Latest / Pediatrics Now: Cases Updates and Discussions for the Busy Pediatric Practitioner / Understanding FPIES: A Silent Food Allergy

Transcript

Understanding FPIES: A Silent Food Allergy · Pediatrics Now: Cases Updates and Discussions for the Busy Pediatric Practitioner

0:00
Music.
0:11
A fascinating talk. Let's listen in. It's my great pleasure to introduce this
0:17
morning's grand round speaker, Dr.
0:19
Milin Pansari, who is a good friend of mine. He's an associate professor of
0:23
pediatrics at Central Michigan University and Children's Hospital of Michigan.
0:28
He did his pediatric residency at Henry Ford Hospital in Detroit and fellowship
0:33
in allergy and immunology at Children's Hospital of Michigan.
0:37
Subsequently, he served as the Associate Fellowship Program Director for Allergy
0:42
Immunology Fellowship Program and also Medical Director for Asthma Program at
0:47
Children's Hospital in Michigan.
0:49
His clinical interests include asthma, anaphylaxis, and food and drug allergies.
0:54
His clinical research projects include improving asthma outcomes in inner-city
0:59
children and anaphylaxis education in local schools,
1:02
as well as improving access to rescue inhalers and epinephrine autoinjectors in inner-city schools.
1:09
At the national level, he's very active in numerous activities,
1:13
including educational, scientific, and advocacy activities for the American
1:18
Academy of Allergy, Asthma, Immunology, and the American College of Asthma,
1:22
Allergy, and Immunology.
1:24
Dr. Pansari, thank you very much for accepting our invitation. The floor is yours.
1:29
Thank you, Dr. Kamath, for your kind introduction. First of all,
1:32
good morning, everybody. And I'm wishing you a very happy Friday.
1:38
You know, today is a special Friday. Today is April 11th.
1:41
And guess what? Today is the International Cheese Fondue Day.
1:45
Do you know what it means?
1:47
It means that we can go raid Cheese Factory, go to Mexican restaurants,
1:52
American burger places, and eat cheese to our heart's content and enjoy.
1:58
Isn't that a wonderful thing?
2:00
But imagine a world, living in a world where even the most innocent food could
2:06
trigger life-threatening reactions.
2:08
And there are really many patients out there who cannot eat these innocent food
2:15
because they develop a serious and a severe reactions.
2:19
This entity is not very uncommon.
2:23
We often would miss that if you have no knowledge about these entities.
2:29
So today, my goal is to bring your attention to one of such clinical syndrome,
2:35
which can potentially result in severe clinical reactions.
2:40
Nope. I'm not talking about anaphylaxis. We know about anaphylaxis.
2:45
I think we do a good job in taking care of patients with anaphylaxis.
2:50
But I'm talking about a rarer entity.
2:53
Imagine patients living in a world having this disease syndrome,
2:59
and we're living in a constant fear, anxiety, worried about when that next reaction could occur.
3:07
I'm not making it up. It is real.
3:10
This disease was not discovered until very recently. In 70s and 80s and 90s,
3:15
many of these patients were not diagnosed appropriately.
3:20
When they went to see a doctor, who would often give them an advice which was
3:26
inconsistent with the clinical symptomatology.
3:30
Often they were told, I don't think food is responsible for this.
3:34
I've never seen this problem in my life.
3:37
And when asking for a specific advice, there was nothing to offer.
3:41
So this patient lived in a continuous sense of despair and with a sense of abandonment.
3:50
Certainly, this is a significant psychological impact when you have an uncommon
3:56
clinical syndrome like this.
3:58
And today, my job is to bring your attention to this uncommon food-induced clinical syndrome.
4:05
For many of you, this may be totally a new entity, but for a few of you,
4:10
you might have seen this patient in your clinical practice.
4:13
I certainly would like to know what was your clinical experience.
4:17
And for presumably many who have not seen one as yet, my goal is to provide
4:23
you a clinical update on this clinical syndrome.
4:26
Let me illustrate this case. Let me illustrate this point by giving you a clinical
4:31
case scenario. A five-month-old infant was admitted to PICU following an acute illness.
4:38
The infant presented with lethargy, sudden onset of severe emesis,
4:43
and later, one large watery diarrhea.
4:46
Infant was clinically well when dropped to the daycare in the morning.
4:50
He also fed well on a Similac infant formula two hours prior.
4:54
When he was brought to the ER, he's obviously a sick-looking infant,
4:58
ash in color skin, lethargic, severe dehydration, hypertensive,
5:02
and incidentally, was afebride.
5:05
His initial lab showed a significant neutrophilia, metabolic acidosis, methemoglobinemia.
5:13
Otherwise, the pertinent clinical history was unremarkable.
5:16
The child was a healthy infant, growing well, exclusively breastfed,
5:20
was diagnosed with cow milk allergy due to his previous emphasis episodes.
5:26
What was the clinical course? The child was admitted to PICU,
5:29
treated for hypovolemic shock and possible sepsis.
5:33
The sepsis workup came back normal, including a CSF in the normal range.
5:39
The infant made a dramatic recovery within 24 hours of presentation.
5:43
So what's your likely diagnosis?
5:45
Is it a case of acute gastroenteritis with severe dehydration?
5:49
Unlikely because the clinical symptoms were very short-lasting and the patient
5:57
made a very rapid recovery, did not have any fever, other signs of infection.
6:02
Acute sepsis, yes, it was a very dramatic presentation, but again,
6:07
equally dramatic recovery and with microbiological cultures being negative,
6:11
again, was less likely diagnosis.
6:13
Is it a case of cow's milk anaphylaxis?
6:16
Certainly not, because the presentation was at least two, three hours after
6:20
his last feed, and he did not have any other system involvement.
6:24
So typically, anaphylaxis would be a multi-system involvement,
6:27
cutaneous, respiratory, GI, and so on and so forth, but he didn't have any of
6:31
those. Is it a case of foot poisoning?
6:33
Foot poisoning is quite uncommon in this particular age group,
6:36
when a child was just infant fate formulas.
6:40
Again, the recovery, again, is quite dramatic. Usually, foot poisoning would
6:44
not have such a dramatic presentation, then what is it?
6:50
F-Pi's. Yes, indeed. You've taken the meat out of my talk today.
6:56
This child is a case of F-Pi's, a food protein enterocolitis.
7:01
This child was not labeled so when he was discharged from the initial hospital.
7:08
He later on was readmitted around 12 to 13 months of age to our institute.
7:13
Again, with a very similar dramatic presentation, he was resuscitated by the
7:17
EMS, actually intubated on site because of concern of seizure and brought to the PICU.
7:24
He, you know, he was, during the route, his tube had come out.
7:29
He remained extubated. He was treated aggressively with IV fluids and IV fluid resuscitation.
7:36
He made a remarkable recovery within 24 hours again.
7:39
And then his presumptive diagnosis
7:42
was severe acute gastroenteritis with hypovolemia, with possible sepsis.
7:48
And then we were consulted for this patient because of mother's concern of possible cow milk allergy.
7:57
She had stopped giving him in cow's milk and she stopped breastfeeding.
8:02
He was only on solids, beaning food, and was surprisingly doing well.
8:08
He had no exposure to milk and dairy until that accidental exposure where the
8:13
grandfather was babysitting the child, gave him a milk formula,
8:16
because mother was away at work.
8:18
So these patients, the clinical hallmark of these patients are they present
8:22
with very dramatic clinical symptoms and also make a dramatic recovery.
8:27
But if you're not aware of such entity, you're not likely to come up with this diagnosis.
8:32
So what is F-PICE? F-PICE is a food protein-induced enterocolitis,
8:37
is a non-IGE-mediated food allergy characterized by delayed gastrointestinal
8:43
symptoms following ingestion of culprit food.
8:46
The hallmark is pronounced GI symptoms.
8:50
And the symptomatology may manifest little late than usual, usually two to four hours or longer.
8:58
As a result, the core relationship with that particular culprit food is often
9:01
missed. But F-Pi's is a story of missed or delayed diagnosis.
9:06
Most of these patients have at least five or ten episodes before they are properly
9:11
diagnosed. Otherwise, they are just investigated for other unlikely etiology diagnosis.
9:17
There's definitely a low awareness amongst the primary care provider.
9:21
A recent survey which looked at 100 odd patients with FPIs, when they did a
9:26
retrospective analysis, how many of these patients had this diagnosis labeled
9:30
prior to their referral?
9:32
Only 22% had proper labeling of the diagnosis.
9:36
Unfortunately, FPIs, there's no diagnostic test available, so it always is clinical diagnosis.
9:42
Many of these patients often have unnecessary diagnosis and invasive testing,
9:47
particularly endoscopies, which is probably not necessary if you make this diagnosis
9:51
early during the disease.
9:55
You also have to remember, F-PICE is not necessarily a benign condition.
9:58
The usual course is a spontaneous recovery with time, but 20% of patients like
10:03
this patient end up with severe hypovolemic shock. Now, recent rare cardiac
10:09
arrest have also been reported, both in infants and older children.
10:14
And this diagnosis is evolving. Your understanding of this disease is changing
10:20
and evolving. We really need to learn more about this disease to do a better
10:24
job in clinical management.
10:27
So, how recent is this diagnosis? The first documented case,
10:32
likely of F-Pi's, was published by two gentlemen, Gribosky and Powell, in 1970.
10:39
It was the case of infant with cow milk F-Pi's.
10:42
The diagnosis was not labeled as F-Pi's,
10:46
but thought to be a milk intolerance or probably a milk-induced colitis due
10:51
to recurrent episodes of traumatic symptoms and improvement after cow milk was
10:56
withdrawn from the child's diet.
10:58
In 1970s, the disease was thought to be exceedingly rare and rarely reported.
11:05
However, over a period of time, there was sporadic increasing report of F-Pies,
11:12
surprisingly to now not cow milk, but variety of solid food, including like rice,
11:20
chicken, green peas.
11:22
More reports were published for older children, so no longer it was necessarily a disease of infants.
11:30
In 2012, a first documented case of scallop-induced F-Pi was reported in adult,
11:38
proven with an oral challenge.
11:42
Recently, most of the food associated with F-Pi are thought to be innocent food,
11:46
not the Big 8, which cause severe allergic reactions.
11:49
But recently in 2020s, there's a new kid in the block.
11:54
Peanut and egg have been increasingly reported as a cause of F-PIs.
12:00
We do not know a reason for this, but perhaps the new recent recommendation
12:05
of infant food feeding guidelines, which recommend early introduction of even
12:11
highly allergenic food, including peanut,
12:13
in young infants between four to six months of age to prevent a development of food allergy.
12:20
So early introduction of food, you develop tolerance to food allergy,
12:25
but do you create a new problem?
12:28
Are you going to see more F-Pi's in this patient? That needs to be elaborated properly.
12:36
So what the landscape of F-Pi's have changed from 1970s.
12:40
Now we know probably any food can cause F-Pi's.
12:46
The common ones are cereal grains, vegetable, most commonly sweet potato,
12:51
carrot, fruits, and fruits like banana, avocado,
12:54
apple, or other solid food, typically in older children, including seafood, peanut, nut, and eggs.
13:02
What has changed in the literature? If you look at the curve of publication
13:06
in a peer-reviewed journal, nothing was known until almost 2000, 2010.
13:12
It's only in the past decade or so, there has been a surge of scientific publication
13:17
in peer-reviewed journal.
13:18
Most of these articles are emphasizing on the clinical elements,
13:23
what are the epidemiological aspects of FPI's, the clinical profile of patients,
13:30
and many of them also have looked
13:32
at longitudinal data about what is the outcome of patients with FPI's.
13:37
None of them have touched on pathophysiology of FPI's.
13:41
I did talk to you about what is the quality of lifestyle for patients,
13:47
a parent, or a caregiver with FPICE.
13:49
And as a result of being ignored by the medical fraternity, the caregivers established
13:59
an organization called FPICE Organization.
14:02
It's established in the United States, but now it has a worldwide membership.
14:08
International FPIES is a non-profit organization which is
14:11
dedicated time for patient advocacy and research funding with the purpose of
14:18
increasing dissemination of knowledge about FPIES and educating caregivers and
14:24
provide them the support they need to take care of children with FPIES.
14:29
It's only until 2016 there's an ICD code for FPIES established.
14:34
Thus, the disease got a name, it got an established diagnosis,
14:41
and now, even for research purposes, we could look back, do a retrospective
14:45
analysis using this coding for FPIES.
14:49
There were various diagnostic criteria proposed by different researchers,
14:54
creating a lot of confusion.
14:55
What is the right criteria for diagnosis of FPIES?
14:57
Particularly so because FPIES is a clinical condition.
15:01
So all the experts came together and they published the consensus guideline
15:06
in 2017 for diagnosis and clinical management of FPIES, which was the first
15:12
scientific publication really facilitating clinical care of FPIES.
15:16
It's only until 2022, a first NIH grant was offered to a Boston Children's Hospital
15:25
group to study the pathology of FPIES.
15:30
In 2023, the Consortium for Food Allergy, which is an organization heavily involved
15:37
in research in food allergy, now also included F-PiS under the umbrella for
15:43
further investigation.
15:45
So the future looks promising because there is more involvement of scientific
15:49
community now to understand the disease of F-PiS and help with clinical management for our patients.
15:57
A recent publication by the NIAID group, a workshop report of FPIES was published
16:06
in 2025, February, stating the current status and future direction in management of FPIES.
16:13
So, what is the prevalence of FPI's in the United States?
16:17
It is estimated 0.51% of the pediatric population may have a diagnosis of FPI's.
16:24
That means there are about 375,000 children running around somewhere waiting
16:30
to come to your office with this clinical symptomatology.
16:33
And hopefully we should not miss this patient with an erroneous diagnosis.
16:38
The prevalence in adult population is about 0.22% estimated 550,000 of adults with F-Pi's.
16:47
So it's reasonably not an uncommon disease.
16:52
F-Pi's is prevalent worldwide. There's a significant variation in prevalence.
16:57
More importantly, the food which triggers F-Pi's symptoms.
17:01
For example, F-Pi's with soy is almost not reported outside the United States.
17:06
In Japan, egg is the most common food trigger.
17:10
In the Mediterranean climate, like Spain, Italy, seafood is the most common culprit.
17:16
In Australia, cereal grains is a common culprit. So there is a variation.
17:21
There is an international drive about learning about this disease entity,
17:25
and the International FPI organization helps coordinate this research work.
17:29
The impact of FPI is significant. It can cause a severe effect on the growth
17:34
of a child, largely due to eating disorders that China might develop because
17:39
of delay in introduction of solid food.
17:41
Also, avoiding nutrient-dense food can result in nutrient insufficiency,
17:46
causing growth alteration.
17:48
So you have to remember this impact of FPI's in development of an infant.
17:54
The most important effect we talked about is the quality of life.
17:59
There is significant impairment in the mental health of a caregiver,
18:03
increase occurrence of anxiety, stress.
18:06
Poor quality of life, and decrease self-efficacy in taking care of children with FPI's.
18:17
Of course, it creates a lot of financial burden because often the parent have
18:20
to lose their job, stay home to take care of the child, and look for alternate,
18:25
more expensive types of formulas or diet, causing a significant financial burden.
18:31
In fact, a recent study showed that the health quality of life of caregivers
18:37
of children with F-PIs have much worse quality measure compared to caregivers
18:43
of children with food allergy in all domain and also in specific domain of measure of quality of life.
18:51
So therefore, it's a silent disease causing problems which need to be recognized.
18:58
And that also should be a part of our care to make sure the mental well-being
19:03
of the caregiver is taken care of.
19:07
How do you diagnose F-Pi's? Pavel was the first person who associated the food
19:12
trigger causing F-Pi's.
19:15
So if you give that culprit food, you have symptoms, you remove the food,
19:19
your symptoms are improved, and at a later time, if you reintroduce the food, the symptoms reoccur.
19:25
So there are numerous other diagnostic criteria established by various authors.
19:30
In 2017, the International Consensus Guideline published the first consensus
19:35
criteria for diagnosis of FPIES.
19:39
So this criteria essentially was clinical, and that's important because FPIES
19:44
is a clinical diagnosis.
19:45
You need appropriate clinical criterias to make this diagnosis.
19:51
The guidelines recommended for diagnosis of FPIES, you need to have two major
19:56
criterion and at least three of the minor criteria.
19:59
The two criteria are occurrence of symptoms, delayed GI symptoms within one
20:04
to four hours after ingestion of suspect food.
20:08
Most importantly, it is not an anaphylaxis, it is not an IgE-mediated,
20:12
so there should not be any evidence of an IgE-mediated reaction like HISE.
20:17
Angioedema, cough, throat closure symptoms, and other significant systemic symptoms.
20:24
The minor criteria are much more fulfilling for a severe manifestation.
20:28
Like if you have a presentation of hypertension, hypothermia,
20:31
a patient to be seen in an emergency room, requires IV fluids,
20:35
or has extreme lethargy and pallor, the diagnosis becomes pretty easy if you
20:40
know about the disease entity.
20:42
If you have another episode in the past, then your suspicion is significantly increased.
20:47
Or if the patient has another food trigger for FPI symptoms,
20:52
the diagnosis might be easier.
20:55
This diagnosis criteria work very well for severe FPI's, but I have my reservation.
21:00
Patients with milder form of FPI's might be missing, will not be diagnosed by using this criteria.
21:06
And there is a spectrum of patients with milder phenotype.
21:11
The most important thing is the patient, apart from this acute illnesses,
21:16
are normal and well-growing infants without any other problem,
21:20
as long as the offending food agent is avoided.
21:24
There's also an entity called chronic F-Pies. This is a little wishy-washy.
21:28
There's no clarity on this.
21:30
Largely, it states that the symptoms are long-lasting.
21:34
It could manifest as a severe presentation where the offending agent is not
21:39
avoided and ingested on a regular basis.
21:42
A child may have a persistent and a progressive vomiting and a diarrhea,
21:45
often with blood, sometimes with dehydration and metabolic acidosis.
21:49
A milder version of these chronic F-Pies may have intermittent episodes of vomiting and diarrhea.
21:54
The most important thing is patients with chronic F-PIs will definitely have
21:59
poor weight gain, failure to thrive, even without dehydration and metabolic acidosis.
22:06
So that's a marker if you're dealing with a patient with chronic F-PIs.
22:09
But I believe many of these patients will be worked up more for malabsorption
22:13
or a chronic gastrointestinal disease before we might think about chronic F-PIs.
22:18
Other important criteria is even after you withdraw the incriminating food agent,
22:23
the recovery is not rapid.
22:24
It may take three or ten longer days for the recovery to occur.
22:30
Many of these patients with chronic F-PIs are properly diagnosed,
22:33
and if you reintroduce that culprit food, they can manifest as an acute F-PIs.
22:39
So, the phenotype might change after avoidance of food for a long period of time.
22:44
Chronic F-Pi, some of the important
22:46
highlights are, is almost never seen outside the infancy age group.
22:51
It has not been reported with solid food.
22:54
Exclusively, it's related to cow's milk and soy. So that at least is a little
22:58
less concerning feature.
23:00
At least we would be able to diagnose F-Pi in young infants.
23:04
But the common story is there's often a delay in diagnosis resulting in a prolonged
23:09
and progressive course until the food is eliminated.
23:14
So the guidelines have tried to establish a clinical profile based on the symptomatology
23:20
to identify are there any particular phenotypes in the clinical observation of all the cases.
23:26
When they reviewed the literature and looked at all the case reports in the
23:30
case series and the case cohort studies, they wanted to find out a pattern.
23:35
Is there a certain clinical characteristic which you have? Does it affect the
23:41
clinical outcome and the course of the disease?
23:43
So that's called phenotype. Any observable clinical features which can be identifiable
23:50
and can be correlated to the endotype or the pathology of FPI's.
23:56
So broadly, they propose four different phenotypes for FPI's.
24:00
One, depending on the age of onset.
24:03
So there's a different outcome for patients who present early the nine months
24:06
of age compared to more than nine months of age.
24:09
Definitely the older children and adults have a different profile and outcome
24:14
in terms of their FPI disease.
24:17
Other phenotype was based on the severity. like a lot of these patients we present
24:22
with a very severe presentation like the one I presented or could be a milder
24:27
version that again based upon like we talked about acute versus chronic F-Piase.
24:33
There's another entity observed in this phenotype evaluation.
24:37
Patients had IgE positivity.
24:40
That means the skin prick test or the serum IgE test for the food was positive.
24:44
This was called as an atypical F-Pi. So about 5 to 30% of the patients with
24:50
F-Pi can have a positive IgE test.
24:53
What it showed that these patients with atypical F-Pi generally had a protracted,
25:00
sometimes unresolved course.
25:03
That means the disease symptoms really lasted for a longer period of time.
25:07
And not surprisingly, about 25% of patients developed true type 1 or IgE-mediated allergic reactions.
25:16
So is this indeed a separate profile?
25:21
Or as we have learned over a period of time,
25:25
not only the prevalence of F5s has increased, but also the IgE-mediated diseases
25:32
like allergic rhinitis, atopic dermatitis,
25:35
allergic asthma, So is this a cause effect or this is just the two entities
25:40
being observed together is not known.
25:44
So, a typical phenotype of an infant FPI would be an infant with cow milk and
25:50
soy is likely to present before six months of age.
25:53
If they're present earlier than that, they are likely to have more of lower
25:57
GI symptoms like diarrhea, including blood in the stool, and likely to have failure to thrive.
26:03
Most of the FPI food symptoms occur with a direct feed, meaning the child has
26:09
to eat the food to develop symptoms. and typically would occur in the initial introduction.
26:14
Most studies show that manifestation of FPI have occurred within the first four to eight initial feeds.
26:23
So that's a little comforting. If a child has been eating food at least 10 or
26:28
12 times or more, it's less likely to develop FPIES.
26:32
A solid FPIES manifest a little later in infancy, between 6 to 12 months of
26:37
age, with a mean of 5 to 7 months.
26:39
Most solid F-Pi's, the common food is cereal grains.
26:43
Rice and oat is the most common in the United States.
26:47
Other solid F-Pi's are fish, egg, and poultry. Usually chicken is considered
26:50
to be low-allergenic food, but chicken F-Pi's are much more commoner than other poultry.
26:56
F-Pi's in older child and adult, increasing reports of F-Pi's in older age group.
27:02
Most present with F-Pi's, acute F-Pi's, chronic F-Pi's almost not known in older child or adult.
27:08
They typically manifest with symptoms with predominant abdominal cramps or pain.
27:13
That's a very common symptomatology.
27:16
Nausea and vomiting is also accompanying these symptoms.
27:20
So often these older children or adults will be misdiagnosed.
27:24
Sometimes you would think it's a foot poisoning or foot intolerance and may
27:28
not pay attention that this indeed could be an F-wise.
27:32
The key observation with findings was, is more common in female population.
27:37
Again, same old story, misdiagnosis, until the patient had anywhere from 6 to 15 episodes.
27:43
Definitely, it's much more persistent. Very few are likely to develop tolerance over time.
27:49
Incidentally, there was higher rates of comorbid GI conditions like irritable
27:54
bowel syndrome or celiac disease in this patient population.
27:57
The most common foot trigger is shellfish, mollusk, or fish.
28:02
So seafood are the most common, followed by egg and also mushroom.
28:07
Many of these patients might be misdiagnosed as mushroom toxicity or poisoning. So be mindful of that.
28:13
So what are the food triggers for F-Pi's? Virtually any food is possible trigger.
28:18
It varies with the geographical variation and the dietary habits of that area.
28:23
Most common are the single food F-Pi's, amounting average around 60% of the patient population.
28:31
However, the single food F-Pi is not so common in the United States.
28:34
Usually two food, a cow milk or a soy with oat or a rice seems to be the most
28:40
common combination in the United States.
28:42
Some of the patients, almost 10% of the patients can have multiple food F-pies
28:46
ranging from 2 to 13 food in a bad situation.
28:51
We do not understand the risk factor for multiple food F-pies.
28:55
A small study of Australian infants showed that if the infant had a reaction
28:59
very early age or if they have F-pies to fruit and vegetable and rice,
29:05
more likely to develop multiple other food F-pies.
29:09
So just to recapitulate, I mean, acute F-Pies in the United States,
29:12
the common triggers are cow's milk, soy, grains including rice and milk,
29:17
egg, fruit, and vegetables.
29:19
In Europe, it's cow's milk, fish, egg, grain, soy. In Australia,
29:25
rice, cow's milk, egg, goat, and poultry.
29:27
Chronic F-Pies, just infant formulas. That's it.
29:32
Interestingly, many food co-associations have been noted in children with F-Pies.
29:35
For example, if you have cow milk F-Pi's, almost 40% chance you'll also react to soy.
29:40
So that's not a good substitute when you have a cow's milk F-Pi's.
29:44
The probable alternates are either
29:46
extremely hydrolyzed formulas or amino acid-based formula for infants.
29:51
If you have solid food F-Pi's, there's almost a 45% chance you may have another
29:56
solid food F-Pi's is the observation.
29:58
These are earlier studies. So I'm sure this co-association may be different
30:04
with time, as we know about more study on this aspect.
30:09
If you have F-Pi's to grain, more likely you'll react to another grain is up
30:15
to 50%. Similarly for poultry, almost 40%. So if you have F-Pi's to chicken,
30:21
turkey, quail, and whatnot would not be a good alternative.
30:24
What about F-Pi's in a breast-fed infant? So there's very limited data,
30:29
but clearly it's very, very uncommon.
30:33
In fact, the European Academy of Allergy Immunology and our American Academy
30:38
of Allergy Asthma Immunology have put out a position statement stating that
30:42
it's uncommon to see F-PYs in exclusively breastfed infants.
30:46
There is no need to recommend any maternal allergen avoidance in asymptomatic infant.
30:53
Rarely, an exclusionary maternal diet might be effective, but generally, not recommended.
30:58
So be careful when you're seeing a patient and your suspicion is F-Pi's.
31:03
It's not likely because of the breastfeeding.
31:06
It could be some other agent which you have not recognized.
31:09
What is F-Pi's pathology? What do we know of?
31:13
All I can say, we really don't know anything about it. I could just say that
31:17
and move to the next slide.
31:19
But I'm just going to recapitulate a few things which is thought to be probably a proposed mechanism.
31:25
It's clearly an interaction between the immune system, the GI tract,
31:32
and autonomic nervous system.
31:34
Although we do not know the exact details. It is presumptively thought that
31:39
there is some disruption in the intestinal barrier which causes leak of the
31:42
protein, activation of local immune system.
31:46
There's a big role for neuroimmune system there, which triggers signaling of
31:50
the vagal nerve, triggering the vomiting center in the brain.
31:55
If you're a lot of vomiting and diarrhea, you're hypovolemia.
31:58
That activates the autonomic nervous system to maintain the homeostasis.
32:02
So we really don't understand very well There is no evidence of any systemic inflammatory changes.
32:08
For example, in patients with food allergies, you can identify IgE in the blood,
32:12
or you can find some T-cell clones specific to that food antigen as an evidence of food allergies.
32:19
But none of that is evident in the blood of these patients.
32:22
So the best explanation is there is some local inflammatory process.
32:27
Probably innate immunity plays an important role, including monocytes,
32:32
macrophages, and neutrophil.
32:34
The stress causes release of cortisol, causing increased margination of neutrophil in the blood.
32:40
And that's what you see as neutrophilic leukocytosis.
32:44
There is a significant proliferation of lymphocytes, but it's a pan-T cell activation,
32:50
meaning there's not one type of T cell.
32:53
It could be Th1, Th2, Th17, Th22, which are all involved in inflammatory responses in the gut.
33:01
Perhaps there's a role of mass cell also.
33:04
But what has been shown that serotonin probably plays an important role in clinical
33:11
manifestation of F-PIs.
33:13
Serotonin is a mediator released by specialized cells in the intestinal epithelium
33:19
called enteroendocrine cells.
33:22
The receptors for serotonin is a 5-HT3 receptor, which is expressed in multiple
33:29
cells, including lymphocytes, macrophage, immune cells,
33:35
intestinal epithelial cells, which are important for fluid and ion exchange across the epithelium.
33:43
On the afferent nerves of spinal
33:46
cord, vagus nerve, which are important mediator of vomiting sensation.
33:52
So serotonin has a role in GI motility, when I say GI, gut secretions,
34:00
gut motility, perception of nausea, vomiting, and abdominal pain.
34:06
I'm saying so because there is one drug which is now used to treat FPI's acute
34:12
symptom called ondincetron, which had been used for longest time to treat vomiting
34:17
with chemotherapy or even gastroenteritis.
34:20
But this drug had been used for FPI's and in acute FPI's symptoms seem to dramatically
34:25
resolve with use of ondincetron.
34:28
So perhaps because it's a serotonin receptor antagonists.
34:33
So probably there's a big role for serotonin, which needs to be looked at carefully
34:37
in pathophysiology of F-PIs.
34:42
How do you diagnose F-PIs? There are no laboratory markers. There are no lab
34:46
tests to confirm F-PIs. It's essentially a clinical diagnosis.
34:50
But you could probably do what is called an oral food challenge,
34:54
which typically is done by allergists in their office.
34:57
It is a medical procedure in which food is eaten slowly in a gradually increasing
35:03
amount under medical supervision to accurately diagnose or rule out true food allergies.
35:10
So we commonly do this for our patients with IgE-mediated food allergies.
35:14
It's very challenging. It's very difficult.
35:18
It's very resourceful when it comes to doing oral food challenges for F-PIs. It is fraught with risk.
35:26
It requires hospitalization and an IV fluid access.
35:32
All of that makes it a very problematic procedure.
35:37
So it's not commonly done. You will have very few centers who actually perform
35:40
oral food challenges for FPI's. Many of them are research center.
35:44
Do you really need to do oral food challenges for patients in FPI?
35:48
If the diagnosis is very compelling, you really don't need to.
35:51
But there is utility of oral food challenges, particularly when the history
35:55
is unclear and when you're considering to introduce new food.
36:00
A lot of these patients are, caregivers are extremely anxious.
36:03
They're worried about introducing any new food in spite of reassurances.
36:07
So perhaps they would want an oral food challenge before you can introduce a new food.
36:12
Obviously, it's very important to determine whether the disease resolution has occurred.
36:16
So these are the two areas where there's a big role for oral food challenges.
36:20
Obviously, you have to sit down and discuss with the patient and caregiver.
36:24
It's always going to be a shared decision because of the risk involved in performing an FPI.
36:29
There is no established accepted protocol.
36:33
This is an example of oral food challenge.
36:36
Obviously, it's only done under supervision of an NMD with an IV access.
36:40
You need to continuously monitor the vital signs.
36:44
The initial step includes administration of protein in a quantity of 0.06 to
36:51
0.6 kilogram of the body weight in a three equal doses.
36:55
You should not exceed more than three grams of total protein because of fear of severe reactions.
37:02
You have to wait at least for two to three hours and then the second step would
37:05
be administer age-appropriate serving of that particular food and then monitor for further six hours.
37:12
So, invariably, you need to hospitalize this patient for observation.
37:17
More than 50% of patients will get a serious, severe reaction if the challenge
37:21
is positive, requiring IV fluids and multiple medications.
37:25
So, bottom line, oral food challenges are not easy to do, not easily performed,
37:31
not many people are doing it, but always a consideration when the need is appropriate.
37:36
What do the management FPI's include?
37:39
Essentially, a management of acute symptoms, depending upon the severity,
37:44
IV fluid resuscitation, and administration of ondincetron has significantly
37:50
improved outcome of patient during the acute manifestation.
37:55
Just like epinephrine is necessary for anaphylaxis, ondincetron is necessary
37:59
when your clinical suspicion is acute FPI's.
38:02
You should be observing this patient at least for six hours after the last clinical
38:07
reaction before being sent home.
38:09
And they should have a normal clinical symptomatology before you would send this patient home.
38:14
We talked about Onel syndrome. It's only recommended for infants more than six months of age.
38:21
There is no safety data for younger infants. It can be administered orally at
38:26
home, IV intramuscular.
38:28
Although it's a very promising drug, it's poorly studied in this patient population.
38:32
You have to be mindful of cardiac disease, particularly if they're prolonged
38:36
QTC interval, arrhythmogenic effects of Andres syndrome have been shown.
38:41
Also, patients who are taking certain drugs which can prolong QTC,
38:45
including a variety of antifungal macrolite antibiotics, should be a consideration.
38:51
All patients with FPI should get a home action plan, just like we have asthma
38:56
action plan, anaphylaxis action plan.
38:58
FPI's patients should also get a plan to take care of reactions at home.
39:02
Particular patients with a severe previous reaction, activating EMS services
39:06
is important and early, even though they might have given oral on the syndrome to curb the symptoms.
39:14
Most patient moderate symptoms should go to ER. Patients mild symptoms,
39:18
that means one or two episodes of vomiting, no lethargy, and in the past had
39:22
recovered at home, probably could stay home and continue with vigorous oral rehydration.
39:28
What is the long-term management of F-PiS? Essentially, avoid,
39:32
avoid, avoid primary trigger.
39:34
Food elimination is the essence of treatment of F-PiS because you don't want
39:38
to keep provoking this clinical reaction.
39:40
Continued reassurance, monitoring for growth and development.
39:43
You can need to seek advice of a nutritionist to provide a proper complementary diet for the infants.
39:50
Enrolling in a peer group support services like the International FPI Organization
39:54
is a great idea for patients with FPI.
39:56
All these patients should be periodically evaluated for IgE sensitization or
40:02
for consideration of oral challenges.
40:04
There are some empiric guidelines, not based upon solid evidence,
40:09
but on expert opinion, which recommend
40:12
how you can introduce a variety of weaning food in young infants.
40:18
You need to select low-risk food like vegetables, fruits like blueberries,
40:24
strawberries, or meat like lamb, or cereals like quinoa, or other millets.
40:30
Tree nuts and seed butter seem to be more tolerant in patients with F-PIs,
40:34
and particular appropriate age group.
40:37
The guidelines recommend that any new food introduced should be given over a
40:41
period of five to ten days.
40:43
So an example of a new food introduction could be, start with one fourth teaspoonful at 9 a.m.
40:48
Repeat after 6 hours. You need to wait for 6 hours because that's a time period
40:51
of clinical manifestation of FPI's.
40:54
And the next would be 6 hours later of double the size.
40:57
Keep doubling the size in consequent days until the child is able to eat appropriate portion.
41:04
The natural history of FPI's is in 60 to 70% of patients will have resolution
41:10
of the symptoms spontaneously.
41:13
We do not have a good data about solid FPI's. Atypical FPI's do not resolve timely.
41:20
So there are numerous clinical retrospective studies looked at time period of
41:25
resolution of clinical symptoms with specific food. For example, Kobe et al.
41:29
Reported that patients with cow milk allergies about 5.1 had a resolution.
41:33
Sorry, patients with cow milk allergy had a complete resolution by five years of age.
41:38
Soy, 6.7, rice, 4.7, and so on and so forth. So, there's a different population.
41:43
The outcome has been different.
41:45
But it is expected most patients with classic FPI's would make a recovery with time.
41:51
Of course, when we know some things, we do not know a lot of things.
41:55
And there's a long list of things we really don't know, which is a problem.
42:00
Because these are the various unmet needs of patients with FPI's.
42:04
Be it for identifying the phenotype, knowing the triggers, knowing the diagnosis
42:09
and proper management and understand the psychosocial impact of patient for the caregivers.
42:16
So essentially, to just summarize, I want you to be alert and be able to diagnose
42:22
patients with F-PIs, particularly patients who present with medical emergencies.
42:27
It is always a challenge, going to be a challenge, to diagnose patients with chronic F-PIs.
42:32
There is no diagnostic laboratory test you could do.
42:36
It has to be a high index of clinical suspicion to make a successful diagnosis clinically of FPI's.
42:42
It is important that you recognize this entity early in the child's life to
42:47
improve their long-term outcome and to get appropriate recommendations.
42:52
You need to seek help of nutritionists and support organization to improve the
42:58
comprehensive well-being of the caretaker and the child.
43:02
These patients need to be monitored periodically for consideration of overall food challenges.
43:08
It's an evolving science. You'll have more information with time with better
43:12
criterias and recommendations for clinical management of F-PIs.
43:18
With this, I'm going to end and I will be happy to take any questions.
43:23
I appreciate your attention. If anybody wants to send me questions as an afterthought,
43:30
I put out my email here, mpansari at dmc.org. I'll be happy to respond.
43:35
So how many of you have seen patients with F-PIs And what was your clinical experience?
43:40
Can somebody chime in on that? And, of course, I'm ready for your questions,
43:44
if any. Thank you, Dr. Pansari, for that.
43:47
Introducing us to the new concept of FPI's. Let's see if anybody has any questions, comments.
43:54
They can either put them in the chat box or they can ask you directly.
44:00
So I have a question. Yes. I actually have experience, not personally.
44:07
I mean, with someone having F-Pies, which is why you described it perfectly
44:13
in the opening case. I was like, okay, that's it.
44:18
But I'm thinking that if it's not milk or something that could need to be a
44:25
part of your life often, what most people would do is avoid the trigger.
44:32
And they wouldn't feel that it would be important to re-challenge themselves
44:38
because they could just avoid the food. The food that I had...
44:44
Experience with the patient and with sweet potatoes. And so they're successfully
44:49
able to avoid sweet potatoes.
44:51
And I don't think they feel like going through that vomiting,
44:56
bloody diarrhea, kind of shock-like experience. And so they can do that.
45:01
But I think it really then is a comment on you don't really know how often this
45:07
occurs or resolves because there are a certain number of people that,
45:12
you know, are out there and you just, they're just not going to re-challenge themselves.
45:16
Yeah, absolutely right. I mean, that's a very judicious comment.
45:20
Exactly. That's what happens in real life. Patients, particularly if they have
45:24
seen a doctor who could not establish this diagnosis, if there's no name tag
45:28
given to it, they are always confused and they know this food has been causing me a problem.
45:33
Why should I be re-exclosing my child to go through all that trouble.
45:36
So they would just continue to avoid that. And until they meet a person who
45:41
could reassure them, you know, things change with time, maybe we can reconsider.
45:45
It's a matter of getting the confidence and talking to them,
45:49
explaining to them what usual outcome is with whatever little we know,
45:53
perhaps would change their mindset.
45:55
But there's no way any parent is going to just say, I know I'm going to try
45:58
this again because they know you like it or not, doc, I'm not going to listen to you.
46:02
This is my experience. You tell me whatever. I'm not going to do that.
46:06
And this is exactly what happened to us. We have some certain patients.
46:08
I don't know. I may have four or five patients only in my practice.
46:13
And two of them, I wanted to do a challenge. But they say, Doc,
46:17
I don't want to do it now. Maybe when the child is older.
46:20
It's another way of telling me I'm not interested. They don't want to tell me,
46:23
no, I don't want to do it. But I totally understand that.
46:26
So there is a role of oral food challenge for such patients,
46:30
but whether they will be willing to do it.
46:34
Because oral food challenge is a supervised test.
46:37
It's a medical, sort of a medical procedure.
46:39
So at least that benefit they will have rather than, you know,
46:42
go eat at home, which they never would do.
46:45
So, yes, but we have to keep talking about this, reassuring a patient,
46:49
know them, this is what you have.
46:51
This is what is expected to happen in spite of our limited knowledge.
46:55
But, you know, that might change their mindset and perhaps, you know,
46:58
they might be willing to do re-exposure.
47:01
And thank you. Excellent talk. Thank you.
47:05
I will come back to you, Dr. Brooks, but there is a question in the chat box.
47:11
What are stool calprotectin and stool alpha-1 antithypsin levels in stool during the episode of.
47:22
F-PIs? So, there's a limited information in that at all. So,
47:28
these are like acute phase reactant in the blood.
47:30
People have noticed with inflammation in the gut, certain markers are released.
47:35
But nobody has looked at particularly using those two proteins to look into the stool.
47:40
At the most, people have looked at stool eosinophils, stool leukocytes and whatnot.
47:44
But F-PIs, nobody has done biopsies for patients with F-PIs.
47:51
Obviously, you're not likely to do it because it's such an acute manifestation and dramatic recovery.
47:56
You are not likely to do any endoscopy and biopsy for this patient.
48:02
Maybe for chronic F-PIs because you want to rule out other gastrointestinal disease.
48:06
So, we really don't have a data. Whatever few times people have done endoscopy,
48:11
all they have found was nonspecific changes, some sort of damage to the villi,
48:16
but nothing observable.
48:19
Observable. So also, there's no evidence, bottom line, of looking at these two
48:26
items as inflammatory markers in F-Pi's.
48:29
Whether F-Pi's is an inflammatory disease, we don't know.
48:33
But once we learn, like I said, there was a recently NIH grant trying to investigate
48:39
the pathology of F-Pi's.
48:40
Perhaps once we know better, people will start looking at different markers
48:43
for F-Pi's. But that's an excellent thought.
48:46
I mean, that's a very astute observation.
48:49
Is there a role for such stool studies?
48:53
Thank you, Dr. Panster. Dr. Brooks, go ahead, ask your question or make a comment.
48:58
I just want to thank you for an excellent description.
49:02
I was first introduced to this disease when I was a fellow in allergy immunology
49:07
some years ago, and the child was worked up for a bloody gastroenteritis by gastroenterology.
49:14
We finally determined he did have a milk allergy and resolved.
49:18
And back then, we called it allergic gastroenteritis. And I took it upon myself
49:24
after he was a year or two to do an oral challenge, and he had exactly what you described.
49:29
He had a massive bloody diarrhea about an hour or two after the challenge and
49:35
became pale and hypotensive and lethargic.
49:39
So I'll never forget this disease. So thank you so much.
49:43
I can guarantee you're not going to forget because you see this once,
49:46
you're going to remember it lifetime.
49:48
And you really want to, you know, you will feel more curious about this disease
49:51
because really it's unfortunate that these patients out there without any labeling
49:55
and they do not because they're not labeled and they're not told what can potentially
49:59
happen which is a very risky proposition Thank you Dr.
50:05
Pansari for that fascinating presentation I really appreciate it Thank you all
50:09
for attending this morning's Grand Round, I'm going to conclude and see you
50:13
all next week Friday at 7.30 in the morning Thank you all Thank you Dr.
50:20
Pansari Bye bye Have a good weekend, good Friday Enjoy the cheese.
50:27
Don't forget to click on the link in this podcast for free credit.
50:30
That may include CME, MOC, or ethics credit, depending on our topic or podcast.
50:36
Music.
50:40
Pediatrics Now is brought to you by University Health's new Women's and Children's
50:45
Hospital and the Department of Pediatrics at the University of Texas Health
50:50
Science Center at San Antonio.
50:52
Our sister podcast is Pediatrics Now for Parents.
50:56
With the exception of Grand Rounds, most topics you hear about here,
51:00
we will have a Pediatrics Now for Parents version.
51:03
It's meant to be one less thing you have to say in the exam room.
51:08
Pediatrics Now for Parents is also found wherever you get your podcasts.