--- module: 041-01 language: en chapter: 41 title: "Multisystem Autoimmune Disease and Vasculitis" module_title: "Foundations" source_sha256: 67341772d77b36727d094f065b4e11eb55669a2f97956ed7d973330fa01ddd97 --- # Multisystem autoimmune disease and vasculitis ## Orientation and loss of tolerance ### Diagnosis rests on phenotype and organ involvement #### Autoantibodies only modify probability ### Central tolerance deletes or edits self-reactive cells ### Peripheral tolerance restrains escaped cells #### Anergy, regulatory T cells, inhibitory receptors ### Triggers: infection, ultraviolet light, smoking, drugs #### Mimicry, epitope spreading, bystander activation ### Disease needs inherited risk, environment, and chance ### Several damage mechanisms may coexist ## Interpreting autoantibodies ### Test only when pretest probability justifies ### Antinuclear antibodies occur in healthy people #### Titre and pattern guide follow-up, not diagnosis ### Anti-double-stranded-DNA titres and complement #### May track lupus kidney activity ### Anti-Ro antibodies carry pregnancy implications ### Antineutrophil-cytoplasmic antibodies occur in mimics ### Inflammatory markers nonspecific, may be normal #### Sediment, complement, imaging, biopsy show damage ## Systemic lupus erythematosus ### Immune complexes, complement, interferon signalling ### Rash, ulcers, non-erosive arthritis, serositis ### Kidney disease can be silent #### Pressure, creatinine, sediment, protein detect it #### Biopsy classifies mechanism and activity ### Neurological symptoms: exclude infection, thrombosis, drugs ### Hydroxychloroquine reduces flares #### Weight-based dosing and retinal surveillance ## Antiphospholipid syndrome ### Persistent antibodies plus thrombosis or pregnancy morbidity #### Antibodies alone do not establish the syndrome #### Anticoagulants and acute illness affect tests ### Catastrophic disease: rapid multiorgan thrombosis #### Anticoagulation, immunomodulation, trigger treatment ### Long-term strategy by event, antibodies, bleeding risk ## Systemic sclerosis ### Vasculopathy, immune activation, progressive fibrosis ### Raynaud and swollen fingers precede skin thickening ### Lung disease and pulmonary hypertension are major killers #### Require systematic screening ### Renal crisis: abrupt hypertension and kidney injury #### Urgent angiotensin-converting-enzyme inhibition #### High-dose glucocorticoids increase risk ### Treat organ mechanisms, not fibrosis as one entity ## Sjögren disease ### Dry eyes: grittiness and corneal injury ### Dry mouth: decay, candidiasis, gland enlargement ### Drugs, dehydration, diabetes, ageing mimic dryness ### Substitutes, dental prevention, systemic therapy ### Gland enlargement, purpura, low complement: lymphoma ## Inflammatory myopathy ### Progressive proximal and neck weakness, dysphagia ### Antisynthetase: myositis with interstitial lung disease ### Inclusion-body myositis: finger flexors, quadriceps #### Responds poorly to conventional immunosuppression ### Creatine kinase rise may be modest ### Immune therapy, malignancy screening, rehabilitation ## Vasculitis framework ### Wall inflammation: stenosis, aneurysm, ischaemia ### Classify by vessel size, organ, histology, cause ### Infection, emboli, drugs mimic vasculitis #### Immunosuppression before excluding infection is catastrophic ### Large vessel: giant-cell and Takayasu arteritis #### Threatened vision: glucocorticoids before biopsy #### Takayasu: pulse asymmetry, bruits, hypertension ### Medium vessel: infarction, aneurysm, skin nodules #### No primary glomerulonephritis ### Small vessel: purpura, nephritis, lung haemorrhage #### Antineutrophil-antibody and immune-complex forms ## Organ-threatening presentations ### Pulmonary-kidney syndrome #### Alveolar haemorrhage with rapid glomerulonephritis #### Haemoptysis can be absent #### Urgent serology, microbiology, biopsy ### Mononeuritis multiplex from nerve-vessel ischaemia ### Mesenteric vasculitis: pain, bleeding, perforation ## Treatment strategy and safety ### Separate induction from maintenance #### Glucocorticoids with cyclophosphamide or B-cell depletion #### Plasma exchange only for selected indications ### Screen hepatitis, tuberculosis, human immunodeficiency virus ### Prophylaxis against opportunistic infection, bone loss ### Monitor activity and toxicity separately #### Normal markers do not prove remission ### Fever or cytopenia: infection, toxicity, or flare #### Cultures before escalating immunosuppression