A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment for the degree of Master of Medicine (Internal Medicine) February 2017 / Introduction: Systemic lupus erythematosus (SLE) is a rare multisystem autoimmune disease which occurs most severely in young females of African descent. Life expectancy is reduced, either directly due to the disease itself or related comorbidities. Aim of study: To determine the prevalence and spectrum of comorbidities in patients with SLE attending the Chris Hani Baragwanath Academic Hospital (CHBAH) Lupus Clinic. Patients and Methods: A retrospective record review of 200 SLE patients attending the CHBAH Lupus Clinic for at least 6 months. Data collected included demographics, clinical and serological evidence of SLE, autoantibody status, treatment modalities and comorbid conditions. The Charlson Comorbidity Index was used to measure the total comorbidity burden. Results: The majority of patients were black females (94%) with a mean age (SD) of 34.6 years (11). Disease duration and American College of Rheumatology (ACR) criteria fulfilled were 7 years and 5 respectively. The median (IQ range) CCI was 1 (0-3). Baseline and cumulative prevalence of one or more comorbidities was 36.5% (95% CI: 29.8-43.6%), and 56.0% (95% CI: 48.8-63.0%), respectively. The most frequent comorbidities were hypertension (HPT) (43.5%), severe infections (29%), tuberculosis (TB) (15%), and HIV infection (9%). Univariate risk factors for serious infection were the number of ACR criteria fulfilled and leucopaenia, while both univariate and multivariate risk factors were anti-Sm antibodies, thrombocytopaenia and the use of immunosuppressive drugs. Risk factors for HPT included age at onset, disease duration, CNS involvement and chloroquine use. Risk factors for TB were disease duration and the use of azathioprine. Protective factors were age of onset, arthritis as a clinical criteria and hypocomplementaemia. Conclusion: In this study of predominantly black females, comorbidities were common but the spectrum differs to those reported in industrialised, Western countries. Infections, both those requiring hospitalisation for intravenous antibiotics, and TB, were amongst the commonest comorbidities, relating to risk factors such as the use of immunosuppressive drugs, autoantibody status and disease duration. Furthermore, despite the high prevalence of HPT, cardiovascular comorbidities were very rare. / MT2017

INTRODUCTION: Several studies have shown an association of anti-C1q antibodies (abs) with systemic lupus erythematosus (SLE) nephritis and disease activity. The aim of this study is to determine the relevance of the anti-C1q abs and the C1q levels, in Black South Africans with SLE and their relevance to disease activity and/or organ damage, specifically renal disease. METHODS: Serum anti-C1q abs and C1q levels were measured in 96 SLE patients who were also assessed for disease activity, using the SELENA Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and organ damage as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC) Damage Index. Furthermore patients were assessed for the presence of an active urine sediment as evidenced by otherwise unexplained proteinuria, haematuria or cellular casts. Serum anti-C1q abs was measured by a commercial Elisa kit and serum C1q by immunoelectrophoresis. RESULTS: Of the 96 patients; the majority, 87 were female (90.65%), with a mean (SD) age and disease duration (SD) of 38.1 (13.0) years and 4.2 (4.4) years respectively. An active urine sediment was found in 21 (21.88%) patients. Elevated anti-C1q abs were present in 12 (12.50%) of the patients and 7 (14.29%) of the patients with renal involvement. Serum anti-C1q abs levels correlated significantly with SELENA SLEDAI scores (p=0.004, r =0.41).Anti-C1q abs levels were significantly higher in patients with an active urine sediment (p= 0.007). C1q levels were decreased in 17/96 (17.71%) patients and 11/49 (22.45%) patients with renal involvement. No associations with any other clinical features were observed. CONCLUSION: The findings indicate that in Black South Africans with SLE, although elevated anti-C1q abs levels were present in only a small minority of patients, the abs were associated with SLE global activity as determined by the SELENA SLEDAI and to the presence of an active urine sediment. These findings suggest that anti-C1q abs are a potential bio-marker of disease activity, especially active renal disease.

Diss. (sammanfattning)--Uppsala : Uppsala universitet, 2009. / Härtill 4 uppsatser.

Thesis (M.D.)--University of Hong Kong, 1987.

Thesis (M.D.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 207-261).

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by disease flares and damage accrual. The increased longevity allows SLE patients to accrue damage which has retarded their survival improvement since the 1980s. In the first study of this thesis, meta-analyses of observational studies revealed that renal and neuropsychiatric damage has been adversely affecting the survival of lupus patients in the past fifty years. While confirmatory studies are required, targeting at renal and neuropsychiatric involvement early might hopefully further improve the survival of SLE patients. As the survival of SLE patients improves, their psychosocial well-being becomes increasingly important. In the second study, anxiety symptoms were found to be significantly more frequent in lupus patients than those with other common inflammatory rheumatic conditions. Additionally, damage accrual and cumulative glucocorticoids accurately predicted anxiety in SLE patients. Related to neuropsychiatric damage, event-related functional brain imaging in the third study showed that new-onset SLE patients had poorer strategic planning skill that required compensatory cortical recruitment for executing comparable cognitive function as in healthy subjects. Even after sufficient control of SLE, they remained to demonstrate inferior strategic planning skill which necessitated compensatory recruitment of cortical areas to boost their executive function. These findings illustrated that cognitive dysfunction persists even after adequate control of SLE. Early recognition of the prognostically challenging renal, cardiovascular and musculoskeletal damage and their predictors is imperative. The fourth study revealed that failure to achieve complete renal remission 12 months after renal presentation predicted renal damage, irrespective of age and the choice of immunosuppressants. As to whether mycophenolate (MMF) or cyclophosphamide (CYC) is better; by meta-analysis, the fifth study concluded that MMF offers similar efficacy as CYC in inducing renal remission and preventing renal damage. As for the cardiovascular system, endothelial dysfunction exerts its impact very early during atherogenesis. As shown in the sixth study, SLE patients na?ve for cardiovascular disease had significantly poorer endothelial function than demographically and anthropometrically matched healthy controls. Higher serum high-sensitivity C-reactive protein level independently predicted poorer endothelial function in SLE patients. Osteoporotic fracture is a major lupus musculoskeletal damage which occurred in 9% of SLE patients as found in the seventh study. Increasing age and duration of corticosteroid use independently predicted osteoporotic fracture. While hormonal replacement therapy appeared fracture protective, its unfavorable long-term consequences limit its indication for fracture prevention. Mitigating fracture risk before fractures occur is the current management strategy. The eighth study found that the significantly higher FRAX? 10-year risk of major osteoporotic and hip fractures amongst SLE patients na?ve for clinical fracture compared with their demographically and anthropometrically matched healthy counterparts was driven by chronic glucocorticoid use and premature menopause. Modifiable factors including low hip bone mineral density (BMD), cumulative glucocorticoids and higher serum anti-dsDNA level independently predicted higher fracture risks. Finally, the relationship between lumbar bone loss and endothelial dysfunction was hitherto identified. Although potential drivers of this relationship remain to be identified, our findings serve to alert physicians to early atherosclerosis in lupus patients particularly in those with low lumbar BMD. / published_or_final_version / Medicine / Master / Doctor of Medicine

published_or_final_version / Medicine / Master / Doctor of Medicine

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 1999. / Härtill 6 uppsatser.