What do you make of this??

My son (8) has had symptoms for almost 3 years now (diarrhea, mucous (no blood), frequency/urgency). Started w/ the stomach flu that never went away. Fast forward to now, 3 colonoscopies, 2 upper endo's, CT scans, multiple drugs, and I can't count how many blood/stool samples, we are still working towards remission. Only family history of bowel disease is me, celiac (he's been negative 5 times over for this- I wish it was that easy!).

Long story short, his most recent colonoscopy showed a high eosinophil count in his ascending colon (among many other things). Yesterday at our f/up appt. his Dr. who has yet to confirm a dx (he has said lymphocytic colitis or indeterminate colitis until he gets a clearer picture) doesn't seem to think much of the high eosinophils. He mentioned he could be trending towards Crohn's yesterday. Are eosinophils and Crohn's linked?

He seems less inclined to point towards the pathologist (below) for things like eosinophilic enterocolitis.

Here is his pathology report. Please let me know your thoughts.
Microscopic Description
(A) 1 slide H&E:
The fragments of duodenal mucosa demonstrate mild blunted villous
architecture. The lamina propria cellularity is mildly increased by
lymphocytes and plasma cells. The epithelial lesions are absent. There is
a mild increase in surface intraepithelial lymphocytes.

(B) 1 slide H&E:
The gastric antral and fundic glandular architecture is preserved. There
are no epithelial lesions. The lamina propria contains the usual
cellularity. Microorganisms are not seen.

(C) 1 slide H&E:
The fragments of esophageal mucosa show mild expansion of the basal layer
and mild expansion of the vascular papillae and patchy increase in
lymphocytes.

(D) 1 slide H&E:
The fragments of ileal mucosa demonstrate partially blunted villous
architecture. The lamina propria cellularity is nonuniformly increased by
lymphocytes, plasma cells and occasional neutrophils. Cryptitis and crypt
abscesses are present. Granulomas are absent. Neutrophils infiltrate the
surface mucosa.

(E) 1 slide H&E:
The fragments of colonic mucosa demonstrate occasional elongated crypts.
There are increased surface and crypt intraepithelial lymphocytes. The
lamina propria cellularity is increased by lymphocytes, plasma cells, and
eosinophils. Focally there are up to 78 eosinophils in a high power
field. Prominent lymphoid aggregates are present. Cryptitis and crypt
abscesses are absent.

(F) 1 slide H&E:
The fragments of colonic mucosa demonstrate foci of elongated crypts. The
lamina propria cellularity is increased by lymphocytes, plasma cells and
eosinophils. Lymphocytes infiltrate the surface epithelium and crypts.
Granulomas are absent. Cryptitis and crypt abscesses are absent.

(G) 1 slide H&E:
Sections demonstrate colonic mucosa with occasional fragments demonstrating elongated and irregular dilated crypts. The lamina propria cellularity is nonuniformly mildly increased by lymphocytes, plasma cells and eosinophils. Lymphocytes infiltrate crypts and surface epithelium. Lymphoid aggregates are present.

Comment
The presence of increased intraepithelial lymphocytes within the surface
epithelium and in the crypts along with architectural changes raises the
possibility of an autoimmune enterocolitis. Other differentials include
inflammatory bowel disease.

Diagnosis
(A) GI biopsy, duodenal bulb/duodenum 3rd:
Chronic duodenitis.
(B) GI biopsy, body/antrum:
No diagnostic abnormality.
(C) GI biopsy, distal esophagus:
Chronic esophagitis.
(D) GI biopsy, terminal ileum:
Chronic ileitis and focal mucositis, see comment.
(E) GI biopsy, ascending colon/cecum:
Chronic colitis with increased mucosal eosinophils, see
comment.
(F) GI biopsy, descending colon/transverse colon:
Chronic colitis, see comment.
(G) GI biopsy, rectum/sigmoid:
Chronic colitis, see comment.


We just started Imuran. Steroids have only helped slighty. He's currently on 20mg prednisone and a gluten-free diet. The diet has really helped him actually have some days of normalcy! Hoping to wean him off steroids soon (we've been on/off for 6 months) and the Imuran work! Pentasa did nothing for him (I think it made him worse). Omega fatty acids seems to be helping, too.

Thanks!!

Sorry to hear about your son. Such a hard age.:frown:
My knowledge is still very limited about medical terminology but I know more will be along to answer that question. DustyKat or Tesscorm would be good at that. Perhaps David also.

I hope you get all this sorted out and get your boy on the road to recovery.:thumleft:

Sorry to hear your son has been suffering for so long. Frustrating not being able to get a clear diagnosis (not that treating Crohn's makes anything simple). Just wanted to send my best - hope the Imuran works for him!

Since your in Kentucky have you had his slide read by cchmc( Cincy children's)
They have one of the top programs in the country for eosinophilic disorders.
There is a week long program in the Cincinnati center for eisinophilic disorders ran by Dr. Putnam . They are adding another Gi soon.
EC is an allergic disorder of the gut so you could find his trigger foods and eliminate them .
Most of kids get a clear scope when the top eight allergens ( milk, egg, wheat, fish, shellfish, soy, peanut, and tree nut) are removed from the diet.
Once the scope is clean then you can trial ( up to three weeks per food) to determine which is his trigger.
Here is a link to apfed

Also kids with food allergies which has a support forum on egids disorders .


I would cchmc has a year wait for their cced program . It is suppose to decrease to 2 months once they get the second doc.
But they will do a re read of the slides at least for you.
En won't help unless your child is on an amino acid based formula such as
Neocate -- e028 splash , neocate jr.
Elecare
Here is that link


Hugs

http://apfed.org/drupal/drupal/Treatment of EGIDs

KFA link
http://community.kidswithfoodallergies.org/displayForum/forum/eosinophilic_disorders

Neocate / elecare amino acid formula link

https://www.neocate.com/shop/c-6-nutricia-category.aspx
http://m.elecare.com/who-helps

Cced info link
http://www.cincinnatichildrens.org/...sorders&utm_medium=shortcut&utm_campaign=cced

Keeping in mind I am still very much learning about the histopathology side of things, based upon the report, I'd say Lymphocytic Colitis and Celiac Disease (the two commonly run together). I realize Celiac was ruled out 5 times, but I assume that was via serology tests? By the way, Celiac is a form of autoimmune enteropathy.

Paging Aussie for another opinion

I just want to welcome you to the forum. But I am so sorry your little boy has been struggling for so long! I'm sorry I really can't add to what MLP and David have already said but, hopefully, Dusty will be along to share her thoughts.

I hope you do see some relief for your son with the IMuran. :ghug:

Have you had him gene tested for celiac disease. My understanding is that there are two genes involved. The gene test can be used to rule out celiac disease.

My little penguin kind of beat me to it.

Where are you having all this done? It sounds as if you have been to more than one place but don't say anything about where you've gone.

Pathology is something of an art form and having the biopsies read by another pathologist, preferably at a high powered program like Cinncy or CHOP or Mayo or Chicago may provide different answers.

And to some extent what works to control the symptoms should inform the diagnosis I would think.

I'm glad dietary changes are helping. Hugs and hopes that you find answers soon.

Thanks guys! We take him to Cincy Childrens and we've been there a little over a year. We don't go to Dr. Putnam, but his GI had his slides reviewed by the IBD panel there on his last scope. Their advice was to treat it like you would IBD and it's still too soon to make a final dx.
My GI is strongly against this being celiac. I'm very familiar with it, not only having the disease myself, but being in the medical field directly working with the IBD and celiac testing, and also being an active member of the celiac society here. I know there is some blunting on his scope, but that can also be linked to IBD and not just celiac. He's been serology tested 3 times (all negative, all normal IgA), upper GI scoped twice with no add'l signs of celiac. He does carry the gene, same as myself. However, he's been GF for a while and although it seems to be an easier diet for him, it by no means "cleared up" like a person with celiac would by eliminating gluten. I've had this discussion so many times with his GI (and he's a wonderfully patient person!) but I don't think he can tell me he doesn't have celiac any different way without shaking it into my head! LOL!
I also suggested EG or Eosinophilic Enterocolitis (since the upper is involved) ,and even mastocytic colitis, and he said those are 1) rarities, and 2) still too soon to make any final dx, and 3) he'd treat them the same way as what he's doing currently with his therapy. I hear him say it looks more like Crohn's but for now he's keeping him in the "lymphocytic colitis/indeterminate colitis" bucket.

Have any of you or your children had high eosinophils on your path report? I have read this can be linked to CD, but I also see all the other diseases listed that have more Eosinophil involvment.

I would LOVE for this to be something simple like food elimination. So frustrating!

mylittlepenguin-can my GI just refer me over to the CCHMC CCED program? I just wonder why he hasn't already done that if he thought it was an eosinophilic disorder?

Hunter, did his previous two scopes have results from the duodenal bulb consistent with this latest scope?

HLA studies have shown an increased incidence of HLA A1, DQ2 and DQ1, and DQ3 in Lymphocytic Colitis patients. Increased eosinophils can also be associated with Lymphocytic Colitis. However, here is an excellent paper on eosinophils in IBD if you're interested.

I've also attached a pathology cheat sheet from a pathologist that I use. See below.

Thanks for the info!
His first scope was an upper endo and colonoscopy. The upper showed "no diagnostic abnormalites" in his path report. His second scope, they only did a colonscopy. We requested an upper during his third scope to make sure we could rule out celiac and that's when we found some of the changes noted in his pathology report in the upper. So no duodenal involvment previously, but his first upper scope was only 3-4 months after his symptoms appeared so it likely wouldn't have shown anything b/c it was too soon for any major damage to have occurred? That's my theory at least....

In addition to his pathology history the following labs have been "abnormal":

Elevated fecal calprotectin (270; ref range is 0-50)
Slightly low ALT
High SEGS/Low Lymphs in his latest Differential (CBC) (Could be related to being on steroids)
CT Enterography: mid jejunal bowel loops may have slightly thickened walls
Slightly elevated RBC's
High BUN/Creatinine ratio
Slightly elevated chromogranin A (they don't think much of this one)

I asked because Celiac can be patchy on the duodenal bulb and can be missed if multiple biopsies aren't taken. Does your GI feel it's the most recent scope that rules out Celiac? Or the negative serology?

As for your theory, I guess it would depend upon the actual cause. Did the disease cause the damage which led to the symptoms or did the disease cause the symptoms which led to the damage.

Fecal Calprotectin can be increased in Microscopic Colitis. As well as other IBD of course.

I think he's ruled out celiac from multiple negative serologies, and the lower bowel involvement (which happened first before the upper stuff started appearing). No scalloping, sprue, etc noted. Also, GF diet has not eliminated symptoms (and GF diet only after serology/scoping of course). I think the ileum involvement is also another factor that seems to point towards IBD with upper involvement?
How I wish this was celiac! I guess I can keep hoping for that!!!

My theory (emphasize theory) is Celiac AND LC. The LC would explain the lower bowel and the Celiac would explain the upper. A gluten free diet in such a case would result in improvements because of the Celiac but not complete alleviation of symptoms because of the LC and obviously you need the villi to heal. Some more reading for you:

http://www.practicalgastro.com/pdf/September08/DickeyArticle.pdf - Celiac and MC and the colon

http://www.ncbi.nlm.nih.gov/pubmed/15370688 - Celiac and the terminal ileum

http://www.ncbi.nlm.nih.gov/pubmed/12591963 - The terminal ileum and microscopic colitis

Frankly, I'm praying for Celiac and/or LC. While LC sucks (it's what I have) I'll take it any day over Crohn's.

David, I would love for you to be right! I've said this very same thing to his GI many many times. How do you explain negative celiac serology with a normal IgA level? His ttg, EMA, deamidated AGA IgA and IgG were all normal. Do you have any info on this?

Thanks again for all your insight and advice! More to bring up on our next appt.

It sounds like you're working with some great doctors. Remember, I'm just some guy on the internet who is compulsive about reading everything he can.

There's a reason endoscopic biopsy is still the gold standard. While the serology tests are quite good, they're still imperfect:

However, incomplete concordance between EmA and tTGA positivity means that combination screening with both assays offers higher sensitivity, as almost a third of patients have only one antibody. As some coeliac patients with normal serum IgA are negative for both antibodies, biopsies should still be performed in seronegative individuals deemed at high risk for coeliac disease.

Click to expand...

http://www.ncbi.nlm.nih.gov/pubmed/11346205

A number of serologic tests are available commercially for identifying individuals who require an intestinal biopsy examination to diagnose celiac disease (CD). The aim of this study was to determine which test, or combination of tests, was most sensitive and specific for this purpose. We performed a literature review of studies that determined the sensitivity and specificity of serologic tests for CD. Studies that compared biopsy examination-confirmed cases of CD with controls with normal intestinal histology were selected for analysis. Sensitivities and specificities for the antigliadin tests were highly variable. Immunoglobulin (Ig)G-based antigliadin (AGA) tests generally were poor in both parameters whereas the IgA-based test was poorly sensitive but more specific. The IgA endomysium (EMA-IgA) and tissue transglutaminase (TTG-IgA) tests were both highly sensitive and specific with values for both parameters exceeding 95% in most studies. There were no identifiable differences between adults and children with respect to these tests. There was no evidence that a combination of tests was better than a single test using either the EMA IgA or TTG IgA. Either the EMA-IgA or TTG-IgA test is most useful for identifying individuals with CD. The variability and generally lower accuracy associated with the AGA tests make them unsuitable for screening purposes. There is no advantage to using a panel of tests as opposed to a single test. Because these data were obtained largely from studies conducted in a research setting, it is possible the tests will be less accurate when used in the clinical setting.

Click to expand...

http://www.ncbi.nlm.nih.gov/pubmed/15825123

Antibodies to gluten are mostly secreted in the intestines rather than the blood. As a result, some believe in this line of testing though you won't find many doctors (other than the doctor who developed it) who will back it yet.

Thanks David. I, too, am just that same person reading everything I can! I don't hold you accountable, but I sincerely appreciate your advice!

We are working with a great doctor, but I work with a great many doctors and they certainly all don't know everything. It's definitely an art, not a science.

Have you read up on deamidated gliaden vs. your old standard gluten antibodies? They are far more accurate, although still not widely accepted just yet, so I hear.

I suppose in the end, his GI seems less concerned about what "it" actually is, and more concerned with treating "it" since he'd likely use the same weapons to combat his disease. I added in the GF diet- he's not too into the whole "diet" aspect of IBD. That's more my thing on my own. He's more convinced it's not the "gluten" per se, but that it's a healthier less processed diet. Either way, he's still on it, and still with some sypmtoms. But I concur that with LC he could still have issues, if that's the case!

I'm more concerned with what his dx is. I guess that's my way of trying to control the situation in a highly uncontrollable environment. So frustrating.

Thanks again and I've read most of your links! Very helpful!

hunter6009 said:

Have you read up on deamidated gliaden vs. your old standard gluten antibodies? They are far more accurate, although still not widely accepted just yet, so I hear.

Click to expand...

I have not. I'll put that on my list. Thanks!

Wanted to offer hugs.
Sometimes it just takes a while to find the right med to treat the Ibd.
It took a year for DS and we tried them all until remicade started to work.
DS has/ had inflammation from end to end,
Mild esophagitis
Duodenitis with blunting
Gastritis
Ileitis with granulomas
Ceacum granulomas
Proctitis

We saw three different gi's at two different hospitals
Had 2 ct scans and 3 scopes and one mre.
So I understand your frustration
Tested 3 or more times for Celiac
Went gluten free corn free etc...
Diet helped some but was not enough.
Lowering fiber helped more which we were doing by default with no gluten .
We even had his biopsy slides read
For mastocystic entercolitis etc....
In the end he has crohn's which needed remicade.
Pred by itself and 6-mp EEN etc.. were just not enough.

If your slides were read at Cincy then they are probably spot on.
Cced only takes you as a patient if there is a question of whether you have egid or not or if you have already been dx
You can self refer we did.
If gluten free helps some I would ask your Gi about EEN
It may help more .
Hope he gets some relief soon.

Hi Hunter and David,

Sounds like a tricky case. When there are a number of possible diagnoses, worth looking at which ones would explain the majority of the abnormal findings.

Elevated calprotectin - would expect elevation with any intestinal inflammation, so doesn't help differentiate between IBD/microscopic colitis/eosinophilic enterocolitis.

Chronic diarrhoea - could be seen with Coeliac and any of the others listed above. Although you would expect a worsening of symptoms with gluten exposure in coeliac, also, a watery diarrhoea with microscopic colitis.

Inflammation in small bowel with architectural change - Crohns, Coeliac, and Eosinophilic enteritis.

Inflammation in the colon - Crohns, Eosinophilic colitis, microscopic colitis. Although the changes to the villus structure would favor Crohns.

CT showing thickening of a section of small bowel - Crohns.

My gut feeling is that you're dealing with Crohn's disease, as it explains all the findings, your son would fit the age group.

A few quick questions: what did the mucosa look like on the colonoscopy, was it inflammed or did it look completely normal? Also, when the small bowel biopsies were taken looking for coeliac, was your son on a gluten free diet at the time? Does your son have allergic symptoms (ie. allergies, hayfever, etc.) or perhaps extra intestinal manifestations of Crohns (typical skin rash, joint pains, mouth ulcers, iritis)? Does he have a peripheral blood eosinophilic or is he perhaps ASCA positive?

These might help with sorting out the diagnosis.

Best wishes.

Unfortunately you can have more than one thing going on.
I know of one kiddo with both EC / EoE and Ibd .

Aussie said:

Hi Hunter and David,


A few quick questions: what did the mucosa look like on the colonoscopy, was it inflammed or did it look completely normal? Also, when the small bowel biopsies were taken looking for coeliac, was your son on a gluten free diet at the time? Does your son have allergic symptoms (ie. allergies, hayfever, etc.) or perhaps extra intestinal manifestations of Crohns (typical skin rash, joint pains, mouth ulcers, iritis)? Does he have a peripheral blood eosinophilic or is he perhaps ASCA positive?

These might help with sorting out the diagnosis.

Best wishes.

Click to expand...

Hi Aussie! Thanks for some insight! To answer your questions:
His most recent colonoscopy his GI stated parts of his colon looked like it had granularity (and maybe friable? But I've read so much I may be dreaming this...). I know for sure he said increased granularity from just visually looking at it. Otherwise he didn't note too many other signs from just looking at it.
He was not on GF diet when biopsies were taken or when he had his serology testing. I am very familiar with the tests for celiac so I understand that those won't show positive without ingesting gluten for a time. He's just recently went GF (scope was 9/18; GF diet started roughly 9/21). It's helped, but certainly not cleared it up like it did for me (I'm a celiac). His GI doesn't feel this is celiac disease.
My son has in the past had some allergic symptoms, but since we live in the allergy capitol of the world (not kidding) most people here do. He's had Restrictive Airway Disorder (step before asthma), and typical allergies. Some eczema as a baby, but runs in the family. Also GERD as an infant. Age, and likely also with the help of his steroids and he's been free of those symptoms for almost 2 years.
As for other manifestations of Crohn's- he's had maybe 2 mouth ulcers in his life (one just recently after his upper scope on his bottom lip). Joint pain, some. They diagnosed his with synovitis in his knee a few years ago but linked it to a viral infection. He has had some (maybe complained for a period of 1 week, on 3-4 seperate occassions in the last 3 years) that his hip or same knee has hurt. Hard to differentiate between sports "injuries"(soccer/cross country), growing pains, or actual joint pain related to autoimmune disease.
I don't believe he's been tested for peripheral blood eosinophilia. Can you tell me more info on this test?
ASCA negative, but that was also done at the very beginning of when his symptoms appeared almost 3 years ago. I requested this test, not the physician we use to see. I don't think he even knew what it was.

Sorry I am late to this hunter...:hug:

I am so very sorry to hear of all your boy is going through and the difficulty you are having in getting a diagnosis.

You have received fab advice so the only things I can add is to say...

The thickened bowel loops jumped out at me. Has an Enterograph or pill cam been suggested to you as a way of better visualising the apparent abnormality in the small bowel?

I was just about to ask if he had EIM's but I realise now that you have covered that. What is happening with his growth and weight?

Do you keep a diary to track his symptoms?
Wiki diary suggestions

Dusty. xxx

DustyKat-
The CT was actually at CT Enterograph. Mostly normal, just maybe mild thickening, but it also said it could be distortion of the picture? Apparently it was fairly minimal.

Ah, okay.

Hi Hunter, eosinophils are a type of white blood cell, it should be on a Full Blood Count (I think this is called a CBC in the US). You will commonly see an elevation in the amount of eosinophils in the blood (ie. Peripheral eosinophilia) with eosinophilic gastroenteritis.

Best wishes.

Hi all ~ I'm so interested while reading your posts. My son is 12 and has been "kind of" diagnosed with EGE, EC and CD. I'm totally confused at this point. The original colonoscopy and endo showed and eos count in his stomach of 150+ and also found eos in his colon and bowel. So he was diagnosed with EGE. A second review of his slides, different slides, showed granulomas which led to an Upper GI with small bowel follow through test. His small intestine / ileum was so inflamed the barium barely trickled through. This led to a "kind of " diagnosis of CD. The following week we did the MRE which was normal and his Promethius test for IBD was negative. So now I'm not sure if he has EGE, EC or CD or one or all 3. Can one of you look at my test results if I post them for you? Thanks so much!!

You can have both unfortunately.
EC ege are allergic disorders triggered by foods .
Typically mixed ( IgE and non igE)
Have you looked at apfed and KFA
Both have good info on egids

Here are the link:
http://apfed.org/drupal/drupal/index.php

http://community.kidswithfoodallergies.org/displayForum/forum/eosinophilic_disorders


As far as normal mre - DS has that here plus normal everything else except biopsies results.

So you can have cd and have lots of normal tests.
Two good places for second egid opinions would be cchmc or national Jewish

For pediatric Ibd
There is a list of good centers on improvecarenow.org
https://improvecarenow.org/about/who-we-are


Since your son has more than the average Ibd kid going on I would suggest a second opinion at one of these
Top ones are
Bch
Chop
Cchmc

Good luck