original article A cross-sectional hospital based study of clinical and patients from central rural India Sachin Ratanlal Agrawal, Iadarilang Tiewsoh, Atulsingh Rajput, Ajitprasad Jain Access this article online Website: www.ijaai.in DOI: 10.4103/0972-6691.116614 Quick Response Code: ABSTRACT Introduction: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder, the expression of which is greatly influenced by the combined effect of genetic, environmental, demographic and geographical factors. Various studies regarding clinical and immunological profile of SLE patients in India has been reported from a different region of India, especially from the urban area. We performed this study to understand the clinical and immunological profile of the SLE patients presenting to tertiary care center in rural central India. Materials and Methods: This study was conducted at a rural teaching hospital in central India. All patients records from 2007 to 2012 available with hospital having a discharge diagnosis of SLE and fulfilling the revised American College of Rheumatology criteria (1997) for SLE were analyzed regarding clinical and immunological profile. Results: We found 87 SLE patients out of 52,133 patients admitted in medicine department from 2007 to 2012 in the hospital record and included in the analysis. Nearly, 98% patients were female and 84% patients were under the age of 40 years. Common features present in these patients were immunological (97.7%), mucocutaneous (83.9%), hematological (72.4%) and renal (69.0%). Malar rash was the most common clinical feature presented in 71.3% patients followed by photosensitivity (63.2%) and oral ulcers (42.5%). Lymphopenia was the most common hematological abnormality present in 48.3%. Involvement of neurological, cardiovascular and respiratory system was found to be less common. Anti-nuclear antibodies were found to be positive in nearly 98% patients. Conclusion: Analysis of clinical profile of hospitalized SLE patients shows that the disease is more common in female patients, especially during the child bearing age group. The present study shows high frequency of mucocutaneous, hematological and renal manifestation in these patients. Key words: Central rural India, clinical and immunological profile, systemic lupus erythematosus Department of Internal Medicine, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, India Address for correspondence: Dr. Sachin Ratanlal Agrawal, Department of Internal Medicine, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha - 442 001, Maharashtra, India. E-mail: dragrawal82@gmail.com 33
INTRODUCTION Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder affecting mainly female gender especially during child bearing age group. The prevalence rate has been reported to be 52/100,000 populations in United States with higher rates reported among black and Hispanic group. [1] Review study conducted from Asia has shown the prevalence rate of disease from 30 to 50/100,000 population. [2] One prevalence study conducted from rural India has shown very low prevalence rate (3.2/100,000 population). [3] In another study conducted in Eastern India found that 3.9% of the children in the rheumatology department had SLE. [4] However, larger epidemiological studies are needed to confirm the finding of these studies regarding the prevalence of disease in India. Due to the role of estrogen in etiopathogenesis of disease, SLE is more common in female as compare with male, especially in child bearing age group with a ratio ranging from 7:1 to 15:1. [5] The disease expression is greatly influenced by the combined effect of genetic, environmental, demographic and geographical factors. Genetic factor superimposed on certain environmental factors plays a very pivotal role in manifesting abnormal immunological response. Considerable variation has been observed regarding various clinical manifestation of SLE among various ethnic groups as well as various geographical regions. The first case of SLE in India was reported in 1955. [6] Subsequently, studies have been conducted in different parts of the country describing the encountered manifestations in the Indian population with SLE. Various studies regarding clinical and immunological profile of SLE patients in India has been reported from different region of India. [7-12] Most of these studies come from northern or western part of India and only one study has been reported from central India. [13] Thus, there exists a gap in our understanding regarding clinical and immunological profile of SLE patients, especially from rural India. We performed this study to understand the clinical and immunological profile of the SLE patients presenting to tertiary care center in rural central India. MATERIALS AND METHODS Setting The study was conducted in Kasturba Hospital Sevagram, which is a 648-bedded tertiary teaching hospital. All patients who are discharge from the hospital are given electronic discharge summary, which consist of detail clinical history, examination and relevant investigations. All discharge diagnosis and summaries are filed with hospital information system and classified as per international classification of disease-10. Data collection We screened retrospectively all patients admitted to medicine department from the period of 2007-2012 through the hospital information system. We chose this period because detail information about the patient was not available through hospital information system prior to this period. All patients having a discharge diagnosis of SLE and fulfilling the revised American College of Rheumatology (ACR) criteria (1997) for SLE were included in the study. We collected the detail information of all these patients with respect to demographic characteristics, duration of disease and assessment of various organs involvement like cutaneous, musculoskeletal, renal, gastrointestinal tract, nervous and cardiopulmonary. We collected data regarding various investigation including complete blood count, urine microscopic examination, 24 h urine protein excretion, serum creatinine, blood urea, chest radiograph and electrocardiogram. We retrieved the information regarding auto antibodies level in all included patients mainly antinuclear antibodies (ANAs) and anti-double-stranded deoxyribonucleic acid (Ds DNA) antibodies. However, due to financial constraints, anti-ds DNA antibodies level could be obtained only in 49 patients out of 87. The Institutional Ethics Committee approved the study design. We did not collect any personal identity information from the discharge certificates. Analysis We did a descriptive analysis of all demographic features of all included patients. We performed the analysis of all clinical features present in SLE patients and calculated the cumulative percentage frequency of all clinical features present in SLE patients. We also calculated the cumulative percentage frequency of various systems involved in SLE patients. RESULTS Out of 52,133 patients admitted in medicine department from 2007 to 2012, 87 patients were found to have SLE. 85 (97.7%) patients were female and 2 (2.3%) were male. The patient s age at the time of presentation varies from 15 years to 60 years with a mean of 31 years (SD 10.75 years). Out of 87 patients, 73 (83.9%) patients were under the age of 40 years. Figure 1 show the various systems involved in SLE patients. Most common features involved in these patients were immunological (97.7%), mucocutaneous (83.9%), hematological (72.4%) and renal (69.0%). Table 1 shows the clinical profile of all SLE patients. Among the various mucocutaneous manifestation, malar rash was the most common clinical feature presented in 62 (71.3%) patients followed by photosensitivity and oral ulcers in 55 (63.2%) and 37 (42.5%) patients respectively. Renal involvement was present in 60 (69%) patients 34
and hemolytic anemia was present in 13 (14.9%) and 7 (8.1%) patients respectively. Regarding immunological profile, 85 patients (97.7%) were positive for ANA. Data about anti-ds DNA antibodies was available for 49 patients, out of which 46 (94%) were found to be positive. Figure 1: arious systems involved in systemic lupus erythematosus patients (n 8 ) Table 1: Clinical and immunological profile of SLE patients Variables No. of cases (%) Age distribution <20 years 19 (21.8) 21-40 years 54 (62.1) >40 years 14 (16.1) Sex distribution Male 2 (2.3) Female 85 (97.7) Clinical features Mucocutaneous manifestation Malar rash 62 (71.3) Discoid rash 28 (32.2) Alopecia 9 (10.34) Oral ulcer 37 (42.53) Photosensitivity 55 (63.2) Hematological Hemolytic anemia 7 (8.1) Leucopenia 16 (18.4) Lymphopenia 42 (48.3) Thrombocytopenia 13 (14.9) Renal Proteinuria (>0.5 g/d) 57 (65.5) Elevated serum creatinine 21 (25.3) Active urinary cast 3 (3.5) Neurological Psychosis 3 (3.5) Seizures 0 CVA 1 (1.15) Musculoskeletal Arthralgia 46 (52.9) Non-specific symptom (unexplained fever, myalgia) 72 (82.8) Serositis Pleural effusion 6 (6.9) Pericardial effusion 2 (2.3) Antinuclear antibodies 85 (97.7) Anti-Ds antibodies (49/87) 46 (93.9) SLE - Systemic lupus erythematosus, CVA - Cerebrovascular accidents of whom the most common feature was proteinuria in 57 (65.5%) patients followed by deranged creatinine and active urinary sediment in 21 (25.3%) and 3 (3.5%) patients respectively. Hematological features were found in 63 (72.4%) patients. Lymphopenia ( 1,500/cumm) was the most common hematological abnormality present in 42 patients (48.3%) followed by leucopenia ( 4,000/cumm) in 16 patients (18.5%). Thrombocytopenia ( 100,000/ cumm) Arthralgia was noticed in 46 patients (52.9%). Regarding neurological problems, 3 patients (3.5%) were found to have psychosis and 1 (1.2%) patient suffered an ischemic stroke. With respect to pulmonary and cardiac involvement, 6 patients (7%) were found to have pleural effusion and 2 patients (2.3%) had pericardial effusion. 3 patients (3.5%) were suffering from interstitial fibrosis and 2 patients had pulmonary tuberculosis. DISCUSSION In the present study of clinical and immunological profile of hospitalized SLE patients, we found that the disease was more common in female patients especially during the child bearing age group. Our study showed higher frequency of immunological, mucocutaneous, hematological and renal involvement in hospitalized patients. Involvement of neurological, cardiovascular and respiratory system was found to be less common. This study signifies detail clinical examination and focused investigation in patients suspected to have SLE, especially in female patients of child bearing age. Various studies have been conducted from different part of the country regarding clinical and epidemiological of SLE [Table 2]. A study done by Malaviya et al. [9] analyzing 1366 SLE patients from different part of India shows significant high proportion of patients presenting with mucocutaneous manifestations specially arthralgia (85%) malar rash (58.5%) and renal involvement (57%). Similar result has been found in our study showing involvement of mucocutaneous and renal manifestations in 83.9% and 70% patients. Malar rash (71.3%) and fever (82.8%) was the most common clinical feature in the present study. However, studies conducted by Binoy et al. [10] and Kosaraju et al. [11] from the south India have shown less prevalence of mucocutaneous manifestation, which might be because of dark complexion of the study population making it difficult to detect these features. Regional variation has been observed regarding renal involvement in SLE patients ranging from 20% to 73%. Study conducted from the northern [7] and western India [12] has shown high prevalence of renal involvement as compare with south India. [8,10,11] Present study has shown similar finding of high prevalence of renal involvement (69%) in the SLE patients. However, one study conducted from central India has shown less prevalence of renal involvement. [13] Prevalence of neuropsychiatric manifestation among SLE patients varies world-wide with higher prevalence noted 35
Table 2: Cumulative percentage frequency of clinical manifestations in patients with SLE from different studies in India Clinical manifestations Malaviya (1988) [7] n=329 (%) Madhavan (1988) [8] n=330 (%) Malaviya (1997) [9] n=1366 (%) Binoy (2003) [10] n=75 (%) Kosaraju (2010) [11] n=48 (%) Saigal (2011) [12] n=60 (%) Present study n=87 (%) Malar rash 85 74 58.5 40 35.41 43.3 71.3 (n=62) Discoid rash NA NA 7 5.3 NA 1.7 32.2 (n=28) Alopecia 82 75 NA 60 18.75 65 10.34 (n=9) Oral ulcer 64 51 57 64 25 61.7 42.53 (n=37) Photosensitivity 67 52 48 32 27.08 75 63.2 (n=55) Arthralgia 92 90 85 89.3 64.58 86.7 52.9 (n=46) Fever NA 74 77 NA 58.33 NA 82.8 (n=72) Hemolytic anemia 7 1 4 1.3 2 25 8.1 (n=7) Leucopenia 16 12.6 NA 14.7 NA 43.3 18.4 (n=16) Lymphopenia 20 7.5 NA NA NA NA 48.3 (n=42) Thrombocytopenia 11 7.5 9 12 NA 33.3 14.9 (n=13) Renal 73 45 57 33.3 20.83 56.7 69 (n=60) Neuropsychiatric 38 29 51 13.3 8.33 13.3 4.6 (n=4) Pulmonary NA NA NA 8 12.5 11.7 12.6 (n=11) Cardiovascular 29 28 NA 5.3 NA 6.7 2.3 (n=2) ANA 98 96 97 93.3 64.28 98.3 97.7 (n=85) Ds DNA 55 60.5 68 76 89.36 65 93.9 (n=46/49) NA - Not available, Ds DNA - Double-stranded deoxyribonucleic acid, ANA - Anti-nuclear antibody, SLE - Systemic lupus erythematosus in the Indian patients as compare to other ethnic groups. [14] Study conducted by Malaviya et al. [9] from India has shown that nearly half of the Indian patients of SLE has neuropsychiatric manifestation during the course of illness with more prevalence from the northern India [6] as compare to western or south India. [10-12] Our study showed only 4 patients (4.6%) presenting with neuropsychiatric manifestation. Higher prevalence of neuropsychiatric manifestations in the previous study might be because of inclusion of the broader group of manifestation included in the study population and lack of standard definition given by ACR in 1997. Hematological involvement was seen in 72.4% patients in the present study. Among the various hematological criteria defined by ACR, lymphopenia was the most prevalence (48.3%) in our study. This might be because of unregulated cell mediated immunity playing a vital role in the pathogenesis of disease. Other significant hematological abnormality found in the present study was leucopenia (18.4%) and thrombocytopenia (14.9%). Overall prevalence of hematological manifestation has been found to be low in various Indian studies with the highest prevalent found to be in the study conducted by Binoy et al. [10] from western India. Pleuroparenchymal involvement in the form of serositis was present only in 8 patients (9.2%); however, study from North and South India [8,9] have shown higher prevalence of cardiovascular manifestations. ANA is highly sensitive diagnostic test that can be used for screening the patients suspected to have SLE on clinical evaluation. However, because of low specificity it cannot be used for confirmation of disease. Our study shows that nearly 98% of patients were positive for ANA by indirect immunoflorescence method, which was consistence with other studies done from different part of India. However, a study conducted from South India [11] have shown low positivity for ANA (64.28%). The possible explanation for this as given by the author might be because of low titer of ANA to be detected by diagnostic test or not long enough follow-up of patients. In contrast to ANA, anti-ds antibody is highly specific test to confirmation of SLE. Various epidemiological studies from the India have shown positivity of anti-ds DNA antibody ranging from 55% to 76% with the exception of the study conducted from South India, [11] which had high positive result in 89% patients. The present study also has very high percentage of positive anti-ds DNA antibody results (94%). Since we could retrieve the data regarding anti-ds DNA antibody level only in 49 patients (56%), this might be giving high number of a positive result regarding anti-ds DNA antibody. Unlike ANA level, anti-ds DNA antibody level correlates very well with disease severity. [15] Our study has certain strengths. Our study included all the consecutive patients of SLE diagnosed based on American Rheumatology Association criteria to minimize sampling bias. We included all the physician verified clinical features based on their discharge summary for the analysis purpose. However, our study has few limitations. First, since it was a cross-sectional study based on hospitalized patients, it might be possible that more severe SLE patients requiring hospitalization was included in the study and SLE patients presenting on out-patient basis might differ in clinical presentation as compare to in-patients. Hence, this clinical profile of the SLE patients may not be truly representative of clinical profile of SLE patients in the community. Second; since follow-up of these SLE patients was not available; hence, we could not observe the change in clinical profile of these patients as the disease progress. Third, we could obtain anti-ds DNA antibody level only in around half of the 36
patients, which might be the reason for very high proportion of patients positive for anti-ds DNA. To conclude, analysis of clinical profile of hospitalized SLE patients shows that the disease is more common in female patients, especially during the child bearing age group. Present study shows high frequency of mucocutaneous, hematological and renal manifestation in these patients. Various geographical variations across the country need to be kept in mind while dealing with these patients. REFERENCES 1. Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: A comparison of worldwide disease burden. Lupus 2006;15:308-18. 2. Osio-Salido E, Manapat-Reyes H. Epidemiology of systemic lupus erythematosus in Asia. Lupus 2010;19:1365-73. 3. Malaviya AN, Singh RR, Singh YN, Kapoor SK, Kumar A. Prevalence of systemic lupus erythematosus in India. Lupus 1993;2:115-8. 4. Mondal R, Nandi M, Ganguli S, Ghosh A, Hazra A. Childhood lupus: Experience from Eastern India. Indian J Pediatr 2010;77:889-91. 5. Lahita RG. The role of sex hormones in systemic lupus erythematosus. Curr Opin Rheumatol 1999;11:352-6. 6. Desai SC, Bhandarkar SD. A case report of acute disseminated lupus erythematosus. Indian J Dermatol Venereol 1955;21:131-4. 7. Malaviya AN, Singh RR, Kumar A, De A, Kumar A, Aradhye S. Systemic lupus erythematosus in northern India: A review of 329 cases. J Assoc Physicians India 1988;36:476-80, 484. 8. Madhavan R. Systemic lupus erythematosus. The Madras experience. J Assoc Physicians India 1988;36:481-4. 9. Malaviya AN, Chandrasekaran AN, Kumar A, Shamar PN. Systemic lupus erythematosus in India. Lupus 1997;6:690-70. 10. Binoy JP, Muhammed F, Kumar N, Razia MV. Clinical profile of systemic lupus erythematosus in North Kerala. J Indian Rheumatol Assoc 2003;11:94-7. 11. Kosaraju K, Shenoy S, Suchithra U. A cross-sectional hospital-based study of autoantibody profile and clinical manifestations of systemic lupus erythematosus in south Indian patients. Indian J Med Microbiol 2010;28:245-7. 12. Saigal R, Kansal A, Mittal M, Singh Y, Maharia HR, Juneja M. Clinical profile of systemic lupus erythematosus patients at a tertiary care centre in Western India. J Indian Acad Clin Med 2011;13:27-32. 13. Shantaram V, Das UN, Srinivasan VR. Clinical profile of systemic lupus erythematosus-nizam Institute of Medical Sciences (Hyderabad) experience. J Indian Rheumatol Assoc 1995;3 Suppl: 7. 14. Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. The geoepidemiology of systemic lupus erythematosus. Autoimmun Rev 2010;9:A277-87. 15. Kumar A. Indian guideline on the management of SLE. J Indian Rheumatol Assoc 2002;10:80-96. How to cite this article: Agrawal SR, Tiewsoh I, Rajput A, Jain A. A of systemic lupus erythematosus patients from central rural India. Indian J Allergy Asthma Immunol 2013;27:33-7. Source of Support: Nil, None declared. Staying in touch with the journal 1) Table of Contents (TOC) email alert Receive an email alert containing the TOC when a new complete issue of the journal is made available online. To register for TOC alerts go to www.ijaai.in/signup.asp. 2) RSS feeds Really Simple Syndication (RSS) helps you to get alerts on new publication right on your desktop without going to the journal s website. You need a software (e.g. RSSReader, Feed Demon, FeedReader, My Yahoo!, NewsGator and NewzCrawler) to get advantage of this tool. RSS feeds can also be read through FireFox or Microsoft Outlook 2007. Once any of these small (and mostly free) software is installed, add www.ijaai.in/rssfeed.asp as one of the feeds. 37