Systemic Lupus Erythematosus in Children

 

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder characterized by widespread inflammation of the connective tissues and immune complex-mediated vasculitis.  In children, it is fundamentally the same disease as in adults, with similar etiology, pathogenesis, clinical manifestations, and laboratory findings.  However, the care of children and adolescents with SLE is very different from that of adults because of the impact of the disease and its therapy on physical and psychological growth and development (discussed below).

 

Etiology

The current best estimate is that SLE affects between 5,000 and 10,000 children in the United States. Although it can occur at any age, SLE becomes more frequent after five years of age and is increasingly prevalent after the first decade of life with a peak in adolescence. 

Childhood SLE affects girls more often than boys (8:1 ratio) and Asians, Blacks and Hispanics are more frequently affected than Caucasians.  

 

Clinical Features

The presenting manifestations of SLE in children are as diverse as they are in adults.  The most common initial symptoms are the gradual onset of fever, malaise, and general deterioration over several months. Children also may have small joint arthritis and renal disease.  The classic malar rash is absent in two-thirds of individuals.

In retrospective reviews from France and Canada, the onset of juvenile SLE is at a median age of 12 to 13 years, with the disease developing in the majority of patients after eight years of age. In these studies, the most common presenting manifestations were as follows:

á      Hematologic: anemia, cytopenia, and/or thrombocytopenia

á      Mucocutaneous: malar rash and/or oral ulcers

á      Musculoskeletal: arthritis or arthralgia

á      Fever

á      Renal abnormalities (ex, nephritis and nephrotic syndrome)

 

Diagnosis

The diagnosis of SLE in children is based on the same American College of Rheumatology criteria used in adults as shown below.  Four of eleven criteria provide a sensitivity and specificity of 96%. 

Criterion

Definition

1. Malar rash

Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds

2. Discoid rash

Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions

3. Photosensitivity

Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation

4. Oral ulcers

Oral or nasopharyngeal ulceration, usually painless, observed by physician

5. Arthritis

Nonerosive arthritis involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion

6. Serositis

a) Pleuritis--convincing history of pleuritic pain or rubbing heard by a physician or evidence of pleural effusion

OR

b) Pericarditis--documented by ECG or rub or evidence of pericardial effusion

7. Renal disorder

a) Persistent proteinuria greater than 0.5 grams per day or grater than 3+ if quantitation not performed

OR

b) Cellular casts--may be red cell, hemoglobin, granular, tubular, or mixed

8. Neurologic disorder

a) Seizures--in the absence of offending drugs or known metabolic derangements; e.g., uremia, ketoacidosis, or electrolyte imbalance

OR

b) Psychosis--in the absence of offending drugs or known metabolic derangements, e.g., uremia, ketoacidosis, or electrolyte imbalance

9. Hematologic disorder

a) Hemolytic anemia--with reticulocytosis

OR

b) Leukopenia--less than 4,000/mm<>3<> total on 2 or more occasions

OR

c) Lyphopenia--less than 1,500/mm<>3<> on 2 or more occasions

OR

d) Thrombocytopenia--less than 100,000/mm<>3<> in the absence of offending drugs

10. Immunologic disorder

a) Positive LE cell preparation

OR

b) Anti-DNA: antibody to native DNA in abnormal titer

OR

c) Anti-Sm: presence of antibody to Sm nuclear antigen

OR

d) False positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test

11. Antinuclear antibody

An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with "drug-induced lupus" syndrome

 

Treatment

The treatment does not differ among adults, children, and adolescents. However, as mentioned above, children and adolescents with SLE have unique problems related to growth and development that affect both the need for and the impact of aggressive therapy. Doses should be minimized whenever possible.

Mild disease: The use NSAIDs (to control musculoskeletal manifestations) in conjunction with hydroxychloroquine (7 mg/kg per day up to a usual maximum of 400 mg per day) is often sufficient in mild SLE without renal or other life-threatening organ system involvement.

Moderate disease: Continued use of high-dose glucocorticoids, mycophenolate mofetil, or other steroid-sparing agents in these children.

Severe disease: Severe SLE (ex, substantial renal or neurologic disease), or those with moderate disease that does not quickly come under control, require more aggressive therapy. Monthly intravenous cyclophosphamide is generally preferred in children with moderate or severe SLE who cannot be maintained on a prednisone dose of less than 0.5 mg/kg per day.

 

Prognosis

With the current treatment, the survival rate is now 90% at 5-10 years after initial diagnosis.  The major causes of mortality are infection (secondary to immunosupression), renal failure, and CNS complications.  More long-term studies are ongoing to determine long term (50 year) survival in children diagnosed with SLE.

 

References

1.     Bader-Meunier, B, Armengaud, JB, Haddad, E, et al. Initial presentation of childhood-onset systemic lupus erythematosus: a French multicenter study. J Pediatr 2005; 146:648.

2.     Brown, JT, Miller, LT.  BRS Pediatrics.  Lippincott Williams and Wilkins 2005.  474-476. 

3.     Hiraki, LT, Benseler, SM, Tyrrell, PN, et al. Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study. J Pediatr 2008; 152:550.

4.     Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum 1997;40:1725.

5.     Lehman, TJ, Sundel, R, TePas E.  Systemic lupus erythematosus in children.  UpToDate 2011. 

6.     Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271.