Post by kickingfrog on Feb 1, 2011 15:13:57 GMT
Also please see:
coeliac.proboards.com/index.cgi?board=othercon&action=display&thread=1322
*******************
Patient Information Addenbrooke’s Hospital
What is refractory coeliac disease (RCD)?
This condition occurs when we are confident that the gluten has been removed entirely
from the diet, and yet the intestine remains inflamed.
RCD can occur in patients who have been on a good gluten free diet for years, but
suddenly start to experience the symptoms of coeliac disease again.
We do not yet know entirely why coeliac disease can become ‘refractory’ in this way. It is
mostly found in patients whose coeliac disease is diagnosed later in life, and in those who
have not managed to keep well to a gluten free diet over some years.
RCD is very rare.
What are the risks of refractory coeliac disease?
In some patients, RCD may be an early stage of a complication of coeliac disease
known as ‘Lymphoma’. This is a very rare type of tumour affecting the immune
tissue of the intestine. By carrying out a special molecular test on previous biopsies,
we can tell whether you are at risk of developing this condition.
Even if we find that you are at risk of developing a lymphoma, we still do not know
how great this risk is. However, we do know that this lymphoma is extremely
uncommon, and that people can have RCD for many years without developing
lymphoma.
If we find that you are in the group of patients with RCD who are at risk, we will
keep a close eye on your intestine. We can then pick up any problems at an early
stage.
What further tests will I need if I have refractory coeliac disease?
We may need to carry out a scan of your abdomen and an X-ray test of the small intestine.
Every year, we will then carry out the following tests to keep a
close eye on the intestine:
An endoscopy to take further biopsies. The endoscope that is used is slightly
longer than the usual one so that we can look further into the small intestine. It is
called an ‘enteroscope’ but the test is in every other detail the same as an
endoscopy.
A ‘video capsule enteroscopy’. This is a small pill that you swallow that contains a
camera and enables us to look further into the small intestine.
Are there any treatments available for refractory coeliac disease?
In many cases no treatment is required beyond occasional checks and additional
endoscopies as described above.
In some cases, the damage to the intestine may require additional help to replace
nutrients that cannot be absorbed. Sometimes these may need to be replaced by
injection.
As there is no easy way of telling whether patients are very sensitive to tiny
amounts of gluten, we may ask you to try a period of a ‘wheat free’ rather than
‘gluten-free’ diet. This ‘sensitive’ coeliac diet is more difficult to manage than the
usual gluten free diet. We would only ask you to continue this if there is evidence that it is helping you.
Some patients may be helped by the use of medications to reduce the activity of the
intestinal immune system – these are routinely used for other inflammatory
conditions of the gut but can have side effects and are therefore not used unless
absolutely necessary.
www.cuh.org.uk/resources/pdf/patient_information_leaflets/PIN1169_refractory_coeliac_disease.pdf
**************************
Study: Lymphoma risks for coeliacs and their families
Posted by Charlotte, Oxford on 2/3/2009
GF board
This study show the risks are falling (with earlier CD detection) but still high (5 fold). The elevated risk for family members is I believe a new finding.
Celiac Disease Linked to Five Times Greater Lymphoma Risk
Celiac.com 02/09/2009 - An extensive recent survey of the Swedish cancer registry reveals that people with celiac disease face a 5-fold increased risk of developing non-Hodgkin lymphoma, but that the risk has decreased by more than 50% over the last 40 years.
Researchers at the National Cancer Institute (NCI) in Bethesda, Maryland, and Sweden's Karolinska Institute recently undertook a review of more than 60,000 lymphoma cases diagnosed in Sweden between 1965 and 2004. They matched those cases to individual lymphoma-free controls with similar characteristics.
Dr. Ying Gao of the NCI and colleagues found 37,869 cases of non-Hodgkin's lymphoma, 8,323 cases of Hodgkin's lymphoma, 13,842 cases of chronic lymphocytic leukemia.
The researchers also enrolled 236,408 matched controls and 613,961 first-degree relatives. The team used hospital discharge information to identify people with a history of celiac disease.
The data revealed that people with a hospital discharge diagnosis of celiac disease faced a 5.35-fold increased risk of developing non-Hodgkin's lymphoma. The data also showed that risk of Hodgkin's lymphoma was mildly elevated, and thst celiac patients showed no elevated risk of developing chronic lymphocytic leukemia.
The data showed that from 1975-1984, patients with celiac disease faced a 13.2-fold greater risk of non-Hodgkin's lymphoma; from 1985-1994, that level fell to a 7.90-fold increased risk, and from 1995-2004 that risk fell again to 3.84-fold increased risk. Siblings of those affected with celiac disease also faced a 2.03-fold greater risk of non-Hodgkin's lymphoma.
At present, doctors do not clearly understand the causal link between the two.
Earlier studies have indicated that the inflammation common to celiac disease leads drives lymphoma development.
According to the research team, the study carries two basic messages:
The first is that earlier detection of celiac disease is helping to lower the risk of developing lymphoma over time, so today, fewer people are detected in the late stages, when the risk of lymphoma is much greater.
The second message is that people with a family history of celiac disease have a greater chance of developing lymphoma.
This family connection was shown to be separate from the personal celiac disease history of the individual.
Together, these revelations suggest that shared mechanisms might contribute to both celiac disease and lymphoma.
The full report appears in the medical journal Gastroenterology, January 2009.
*****************************
Coeliac disease and risk of lymphoma
Coeliac disease has been associated with an increased risk of developing some types of lymphoma. This was first noted in the 1930s, and was originally associated with a rare type of lymphoma of the small intestine called enteropathy-type T cell lymphoma (ETTL).
More recently, researchers have found that while ETTL is the most common type of lymphoma associated with coeliac disease, there is an increased risk of other types of non Hodgkin’s lymphomas.
We don’t know exactly what the increased risk of lymphoma is.
But importantly, the majority of people with coeliac disease do not develop lymphoma.
Compared with the general population, people with coeliac disease also have an increased risk of developing some other cancers, including oesophageal cancer and adenocarcinomas of the small bowel.
However, researchers have yet to agree on the exact risk, and opinions vary. One study reported that people with coeliac disease have a lower risk of breast cancer.
This can be a great deal to take in, especially while adjusting to the diagnosis of coeliac disease, and changes to your diet.
But it is important to remember that doctors now believe that following a gluten free diet can reduce your risk of developing cancer so it becomes the same as that of the general population.
In 1989 a medical study in Birmingham concluded that people with coeliac disease who had followed a gluten free diet for 5 years or more, had the same risk of cancer as the general population.
You can read the results of this study on the BMJ Journals website.
A Swedish study showed that the risk of non Hodgkin’s lymphoma in people with coeliac disease was significantly higher than in the general population, but the risk fell from the 1970s to the 1990s.
This may be because coeliac disease is better managed nowadays and also because milder forms of the disease are picked up through screening.
We need more research, to understand more about the cancer risks associated with coeliac disease, and to find out whether people with this condition should have cancer screening.
If you have coeliac disease, it is important to stick to a strict gluten free diet.
This will help reduce symptoms of other conditions associated with coeliac disease, such as osteoporosis and autoimmune disorders, as well as your cancer risk.
If you are worried that you might have coeliac disease, then talk to your GP.
www.cancerhelp.org.uk/about-cancer/cancer-questions/lymphoma-and-coeliac-disease
********************
Malignancy in coeliac disease--effect of a gluten free diet.
Gut 1989;30:333-338 doi:10.1136/gut.30.3.333
G K Holmes,
P Prior,
M R Lane,
D Pope,
R N Allan
+ Author Affiliations
Gastroenterology Unit, General Hospital, Birmingham.
Abstract
Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up.
The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short.
The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period.
Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas.
Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin's lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4).
The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population.
The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p < 0.001), and also of lymphoma (RR = 77.8, p < 0.001).
A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found.
The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.
***************************************
From CUK
Refractory Coeliac Disease
...RCD can be defined as a Marsh stage 3 biopsy despite following a gluten-free diet and with other causes of villous atrophy having been excluded. Marsh stage 3 is defined as raised intraepithelial lymphocytes and crypt hyperplasia with progression of the inflammation to villous atrophy (5).
There are 2 types of RCD which require polymerase chain evaluation (PCR) of small intestinal biopsy material to be diagnosed.
Type 1 RCD – there is polyclonal expansion of T-cells as shown by polyclonality of the T-cell receptor loci.
Type 2 RCD – defined as the presence of monoclonality of the gamma T-cell receptor (TCR).
RCD is associated with a higher risk of complications and mortality, especially Type 2 RCD.
People with Type 2 RCD are at an increased risk of developing malignancy, particularly enteropathy-associated T-cell lymphoma (EATL) (6) and prognosis is poor. Aberrant intraepithelial lymphocytes in Type 2 RCD are considered a premalignant cell population from which enteropathy T-cell lymphoma can evolve. Nutrition will be impaired because of ongoing malabsorption.
...
Due to the rarity of RCD very few adequate clinical trials have been carried out. Treatments are based on case reports, observational reports and expert opinion (1).
When a patient is not responding to a gluten-free diet it is essential that an experienced dietitian performs a dietary evaluation (7). Regular dietetic input is important to assess nutritional adequacy and despite not responding to the diet it is essential that someone with RCD continues to follow a strict gluten-free diet as part of their management plan.(1).
Admission to hospital may be needed to monitor adherence to the gluten-free diet. Nutritional treatment should include incorporating strategies to address any nutritional deficiencies (1).
Drug treatments may include steroids, immunosuppressive drugs, chemotherapy or a combination of these (8). However these have had varying results and whichever treatment is chosen ongoing review from the healthcare team is essential.
Prednisolone, budesonide or a combination of prednisolone and azathioprine can be given to induce clinical remission and mucosal recovery in most people with Type 1 RCD (1).
In a few individuals with Type 1 RCD an elemental diet has been shown to induce long term immunopathologic, histologic and clinical improvement (8). However, more research is required before this can be considered a valid treatment option for Type 1 RCD.
Treatment for Type 2 RCD is more difficult (9) and the consensus on treatment can vary. The majority of people with Type 2 RCD respond clinically to steroids however mucosal recovery is less likely and does not prevent the development of EATL (1). Due to the possibility of developing overt lymphoma, there is a need for close monitoring and follow up (9). Large randomised controlled trials which would require collaboration between several specialist centres is needed to provide an evidence base for the treatment of Type 2 RC
1.Rubio-Tapia A and Murray J A. (2010). Classification and management of refractory coeliac disease. GUT 59: 547 - 557
2.Verbeek W H M, Schreurs M W J, Visser O J, Von Blomberg BME, Al-Toma A, and Mulder CJJ. (2008) Novel approaches in the management of refractory coeliac disease. Expert review of clinical immunology 4: 205 – 219
3.Ciclitira PJ, Dewar DH, McLaughlin SC et al (2010) The management of adults with coeliac disease. London: British Society of Gastroenterology (BSG).
4.Daum S, Cellier C and Mulder CJJ. (2005). Refractory coeliac disease. Best Practice and Research Clinical Gastroenterology 19 (3): 413 - 424
5.Cellier C, Delabesse E, Helmer C et al (2000). Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. The Lancet 356: 203-208
6.Al-toma A, Verbeek WHM, Hadithi M, von Blomberg BME and Mulder CJJ. (2007) Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: restrospective evaluation of single-centre experience. GUT. 56:1373 – 1378
7.Hadithi M and Pena AS. (2011). Current methods to diagnose the unresponsive and complicated forms of coeliac disease. European Journal of Internal Medicine 21: 247 - 253
8.Olaussen R, Lovik A, Tollefsen S, Andresen P, Vatn M, De Lange T, Bratlie J, Brandtzaeg P, Farstad I N and Lundin K. (2005). Effect of elemental diet on mucosal immunopathology and clinical symptoms in Type 1 Refractory coeliac disease. Clinical Gastroenterology and Hepatology 3: 875 - 885
9.Ho-Yen C et al (2009) Recent advances in refractory coeliac disease: a review. Histopathology 54: 783-79
coeliac.proboards.com/index.cgi?board=othercon&action=display&thread=1322
*******************
Patient Information Addenbrooke’s Hospital
What is refractory coeliac disease (RCD)?
This condition occurs when we are confident that the gluten has been removed entirely
from the diet, and yet the intestine remains inflamed.
RCD can occur in patients who have been on a good gluten free diet for years, but
suddenly start to experience the symptoms of coeliac disease again.
We do not yet know entirely why coeliac disease can become ‘refractory’ in this way. It is
mostly found in patients whose coeliac disease is diagnosed later in life, and in those who
have not managed to keep well to a gluten free diet over some years.
RCD is very rare.
What are the risks of refractory coeliac disease?
In some patients, RCD may be an early stage of a complication of coeliac disease
known as ‘Lymphoma’. This is a very rare type of tumour affecting the immune
tissue of the intestine. By carrying out a special molecular test on previous biopsies,
we can tell whether you are at risk of developing this condition.
Even if we find that you are at risk of developing a lymphoma, we still do not know
how great this risk is. However, we do know that this lymphoma is extremely
uncommon, and that people can have RCD for many years without developing
lymphoma.
If we find that you are in the group of patients with RCD who are at risk, we will
keep a close eye on your intestine. We can then pick up any problems at an early
stage.
What further tests will I need if I have refractory coeliac disease?
We may need to carry out a scan of your abdomen and an X-ray test of the small intestine.
Every year, we will then carry out the following tests to keep a
close eye on the intestine:
An endoscopy to take further biopsies. The endoscope that is used is slightly
longer than the usual one so that we can look further into the small intestine. It is
called an ‘enteroscope’ but the test is in every other detail the same as an
endoscopy.
A ‘video capsule enteroscopy’. This is a small pill that you swallow that contains a
camera and enables us to look further into the small intestine.
Are there any treatments available for refractory coeliac disease?
In many cases no treatment is required beyond occasional checks and additional
endoscopies as described above.
In some cases, the damage to the intestine may require additional help to replace
nutrients that cannot be absorbed. Sometimes these may need to be replaced by
injection.
As there is no easy way of telling whether patients are very sensitive to tiny
amounts of gluten, we may ask you to try a period of a ‘wheat free’ rather than
‘gluten-free’ diet. This ‘sensitive’ coeliac diet is more difficult to manage than the
usual gluten free diet. We would only ask you to continue this if there is evidence that it is helping you.
Some patients may be helped by the use of medications to reduce the activity of the
intestinal immune system – these are routinely used for other inflammatory
conditions of the gut but can have side effects and are therefore not used unless
absolutely necessary.
www.cuh.org.uk/resources/pdf/patient_information_leaflets/PIN1169_refractory_coeliac_disease.pdf
**************************
Study: Lymphoma risks for coeliacs and their families
Posted by Charlotte, Oxford on 2/3/2009
GF board
This study show the risks are falling (with earlier CD detection) but still high (5 fold). The elevated risk for family members is I believe a new finding.
Celiac Disease Linked to Five Times Greater Lymphoma Risk
Celiac.com 02/09/2009 - An extensive recent survey of the Swedish cancer registry reveals that people with celiac disease face a 5-fold increased risk of developing non-Hodgkin lymphoma, but that the risk has decreased by more than 50% over the last 40 years.
Researchers at the National Cancer Institute (NCI) in Bethesda, Maryland, and Sweden's Karolinska Institute recently undertook a review of more than 60,000 lymphoma cases diagnosed in Sweden between 1965 and 2004. They matched those cases to individual lymphoma-free controls with similar characteristics.
Dr. Ying Gao of the NCI and colleagues found 37,869 cases of non-Hodgkin's lymphoma, 8,323 cases of Hodgkin's lymphoma, 13,842 cases of chronic lymphocytic leukemia.
The researchers also enrolled 236,408 matched controls and 613,961 first-degree relatives. The team used hospital discharge information to identify people with a history of celiac disease.
The data revealed that people with a hospital discharge diagnosis of celiac disease faced a 5.35-fold increased risk of developing non-Hodgkin's lymphoma. The data also showed that risk of Hodgkin's lymphoma was mildly elevated, and thst celiac patients showed no elevated risk of developing chronic lymphocytic leukemia.
The data showed that from 1975-1984, patients with celiac disease faced a 13.2-fold greater risk of non-Hodgkin's lymphoma; from 1985-1994, that level fell to a 7.90-fold increased risk, and from 1995-2004 that risk fell again to 3.84-fold increased risk. Siblings of those affected with celiac disease also faced a 2.03-fold greater risk of non-Hodgkin's lymphoma.
At present, doctors do not clearly understand the causal link between the two.
Earlier studies have indicated that the inflammation common to celiac disease leads drives lymphoma development.
According to the research team, the study carries two basic messages:
The first is that earlier detection of celiac disease is helping to lower the risk of developing lymphoma over time, so today, fewer people are detected in the late stages, when the risk of lymphoma is much greater.
The second message is that people with a family history of celiac disease have a greater chance of developing lymphoma.
This family connection was shown to be separate from the personal celiac disease history of the individual.
Together, these revelations suggest that shared mechanisms might contribute to both celiac disease and lymphoma.
The full report appears in the medical journal Gastroenterology, January 2009.
*****************************
Coeliac disease and risk of lymphoma
Coeliac disease has been associated with an increased risk of developing some types of lymphoma. This was first noted in the 1930s, and was originally associated with a rare type of lymphoma of the small intestine called enteropathy-type T cell lymphoma (ETTL).
More recently, researchers have found that while ETTL is the most common type of lymphoma associated with coeliac disease, there is an increased risk of other types of non Hodgkin’s lymphomas.
We don’t know exactly what the increased risk of lymphoma is.
But importantly, the majority of people with coeliac disease do not develop lymphoma.
Compared with the general population, people with coeliac disease also have an increased risk of developing some other cancers, including oesophageal cancer and adenocarcinomas of the small bowel.
However, researchers have yet to agree on the exact risk, and opinions vary. One study reported that people with coeliac disease have a lower risk of breast cancer.
This can be a great deal to take in, especially while adjusting to the diagnosis of coeliac disease, and changes to your diet.
But it is important to remember that doctors now believe that following a gluten free diet can reduce your risk of developing cancer so it becomes the same as that of the general population.
In 1989 a medical study in Birmingham concluded that people with coeliac disease who had followed a gluten free diet for 5 years or more, had the same risk of cancer as the general population.
You can read the results of this study on the BMJ Journals website.
A Swedish study showed that the risk of non Hodgkin’s lymphoma in people with coeliac disease was significantly higher than in the general population, but the risk fell from the 1970s to the 1990s.
This may be because coeliac disease is better managed nowadays and also because milder forms of the disease are picked up through screening.
We need more research, to understand more about the cancer risks associated with coeliac disease, and to find out whether people with this condition should have cancer screening.
If you have coeliac disease, it is important to stick to a strict gluten free diet.
This will help reduce symptoms of other conditions associated with coeliac disease, such as osteoporosis and autoimmune disorders, as well as your cancer risk.
If you are worried that you might have coeliac disease, then talk to your GP.
www.cancerhelp.org.uk/about-cancer/cancer-questions/lymphoma-and-coeliac-disease
********************
Malignancy in coeliac disease--effect of a gluten free diet.
Gut 1989;30:333-338 doi:10.1136/gut.30.3.333
G K Holmes,
P Prior,
M R Lane,
D Pope,
R N Allan
+ Author Affiliations
Gastroenterology Unit, General Hospital, Birmingham.
Abstract
Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up.
The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short.
The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period.
Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas.
Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin's lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4).
The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population.
The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p < 0.001), and also of lymphoma (RR = 77.8, p < 0.001).
A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found.
The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.
***************************************
From CUK
Refractory Coeliac Disease
...RCD can be defined as a Marsh stage 3 biopsy despite following a gluten-free diet and with other causes of villous atrophy having been excluded. Marsh stage 3 is defined as raised intraepithelial lymphocytes and crypt hyperplasia with progression of the inflammation to villous atrophy (5).
There are 2 types of RCD which require polymerase chain evaluation (PCR) of small intestinal biopsy material to be diagnosed.
Type 1 RCD – there is polyclonal expansion of T-cells as shown by polyclonality of the T-cell receptor loci.
Type 2 RCD – defined as the presence of monoclonality of the gamma T-cell receptor (TCR).
RCD is associated with a higher risk of complications and mortality, especially Type 2 RCD.
People with Type 2 RCD are at an increased risk of developing malignancy, particularly enteropathy-associated T-cell lymphoma (EATL) (6) and prognosis is poor. Aberrant intraepithelial lymphocytes in Type 2 RCD are considered a premalignant cell population from which enteropathy T-cell lymphoma can evolve. Nutrition will be impaired because of ongoing malabsorption.
...
Due to the rarity of RCD very few adequate clinical trials have been carried out. Treatments are based on case reports, observational reports and expert opinion (1).
When a patient is not responding to a gluten-free diet it is essential that an experienced dietitian performs a dietary evaluation (7). Regular dietetic input is important to assess nutritional adequacy and despite not responding to the diet it is essential that someone with RCD continues to follow a strict gluten-free diet as part of their management plan.(1).
Admission to hospital may be needed to monitor adherence to the gluten-free diet. Nutritional treatment should include incorporating strategies to address any nutritional deficiencies (1).
Drug treatments may include steroids, immunosuppressive drugs, chemotherapy or a combination of these (8). However these have had varying results and whichever treatment is chosen ongoing review from the healthcare team is essential.
Prednisolone, budesonide or a combination of prednisolone and azathioprine can be given to induce clinical remission and mucosal recovery in most people with Type 1 RCD (1).
In a few individuals with Type 1 RCD an elemental diet has been shown to induce long term immunopathologic, histologic and clinical improvement (8). However, more research is required before this can be considered a valid treatment option for Type 1 RCD.
Treatment for Type 2 RCD is more difficult (9) and the consensus on treatment can vary. The majority of people with Type 2 RCD respond clinically to steroids however mucosal recovery is less likely and does not prevent the development of EATL (1). Due to the possibility of developing overt lymphoma, there is a need for close monitoring and follow up (9). Large randomised controlled trials which would require collaboration between several specialist centres is needed to provide an evidence base for the treatment of Type 2 RC
1.Rubio-Tapia A and Murray J A. (2010). Classification and management of refractory coeliac disease. GUT 59: 547 - 557
2.Verbeek W H M, Schreurs M W J, Visser O J, Von Blomberg BME, Al-Toma A, and Mulder CJJ. (2008) Novel approaches in the management of refractory coeliac disease. Expert review of clinical immunology 4: 205 – 219
3.Ciclitira PJ, Dewar DH, McLaughlin SC et al (2010) The management of adults with coeliac disease. London: British Society of Gastroenterology (BSG).
4.Daum S, Cellier C and Mulder CJJ. (2005). Refractory coeliac disease. Best Practice and Research Clinical Gastroenterology 19 (3): 413 - 424
5.Cellier C, Delabesse E, Helmer C et al (2000). Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. The Lancet 356: 203-208
6.Al-toma A, Verbeek WHM, Hadithi M, von Blomberg BME and Mulder CJJ. (2007) Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: restrospective evaluation of single-centre experience. GUT. 56:1373 – 1378
7.Hadithi M and Pena AS. (2011). Current methods to diagnose the unresponsive and complicated forms of coeliac disease. European Journal of Internal Medicine 21: 247 - 253
8.Olaussen R, Lovik A, Tollefsen S, Andresen P, Vatn M, De Lange T, Bratlie J, Brandtzaeg P, Farstad I N and Lundin K. (2005). Effect of elemental diet on mucosal immunopathology and clinical symptoms in Type 1 Refractory coeliac disease. Clinical Gastroenterology and Hepatology 3: 875 - 885
9.Ho-Yen C et al (2009) Recent advances in refractory coeliac disease: a review. Histopathology 54: 783-79