Infectious Diseases Case Conference Part II

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Infectious Diseases Case ConferencePart II

• Jason H. Kettler and Asif Zia
• May 17, 2004
• Wake Forest University

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Case Presentation

• 30 year old Hispanic male
• Underlying HIV infection
• CD4 count 10 HIV VL 475K (3/25/4)
• Begun on FTC/TDF/LPVr w/ ? in VL to 714 (4/11)
• Intolerant of LPVr ? EFV substituted
• Most recent CD4 count 30 VL lt50! (5/4/4)
• Admitted 3/27-4/14 following presentation to the
  ED with N/V/D/RUQ pain

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Case Presentation

• Also previously known to have disseminated
  histoplasmosis on the basis of ID consultants
  notations from Concord, NC
• Clinically manifested by skin ulcerations and
  abnormal chest CT
• Diagnosis established by positive urine and serum
  antigen at NCBH in 3/2004
• Txed w/ AmB x ?14d ? itra 200 mg po qD

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Case Presentation

• Also of note pt. has a h/o CNS toxoplasmosis
  (again old records) and during March hospzn
  had a cranial MRI demonstrating bilat. basal
  ganglia lesions also known to have () toxo IgG
  on 4/1
• Upon D/C to Holly Haven ? pyrimethamine
  clindamycin (h/o sulfa hypersensitivity)

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Case Presentation

• Also w/ ?history of Hepatitis C
• HCV Ab negative 3/28/4
• No transaminitis
• Isolated elevation of alk. phos. (249) with
  normal bilirubin
• In light of notion of inability of some to mount
  antibody responses w/ advanced immunosuppression
  ? VL checked ? lt615

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Case Presentation

• Owing to GI sxs coupled with finding of anemia
  during last hospitalization ? EGD undertaken 4/13
• Pathology c/w marked chronic active gastritis
  with ulceration
• D/Cd on no specific therapy
• Following discharge

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Case Presentation

• Pt. brought back into the hospital through the ED
• Persistent GI complaints
• ID consult for recommendations on evaluation and
  treatment of possible CMV gastritis
• By the way, also colonized with VRE
• Doesnt speak any English

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A few questions to answer

• How is the diagnosis of CMV gastritis
  established?
• What is the role for any adjunctive testing?
• PCR, for example
• What treatment, if any, should be employed?

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CMV a few basics

• A large ds-DNA virus of the family Herpesviridae
• In vivo, CMV-infected cells are found in tissues
  of epithelial and endothelial origin, whereas in
  vitro CMV replication is fully permissive only in
  _________________

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CMV a few basics

• A large ds-DNA virus of the family Herpesviridae
• In vivo, CMV-infected cells are found in tissues
  of epithelial and endothelial origin, whereas in
  vitro CMV replication is fully permissive only in
  human fibroblasts
• In immunocompetent pts., CMV disease is usually
  associated with a mono-like illness

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CMV and AIDS

• Viremia with CMV is common in asymptomatic
  persons w/ low CD4 counts
• Rare cells containing CMV inclusion bodies may be
  seen on HP specimens even when other pathogens
  are causing organ dysfunction
• Patients are known to recover with no therapy
  directed at the CMV

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AIDS-related CMV GI Disease

• Many studies have suggested that CMV end-organ
  disease results from the hematogenous spread of
  CMV
• Presence of CMV in the blood is a RF for the
  dvpt. of CMV disease in AIDS patients
• CD4 T-lymphocyte activity is critical for
  preventing CMV replication and end-organ disease

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Clinical Manifestations

• Nearly all patients w/ GI-related CMV disease
  have a CD4 ct. of lt50
• Sxs determined by location
• esophagitis? odynophagia/substernal pain
• pain is persistent and focal in contrast to
  Candida
• gastritis ? substernal /or epigastric pain
• small bowel dz? abd. pain /- diarrhea
• colitis? intractable diarrhea, oft. w/
  hematochezia
• proctitis ? tenesmus

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Diagnostic Criteria

• CMV GI disease is most accurately diagnosed by
  the clinical triad of
• cardinal symptoms, visualization of mucosal
  ulcers or erosions, histologic evidence of
  tissue destruction caused by CMV
• Viral culture of mucosal biopsies for CMV does
  not have much clinical utility because mucosal
  CMV shedding is neither sensitive nor specific
  for CMV GI disease

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Role for PCR testing

• Data on the use of qualitative CMV PCR on blood
  suggest that it may help to predict eventual
  development of CMV disease
• Prospective cohort of 97 AIDS pts. (all w/ CD4
  cts. lt50)
• 16/27 (59) who were CMV PCR () at b/l dvpd. CMV
  dz w/in 12 mos. compared w/ only 3/70 (4) who
  were CMV PCR (-) (AIDS 1997)

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Treatment

• HAART ? immune restoration
• Only 2 randomized trials for CMV GI dz
• Consensus of clinical experts is that pts. should
  receive 3-6 weeks of BID IV ganciclovir or
  foscarnet
• Maintenance therapy generally not required
• Valganciclovir an attractive alternative
• Only indicated for CMV retinitis, but is likely
  to have similar efficacy to IV GCV

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VGCV

• In anecdotal reports, VGCV has been used for
  terminal tx of CMV colitis and esophagitis
• MOA virustatic inhibits viral DNA synthesis
• SEs anemia/neutropenia, N/V/D, fever, HA,
  confusion, retinal detachment
• VGCV at a dose of 900 mg is roughly equivalent to
  IV GCV at a dose of 5 mg/kg

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Our Patient

• ? CMV gastritis
• Dx plausible but not proven
• Obtain CMV PCR on blood
• Eye exam
• Ask path to review slide and perform
  immunoperoxidase stain on gastric bx
• Begin empiric GCV 5 mg/kg IV q12h
• Start G-CSF

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Our Patient

• PCR ? not done
• Eye exam ? negative
• Disposition
• To Holly Haven on 900 mg po BID of VGCV
• Completed 12 days of therapy in total