Posted 1/4/2018 9:58 AM (GMT -7)
See cut and paste below
Diagnostic techniques for CMV infection
Serology: Serology is useful to determine previous viral exposure and identify patients at risk, as only seropositive patients (positive IgG antibodies in blood) may develop CMV disease[30,31].
Antigenemia assay: It detects viral protein pp65 produced in peripheral blood polymorphonuclear leukocytes. It is a simple and rapid technique, with a sensitivity of 60%-100% and a specificity of 83%-100%[32,33]. However, it does not differentiate between latent infection and active disease, no association exists with virus reactivation in the intestinal mucosa[31,34], and false negatives can occur in neutropenic patients.
PCR DNA amplification assay in blood: This test is supplanting antigenemia. Sensitivity ranges 65%-100% and specificity ranges 40%-92%[32,36,37]. This diagnostic method cannot differentiate between latency and activity states, so it is necessary to determine a cut-off above which active infection is diagnosed in patients with IBD[30,35], as well as in solid organ transplantation, where a viremia > 1000 copies/100 000 leukocytes indicates symptomatic CMV infection. This method can be used both to detect disease and to monitor treatment response; a slow or absent decline in DNA levels after treatment could be an early indicator of drug resistance, and positive result after therapy indicates continuing treatment. Most studies in patients with IBD have reported a correlation between identification of CMV by PCR in blood and detection colonic CMV by haematoxylin and eosin (HE) or immunohistochemistry (IHC)[34,41-43].
PCR assay in stool: A qualitative and quantitative PCR assay for CMV DNA has been performed on human faecal specimens from immunocompromised patients[44,45].
Diagnostic techniques for CMV colitis
Histological diagnosis is considered the “gold standard” for diagnosing CMV disease in the gastrointestinal tract[46-51]. Several methods are available.
Histology by HE: Typically reveals cytomegalic cells that are 2 or 4 fold larger than normal cells, containing basophilic intranuclear inclusions in eccentric location surrounded by a clear halo, giving it an “owl’s eye” appearence. Cells show a thickened nuclear membrane and smaller granular intracytoplasmic inclusions. Colonic biopsies should be taken from inflamed mucosa near or within the ulcer. This method has very high specificity (92%-100%), but its main problem is a poor sensitivity (10%-87%), making the diagnosis requires many samples and a trained pathologist[46,47]. Anecdotally cytomegalic cells have been described in colon biopsies from normal mucosa in healthy individuals[48,49].
IHC in colon biopsies: It involves the identification of CMV antigens in infected cells. It has a higher sensitivity than HE (78%-93%)[50,51]. Other techniques, however, do not rely on histology.
PCR DNA amplification assay in colon mucosa: PCR DNA amplification assay in colon mucosa has the greatest accuracy for virus detection[29,52,53] and may be used as a qualitative or quantitative method. PCR DNA levels in the colon are not related to viremia levels measured in blood[31,43,54,55]. Some studies detected prevalences greater than 30% in IBD patients, although the significance of a positive result in absence of histological signs of CMV infection is unclear. Very few studies have shown a correlation between histology (HE/IHC) and PCR results[31,43]. This suggests that detection of low DNA levels could determine latent infection and requires a cut-off level of viremia to distinguish infection from disease. In other words, a positive result in colon does not necessarily reflect the involvement of CMV in UC flare-ups. A recent study from France suggests a cut-off of > 250 copies/mg for CMV disease with a sensitivity of 100% and a specificity of 66%. To avoid false positives, and awaiting further studies, this determination should be performed only in patients with active UC refractory to conventional treatment.
Viral culture: Viral culture was previously regarded as the gold standard in CMV detection. Culture has a sensitivity of 45%-78% and a very high specificity (89%-100%). The virus is placed in a fibroblast tissue culture and diagnosis is made once the virus causes cytopathic changes in fibroblasts. The problem is that the result takes days to weeks, so this method is not used in clinical practice.
Typical endoscopic findings of CMV colitis: Typical endoscopic findings of CMV colitis are microerosions, deep ulcers and pseudotumoral lesions. Most studies in patients with IBD, specifically in active UC, have not found specific endoscopic features[43,54,59,60]. Anecdotal studies describe some characteristic endoscopic (large, irregular, punched-out or longitudinal ulcers) with virus. Discrepancy can be explained by the different criteria used to define CMV infection or disease.
In conclusion, different methods of detection of CMV have different sensitivities and specificities. In the setting of a severe UC flare-up refractory to conventional treatment, colonic IHC or PCR in blood should be performed, PCR presents a good correlation with the results of HE and IHC. Serology and antigenemia only are useful as negative predictors for CMV infection, since they do not correlate with actual CMV colitis. The role of PCR positivity in colon remains to be determined, it is not known how to interpret its positivity in the absence of histological changes. However, recent studies imply positivity of this method in the disease prognosis. Current European guidelines recommend the use of tissue PCR or IHC to detect CMV in patients with UC resistant to immunomodulators, whereas older American guidelines recommend performing sigmoidoscopic biopsy and viral culture in refractory cases of UC.
Male Mid 30's
Diagnosed Proctosigmoiditis (UC) February 2015
Current Meds: Lialda 1.2gm 2x daily, generic rowasa as needed
Perianal Abscess June 2015
Fistulotomy December 2015...Doc's still say it's UC, not Crohn's
Specific Carbohydrate Diet started June 2015. Still going strong.
"Happiness doesn't depend on who you are or what you have, it depends solely on what you think." -Dale Carnegie