Question
Serum sickness
Answer
Serum sickness is the prototype example of Type III (immune-complex-mediated) hypersensitivity, occurring when the immune system mounts an antibody response against a foreign protein/serum administered therapeutically, forming circulating immune complexes that deposit in tissues and trigger inflammation.
Classical cause: historically described following administration of heterologous (animal-derived) antiserum — e.g., horse-derived antitoxin/antivenom (diphtheria antitoxin, tetanus antitoxin, snake antivenom) — where the recipient’s immune system recognizes the foreign (non-human) serum proteins as antigens; modern equivalents can occur with certain drugs (e.g., some monoclonal antibody therapeutics) acting as haptens or foreign proteins.
Pathogenesis: 7–10 days after administration of the foreign protein, the host mounts an antibody response against it; the resulting antigen-antibody (immune) complexes form in the circulation in moderate antigen excess (the size/solubility of complexes formed under these conditions favours tissue deposition rather than efficient phagocytic clearance), depositing in small blood vessels, joints, and the kidneys, where they activate complement (generating anaphylatoxins C3a/C5a) and recruit neutrophils, causing local vasculitis and tissue inflammation/damage.
Clinical features: fever, urticarial or morbilliform skin rash, lymphadenopathy, arthralgia/arthritis, and sometimes glomerulonephritis — typically appearing about a week after exposure to the foreign serum/drug, and generally self-limiting, resolving as the immune complexes are cleared once antibody production wanes or the antigen is eliminated.
Management: largely supportive (antihistamines, NSAIDs for symptomatic relief); discontinuation of the offending agent if still being administered; corticosteroids for severe cases.
Broader significance: serum sickness is the classical model illustrating Type III hypersensitivity, which is also the mechanism underlying other immune-complex diseases such as systemic lupus erythematosus and post-streptococcal glomerulonephritis.