Food protein-induced enterocolitis syndrome

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Food protein-induced enterocolitis syndrome (FPIES) is a systemic, non IgE-mediated food allergy to a specific trigger within food, most likely food protein. In its acute form, FPIES presents with vomiting that typically begins 1 to 4 hours after trigger food ingestion, alongside paleness of the skin, lethargy, and potentially blood-tinged diarrhea. In the severe form of acute FPIES, continued vomiting may cause severe dehydration or hypotensive shock-like state, requiring hospitalization. In its chronic form, continued exposure to trigger foods results in chronic or episodic vomiting, poor weight gain, failure to thrive, and watery or blood-tinged diarrhea. [1] FPIES can potentially develop at any age, from infancy to adulthood, but most commonly develops within the first few years of life and resolves in early childhood. [1] [2] [3] [4] Atypical FPIES presents with evidence of specific IgE-sensitization via positive specific serum or skin IgE testing to trigger foods; atypical FPIES may prolong time to disease resolution or increase risk of conversion to IgE-mediated food allergy. [5]

Contents

Epidemiology

Historically, symptoms resembling FPIES were first reported in the 1960s, but awareness of the disease was limited for decades after. More recently, awareness has increased with establishment of an ICD-10 code in 2016, and the publication of the first international consensus guidelines for FPIES diagnosis by the AAAAI in 2017. [1] [6]

To date, various studies have estimated FPIES incidence to be between 0.015% and 0.7%. However, establishing the true prevalence of FPIES has been hindered by the scarcity of population-level epidemiological studies, the relatively recent establishment of uniform diagnostic criteria, and under-diagnosis due to disease rarity and lack of awareness. [7] A 2019 United States population-level survey estimated a FPIES prevalence of 0.51% in children. [8] Similar prevalences in children have been found in population-level estimates from Israeli and Spanish studies. [9]

Adult-onset FPIES is far rarer and not as well understood at this time. The prevalence is uncertain, but reported cases thus far have been predominantly female. [10] Median age of onset in reported cases has been between ages 20-40 with 6-8 years of symptoms before diagnosis. [5]

Comorbid Atopy

Numerous studies have found that children with FPIES, compared to those who do not, have significantly higher rates of atopic conditions such as asthma, atopic dermatitis (eczema), IgE-mediated food allergy, and allergic rhinitis. [11] [12] However, the data does not suggest that prior history of FPIES puts children at risk developing those atopic conditions in the future.

Diagnosis

Diagnosis is clinical, based on reported symptoms, as specific IgE and skin prick tests are typically negative (except in cases of atypical FPIES). [13] Differential diagnoses must also be ruled out (see section below). No laboratory test or procedure is currently recommended for FPIES diagnosis.

The underlying pathophysiology of FPIES is not understood at this time, though it is generally understood to be non-IgE mediated. One study found that in patients with non-IgE mediated food allergy, Th2 lymphoproliferative responses were similar to that of patients with IgE-mediated allergies, suggesting an underlying T-cell mechanism of action. [14] Another study found elevated IL-17 markers, elevated innate inflammatory markers, and increased T-cell activation after FPIES reaction. [15]

Acute FPIES

Per international consensus guidelines published in 2017 by the American Academy of Allergy, Asthma and Immunology, acute FPIES diagnosis may be established in a patient who meets the following major criterion and at least three minor criteria: [16]

Major criterion: Vomiting approximately 1-4 hours following oral consumption of a suspected trigger food, without signs of classic IgE-mediated skin or respiratory allergic symptoms (i.e. hives, itchy skin, stridor, wheezing, tightness in throat).

Minor criteria:

Current acute FPIES guidelines further divide acute FPIES reactions into mild to moderate and severe disease presentation. Mild to moderate disease typically presents with 1-3 episodes of vomiting around 1-4 hours after trigger ingestion, reduced activity level pallor, which usually self-resolves without medical intervention, and/or mild diarrhea. Severe disease typically presents with 4+ episodes of bilious and/or projectile vomiting within 1-4 hours, along with possible hypotension, shock, severe dehydration, diarrhea, lethargy, hypothermia, abdominal distension, and/or need for IV rehydration. [1] [16] [2] [3] Laboratory studies in more severe cases might reveal hypoalbuminemia, anemia, eosinophilia, and elevated white blood cell count with a left shift.

Adult-onset FPIES may present differently: based on limited data, adults most commonly present with severe cramping abdominal pain hours after trigger food ingestion; vomiting is only present in around 60% of cases. Nausea and diarrhea may also be present, but the pattern of symptoms varies. Adult-onset FPIES is not recognized under the 2017 consensus guidelines, which may lead to misdiagnosis or under-diagnosis. [5] [10] [17]

Chronic FPIES

Per current guidelines, chronic FPIES with more frequent exposure to trigger foods (typically either milk or soy in baby formula) has a severe presentation: progressive vomiting with diarrhea, which may result in dehydration, metabolic acidosis, failure to thrive and/or hospitalization. Less frequent exposure to trigger foods may present with mild, intermittent vomiting, diarrhea, and/or poor weight gain, but without dehydration or hypotension. Crucially, chronic FPIES is confirmed by the cessation of symptoms within days of removing suspected trigger foods from the diet; additionally, re-introduction of trigger food at a later date will result in an acute FPIES reaction. [1]

Differential Diagnosis

FPIES can be told apart from IgE-mediated food allergy (the most common type of food allergy) by both timing and symptoms. IgE-mediated allergic reactions occur within seconds to minutes of food ingestion, whereas FPIES is a delayed reaction which presents at minimum 30-60 minutes after ingestion. Whereas IgE-mediated reactions may present with itchy rash, hives, wheezing, difficulty breathing, or anaphylaxis; these symptoms do not present in FPIES. [1] [7]

Other differential diagnoses for FPIES include infectious gastroenteritis, celiac disease, inflammatory bowel disease, necrotizing enterocolitis, food protein-induced enteropathy, food protein-induced proctocolitis, and eosinophilic gastroenteritis, among others. [18]

Of note, some data indicates that current consensus diagnostic guidelines may under-diagnose in certain cases; one study found that up to 1/4 of patients with high clinical suspicion of FPIES in a multi-center cohort study in Spain did not meet the 2017 international consensus guidelines, which may suggest different FPIES presentation depending on geographic location, or varying severity of FPIES. [19]

Management

Trigger Avoidance

There is currently no treatment for FPIES except avoidance of known trigger foods. The most common FPIES triggers across most published studies have been cow's milk, soy, grains (especially oats and rice). However, reactions are possible to a number of solid foods, such as eggs, fish, shellfish, meats, peanut, tree nuts, sweet potatoes, and fruits (i.e. banana, avocado, etc.). [1] [2] [3] [6] [12] The list of potential food triggers is varied and can be somewhat region specific; for example, studies in Spain report higher rates of seafood FPIES. [6] There are also cases of FPIES being transmitted through foods in breast milk in rare occasions. [20]

Management of FPIES reaction

During an acute FPIES episode, if symptoms are mild (1-2 vomiting episodes) ondansetron or infacol may be given to control vomiting in children over 6 months of age, along with oral rehydration. If vomiting persists or if child has more severe symptoms (i.e. lethargy, pallor, hypotonia) then the child should be taken to an emergency room or hospital for intramuscular or intravenous ondansetron with IV rehydration. [7] [21] The use of epinephrine or antihistamines is not recommended, as FPIES is not an IgE-mediated reaction.

Chronic FPIES reactions may present with more severe dehydration, hypotension, metabolic acidosis and/or failure to thrive, which requires hospitalization for IV rehydration and nutritional management.

Prognosis

Data regarding time to FPIES resolution varies significantly, and appears to depend on factors such as the specific food trigger and whether it is atypical FPIES. On balance, available data suggests that a majority of FPIES cases to common trigger foods (cow's milk, rice, oat, soy) resolve by age 5, if not sooner. [1] [12] [22] [23]

Related Research Articles

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Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. Symptoms may include red eyes, an itchy rash, sneezing, coughing, a runny nose, shortness of breath, or swelling. Note that food intolerances and food poisoning are separate conditions.

An allergen is an otherwise harmless substance that triggers an allergic reaction in sensitive individuals by stimulating an immune response.

Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typically causes more than one of the following: an itchy rash, throat closing due to swelling that can obstruct or stop breathing; severe tongue swelling that can also interfere with or stop breathing; shortness of breath, vomiting, lightheadedness, loss of consciousness, low blood pressure, and medical shock. These symptoms typically start in minutes to hours and then increase very rapidly to life-threatening levels. Urgent medical treatment is required to prevent serious harm and death, even if the patient has used an epipen or has taken other medications in response, and even if symptoms appear to be improving.

A radioallergosorbent test (RAST) is a blood test using radioimmunoassay test to detect specific IgE antibodies in order to determine the substances a subject is allergic to. This is different from a skin allergy test, which determines allergy by the reaction of a person's skin to different substances.

<span class="mw-page-title-main">Immunoglobulin E</span> Immunoglobulin E (IgE) Antibody

Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.

<span class="mw-page-title-main">Food allergy</span> Hypersensitivity reaction to a food

A food allergy is an abnormal immune response to food. The symptoms of the allergic reaction may range from mild to severe. They may include itchiness, swelling of the tongue, vomiting, diarrhea, hives, trouble breathing, or low blood pressure. This typically occurs within minutes to several hours of exposure. When the symptoms are severe, it is known as anaphylaxis. A food intolerance and food poisoning are separate conditions, not due to an immune response.

<span class="mw-page-title-main">Aspirin-exacerbated respiratory disease</span> Chronic inflammatory disease affecting the sinuses and lungs

Aspirin-exacerbated respiratory disease (AERD), also called NSAID-exacerbated respiratory disease (N-ERD) or historically aspirin-induced asthma and Samter's Triad, is a long-term disease defined by three simultaneous symptoms: asthma, chronic rhinosinusitis with nasal polyps, and intolerance of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). Compared to aspirin tolerant patients, AERD patients' asthma and nasal polyps are generally more severe. Reduction or loss of the ability to smell is extremely common, occurring in more than 90% of people with the disease. AERD most commonly begins in early- to mid-adulthood and has no known cure. While NSAID intolerance is a defining feature of AERD, avoidance of NSAIDs does not affect the onset, development or perennial nature of the disease.

<span class="mw-page-title-main">Allergen immunotherapy</span> Medical treatment for environmental allergies

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<span class="mw-page-title-main">Peanut allergy</span> Type of food allergy caused by peanuts

Peanut allergy is a type of food allergy to peanuts. It is different from tree nut allergies, because peanuts are legumes and not true nuts. Physical symptoms of allergic reaction can include itchiness, hives, swelling, eczema, sneezing, asthma attack, abdominal pain, drop in blood pressure, diarrhea, and cardiac arrest. Anaphylaxis may occur. Those with a history of asthma are more likely to be severely affected.

<span class="mw-page-title-main">Soy allergy</span> Type of food allergy caused by soy

Soy allergy is a type of food allergy. It is a hypersensitivity to ingesting compounds in soy, causing an overreaction of the immune system, typically with physical symptoms, such as gastrointestinal discomfort, respiratory distress, or a skin reaction. Soy is among the eight most common foods inducing allergic reactions in children and adults. It has a prevalence of about 0.3% in the general population.

<span class="mw-page-title-main">Milk allergy</span> Type of food allergy caused by milk

Milk allergy is an adverse immune reaction to one or more proteins in cow's milk. Symptoms may take hours to days to manifest, with symptoms including atopic dermatitis, inflammation of the esophagus, enteropathy involving the small intestine and proctocolitis involving the rectum and colon. However, rapid anaphylaxis is possible, a potentially life-threatening condition that requires treatment with epinephrine, among other measures.

<span class="mw-page-title-main">Egg allergy</span> Type of food allergy caused by eggs

Egg allergy is an immune hypersensitivity to proteins found in chicken eggs, and possibly goose, duck, or turkey eggs. Symptoms can be either rapid or gradual in onset. The latter can take hours to days to appear. The former may include anaphylaxis, a potentially life-threatening condition which requires treatment with epinephrine. Other presentations may include atopic dermatitis or inflammation of the esophagus.

<span class="mw-page-title-main">Tree nut allergy</span> Medical condition

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<span class="mw-page-title-main">Fish allergy</span> Type of food allergy caused by fish

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<span class="mw-page-title-main">Shellfish allergy</span> Type of food allergy caused by shellfish

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<span class="mw-page-title-main">Sesame allergy</span> Food allergy caused by sesame seeds

A food allergy to sesame seeds has prevalence estimates in the range of 0.1–0.2% of the general population, and are higher in the Middle East and other countries where sesame seeds are used in traditional foods. Reporting of sesame seed allergy has increased in the 21st century, either due to a true increase from exposure to more sesame foods or due to an increase in awareness. Increasing sesame allergy rates have induced more countries to regulate food labels to identify sesame ingredients in products and the potential for allergy. In the United States, sesame became the ninth food allergen with mandatory labeling, effective 1 January 2023.

References

  1. 1 2 3 4 5 6 7 8 Nowak-Węgrzyn A, Chehade M, et al. (2017). "International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology". J. Allergy Clin. Immunol. 139 (4): 1111–1126.e4. doi: 10.1016/j.jaci.2016.12.966 . hdl: 10044/1/48017 . PMID   28167094.
  2. 1 2 3 Nowak-Węgrzyn A, Jarocka-Cyrta E, Moschione Castro A (2017). "Food Protein-Induced Enterocolitis Syndrome" (PDF). J Investig Allergol Clin Immunol. 27 (1): 1–18. doi: 10.18176/jiaci.0135 . PMID   28211341.
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  4. ↑ Ruffner, MA (November 2014). "Food Protein-Induced Enterocolitis Syndrome: Insights From Review of a Large Referral Population" (PDF). Pediatrics. 134: S157. doi:10.1542/peds.2014-1817PP. PMID   25363948. S2CID   46053309. Archived from the original (PDF) on 19 July 2018.
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  6. 1 2 3 Bartnikas, Lisa M.; Nowak-Wegrzyn, Anna; Schultz, Fallon; Phipatanakul, Wanda; Bingemann, Theresa A. (May 2021). "The evolution of food protein–induced enterocolitis syndrome". Annals of Allergy, Asthma & Immunology. 126 (5): 489–497. doi:10.1016/j.anai.2021.01.001. PMC   8102378 . PMID   33444729.
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  8. ↑ Nowak-Wegrzyn, Anna; Warren, Christopher M.; Brown-Whitehorn, Terri; Cianferoni, Antonella; Schultz-Matney, Fallon; Gupta, Ruchi S. (October 2019). "Food protein–induced enterocolitis syndrome in the US population–based study". Journal of Allergy and Clinical Immunology. 144 (4): 1128–1130. doi:10.1016/j.jaci.2019.06.032. PMC   7923683 . PMID   31288044.
  9. ↑ Katz, Yitzhak; Goldberg, Michael R.; Rajuan, Nelly; Cohen, Adi; Leshno, Moshe (March 2011). "The prevalence and natural course of food protein–induced enterocolitis syndrome to cow's milk: A large-scale, prospective population-based study". Journal of Allergy and Clinical Immunology. 127 (3): 647–653.e3. doi:10.1016/j.jaci.2010.12.1105. PMID   21377033.
  10. 1 2 Crespo, Jimena; Pérez-Pallise, María Esperanza; Skrabski, Filip; Zambrano, Gabriela; Rojas-Pérez-Ezquerra, Patricia; Noguerado-Mellado, Blanca; Zubeldia, José Manuel; Infante, Sonsoles (November 2022). "The Natural Course of Adult-Onset Food Protein-Induced Enterocolitis Syndrome". The Journal of Allergy and Clinical Immunology: In Practice. 10 (11): 2986–2992. doi:10.1016/j.jaip.2022.06.013.
  11. ↑ Ruffner, Melanie A.; Wang, Kathleen Y.; Dudley, Jesse W.; Cianferoni, Antonella; Grundmeier, Robert W.; Spergel, Jonathan M.; Brown-Whitehorn, Terri F.; Hill, David A. (March 2020). "Elevated Atopic Comorbidity in Patients with Food Protein–Induced Enterocolitis". The Journal of Allergy and Clinical Immunology: In Practice. 8 (3): 1039–1046. doi:10.1016/j.jaip.2019.10.047. PMC   7064432 . PMID   31759160.
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  13. ↑ NIAID-Sponsored Expert Panel; Boyce, J. A.; Assa'Ad, A.; Burks, A. W.; Jones, S. M.; Sampson, H. A.; Wood, R. A.; Plaut, M.; Cooper, S. F.; Fenton, M. J.; Arshad, S. H.; Bahna, S. L.; Beck, L. A.; Byrd-Bredbenner, C.; Camargo Jr, C. A.; Eichenfield, L.; Furuta, G. T.; Hanifin, J. M.; Jones, C.; Kraft, M.; Levy, B. D.; Lieberman, P.; Luccioli, S.; McCall, K. M.; Schneider, L. C.; Simon, R. A.; Simons, F. E.; Teach, S. J.; Yawn, B. P.; Schwaninger, J. M. (December 2010). "Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel". Journal of Allergy and Clinical Immunology. 126 (6): S1–S58. doi:10.1016/j.jaci.2010.10.007. PMC   4241964 . PMID   21134576.
  14. ↑ Morita, Hideaki; Nomura, Ichiro; Orihara, Kanami; Yoshida, Koichi; Akasawa, Akira; Tachimoto, Hiroshi; Ohtsuka, Yoshikazu; Namai, Yoshiyuki; Futamura, Masaki; Shoda, Tetsuo; Matsuda, Akio; Kamemura, Norio; Kido, Hiroshi; Takahashi, Takao; Ohya, Yukihiro (February 2013). "Antigen-specific T-cell responses in patients with non–IgE-mediated gastrointestinal food allergy are predominantly skewed to TH2". Journal of Allergy and Clinical Immunology. 131 (2): 590–592.e6. doi:10.1016/j.jaci.2012.09.005. PMID   23083674.
  15. ↑ Berin, M. Cecilia; Lozano-Ojalvo, Daniel; Agashe, Charuta; Baker, Mary Grace; Bird, J. Andrew; Nowak-Wegrzyn, Anna (September 2021). "Acute FPIES reactions are associated with an IL-17 inflammatory signature". Journal of Allergy and Clinical Immunology. 148 (3): 895–901.e6. doi:10.1016/j.jaci.2021.04.012. PMC   8675150 . PMID   33891982.
  16. 1 2 Nowak-Węgrzyn, Anna; Chehade, Mirna; Groetch, Marion E.; Spergel, Jonathan M.; Wood, Robert A.; Allen, Katrina; Atkins, Dan; Bahna, Sami; Barad, Ashis V.; Berin, Cecilia; Brown Whitehorn, Terri; Burks, A. Wesley; Caubet, Jean-Christoph; Cianferoni, Antonella; Conte, Marisa (April 2017). "International consensus guidelines for the diagnosis and management of food protein–induced enterocolitis syndrome: Executive summary—Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology". Journal of Allergy and Clinical Immunology. 139 (4): 1111–1126.e4. doi:10.1016/j.jaci.2016.12.966. hdl: 10807/130792 . PMID   28167094.
  17. ↑ Du, Yue (Jennifer); Nowak-Węgrzyn, Anna; Vadas, Peter (February 2018). "FPIES in adults". Annals of Allergy, Asthma & Immunology. 121 (6): 736–738. doi:10.1016/j.anai.2018.08.003.
  18. ↑ Feuille E, Nowak-Węgrzyn A (2015). "Food Protein-Induced Enterocolitis Syndrome, Allergic Proctocolitis, and Enteropathy". Curr Allergy Asthma Rep. 15 (8): 50. doi:10.1007/s11882-015-0546-9. PMID   26174434. S2CID   6651513.
  19. ↑ Vazquez-Ortiz, Marta; Argiz, Laura; Machinena, Adrianna; Echeverria, Luis; Blasco, Cristina; Prieto, Ana; Infante, Sonsoles; Vila, Leticia; Garcia, Emilio; Gonzalez-Delgado, Purificación; Vazquez-Cortes, Sonia; Barni, Simona; Martinon-Torres, Frederico; Gomez-Carballa, A.; Boyle, R. (May 2020). "Diagnostic criteria for acute FPIES: What are we missing?". The Journal of Allergy and Clinical Immunology: In Practice. 8 (5): 1717–1720.e2. doi:10.1016/j.jaip.2019.11.034.
  20. ↑ Monti G, Castagno E, Liguori SA, Lupica MM, Tarasco V, Viola S, et al. Food protein-induced enterocolitis syndrome by cow's milk proteins passed through breast milk. The Journal of Allergy and Clinical Immunology 2011; 127:679-80. PMID: 21146866
  21. ↑ Leonard, Stephanie A.; Miceli Sopo, Stefano; Baker, Mary Grace; Fiocchi, Alessandro; Wood, Robert A.; Nowak-Węgrzyn, Anna (May 2021). "Management of acute food protein-induced enterocolitis syndrome emergencies at home and in a medical facility". Annals of Allergy, Asthma & Immunology. 126 (5): 482–488.e1. doi:10.1016/j.anai.2021.01.020.
  22. ↑ Wang, Kathleen Y.; Lee, Juhee; Cianferoni, Antonella; Ruffner, Melanie A.; Dean, Amy; Molleston, Jerome M.; Pawlowski, Nicholas A.; Heimall, Jennifer; Saltzman, Rushani W.; Ram, Gita S.; Fiedler, Joel; Gober, Laura M.; Spergel, Jonathan M.; Brown-Whitehorn, Terri F. (February 2019). "Food Protein–Induced Enterocolitis Syndrome Food Challenges: Experience from a Large Referral Center". The Journal of Allergy and Clinical Immunology: In Practice. 7 (2): 444–450. doi:10.1016/j.jaip.2018.09.009.
  23. ↑ Cherian S, Varshney P (April 2018). "Food Protein-Induced Enterocolitis Syndrome (FPIES): Review of Recent Guidelines". Curr Allergy Asthma Rep. 18 (4): 28. doi:10.1007/s11882-018-0767-9. PMID   29623454. S2CID   4705873.
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