--- module: 058-01 language: en chapter: 58 title: "Allergy, Anaphylaxis, Immunodeficiency, Transplantation, and Immune Therapy" module_title: "Foundations" source_sha256: 0a47403e91ab83dccf1a380458c792710f9135e79cd53357bb5f775f7694cab0 --- # Allergy, immunodeficiency, transplantation, immune therapy ## Orientation ### Eliminate threats without injuring self or harmless antigens #### Failure: allergy, autoimmunity, immunodeficiency ### Immune-modifying treatments carry toxicities ### Find the defective pathway, prevent complications first ## Hypersensitivity mechanisms ### Immediate: allergen cross-links bound immunoglobulin E #### Histamine, tryptase, leukotrienes, prostaglandins #### Vasodilation, leak, smooth-muscle contraction ##### Urticaria, angioedema, bronchospasm, shock ### Sensitisation is not always clinical allergy ### Cytotoxic antibodies: cells, matrix, complement, receptors ### Immune complexes inflame vessels, glomeruli, joints, skin ### Delayed: T-cell mediated, hours to days #### Contact dermatitis, many drug eruptions ## Allergy history and testing ### Record trigger, route, dose, timing, prior tolerance ### Cofactors amplify: exercise, alcohol, infection, asthma ### Separate allergy from intolerance, toxicity, vasovagal #### Inaccurate label denies first-line therapy ### Specific immunoglobulin E tests show sensitisation #### Alter probability, not severity #### Broad food panels create false positives ### Supervised challenge often the diagnostic standard ## Anaphylaxis ### Rapid systemic threat to airway, breathing, circulation #### Skin features sometimes absent #### Treat without laboratory confirmation ### Intramuscular adrenaline into anterolateral thigh ### Supine, legs elevated; standing risks collapse #### Lateral in pregnancy, recovery if unconscious ### Oxygen, access, rapid isotonic crystalloid ### Adjuncts do not replace adrenaline #### Antihistamines relieve skin symptoms only #### Corticosteroids not immediately life-saving ### Refractory: monitored intravenous adrenaline infusion #### Beta blockade may blunt response, consider glucagon ### Biphasic recurrence guides observation ### Discharge: referral, autoinjector, action plan ## Urticaria, angioedema, and allergic disease ### Wheals migrate and resolve within a day ### Chronic spontaneous urticaria often autoimmune #### Second-generation antihistamines first-line ### Histamine angioedema: itch, wheals, allergy therapy ### Bradykinin angioedema #### From converting-enzyme inhibitors or hereditary defects #### No urticaria, poor response to adrenaline #### Protect airway, cause-specific inhibitors ### Atopic diseases share barrier and type-two pathways ### Oral immunotherapy raises threshold, not free intake ## Primary immunodeficiency ### Antibody, T-cell, phagocyte, complement, regulation ### Warning patterns beyond common infection #### Severe, recurrent, opportunistic, unusual sites #### Poor growth, abscesses, delayed cord separation ### Tests by phenotype; age, drugs, illness alter results ### Immunoglobulin replacement for antibody failure ### Avoid live vaccines in cellular defects ### Stem-cell transplant or gene therapy if severe ## Secondary immunodeficiency ### Pattern predicts organisms #### Neutropenia: bacteria and fungi #### T-cell impairment: viral, mycobacterial, protozoal #### Antibody failure: encapsulated bacteria ### Human immunodeficiency virus depletes CD4 T cells #### Prompt combination therapy suppresses virus ### Asplenia: fulminant encapsulated infection ## Immune-suppressive and biologic therapy ### Glucocorticoids broadly suppress inflammation #### Metabolic, bone, eye, mood toxicity #### Adrenal suppression: avoid abrupt withdrawal ### Toxicity follows mechanism #### Tumour-necrosis-factor blockade reactivates tuberculosis #### Complement blockade raises meningococcal risk #### Checkpoint inhibitors inflame almost any organ ### Screen and give non-live vaccines beforehand ### Fever muted, infection with normal leukocytes ### Febrile neutropenia: immediate antipseudomonal cover ## Transplantation ### Rejection by timing #### Hyperacute: minutes to hours #### Acute: days to months #### Chronic: vascular and interstitial injury ### Other graft insults often need biopsy ### Calcineurin inhibitor, antiproliferative, corticosteroid #### Calcineurin toxicity needs level monitoring ### Infection: early surgical, later opportunistic ### Stem-cell conditioning damages marrow and mucosa #### Graft-versus-host disease, graft-versus-tumour benefit