Chapter 8 Serum Sickness Flashcards
What is serum sickness?
A systemic disease caused by the formation of immune complexes, typically deposited in vessel walls of tissues/organs.
What type of hypersensitivity reaction is serum sickness?
Hypersensitivity type III reaction.
Who elucidated serum sickness and in what year?
Clemens von Pirquet in 1906.
What are the common tissues/organs where immune complexes deposit in serum sickness?
Glomeruli, synovial membrane, lymph nodes, and skin.
What are the common clinical signs of serum sickness in horses?
Fever, skin eruptions of purpura, lymphadenopathy, arthralgia, polysynovitis, albuminuria/proteinuria, and acute renal failure.
What is a key historical observation about antibodies in serum sickness?
Antibodies, which should protect against disease, are also responsible for disease.
Is there a breed and sex predisposition to serum sickness in horses?
No, there is no known breed and sex predisposition.
What is the main immunoglobulin involved in serum sickness?
IgG and IgM.
What are the main factors that determine immune complex formation in serum sickness?
Quality of antigens and immune-complexes, condition of circulation and vascular beds, antigen-antibody concentration.
What happens in the initial phase of antigen-antibody complex formation in serum sickness?
Initially, there is an excess of antigen, leading to small immune complexes that do not deposit or activate complement.
What role do liver sinusoidal endothelial cells play in serum sickness?
They clear antigen-antibody complexes from the circulation via Fc-gamma receptor II.
How are large antigen-antibody immune complexes removed from the circulation?
By mononuclear phagocyte system (MPS), particularly macrophages in the red pulp of the spleen.
What is the consequence of medium-size immune complex formation in serum sickness?
They deposit along the endothelial surface of certain vascular beds, activating complement.
What happens when complement is activated by medium-size immune complexes?
It results in an inflammatory cascade with endothelial cell swelling, fibrin deposition, increased vascular permeability, and chemoattraction of neutrophils.
What is necrotizing vasculitis?
A condition where neutrophil activation leads to destruction of the basement membrane and surrounding tissues.
What are common etiologic associations of serum sickness in humans?
Use of xenogeneic serum to treat toxin-mediated and infectious diseases, administration of antivenoms, anti-toxins, and prevention of allograft rejection.
What are some examples of exogenous immunogenic proteins that can cause serum sickness in horses?
Equine polyclonal antibody products, snake antivenins, tetanus, botulinum, Clostrium difficile antitoxins, hyperimmune plasma products, plasma and serum transfusions.
What are the common diagnostic methods for confirming immune complex-mediated diseases in humans?
Detection of circulating immune-complexes using radioimmunoassay, enzyme-linked immunosorbent assay, solid phase anti-C3 assay, measurement of C3 and C4 concentrations.
What are the histopathologic findings in immune complex-mediated diseases?
Presence of electron-dense deposits in the endothelial basement membrane, immune-complexes, complement and fibrin deposition, necrotizing vasculitis.
What is the main focus of serum sickness management?
Removal of the offending antigen, decreasing inflammation, and decreasing antibody production.
What is the role of glucocorticoids in treating serum sickness?
They decrease inflammation to halt tissue injury.
What is a key supportive therapy for serum sickness?
Supportive therapy to control clinical signs, particularly renal damage.
What is the best prevention strategy for serum sickness?
Documentation of the offending antigen and future avoidance of administration.
What are immune complexes composed of in serum sickness?
Antigen and antibody bound together.
How are immune complexes typically cleared from circulation?
By the liver sinusoidal endothelial cells and mononuclear phagocyte system.
What happens when there is an excess of antigen in serum sickness?
Small immune complexes form that do not deposit or activate complement.
What is the effect of complement activation in serum sickness?
It triggers an inflammatory cascade that includes endothelial cell swelling, fibrin deposition, and neutrophil chemoattraction.
What leads to necrotizing vasculitis in serum sickness?
Activated neutrophils release proteolytic enzymes and oxidative agents, causing tissue destruction.
What are the key components involved in the inflammatory cascade of serum sickness?
Complement components such as C3a and C5a, and neutrophils.
What is the role of complement component C1q in serum sickness?
It initiates the cascade of complement activation.
What is the significance of platelet aggregation in serum sickness?
It occurs at the site of immune complex deposition, contributing to inflammation and tissue damage.
What is the historical context of serum sickness in humans?
It was common due to the use of xenogeneic serum for toxin-mediated and infectious diseases.
What modern treatments have minimized the immunogenicity of antivenoms and anti-toxins?
Use of Fab fragments of immunoglobulins instead of whole immunoglobulins.
What are the most common modern causes of serum sickness in humans?
Reactions to drugs such as penicillin, cephalosporin, and sulfonamides.
What is the importance of detecting C3 and C4 concentrations in diagnosing immune complex diseases?
Low values indicate consumption of complement components and suggest immune complex disease.
How is histopathologic evaluation used in diagnosing serum sickness in horses?
By identifying electron-dense deposits, immune-complexes, and signs of necrotizing vasculitis in tissue samples.
What are the primary goals of treating serum sickness?
Removing the offending antigen, decreasing inflammation, and controlling antibody production.
What is the recommended dose of dexamethasone for treating serum sickness in horses?
0.05–0.2 mg/kg IV or PO every 12 or 24 hours.
What are the potential side effects of long-term glucocorticoid therapy in horses?
Polyuria, polydipsia, laminitis, gastrointestinal ulceration, hepatopathy, and secondary infections.
How should glucocorticoid therapy be tapered in horses with serum sickness?
Decrease the dose by 10–20% every 24 to 48 hours.
What is the role of prednisolone in treating serum sickness?
It can be used as an alternative to dexamethasone for long-term therapy.
What supportive therapies are crucial for managing renal damage in serum sickness?
Maintaining hydration, electrolyte balance, and monitoring renal function.
What is the significance of documenting the offending antigen in serum sickness?
To prevent future occurrences by avoiding re-administration of the antigen.
What are common clinical signs of serum sickness in human patients?
Fever, rash, arthralgia, lymphadenopathy, and proteinuria.
What is the pathophysiology of serum sickness?
Formation and deposition of antigen-antibody immune complexes leading to complement activation and inflammation.
Why is it important to monitor horses receiving plasma transfusions for serum sickness?
To detect and manage any adverse reactions promptly.
What laboratory findings indicate glomerulonephritis in serum sickness?
Albuminuria/proteinuria and azotemia.
What is the role of Fc-gamma receptor II in serum sickness?
It binds the antibody heavy chain constant region, aiding in the clearance of immune complexes.
