Refractory Coeliac

Has anyone been tested for "Refractory Coeliac disease?" if and it was positive where do you go to next question as there is little information out there.

[FionaGFG Administrator]

Great question Tony.

I've noticed that few members of our facebook group have heard of this or know what it is. For those that don't in essence it's the term used for Coeliac Disease where patients don't respond well to a strict gluten free diet. As we all know going gluten free can present a whole host of other wierd and wonderful symptoms and it can take 2-3 years for the stomach to actually heal fully.

However, if anyone does not seem to feel better or respond well on a strict gluten free diet then it's worth talking through your concerns with your Gastro team at hospital.

FEEDBACK:

Like Tony I'd love to know if any members here have been diagnoised:

- how

- what support/ treatment you / your child received

*Skip to the end for the SPEED READ reply...; )

FYI:

As you're probably all aware NICE guidelines only recently focused on HOW to diagnose CD, NOT how to care/ monitor patients afterwards.

So I've always found this 'Best Practice' guide from the Society of Gastroenterologists very useful in terms of what should be happening next.

See: bsg.org.uk/images/stories/c...

Often typical symptoms of Refractory disease are an initial improvement (around 6mths on a GF diet), then a re-occurrence of Coeliac symptoms. Once bloods have been tested (to confirm no-one is cheating on the diet!) and a 2nd Endo has taken place to review your initial biopsy and 2nd one Drs will then look what could be causing your problems.

The BSG Guide defines Refractory Coeliac Disease as:

"Clinical diagnosis:

Refractory coeliac disease has been defined in those who, despite a strict gluten-free diet, have continued clinical manifestations that are associated with marked histological abnormalities (Marsh III) after one year. One year is an arbitrary period to reflect the slow histological recovery seen in many patients, although clearly the clinical picture needs to be considered. Weight loss, low albumin, severe diarrhoea and disproportionate anaemia warrant expeditious investigation."

i.e. after 2nd endo biopsies reveal significant damage still (as per the Marsh Scale).

*this is why a 2nd endo can be so important if you continue to have problems despite going GF. Only a 2nd biopsy can help compare and contrast with your first results to assess healing internally or continued damage.

"Histological diagnosis:

Individuals with refractory coeliac disease often have an abnormal population of intra-epithelial lymphocytes detectable in their small bowel mucosa and sometimes elsewhere in their gastrointestinal tract. In active coeliac disease, intra-epithelial lymphocytes are predominantly CD8+ and express surface CD3, a universal lymphocyte marker, together with polyclonal T cell receptors. In a study of refractory patients 84% were found to have an abnormal population of intra-epithelial lymphocytes, which are CD103+, CD8- and CD4- and without surface CD3-TCR complexes, although CD3 is found intracellularly (133). In addition the majority of these can be shown to have a clonal TCR-? gene rearrangement, detectable by PCR analysis of biopsy specimens. The presence of this aberrant T cell phenotype has been termed Type II refractory coeliac disease with the minority without these cells denoted Type I."

Plus..

"If an individual is suspected as having refractory coeliac disease, it is recommended that additional immunohistochemistry analysis is performed to look for abnormal IEL population and TCR gene rearrangements as this will predict the increased risk of lymphoma. This IEL population can be found diffusely in the gastrointestinal tract and standard biopsy from the duodenum is likely to be sufficient. A formalin fixed, paraffin-embedded sample is satisfactory for staining and PCR analysis."

i.e. Normally the 2nd biopsy will also show other problems in bowel make up (as described above). Depending on results this is then classed as type 1 or type 2 refractory disease. The immunochemistry should be analyzed by your gastro team.

Note: There are some other conditions which can mimic refractory Coeliac Disease

eg "A final group of conditions which may be confused with refractory coeliac disease are immunodeficiency states. These include combined variable immunodeficiency, hypogammaglobulinaemia and human immunodeficiency virus infection. Absence of IgG or IgM and low CD4 counts predispose the small bowel to recurrent infections, which present with weight loss, diarrhoea and villous atrophy."

There appears to be great debate in the Gastro world as to whether Refractory CD is given as a diagnosis to easily without looking for other causes of problems (eg other intolerance, tropical bugs, or just plain old cross contamination!),

"For example in one study of 55 patients labelled to have refractory coeliac disease in all but 9 patients an identifiable alternative cause for continued symptoms diagnosis was found – in most cases inadvertent gluten intake."

It appears that the BSG guide recommends the typical treatment for confirmed Refractory Disease as a mix of nutrition, GF diet and steroids...

"Patients with weight loss and impaired absorption have been given parenteral nutrition and this can reverse the catabolic state of refractory patients. Anecdotally, the use of steroids has been reported to induce clinical remission."

Plus...

"There are several case series reporting histological and symptomatic recovery with oral prednisolone and this is often tried in the first instance. No controlled trials exist and no universal dose regimen has been adopted. As treatment is likely to be prolonged, a low-moderate dose is suggested by some 10mg/daily (135). Mucosal recovery and symptomatic progress should be monitored because if treatment is not successful steroids should be withdrawn. Azathioprine has been used in conjunction with prednisolone to provide long-term immunosuppression as a logical steroid sparing agent. One case series using prednisolone, followed by 2mg/kg azathioprine for one year, reported improvement in 8 out of 10 Type I refractory coeliac patients but no improvement in 8 patients with type II disease..."

Other cases show..

"Cyclosporin has also been used and one pilot study treated 13 patients with standard immunosuppressive doses (serum range 100-200 mg/ml) for 12 months ( (138). Eight out of 13 improved histologically and 2 further showed a clinical improvement with no serious adverse effects. In 5/13 villous architecture returned to normal. In all these studies there is no long-term follow up and late relapse has been reported when therapy is withdrawn."

SPEED READ:

The long and short of the BSG guidance is that patients who are suspected of having refractory CD (ie after poor diet, other intolerances having been excluded as the cause) are...

"Due to the complex nature in such cases, it is recommended that patients thought to have refractory coeliac disease should be referred to a specialist centre for further investigation and treatment."

TELL US:

What your experience has been?

[Hidden in reply to FionaGFG]

"For example in one study of 55 patients labelled to have refractory coeliac disease in all but 9 patients an identifiable alternative cause for continued symptoms diagnosis was found – in most cases inadvertent gluten intake."

"In most cases inadvertent gluten intake". Would this also include gluten contained in the "Gluten-free diet" ie 200ppm if weight loss etc was not an issue?

[Dona]

I have Type 1 refractory CD, i have known for a year, its been very hard, I have to travel to sheffield from runcorn to see a professor sanders, as there was no one local enough to know about type 1 as i was diagnosed with type 2, at present am on mercapturprine, a chemo medication, if this doesnt work i could have less than 2 years, as a mum with 2 young children this is causing heartache, i have 3 monthly check ups, bloods every 2 weeks, i still feel sick, bloating, tiredness is a big one, and am awaiting the results of a full bone scan. There is not alot of information on this or people with the condition

[Jacks in reply to Dona]

Hi Dona, I really am so sorry to hear about your diagnosis. I have read a few articles by Dr Joseph A Murray, who seems to be the RCD expert. He links most cases of RCD to still ingesting gluten accidentally or within the gf diet (as in too much gf food), to being older at diagnosis, having malnutrition or to additionally having crohns disease. He has indicated the importance of additional nutritional supplementation (intravenously). If you do a websearch you'll see the journal papers. ps I'm also under DS.

[Dona]

thanks jacks, just come out of hospital after collapsing in sunday its now tues, i will look into this, have to go to sheffiled next week as warrington hospital couldnt really help except for strong painkillers and get me comfortable til then, the DS is a lovely person who nos wot he is talking about, he did say if hes lucky one a year passes him with RCD