Pediatric Systemic Lupus Erythematosus Workup
- Author: Marisa S Klein-Gitelman, MD, MPH; Chief Editor: Lawrence K Jung, MD more...
The initial laboratory evaluation should include a complete blood count (CBC) with platelets and reticulocyte count; a 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 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. Initial assessment of quantitative immunoglobulins is useful, because patients with lupus often have hypergammaglobulinemia and have a higher incidence of immunodeficiency, including immunoglobulin A deficiency and other antibody defects. 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 for atherosclerosis, with the patient’s fasting lipid profile, homocysteine level, fasting glucose level, and body mass index obtained. Risks should be stratified and treated. Hepatitis demonstrated by laboratory evaluation is not uncommon.
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.
Cognitive function testing should be considered in patients with systemic lupus erythematosus (SLE), particularly if changes in behavior or school function are observed. Testing should include academics, executive function, attention, and memory. Recently, a set of tests has been established by consensus criteria as a screening evaluation.
The Pediatric Automated Neuropsychological Assessment Metrics, a computer-based neuropsychological evaluation tool, has been initially validated in children diagnosed with SLE. However, further testing is needed to determine its sensitivity and specificity to change in clinical status.
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. Currently there is ongoing work to define disease flare and remission criteria both for systemic disease and lupus nephritis in children.
Obtain chest radiographs and electrocardiograms. Other imaging studies should be guided by clinical manifestations and may include the following:
Magnetic resonance imaging (MRI) of the brain - However, many patients with central nervous system (CNS) lupus do not have MRI abnormalities or have nonspecific bright areas that do not correlate with clinical observations of CNS deficits
Nuclear medicine evaluation for renal function
High-resolution computer tomography (CT) scanning to diagnose and evaluate for pulmonary fibrosis
Dual-energy radiographic absorptiometry to evaluate bone density
Angiography (usually MR or CT) to assess for thrombi for lupus-related antiphospholipid syndrome (APS)
The most common procedure used in the diagnostic evaluation of systemic lupus erythematosus (SLE) is a tissue biopsy to confirm the 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. However, skin biopsy is rarely necessary to make the diagnosis of SLE. 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.
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. The location of immune complexes (ie, subepithelial, subendothelial, intramembranous) is also important in prognosis.
Renal biopsy findings are classified according to the World Health Organization (WHO) classification and correlate with clinical morbidity and mortality. Staging for WHO histologic class and for acuity and chronicity of renal histologic manifestations is important in determining optimal therapy.
Patients may have combinations of the following classifications on biopsy findings, and all types should be reported:
Class I - Defined by normal findings on light microscopy, immunofluorescence, and electron microscopy
Class IIA disease - Has minimal mesangial deposits and a good prognosis
Class IIB disease - Associated with lymphocytic infiltration and a variable prognosis
Class III disease - Characterized by focal, segmental, proliferative mesangial changes and is associated with chronic renal disease; it is subtyped into (1) active necrotizing lesions, (2) active sclerosing lesions, and (3) sclerosing lesions
Class IV disease - 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; this stage is subtyped into (1) without segmental lesions, (2) with active necrotizing lesions, (3) with active sclerosing lesions, and (4) sclerosing lesions
Class V disease - Defined as a membranous process with significant proteinuria, which is often poorly responsive to treatment; this is subdivided into (1) pure membranous lesions, (2) associated with lesions of Class II, (3) associated with lesions of Class III, and (4) associated with lesions of Class IV
Class VI disease - Advanced sclerosing glomerulonephritis (≥90% global sclerosis without activity)
Osler W. On the visceral manifestations of the erythema group of skin diseases. Am J Med Sci. 1904. 27:1.
Suzuki M, Ross GF, Wiers K, Nelson S, Bennett M, Passo MH, et al. Identification of a urinary proteomic signature for lupus nephritis in children. Pediatr Nephrol. 2007 Dec. 22(12):2047-57. [Medline].
Yurasov S, Wardemann H, Hammersen J, et al. Defective B cell tolerance checkpoints in systemic lupus erythematosus. Journal of Experimental Medicine. 2005. 201:703-711. [Medline].
Blanco P, Palucka AK, Gill M, Pascual V, Banchereau J. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science. 2001 Nov 16. 294(5546):1540-3. [Medline].
Vallin H, Blomberg S, Alm GV, Cederblad B, Rönnblom L. Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature dendritic cells. Clin Exp Immunol. 1999 Jan. 115(1):196-202. [Medline]. [Full Text].
Garcia-Romo GS, Caielli S, Vega B, et al. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci Transl Med. 2011 Mar 9. 3(73):73ra20. [Medline]. [Full Text].
Armstrong DL, Reiff A, Myones BL, Quismorio FP Jr, Klein-Gitelman M, McCurdy D. Identification of new SLE-associated genes with a two-step Bayesian study design. Genes Immun. 2009 May 14. [Medline].
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep. 40(9):1725. [Medline].
Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug. 64(8):2677-86. [Medline]. [Full Text].
Male C, Foulon D, Hoogendoorn H, Vegh P, Silverman E, David M, et al. Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus. Blood. 2005 Dec 15. 106(13):4152-8. [Medline].
Ross GS, Zelko F, Klein-Gitelman M, et al. A proposed framework to standardize the neurocognitive assessment of patients with pediatric systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2010 Jul. 62(7):1029-33. [Medline]. [Full Text].
[Guideline] Brunner HI, Ruth NM, German A, Nelson S, Passo MH, Roebuck-Spencer T. Initial validation of the Pediatric Automated Neuropsychological Assessment Metrics for childhood-onset systemic lupus erythematosus. Arthritis Rheum. 2007 Oct 15. 57(7):1174-82. [Medline].
Brunner HI, Mina R, Pilkington C, et al. Preliminary criteria for global flares in childhood-onset systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2011 Sep. 63(9):1213-23. [Medline]. [Full Text].
Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004 Feb. 65(2):521-30. [Medline].
Mina R, von Scheven E, Ardoin SP, et al. Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2012 Mar. 64(3):375-83. [Medline]. [Full Text].
Podolskaya A, Stadermann M, Pilkington C, Marks SD, Tullus K. B cell depletion therapy for 19 patients with refractory systemic lupus erythematosus. Arch Dis Child. 2008 May. 93(5):401-6. [Medline].
Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Feb 26. 377(9767):721-31. [Medline].
Wenderfer SE, Lane JC, Shatat IF, von Scheven E, Ruth NM. Practice patterns and approach to kidney biopsy in lupus: a collaboration of the Midwest Pediatric Nephrology Consortium and the Childhood Arthritis and Rheumatology Research Alliance. Pediatr Rheumatol Online J. 2015 Jun 19. 13:26. [Medline]. [Full Text].
Hajizadeh N, Laijani FJ, Moghtaderi M, Ataei N, Assadi F. A treatment algorithm for children with lupus nephritis to prevent developing renal failure. Int J Prev Med. 2014 Mar. 5 (3):250-5. [Medline]. [Full Text].
Rodriguez-Pla A, Patel P, Maecker HT, Rossello-Urgell J, Baldwin N, Bennett L, et al. IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes. J Immunol. 2014 Jun 15. 192 (12):5586-98. [Medline].
Jeremiah N, Neven B, Gentili M, Callebaut I, Maschalidi S, Stolzenberg MC, et al. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest. 2014 Dec. 124 (12):5516-20. [Medline]. [Full Text].