[ID] CMV colitis in immunocompromised patients(progress; topic review)
[Category] Topic;
1. Workup; 2. Management; 3. Tip and Teaching point; 4. References;
CMV colitis
1.Clinical
manifestation.
Clinical significance:
“Active CMV infection” and “CMV disease” are associated with acute allograft
failure/death
“Active CMV
infection: the presence of
CMV replication in blood regardless of whether signs or symptoms are present.
“CMV disease” is the presence of detectable
CMV in a clinical specimen accompanied by other clinical manifestations. CMV
disease may manifest as either CMV syndrome or tissue-invasive CMV disease.
In CMV disease,
“CMV syndrome”: detectable viral replication in blood with fever,
malaise, arthralgia, leukopenia, thrombocytopenia in the absence of
tissue-invasive disease.
“Tissue-invasive CMV disease” with end-organ disease (enteritis, colitis,
hepatitis, nephritis, pneumonitis, meningitis, encephalitis, retinitis; GI,
Kidney, Lung, Brain, Eye).
Most common Sx = GI disease.
Happens mostly after finishing 3
months of CMV prophylaxis after transplantation.
<GI>
Enteritis and/or colitis – Nausea, vomiting,
diarrhea, and/or abdominal pain.
Hepatitis
with elevated OT/PT with CMV viremia
Pancreatitis with elevated amylase and lipase and CMV
viremia.
Nephritis
– CKD with histologic features of CMV infection in a kidney biopsy specimen.
(Kidney
Biopsy)
Pneumonitis
– Cough, shortness of breath, and pulmonary infiltrates on radiographic imaging
plus CMV in BAL
(Bronchoscopy)
Meningoencephalitis
– Headache, nuchal rigidity, mental status changes, or paralysis, plus CMV in
cerebrospinal fluid.
(LP
puncture)
Retinitis
– Retinal edema or hemorrhage
(Ophthalmologist
workup)
2.Workup:
-How to
diagnose?
We confirm the diagnosis of CMV
infection or disease with nucleic acid testing (NAT).
NAT using the polymerase chain reaction (PCR) for the detection of CMV.
Threshold: not clear to
differentiate among latent infection, low-level active infection, and CMV
disease. Clinical judgment must be used!!(e.g. CMV syndrome: mean 9120 IU; tissue-invasive
CMV disease: mean 20,893 IU.)
cf. Current COVID-19 test: 1) molecular tests, such as RT-PCR tests(reverse
transcription polymerase chain reaction; amplifies many copies of a segment of
the “N” gene by using primer and DNA polymerase; 30-45 cycles of PCR needed to
be detected.), that detect the virus's genetic material, 2) antigen tests that detect
specific proteins on the surface of the virus.
-What about
serology test? such as IgG, IgM
Enzyme immunoassays(EIA) and
indirect and anticomplement immunofluorescence(ACIF) assays are the most
commonly used.(cf. Enzyme-Linked Immunosorbent Assay = ELISA)
-
Recent and Acute infection:
CMV-specific IgM Ab(+);
CMV-specific IgM antibodies are
typically detectable within the first two weeks after the development of
symptoms and may persist for several months. Among patients with acute
CMV infection who had serial serum samples available for analysis, CMV-specific
IgM antibodies were detectable for a period of four to six months after the
onset of symptoms. Therefore, a positive CMV-specific IgM antibody alone may provide misleading information if a
prior baseline test is not available (in cases in which it represents prior
infection rather than current infection).
-
X4 or more increase in CMV-specific
IgG titers in
paired specimens obtained at least 2 weeks apart; CMV-specific IgG antibodies are often not
detectable until two to three weeks following the onset of symptoms and persist
lifelong
-How to
evaluate its significance?
Sx.
and/or Organ involvement(more significant
consequence)
3.Management(Indication to start antiviral):
Active CMV infection
vs CMV disease
Among transplant recipients who have active CMV infection
but who are asymptomatic, we stop the antimetabolite immunosuppressant (ie, azathioprine or mycophenolate). We do
not use antiviral treatment in such patients, unless they develop symptoms or
viremia does not resolve with stopping the antimetabolite. However, many
centers add an antiviral agent upon recognition of CMV reactivation, especially
in high-risk patients. Decision points to dictate aggressiveness in this
setting should include consideration of dose of immunosuppression or cumulative
exposure to immunosuppression and whether the patient is CMV-seropositive (CMV
R+) or seronegative (CMV R-) as the latter group has a higher risk for rapid
development of disease. (See 'Active CMV infection' above.)
●Among all transplant recipients who have
CMV disease (either CMV syndrome or tissue-invasive disease), we initially stop
the antimetabolite immunosuppressant (ie, azathioprine or mycophenolate) and
provide antiviral treatment. Our selection of agent depends on the severity of
the clinical manifestations and the level of viremia and, among some patients,
the pattern of drug resistance. (See 'CMV disease' above.)
•Among all patients with life-threatening
CMV disease (eg, pneumonitis, meningoencephalitis), high viral loads, or
moderate to severe gastrointestinal disease, we recommend full treatment doses
of antiviral therapy with intravenous (IV) ganciclovir rather
than oral valganciclovir (Grade 1B). Ganciclovir has been shown to
be effective among kidney transplant patients with severe CMV infections. The
dose of ganciclovir is 5 mg/kg IV every 12 hours (adjusted for kidney
function).
•Among patients with mild CMV disease (ie,
those with minimal signs and symptoms) who are expected to have good absorption
of oral medications, we recommend full treatment doses of oral valganciclovir rather
than IV ganciclovir (Grade 1B). Oral valganciclovir has been
shown to be as effective as ganciclovir in patients with mild to moderate CMV
infection and spares patients from the risks and cost of central venous access.
The dose of valganciclovir is 900 mg orally twice daily (adjusted for kidney
function). (See 'Antiviral therapy' above.)
●We generally continue one of the antiviral
regimens at the full treatment doses described above until the clinical signs
and symptoms of CMV disease have completely resolved and there is no evidence
of CMV viremia in two blood PCRs performed at least one week apart. The typical
duration of full treatment doses of antiviral therapy is 21 days but can range
from 14 to 28 days or longer. Once symptoms and viremia have resolved, we treat
all patients with a one- to three-month course of oral valganciclovir at
900 mg once daily (adjusted for kidney function) to prevent relapse; this
reduced dose of valganciclovir is sometimes referred to as secondary
prophylaxis. (See 'Duration of therapy' above.)
●Ganciclovir resistance
has become more common with the institution of preventive treatment of CMV.
Patients with ganciclovir-resistant CMV may require a higher dose of
ganciclovir, or IV foscarnet, depending
on the identified genotype. Patients with life-threatening disease (such as CMV
pneumonitis) that progresses despite antiviral agents and reduction of
immunosuppression agents may be treated with cytomegalovirus immune globulin (CytoGam,
CMV Ig) or intravenous immune globulin (IVIG)
irrespective of the mutation that is identified and if no mutation is
identified. (See 'Drug-resistant CMV' above.)
-4.How to dose ganciclovir? and anything additional
concerning to start meds?
Px.
CMV disease
increases allograft loss and mortality:
●In a single-center study of 51 CMV D+/R-
patients who developed CMV disease after stopping antiviral prophylaxis (49
percent with CMV syndrome and 51 percent with tissue-invasive CMV disease), CMV
disease was associated with a 2.8-fold increased risk of allograft loss or
death, whereas CMV syndrome was not [2].
●In a multicenter study of 15,848 United
States kidney transplant recipients assembled using large administrative data,
CMV disease occurring >100 days posttransplant was identified in 4 percent
of patients, and CMV disease occurring <100 days posttransplant was identified
in 1.2 percent of patients. In multivariable analysis, CMV disease occurring
101 to 365 days posttransplant, and CMV disease occurring >365 days
posttransplant were associated with a 1.5- and 2.1-fold increased risk of
death, respectivel
[
댓글
댓글 쓰기