Long-Term Clinical Outcomes in a Cohort of Adults With Childhood-Onset Systemic Lupus Erythematosus

Abstract

Objective: Childhood-onset systemic lupus erythematosus (SLE) is a severe, lifelong, multisystem autoimmune disease. Long-term outcome data are limited. This study was undertaken to identify clinical characteristics and health-related quality of life (HRQoL) of adults with childhood-onset SLE.

Methods: Patients participated in a single study visit comprising a structured history and physical examination. Disease activity (scored using the SLE Disease Activity Index 2000 [SLEDAI-2K]), damage (scored using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and HRQoL (scored using the Short Form 36 Health Survey) were assessed. Medical records were reviewed.

Results: In total, 111 childhood-onset SLE patients were included; the median disease duration was 20 years, 91% of patients were female, and 72% were white. Disease activity was low (median SLEDAI-2K score 4), and 71% of patients received prednisone, hydroxychloroquine (HCQ), and/or other disease-modifying antirheumatic drugs. The vast majority of new childhood-onset SLE-related manifestations developed within 2 years of diagnosis. Damage such as myocardial infarctions began occurring after 5 years. Most patients (62%) experienced damage, predominantly in the musculoskeletal, neuropsychiatric, and renal systems. Cerebrovascular accidents, renal transplants, replacement arthroplasties, and myocardial infarctions typically occurred at a young age (median age 20 years, 24 years, 34 years, and 39 years, respectively). Multivariate logistic regression analysis showed that damage accrual was associated with disease duration (odds ratio [OR] 1.15, P < 0.001), antiphospholipid antibody positivity (OR 3.56, P = 0.026), and hypertension (OR 3.21, P = 0.043). Current HCQ monotherapy was associated with an SDI score of 0 (OR 0.16, P = 0.009). In this cohort, HRQoL was impaired compared to the overall Dutch population. The presence of damage reduced HRQoL scores in 1 domain. High disease activity (SLEDAI-2K score ≥8) and changes in physical appearance strongly reduced HRQoL scores (in 4 of 8 domains and 7 of 8 domains, respectively).

Conclusion: The majority of adults with childhood-onset SLE in this large cohort developed significant damage at a young age and had impaired HRQoL without achieving drug-free remission, illustrating the substantial impact of childhood-onset SLE on future life.

Figure 1

First occurrence of disease manifestations (by organ system) over time since diagnosis of childhood‐onset systemic lupus erythematosus (SLE). Skin category includes malar rash, discoid rash, ulcers, photosensitivity, cutaneous vasculitis, and other ongoing inflammatory SLE‐related rashes. Musculoskeletal category includes arthritis and myositis. Hematologic category includes hemolytic anemia, thrombocytopenia, leukopenia, lymphopenia, neutropenia, and thrombotic thrombocytopenic purpura. Renal category includes persistent proteinuria and lupus nephritis. Cardiovascular category includes pericarditis, myocarditis, endocarditis, myocardial infarction, angina pectoris, cerebrovascular accident, transient ischemic attack, arterial thrombosis, venous thrombosis, and embolus. Central nervous system category includes aseptic meningitis, cerebrovascular disease, demyelinating disease, lupus headache, myelopathy, chorea, convulsions, acute confusional state, anxiety disorder, mood disorder, and psychosis. Pulmonary category includes pleuritis, pneumonia, fibrosis, shrinking lung, pulmonary arterial hypertension, and interstitial lung disease. Peripheral nervous system category includes autonomous nervous system disorder, mononeuropathy, myasthenia gravis, Guillain‐Barré syndrome, cranial nerve neuropathy, plexopathy, and polyneuropathy. Gastrointestinal category includes peritonitis, pancreatitis, autoimmune hepatitis, and liver cirrhosis.

Figure 2

Childhood‐onset systemic lupus erythematosus–related damage defined by a Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score of ≥1. A, Percentage of patients with damage according to organ system. B, Number of patients with and without damage, by disease duration category. C, Percentage of cumulative specific organ damage relative to the sum of damage scores in all organ systems, displayed by disease duration category. DM = diabetes mellitus.

Figure 3

Health‐related quality of life expressed as mean Short Form 36 (SF‐36) health survey scores per domain. Spidergrams (63) show mean scores within each domain of the SF‐36, ranging from 0 (worst) to 100 (best). A, SF‐36 scores of childhood‐onset systemic lupus erythematosus (SLE) patients versus those of the overall Dutch population. B, SF‐36 scores of patients with low SLE Disease Activity Index 2000 (SLEDAI‐2K) scores (≤4), intermediate scores 5, 6, 7, and high scores (≥8). C, SF‐36 scores of patients with affirmative responses to questions about effects on physical appearance (e.g., ongoing inflammatory rash and/or alopecia) versus patients without these symptoms and patients with SLEDAI‐2K scores ≥8. D, SF‐36 scores of patients with damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI] score ≥1) versus patients without damage (SDI score 0). GH = general health perception domain; PF = physical functioning domain; RP = role limitations due to physical problems domain; BP = bodily pain domain; VT = vitality domain; MH = mental health domain; RE = role limitations due to emotional problems domain; SF = social functioning domain. * = P < 0.05. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.40697/abstract.