Lupus ( SLE )

Systemic lupus erythematosus (SLE) is a diagnosis that must be based on
the proper constellation of clinical findings and laboratory evidence.
Familiarity with the diagnostic criteria helps clinicians to recognize SLE
and to subclassify this complex disease based on the pattern of
target-organ manifestations.

The 1982 American College of Rheumatology (ACR) criteria summarize
features necessary to diagnose SLE.20, 21 They are summarized below with a
useful mnemonic. The presence of 4 of the 11 criteria yields a sensitivity
of 85% and a specificity of 95% for SLE. Keep in mind that individual
features are variably sensitive and specific. Patients with SLE may
present with any combination of clinical features and serologic evidence
of lupus. The following is the ACR diagnostic criteria in SLE, presented
in the "SOAP BRAIN MD" acronym:

* Serositis - Pleurisy, pericarditis on examination or diagnostic ECG
or imaging
* Oral ulcers - Oral or nasopharyngeal, usually painless; palate is
most specific
* Arthritis - Nonerosive, two or more peripheral joints with
tenderness or swelling
* Photosensitivity - Unusual skin reaction to light exposure
* Blood disorders - Leukopenia (<4000 cells 103/µL on more than one
occasion), lymphopenia (<1500 cells/µL on more than one occasion),
thrombocytopenia (<100 X103/µL in the absence of offending medications),
hemolytic anemia
* Renal involvement - Proteinuria (>0.5 g/d or 3+ positive on dipstick
testing) or cellular casts
* ANAs - Higher titers generally more specific (>1:160); must be in
the absence of medications associated with drug-induced lupus
* Immunologic phenomena - dsDNA; anti-Smith (Sm) antibodies;
antiphospholipid antibodies (anticardiolipin immunoglobulin G [IgG] or
immunoglobulin M [IgM] or lupus anticoagulant); biologic false-positive
serologic test results for syphilis, lupus erythematosus (LE) cells
(omitted in 1997)
* Neurologic disorder - Seizures or psychosis in the absence of other
causes
* Malar rash - Fixed erythema over the cheeks and nasal bridge, flat
or raised
* Discoid rash - Erythematous raised-rimmed lesions with keratotic
scaling and follicular plugging, often scarring

In patients with high clinical suspicion or high ANA titers, additional
testing is indicated. This commonly includes evaluation of antibodies to
dsDNA, complement, and ANA subtypes such as Sm, SSA, SSB, and
ribonucleoprotein (RNP) (often called the ENA panel). Screening laboratory
studies to diagnose possible SLE should include a CBC count with
differential, serum creatinine, urinalysis with microscopy, ANA, and,
perhaps, basic inflammatory markers. The following are autoantibody tests
used in the diagnosis of SLE:22

* ANA - Screening test; sensitivity 95%; not diagnostic without
clinical features
* Anti-dsDNA - High specificity; sensitivity only 70%; level variable
based on disease activity
* Anti-Sm - Most specific antibody for SLE; only 30-40% sensitivity
* Anti-SSA (Ro) or Anti-SSB (La) - Present in 15% of patients with SLE
and other connective-tissue diseases such as Sjögren syndrome; associated
with neonatal lupus
* Anti-ribosomal P - Uncommon antibodies that may correlate with lupus
cerebritis
* Anti-RNP - Included with anti-Sm, SSA, and SSB in the ENA profile;
may indicate mixed connective-tissue disease with overlap SLE,
scleroderma, and myositis
* Anticardiolipin - IgG/IgM variants measured with enzyme-linked
immunoassay (ELISA) among the antiphospholipid antibodies used to screen
for antiphospholipid antibody syndrome
* Lupus anticoagulant - Multiple tests (eg, Direct Russell Viper Venom
test) to screen for inhibitors in the clotting cascade in antiphospholipid
antibody syndrome
* Coombs test - Coombs test–positive anemia to denote antibodies on
RBCs
* Anti-histone - Drug-induced lupus ANA antibodies often this type
(eg, with procainamide or hydralazine; perinuclear antineutrophil
cytoplasmic antibody [p-ANCA]–positive in minocycline-induced drug-induced
lupus)

Other laboratory tests used in the diagnosis of SLE include the following:

* Inflammatory markers: Levels of inflammatory markers, including the
erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), may be
elevated in any inflammatory condition, including SLE. CRP levels change
more acutely, and the ESR lags behind disease changes.
* Complement levels: C3 and C4 levels are often depressed in patients
with active SLE because of consumption by immune complex–induced
inflammation. In addition, some patients have congenital complement
deficiency that predisposes them to SLE.
* A CBC count may help to screen for leukopenia, lymphopenia, anemia,
and thrombocytopenia, and urinalysis and creatinine studies may be useful
to screen for kidney disease.
* Liver test results may be mildly elevated in acute SLE or in
response to therapies such as azathioprine or nonsteroidal
anti-inflammatory drugs (NSAIDS).
* Creatinine kinase levels may be elevated in myositis or overlap
syndromes.

Imaging Studies

* Joint radiography often provides little evidence of SLE given the
absence of erosions, even in the presence of Jaccoud arthropathy with
deformity or subluxations. The most common radiographic changes in SLE
include periarticular osteopenia and soft-tissue swelling.
* Chest radiography and chest CT scanning can be used to monitor
interstitial lung disease and to assess for pneumonitis, pulmonary emboli,
and alveolar hemorrhage.
* Brain MRI/magnetic resonance angiography (MRA) is used to evaluate
CNS lupus for white-matter changes, vasculitis, or stroke, although
findings are often nonspecific.
* Echocardiography is used to assess for pericardial effusion,
pulmonary hypertension, or verrucous Libman-Sacks endocarditis.

Procedures

* Lumbar puncture may be performed to exclude infection with fever or
neurologic symptoms. Nonspecific elevations in cell count and protein
level and decrease in glucose level may be found in the cerebrospinal
fluid of patients with CNS lupus.
* Renal biopsy is used to identify the specific type of
glomerulonephritis, to aid in prognosis, and to guide treatment. Another
benefit of renal biopsy is in distinguishing renal lupus from renal
thrombosis, which may complicate antiphospholipid antibody syndrome and
require anticoagulation rather than immunomodulatory therapy.
* Skin biopsy can help to diagnose SLE or unusual rashes in patients
with SLE. Many different rashes may herald SLE, making review by a
dermatopathologist important.

Histologic Findings

Renal biopsy is used to confirm the presence of lupus nephritis, to aid in
classification of SLE nephritis, and to guide therapeutic decisions. The
World Health Organization classification for lupus nephritis is based on
light microscopy, electron microscopy, and immunofluorescence findings.

International Society of Nephrology 2003 Revised Classification of SLE
Nephritis23

Class Classification Features

Class I

Minimal mesangial

Normal light microscopy findings; abnormal electron microscopy findings

Class II

Mesangial proliferative

Hypercellular on light microscopy

Class III

Focal proliferative

<50% of glomeruli involved

Class IV

Diffuse proliferative

>50% of glomeruli involved; classified segmental or global; treated

aggressively

Class V

Membranous

Predominantly nephrotic disease

Class VI

Advanced sclerosing

Chronic lesions and sclerosis

Lupus skin rash often demonstrates inflammatory infiltrates at the
dermoepidermal junction and vacuolar change in the basal columnar cells.
Discoid lesions demonstrate more-significant skin inflammation, with
hyperkeratosis, follicular plugging, edema, and mononuclear cell
infiltration at the dermoepidermal junction. In many SLE rashes,
immunofluorescent stains demonstrate immunoglobulin and complement
deposits at the dermoepidermal basement membrane.