What are the Criteria for Diagnosing Systemic Lupus Erythematosus (SLE)?

Patient Presentation
A 10-year-old female came to clinic for a second opinion. The patient was well until approximately 6 months ago when she developed ankle pain.
She was treated with anti-inflammatory medications and the symptoms resolved, but during this time she had an erythrocyte sedimentation rate of 62 mm/hr.
Over the past 2-3 months she has had increasing joint pain, intermittent fever and worsening rash. During this time, she was noted to have pyruria and was treated with antibiotics, and at another point she was thought to have mononucleosis but testing was negative.
Over the past few months, she has been stiff in her legs and hands in the morning and for several hours afterwards. She has swelling of her ankles and hands. There is no Raynaud’s phenomenon.
The past medical history shows a hemoglobin of 11.3 one year ago. She has had a rash on her face and hands felt to be due to eczema that was treated by steroids and emollients for 1 year.
The family history is negative.
The review of systems is positive for thinning hair, extreme fatigue, occasional episodes of substernal chest pain, and a 3 kilogram weight loss. Her review of systems is negative for tinnitis, vertigo, focal neurological symptoms, pulmonary symptoms or changes in bowel or bladder habits.
The pertinent physical exam shows a temperature of 38.0 Celsius, blood pressure of 109/57 mg/Hg, weight of 26.5 kg (10th percentile), and a height of 133.7 cm (10th percentile).
She has mild facial edema, prominent malar rash that is deep red in color with multiple coalescent plaques. There are flat, purple macules on both ears and on the dorsum of all fingers. She has a few splinter hemorrhages in her fingernails.
She has some scaly plaques on her lower extremeties. There are multiple erosions in her mouth and buccal mucosa. There is no lymphadenopathy.
On musculoskeletal examination, she has swelling, tenderess, and pain on motion of most small joints of her hands. Both elbows, knees and ankles are warm with swelling and have some limited motion. She has some pain on motion of shoulders and hips.
She walks with her hips and knees flexed and is quite stiff and uncomfortable. The rest of her examination was normal.
The laboratory evaluation included a complete blood count which showed a hemoglobin of 6.8 mg/dl, hematocrit of 20%, white blood cell count of 3.5 x 1000/mm2 and a smear that showed microcytic, hypochromic red blood cells with 1+ teardrops, target cells, and schistocytes. Her C-reactive protein was normal at <0.5 mg/dl.
Her urinalysis showed a specific gravity of 1.025, pH of 6.5 with 3+ protein, 1-10 granular casts, 10-20 hyaline cases, 10-25 white blood cells/ high power field, and 4-10 red blood cells/high power field.
Her electrolytes were normal including calcium, magnesium and phosphorous. Her blood urea nitrogen was 11.6 mg/dl and creatinine was 0.6 mg/dl. Her Alanine Aminotransferase and Aspartate Aminotransferase were slightly elevated, but she had a normal bilirubin. Coagulation studies were normal.
A C3, C4, total hemolytic complement, and an anti-nuclear antibody were pending.
The radiologic evaluation showed a normal chest radiograph.
Because of the increasing systematic symptoms of weight loss, fever, anemia, leukopenia, worsening rash and an abnormal urinalysis with casts and proteinuria, she was clinically diagnosed with systemic lupus erythematosus. She was referrred for urgent evaluation to a pediatric rheumatologist and nephrologist
who confirmed the diagnosis. Her antinuclear antibody came back high at > 1:2560 in a speckled pattern. She was started on hydroxychloroquine and steroids.
The patient’s clinical course over the next few years has included diffuse proliferative lupus glomerulonephritis, difficult to control hypertension and chronic anemia necessitating blood transfusions.

Discussion
Systemic Lupus Erythematosus (SLE) is a chronic rheumatic disease caused by a copious overproduction of autoantibodies leading to immune complex formation, and binding or deposition of the complexes into tissues. There is wide-spread immune disregulation. This causes damage to any organ in the body but especially the kidney, blood, skin and the central nervous system.
It was first described in the 13th century and its incidence varies by location and ethnicity. It occurs in females more often. The disease may occur at birth but is generally less common in children < 8 years old. Twenty percent of patients present by the second decade of life.

Because SLE can affect any organ, SLE can be in the differential diagnosis of almost any clinical presentation. The most common manifestations are arthritis, dermatitis and nephritis. Specifically patients often complain of prolonged fever, malaise, fatigue, joint pain, and rash.

Initial laboratory studies often include:

  • Complete blood count with platelets, reticulocyte count
  • Electrolytes
  • Liver function tests
  • Kidney function tests
  • Erythocyte sedimentation rate and/or C-reactive protein
  • Anti-nuclear antibody (ANA), anti-double-stranded DNA, anti-Smith antibody and antiphospholipid antibodies (and possibly other autoantibodies also)
  • C3, C4 and total hemolytic complement – these are often low and are markers of disease activity
  • Quantitative immunoglobulins – patients with lupus have high rates of immunodeficiency
  • Chest radiograph and echocardiography – for cardiopulmonary disease
  • Pulmonary function tests – to determine baseline
  • Other tests and imaging for specific presentations such as petechiae, coagulopathy, cerebritis, etc.
  • Biopsies of the kidney, liver or skin may be necessary to determine diagnosis and/or treatment

Treatment includes close follow-up of the patient for progression of disease, and side effects to treatment. This often needs the expertise of many specialists including rheumatology, nephrology, ophthalmology, critical care, social work, physical therapy, and many others.
Common medications used include anti-malarial drugs, steroids, and immunosuppressive agents to treat the primary disease. Antihypertensive agents, calcium and Vitamin D supplements and non-steroidal anti-inflammatory drugs are needed for primary disease and for ameliorating medication side effects.

Learning Point
According to the American College of Rheumatology, there are 11 criteria used for making the diagnosis of SLE in adults. They can be used as a guideline in children. Any 4 criteria are sufficient. ANA is almost always present.
The criteria include:

  • Mucocutaneous
    • Malar rash
    • Discoid rash
    • Nasal or oral ulcer
    • Photosensitivity rash
  • Systemic
    • Arthritis
    • Hemolytic anemia, thrombocytopenia, leukopenia, or lymphopenia
    • Pleuritis or pericarditis
    • Proteinuria (> 500 mg/dl) or evidence of nephritis on urinalysis
    • Seizure or psychosis

    Laboratory

    • Postive ANA
    • Positve anti-double-stranded DNA, anti-Smith, or antiphospholipid antibody

The child in this case met 6 criteria: malar rash, oral ulcer, arthritis, hemolytic anemia leukopenia, proteinuria and positive ANA.

Questions for Further Discussion
1. What are some of the common neuropsychiatric presentations of SLE?
2. What are some of the common cardiopulmonary presentations of SLE?
3. What are common medication side effects?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:847-851.

Klein-Gitelman, MS. Systemic Lupus Erythematosus. eMedicine. Available from the Internet at http://www.emedicine.com/ped/topic2199.htm (rev. 7/20/2004, cited 5/2/2005).

Author
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa

Date
June 13, 2005