Biologic Response Modifiers Flashcards
What is the normal role of cytokines, such as TNF-alpha?
Modulate the inflammatory process
Produced by monocytes, macrophages and T cells in response to pathogens.
This is particularly important with T cell immune response involved in destructing cells harbouring intracellular pathogens, formation of granulomas and ensuring cell mediated process. Ensures that the pathogens in cells are killed or remain dormant (ie no propagation)
What do BRM do?
They are either antibodies to pro inflammatory cytokines or proteins that target the cytokine receptors.
➡️ net effect is an inhibition of pro inflammatory cytokines
How do BMR increase the risk of infection?
Affect T cell immune response -involved in destructing cells harbouring intracellular pathogens, formation of granulomas and ensuring cell mediated process.
IE keeps pathogens inside cells dormant or kills them.
➡️ BMR blunt and impair this response.
➡️ get reactivation of latent infections
➡️ have inadequate response to pathogens requiring cell-mediated immunity
What are the infections that are at an increased risk of BMR (in general)?
Increased risk of reactivating latent TB
Increased fungal infection
Increase in non-TB mycobacterium
Increased intracellular pathogens, listeria
Reactivations os strongyloides
+/- increased reactivation of VZV, HSV, Hep B (adult literature)
Is there an increased risk of streptococcus pneumonia?
No, there is no increased risk of common pathogens
Is there an increased risk of post-operative infections?
No.
What fungal infections more common in these kids?
histoplasma
blastomyces
coccidoides
strongyloides
What is the role of BMC and EBV?
There are case reports of reactivation with the development of lymphoma , although the risk of this is unclear.
Are there any factors that can predict the risk of infections with BMR?
Risk of infection is proportional to the length of BMR therapy.
Does the risk of infection stop as soon as BMR is finished?
No. The increased risk of infection may persist for weeks and possibly months after discontinuing the drug because the long half-life (3-24 days).
What are the risks to the foetus for mom who is on BMR?
It is unclear the effects of BRM on the developing fetal immune system. There is little to no evidence thus far of increased risk of infections in the children of women who received BRM during pregnancy or lactation.
What needs to be done prior to starting BRM?
Latent TB risk: TST (>5mm) + CXR. You can consider interferon-gamma given the increased sensitivity in children who are immunosuppression.
Document vaccination status
Counsel family re their vaccination status
Consider serologies
Counsel re safety
What do you do if the risk of latent TB is high but the testing is inconclusive or negative?
Treat empirically with isoniazid x 9 months and start BRM 1 months after finishing this.
What serologies should you consider to send?
Histoplasma, toxoplasma and other intracellular pathogens
Hepatitis B, EBV, VZV
What counselling should you provide re safety and exposure?
Food safety - avoid undercooked meats or delicatessen meats, raw eggs or unpasturized milk products
Maintain dental hygiene (IE risk)
Avoid exposure to heavy concentrations of garden soil, pets and other animals (cat litter Toxo, kittens Bartonella, reptiles salmonella)
Avoid high risk activities: excavation sites or spelunking,
Avoid travel to areas endemic to pathogenic fungi - southwestern USA and TB areas
