Virus to blame for refractory UC?

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Uniform Charlie
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Date Joined Jul 2015
Total Posts : 547
   Posted 1/3/2018 5:28 AM (GMT -7)   
Another article that is not brand new,
but I don't recall seeing it. Researchers may have found a virus that plays a role in refractory UC.

/www.nature.com/articles/modpathol2017149

Identification of clinically relevant cytomegalovirus infections in patients with inflammatory bowel disease.

"Several lines of evidence indicate that cytomegalovirus infection can be substantially associated with onset of inflammatory bowel disease, especially in patients refractory to immunosuppressive treatment. As cytomegalovirus is widely spread in the population, here we present a quantitative detection system suitable to differentiate clinically relevant cytomegalovirus infection from common latent cytomegalovirus. Using a quantitative real-time PCR approach, cytomegalovirus viral load was evaluated in 917 formalin-fixed and paraffin-embedded colon biopsy samples of 136 patients diagnosed with inflammatory bowel disease. Besides initial cytomegalovirus testing, the PCR system was also used to monitor therapy response after antiviral treatment. Cytomegalovirus DNA was detected in 37 patients (27%) with varying viral loads ranging from 5 to 8.7 × 105 copies/105 cells. Thereof, 13 patients (35%) received an antiviral treatment with 12 of them going into remission (92%). Later, five patients displayed a relapse and three patients who agreed to restart antiviral treatment again showed positive therapy response."

Post Edited (Uniform Charlie) : 1/3/2018 6:15:58 AM (GMT-7)


quincy
Elite Member


Date Joined May 2003
Total Posts : 29947
   Posted 1/3/2018 12:33 PM (GMT -7)   
Still a separate issue.....its only role is that it's there.

q
*Heather* I give suggestions, do with them what you will.
Status: ...Asacol 3 @ 2x daily; Salofalk enema @ 3rd night (nightly/ flares, tapered/maintenance)
~diagnosed January 1989 UC (proctosigmoiditis)
~Bentylol 20mg as needed; Zantac 150mg; Pulmicort/Airomir (asthma); Effexor XR 75mg (depression); Rosuvastatin 10mg (cholesterol); Telemesartin 80mg / Amlodipine 5mg (BP)
~vitamins/minerals/supplements; Probiotics....(RenewLife Ultimate Flora Critical Care + Genuine Health Advanced Gut Health 15 billion @ bedtime)
~Metamucil capsules 6 @ 2x daily with meals; Vitamin D 4500 IU
~URSO 500mg @ 2x daily for Primary Biliary Cholangitis
"TREAT (FROM)BOTH ENDS" worth it !!

DBwithUC
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Date Joined Feb 2011
Total Posts : 3982
   Posted 1/3/2018 4:00 PM (GMT -7)   
the article does not clearly disentangle onset from maintenance. maybe it is the beginning of designating refractory UC as a different disease.
11/08: ischemic colitis and scope perf colon. 12cm colon/ileocecal resected. IV antib:sepsis.
01/10: Dx: Mod. UC pancolitis. Rx: Lialda 3x.
02/11: Major flare w/antib:sinus. Rx: 40mg Pred taper. 6mp.
07/11: Histol remiss rt/trans; worse sigmoid. Rx: Rowasa & hydrocort
---
Curr: 1-2 soft-formed stool, no urgency: Lialda 2x, NO PRED, probiotics, Vit-D/C

Uniform Charlie
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Date Joined Jul 2015
Total Posts : 547
   Posted 1/3/2018 5:22 PM (GMT -7)   
The article also does not differentiate between UC and Crohn's, although I was specifically searching for UC studies. Even with the small sample size, it's interesting that so many patients responded to antiviral meds...12 out of 13 achieving remission.
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

Connor77
Regular Member


Date Joined Jul 2016
Total Posts : 410
   Posted 1/3/2018 11:02 PM (GMT -7)   
Looking back at my own history, they looked for CMV by biopsy of bowel ulcers. I don't think they ran a serology test, maybe because such a test is not available here. My limited understanding of CMV is that even if it doesn't directly cause IBD, it can, over time, cause immuno-deficiency which in turn wreaks havoc with the intestinal environment. It could be one explanation for why some IBD patients are so prone to infection.

Does anyone know if there's an effective blood test for CMV anywhere in North America? It would have to be one that looks for both antibodies and the virus itself, doing a viral load titre.
DX left-sided UC 2015, 3 fulminant flares since then
Diagnosed with mycobacterium avium paratuberculosis (MAP) September 2017
Commenced AMAT (rifampin, clarithromycin, clofazimine) November 1 2017
Intolerant to clofazimine, stopped taking
Others: prednisone 10mg, Entyvio every 4 weeks, Low Dose Naltrexone 3mg at bedtime, natural ferments

Uniform Charlie
Veteran Member


Date Joined Jul 2015
Total Posts : 547
   Posted 1/4/2018 9:58 AM (GMT -7)   
@Connor:

See cut and paste below

DIAGNOSTIC TECHNIQUES
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[23], no association exists with virus reactivation in the intestinal mucosa[31,34], and false negatives can occur in neutropenic patients[35].

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[38]. 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[39], and positive result after therapy indicates continuing treatment[40]. 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[56], 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[30]. 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[54] 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[10], so this method is not used in clinical practice[57].

Typical endoscopic findings of CMV colitis: Typical endoscopic findings of CMV colitis are microerosions, deep ulcers and pseudotumoral lesions[58]. 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[61]. 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[30]. 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[54]. Current European guidelines[62] recommend the use of tissue PCR or IHC to detect CMV in patients with UC resistant to immunomodulators, whereas older American guidelines[63] 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
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