Doctor123.org

Lupus Erythematosus, Pediatric

Basics

Description

- Malar (butterfly) rash - Discoid rash - Photosensitivity - Oral or nasal ulcers - Arthritis - Cytopenia - Anemia, leukopenia (<4,000/mm3), lymphopenia (<1,500/mm3), or thrombocytopenia (<100,000/mm3)

- History of photosensitivity or malar rash common but not necessary - Many patients have systemic complaints, such as fever, fatigue, and malaise. - Many patients complain of joint pain, Raynaud phenomenon, or alopecia. - Chest pain from pericarditis or pleural effusions may be present. - Signs and symptoms: - Immune complex " “mediated vasculitis, which can occur in almost any organ system - Cutaneous lesions: very variable; include - Erythematous malar or "butterfly " ¯ rash - Maculopapular rashes (can occur anywhere on body) - Periungual erythema - Mucosal membrane vasculitis

- Arthritis: can affect large and small joints; usually symmetric and nonerosive - Hematologic pathology includes the following: - Hemolytic anemia - Anemia of chronic disease - Leukopenia - Lymphopenia - Thrombocytopenia

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by production of antibodies to various components of the cell nucleus, in conjunction with a variety of clinical manifestations. ‚

Epidemiology

  • Age20% of lupus begins in childhood, but it is very rare younger than 5 years old.
  • Female-to-male ratio:Between 3 " “5:1 (prepubertal) and 9 " “10:1 (postpubertal)
  • SLE occurs about 3 times more often in African Americans than Caucasians. It is also more common in Hispanic, Asian, and Native Americans.

Incidence

  • Peak incidence: between ages 15 and 40 years
  • Incidence in children is from 10 " “20 cases/100,000 children per year.

Prevalence

  • U.S. estimate: 5,000 " “10,000 children

Risk Factors

Genetics

  • Increased frequency in 1st-degree family members of patients with SLE
  • 10% of patients have ≥1 affected relative.
  • Concordance rate of 25 " “50% in monozygotic twins and 5% in dizygotic twins
  • Some major histocompatibility complex antigens are associated with increased incidence of lupus, such as HLA-DR2 and DR3 in whites and DR2 and DR7 in blacks.

Etiology

Although exact etiology is unknown, lupus is an autoimmune disease, with genetic, environmental, and hormonal factors playing a role. ‚

Diagnosis

Classification criteria: 4 of the following 11 criteria, developed by the American College of Rheumatology, must be met to classify a patient as having SLE: ‚

  • Malar (butterfly) rash
  • Discoid rash
  • Photosensitivity
  • Oral or nasal ulcers
  • Arthritis
  • CytopeniaAnemia, leukopenia (<4,000/mm3), lymphopenia (<1,500/mm3), or thrombocytopenia (<100,000/mm3)
  • Neurologic disease: seizures or psychosis
  • Nephritis: >0.5 g/day proteinuria or cellular casts
  • Serositis: Pleuritis or pericarditis
  • Positive immunoserology (revised 1997): antibodies to double-stranded DNA or Smith nuclear antigen, false-positive serologic test for syphilis, lupus anticoagulant, or antiphospholipid antibodies
  • Positive ANA
  • Meeting 4 of 11 classification criteria is highly sensitive and specific for diagnosis of SLE.

History

  • History of photosensitivity or malar rash common but not necessary
  • Many patients have systemic complaints, such as fever, fatigue, and malaise.
  • Many patients complain of joint pain, Raynaud phenomenon, or alopecia.
  • Chest pain from pericarditis or pleural effusions may be present.
  • Signs and symptoms:Immune complex " “mediated vasculitis, which can occur in almost any organ systemCutaneous lesions: very variable; includeErythematous malar or "butterfly " ¯ rashMaculopapular rashes (can occur anywhere on body)Periungual erythemaMucosal membrane vasculitisArthritis: can affect large and small joints; usually symmetric and nonerosiveHematologic pathology includes the following:Hemolytic anemiaAnemia of chronic diseaseLeukopeniaLymphopeniaThrombocytopeniaNeurologic symptoms include the following:HeadachesPsychosisDepressionSeizuresOrganic brain syndromesPeripheral neuropathiesRenal pathology (present in up to 75% children with SLE)Includes mesangial changes and glomerulonephritis (focal, diffuse proliferative, or membranous)First signs of renal disease in lupus patient are often proteinuria and active urinary sediment.Hypertension, nephrotic syndrome, and renal failure can also occur.Serositis: usually seen as pericarditis or pleuritis but peritonitis can also occurConstitutional symptoms are very common: fatigue, weight loss, fever.

Physical Exam

  • Rash: may be malar, discoid, or vasculitic. Periungual erythema may also be seen.
  • Oral or nasal ulcers (usually on hard or soft palate) that are painless and often go unnoticed by patients
  • Arthritis of large and small joints
  • Pericardial friction rub if patient has pericarditis
  • Edema may be present secondary to renal disease.
  • CNS changes such as personality changes, psychosis, or seizures

Diagnostic Tests & Interpretation

Lab

  • ANAFound in >95% of patients with SLE, but a positive ANA can occur in many diseases and in up to 20% of normal population
  • Anti " “double-stranded DNA and anti " “Smith nuclear antigenVery specific to lupus, but not all patients with lupus have these autoantibodies. In many patients, anti-DNA levels vary with activity of disease.
  • CBCAnemia, leukopenia, lymphopenia, and/or thrombocytopenia may be seen.
  • UrinalysisMay show proteinuria or active urinary sediment if there is renal dysfunction
  • Complement levelsCan fall very low during a lupus flare (C3 and C4)
  • PTTPatients may also have prolonged PTT, as result of antiphospholipid (APL) antibodies, often seen in SLE.Patients with APL antibodies are at increased risk for thrombotic events, such as deep venous thrombosis, stroke, and fetal loss during pregnancies.

Differential Diagnosis

  • Systemic-onset juvenile idiopathic arthritis
  • Oncologic disease (leukemia, lymphoma)
  • Viral or other infectious illness
  • Other vasculitic disorders
  • Dermatomyositis
  • Fibromyalgia
  • Drug-induced lupus
  • Pitfalls:Avoid overdiagnosis; positive ANA in the absence of clinical signs or symptoms of SLE is not lupus.

Treatment

Medication

  • NSAIDsMay be used for musculoskeletal and mild systemic complaints, although ibuprofen has been noted to cause aseptic meningitis in a small number of patients with SLE.NSAIDs can also exacerbate renal disease in lupus.
  • Hydroxychloroquine often used to help control cutaneous manifestations and to help minimize the chance of lupus flares
  • Steroids often necessary to control systemic and renal manifestations
  • Patients with renal disease often need immunosuppressive agents such as cyclophosphamide (usually given as monthly IV boluses). Mycophenolate mofetil, cyclosporine, or azathioprine may also be used.
  • Patients with mainly arthritic symptoms may be treated with weekly methotrexate, PO or SC.
  • Patients with antiphospholipid antibodies can be treated with a baby aspirin daily. If they have already had a significant clotting event, they need stronger anticoagulation.
  • Angiotensin-converting enzyme (ACE) inhibitors are often used to help prevent renal damage from proteinuria.
  • Patients with abnormal lipid profiles that do not respond to diet may need statins.
  • Rituximab (anti-CD20 antibody) causes B-cell depletion and is used in SLE, especially for thrombocytopenia.
  • Belimumab, a BLyS (B-lymphocyte stimulator) inhibitor, has been approved in adults but not yet in children.
  • Antibodies to CD40 and C5 are also being studied
  • Plasmapheresis and IVIG have been used as well.

Additional Treatments

General Measures

Avoid excessive sun exposure and use sunscreen liberally. ‚

Additional Therapies

For very severe lupus, bone marrow immunoablation or transplantation are options. ‚

Ongoing Care

Prognosis

  • Extremely variable. Renal disease and CNS involvement are poor prognostic signs, whereas systemic complaints and joint findings are not.
  • 10-year survival in children presenting with SLE is >90%.

Complications

  • End-stage renal disease
  • Infections secondary to treatments used to control disease
  • Atherosclerosis and myocardial infarctions at a young age
  • Libman-Sacks endocarditis, which increases risk of subacute bacterial endocarditis
  • Neonatal lupusNeonatal lupus erythematosus (NLE) is due to maternal autoantibodies (usually SS-A or SS-B antibodies) that cross the placenta and can cause rashes, congenital heart block, cytopenias, and/or hepatitis in the newborn.Most symptoms of NLE resolve by 6 months of age, but heart block, if it occurs, is permanent.Many mothers of babies with NLE are asymptomatic and unaware that they have these autoantibodies.The rash, erythema annulare, can begin a few days after delivery or within the first few weeks of life.Topical steroids can minimize skin lesions.Congenital heart block is due to damage of the conducting system of the developing fetal heart.Bradycardia may be noted by 22 weeks ' gestation, and CHF with nonimmune hydrops fetalis may ensue.

Additional Reading

  • Brunner ‚ HI, Huggins ‚ J, Klein-Gitelman ‚ MS. Pediatric SLE " ”towards a comprehensive management plan. Nat Rev Rheumatol. 2011;7(4):225 " “233. ‚ [View Abstract]
  • Gottlieb ‚ BS, Ilowite ‚ NT. Systemic lupus erythematosus in children and adolescents. Pediatr Rev. 2006;27(9):323 " “330. ‚ [View Abstract]
  • Macdermott ‚ EJ, Adams ‚ A, Lehman ‚ TJ. Systemic lupus erythematosus in children: current and emerging therapies. Lupus. 2007;16(8):677 " “683. ‚ [View Abstract]
  • Silverman ‚ E, Eddy ‚ A. Systemic lupus erythematosus. In: Cassidy ‚ JT, Petty ‚ RE, Laxer ‚ RM, et al, eds. Textbook of Pediatric Rheumatology. Philadelphia, PA: Elsevier; 2011:315 " “343.
  • Yildirim-Toruner ‚ C, Diamond ‚ B. Current and novel therapeutics in the treatment of systemic lupus erythematosus. J Allergy Clin Immunol. 2011;127(2):303 " “312. ‚ [View Abstract]

Codes

ICD09

  • 695.4 Lupus erythematosus
  • 710.0 Systemic lupus erythematosus

ICD10

  • L93.0 Discoid lupus erythematosus
  • M32.9 Systemic lupus erythematosus, unspecified
  • L93.2 Other local lupus erythematosus
  • M32.10 Systemic lupus erythematosus, organ or system involv unsp
  • M32.19 Oth organ or system involv in systemic lupus erythematosus

SNOMED

  • 200936003 lupus erythematosus (disorder)
  • 55464009 Systemic lupus erythematosus (disorder)
  • 95332009 rash of systemic lupus erythematosus (disorder)
  • 239887007 systemic lupus erythematosus with organ/system involvement (disorder)
  • 80258006 Drug-induced lupus erythematosus (disorder)

FAQ

  • Q: If a patient has a positive ANA but no clinical signs of SLE, how often should the ANA be followed?
  • A: A positive ANA will usually remain positive indefinitely, but it has no real significance in the absence of clinical or other laboratory disturbances. Up to 20% of the normal population may have a positive ANA, so there is no need to repeat the test.
  • Q: Can SLE patients with end-stage renal disease obtain renal transplants?
  • A: Yes, and SLE usually does not recur in the new kidney.