	.277^
Chronic pulmonary disease	1 (0.55%)	1 (0.91%)	0 (0%)	1.000^
Bronchial asthma	1 (0.55%)	1 (0.91%)	0 (0%)	1.000^
Rheumatologic diseases	9 (4.92%)	6 (5.45%)	3 (4.11%)	1.000^
Diabetes	10 (5.46%)	2 (1.82%)	8 (10.96%)	.015^
Cancer without metastases	1 (0.55%)	0 (0%)	1 (1.37%)	.399^
Hyper/hypothyroidism	41 (22.4%)	20 (18.18%)	21 (28.77%)	.093*
Tuberculosis	5 (2.73%)	3 (2.73%)	2 (2.74%)	1.000^
Hypertension	22 (12.02%)	7 (6.36%)	15 (20.55%)	.004*
Number of comorbidities
0	106 (57.92%)	71 (64.55%)	35 (47.95%)	.025^
1	62 (33.88%)	34 (30.91%)	28 (38.36%)
2	12 (6.56%)	5 (4.55%)	7 (9.59%)
3	3 (1.64%)	0 (0%)	3 (4.11%)

Notes: *Chi-square.

^Fisher’s test.

^# t test.

Despite the significant findings, the study has certain limitations. A major limitation of the study is the absence of a control group, which prevents direct comparison and limits the ability to determine whether the prevalence of comorbidities is significantly higher or lower in SSc patients relative to the general population. The smaller sample size (n = 183) restricts the generalisability of findings, and its cross-sectional design does not allow the assessment of disease progression. Reliance on medical records for data collection may introduce reporting biases, while the lack of regional socioeconomic stratification limits further interpretation of disparities. Additionally, referral bias from tertiary care centres may lead to an overrepresentation of severe cases.

The significant comorbidity burden in SSc patients, particularly thyroid disorders, hypertension and diabetes, underscores the need for comprehensive evaluation and personalised treatment strategies to optimise outcomes. Both age and disease duration appear to be important, potentially synergistic contributors to this burden. Routine screening for these common comorbidities is crucial, with age-specific management protocols prioritised due to the strong association of hypertension and diabetes with age. Early detection through routine screening helps prevent complications such as cardiovascular events, metabolic imbalances and organ dysfunction. Addressing regional disparities, particularly the higher burden in southern India, requires improved healthcare access in resource-limited areas. Enhancing early detection and intervention through region-specific strategies can help reduce disease complications. Patient education on lifestyle modifications and treatment adherence is essential for better disease management. Due to the cross-sectional nature of the study, the influence of treatment regimens, autoantibody profiles and extracutaneous systemic involvement on the prevalence of comorbidities could not be assessed. Further longitudinal studies with larger cohorts are needed to explore regional and demographic disparities, providing deeper insights into disease progression and enabling more tailored management strategies. Moreover, studies with larger cohorts and comprehensive data on socioeconomic status, lifestyle factors and medication use are warranted to better elucidate their impact on the prevalence of comorbidities in SSc.

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