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CLINICAL PATHOLOGICAL CHARACTERISTICS OF SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS PRESENTING AT A TERTIARY CARE HOSPITAL - A SINGLE CENTRE STUDY.

Byline: Syed Ali Shiram, Mushtaq Ahmed and Shazia Nisar

ABSTRACT

Objective: To determine the frequency of clinopathological characteristics of systemic lupus erythematosus (SLE) patients presenting to Military Hospital (MH) Rawalpindi.

Study Design: Descriptive cross sectional study.

Place and Duration of Study: The study was carried out at MH Rawalpindi, from Jan 2011 to Dec 2013.

Material and Methods: All patients presenting to Rheumatology department, MH Rawalpindi with a diagnosis of SLE were included in this study. Presenting features, clinical profile and laboratory parameters of patients were recorded.

Results: A total of 76 patients were included in this study, 70 (92.1%) were females and 6 (7.9%) male patients with female-male ratio of 11.6: 1. Mean age at presentation was 33 +- 8.31 years. Seventy two patients (94.7%) were anti nuclear antibody (ANA) positive, 63 (83%) were positive for anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibody and 6 (7.9%) were anti Smith positive. Seventy (92.1%) patients had musculoskeletal symptoms, 65 patients (85.5%) had fever, 36 (47.4%) patients had cutaneous symptoms, and 20 patients (26.3%) had oral ulcers. About 13 patients (17.1%) had alopecia and 15 patients (19.7%) had serositis. Forty two patients (55.3%) had nephritis, 20 patients (26.3%) had lupus cerebritis, 57 patients (75%) had hematological involvement, 9 patients (11.83%) had pulmonary involvement, 8 patients (10.5%) had rheumatoid arthritis (RA) factor positive and 7 patients (9.2%) had overlap syndrome.

Conclusion: Renal and hematological involvement was more common in this study population while mucocutaneous features and neuropsychiatric features were comparable to many local studies with exception to that of Lahore based study that showed much higher percentage of these features. These results reflect the need to have a high index of suspicion for kidney and hematological involvement in SLE patients.

Keywords: Clinical characteristics, prevalence, systemic lupus erythematosus (SLE), Pakistan.

INTRODUCTION

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease presenting with a wide variety of manifestations involving almost every organ of the body. The diagnosis of SLE is based on a combination of clinical and laboratory findings. The presence of 4 of the 11 American College of Rheumatology (ACR) criteria is used for classification purposes with the sensitivity of 85% and specificity of 95%1. These 11 criteria include butterfly rash, discoid lupus, photosensitivity, arthralgias, renal involvement, oral ulcers, serositis, hematological involvement, neurological involvement, immunological phenomena with positive anti-dsDNA antibody or anti-smith antibodies and positive ANA.

Systemic Lupus International Collaborating Clinics (SLICC) group revised the American college of Rheumatology (ACR) classification criteria for SLE in 2012 and classified a person as having SLE if there is biopsy-proven lupus nephritis with ANA or anti-dsDNA antibodies or if 4 of the diagnostic criteria, including at least 1 clinical and 1 immunologic criterion, have been fullfilled2.

In United States of America the prevalence of SLE has been estimated to range from approximately 5.8 to 130 per 100,000 population3. There is considerable variation in prevalence in Asia-Pacific countries; however, overall prevalence ranged from 4.3 to 45.3 per 100,000, and the overall incidence is from 0.9 to 3.1 per 100,000 per year4.

Asia is the largest continent of the world and it houses different ethnic and cultural groups of the population in different countries. There is a diversity of culture and climate within individual countries as well. Many studies have been done in the world including Asia, and some in Pakistan showing differences in the clinical spectrum of disease manifestations that reflect the varying environmental, socioeconomic, and genetic factors involved in the pathogenesis of disease5-8.

The rationale of this study was to determine the clinico-pathological features in patients presenting to Military Hospital Rawalpindi and to compare it with those of other Pakistani and Asian studies.

MATERIAL AND METHODS

This study was conducted at MH Rawalpindi, Rheumatology department. Permission was obtained from hospital ethical committee prior to conducting the study. Informed Verbal consent was taken from all the patients. The descriptive cross sectional study comprised documentation of all indoor and outdoor SLE cases meeting the 4 out of 11 Revised American College of Rheumatology (ACR) criteria for lupus presenting to rheumatology department Military Hospital, Rawalpindi from Jan 2011 till Dec 2013. Consecutive sampling technique was applied for data collection. Clinical and laboratory data of all the patients was recorded. Statistical analysis was done using SPSS 11.5. Descriptive statistics were given as figures and percentages and p-value was calculated using chi square test to determine any statistical significant difference among findings in different studies. The difference was considered statistically significant if p-value was equal to or less than 0.05.

RESULTS

A total of 76 patients were included in this study out of which 70 (92.1%) were females and 6 (7.9%) male patients with the female-male ratio of 11.6: 1. Mean age at presentation was 33 +- 8.31 years. Seventy patients (92.1%) had musculo-skeletal symptoms comprising arthralgias with joint pain and swelling but joint deformity was not seen in any patient with SLE alone though it was found in 2 out of 7 patients having overlap syndrome. Sixty five patients (85.5%) had fever which was low grade without any rigors. Cutaneous symptoms that included butterfly rash, discoid lupus along with photosensitivity were seen in 36 patients (47.4%). Twenty patients (26.3%) had oral ulcers. Thirteen patients (17.1%) had alopecia that was non-scarring, 15 (19.7%) patients had serositis mostly pleural effusion and ascites while none had pericardial effusion. Lupus nephritis documented by either increasing creatinine, proteinuria (>0.5g) or casts was seen in 42 patients (55.3%).

Twenty patients (26.3%) had neurological symptoms including headache, seizures and neuropsychiatric symptoms comprising hallucination and psychosis, 57 patients (75%) had hematological involvement comprising either leucopenia or thrombo-cytopenia or anemia. Nine patients (11.83%) had pulmonary involvement mainly pleurisy (9.2%), pulmonary fibrosis (1.31%) and pulmonary hemorrhage (1.31%). Seven patients (9.2%) had pattern consistent with overlap syndrome (figure).

Table-I: Comparison of this study with other Pakistani studies.

###This###Tahir et###p-###Ishaq et###p-###Rabbani et###p-###Batool et###p-

###study###al14###value###al15###value###al16 (Agha###value###al13###value

###(Rawalpindi)###(Karachi)###Khan)###(Lahore)

No of patients###76###49###105###198###61

Female-Male ratio###11.6:1###16:1###7:1###4:1

Mean age at

###33###31

presentation

Musculoskeletal###92.1###98###0.1646###77###0.0195###38###0.0001###90.2###0.6895

Renal###55.3###38###0.0718###22.8###0.0001###33###0.0007###75.4###0.0145

Neuropsychiatric###26.3###14###0.1106###14###0.0431###29###0.6836###65.5###0.0001

Hematological###75###22###0.0001###26###0.0001###98.4###0.0001

Serositis###19.7###8.6###0.0288###29###0.1275###39.3###0.0115

Pulmonary###11.83###12###0.9461###2.8###0.0165###23###0.0838

Cardiac###0###12###0.0001###13.1###0.0011

Cutaneous###47.4###64###0.0819###37###0.1681###29###0.0036###40###0.3468

Oral ulcers###26.3###58###0.0005###22.8###0.4994###20###0.2733

Alopecia###17.1###34###0.0246###22###0.3967###86.9###0.0001

ANA###94.7###100###0.1026###86###0.0001###90.0###0.3065

Anti-dsDNA###83###64###0.0131###74###0.1683###74###0.1106###85.2###0.7095

Anti smith###7.9###50###0.0001###26.0###0.0037

Autoimmune profile revealed that ANA was the most prevalent antibody followed by anti-dsDNA antibody whereas anti-smith antibody was seen in only minority of patients. Eight patients (10.5%) had RA factor positive out of which only 3 patients (4%) had features of rheumatoid arthritis. Two (2.63%) out of those 3 patients with rheumatoid arthritis had hand joint deformities and 1 (1.31%) patient had not developed any deformity yet.

DISCUSSION

This is a unique study as it shows comparison of not only the Pakistani data but also the comparison with different studies of regional countries at the same time. SLE is a multi-system autoimmune disease the exact mechanism of which is unclear however various factors implicated in the disease pathogenesis include hormonal, immunological and environmental factors on the background of genetic predisposition9,10. It is predominantly seen in female patients. This increased female preponderance depicts the hormonal factors especially increased estrogen role in altering the immune responses in women of childbearing age11,12. In this study female-male ratio was 11.6: 1 which shows some similarity to other Pakistani and regional studies except for the study conducted by Batool S et al13 that showed a lowest ratio of 4: 1 (table-I) and study carried out in Dubai that revealed a highest ratio of 20.5: 1 (table-II).

This difference in Lahore based study could be a random finding considering small sample size13. Mean age of presentation in this study was 33 years that is comparable to some regional studies (table-II). In this study musculoskeletal symptoms comprising joint pains remained the most common symptom (92.1%) quite comparable to Lahore based study but less than that studied by Tahir et al14 in which it is noted to be highest (98%).These symptoms were much higher than other Pakistani studies by Ishaq et al15 and Agha khan based study by Rabbani et al16 (p-value 90% of anemia. Iranian data echoed a similar outcome of hematological involvement in about 66% of patients (table-II). These differences could be because the patients undergoing treatment in different centers had better hematological profile than those without management or delay in treatment before reaching tertiary care hospital.

Cutaneous features also had significant differences from some local and regional studies. Although a declining trend in the malar rash was noted in Karachi based study by Ishaq et al15 (37%), a significant decrease was present in Agha khan based study by Rabbani et al16 showing it to be much less at 29% (p-value<0.05) but these features were more often seen in the study by Tahir et al14 at 64%. The results of this study were consistent with many regional countries except those of Akbarian et al19 in Iran where cutaneous features were noted to be highest at 81.1%, while in Korean study24 these features were significantly less constituting only 25.5% of the sample population (p-value of 0.0001). Alopecia, though comparable to some previous Pakistani studies had a striking difference from that of Batool et al13 that had the highest percentage of alopecia (88.6%) among Pakistani studies (table-I). This data regarding alopecia was also lower than most other regional studies (table-II).

These differences also highlight the hormonal and environmental factors especially ultraviolet (UV) light affecting varyingly in disease pathogenesis9,12. Oral ulcers were also comparatively lower than previous Pakistani study by Tahir et al14 but similar to Karachi based studies (table-I) and it was also lower than that of Indian, Saudi Arabian, and Singapore based studies (table-II). This variation might reflect the painless nature of lesions leading to under-reporting by patients at initial presentation.

The pulmonary manifestations were noted in 11.83% comprising pleural effusion, pulmonary fibrosis and alveolar hemorrhage. These results were consistent with other Pakistani studies including those of Tahir et al14 and Lahore based study13. The Agha khan based study16 depicted17 lung involvement while Ishaq et al15 showed 2.8% pulmonary involvement and 8.6% serositis. But these figures were lower than that of Saudi Arabian study21 (20.4 %) with 15.9% pleurisy and 4.5% pulmonary fibrosis and Iran based study19 (21.5%). There was no cardiac involvement in these patients as was also noted by Ishaq et al15 in contrast to other local and regional studies that showed cardiac features of ranging from 12-30%. (table-I and II). Overall serositis including pleural effusion and ascites was seen in 19.7% of this patient population.

Overlap syndrome with other connective tissue diseases including rheumatoid arthritis and scleroderma was noted in 9.2% similar to that of Iranian study19 where it was 7.6%. There was no mention of it in other local studies.

Among autoimmune profile ANA was present in more than 90% of these patients that matched with many local and regional studies (table-I, II) but anti-dsDNA antibody was also seen in majority of patients (83%) in this study which is consistent with other local studies but significantly higher than study by Tahir et al14 where it was 64%. Regionally dsDNA was comparable to Iran and Dubai based study but higher than Kuwait, Hong Kong and Indian studies and less than Saudi Arabia based study (p-value<0.05) (table-II).

The limitations of this study include a small sample size of 76 patients as compared to many studies done in Asia. Findings of this study cannot be generalized as the study was conducted in a single tertiary care hospital. Increased incidence of renal and neurological features might represent the late presentation to the tertiary care hospital and delay in diagnosis and treatment.

CONCLUSION

Renal and hematological involvement was more common in this study population while mucocutaneous features and neuropsychiatric features were comparable to many local studies with exception to that of Lahore based study that showed much higher percentage of these features. These results reflect the need to have a high index of suspicion for kidney and hematological involvement in SLE patients.

CONFLICT OF INTEREST

This study has no conflict of interest to declare by any author.

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Publication:Pakistan Armed Forces Medical Journal
Article Type:Clinical report
Geographic Code:90ASI
Date:Feb 28, 2018
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