--- module: 041-02 language: en chapter: 41 title: "Multisystem Autoimmune Disease and Vasculitis" module_title: "Autoimmune probability, vascular injury patterns, and safe immune suppression" source_sha256: ab9c4f373aa858fa312f932067bdda8eb9fde92f9a627b6ea4ef91dfed593885 --- # Autoimmune probability and safe immune suppression ## Causal coherence and mechanism ### Common features need not share one mechanism ### Link features to injury, pathway, time course #### Actively test infection, malignancy, drugs ### No single tolerance checkpoint is perfect #### Genes alter several weak checkpoints #### Infection supplies costimulation, exposes hidden antigens ### Effectors: antibodies, complexes, T cells, cytokines #### Antiphospholipid antibodies promote thrombosis #### Naming the mechanism predicts meaningful signals ## Antibody testing ### Testing follows a defined clinical question ### Antinuclear antibody sensitive, low predictive value #### Repeating rarely measures activity ### Antineutrophil antibodies also positive in infection, drugs ### Ask what a positive changes, what a negative excludes ### Separate activity, classification, prognostic antibodies ## Lupus organ surveillance ### Serial pressure, creatinine, protein, sediment #### Dysmorphic cells or casts: glomerular inflammation ### Markers must not overrule a stable kidney phenotype ### Biopsy shows class, activity, scar, alternatives #### Match treatment to salvageable inflammation ### Active sediment progresses despite normal creatinine #### Low muscle mass hides filtration loss ### Neuropsychiatric symptoms need sceptical attribution #### A cerebritis label misses infection ## Antiphospholipid syndrome ### Events plus persistent laboratory evidence ### Lupus anticoagulant paradox #### Prolongs clotting assays yet raises thrombosis ### Thrombosis, pregnancy, anticoagulants distort tests ### Catastrophic: rapid multiorgan thrombosis #### Anticoagulation, trigger suppression, plasma exchange ## Systemic sclerosis ### Vasculopathy, autoimmunity, fibrosis interact ### Ulcers, pitting scars, gangrene: structural disease #### Capillaroscopy separates primary Raynaud ### Breathlessness has many causes #### Lung disease, pulmonary hypertension, heart, aspiration ### Renal crisis: pressure rise, kidney injury, haemolysis #### Continue inhibitor despite creatinine rise #### Normal pressure may not exclude crisis if usually low ## Sjögren disease and myopathy ### Tear loss damages corneal epithelium ### Saliva loss impairs buffering, defence, remineralisation ### Objective tests separate gland failure from dryness ### Tubular acidosis, purpura signal systemic activity ### Myopathy recognised by power, not creatine kinase #### Serial neck, shoulder, hip, swallowing, breathing ### Inclusion-body myositis resists immune therapy ### Magnetic resonance guides biopsy to active muscle ## Vascular patterns and giant-cell arteritis ### Localise by vessel calibre and organ pattern ### Large: pulse deficits, bruits, aortic dilatation ### Medium: aneurysm, infarction, mononeuritis ### Small: purpura, glomerular haematuria, capillaritis #### Framework directs imaging versus biopsy ### Giant-cell arteritis: treat at once if vision threatened #### Normal markers reduce but do not eliminate risk #### Imaging and biopsy remain useful after treatment ## Pulmonary-kidney syndrome ### Alveolar haemorrhage without haemoptysis ### Glomerulonephritis: blood, protein, casts ### Alternatives: anti-basement-membrane disease, lupus ### Plasma exchange for selected mechanisms only ### Infection and haemorrhage both cause opacity #### Cultures before and after immunosuppression ### Negative antibody does not discard a strong picture ### Supportive care does not wait for classification ## Safe immune suppression ### Induction stops threat, maintenance limits toxicity ### Steroid harm begins immediately ### Cyclophosphamide: marrow, bladder, fertility, malignancy ### Baseline infection, vaccines, tuberculosis, hepatitis ### Prophylaxis: Pneumocystis, viral reactivation ### Strongyloides hyperinfection can be fatal ### Scheduled monitoring, visible cumulative steroid dose ### Contraception and fertility addressed before treatment ## Activity versus toxicity ### Fever or opacity: flare, infection, drug toxicity ### Escalation without new specimens can harm ### Waiting for certainty in organ emergencies harms #### Act in proportion to organ threat ### Record mechanism, organ, activity, damage, infection ### Non-response is not simply insufficient dose #### Reassess diagnosis, scar, adherence, infection