Allergy Timing: Watching the Clock

Immunology is a fascinating and sometimes confusing topic.  This is especially true when considering how the immune system can seemingly turn on its host, causing an allergic response.  Typically, the body will create antibodies against harmful foreign material, such as a virus.  Some individuals will create antibodies against foreign material that is not harmful, such as a food antigen.

 

Anaphylactic & Anaphylactoid

 

When you typically think of an allergic reaction, you think of anaphylactic shock.  The antigen reacts with IgE antibodies which triggers mast cell degranulation (cell granules secreting compounds) and histamine release.  This leads to airway constriction, low blood pressure, fast heartbeat, and respiratory distress.  Common triggers include insect stings, foods, drugs, and latex.  Symptoms commonly occur immediately or within 20 minutes of exposure.  However, delayed response up to several hours may occur after oral ingestion [1].  Very rare cases report delayed reactions up to 24 hours.  This is also the case for most IgE-mediated responses (hives, swelling, vomiting, etc.).

 

The non-immune mediated version of anaphylactic reactions is known as an anaphylactoid reaction.  The antigen instead causes a direct histamine release not related to IgE antibodies or mast cell degranulation [2].  Since IgE antibodies are not involved, an anaphylactoid reaction can occur upon first exposure, whereas anaphylaxis requires prior sensitization or cross-reactivity (think: reacting to latex the first time after being exposed to banana which are very similar) [3].  This type of reaction also cannot be tested via typical IgE-based skin prick and blood tests.  Symptoms commonly occur immediately or delayed a few hours after oral ingestion as in anaphylactic responses.

 

Other Non-IgE Allergic Responses

 

Many reactions can occur through the same non-IgE mediated pathway described above.  Eczema, rash, reflux, colic, bloody stool, diarrhea, constipation, mucous in stool, vomiting, failure to thrive, lethargy, and more are all possible non-IgE allergy symptoms [4].  These are different from an intolerance in that an intolerance is due to low enzyme levels causing the inability to properly digest a particular food molecular, such as lactose, while a non-IgE mediated allergy is an immune response [5].  Non-IgE allergies are difficult to diagnose due to delayed symptoms and lack of easily accessible diagnostic measures [6]. 

 

This type of reaction commonly affects the gastrointestinal (gut) mucosa.  This mucosal barrier is designed to balance digestion, absorption, cohabiting beneficial flora, and maintaining pathogenic immune defense all at once.  This balance is developed during infancy which aligns with early patient onset and then often “outgrowing” the allergy later in life [6].  This immune and gastrointestinal system development explains why non-IgE is much more likely to resolve over time compared to IgE allergies.  We dig deeper into each category of non-IgE allergic disorder here.

 

Non-IgE reaction timing varies widely, with some occurring within an hour of exposure and others taking up to 48 hours.  This depends on the patient’s sensitivity levels and the type of reaction.  Children with acute (immediate and severe) reactions will see an improvement within hours of elimination while those with chronic (persistent and varies in severity) responses can take 3-10 days or longer to recover. 

Chronic Non-IgE Reactions + Breastfeeding?

Many parents are told that it takes upwards of 2 weeks or more for ingested proteins to clear from breast milk.  Research outlined in our article here indicates that timeline is less than 24 hours.  What gives? 

 

Let us look first at children who are immediately switched to a hypoallergenic formula post-reaction.  Those children continue to experience symptoms for 3-10 days or longer in some cases as their bodies heal.  While an acute reaction will see immediate improvements, a chronic one will need much more healing time.  This is the exact same situation for breastfed babies.  The mother’s elimination diet will result in breast milk clear of the targeted proteins within a day and the subsequent infant response is not because her milk continues to harbor allergen proteins for weeks on end. 

 

Formula or Breast Milk

 

The question arises then whether families should go directly to specialized formula or continue to breastfeed?  The benefit to formula is that there is a very specific ingredient deck on the canister, and you know exactly what it contains while breast milk does not have an ingredient label (yet). For moms just starting to learn the allergy ropes, it can be very difficult to navigate, and she may decide that formula is best.  However, mothers who want to continue breastfeeding should most certainly do so. 

 

Medical professionals often recommend formula for a 2-week minimum while mom’s elimination diet takes effect.  That is not necessary as we now know that it does not take that long to clear.  If breastfeeding is your choice, you may keep doing so knowing that your cellular metabolism will slowly reduce the allergen concentration over the course of a day, or supplement with formula for that day. 

 

Continued Symptoms? 

 

Children may continue to exhibit symptoms past the above timeline for a variety of reasons.  Those consuming formula may react to specific ingredients and need a different option.  We discuss the different types of formula here.  A small subset of infants reacts to even elemental formulas which is why it may be vital for mom to continue pumping to keep up supply until a safe formula is found [7].

 

Parents who continue their breastfeeding journey may experience other complications.  Hidden allergens in foods, supplements, beverages, and seasoning may inadvertently continue to add the culprit back to breast milk.  It is also possible that mom may not remove the right allergen, or that there are multiple food allergies, which can take time to determine through trial and error [6].

 

Personal Experience

 

Our oldest daughter, June, presented with extreme colic and mucous stool within a few days of life.  We were told it was normal and sent home.  At a few weeks old, she had severe full-body eczema and several bloody diapers.  We were told that she may have a dairy “intolerance” and to remove it from my diet.  Her symptoms continued for many days before a Gastroenterologist took pity on me and admitted us to the hospital. 

 

June was placed on a 24-hour starvation diet were-in we could give her a little sip of Pedialyte only when she was inconsolable.  After that they gave her Elecare and we were told to stop breastfeeding altogether.  I deeply wanted to continue breastfeeding, so they said I could remove all allergens from my diet for 2 weeks while giving Elecare and try nursing after my milk cleared.  We did exactly that.  June continued to suffer and slowly heal from her eczema, colic, and gastro issues over the course of those two weeks.  When we started nursing, she still had some symptoms. 

 

When our youngest, Rose, exhibited the same symptoms at a few days old, I had myself a good ugly-cry and went back to the elimination diet.  This time, we continued nursing as I now knew the actual molecular scientific data explained above.  Her improvement timeline was nearly identical to June’s, only this time I didn’t have to pump like a madwoman and continuously worry about whether she would return to the breast after formula. 

 

Takeaways

 

It is so critical to know that this is YOUR decision.  The misinformation and extended healing timeline can be so frustrating and heart breaking.  At the end of the day, utilize your medical professional, personal experience, and research to guide what is best for your family. 

 

 

  1. Jurewicz, Mary Ann. "Anaphylaxis: when the body overreacts." Nursing 30.7 (2000): 58.

  2. Jiang, Wenjun, et al. "A mast-cell-specific receptor mediates Iopamidol induced immediate IgE-independent anaphylactoid reactions." International immunopharmacology 75 (2019): 105800.

  3. Lang, David M. "Anaphylactoid and anaphylactic reactions." Drug Safety 12.5 (1995): 299-304.

  4. Jyonouchi, Harumi. "Non-IgE mediated food allergy." Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy) 7.3 (2008): 173-180.

  5. Montgomery, Robert K., et al. "Lactose intolerance and regulation of small intestinal lactase activity." Nutrition and gene expression. CRC Press, 2018. 23-53.

  6. Jyonouchi, Harumi. "Non-IgE mediated food allergy." Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy) 7.3 (2008): 173-180.

  7. Contreras Ramírez, Mónica, et al. "Two Case Reports of Allergies to Amino Acid Based Formula in Patients with Short Bowel Syndrome." Revista Colombiana de Gastroenterologia 31.2 (2016): 165-168.

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