eMedicine Specialties > Pediatrics: General Medicine > Rheumatology

Systemic Lupus Erythematosus: Differential Diagnoses & Workup

Author: Marisa S Klein-Gitelman, MD, MPH, Associate Professor of Pediatrics, Northwestern University Feinberg School of Medicine; Head, Division of Rheumatology, Children's Memorial Hospital
Contributor Information and Disclosures

Updated: Dec 8, 2008

Differential Diagnoses

Acute Lymphoblastic Leukemia
Hepatitis B
Acute Myelocytic Leukemia
Hereditary Periodic Fever Syndromes
Acute Poststreptococcal Glomerulonephritis
Hodgkin Disease
Anemia, Acute
Hyperthyroidism
Anemia, Chronic
Hypothyroidism
Angioedema
IgA and IgG Subclass Deficiencies
Anti-GBM Antibody Disease
Kawasaki Disease
Antiphospholipid Antibody Syndrome
Lymphadenopathy
Anxiety Disorder: Generalized Anxiety
Mitral Valve Insufficiency
Anxiety Disorder: Obsessive-Compulsive Disorder
Mitral Valve Prolapse
Anxiety Disorder: Specific Phobia
Mixed Connective Tissue Disease
Anxiety Disorder: Trichotillomania
Mononucleosis and Epstein-Barr Virus Infection
Appendicitis
Mood Disorder: Bipolar Disorder
Arthritis, Conjunctivitis, Urethritis Syndrome
Mood Disorder: Depression
Arthritis, Septic
Mood Disorder: Dysthymic Disorder
Autoimmune and Chronic Benign Neutropenia
Myocardial Infarction in Childhood
Autoimmune Chronic Active Hepatitis
Myocarditis, Nonviral
B-Cell and T-Cell Combined Disorders
Neonatal Lupus and Cutaneous Lupus Erythematosus in Children
Behcet Syndrome
Nephritis
Cardiomyopathy, Dilated
Nephrotic Syndrome
Chronic Granulomatous Disease
Oliguria
Cognitive Deficits
Parvovirus B19 Infection
Common Variable Immunodeficiency
Pericarditis, Bacterial
Complement Deficiency
Pleural Effusion
Complement Receptor Deficiency
Polyarteritis Nodosa
Eating Disorder: Anorexia
Proteinuria
Endocarditis, Bacterial
Rheumatic Fever
Evans Syndrome
Rheumatic Heart Disease
Fever Without a Focus
Serum Sickness
Fibromyalgia
Sjogren Syndrome
Fulminant Hepatic Failure
Systemic Sclerosis
Goodpasture Syndrome
Thyroid Storm
Graves Disease
Thyroiditis
Heart Failure, Congestive
Urticaria
Hematuria
Hemolytic-Uremic Syndrome
Henoch-Schoenlein Purpura

Other Problems to Be Considered

ACR classification criteria require 4 of 11 specific findings, which have 96-99% specificity (see History). Differential diagnoses should include the following:

Infection
Malignancy
Toxic exposures
Other multisystem diseases

Workup

Laboratory Studies

The following may be observed in patients with systemic lupus erythematosus (SLE):

  • Initial laboratory evaluation should include CBC count with platelets and reticulocyte count; complete chemistry panel to evaluate electrolytes, liver, and kidney function; urine analysis; and a measure of acute phase reactants (eg, erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]).
  • Diagnostic laboratory studies include antinuclear antibody (ANA), anti–double-stranded DNA, anti-Smith antibody, lupus anticoagulant, and antiphospholipid antibody panel.
  • Obtain other autoantibodies, which may be associated with specific disease manifestations, including anti-Ro, anti-La antibodies associated with Sjögren syndrome, and antiribonucleoprotein (anti-RNP) antibodies.
  • In addition to anti–double-stranded DNA, complement levels, including total hemolytic complement, C3, and C4, are markers of disease activity and are found to be low in most patients with active disease.
  • Quantitative immunoglobulins are useful, because patients with lupus often have hypergammaglobulinemia and have a higher incidence of immunodeficiency.
  • Other autoantibodies obtained should be guided by clinical and laboratory manifestations, such as petechiae, anemia, coagulopathy, cerebritis, and thyroid abnormalities.
  • Patients should be evaluated for traditional risk factors of atherosclerosis, including fasting lipid profile, homocysteine level, fasting glucose level, smoking history, body mass index, family history of atherosclerosis, and physical activity. Risks should be stratified and treated.

Imaging Studies

  • Obtain chest radiographs and ECG.
  • Other imaging studies should be guided by clinical manifestations and may include the following:
    • MRI of the brain
    • Renal ultrasonography
    • Nuclear medicine evaluation for renal function
    • High-resolution CT scan to diagnose and evaluate for pulmonary fibrosis
    • Dual-energy x-ray absorptiometry (DEXA) to evaluate bone density

Other Tests

  • Obtain pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DLCO), to evaluate baseline pulmonary status and to look for subtle disease not seen on chest radiographs.
  • Test of cognitive function should be considered in patients with systemic lupus erythematosus, particularly if changes in behavior or school function are observed. Currently, pediatric rheumatologists are determining the appropriate tests that should be used to standardize this evaluation. Testing should include academics, executive function, attention, and memory.

Procedures

  • The most common procedure in the diagnostic evaluation of systemic lupus erythematosus is a tissue biopsy to confirm diagnosis and to evaluate disease severity. This is particularly useful in evaluating the severity of renal involvement.
  • Skin biopsy is used for diagnostic purposes when the diagnosis is not clear; lesional and sun-exposed skin may show positive immunofluorescence for complement and immune complexes. Skin biopsy is rarely necessary to make the diagnosis of systemic lupus erythematosus.
  • Renal or liver biopsy is obtained more often for evaluation of disease severity and to determine the intensity of the medical regimen required for treatment.

Histologic Findings

  • Fibrinoid deposits are found in blood vessel walls of affected organs. The parenchyma of these organs may contain hematoxylin bodies representing degenerated cells. Other histologic manifestations are associated with the particular organ. Immunofluorescence often reveals immune complexes and complements. The most important histology related to treatment decision is renal histopathology. Location of immune complexes (ie, subepithelial, subendothelial, intramembranous) is also important in prognosis.
  • Biopsy findings are classified according to the World Health Organization (WHO) classification and correlate with clinical morbidity and mortality. This classification system has been recently updated.4 Patients may have combinations of the following classifications on biopsy findings, and all types should be reported.
    • Class I is defined by normal findings on light microscopy, immunofluorescence, and electron microscopy.
    • Class IIA disease has minimal mesangial deposits and a good prognosis, whereas class IIB is associated with lymphocytic infiltration and a variable prognosis.
    • Class III disease is characterized by focal segmental proliferative mesangial changes and is associated with chronic renal disease.
    • Class IV disease is defined as diffuse proliferation, with most glomeruli demonstrating cellular proliferation of epithelial, endothelial, and mesangial cells with cellular or fibrous crescent formation. Class IV has been further subdivided into segmental disease (IV-S) and global disease (IV-G). Class IV is associated with an increased risk of end-stage renal disease. Class IV disease involves advanced sclerosing lesions.
    • Class V disease is defined as a membranous process with significant proteinuria, which is often poorly responsive to treatment. 

Staging

  • Lupus is not generally staged as a disease. However, staging criteria have been proposed to help assess the degree of illness.
  • Determining which set of organs is inflamed is useful to decide treatment options.
  • Kidney disease is classified as described in Histologic Findings. Staging for both WHO histologic class and for acuity and chronicity of renal histologic manifestations is important in determining optimal therapy.

More on Systemic Lupus Erythematosus

Overview: Systemic Lupus Erythematosus
Differential Diagnoses & Workup: Systemic Lupus Erythematosus
Treatment & Medication: Systemic Lupus Erythematosus
Follow-up: Systemic Lupus Erythematosus
References
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Further Reading

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Keywords

systemic lupus erythematosus, lupus, SLE, lupus erythematosus, LE, fevers of unknown origin, arthralgia, anemia, nephritis, psychosis, fatigue, rheumatic disease, atherosclerosis, hemolytic anemia, thrombocytopenia, leukopenia, lymphopenia, nephritis, nephrotic syndrome, serositis, arthritis, memory loss, psychosis, transverse myelitis, hemoptysis, edema of the lower extremities, headache, painful mouth sores, pleuritis, pericarditis, livedo reticularis, alopecia, Raynaud phenomenon, tendonitis, myositis, lymphadenopathy, hepatosplenomegaly, stroke, pseudotumor cerebri, cerebral venous thrombosis, aseptic meningitis, chorea, global cognitive deficits, mood disorders, transverse myelitis, hyperthyroidism

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Contributor Information and Disclosures

Author

Marisa S Klein-Gitelman, MD, MPH, Associate Professor of Pediatrics, Northwestern University Feinberg School of Medicine; Head, Division of Rheumatology, Children's Memorial Hospital
Marisa S Klein-Gitelman, MD, MPH is a member of the following medical societies: American College of Rheumatology
Disclosure: Nothing to disclose.

Medical Editor

Barry L Myones, MD, Associate Professor, Departments of Pediatrics and Immunology, Pediatric Rheumatology Section, Baylor College of Medicine; Director of Research, Pediatric Rheumatology Center, Texas Children's Hospital
Barry L Myones, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American College of Rheumatology, American Heart Association, American Society for Microbiology, Clinical Immunology Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Thomas JA Lehman, MD, FAAP, FACR, Clinical Professor of Pediatrics, Department of Pediatrics, Division of Pediatric Rheumatology, Weill-Cornell University; Chief, Hospital for Special Surgery
Thomas JA Lehman, MD, FAAP, FACR is a member of the following medical societies: PM American Allergy Society
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa
Disclosure: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; Merck, Amgen, Biogen, Zimmer, Wyeth, Johnson&Johnson, Stryker, Medtronic, Zimmer.Abbott,  Ownership interest Other; West Penn Allegheny Health System Consulting fee Consulting; Alpharma Honoraria Consulting; Proctor&Gamble Grant/research funds Independent contractor

 
 
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