In summary, they wanted to do a research study because the prevalence and natural history for FPIES have not been determined. The objective was to determine the prevalence, clinical manifestations, and rate of recovery for FPIES in this first large scale population based PROspective study. They studied the feeding history of 13,019 infants!! They studied them from birth (prospective vs. retrospective as other studies have been). The study was limited to cows milk protein induced enterocolitis (as apparently in Isreal that is predominant). Of the 13,019 infants- 44 had confirmed FPIES. The most common symptoms were: recurrent vomiting (100% of the patients experienced this marker for FPIES), lethargy, diarrhea, pallor, and bloody diarhea. They also note that all patients experienced symptoms within the first 6mo.(but they were being followed for this study so this had to have helped with diagnostics); also that by 3yrs of age, 90% of the 44 had recovered from the FPIES, they did not report any reactions to soy among these 44 (or other foods) but do note that 8 (of the 44) also had IgE allergy to cows milk proteins.
The article starts out with it's references- dating back to a 1967 paper from Gryboski who studied 21 children with FPIES, and where the original description can be found. Noting that their symptoms were vomiting, diarrhea, vomiting with diarrhea, and colic with resolution of symptoms upon removal of cows milk protein and recurrence of symptoms with reintroduction. They note that the next big study was 20yrs later when Dr.Sicherer studied 22 patients (11 to milk, 11 to soy and 7 of those reacted to both) with the same above criteria for delayed vomiting, diarrhea, resolution of symptoms with removal of proteins and recurrence with reintroduction. It goes on to report how studies have shown that there are some lab reports that may indicate positive correlation with FPIES but are not necessary; such as increased neutrophils in the blood counts 5-8hrs after ingestion and that the mechanisms are not clearly understood but have found involvement with Tumor Necrosis Factor-alpha (TNF-a) increase response and a decrease in Transforming Growth Factor-beta (TGF-b) may be an important role in understanding the mechanisms for diagnosis. In covers that other studies have shown that FPIES can be triggered by other food proteins and common ones include: rice,oats,barley,peas,sweet potato,chicken and turkey. They also go on to say that the largest report to date was on 35 children and that milk protein is actually the 3rd most common offender.
Something I find very interesting to find in print, in an FPIES study, is something so many moms have observed as "classic" ways of determining if symptoms are FPIES trigger while trialing a new food....stop the trial, rest, and restart, if symptoms return stronger- consider it a fail, is something so many moms have connected- on our own. This study puts it into print...."A distinguishing feature of FPIES is that reintroduction of the offending food, either inadvertently or by an oral food challenge, leads to characteristic symptoms delayed approx.2hrs after the ingestion of the offending food".
The article clarifies that this study is the first largest population based study on FPIES (to cows milk protein). The criteria used for their cows milk protein induced FPIES diagnosis was:
- less than 9mo. of age at onset of symptoms
- GI symptoms: repetitive vomiting, diarrhea, or both within 24hrs.
- absence of IgE sources
- resolution of symptoms with removal of cows milk proteins
- positive symptoms with re-challenge
The study statisical analysis on their population including: infant sex, gestational week, birth weight, maternal age, type of delivery, number of siblings, dairy product consumption of mother, and religion (Jewish or non-Jewish), and finally age of when cows milk proteins were introduced. The study found the correlation with FPIES to be with type of delivery and religion of the parents.
It goes on to discuss that of the population base of 13,019 infants, 44 were given the diagnosis of FPIES based on classic criteria:
- recurrent vomiting
- lethargy
- diarrhea
- pallor
- bloody diarrhea
There was also discussion about the oral challenge and how not every infant reacted on the first dose, stating most infants tolerated up to 121ml or more without symptoms but all experienced symptoms by the 2hr time frame (not sure what this showed because with delayed reactions such as this you would have to stop at 5ml and wait 2hrs for symptoms to see if 5ml was indeed enough to elicit a reaction response. They did note this also, in their discussion points of the article: "Because all doses were given within 4 hours or less, it is not possible to know which dose was responsible for the reaction. An optimal study design would be to administer a single dose and increase it every 2 or more days." The other interesting finding to note was that all the infants who participated in the oral food challenge recovered on oral re hydrating drinks and close monitoring- none required an IV (although, again note that a few parents refused the oral challenge due to such severe reaction on first exposures).
The study also addressed "rate of recovery"...ie, when did they outgrown it? Reporting that 50% of the patients had outgrown it by 1yr, 75% by 18mo., and 88.9% by 2yrs.; with only 2 patients still remaining positive for symptoms by 42mo. Of very interesting note is that "among the patients undergoing an oral food challenge, there was a tendency for them to have a later recovery age compared with those for whom the parents refused a challenge". Which I interpret to mean, without strict avoidance; there is greater chance of sensitizing the cell mediators memory which leads to longer time for outgrowing. Strict avoidance is necessary.
In discussion points, a few points of interest for further study is the criteria for diagnosis (involvement of diarrhea, as found that diarrhea is not always present and appears to more of a result of chronically exposed children). And, as mentioned above, the study was inconclusive for the amount of milk that could induce the reaction. Interesting to note that, with this population base, C-section delivery and religion were noted as risk factors although unclear why.
Of note, they noted that Dr.Sicherer's study has been conducted on FPIES in solid foods, where none of the infants in this study developed FPIES to solid foods. They reviewed Dr.Sicherer's study to find that only 7 of the patients he studied had FPIES to solid foods and considered this a "more severe and unique subgroup of FPIES". Also noted that none of the infants in this study required IV placement for their oral food challenges and the study questions if this is necessary as per protocols in hospital now.
They summarized with a statement I agree completely on: "....the prevalence of FPIES is relatively high, and thus pediatricians should be aware of this condition to avoid unnecessary hospitalizations and over treatment". And I would add to that avoiding under-treatment as well.
