Diagnosis and management of juvenile-onset SLE Louise Watson Faekah Gohar Michael W Beresford Abstract Systemic lupus erythematous (SLE) is a rare, multi-system, autoimmune disorder. Juvenile-onset SLE (JSLE) differs from the adult form in terms of severity, variation in organ involvement and gender ratio. As well as being a challenging diagnosis to make in the younger age group, the management of JSLE compared to adult-onset SLE requires special consideration towards both the significant long-term consequences of the disease, and its onset during a crucial time in growth and development. The variety of genetic, autoantibody and host immune responses featuring in the disease results in a clinically heterogeneous phenotype. A personalized approach is required to provide optimal care for an individual’s needs and therefore an overview of generic rather than specific management guidelines are presented here. A comprehensive, multi-disciplinary team approach to the management of JSLE is crucial. To date, clinical trials informing interventions in JSLE are very limited. Trials in adult-onset SLE have informed much of the treat- ment of JSLE. Patient and family involvement in research to improve outcomes is essential in JSLE. New therapies, including biological thera- pies, are becoming available. New treatment combinations have been used to induce and maintain clinical remission. In order to develop novel therapeutic targets to improve patient outcome, further investiga- tions of the genetic and immune pathways involved in the pathogenesis of JSLE are needed. Keywords diagnosis; JSLE; juvenile-onset SLE; management; systemic lupus erythematosus Background Systemic lupus erythematous (SLE) is a rare, autoimmune, multi-system disorder. It is of unknown aetiology but is charac- terized by autoantibodies against nuclear antigens, such as antinuclear antibodies (ANA) and double stranded DNA (dsDNA). Like most autoimmune conditions, SLE is more prev- alent in females. However the sex difference is less striking in juvenile-onset SLE (JSLE) than in adult-onset disease. In JSLE, the female to male ratio is around 5:1 in contrast to 9:1 seen in adult SLE. This gender distribution may be influenced by sex hormones during puberty. The incidence of JSLE is reported to be 0.36e0.9 per 100,000 children per year. However this varies significantly according to racial background, with a higher inci- dence of JSLE in patients of Black African or Asian descent. Hormonal, environmental and genetic factors play a contrib- utory role in the development of SLE. Individuals with SLE may have a genetic susceptibility to disease as almost half of all children with SLE have a family history of autoimmunity. Envi- ronmental factors including drugs, ultra violet light exposure, pregnancy and response to infectious stimuli such as viruses, also play a role. C1q deficiency is a rare inherited complement deficiency and these patients have an almost certain chance of developing SLE over their lifetime. Typically JSLE presents with non-specific constitutional symptoms, such as fever, lymphadenopathy and weight loss, which can make diagnosis difficult. These features may or may not accompany end-organ disease. Musculoskeletal, cutaneous and renal system involvement are common at presentation and can occur in varying severity. Less frequent but important manifestations are neurological features, which occur in up to 10% of JSLE patients and can present with headaches, altered consciousness or even psychosis. Liver, ophthalmic, and especially cardiac and pulmonary involvement are all rare manifestations in the juvenile form of SLE. The main differential diagnoses of JSLE include other systemic autoimmune conditions, for example juvenile dermatomyositis or systemic juvenile idiopathic arthritis, bacterial or viral infections, immunodeficiency or malignancy. Thorough evaluation and inves- tigation are often required to distinguish JSLE from these conditions. A combination of clinical features and laboratory markers is used to diagnose SLE. Classification criteria developed by the American College of Rheumatology (ACR) are generally used in forming the diagnosis (see Table 1). Four out of the 11 stated criteria are highly suggestive of SLE. The multi-systemic nature of the condition means that JSLE may present to different specialists causing a delay in the initial diagnosis. Clinical features may take some time to evolve, and children may not initially meet all of the features to fulfil a formal diagnosis. Long-term morbidity is significant, related to both disease damage and treatment toxicity, and the 10-year mortality remains around 10% with JSLE patients having a lower life expectancy than the general population. More severe and active disease is associated with a worse life expectancy and JSLE has a higher risk of death than adult-onset SLE. Lupus-like disorders JSLE can present in a secondary form either following the administration of certain drugs, so called ‘drug-induced’ lupus, or secondary to maternal lupus causing neonatal lupus in the newborn period. These are usually associated with transient autoantibodies and skin involvement, which resolve either with cessation of the offending medication or gradually over time. Louise Watson MBChB MRCPCH MA is Clinical Research Fellow at the University of Liverpool, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK. Conflicts of interest: none. Faekah Gohar MBChB BMedSc is Academic Clinical Fellow at the University of Liverpool, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK. Conflicts of interest: none. Michael W Beresford MBChB MRCP(UK) MCRPCH PhD is Professor in Child Health and Honorary Consultant Paediatric Rheumatologist at the University of Liverpool, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK. Conflicts of interest: none. SYMPOSIUM: CONNECTIVE TISSUE AND BONES PAEDIATRICS AND CHILD HEALTH 21:12 539 Ó 2011 Elsevier Ltd. All rights reserved.