A 12-year-old girl is admitted to general paediatrics with fever, malaise and pain in the small joints of both hands. Sepsis work-up is negative, and she is referred to rheumatology for an opinion. Further examination reveals faint malar rash, evidence of arthritis in many small joints of hands and toes, knees and ankles. Laboratory investigations reveal anaemia, leucopenia, lymphopenia, low compliment levels, positive Coombs test, positive ANA and high titres of anti-ds DNA antibodies. Echocardiogram reveals a small pericardial effusion. Does she have juvenile lupus?
Bottom Line
Juvenile systemic lupus erythematosus (JSLE) is a multi-system autoimmune disease, characterised by antibodies against nuclear material
Presenting features are frequently variable and unpredictable and can be nonspecific. A high index of suspicion is necessary for early diagnosis of JSLE
Treatment includes immunosuppression and depends on the severity of the disease and major organ involvement
JSLE and its treatment can have a significant emotional impact on adolescents; failure to address this will lead to poor compliance leading to poor outcomes.
What is Juvenile Systemic Lupus Erythematosus?
JSLE is a multi-system autoimmune disease, affecting girls more than boys. The exact aetiology is unknown but thought to be multi-factorial. The primary defect appears to be a loss of immune tolerance to self-antigens leading to auto-reactive immune cells and antibodies. Several potential genes that may increase one’s susceptibility to JSLE are being evaluated.
What are the common presenting features?
Common features include gradual onset of fever, malaise and weight loss, malar rash, nonspecific rashes, oral ulcers, arthralgia, arthritis, nephritis, anaemia, leukopenia, lymphopenia and thrombocytopenia.
Erythrocyte Sedimentation Rate is frequently raised during exacerbation of JSLE; C-reactive protein is usually not elevated (except in conjunction with arthritis, serositis or infection).
Approximately a third of the patients have a family history of autoimmunity.
What are the tests to confirm the diagnosis?
Laboratory investigations complement clinical features and are not diagnostic on their own. ANA (antinuclear antibodies) are almost always positive but are not specific for SLE; anti-double-stranded DNA and anti-Smith antibodies are highly specific.
Other investigations performed when JSLE is suspected include; full blood count, erythrocyte sedimentation rate, complement (C3, C4) levels, anti-Ro, anti-La and anti-RNP antibodies, urine analysis for proteinuria, renal function tests and liver function tests.
How is JSLE diagnosed?
Rheumatologists usually diagnose JSLE. The 1997 modified ACR (American College of Rheumatology) criteria, and more recently the Systemic Lupus International Collaborating Clinics (SLICC) group classification criterion (2012), are commonly used to diagnose JSLE. In general, both criteria require the presence of certain clinical and laboratory features.
Which professionals are involved in the management of JSLE?
A consultant paediatric rheumatologist should lead the management. In view of the multisystem involvement, it may be necessary for other specialists like paediatric nephrologists, cardiologists, haematologists and neurologists to be involved. Specialist nurses and members of the multidisciplinary team are crucial in supporting the patient and their families through the chronic disease course of JSLE.
What are the less common presentations of JSLE?
JSLE is a multisystem disorder. Nearly any organ system can be affected. Less common features at presentation include abdominal pain (pancreatitis, cholecystitis and peritonitis), parotitis, ocular involvement (retinopathy, papillitis and keratitis), facial swelling, genital ulceration, chorea, psychosis, transverse myelitis, polyneuropathy, pleuritis, alveolar haemorrhage, Sicca syndrome and haemolytic uremic syndrome.
How to treat JSLE?
There is no cure for JSLE.
Immunosuppression is used to maximise disease control and prevent permanent organ damage. Treatment is individualised based on the disease activity and organ involvement. Most patients receive glucocorticosteroids.
Other immunosuppressive therapies, either on their own or in various combinations, include hydroxychloroquine, mycophenolate mofetil, azathioprine, methotrexate and cyclophosphamide.
Non-steroidal anti-inflammatory drugs are used for musculoskeletal symptoms.
Biologic therapies such as B-cell depletion by rituximab are being evaluated.
An autologous stem cell transplant may be necessary for severe intractable disease.
Adjunct therapies: sunscreen is recommended (UV light can trigger flares), supplement calcium and Vitamin D if needed, and manage proteinuria and hypertension.
Education about the disease and the various therapies is crucial. Failure to address these can lead to poor compliance. Regular exercise and a balanced diet should be advocated to maintain general health.
What is the prognosis of children with JSLE?
The 10-year survival in JSLE in 1980s was around 85%. The prognosis with current therapies is generally good, but long-term outcomes are yet unknown.
Improved prognosis is partly due to earlier diagnosis and more aggressive therapies.
The main reasons for unsatisfactory outcomes include; poor compliance with treatment, intercurrent infections, neurological involvement and renal involvement.
References
Murphy G, Lisnevskaia L, & Isenberg D (2013). Systemic lupus erythematosus and other autoimmune rheumatic diseases: challenges to treatment. Lancet, 382(9894), 809–18. doi:10.1016/S0140-6736(13)60889-2
Petri M, Orbai AM, Alarcón GS, et al (2012). Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis and rheumatism, 64(8), 2677–86. doi:10.1002/art.34473
Ravelli A, et al. Glucocorticoids in paediatric rheumatology. Clin Exp Rheumatol. 2011 Sep-Oct;29(5 Suppl 68):S148-52
Ruperto N, Ravelli A, Cuttica R, et al (2005). The Pediatric Rheumatology International Trials Organization criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the disease activity core set. Arthritis and rheumatism, 52(9), 2854–64. doi:10.1002/art.21230
