ID - Transplant Flashcards
Immune defects associated with these malignancy (and their therapies)
- AML, MDS
- Aplastic anaemia
- CLL and MM
- Lymphoma
- AML, MDS
– Qualitative/quantitative neutropenia - Aplastic anaemia
– Severe, prolonged neutropenia - CLL and MM
– Hypogammaglobulinemia - Lymphoma
– Functional asplenia
Consequence of chemo impacting neutrophils?
Cytotoxic agents
–> bacterial, fungal infection
Cancer drugs -> T cells impact ?
Consequences?
Purine analogues – Fludarabine, cladribine
Antithymoctye globulin
CD4+ T cell dysfunction:
* Herpes viruses
* Hep B reactivation
* PJP
What does s. pneumonia look like in microscopy
diplococci
Classic presentation of S Viridans in HIV patient
fevers, rash and stomatitis (think where it lives)
Associated with Viridans Group Strep (VGS) shock syndrome
– about 24-48 hr in 1/3 of cases
– Can have ARDS in ¼ of cases (like TSS)
- Endocarditis rare
RFs S Viridans in HIV
neutropenia, mucositis, high-dose cytarabine– use of Cipro (Cipro barely gets above MIC to be effective Gram Positive abx)
Neutropenic Enterocolitis (Typhlitis)
- Necrotizing inflammation with transmural infection of damaged bowel wall
- Mixed infection – GN, GP, anaerobic
- Can be accompanied by bacteremia
- Medical Management (less often surgical)
Mgmt Neutropenic Enterocolitis
Medical Management (less often surgical)
Skin lesion caused by pseudomonas aeriginosa?
erythema gangrenosum
Timing of fungal infections in neutropaenia
yeasts early (candida), mould later (aspergillus)
Difference between yeasts and moulds?
(and examples of each)
moulds: multicellular hyphae
- e.g. aspergillus, fusarium
Yeasts: single celled forms that reproduce by budding
- e.g. candida, cryptococcus,
Dimorphic exist also (Yeast in blood, but grow as mould in room temperatures)
- e.g. histoplasma, penicillium
How to anti-fungals usually work?
usually act on cell wall,
- exception if 5-FC which is converted to 5-FU and inhibits DNA synthesis (pyramidine analogue)
Anti-fungal for prophylaxis in high/ intermediate risk haem amlignancy/ HSCT?
Posaconazole in high risk
Fluconazole in Intermediate risk
What is the most rapidly cidal agent for Candida?
Caspofungin (the penicillin of anti-fungals)
Anti-fungal agent ineffective in cryptococcus?
Caspofungin
Cryptococcus (Zygomycetes) lack significant beta-glucan in their cell walls
Anti-fungal agent that covers everything?
posaconazole
Anti-fungal agent ineffective in moulds?
fluconazole (also flucytosine)
Important non-medical management candidaemia
MUST REMOVE IV LINES, dilated Eye exam
What is the most rapidly cidal agent for Aspergillus?
Voriconazole
Agents for cryptococcus
Flucytosine with Ampho
Hepatosplenic Candidiasis Syndrome
- Inflammatory response to fungi invaded by portal vasculature
- Presents after engraftment (Return of ANC)
- Abdominal pain, increased LFTs, prolonged fever
- Differential – bacteria, lymphoma, fungus
- C albicans most common
Lots of little abscesses in spleen/ liver after white cells returned and body sees all the things again
When to think invasive molds
- With profound neutropenia < 100 cells/mm 3 and >10-15 days)
- Most common AML – 20 x > than seen with lymphoma/
- Evidence of Sinusitis
or - Radiographic evidence of Evidence of Pulmonary disease
- If patient has received Fluconazole prophylaxis before.
Diagnosis of invasive moulds
- We rarely make diagnosis now by culture – usually inferred through molecular tests AND CT scan findings:
- (1–3)-beta-D-glucan test – Candida/Aspergillus/Fusarium (NOT Crypto/Zygomycetes)
– 60-90% sensitive - Galactomannan assay – only picks up aspergillus/penicillium –may have a role in BAL fluid in high risk patients – better sensitivity then culture (80 vs 50%)
- they both have a poor NPV
- PCR of BAL + GM diagnosis of proven/probable IPA were 90.2% and 96.4%.
Invasive aspergillosis treatment
– Voriconazole – PREFERRED
* Follow levels (>2 mg/L favourable response)
* Response is decrease Aspergillus galactomannan level
– No role for combination anti-fungals
– Reduce immunosuppression if possible
– Treatment duration
N Engl J Med, Vol. 347, No. 6
- 6-12 weeks
- Until immune recovery
- Until resolution of disease
– Secondary prophylaxis for further intense immunosuppression
AE/ Issues with amphotericin
- Renal failure - ~40-80%
- RTA1 – acidosis, Hypokalaemia
- Intense rigors with infusion
- Cost – newer lipid formulation to combat above
– do work – however cost $$$
- No Oral options
Donor recipient stauts -> highest CMV re-activation risk (in HSCT)
Highest in BMT D-/R+ (CMV in their body )
– DIFFERENT THAN SOT!!! (D+/R-)
CMV Infection versus CMV disease
CMV Infection = illness, versus CMV disease = seropositivity
CMV on lung biopsy
gold std “Owls’ eyes” in lung bx, now BAL DNA
CMV on colitis histology
(inclusion bodies) PCR of tissue
Manifestiations of GVHD
Acute (early ) w/I 100 day
* Fever/rash, GI tract manifestation (hepatitis)
(Herpes viruses/Hepatitis B)
Chronic – late
* Skin – lichen planus, scleroderma
* Hepatic – cholestasis
* Keratoconjunctivitis
* GI
* Pulmonary syndromes
What is this on modified acid stain?
Nocardia
branching acid fast bacilli indicates nocardiosis,
Complications of nocardia in immunocompromised patients
branching acid fast bacilli indicates nocardiosis,
Often have concomitant pneumonia (Cavitary)
Treatment Nocardia
Trimethoprim-sulfamethoxazole
CMV prophylaxis in solid organ transplant patients
Valganiciclovir
3-6 months after transplant
PTLD
Post transplant lymphoproliferative disorder
Virus related to PTLD
EBV
Risk factors for PTLD
history of organ transplantation and immunosuppression (mandatory to have)
D +, R – 20%
Receipt of organ rich in lymphoid tissue
Intestine (up to 30%) > lung > Heart> Liver (up to 10%) > Kidney(up to 1%)
Antilymphocytic ab use
Management of PTLD?
Decreasing immunosuppression + RITUXIMAB + Chemo
Timing of transplant and PTLD?
Biphasic pattern
- 20% cases 1 styr post txplt
- Second peak 7-10 years post txplt
Test for BK virus renal failure?
BK inclusion in renal tubular epithelium on renal biopsy.
BKV DNA is detected in the urine, followed by detection in the plasma (sensitive but not specific)
Remember rejection could present same way – thus RENAL BX GOLD STD for diagnosis
Treatment for BK virus renal failure
Decrease immunosuppression most effective
No specific anti-viral treatment has consistently worked
PML
Progressive Multifocal Leukoencephalopathy\
Rare demyelinating disease of the central nervous system that
results from reactivation of latent JC polyoma virus
Agents that -> PML
Natalizumab (α4-integrin)
TNF-alpha inhibitors
Rituximab
Presentation of PML
Insidious onset and steady progression of focal symptoms that include behavioural, speech, cognitive, motor (eg, head tremor), and visual impairment
Prescreening transplant
Strongyloides stercoralis
a soil transmitted helminth mainly diffused in tropical and subtropical regions
Strongyloides hyperinfection
when immunosuppression -> decrease of ususal immune surveillance,
- triggering an augmentation of the normal life cycle of the parasite and causing massive increases in the reproductive cycle of larvae.
- Larvae proliferate dramatically in the duodenum, migrate through the bowel wall, and then travel through the venous system to the lungs and back to the small bowel
Strongyloides hyperinfection
when immunosuppression -> decrease of usual immune surveillance,
- triggering an augmentation of the normal life cycle of the parasite and causing massive increases in the reproductive cycle of larvae.
- Larvae proliferate dramatically in the duodenum, migrate through the bowel wall, and then travel through the venous system to the lungs and back to the small bowel
- Gram Negative meningitis as worms migrate bowel wall
Treatment for strongyloides?
ivermectin
