Refractory CD

[kickingfrog]

Also please see:

coeliac.proboards.com/index.cgi?action=display&board=othercon&thread=939&page=1
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Refractory CD

Posted by Charlotte, oxford on 6/7/2006

GF board


This is of list of refs on refractory CD posted previously with a couple of more recent refs:

The first suggests renaming it Ulcerative CD. There some updates on therapies.
The UK consultants mentioned: Dr Rakesh Chaudhary, Clinical Research Fellow Telephone [phone] Email r.chaudhary @ imperial.ac.uk or Professor Subrata Ghosh, (both Department Division of Medicine, Imperial College, London) Telephone [phone]
Email s.ghosh @ imperial.ac.uk or Sue M Turner, Department of Gastroenterology, Bristol Royal Infirmary, ([e-mail])
might be worth contacting via your consultant.

This is a difficult and very specialised area, and not all RCD is the same as I'm sure you know. You may need unpublished info on latest therapies. I suspect there are small support groups - certainly people you could usefully contact - in America - have you tried any of the American Celiac boards?

www.gastrolab.net/yaucd.htm

The Wasa Workgroup on Intestinal Disorders, c/o Hans Bjorknas, GASTROLAB, Kyrkoespl 18 B 37, 65100 Vasa, Finland Phone/FAX [phone] Email: [e-mail]

The main feature of Coeliac disease or coeliac sprue is a mucosal damage in the small bowel due to dietary exposition to prolamins in wheat, rye and barley in individuals with a genetic susceptibility. The treatment of this disease is straightforward - a lifelong gluten-free diet. This treatment will most often cure the disease and diminish the risk for any sequelaes.
In a small group of patients the gluten free diet does not cure the abnormalities associated with coeliac disease.
These patients are mostly older and the have suffered from symptoms due to coeliac disease for years before the diagnosis is made. This form of coeliac disase has several ill-defined names. The name most often used is "Refractory coeliac disease".

The main features of this condition are:
- coeliac disease, which has not been treated because the diagnose has never been made before the ulcerative manifestations cause symptoms
- ulcerative lesions that endoscopically look benign and which can occur anywhere in the small bowel
- nonresponsiveness to glutenfree diet
- nonresponsiveness to normal treatment of duodenal ulcer disease
- nonresponsiveness to other conventional treatments including corticosteroids, making the prognosis poor in many instances
- a clear association with T cell lymphoma, making this condition a premalignant and in many instances a malignant condition

Scand J Gastroenterol Suppl. 2000;(232):32-7. Related Articles, Links
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11232488&dopt=Abstract

Refractory coeliac disease: a window between coeliac disease and enteropathy associated T cell lymphoma.
Mulder CJ, Wahab PJ, Moshaver B, Meijer JW. Depts. of Gastroenterology and Pathology, Rijnstate Hospital, P.O. Box 5555, 6800 TA Arnhem, The Netherlands.

Best Pract Res Clin Gastroenterol. 2005 Jun;19(3):413-24.
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15925846&query_hl=5&itool=pubmed_docsum

Refractory coeliac disease.

Daum S, Cellier C, Mulder CJ.
Department of Medicine I, Gastroenterology, Infectious Diseases and Rheumatology, Charite, Campus Benjamin Franklin, Berlin, Germany. [e-mail]

Eur J Gastroenterol Hepatol. 2005 Jun;17(6):667-9.

Aliment Pharmacol Ther. 2003 Sep 1;18(5):487-94

Azathioprine and prednisone combination therapy in refractory coeliac disease.

Goerres MS, Meijer JW, Wahab PJ, Kerckhaert JA, Groenen PJ, Van Krieken JH, Mulder CJ. Department of Gastroenterology, Rijnstate Hospital, Arnhem, The Netherlands. [e-mail]

Refractory coeliac disease: remission with infliximab and immunomodulators.

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15879730&query_hl=5&itool=pubmed_docsum
Turner SM, Moorghen M, Probert CS. Department of Gastroenterology, Bristol Royal

www.blackwell-synergy.com/links/doi/10.1111/j.1572-0241.2002.05917.x/abs/
American Journal of Gastroenterology Volume 97 Issue 8 Page 2016 - August 2002

Etiology of nonresponsive celiac disease: results of a systematic approach
Ahmad S.
AbdulkarimM.D.a, Lawrence J. BurgartM.D.a, Jacalyn SeeM.S.R.D.L.D.a, Joseph A. MurrayM.D.
……
Gastroenterology 1998 Mar;114(3):471-81

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9496937&dopt=Citation

Abnormal intestinal intraepithelial lymphocytes in refractory sprue.Cellier C, et al Department of Gastroenterology, Hopital Laennec, Paris, France.

Rom J Gastroenterol. 2005 Jun;14(2):147-9. Related Articles, Links
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15990934&query_hl=9&itool=pubmed_docsum

Does treatment of coeliac disease require full mucosal recovery?

Mulder CJ. Department of Gastroenterology, VU University Medical Center, P.O. Box 7057, 1005 MB Amsterdam, The Netherlands. [e-mail]

Gut 2003;52:205-211© 2003 by BMJ Publishing Group & British Society of
COELIAC DISEASE
gut.bmjjournals.com/cgi/content/abstract/52/2/205

Refractory coeliac sprue is a diffuse gastrointestinal disease

V Verkarre1, et al, Department of Pathology and Université René Descartes-Paris V (EA219), AP-HP, Hôpital Necker-Enfants Malades, 75015 Paris, France,

Posted: Fri Jan 09, 2004 5:07 pm Post subject:
Refractory CD
Elemental diet in the treatment of Type 1 refractory coeliac disease
www.med.uio.no/rh/forskning/tematisk/cevi/projects/diet.html

Eur J Gastroenterol Hepatol. 2005 Dec;17(12):1401-5.
www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16292096&query_hl=2&itool=pubmed_docsum

Ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma.
Elsing C, Placke J, Gross-Weege W.
Department of Gastroenterology and Surgery, St Elisabeth Hospital, Dorsten, Germany.

Rom J Gastroenterol. 2005 Jun;14(2):147-9.
www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15990934&query_hl=2&itool=pubmed_docsum


Best Pract Res Clin Gastroenterol. 2005 Jun;19(3):413-24.
www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15925846&query_hl=2&itool=pubmed_docsum

Refractory coeliac disease.
Daum S, Cellier C, Mulder CJ.

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[kickingfrog]

Re: Refractory Coeliac Disease recent publications

Posted by Charlotte, Oxford on 25/3/2011


Recent research. None of it very relevant to RCD2 I’m afraid. Chris Mulder still remains appears to remain the most active in RCD research .....

Gut doi:10.1136/gut.2009.186007 Paper
Continual Monitoring of Intraepithelial Lymphocyte Immunophenotype and Clonality Is More Important Than Snapshot Analysis in the Surveillance of Refractory Coeliac Disease Hongxiang Liu et al
Conclusions: Continual monitoring of both immunophenotype and clonality of IEL is more important than snapshot analysis for RCD diagnosis and follow-up, and could provide a useful tool for surveillance of patients at risk of EATL.
NB Professor Ming-Qing Du at Cambridge
www.path.cam.ac.uk/research/investigators/du/publications.html

radiology.rsna.org/content/early/2011/02/15/radiol.11101808.abstract
MR Enteroclysis in Refractory Celiac Disease: Proposal and Validation of a Severity Scoring System Stijn J. B. Van Weyenberg et al
Abstract
Purpose: To determine magnetic resonance (MR) enteroclysis findings in patients with uncomplicated celiac disease (CD), refractory CD (RCD) type I, and RCD type II, to develop and validate a scoring system to identify patients with RCD II and to determine the diagnostic accuracy of MR enteroclysis to detect CD-related malignancies.
Conclusion: MR enteroclysis can be used to investigate the presence of RCD II or malignancy in symptomatic patients with CD.

IBD Drug May Help Treat Refractory Celiac Disease
www.celiaccentral.org/News/News-Feeds/View-Research-News/Celiac-Disease-Research/134/month--201101/vobid--4738/
(Small intestinal release mesalamine for treatment of refractory celiac disease type 1. Jamma S, Leffler D, Dennis M, et al. J Clin Gastroenterol. 2011;45:30–33)

1/28/2011
While most celiac disease symptoms are resolved with a gluten-free diet, patients who suffer from refractory celiac disease do not find relief even after the dietary change.

Medications may be used to alleviate some of the symptoms, but most treatments are inadequate for these severe cases, according to researchers. A team at Beth Israel Deaconess Medical Center, however, may have found a new option.

Published in the Journal of Clinical Gastroenterology, a new study found that individuals with refractory celiac [RCD type 1] disease may respond to a drug typically used to treat inflammatory bowel disease such as Crohn’s disease and ulcerative colitis. The drug, small intestinal release mesalamine (SIRM), was administered to 10 patients with refractory celiac disease. Six of the patients also took oral budesonide along with SIRM. Within 4 weeks, half of the patients reported complete symptom relief, and another individual cited partial relief. Two of the participants were able to stop using budesonide during the trial. One patient discontinued the SIRM treatment due to headaches.

The research team, which included NFCA Scientific/Medical Advisory Board Members Dan Leffler, MD, MS, and Ciaran Kelly, MD, and Ask the Dietitian’s Melinda Dennis, MS, RD, LDN, concluded that SIRM could be a safe, effective treatment for refractory celiac disease, but that additional trials would be needed.

Comment by Peter Green on this:

journals.lww.com/jcge/Fulltext/2011/01000/Mesalamine_for_Refractory_Celiac_Disease__An_Old.1.aspx
Mesalamine for Refractory Celiac Disease: An Old Medicine for a New Disease
Green, Peter H.R. MD; Lebwohl, Benjamin MD, MS

Journal of Clinical Gastroenterology: January 2011 - Volume 45 - Issue 1 - p 1–3
doi: 10.1097/MCG.0b013e3181fb4535 Editorials
Extract:
Not all patients with CD respond to the gluten-free diet. Some never respond in the first place, whereas others lose reponsiveness. The frequency of this phenomenon is unknown, and estimates of the prevalence of poorly responsive CD vary widely from 7% to 30% of all individuals with CD.12 More recently, our understanding of refractory celiac disease (RCD) has been shaped by the crucial dichotomy between RCD types 1 and 2, the latter of which has a poor short-term prognosis and is closely associated with enteropathy-associated T-cell lymphoma.13 These 2 types of RCD are differentiated by the T-cell make-up in the intestinal epithelium. A monoclonal T-cell receptor rearrangement and a loss of the normal CD3 surface expression and loss of CD4 and CD8 are indicative of RCD type 2, whereas a polyclonal T-cell receptor and normal expression of CD3/CD4/CD8 denote RCD type 1. As such, the use of immunohistochemistry, flow cytometry, and T-cell receptor polymerase chain reaction on intestinal biopsies has emerged as a valuable diagnostic and prognostic tool for assessing individuals with RCD.
Despite this advance and well-performed studies of the prognosis of RCD types 1 and 2 at referral centers,14,15 we remain ignorant of the prevalence of these conditions. Much of this uncertainty stems from the fact that patients who do not respond to the gluten-free diet do not necessarily have RCD. Some may not have CD to begin with, and others may have one of several conditions associated with CD, such as small intestinal bacterial overgrowth,16 microscopic colitis,17 and pancreatic exocrine insufficiency.18 Such conditions should be evaluated before the labeling of patients with RCD. Nevertheless, in 1 cohort of patients with or without symptoms undergoing follow-up biopsy, the proportion of patients with persistent abnormalities was found to be 34% in 5 years.19 In that cohort, the lack of histologic recovery was associated with an increased risk of death, though this did not meet statistical significance. Although that study likely overestimated the prevalence of persistent histologic abnormalities due to a selection bias, RCD type 1 may be quite common. But the issue remains understudied; the analysis of thawed serum has shown that the prevalence of CD has increased over the past 50 years,20 but we do not have a grasp of whether RCD is increasing as well.

www.docstoc.com/docs/39913459/Update-on-the-Management-of-Refractory-Coeliac-Disease NB full text

Update on the management of refractory coeliac disease.2007
Al-Toma A, Verbeek WH, Mulder CJ. J Gastrointestin Liver Dis. 2007 Mar;16(1):57-63
Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.

[kickingfrog]

...re RCD2 treatment

Posted by Charlotte, Oxford on 28/3/2011...New publication re another fuller trial of Cladribine, a leukemia & lymphoma drug, also being trialled for MS (but not approved yet). It seems only Mulder's team are trialling this at present. These results do seem more promising. Full text here.

.....

www.ncbi.nlm.nih.gov/pmc/articles/PMC3027018/
Evaluation of Cladribine treatment in refractory celiac disease type II

Greetje J Tack, Wieke HM Verbeek, Abdul Al-Toma, Dirk J Kuik, Marco WJ Schreurs, Otto Visser, and Chris JJ Mulder Mar 2011

Abstract

AIM: To evaluate cladribine [2-chlorodeoxyadenosine (2-CdA)] therapy in refractory celiac disease (RCD) II.
METHODS: An open-label cohort-study of RCD II patients treated with 2-CdA was performed between 2000 and 2010. Survival rate, enteropathy associated T-cell lymphoma (EATL) occurrence, clinical course, and histological and immunological response rates were evaluated.
RESULTS: Overall, 32 patients were included with a median follow-up of 31 mo. Eighteen patients responded well to 2-CdA. Patients responsive to 2-CdA had a statistically significant increased survival compared to those who were unresponsive. The overall 3- and 5-year survival was 83% in the responder and 63% and 22% in the non-responder group, respectively. The overall 2-year clinical, histological and immunological response rates were 81%, 47% and 41%, respectively. Progression into EATL was reported in 16%, all of these patients died.
CONCLUSION: Treatment of RCD II with 2-CdA holds promise, showing excellent clinical and histological response rates, and probably less frequent transition into EATL.