Immunosuppression vs. Infection Flashcards
How would you manage this patient with recurrent infection who is on chronic immunosuppression? (initial spiel for any case before the “balancing”)
Acknowledge: “this is a difficult Mx issue - one side you have the risk of significant end-organ damage posed by a chronic condition (or rejection) but on the other side there is a risk of increased mortality from unremitting infection.”
“The most important thing is to Establish the risk associated with each variable in question”
- Infection
- how acute is the problem? - note that chronic deep-seated infections such as osteomyelitis may be unable to be controlled without lessening immunosuppression
- how severe is the problem? - are there markers of end-organ dysfunction?
- can we treat the infection without decreasing the immunosuppression - some infections are exquisitely immunosensitive, such as PML, BK virus
- ImmSx
- how active is the condition - is there an active need for immunosupression
- has it been severe in the past - ie predicting a severe phenotype
“I will always discuss the risk and benefit with the patient”
“I would ensure that modifiable risk factors are addressed”
Non-pharm
- Vaccination - seasonal flu, Pneumovax
- Smoking cessation
- Optmise nutrition
- Avoid high-risk exposures
Pharm
- Prophylactic antimicrobials - if not given already
- Investigate for immunodeficiency: e.g. rule out HIV, autoimmune leukopaenia, hypogammaglobulinemia, consider IVIG if deficiency present
- Ensure patient is not over immunosuppressed: would like to review drug levels
- Ensure no significant drug interaction - e.g. MTX and Bactrim***
So what is your approach in balancing the immunosuppression vs. infection in this particular case once you have dealt with modifiable risk factors?
Assess the risk of acute infection
- How acute & severe is it (is there _end-organ damag_e)
- Wherever possible, I’d prefer to treat the infection without decreasing the immunosuppression (reasonable if acute but not-so-severe infection)
- However, this may not be possible if the infection is chronic deep-seated (e.g. OM), severe or ImmSx associated infections such as BK, PML (exquisitely immunosensitive)
Assess the risk posed by decreasing the ImmSx
- How active/severe is condition - clinically and biochemically
- Is there an active need for immSx? If not active, maybe reasonable to decrease/WH it
- Note that this patient has had (severe vs. mild disease only) previously, so I would be very cautious about decreasing the immSx
- Will consider alternative ImmSx regime
- In any case, will need to carefully monitor for any evidence of active disease
MTX and Bactrim together - thoughts?
They are both inhibitors of folic acid metabolism - hence the risk of BM toxicity is high.
Also Bactrim decreases renal excretion of MTX → potential toxicity
Which micro-organisms are you worried about the most in hyposplenism or asplenic patients? (4)
Overwhelming infection by encapsulated organisms.
- Streptococcus pneumonia (40-60%)
- Neisseria meningitidis
- Haemophilus influenzae
- Malaria
If splenic function is in doubt, what can you check for?
Howell-Jolly bodies in blood film
Which vaccines are recommended for asplenic patients? (4)
- 5 yearly pneumococcal
- 5-yearly conjugated meningococcal ACWY vaccine
- One-off Haemophilus influenza vaccine
- Yearly influenza vaccie
What is the usual duration of prophylactic ABx following splenectomy and when would you recommend life-long prophylaxis? (3)
Amoxicillin 250mg or Cephalosporin or Macrolide.
3 years except
- Have survived overwhelming infection
- Significant immunocompromisation
- Haematological malignancy or GvHD
What are the causes of Hypogammaglobulinaemia? (6)
Decreased production
- Congenital (primary)
- Drugs - immunosuppressives, anti-inflammatories (e.g. steroids), anti-epileptics, Rituximab or B-cell acting drugs
- Malignancy - CLL, lymphoma, myeloma
Increased loss
- Nephrotic syndrome
- Protein-losing enteropathies
- Trauma/burns
Which infections are you particularly worried about in patients with Hypogammaglobulinaemia?
Encapsulated bacteria
Recurrent sino-pulmonary infections → bronchiectasis
Chronic diarrhoea (e.g. Giardia, campylobacter, rota)
Invasive infections - deep seated infections
Longcase patients on chemo or haematological patient with MF or aplastic anaemia - comment/spiel?
“I am aware that these patients are at risk of prolonged neutropaenia which increases the risk of more severe bacterial infection and Fungal infection”
“I would educate patient WRT their response to febrile illness, has a number to call (e.g. onc CNC) and present to ED”
What test would you send off for suspected meningitis/encephalitis in immunocompromised patients?
Cryptococcal Ag + culture
Mycobacterial PCR/culture
Viral PCR - CMV, EBV, VZV, HSV, Enterovirus, JCV
MCS.
What additional test would you send off from the stool if you suspect GI infection in immunocompromised? (3)
Other than stool cultures and viral PCRs, I would send off
- Strongyloides serology + microscopy of faeces
- Cryptosporidium
- Microsporidium
In which patient groups would you consider PJP prophylaxis? other than solid/stem cell transplants or HIV patients? (3)
Steroids >20mg/day + other cause of ImmSx (e.g. cyclophosphamide)
Primary immunodeficiencies
High-dose steroids + TNF inhibitor
Good spiel to say when the dose of immSx are quite high
I note that the patient is on significant dose of ImmSx - I suspect the graft funciton may be less than adequate, which puts them at risk of not only the opportunistic infections but also more severe infection from common community acquired infections”
What is your cut-off for calling CMV syndrome/disease?
Blood CMV DNA PCR copies/mL
In general no widely accepted PCR thresholds that differentiate among latent infection, low-level active infection and CMV disease and clinical judgement must be used when evaluating PCR results
CMV syndrome: mean viral load ~10,000
CMV tissue invasive disease mean viral load ~20,000
Histological examination of biopsied tissue
