Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa

Abstract

Background Systemic Lupus Erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE (pSLE) on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa (SA). Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serologic characteristics was extracted from medical records. Results were compared to a well-described North American pSLE cohort. Results Seventy-two SA patients were enrolled in the study; mean age 11.5 years, 82% female. The racial distribution was 68% Coloured, 24% Black, 5% White, and 3% Asian/Indian. Most patients presented with severe lupus nephritis (LN) documented by renal biopsy (61%). Of patients with LN, 63% presented with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate, and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K [SLEDAI-2K] 20.6). The SLEDAI-2K at enrollment in the PULSE cohort (5.0) did not differ from the North American pSLE cohort (4.8). Sixty three % of PULSE cohort had end organ damage with System Lupus International Collaborating Clinic-Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, 9 (13%) developed ESRD with 6 (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrollment in the SA registry. SA patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study reveals a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

Comparison of urinary parameters, biomarkers, and outcome of childhood systemic lupus erythematosus early onset-lupus nephritis

“…Complement and immunoglobulin deposition is a characteristic finding in ELN renal biopsies and low serum C3 and C4 have been considered as disease activity biomarkers. But, it was rarely reported in pediatric patients [7,16,17]. Activation of the classical complement system by immune complex contributes to inflammation and tissue injury.…”

Improving musculoskeletal health for children and young people – A ‘call to action’

“… Research capacity building is dependent on having a local workforce trained in paediatric rheumatology and research methods to facilitate grant success and high impact publications. The Paediatric Update on Lupus in South Africa (PULSE) cohort [ 1 ], was an international collaboration and provided the first profile of JSLE in an African cohort demonstrating higher rates of catastrophic disease (blindness, stroke, renal failure), higher rates of nephritis and severe cardiovascular manifestations when compared with the US [ 2 ]. This valuable data enabled local units to advocate better care for CYP with SLE, targeted education locally to HCPs and provided preliminary data to leverage future research funds.…”

Advances in the care of children with lupus nephritis

“…The Italian Collaborative Study (70) and the 1000 Canadian Faces of Lupus Cohort (71) both provided useful information as well. In addition, cohorts such as the UK JSLE Cohort Study (4,23,31,55), the PULSE cohort in Africa (72), and the Israeli National Registry of Children with Rheumatic Diseases (73) are actively enrolling pediatric lupus patients elsewhere around the world. The Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group are two research networks that specialize in conducting studies in pediatric rheumatology, including cSLE.…”