Lecture 10 Collagen Vascular Diseases

Pathology

Lecture 10 Collagen Vascular Diseases

1) To be familiar with current hypotheses regarding the pathogenesis of SLE. Autoimmune diseases, like Systemic Lupus Erythematosus (SLE), represent a state of loss of immunologic tolerance. Mechanisms of tolerance include: clonal anergy (non-reactive lymphocytes), suppression by suppressor T cells, clonal deletion by apoptosis, and antigen sequestration. SLE occurs through loss of tolerance including: loss of anergy, failed apoptosis, loss of suppressor T cells, molecular changes (antigens mimicking self or self components becoming unrecognizable), Polyclonal lymphocyte activation either bypasses or overwhelms regulatory controls, and emergence of sequestered antigen.

2) To understand common laboratory tests for SLE. The antinuclear antibody test, ANA test, is positive for many connective tissue diseases but is more specific for SLE when the antinuclear antibodies react with double-stranded DNA. Microscopically this appears as a characteristic peripheral nuclear staining or “rim” pattern. Other tests include: direct immunofluorescence of skin, hematalogic evaluation (hemolytic anemia, anti-platelet antibodies), and renal biopsy.

3) To know the general mechanisms for tissue damage in SLE. Injury is manifested primarily in skin, joints, kidney, serosal membranes and CNS. Antinuclear antibodies as well as other antibodies mediate pathogenic mechanisms (humoral and cellular). Cell injury may be an initiator allowing access to nuclear components. Antiphospholipid (anti-cardiolipin) antibodies are directed against phospholipids-β2-glycoprotein complex (may give false positive for syphilis) and act as an anticoagulant, although they paradoxically cause arterial and venous thrombosis.

4) To be able to describe the lesions in organs commonly affected in SLE.

Arteries, arterioles: Vasculitis and/or fibrosis

Kidney: Various forms of glomerulonephritis, most severe is diffuse proliferative.

Skin: Malar (cheeks, bridge of nose) rash; positive IF

Joints: non-erosive arthritis.

CNS: Neuropsychiatric findings; often due to vasculits

Serosal membranes: Inflammation, fibrosis.

Cardiovascular system: Libman-Sacks endocarditis; may also have pericarditis or myocarditis.

5) To know the general course, prognosis and therapy of SLE. Presents in teen-aged or young adult female with complaints of skin rash, photosensitivity, joint pain, fever, and/or hematuria. Survival rates are about 90% live for 5 years and 80% for 10 years. Patients most commonly die of renal failure and infection. Therapy includes corticosteroids, immunosuppressants, and plasmapheresis.

6) To be familiar with the types of antinuclear antibodies present in common collagen vascular diseases. Types of antinuclear antibodies include: antibodies to DNA, histones, and nonhistone proteins bound to RNA, as well as nuceolar antigens.

7) To know the main patterns of pathology in scleroderma, polymyositis/dermatomyositis, and mixed connective disease.

Disease / Patterns of pathology
Scleroderma / Severe, immune-mediated fibrosis throughout the body, microvascular abnormality (intimal fibrosis, capillary dilation, endothelial injury), and ANAs against DNA topoisomerase and centromeres.
Polymyositis/
dermatomyositis / Chronic inflammatory process involving proximal muscles of the extremities, skin may also be involved (dermatomyositis) causing rash.
Mixed connective disease / Combined features of SLE, polymyositis, and systemic sclerosis. Uncommon to have renal injury and very good response to steroid therapy.

8) To be familiar with the clinical, laboratory and pathology features of rheumatoid arthritis.

Clinical: Chronic inflammatory disorder affecting primarily synovial joints in women aged 20-50. Presents as swelling and stiffness of the joints (mostly proximal interphalangeal and metacarpophalangeal joints) with ulnar deviation of the fingers. Other systems may also be involved (lung, peripheral nerves), mediated by a vasculitis.

Laboratory: Rheumatoid Factor (RF), immunoglobulin (often IgG) acting as antigen for another immunoglobulin (often IgM) acting as antibody to form an immune complex, may be identified in serum, joint tissue or fluid (80% sensitive for arthritis). Occurs most often in HLA-DR4 positive individuals.

Pathology: Autoimmune origin with genetic and environmental factors. Often characterized by presence of RF. Initially presents as acute inflammatory reaction, then hyperplasia and hypertrophy of synovial lining cells develops, bone and cartilage deformities can result from granulation tissue (pannus) extending to subcondrial tissue. Scarring, contracture and deformity result from destructive inflammation of ligaments, tendons and bursae. Subcutaneous rheumatoid nodules may also develop.