Skip to content

The diagnostic challenge of FPIES

, ,


A 3-month-old girl presents to the emergency department (ED). Her mother has been concerned since she was weaned from breast milk onto formula. She seems more “sicky” after feeds. A week ago she had some formula and after a few hours vomited several times, looked pale and then had diarrhoea. She was diagnosed with gastroenteritis and her mother reverted to breastfeeding again. Today she was given a bottle of formula. Three hours later she vomited six times and, again, looked pale and floppy.

In triage her oxygen sats are 97%, her pulse is 170, her respiratory rate is 50 breaths a minute, temperature 36.6°C and capillary refill time is 3 to 4 seconds. She has a patent airway with no respiratory distress but appears shocked.
A venous blood gas shows a metabolic acidosis with respiratory compensation.

She has a raised sodium of 150, raised urea of 8.1 but otherwise normal renal function, FBC, CRP and LFTs.

You ask a senior for help. “I’m looking after a 3 month old girl who came in with profuse vomiting shortly after having cows milk protein formula. She now appears to be shocked with a metabolic acidosis. Where do I go next?”

The vomiting infant

The vomiting infant poses several challenges. The differential is wide, and each has a different management. Take a look at this framework for looking at vomiting.

If the vomiting is so severe as to cause shock carefully consider surgical causes.

Surgical causes of vomiting in infancy

Malrotation and volvulus

In the malrotated gut, the intestine twists around the superior mesenteric artery (SMA) causing an obstruction. This is volvulus. It often presents in the neonatal period with bilious (green) vomits, a distended abdomen and shock. Treat the underlying shock and insert an NG tube and put it on free drainage. You need to have an early conversation with your friendly paediatric surgeons and consider an upper GI contrast study.


In intussusception, the small intestine telescopes into itself causing bowel obstruction and ischaemia. Intussusception presents with acute abdominal pain with pallor, sometimes separated by periods of lethargy. Cherry-red coloured bloody stools are a late sign secondary to bowel ischaemia. Treat underlying shock, have an early conversation with paediatric surgeons and organise an abdominal ultrasound study, looking for the ‘Doughnut sign’.

Pyloric Stenosis

Pyloric stenosis is a congenital abnormality of the pylorus with a hypertrophied longitudinal layer of muscle. At six to eight weeks of age, as the baby’s volume of feeds increases, this thicker layer of the stomach can lead to an obstructed lumen at the distal end of the stomach. It presents with projectile (no, really projectile) vomits in the second or third month of life. The classic blood gas shows a hypokalaemic, hypochloraemic metabolic alkalosis, but it can be normal. If you have a high clinical suspicion perform an abdominal ultrasound.

But it’s not all surgical. Let’s turn our attention to the medical causes of vomiting in infancy.

Medical causes of vomiting in infancy


Of course, this could be sepsis. Vomiting and shock all point to sepsis. And you’ll need to manage as if it were. But what else could it be?

Urinary Tract Infection

vomiting without diarrhoea in an unwell infant should always prompt clinicians to consider a urinary tract infection, particularly in a febrile infant. In the sick infant with vomiting and diarrhoea without a corroborating family history of sick contacts with similar symptoms, don’t be reassured by the presence of diarrhoea – an unhappy gut due to a UTI can lead to diarrhoea too.

Inborn errors of metabolism (IEOM)

IEOM can often present with profuse vomiting, dehydration and acidosis. Maintain a high clinical suspicion in early newborn presentations, failure to thrive in infancy or a family history of stillbirth, sudden infant death or consanguinity. The basics of blood gases Always check a blood gas and ammonia in a sick infant to out rule time-critical metabolic emergencies. DFTB has a wealth of metabolic resources in our module and posts.

Could this be a cow’s milk protein allergy?

Non-IgE Mediated Cows Milk Protein Allergy – In the case of this infant, the degree of vomiting and dehydration was disproportionate to what is normally expected in a Non-IgE Cows Milk protein (CMP) allergy.

IgE Mediated Cows Milk Protein (CMP) allergy – IgE Mediated CMP allergy can present with vomiting after an ingested allergen, however, other associated signs of hypersensitivity reactions (ie urticaria, angioedema, wheeze or stridor) are usually present.

How about FPIES?

FPIES is a delayed-type non-IgE mediated food protein allergy most often seen in infancy. Enteral exposure to an allergen can lead to the onset of repetitive vomiting within 4 hours. Symptoms can progress to lethargy, pallor, floppiness and even hypovolaemic shock.


ANY food protein, especially

  • Cows Milk Protein
  • Hens Egg
  • Fruit & Vegetables
  • Fish

Infants presenting with an acute FPIES reaction can appear septic.
There is no specific biomarker or diagnostic test for FPIES.
Take a careful history establishing a timeline of symptoms in the context of a feeding history.

Management of FPIES in the Emergency department

  1. Treat underlying shock (bolus 10ml/kg & reassess)
  2. Check blood glucose (BM) and correct if hypoglycaemic (Dextrose 10% 2ml/kg)
  3. If clinical suspicion for sepsis, obtain blood cultures, inflammatory markers, cover with appropriate antibiotics (as per local guidance)
  4. Consider maintenance fluid to correct deficit
  5. Investigate for surgical causes, serious bacterial infection or IEOM as appropriate
  6. If there is a high suspicion for FPIES:
    • Avoid food triggers
    • Treat vomiting with ondansetron
    • Discuss with local allergy specialists

Cows milk protein was identified as the most likely trigger. She started on hydrolysed formula and the symptoms dissipated.

If you don’t think of FPIES, you won’t see it!


Jlidi S, Ben Youssef D, Ghorbel S, Mattoussi N, Khemakhem R, Nouira F, Chaouachi B. La sténose hypertrophique du pylore du nourrisson: a propos de 142 cas [Infantile hypertrophic pyloric stenosis. Report of 142 cases]. Tunis Med. 2008 Jan;86(1):63-7

Justice FA, Auldist AW, Bines JE. Intussusception: trends in clinical presentation and management. J Gastroenterol Hepatol. 2006 May;21(5):842-6

Liacouras CA. Evaluation and management of a child with vomiting. Pediatr Case Rev. 2002 Jan;2(1):3-13

McCollough M, Sharieff GQ. Abdominal surgical emergencies in infants and young children. Emerg Med Clin North Am. 2003 Nov;21(4):909-35

Nowak-Wegrzyn A, Berin MC, Mehr S. Food protein-induced enterocolitis syndrome. J Allergy Clin Immunol Pract 2020;8:24–35.

Nowak-Węgrzyn A, Chehade M, Groetch ME, et al. 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 2017;139:1111–26.

Raghuveer TS, Garg U, Graf WD. Inborn errors of metabolism in infancy and early childhood: an update. Am Fam Physician. 2006 Jun 1;73(11):1981-90

Stiefel G, Alviani C, Afzal NA, Byrne A, du Toit G, DunnGalvin A, Hourihane J, Jay N, Michaelis LJ, Erlewyn-Lajeunesse M. Food protein-induced enterocolitis syndrome in the British Isles. Arch Dis Child. 2021 Aug 26:archdischild-2020-320924

Venter C, Brown T, Shah N, et al. Diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy – a UK primary care practical guide. Clin Transl Allergy 2013;3:23.


  • Shane is a PEM Education Fellow at the Leicester Royal Infirmary in the UK. PEM MSc at University of Edinburgh. Excellent procrastinator, average footballer, terrible at latte art. He/him.

  • Adele is a Registrar in Emergency Medicine at Leicester Royal Infirmary in the UK. Mother & photographer. Preferred pronouns: She/her. She/her.

  • Since 2012, Gary has been a Consultant in Paediatric Allergy at the University Hospitals of Leicester NHS Trust, having been trained at St Mary Hospital, London and University Hospital Southampton Foundation Trust. He completed an Allergy MSc at Imperial College London and now regularly lectures on the food allergy module for the Allergy MSc at University of Southampton. Gary has previously served as one of the RCPCH specialist advisory committee members for Allergy, Immunology and Infectious Diseases. Gary is the lead author for the BSACI nut allergy guidelines and has recently co-lead a national BPSU study on FPIES. He is on the board of trustees for Allergy UK. Preferred pronouns: He/him.


Intubated awake HEADER

Awake, and Paralysed: A Never Event

, ,
Vasoactive drugsHEADER

A Beginner’s Guide to Vasoactive Drug use in Children with Septic Shock

, , ,

Propofol-related Infusion Syndrome

, ,

Paediatric Neck Lumps


Maintenance Fluids in Critical Illness


The BUCKLED trial

Appendix HEADER

Paediatric Appendicitis

Childrens books HEADER

The power of children’s books

Copy of Trial (1)

Bubble Wrap PLUS – November 2023

Copy of Trial (1)

The 75th BUBBLE WRAP X Sheffield Children’s Hospital Emergency Department

How to read a paper HEADER

How To Read a Scientific Paper


Paediatric Idiopathic Intracranial Hypertension

Infantile spasms header

Infantile Spasms


Unwrapping PEM excellence at IAEM23

Sexual behaviour HEADER

Sexual Behaviour in Children – what is “normal”?

Leave a Reply

Your email address will not be published. Required fields are marked *

2 thoughts on “The diagnostic challenge of FPIES”

  1. Great post. One thing, in the cmpa section it says:
    no other associated signs of hypersensitivity reactions (ie urticaria, angioedema, wheeze or stridor) are usually present.
    Is the ‘no’ an error?