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Anti-TNFs associated with eosinophilic esophagitis

my little penguin

Moderator
Staff member
Eosinophilic disease has been discussed for years as a possible precursor for IBD in kids
EoE is difficult to dx due the random patches of eosinophils in the esophagus.
So which came first chicken or egg
Just as arthritis /psoriasis are linked to ibd due to genetics
Not surprised to see it found in kids with ibd since eosinophils are response to inflammation in the body and probably have a genetic link as well
As far as anti tnf , this is known that anti tnf and other biologics do not cause additional disease burden … but can unmask a disease that would happen anyways just faster .

kiddie ibd needs to be studied more to determine cause .
There are only 2-3 veo ibd clinics in the entire country studying why such young kids get this disease and why it behaves differently in them
More needs done
 

my little penguin

Moderator
Staff member
Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are immune-mediated diseases with some potential intersections in pathogenesis and epidemiology. In a longitudinal analysis of insurance claims data from over 130 million U.S. patients, investigators found a threefold to fivefold increased risk for EoE in patients with Crohn disease or ulcerative colitis compared with individuals without either disease. There was also a threefold to sixfold increased risk for IBD in patients with known EoE compared with individuals without EoE. IBD complications were slightly more common in patients with concurrent EoE, while conversely, patients with EoE were less likely to have complications if they had concurrent IBD. The latter might be explained by the use of immunomodulators (including steroids) in patients with IBD, which would also suppress eosinophils in the esophagus.
 

my little penguin

Moderator
Staff member
Abstract
Background: The overlap between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) has not been extensively examined. We aimed to assess the prevalence of esophageal eosinophilia in patients with IBD. Methods: We conducted a retrospective cohort study using diagnostic codes to identify adults with EoE and IBD between 2008 and 2016 at a tertiary care center. Electronic medical records were reviewed to extract clinical, endoscopic, and treatment data. Patients with esophageal eosinophilia and IBD were compared to EoE cases without IBD. Results: Of 621 EoE patients and 4,814 IBD patients identified, 35 had a code for both diseases and 12 were confirmed to have overlapping IBD and esophageal eosinophilia. The prevalence of esophageal eosinophilia in IBD was 12/4814 (0.25%), and the prevalence of confirmed EoE in IBD was 5/4,814 (0.10%). There were no substantial clinical, endoscopic, or histologic differences between EoE patients with and without IBD. IBD was diagnosed before esophageal eosinophilia 92% of the time, with an average time between diagnoses of 9.6 years. Of the IBD patients, 71% were started on biologic anti-tumor necrosis factor-α therapy an average of 7.6 years prior to developing esophageal eosinophilia. Conclusions: The prevalence of esophageal eosinophilia in IBD is 5 times higher than expected in the general population (0.25 vs. 0.05%) and EoE in IBD is 2 times higher than expected (0.10 vs. 0.05%). Upper gastrointestinal (GI) symptoms in patients with IBD should merit evaluation not only for upper GI Crohn’s disease, but also for esophageal eosinophilia.

© 2019 S. Karger AG, Basel
 
I can tell you that I have personally seen eosinophilic esophagitis caused by anti-TNF medication. MLP, this is a real side-effect.
 

Maya142

Moderator
Staff member
It could be or perhaps it was already present? Such as arthritis and Crohn's - the type of arthritis my daughter shares genes associated with Crohn's. Which came first? In her case, the arthritis appears to have, though we can track GI symptoms from a younger age than arthritis symptoms. Did her meds cause the Crohn's or did the Crohn's appear only once she was on an anti-TNF that did not treat Crohn's because her earlier anti-TNF was treating the Crohn's (she was initially on Humira which obviously does treat Crohn's but later switched to an anti-TNF that does not work for IBD)? We simply just do not know. There is a lot of research suggesting that her type of arthritis starts in the gut. Interestingly, her older sister has (so far) not developed Crohn's although she has been on biologics that do treat IBD and some that do not.

I know paradoxical psoriasis has also been looked at similarly - in fact, there are parents on this forum with kids whose psoriasis was thought to be paradoxical but did not go away when they stopped anti-TNFs.

I would caution against just using anecdotal reports to say it's a real side effect - some studies suggest it could be, while others suggest it's a precursor to Crohn's. They are all very interesting papers but I think we just don't know enough yet.
 

crohnsinct

Well-known member
Yep! O's dermatologist is now saying she had a little psoriasis before she was even diagnosed with Crohn's and continues to have it even though we technically withdrew all anti tnf's (have since added in Humira) so the diagnosis is now just psoriasis as opposed to paradoxical psoriasis. She also explained that dermatologists are moving away from blaming the anti tnf because auto immune diseases tend to travel in pairs anyway.

For us it doesn't much matter. Even if we were warned that Remicade might cause psoriasis even the ridiculously severe and horrible psoriasis that O has, we probably still would've grabbed it because her colon was chop meat. IDK anything about EOE so can't say the same would hold true.
 

crohnsinct

Well-known member
Hmmm just read the paper and all they are saying is there is an association. Ummm o.k.. Hang out here long enough and we could have told you that. We could tell you all the associations.

They happen to mention anti tnf use and don't say it caused it but that it warrants further study. That's fine and a fair statement but the population is skewed to include patients on anti tnf's because they studied pediatric patients and let's face it most kids with IBD are placed on biologics at dx because of disease severity, the desire to control disease quickly and thereby change the disease course and growth. Further the first line biologics that pediatric GI's use are the anti tnf's because they have been around longer and they know more about them. Although I am seeing a trend toward Stelara and Entyvio lately do to their gut selectivity.
 

my little penguin

Moderator
Staff member
So your kiddo developed EoE while on remicade and nothing but amino acid based formula ?
Or was the formula polymeric ?
They thought my kiddo had EoE prior to crohns dx
Normally EoE is treated with elemental only formula in kids -this gives a clean scope
Then they add in one food at a time scoping every 3 months till you get enough of a diet
Or older kids use a slurry of buesonide /swallowed Flovent to coat the esophagus letting them eat the offending foods

so to find eosinophils on a scope while on amino acid based formula only is extremely rare
Did they find it after reintroducing foods ?
Stopping steriods ?
Polymeric formula ?
No history of food allergies ?
Food allergies and EoE tend to go hand in hand with a mix of both .

some kiddos who had done slit therapy for food allergies (controversial years ago) later developed EoE to other foods after they could tolerate their food allergen .

my kiddo was dx with a acute febrile neutrophilic dermatosis (Sweets Syndrome-auto inflammatory) while in humira and methotrexate-both can be used to treat it .
But he had symptoms since he was a toddler they just got worse as he got older .
Arthritis was dx while on humira but he had symptoms of arthritis in his hands at a very early age -we didn’t recognize it at the time .

as I said before
Larger studies need done on ibd kiddos
Especially veo ibd kiddos since so much is unknown
 

my little penguin

Moderator
Staff member
Places for support


Top notch place in the country
 
It cleared up a few months after stopping the anti-TNF, no long-term problem. Who knows if it would have become a long-term problem if he'd continued on infliximab despite the esophagitis. The fact that the study in the OP found a connection is no surprise to me--I just appreciate seeing that others have also noticed this connection.
 

my little penguin

Moderator
Staff member
So trying to understand this
Your child was dx with EoE by your Gi while on remicade
Did the Gi treat the EoE ? What was the recommended treatment ?

You stopped remicade and his scope was clean -
While eating a full diet of solid foods not limiting any of the top eight allergens or beef for more than 12 weeks and not on formula at all ??

I thought your child switched back to formula only and /or Steriods when remicade was stopped prior to surgery to remove part of his intestine - And before you started stelara..
Isn’t he on formula (een) only plus Stelara now ?


if he is eating a full diet without restrictions and on Stelara with no signs of Eos on scopes
That is is incredible
I would be cautiously happy if it cleared while on Stelara but still on een . Since een is a treatment for EoE .

tagging @jadegreen since her kiddo deals with EGID (not crohns )
 
This was all two years ago. Remicade caused esophagitis despite full EEN. The esophagitis was not treated separately, but it did go away several weeks after the next dose of Remicade was due.

I believe the association of anti-TNFs with EOE has not been studied before, and the paper in the OP is the first time it's been noticed.
 

my little penguin

Moderator
Staff member
So did the Gi dx your child with eosinophilic eosphagitis? Or was only eosphagitis found on the scope?

there is a big difference-

EoE require a specific number of eos to be found per high power field to be dx and once found you have for life similar to arthritis and crohns.

Eosphagitis on the other hand simple can be caused by reflux from formula, crohns or other things . This can go away.

second the type of formula used for een is critical in EoE.
Was your child on amino acid based formula such as neocate jr, neocate splash or elecare jr (main ones available in the US) at the time the EoE was dx ?
What specific brand of formula was your child on?

Formula with intact protein structures such as peptamen jr ,peptide, Kate farms , boost ,orgain ,pediasure are no different than solid food in EoE even if it’s een. The body is attacking the protein structure in the food similar to an allergic reaction which is why so many eosinophils are produced. It’s also why it’s found in kids with food /pollen allergies more often. Their bloodwork tends to show high eosinophils as well when reacting.
 
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MLP, what's your point? Are you trying to claim that anti-TNFs do not ever cause eosinophilic esophagitis? I specifically saw this happen.
 

my little penguin

Moderator
Staff member
I only asked two simply questions which are important
1.) Was your child dx with eosinophilic esophagitis by your Gi ?

It’s just a yes or no answer

2.) And was your child on elemental formula at the time of dx ?

Again yes or no answer

if both are yes and your child was able to reverse EoE that is a huge and needs to be submitted as a case study by your Gi

In 14 plus years of dealing with parents of kids who have EoE
None have eliminated the disease regardless of cause .
Many treated and got remission through steriods or elemental formula /diet restriction
But none eliminated it

that is why it’s important to know

whether anti tnf cause an increased risk of EoE is for a much larger case study

But to eliminate the disease once dx is unheard of
 

my little penguin

Moderator
Staff member
This can be extremely helpful to know the answers for other parents/kids on other forums
Every little bit helps these EoE kids and adults
To understand the disease better
 
Ok, I'll break it down for you:

Remicade caused esophagitis (certainty: 100%. Esophagitis was obvious due to symptoms, and causation was obvious due to timing and repetition.)

I believe the esophagitis was eosinophilic in nature due to other allergy activation (eyes, nose) caused by the Remicade at the time and due to high eosinophils in the blood. It is known that Remicade causes this kind of heightened allergic state in some people. No further investigation was performed.

Obviously if a drug induces allergic overreactions and the drug is stopped, it shouldn't be a surprise that the drug-induced eosinophilic esophagitis would stop when the drug is stopped in many cases.

(he was on polymeric EEN at the time)
 

Maya142

Moderator
Staff member
I think what MLP is getting is that esophagitis is just inflammation in the esophagus. My daughter has had that show up on scopes - due to reflux. It could also be due to Crohn's in some cases. Eosinophilic esophagitis is a specific type of esophagitis. The key is what biopsies show. If it's eosinophilic esophagitis, then a certain number of eosinophils need to be seen on BIOPSY - there are both endoscopic and histologic criteria for diagnosis. High eosinophils in blood work are not part of the criteria that I have ever seen. If you have seen other criteria, then feel free to post them.

It is important to post accurate information on forums, particularly since new parents come here for guidance. Since there are very few med options for children with IBD, it's especially important to post accurate info about meds, since trying them is a scary step for most parents. In the 8+ years I've been on the forum, I can't think of a single child whose disease was controlled without meds, except for one. So it's really very important to back up what you say.

That is why we are trying to understand what you're saying. To me, so far it appears that his biopsies did not show eosinophilic esophagitis based on what you have said and that he was not diagnosed with it by his GI or any other medical professional.
 
As I said, I saw esophagitis caused by remicade, and I believe it was eosinophilic esophagitis, consistent with the study in the OP. It's a side-effect that people should be aware of.

I would like to know why you guys find it so hard to believe that anti-TNFs can cause a number of unusual immune-mediated side effects. It's quite obvious that they do, and based on the study in the OP I think we can be pretty sure that EOE is one of those side-effects. That doesn't mean that these medicines don't do more good than bad in many cases, but let's not pretend that there are no possible downsides.
 
All I did was post a link and you guys jumped all over it with a great deal of hostility as though the association was obviously wrong. Go back and read the OP. Have you done your own study?
 
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Maya142

Moderator
Staff member
Nobody was trying to jump all over it - MLP was informing you of other research connected with EoE and IBD and what it has shown.Two of us are Moderators and are responsible for forums. You said - with certainty - that you knew it was eosinophilic esophagitis and you knew it was caused by Remicade. That is not true - you have assumed it is. Whether or not it is possible is moot - the point is, you were stating the veracity of a study based on a supposition.

No one is denying anti-TNFs can cause undesirable and indeed, paradoxical immune effects. We all know paradoxical psoriasis exists. My daughter developed drug induced Lupus from a biologic (not an anti-TNF though) but in our case, it was tested for by her GI and confirmed by her rheumatologist. Her diagnosis was confirmed by blood work and symptoms and I can say with certainty that that biologic caused it. She was taken off it and recovered, although it took a few months.

The issue here is not whether anti-TNFs can cause EoE - some studies state an association. Correlation, not causation.

Rather, the issue here is that you are saying, with certainty, in your child's case, he had EoE that was caused by Remicade and therefore EoE can be caused by anti-TNFs. The former is definitely untrue (i.e. he was not formally diagnosed with EoE by any medical professional) and the latter is so far only under investigation.
 
You are getting hung up on "formal" diagnosis. Remicade caused esophagitis in my son's case, and I believe based on all of the information available to me that it was most likely eosinophilic. I do not know of any other esophagitis that Remicade may cause, but I agree that it's possible that Remicade might cause entirely different types of esophagitis as well. If you are aware of any other kinds of esophagitis that Remicade can cause, let me know and I will update my probabilities. This is the only esophagitis I have seen associated with Remicade in the literature, so I think we should be able to agree that it is the most likely type of esophagitis caused by Remicade and present in my son's case.

In order to make this all clearer, here's a summary so far:

Me: Anti-TNFs may sometimes cause EOE
MLP: Anti-TNFs don't cause EOE. The correlation is unrelated to anti-TNFs.
Me: I've seen causation of EOE
MLP: No you haven't
Me: Yes I have
You/MLP: No you haven't
Me: I've seen causation of esophagitis, and it was most likely EOE.
You: But you don't know it was EOE
Me: I've seen anti-TNF cause esophagitis, and I believe it was most consistent with EOE. If you want to insist, "anti-TNFs cause other esophagitis but not EOE", go ahead and I will listen. Remicade causes esophagitis in some cases, which I have personally seen, and it certainly doesn't surprise me that EOE would be one type of esophagitis caused by Remicade. That's why I posted the OP--so people would be aware that anti-TNFs can cause esophagitis.
 
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crohnsinct

Well-known member
Hmmm for any newbies reading esophagitis associated with Remicade aside there is definitely esophagitis associated with Crohns, with EEN, with steroid use etc.. O had esophagitis at dx and then on another repeat scope. It is a pretty common occurrence with Crohn's. Her's was not eosinophilic.

I also think it is important to be concerned with formal diagnosis because it affects treatment etc. It is important for someone to know if your son had formally dx'd EOE as you state the treatment for your son was withdrawing Remicade. If a person with formally dx'd EOE reads your antidotal account they may be led to believe that if they withdrew an anti tnf drug, their EOE would resolve but they wouldn't be comparing apples to apples....and yes, of course, people should always approach treatment under the advice of their physician and not what they read on the internet but we all can't help but read things here and find hope, questions etc. O has had numerous working diagnosis such as psoriatic arthritis, SIBO, IBS, Uveitis, and many others. But it is important to not just take something that seems like it is a certain condition and run with it without proper. testing. However, as a parent you have your "gut" feelings and you are entitled to them. I never agreed with many of the working diagnosis that O had and "felt" that she had other things that they weren't diagnosing. It is great to share our experiences here. This is how we learn. But it is important to present accurate information and not state our theories as fact.

The OP study just states there is an association. Meaning they happened in the same population. Not a cause. Just warrants further study. The population skews the results because most people who are dx'd with EOE are dx'd when kids. The people they looked at are kids. Kids with Crohn's are usually placed on anti tnf drug at dx. I would be more interested to see how many adults dx'd with Crohn's and placed on anti tnf drugs then later developed EOE...perhaps that is part of the further study?

These association/warrants further study papers are written all the time. If we took every one of them as fact we would make ourselves crazy. Some go on to have further study and are proven, some are not and some never move on to further study because the outcome really doesn't matter to anyone.

All this said, I am glad that your son is feeling better and that he had you advocating to find him the relief he needed. Long may it continue!
 
I think the widespread bias against attributing side effects to medication is the most notable thing here. I've seen this repeatedly both here and in other places and regarding other conditions. Doctors are prone to this bias as well.

I think people just really *want* to believe in the perfection of medicine. They *want* to believe that tradeoffs don't exist--that things are only good or bad.
 

Maya142

Moderator
Staff member
There are risks and benefits of course. CIC said it best - I'm mostly concerned about new parents. I know when my daughter was diagnosed, I agonized for many sleepless nights before agreeing to biologics. I was absolutely terrified. But they completely changed her life. I'm not saying she never had side effects - I spoke about drug-induced Lupus, and it took her months to recover and it was a miserable experience.

But overall, the benefits far outweigh the risks or GIs wouldn't prescribe them. And there are so few available medications for Crohn's that I think it's important make sure all info is accurate. I know Remicade didn't suit your son but it is a first-line treatment for many kids, so it's important for us to post facts and not present theories as facts.

The most important thing here is also what @crohnsinct stated - your child is now doing well after surgery and is on the right biologic for him.
 
My son is the one MLP mentioned with EOE. It is the case that eosinophils in the blood are not used to diagnose EOE. One's history and a biopsy of the esophagus is used to diagnose EOE. Elevated eosinophils in the blood can be caused by a number of things. Heck, maybe anti-TNFs sometimes, who knows? Well, nobody knows for sure yet. The body is so complex and each of us is so individual.

I'm a very drug-averse person, we have avoided using drugs to treat both my son's EOE (dx 3 years ago after 3 years of struggle) and my own Crohn's disease so far, and I have to say that this forum has been very supportive of a non-drug approach, unlike another forum I tried. So, with my preferences stated, I too think it's important to have accurate diagnoses when sharing information with medical professionals and with our peers. It's also important to distinguish between a high quality study and an association that has been noticed by a, no-doubt, qualified researcher. Sadly, so many of these associations don't get well-studied for a long time, and it can leave us feeling very frustrated and in the dark as parents and patients. I've spent a lot of time reading EOE literature, and have found myself frustrated many-a-time.

I do appreciate all the articles that Pangolin and everyone else shared, and I'll probably spend some time in the coming week reading them. I'm feeling concerned that my son w/EOE isn't growing well and I can't help but think of my own brother who stopped growing and was diagnosed with Crohn's at 11 yrs old (my son is 9.5).
 

my little penguin

Moderator
Staff member
@jadegreen
I am so sorry to hear your little one is not growing
We were told the two big red flags for Gi are
Lack of weight gain (or loss )
And slow or no growth
Two things kids are designed to do

my kiddo was dx due to no weight gain for 2 years (age 5 to 7 )
Then slow weight loss (0.5 lbs every two weeks )

definitely talk to your child’s gi
Hopefully it’s just a minor bump in formula needed ..
 

my little penguin

Moderator
Staff member
@jadegreen
One thought
Is he gaining a lot of weight or changing shoe sizes fast ?
Prior to puberty growth spurt …
Both my boys (one non ibd as well as ibd kiddo )
First gained a lot of weight quickly
Then went through shoe sizes like crazy
Typically it’s a year or two older but …
Every family is different
Weight gain first
Then rapid growth of short bond (hands feet )
Then long bones -rapid height growth …
Just in case it’s normal stuff
I can say even with crohns at age 7 (no weight gain )
At almost 18 he is close to 5’11” and 160 lbs
Still growing due to delayed growth
So if treated quickly even crohns kids can grow to normal heights
 
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