Chapter 22: Rheumatologic Diseases

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])

Lupus Erythematosus

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

• Cutaneous lupus subsets

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