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11/7/18 > Neutropenia, SOT, HSCT > Flashcards

Neutropenia, SOT, HSCT Flashcards

1
Q

Intensity of therapeutic immunosuppression

A

Induction therapy - highest

Maintenance therapy - less, +/- GVHD Tx

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2
Q

Lymphocyte-depleting agents increase risk . . .

A

cytomegalovirus (CMV),

polyoma BK virus,

Pneumocystis species,

and other fungi.

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3
Q

EBV–associated posttransplant lymphoproliferative disease (PTLD)

higher risk in patients taking . . .

A

lymphocyte-depleting agents and

in those receiving sirolimus and tacrolimus

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4
Q

Timeline and risk for infection SOT

A

Early Period (<1 Month ): surgical site and other nosocomial infections, IFI, and site specific related to the transplanted organ

Middle Period (1-6 Months ): viruses, opportunistic pathogens, IFI, Tb

Late Period (>6 Months )a: community accuired infections (more severe presentations) + infections associated to middle period

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5
Q

Immune risks for infection BMT timeline . . .

A

– Neutropenia (early)

  • Bacterial infections
  • Fungal infections

– Impaired cellular and humoral immunity (late)

  • Bacterial infections
  • Fungal infections
  • Viral infections
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6
Q

Approach for the boards SOT, BMT, neutropenia

A

– Patient’s age, disease, history impact risks after BMT

– What kind of BMT did the patient have?

– Is the patient early vs. late after BMT?

Type of BMT and timeline impacts immunity, drugs and exposures

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7
Q

Pulmonary Complications BMT

A

– Aspiration events with severe mucositis early after BMT

– Encapsulated sinopulmonary pathogens late after BMT

  • Filamentous fungi early and late (A. fumigatus)
  • Respiratory virus infection follows seasonal epidemiology

Adenovirus: reactivation and acute infection (particular issue with kids)

– HSV classically described with prior airway manipulation

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8
Q

Early non‐infectious lung injury

A
  • Diffuse alveolar hemorrhage: Vasculitis, drug‐induced injury, cancer‐chemotherapy / thrombocytopenia
  • Idiopathic pneumonia syndrome
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9
Q

Think Fusarium spp if . . .

A

Positive BCx and skin lesions (also PNA?)

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10
Q

DDx of Late pulmonary syndromes

A

– CMV disease

– Respiratory virus infections

– PCP

• Non‐infectious – Bronchiolitis obliterans syndromes

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11
Q

CMV Infection after BMT

– Highest risk group

A
  • Reactivation: Highest risk group for viral disease: D‐ / R+
  • Primary infection: D+ / R‐ or blood products (rare)

• Pneumonitis • Gastrointestinal disease • Encephalitis, retinitis less frequent

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12
Q

CMV Tx after BMT

A

– Pre‐emptive with ganciclovir driven by PCR

• Not prophylaxis (SOT) with ganciclovir;

– Induction therapy with maintenance GCV

– Resistance to GCV is rare (as opposed to SOT)

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13
Q

Pneumocystis Pneumonia Prophylaxis in BMT

A

– Bactrim

• Dapsone, atovaquone, aerosolized pentamidine

– Less effective, other infections occur**

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14
Q

Pneumonia + encephalitis + fever in patient w/o BACTRIM prophylaxis, THINK . . .

A

Toxoplasmosis

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15
Q

Bronchiolitis Obliterans

A

Chronic GVHD of lung; late s/p BMT

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16
Q

GVHD: Acute (early after HSCT)

A

– Fever

– Rash

– GI: hepatic, colon

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17
Q

GVHD: Chronic (later after HSCT)

A

– Skin changes (lichen planus, sceroderma)

– Hepatic (cholestatic)

– Ocular (keratoconjunctivitis)

– GI (oral, dysphagia)

– Pulmonary syndromes

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18
Q

Chronic diarrhea mimicking GVHD

A

Norovirus

19
Q

Adenovirus Infection after BMT

A
  • More common in children, high risk BMT
  • Enteritis, cystitis, upper respiratory infection, pneumonia, encephalitis, hepatitis
20
Q

DDx of Hemorrhagic Cystitis

A
  • Conditioning related (early) – Cyclophosphamide
  • BK virus (later)
  • Adenovirus (later)
21
Q

Selected DDx of Neurologic Syndromes

A

– HHV6*

– West nile virus

– JCV – PML (especially with T‐depleting Abs)

– Pulmonary + CNS lesions: • Invasive fungal infections • Nocardia • Toxoplasmosis

• carbapenems, cefepime, PRES*

22
Q

HHV‐6 after BMT

A

Meningoencephalitis

ACV‐resistant. Treat with ganciclovir, foscarnet, cidofovir

23
Q

Posterior reversible encephalopathy (PRES), associated with . . .

A

Calcineurin inhibitors: Cyclosporin*, tacrolimus

24
Q

PLAY THE ODDS

A
  • Patient completing valganciclovir prophylaxis 6 weeks prior presenting with fatigue, low grade fever and leukopenia • CMV Syndrome
  • Donor died from skiing accident in fresh water lake in Florida and recipient presents 3 weeks post transplant with encephalitis • ACANTHAMOEBA
  • Renal transplant recipient on valganciclovir prophylaxis presents with asymptomatic renal dysfunction • BK Virus
  • Lung transplant recipient planted vegetable garden 2 weeks prior while on posaconazole prophylaxis and presents with productive cough and cavitary lung lesion • NOCARDIA
25
Q

Listeria monocytogenes in SOT

A

• Bacteremia with or without meningitis

26
Q

Nocardia in SOT

A
  • Most often pulmonary nodules, CNS (15-20%), skin (15%), or bone (2-5%)
  • Nocardia is Neurotropic; r/o asymptomatic brain abscess

Branching, Gram positive rods • Partially acid-fast by modified Kinyoun stain

• TMP-SMX considered drug of choice

27
Q

CMV Syndrome

A
  • CMV blood PCR postive and
  • Fever and
  • One or more of the following - Malaise, leukopenia, atypical lymphocytosis, thrombocytopenia, elevated hepatic enzymes
28
Q

Greatest risk for CMV disease after SOT

A

D+/R-

and

ALA Therapy (R+)

29
Q

CMV prophylaxis s/p SOT

A

Bottomline:

  • D+/R- or ALA for rejection → Universal
  • R+ → Universal or Preemptive
30
Q

GI CMV disease after SOT

A

CMV disease of GI tract may not have detectable viremia; diagnosis often requires tissue biopsy

Viral load may continue to rise during first 2 wks of Rx

31
Q

EBV - PTLD risk factors

A
  • Primary EBV infection • (D+ / R-)
  • Antilymphocytic antibody therapy
  • Organ transplanted • (intestine > lung > heart > liver > kidney)
32
Q

EBV - PTLD

  • Clinical manifestation
  • Diagnosis
  • Tx
A
  • Clinical manifestation: Febrile mono-like illness + lymphadenopathy • Solid tumors
  • Diagnosis: biopsy
  • Tx: Reduce Immunosuppression • Rituximab - anti-CD20 monoclonal antibody
33
Q

BK virus nephropathy pearls

A
  • Cause of nephropathy post renal transplant • Up to 15% of patients
  • Manifests as unexplained renal dysfunction (as does rejection)
  • Renal Bx - “Gold Standard” for diagnosis
  • Blood PCR as indicator for biopsy
  • Detection in Low PPV but High NPV
  • Tx: Reduce immunosuppression
34
Q

SOT: Toxoplasmosis Risk factors and Tx

A

• Acquired from donor, reactivation, blood transfusion or ingestion

• D+ / R-

  • HEART > LIVER > KIDNEY TRANSPLANT
  • TREATMENT: sulfadiazine-pyrimethamine-leucovorin
35
Q

Selected Unexpected D+ derived infections in SOT

A
  • Lymphocytic choriomeningitis virus (LCMV): Hamsters and rodents
  • Rabies virus
  • Chagas’ Disease (Trypanosoma cruzi)
  • HIV, HCV, HBV, West Nile Virus (WNV)
  • Remember the “Window” prior to development of antibodies
36
Q

OTHER PEARLS FOR BOARDS… SOT

A
  • If you’re thinking PCP but its not  think TOXO
  • Patient presenting atypically during first month post transplant  think donor transmitted infection
  • Remember drug interactions and syndromes • TTP and PRESS (RPLS) induced by calcineurin inhibitors • Sirolimus-induced pneumonitis
  • Remember Strongyloides hyperinfection syndrome
  • TB- Don’t miss a case!
  • BK, CMV and EBV/PTLD – know how to diagnose and manage
37
Q

Immune suppression drug associations

Rituximab (anti‐CD20)

Alemtuzimab (anti‐CD52)

BCR – ABL Tyrosine – kinase inhibitors – (ex. imatinib, dasatinib, nilotinib, more)

A
  • Rituximab (anti‐CD20) • Hepatitis B reactivation, PML
  • Alemtuzimab (anti-CD52): Herpes viruses (esp. CMV), fungal infections (PJP, Aspergillus)
  • Imatinib, dasatinib, nilotinib, etc: • (VZV reactivation, Hep B reactivation).
  • JAK/STAT inhibitors (ex. tofacitinib, ruxolitinib): VZV, CMV, PCP, M. Tb
38
Q

Neutropenic “syndromes”

Viridans Streptococci

A
  • Key points: neutropenia, mucositis, high‐dose cytosine arabinoside, fluoroquinolone
  • Can present with fever, flushing, chills, stomatitis, pharyngitis • VGS shock syndrome
  • Endocarditis unusual (<10%)
  • S. mitis, S. oralis
39
Q
  • Typical patient‐ neutropenic, progressive sepsis
  • Recognize holes in protection, specific syndromes
A
  • – ARDS, rash, quinolones, mucositis ⇒ viridans Streptococci
  • – Sepsis with β‐lactams ⇒ Stenotrophomonas, ESBL
  • – Sepsis with carbepenems ⇒ KPC
  • – Lung and skin lesions ⇒ P. aeruginosa, Fungi
  • – Skin lesions, gram + ⇒ Corynebacterium jeikeium
  • – Mucositis (upper, lower tract) ⇒ Fusobacterium spp., Clostridium spp., Stomatococcus mucilaginosis
40
Q

Neutropenia and Skin Lesions

A
  • Candidiasis – Small, tender papules
  • Aspergillus – ulcerative, necrotic, minimal erythema
  • Other filamentous fungi (Fusarium, P. boydii) – Multiple, erythematous, different stages
  • P. aeruginosa – Ecthyma gangrenosum
41
Q

Neutropenia and Fusarium

A

Invasive pulmonary disease with skin lesions

42
Q

Neutropenic Enterocolitis

A

• Neutropenic enterocolitis (typhlitis) – Can be accompanied by bacteremia • Hint: mixed, anaerobic (C. septicum, C. tertium, B. cereus)

43
Q

Hepatosplenic Candidiasis

A

Fungi invaded by portal vasculature

• Presentation after engraftment: abdominal pain, increased LFTs (alk phosph), fever, leg / flank pain

44
Q

Alemtuzumab

• Anti‐CD52 Ab (Campath)

A
  • Reactivation of CMV is the most common infectious complication
  • Other risks: PCP, IFI (T cell)

11/7/18 (2 decks)

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