Autoimmune Diseases: Mechanisms, Classification, Diagnosis and Clinical Emergencies
Study level: Clinical medicine, emergency medicine and pathology | Topic: Immunopathology
Core idea: Autoimmune disease occurs when immune tolerance to self-antigens is lost and self-reactive lymphocytes or antibodies cause tissue injury. The disease may be organ-specific or systemic, often follows a relapsing-remitting course, and can produce life-threatening renal, neurologic, endocrine, respiratory, haematologic or vascular complications.
Learning objectives
- Define autoimmunity and distinguish harmless autoreactivity from autoimmune disease.
- Explain central and peripheral self-tolerance and how genetic and environmental factors break tolerance.
- Describe antibody-mediated, immune-complex and T-cell-mediated tissue injury.
- Classify autoimmune disorders as organ-specific or systemic and recognise representative diseases.
- Choose investigations rationally, interpret autoantibodies in clinical context and avoid false-positive diagnoses.
- Recognise emergency presentations and outline safe, multidisciplinary management principles.
1. Definitions and essential distinctions
Autoimmunity is an immune response directed against an antigen belonging to the host. Low-level autoreactive B and T cells are common in healthy people; their presence alone is not disease. Autoimmune disease means clinically important autoimmunity that produces inflammation, loss of function, structural damage or organ failure.
| Term | Meaning | Clinical implication |
|---|---|---|
| Self-tolerance | Specific unresponsiveness to the body’s own antigens. | Prevents destructive responses against normal tissues. |
| Autoantibody | Antibody that binds a self-antigen. | May be pathogenic, a disease marker, or an incidental finding. |
| Autoimmune disease | Autoimmunity plus demonstrable tissue injury or dysfunction. | Requires a clinical syndrome, not an isolated laboratory result. |
| Autoinflammatory disease | Predominantly dysregulated innate immunity, often without disease-specific autoantibodies. | Do not automatically label every inflammatory syndrome autoimmune. |
| Allergy/hypersensitivity | Exaggerated immune response to usually harmless foreign antigen. | Different antigen target; hypersensitivity may coexist with autoimmunity. |
2. Normal self-tolerance: the protective checkpoints
2.1 Central tolerance
Central tolerance develops while lymphocytes mature. In the thymus, immature T cells that bind self-peptide–MHC with high affinity undergo clonal deletion (negative selection). Medullary thymic epithelial cells express tissue-restricted antigens under the AIRE transcription factor, allowing deletion of T cells that could attack endocrine and other peripheral tissues. Some self-reactive thymocytes are diverted into the regulatory T-cell (Treg) lineage. In bone marrow, immature B cells undergo receptor editing, deletion or anergy when their B-cell receptor strongly recognises self.
2.2 Peripheral tolerance
Central deletion is incomplete, because not every self-antigen is displayed during lymphocyte development. Peripheral tolerance controls escaped cells through:
- Anergy: antigen recognition without adequate co-stimulation makes a lymphocyte functionally unresponsive.
- Deletion: repeated stimulation can trigger apoptosis of autoreactive cells.
- Suppression by Tregs: FOXP3-positive Tregs release inhibitory cytokines and consume IL-2; CTLA-4 reduces co-stimulation.
- Inhibitory checkpoints: CTLA-4 and PD-1 pathways dampen T-cell activation.
- Sequestration: some antigens are normally hidden in immune-privileged sites and are exposed after trauma or inflammation.
- Ignorance and limited access: a self-reactive clone may remain inactive if antigen concentration, presentation or inflammatory signals are insufficient.
Exam chain: defective central deletion supplies autoreactive clones; infection or tissue damage supplies inflammation and co-stimulation; genetic susceptibility shapes the target; chronic immune activation and epitope spreading maintain the disease.
3. Why tolerance fails: causes and risk factors
| Factor | Mechanism | Examples or consequences |
|---|---|---|
| Genetic susceptibility | HLA variants alter which self-peptides are presented; non-HLA genes affect Tregs, cytokines, complement, B-cell signalling and checkpoints. | HLA-DR3/DR4 with type 1 diabetes; HLA-DR4 with rheumatoid arthritis; HLA-B27 with spondyloarthritis. |
| Sex and hormones | Sex-linked immune regulation and oestrogen effects influence B-cell survival and antibody production. | Many systemic autoimmune diseases are more common in women; pregnancy may improve or worsen different conditions. |
| Infections | Molecular mimicry, bystander cytokines, tissue injury and activation of previously silent clones. | Post-streptococcal rheumatic disease; infection-associated arthritis; viral triggers of flares. |
| Molecular mimicry | Microbial epitopes resemble self-epitopes, so cross-reactive T cells or antibodies damage host tissues. | Cross-reactivity after infection can initiate autoimmunity in a genetically susceptible person. |
| Bystander activation | Local interferons, cytokines and danger signals activate autoreactive cells that were not specific for the organism. | Inflamed tissue becomes permissive to autoimmune damage. |
| Epitope spreading | Initial injury releases new self-epitopes; the immune response broadens from the original target to additional targets. | Progressive, chronic disease despite removal of the initial trigger. |
| Cryptic antigens and tissue damage | Trauma, necrosis or altered protein processing exposes previously hidden or modified self-antigens. | Autoimmunity after tissue injury or drug-induced alteration of proteins. |
| Drugs and chemicals | Drug-protein binding creates neoantigens or alters immune regulation. | Drug-induced lupus, autoimmune haemolysis or vasculitis; always review the medication timeline. |
| Microbiome, smoking and ultraviolet light | Change barrier integrity, antigen exposure and inflammatory signalling. | Smoking increases rheumatoid risk; ultraviolet light can promote lupus flares. |
| Failure of clearance | Defective complement or phagocytic clearance leaves apoptotic debris and nuclear antigens available for immune-complex formation. | Important in systemic lupus erythematosus. |
4. Immunopathogenic mechanisms of tissue damage
4.1 Antibody-mediated disease (often called type II hypersensitivity)
- Cell destruction: IgG or IgM binds cell-surface antigens and activates complement, phagocytosis or antibody-dependent cellular cytotoxicity. Examples include autoimmune haemolytic anaemia and immune thrombocytopenia.
- Receptor stimulation: an antibody acts as an agonist. Thyroid-stimulating immunoglobulin activates the TSH receptor in Graves disease.
- Receptor blockade: an antibody prevents a normal ligand from binding. Anti-acetylcholine-receptor antibodies impair neuromuscular transmission in myasthenia gravis.
- Structural disruption: antibodies against cell-adhesion proteins produce blistering, as in pemphigus vulgaris.
4.2 Immune-complex disease (type III pattern)
Soluble antigen–antibody complexes deposit in small vessels, glomeruli, skin, joints or serosal surfaces. Complement activation generates C3a and C5a, recruits neutrophils and produces vasculitis, glomerulonephritis and arthritis. Systemic lupus erythematosus is the classic example. Low serum complement can indicate active consumption, but normal complement does not exclude disease.
4.3 T-cell-mediated disease (type IV pattern)
CD4 T cells release cytokines that activate macrophages and recruit inflammatory cells; CD8 cytotoxic T cells kill target cells directly. Type 1 diabetes destroys pancreatic beta cells, multiple sclerosis targets myelin and autoimmune hepatitis injures hepatocytes through combined T-cell and antibody mechanisms.
4.4 Mixed mechanisms
Most autoimmune diseases are not pure textbook categories. A patient may have autoantibodies, immune complexes, T-cell injury, thrombosis and cytokine-driven inflammation at the same time. Mechanism guides the test and treatment but does not replace clinical diagnosis.
5. Classification
| Pattern | Main target | Examples | Typical clues |
|---|---|---|---|
| Organ-specific | One organ or a restricted tissue antigen. | Type 1 diabetes, Graves disease, Hashimoto thyroiditis, myasthenia gravis, multiple sclerosis, autoimmune hepatitis, coeliac disease, Addison disease. | Symptoms follow loss or stimulation of one organ, although extra-organ manifestations may occur. |
| Systemic | Widely distributed antigens such as nuclear or vascular components. | SLE, rheumatoid arthritis, systemic sclerosis, Sjögren syndrome, systemic vasculitis, antiphospholipid syndrome. | Multisystem inflammation, constitutional symptoms and variable organ involvement. |
| Overlap syndromes | Features of more than one defined disorder. | SLE–scleroderma overlap, mixed connective-tissue disease. | Do not force a patient into one label when phenotype evolves over time. |
6. High-yield autoimmune diseases
| Disease | Core immune target/mechanism | Clinical pattern | Useful tests and emergencies |
|---|---|---|---|
| Systemic lupus erythematosus (SLE) | Loss of tolerance to nuclear antigens; immune complexes and complement consumption. | Photosensitive rash, oral ulcers, inflammatory arthritis, serositis, cytopenias, nephritis and neuropsychiatric disease. | ANA is sensitive; anti-dsDNA and anti-Sm are more specific; urinalysis, urine protein, creatinine, CBC and C3/C4 assess activity. Emergencies: lupus nephritis, CNS lupus, pulmonary haemorrhage, severe cytopenia and thrombosis. |
| Rheumatoid arthritis | Chronic synovial T-cell/macrophage inflammation; anti-CCP and rheumatoid factor may precede symptoms. | Symmetric small-joint inflammatory polyarthritis, morning stiffness, erosions, nodules, lung and vascular disease. | RF and anti-CCP support diagnosis but are not diagnostic alone. ESR/CRP and radiographs assess activity/damage. Emergencies: cervical-spine instability, vasculitis, atlanto-axial compression and serious infection during immunosuppression. |
| Type 1 diabetes mellitus | T-cell destruction of pancreatic beta cells with islet autoantibodies as markers. | Polyuria, polydipsia, weight loss and ketosis after progressive beta-cell loss. | Glucose, ketones, electrolytes, blood gas and HbA1c. Autoantibodies include GAD, IA-2, insulin and ZnT8. Emergency: diabetic ketoacidosis. |
| Graves disease | TSH-receptor antibodies stimulate thyroid hormone production. | Hyperthyroidism, goitre, tremor, weight loss, ophthalmopathy and sometimes dermopathy. | TSH, free T4/T3 and TSH-receptor antibodies. Emergency: thyroid storm with fever, delirium, tachyarrhythmia, heart failure or gastrointestinal symptoms. |
| Hashimoto thyroiditis | Th1/T-cell injury and antibodies against thyroid peroxidase and thyroglobulin. | Gradual hypothyroidism, goitre early and atrophy later; associated with other autoimmune disease. | TSH, free T4 and anti-TPO. Emergency: severe decompensated hypothyroidism (myxoedema coma). |
| Myasthenia gravis | Antibodies block or destroy acetylcholine receptors or interfere with MuSK signalling. | Fluctuating fatigable ocular, bulbar and limb weakness; sensation and pupils are usually spared. | AChR/MuSK antibodies, nerve stimulation and chest imaging for thymoma. Emergency: myasthenic crisis with respiratory or bulbar failure; distinguish from cholinergic toxicity and sepsis. |
| Multiple sclerosis | Autoreactive T cells and antibodies cause CNS demyelination and axonal injury. | Neurologic deficits separated in time and space: optic neuritis, sensory loss, weakness, ataxia and bladder dysfunction. | MRI brain/spine and CSF oligoclonal bands support diagnosis. Emergency-like severe relapse requires urgent neurologic assessment; exclude infection and spinal compression. |
| Autoimmune haemolytic anaemia | IgG warm or IgM cold antibodies bind red-cell antigens. | Fatigue, jaundice, splenomegaly, dark urine and anaemia; cold disease may cause acrocyanosis. | CBC, reticulocytes, bilirubin, LDH, haptoglobin and direct antiglobulin (Coombs) test. Emergency: hypoxia, haemodynamic instability or rapidly falling haemoglobin. |
| Immune thrombocytopenia (ITP) | Antiplatelet antibodies accelerate splenic platelet clearance and impair production. | Isolated thrombocytopenia, petechiae, purpura, mucosal bleeding; splenomegaly suggests another diagnosis. | Repeat CBC and blood film; exclude HIV, hepatitis, drugs and marrow disease. Emergency: intracranial, gastrointestinal or uncontrolled mucosal bleeding. |
| Autoimmune hepatitis | Loss of tolerance to hepatic antigens with interface hepatitis. | Fatigue, jaundice, hepatomegaly or acute liver failure; may be silent until cirrhosis. | ALT/AST, bilirubin, INR, IgG, ANA, anti-smooth-muscle or anti-LKM antibodies and liver biopsy. Emergency: acute liver failure with encephalopathy and coagulopathy. |
| Coeliac disease | HLA-associated T-cell response to gluten with anti-tTG and anti-endomysial antibodies. | Diarrhoea, malabsorption, anaemia, weight loss, dermatitis herpetiformis and osteoporosis. | IgA anti-tTG plus total IgA; biopsy when indicated. Do not remove gluten before testing without specialist advice. Assess dehydration, severe electrolyte disturbance and nutritional deficiency. |
| Primary adrenal autoimmune disease (Addison disease) | Immune destruction of adrenal cortex; 21-hydroxylase antibodies are common. | Weight loss, postural symptoms, hyperpigmentation, hyponatraemia, hyperkalaemia and hypoglycaemia. | Morning cortisol, ACTH, electrolytes and stimulation testing. Emergency: adrenal crisis with shock, vomiting, abdominal pain, hypoglycaemia or altered mental status. |
| Systemic vasculitis | Autoantibodies, immune complexes or T cells inflame vessel walls. | Fever, weight loss, purpura, neuropathy, renal disease, pulmonary haemorrhage or ischaemic organ injury. | Urinalysis, creatinine, CBC, ESR/CRP, complement, ANCA, hepatitis/HIV tests and biopsy of affected tissue. Emergency: pulmonary–renal syndrome, haemoptysis, rapidly progressive glomerulonephritis or mesenteric ischaemia. |
| Antiphospholipid syndrome (APS) | Antibodies to phospholipid-binding proteins promote thrombosis and pregnancy morbidity. | Venous/arterial thrombosis, recurrent pregnancy loss, thrombocytopenia and livedo reticularis. | Lupus anticoagulant, anticardiolipin and anti-beta-2-glycoprotein I, confirmed persistently. Emergency: stroke, pulmonary embolism, limb ischaemia or catastrophic APS with multiorgan thrombosis. |
7. Clinical presentation: patterns that should trigger consideration
- Constitutional: unexplained fever, fatigue, night sweats, weight change or malaise.
- Inflammatory musculoskeletal: prolonged morning stiffness, swollen joints, enthesitis or recurrent sterile synovitis.
- Skin and mucosa: photosensitive rash, purpura, livedo, ulcers, alopecia, vitiligo or blistering.
- Renal: haematuria, proteinuria, cellular casts, hypertension or rising creatinine.
- Haematologic: unexplained haemolysis, leukopenia, thrombocytopenia or pancytopenia.
- Endocrine: new diabetes, thyroid dysfunction or adrenal insufficiency combined with other autoimmune disease.
- Neurologic: fluctuating weakness, optic neuritis, transverse myelitis, peripheral neuropathy or encephalopathy.
- Vascular/pulmonary: thrombosis, haemoptysis, pulmonary hypertension or unexplained alveolar haemorrhage.
8. Diagnostic approach
8.1 Start with the syndrome, not the antibody
- Define the dominant organ syndrome and its time course: acute, relapsing, progressive or multisystem.
- Ask about family history, infections, pregnancy, medications, smoking, ultraviolet exposure, occupational triggers and prior autoimmune disease.
- Examine the skin, joints, mucosa, lymph nodes, thyroid, nervous system, renal volume status and signs of vasculitis.
- Exclude common mimics: infection, malignancy, endocrine disease, drug toxicity, nutritional deficiency and primary organ disease.
8.2 Baseline investigations
| Test | What it contributes | Important limitation |
|---|---|---|
| CBC and blood film | Anaemia, haemolysis pattern, leukopenia, eosinophilia and thrombocytopenia. | Abnormalities are not specific for autoimmunity. |
| ESR and CRP | Inflammatory burden and treatment response. | CRP may be normal in some lupus flares; both rise in infection. |
| Renal profile and urinalysis | Creatinine, electrolytes, protein, blood and casts identify renal involvement. | Urinalysis is essential even without urinary symptoms. |
| Liver profile and albumin/INR | Hepatic injury, synthetic failure and protein loss. | Interpret with drug, viral and metabolic causes. |
| Complement C3/C4 | Consumption supports immune-complex activity, especially SLE. | Normal levels do not exclude disease; low complement may be inherited or hepatic. |
| ANA | Sensitive screening test for connective-tissue disease. | Low titres occur in healthy people, infection and drug exposure; ANA alone is not SLE. |
| Specific autoantibodies | Anti-dsDNA/Sm, ENA, anti-CCP, ANCA, thyroid, tissue-transglutaminase, AChR and organ-specific antibodies refine probability. | Use a pre-test clinical probability; false positives and false negatives occur. |
| Imaging/biopsy | Ultrasound, radiography, MRI, echocardiography or tissue biopsy demonstrate damage and sometimes establish the diagnosis. | Biopsy site and timing matter; involve the relevant specialist. |
8.3 Interpreting autoantibodies safely
- A positive result is evidence of immune recognition, not proof of symptomatic disease.
- Pre-test probability changes the positive predictive value: indiscriminate antibody panels generate incidental positives.
- Titre, pattern, persistence and antigen specificity matter, but clinical findings remain decisive.
- Repeat testing is useful when the result is unexpected, discordant or required by classification criteria; repeated testing of stable known antibodies rarely adds value.
- Never delay treatment of a life-threatening syndrome while waiting for confirmatory autoantibodies or biopsy.
9. Management principles
Treatment is disease-specific and should be led by the appropriate specialist. The broad goals are to remove or control triggers, suppress destructive immunity, replace deficient hormones, prevent irreversible organ damage and reduce treatment-related infection and toxicity.
| Strategy | Examples | Safety principles |
|---|---|---|
| Trigger and risk reduction | Stop an offending drug, smoking cessation, sun protection in lupus, infection treatment, nutritional support. | Do not stop essential medicines abruptly without a safe alternative. |
| Anti-inflammatory therapy | NSAIDs for selected musculoskeletal symptoms; corticosteroids for flares or organ-threatening disease. | Assess renal, gastrointestinal, glucose, blood-pressure and infection risks; taper steroids according to disease and specialist plan. |
| Conventional immunosuppression | Methotrexate, azathioprine, mycophenolate, cyclophosphamide, ciclosporin or tacrolimus, depending on disease. | Baseline CBC, renal/liver tests, pregnancy review, vaccination and infection screening are essential. |
| Targeted biologics/small molecules | Anti-TNF, anti-IL-6, anti-CD20, CTLA-4-Ig and other pathway-specific agents. | Screen for tuberculosis/hepatitis where relevant; teach patients to seek care for fever or infection. |
| Immune removal or replacement | IVIG, plasma exchange, immunoadsorption and selected cellular therapies. | Used for defined severe indications; monitor thrombosis, fluid shifts, renal effects and infection. |
| Organ replacement | Insulin, thyroid hormone, adrenal steroid replacement, transfusion or renal replacement therapy. | Education about stress dosing, sick-day rules, adherence and emergency identification saves lives. |
| Prevention and rehabilitation | Vaccination, bone protection, cardiovascular risk control, physiotherapy and psychosocial support. | Live vaccines may be unsafe during significant immunosuppression; individualise timing. |
10. Emergency recognition and first priorities
Immediate ABCDE assessment: Autoimmune disease does not protect against ordinary emergencies. Treat airway, breathing, circulation, disability, exposure, glucose, temperature and sepsis risk while clarifying the immune diagnosis.
| Emergency pattern | Red flags | Immediate priorities |
|---|---|---|
| Adrenal crisis | Shock, vomiting, abdominal pain, hypoglycaemia, hyponatraemia/hyperkalaemia, confusion. | Urgent resuscitation, intravenous stress-dose steroid and isotonic fluid/glucose according to local protocol; take cortisol/ACTH before treatment only if this does not delay life-saving care. |
| Thyroid storm | Fever, delirium, severe tachycardia/atrial fibrillation, heart failure, diarrhoea or vomiting. | Resuscitation, cooling, beta-blockade when safe, antithyroid therapy and specialist critical care. |
| Myxoedema coma | Hypothermia, bradycardia, hypotension, hypoventilation, altered mental status and hyponatraemia. | Airway/ventilation support, cautious warming, thyroid hormone and empiric corticosteroid with endocrine input. |
| Myasthenic crisis | Rapidly worsening dysphagia, weak cough, orthopnoea, falling vital capacity or hypercapnia. | Early airway planning, respiratory monitoring, avoid drugs that worsen neuromuscular transmission and involve neurology/ICU. |
| Pulmonary–renal vasculitis | Haemoptysis, hypoxia, falling haemoglobin, haematuria, casts and rapidly rising creatinine. | Oxygen/ventilation, urgent nephrology/rheumatology, infection exclusion and tissue-directed immunosuppression when indicated. |
| Catastrophic APS or major thrombosis | Multiorgan ischaemia, stroke, PE, limb pain, livedo and thrombocytopenia. | Stabilise, image urgently, anticoagulate when appropriate and involve haematology/critical care. |
| Severe autoimmune cytopenia | Symptomatic anaemia, bleeding, haemolysis, shock or neurological signs. | Type and cross-match, treat bleeding/haemolysis, urgent haematology review; avoid assuming every thrombocytopenia is ITP. |
| Immunosuppressed sepsis | Subtle fever or hypothermia, hypotension, confusion, focal infection or rapidly progressive deterioration. | Early cultures, broad empiric antimicrobials and source control; do not attribute fever to autoimmune flare until infection is assessed. |
11. Short clinical cases
Case 1: lupus nephritis
A young adult with photosensitive rash and arthralgia develops hypertension, oedema, haematuria and proteinuria. Think immune-complex glomerulonephritis. Order urinalysis with microscopy, protein quantification, creatinine, CBC, ANA, anti-dsDNA and complement; urgent nephrology assessment and renal biopsy may guide therapy. A positive ANA without renal findings would not establish lupus nephritis.
Case 2: fatigable weakness
A patient has diplopia late in the day, nasal speech and difficulty swallowing but normal sensation. Myasthenia gravis is likely. Measure respiratory function serially, assess bulbar protection, search for precipitating infection or medication, and involve neurology early. A normal pulse oximeter does not exclude impending ventilatory failure.
Case 3: shock in known Addison disease
Vomiting, abdominal pain, confusion, low blood pressure and hypoglycaemia in a patient who missed steroid replacement indicate adrenal crisis until proven otherwise. Resuscitation and urgent steroid replacement take priority over waiting for antibody testing.
12. Exam-focused comparison
| Question | Best answer |
|---|---|
| Why can autoreactive lymphocytes exist in healthy people? | Central deletion is incomplete; peripheral anergy, deletion, ignorance and Treg suppression normally keep them harmless. |
| Which mechanism stimulates a receptor? | Pathogenic agonist autoantibody, as the TSH-receptor antibody in Graves disease. |
| Which mechanism blocks neuromuscular transmission? | Antibodies to the acetylcholine receptor or MuSK in myasthenia gravis. |
| What does low complement suggest? | Consumption, often immune-complex activity; it supports but does not independently diagnose SLE. |
| Does ANA diagnose lupus? | No. ANA is sensitive but not specific; interpret with clinical features and disease-specific tests. |
| Why are infections dangerous during immunosuppression? | Immunosuppressive drugs blunt fever and inflammatory signs while increasing pathogen risk; infection can mimic a flare. |
13. Quick self-test
- Differentiate central from peripheral tolerance.
- Explain molecular mimicry, bystander activation and epitope spreading.
- Match SLE, Graves disease, myasthenia gravis and type 1 diabetes with their dominant immune mechanism.
- Why is a disease-specific syndrome required before diagnosing autoimmune disease from a positive antibody?
- List five autoimmune emergencies and their first clinical priorities.
Answers
- Central tolerance acts during lymphocyte development in thymus/bone marrow; peripheral tolerance controls escaped clones in tissues and lymph nodes.
- Molecular mimicry is cross-reactivity with a microbial antigen; bystander activation is cytokine-driven activation of nearby autoreactive cells; epitope spreading is broadening to additional self-epitopes after tissue damage.
- SLE: immune complexes; Graves: receptor-stimulating antibody; myasthenia: receptor-blocking antibody; type 1 diabetes: T-cell beta-cell destruction.
- Autoantibodies may be transient, incidental or markers without pathogenic function; false positives are common when pre-test probability is low.
- Examples: adrenal crisis, thyroid storm, myxoedema coma, myasthenic crisis, pulmonary–renal vasculitis, catastrophic APS, severe autoimmune cytopenia and immunosuppressed sepsis. All require ABCDE stabilisation and disease-specific urgent treatment.
Key take-home points
- Autoimmune disease is loss of tolerance plus tissue injury, not merely a positive autoantibody.
- Central deletion, peripheral anergy, Tregs and inhibitory checkpoints normally protect self.
- Genetic susceptibility and environmental triggers interact; no single factor explains most diseases.
- Antibodies may destroy cells, stimulate or block receptors, or form immune complexes; T cells may directly destroy tissue.
- Always screen for silent renal, haematologic and neurologic involvement in systemic disease.
- In an ill immunosuppressed patient, exclude infection while assessing autoimmune flare.
- Recognise endocrine crisis, respiratory muscle failure, pulmonary–renal syndrome, thrombosis and severe cytopenia early.
