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  <head>
    <title>041-01 Foundations</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Multisystem autoimmune disease and vasculitis">
      <outline text="Orientation and loss of tolerance">
        <outline text="Diagnosis rests on phenotype and organ involvement">
          <outline text="Autoantibodies only modify probability"/>
        </outline>
        <outline text="Central tolerance deletes or edits self-reactive cells"/>
        <outline text="Peripheral tolerance restrains escaped cells">
          <outline text="Anergy, regulatory T cells, inhibitory receptors"/>
        </outline>
        <outline text="Triggers: infection, ultraviolet light, smoking, drugs">
          <outline text="Mimicry, epitope spreading, bystander activation"/>
        </outline>
        <outline text="Disease needs inherited risk, environment, and chance"/>
        <outline text="Several damage mechanisms may coexist"/>
      </outline>
      <outline text="Interpreting autoantibodies">
        <outline text="Test only when pretest probability justifies"/>
        <outline text="Antinuclear antibodies occur in healthy people">
          <outline text="Titre and pattern guide follow-up, not diagnosis"/>
        </outline>
        <outline text="Anti-double-stranded-DNA titres and complement">
          <outline text="May track lupus kidney activity"/>
        </outline>
        <outline text="Anti-Ro antibodies carry pregnancy implications"/>
        <outline text="Antineutrophil-cytoplasmic antibodies occur in mimics"/>
        <outline text="Inflammatory markers nonspecific, may be normal">
          <outline text="Sediment, complement, imaging, biopsy show damage"/>
        </outline>
      </outline>
      <outline text="Systemic lupus erythematosus">
        <outline text="Immune complexes, complement, interferon signalling"/>
        <outline text="Rash, ulcers, non-erosive arthritis, serositis"/>
        <outline text="Kidney disease can be silent">
          <outline text="Pressure, creatinine, sediment, protein detect it"/>
          <outline text="Biopsy classifies mechanism and activity"/>
        </outline>
        <outline text="Neurological symptoms: exclude infection, thrombosis, drugs"/>
        <outline text="Hydroxychloroquine reduces flares">
          <outline text="Weight-based dosing and retinal surveillance"/>
        </outline>
      </outline>
      <outline text="Antiphospholipid syndrome">
        <outline text="Persistent antibodies plus thrombosis or pregnancy morbidity">
          <outline text="Antibodies alone do not establish the syndrome"/>
          <outline text="Anticoagulants and acute illness affect tests"/>
        </outline>
        <outline text="Catastrophic disease: rapid multiorgan thrombosis">
          <outline text="Anticoagulation, immunomodulation, trigger treatment"/>
        </outline>
        <outline text="Long-term strategy by event, antibodies, bleeding risk"/>
      </outline>
      <outline text="Systemic sclerosis">
        <outline text="Vasculopathy, immune activation, progressive fibrosis"/>
        <outline text="Raynaud and swollen fingers precede skin thickening"/>
        <outline text="Lung disease and pulmonary hypertension are major killers">
          <outline text="Require systematic screening"/>
        </outline>
        <outline text="Renal crisis: abrupt hypertension and kidney injury">
          <outline text="Urgent angiotensin-converting-enzyme inhibition"/>
          <outline text="High-dose glucocorticoids increase risk"/>
        </outline>
        <outline text="Treat organ mechanisms, not fibrosis as one entity"/>
      </outline>
      <outline text="Sjögren disease">
        <outline text="Dry eyes: grittiness and corneal injury"/>
        <outline text="Dry mouth: decay, candidiasis, gland enlargement"/>
        <outline text="Drugs, dehydration, diabetes, ageing mimic dryness"/>
        <outline text="Substitutes, dental prevention, systemic therapy"/>
        <outline text="Gland enlargement, purpura, low complement: lymphoma"/>
      </outline>
      <outline text="Inflammatory myopathy">
        <outline text="Progressive proximal and neck weakness, dysphagia"/>
        <outline text="Antisynthetase: myositis with interstitial lung disease"/>
        <outline text="Inclusion-body myositis: finger flexors, quadriceps">
          <outline text="Responds poorly to conventional immunosuppression"/>
        </outline>
        <outline text="Creatine kinase rise may be modest"/>
        <outline text="Immune therapy, malignancy screening, rehabilitation"/>
      </outline>
      <outline text="Vasculitis framework">
        <outline text="Wall inflammation: stenosis, aneurysm, ischaemia"/>
        <outline text="Classify by vessel size, organ, histology, cause"/>
        <outline text="Infection, emboli, drugs mimic vasculitis">
          <outline text="Immunosuppression before excluding infection is catastrophic"/>
        </outline>
        <outline text="Large vessel: giant-cell and Takayasu arteritis">
          <outline text="Threatened vision: glucocorticoids before biopsy"/>
          <outline text="Takayasu: pulse asymmetry, bruits, hypertension"/>
        </outline>
        <outline text="Medium vessel: infarction, aneurysm, skin nodules">
          <outline text="No primary glomerulonephritis"/>
        </outline>
        <outline text="Small vessel: purpura, nephritis, lung haemorrhage">
          <outline text="Antineutrophil-antibody and immune-complex forms"/>
        </outline>
      </outline>
      <outline text="Organ-threatening presentations">
        <outline text="Pulmonary-kidney syndrome">
          <outline text="Alveolar haemorrhage with rapid glomerulonephritis"/>
          <outline text="Haemoptysis can be absent"/>
          <outline text="Urgent serology, microbiology, biopsy"/>
        </outline>
        <outline text="Mononeuritis multiplex from nerve-vessel ischaemia"/>
        <outline text="Mesenteric vasculitis: pain, bleeding, perforation"/>
      </outline>
      <outline text="Treatment strategy and safety">
        <outline text="Separate induction from maintenance">
          <outline text="Glucocorticoids with cyclophosphamide or B-cell depletion"/>
          <outline text="Plasma exchange only for selected indications"/>
        </outline>
        <outline text="Screen hepatitis, tuberculosis, human immunodeficiency virus"/>
        <outline text="Prophylaxis against opportunistic infection, bone loss"/>
        <outline text="Monitor activity and toxicity separately">
          <outline text="Normal markers do not prove remission"/>
        </outline>
        <outline text="Fever or cytopenia: infection, toxicity, or flare">
          <outline text="Cultures before escalating immunosuppression"/>
        </outline>
      </outline>
    </outline>
  </body>
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