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CONNECTIVE TISSUE DISEASES

  • Group of systemic autoimmune diseases

  • Screening

    • Antinuclear antibody (ANA): performed using indirect immunofluorescence (IF)

    • Varying concentrations of patient serum are incubated with a tissue substrate (usually human epithelial tumor line HEp-2), and any autoantibodies to nuclear antigens present in the serum bind to the substrate

    • A fluoresceinated antibody is added, and the tissue is observed under fluorescent microscopy to check for a specific staining pattern

      • Results reported as

        • Titer: level of antinuclear antibodies significant enough to be defined as a positive ANA. The standard definition is the titer exceeding that found in 95% of normal individuals (5% of normal individuals can be ANA-positive, with titers usually ≥1:320 and a speckled or homogeneous pattern)

        • Pattern: corresponds to the presence of a specific antibody. A certain pattern may indicate the presence of various rheumatologic diseases

        • A positive ANA is seen in

          • Systemic lupus erythematosus (SLE): 99%

          • Systemic sclerosis (SSc) patients: 97%

          • Dermatomyositis (DM) patients: 40 to 80%

  • ANA patterns and their corresponding antibodies

    • Homogeneous pattern (Fig. 22-1): complete nuclear fluorescence; specific for SLE

      • – Double-stranded DNA (dsDNA) or native DNA: 70% SLE, associated with lupus nephritis

      • – Histone: 50 to 70% SLE; also the antibody found in drug-induced SLE (but not in drug-induced subacute cutaneous lupus erythematosus)

    • Rim pattern: fluorescence at edges of nucleus, anti-DNA, antihistone and antilaminin antibodies: SLE (most specific) but also may be seen in chronic active hepatitis

    • Speckled pattern (Fig. 22-2):

      • – SS-A/Ro: 30 to 40% SLE; often with subacute cutaneous lupus erythematosus (SCLE), drug-induced SCLE, and neonatal LE; also seen in Sjögren syndrome (SS), DM

      • – SS-B/La: 15% SLE often with SCLE, drug-induced SCLE, neonatal LE

      • – Antiribonucleoprotein (RNP): 30% SLE; associated with mixed connective tissue disease (MCTD)

      • – Anti-Smith (Sm): 20 to 30% SLE; very specific

  • Extractable nuclear antigens (ENAs)

    • Soluble cytoplasmic and nuclear components that are bound by autoantibodies

    • Antibodies include Ro, La, Sm, RNP, Scl-70, and Jo-1

    • ENA-4 test

      • – Identifies Ro, La, RNP, and Sm

      • – Used to diagnose SLE, MCTD, and SS

    • Nucleolar pattern (homogeneous, speckled, or clumpy staining of nucleolus)

      • – RNA polymerase I (RNA pol 1): 4 to 23% SSc

      • – U3-RNP/fibrillarin: SSc

      • – Topoisomerase I (Scl-70): 22 to 40% of SSc, associated with diffuse SSc

      • – PM-Scl: SSc-polymyositis overlap

    • Centromere pattern (antibodies to kinetochore proteins)

      • – Approximately 22 to 36% of SSc patients

      • – Approximately 60 to 90% of limited SSc patients (e.g., CREST syndrome [calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia])

FIGURE 22-1

Homogeneous pattern. (Used with permission from Dr. Robert Jordon.)

FIGURE 22-2

Speckled pattern. (Used with permission from Dr. Robert Jordon.)

Lupus Erythematosus

  • Autoimmune disorder with a spectrum of presentations; may be cutaneous and/or systemic

  • Cutaneous lupus subsets

    • Acute ...

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