Type III hypersensitivity reactions Notes

NOTES NOTES TYPE III HYPERSENSITIVITY REACTIONS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Hypersensitivity reaction mediated by immune complexes ▫ Antibodies (IgG) binding to soluble antigens → antigens not bound to cell surfaces ▪ Formation of immune complexes → complement activation (esp. C3a, C4a, C5a) ▫ Anaphylatoxins → increase vascular permeability → edema ▫ Chemokins → recruitment of phagocytes, neutrophils, mast cells → degranulation of lysosomal enzymes, reactive oxygen species → inflammation, tissue necrosis (fibrinoid necrosis) ▫ May also elicit systemic inflammation ▪ Common sites of immune complex accumulation ▫ Blood vessel walls → vasculitis ▫ Kidneys → glomerulonephritis ▫ Joints → arthritis ▪ If triggered by single exposure to antigen, resolves after catabolism of immune complexes → acute serum sickness ▪ If repeated/prolonged exposure → chronic serum sickness ▫ Systemic erythematosus lupus (SLE), polyarteritis nodosa, poststreptococcal glomerulonephritis, reactive arthritis Common Type III hypersensitivity reactions ▪ Henoch–Schönlein purpura ▪ Hypersensitivity vasculitis ▪ Reactive arthritis ▪ Farmer’s lung ▪ Post-streptococcal glomerulonephritis ▪ Serum sickness ▪ Arthus reaction 226 OSMOSIS.ORG ▪ Systemic lupus erythematosus ▪ Subacute bacterial endocarditis ▪ Rheumatoid arthritis SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ ▪ Fever, fatigue, weight loss Skin: rash, urticaria Kidney: proteinuria Joints: arthralgias Mucosa: ulcers Serosa: pleuritis, pericarditis DIAGNOSIS LAB RESULTS ▪ Antibody testing ▪ Histopathology to observe fibrinoid necrosis ▫ Necrosis of vessel wall with infiltration of neutrophils, eosinophils, complement, plasma proteins; staining pattern reminiscent of fibrin Figure 38.1 A vessel displaying fibrinoid necrosis in Churg–Strauss syndrome, which is a type III hypersensitivity reaction.

Chapter 38 Type III Hypersensitivity Reactions ▪ Immunofluorescence microscopy to visualize immune complexes ▪ Complement levels in blood ▫ Track disease progression TREATMENT MEDICATIONS ▪ SLE ▫ Administration of anti-inflammatory, corticosteroids, cytotoxic medications to decrease inflammatory activity SERUM SICKNESS osms.it/serum-sickness PATHOLOGY & CAUSES ▪ Systemic Type III hypersensitivity reaction against foreign antibodies in serum ▪ Exposure to foreign serum → triggers B cells to become plasma cells, produce IgG antibodies against foreign antibodies → immune complexes formed, deposited in basement membrane → complement activation, immune cells recruitment → lysosomal enzymes, reactive oxygen species, cytokines produced → local, systemic inflammatory response ▪ Initial exposure ▫ 4–10 days to develop reaction ▪ Second exposure ▫ Faster, more potent reaction ▪ Resolves after withdrawal of culprit agent CAUSES ▪ Medications (e.g. cefaclor, anti-seizure medications); infections (e.g., hepatitis B); vaccines SIGNS & SYMPTOMS ▪ Allergy-like response ▪ Present within 1–2 weeks if initial exposure, 12–36 hours if second exposure ▫ General malaise, erythema, itching, arthralgia ▪ Fever > 38.5°C/101.3°F, rash, lymphadenopathy, polyarthritis, proteinuria DIAGNOSIS LAB RESULTS ▪ Complete blood count (CBC) ▫ Neutropenia, increase in lymphocytes ▪ Elevation of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) ▪ Urinalysis ▫ Mild proteinuria (50%) OTHER DIAGNOSTICS ▪ Clinical presentation; suspected when allergy-like symptoms present after administration of potential responsible agent (e.g. antivenom serum after bitten by snake) ▪ Testing to exclude infections (e.g. hepatitis B) TREATMENT MEDICATIONS ▪ Relieve symptoms with antihistamines, analgesics ▪ Glucocorticoids for individuals with severe clinical features (e.g. very high fever, severe arthritis, extensive rashes) OTHER INTERVENTIONS ▪ Discontinue, avoid offending agent OSMOSIS.ORG 227