SLE

• • Epidemiology: 20 - 40 years age group; 1:2500; m:f ratio 9:1; children and older adults the m: f is same; common in African Americans.

    • Risk factors: Genetics and environment

  • Pathology:

    • Type III hypersensitivity reaction (due to deposition of immune complex and subsequent activation of complement cascade)

    • Morphology of SLE: LE cells in tissue (neutrophils containing phagocytosed nuclei.

      • SLE in renal disease has 5 classes:

        • Class I: no disease

        • Class II: Mesangial - increase in mesangial matrix due to deposition of immune complexes.

        • Class III: Focal proliferative glomerulonephritis - few glomeruli have proliferation of endothelial and mesangial cells; associated with increased number of neutrophils and possibly fibrinoid necrosis.

        • Class IV: Diffuse proliferative glomerulonephritis - most if not all glomeruli have changes seen in Class III.

        • Class V: Membranous glomerulonephropathy - glomeruli have thickened basement membranes, producing a "wire-loop" pattern.

  • Clinical presentation: Mnemonic: MD SOAP BRAIN

    • Malar rash

    • Discoid rash

    • Serositis: pericarditis, pleural effusion, peritonitis, synovitis

    • Oral ulcers

    • Arhtralgias: include myalgia, arthritis, arthralgia are often the first complain of Pts diagnosed with SLE.

    • Photosensitivity

    • Blood d/o: hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia

    • Renal dysfunction: proteinuria >0.5 g/dL; cellular casts

    • ANA abs

    • Immunologic d/o: anti-dsDNA ab, anti-Smith ab, antiphospholipid ab (+ve lupus anticoagulant, abnormal level of IgM, IgG anticardiolipin, false positive test for syphilis. Cardiolipin is a constituent material used in a syphilis test (which one?)

    • Neurological d/o: sz, psychosis, including chorea

    • Other features: Sx: fever, wt. loss, malaise, Raynaud's phenomenon, miscarriages, meds (INH, hydralazine, procainamide)

    • Two conditions commonly associated with SLE are antiphospholipid antibody syndrome (APA or APLAS), and drug-induced lupus.

  • Opportunistic infections are the most common cause of death. Renal (ESRD) and CNS diseases are the 2nd most common cause of death.

  • ANA is a sensitive screening test, anti-dsDNA is specific. Anti-Sm is also specific. Complement levels become depressed during active dz, but returns to normal during remissions.

Clinical and Immunologic Criteria Used in the Systemic Lupus International Collaborating Clinics Classification Criteria:

Classification Rule: Classify a patient as having SLE if

The patient satisfies four of the criteria listed including at least one clinical and one immunologic criterion

OR

The patient has biopsy-proven nephritis compatible with SLE and with ANA or anti-dsDNA antibodies

Clinical Criteria:

1. Acute cutaneous lupus including:

• Lupus malar rash (do not count if malar discoid)

• Bullous lupus

• Toxic epidermal necrolysis variant of systemic lupus erythematosus

• Maculopapular lupus rash

• Photosensitive lupus rash

• In the absence of dermatomyositis

OR

• Subacute cutaneous lupus (nonindurated psoriasiform and/or annular polycyclic lesions that resolve without scarring, although occasionally with postinflammatory dyspigmentation or telangiectasias)

2. Chronic cutaneous lupus including:

• Classic discoid rash

  • Localized (above the neck)

  • Generalized (above and below the neck)

• Hypertrophic (verrucous) lupus

• Lupus panniculitis (profundus)

• Mucosal lupus

• Lupus erythematosus tumidus

• Chilblains lupus

• Discoid lupus/lichen planus overlap

3. Oral ulcers

• Palate

• Buccal

• Tongue

OR

Nasal ulcers

In the absence of other causes, such as vasculitis, Behçet disease, infection (herpes), inflammatory bowel disease, reactive arthritis, and acidic foods.

4. Nonscarring alopecia (diffuse thinning or hair fragility with visible broken hairs)

In the absence of other causes such as alopecia areata, drugs, iron deficiency, and androgenic alopecia.

5. Synovitis involving two or more joints, characterized by swelling or effusion OR tenderness in two or more joints and 30 minutes or more of morning stiffness

6. Serositis

• Typical pleurisy for more than 1 day

OR

• Pleural effusions

OR

Pleural rub

• Typical pericardial pain (pain with recumbency improved by sitting forward) for more than 1 day

OR

• Pericardial effusion

OR

• Pericardial rub

OR

• Pericarditis by ECG

In the absence of other causes, such as infection, uremia, and Dressler syndrome

7. Renal

• Urine protein/creatinine (or 24-hour urine protein) representing 500 mg of protein per 24 hours

OR

• Red blood cell casts

8. Neurologic

• Seizures

• Psychosis

• Mononeuritis multiplex

  • In the absence of other known causes such as primary vasculitis

• Myelitis

• Peripheral or cranial neuropathy

  • In the absence of other known causes such as primary vasculitis, infection, and diabetes mellitus

• Acute confusional state

  • • In the absence of other causes, including toxic-metabolic, uremia, or drugs

9. Hemolytic anemia

10. Leukopenia (<4000/mm3 at least once)

In the absence of other known causes such as Felty syndrome, drugs, or portal hypertension

OR

• Lymphopenia (<1000/mm3 at least once)

  • In the absence of other known causes such as corticosteroids, drugs, or infection

11. Thrombocytopenia (<100,000/mm3 at least once)

In the absence of other known causes such as drugs, portal hypertension, or TTP

Immunologic Criteria

1. ANA above laboratory reference range

2. Anti-dsDNA above laboratory reference range, except ELISA: twice above laboratory reference range

3. Anti-Sm

4. Antiphospholipid antibody as determined by any of the following

• Lupus anticoagulant

• False-positive RPR

• Medium or high titer anticardiolipin (IgA, IgG, or IgM)

• Anti-beta2 glycoprotein I (IgA, IgG, or IgM)

5. Low complement

• Low C3

• Low C4

• Low CH50

6. Direct Coombs test in the absence of hemolytic anemia

The recent guidelines for the clinical use of antinuclear antibody tests issued by a Committee of the College of American Pathologists (CAP), suggest widespread misunderstanding of the clinical value of testing for the level of anti-ssDNA (single-stranded DNA or total DNA) IgG antibodies. This misunderstanding may stem from misconceptions about the manner in which clinicians use, in clinical context, immunoassays that have results expressed on a wide numerical scale.

When the anti-ssDNA antibody (Ab) test is used for the differential diagnosis of new patients suspected of an inflammatory rheumatic disease the clinical sensitivity for systemic lupus erythematosus (SLE) is close to 100%, and the specificity about 85%. Since anti-dsDNA (double stranded DNA) is present in only about 65% of new SLE patients, an abnormal anti-ssDNA Ab test in the remaining 35% provides the clinician with a valuable clue to search for other criteria for SLE. Contrary to a widely held belief that anti-ss-DNA Ab occurs frequently in patients with rheumatoid arthritis (RA), anti-ssDNA is present only in 10–15% of this patient population and then at relatively low levels. There is evidence that anti-ssDNA, like anti-dsDNA, is involved in the pathogenesis of lupus nephritis. Moreover, the increase in anti-ssDNA Ab level appeared to be the best predictor of forthcoming increase in anti-dsDNA and SLE flare. In a context of symptoms different from those of rheumatic diseases, anti-ssDNA antibodies may be elevated in a relatively high proportion of patients with any of several diseases; leukemia, preeclampsia, chronic hepatitis, renal complications of diabetes, and some inflammatory neurological diseases. In conclusion, anti-ssDNA helps to rule out SLE, helps in the diagnosis of SLE when anti-dsDNA is not present and is useful in follow-up of SLE patients. Like most other quantifiable laboratory indicators of abnormality, anti-ssDNA Ab test is also useful in clinical context for the diagnosis and prognosis of several other condition.