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Q:

10/11/2017
A 15-month-old female developed generalized hives after ingestion of flavored banana milk with no history of other systemic symptoms. She had another episode of hives with homemade ice cream. She tolerates cow`s milk. She continues to have regular diet with no restrictions. The mother denies any history of fever, flu-like symptoms or diarrhea one the day of initial reaction. The second reaction, she had nasal symptoms on that day. There is no new medication use or history of insect venom allergy. The mother is concerned about possible "Propylene Glycol" allergy given this was the only common ingredients! What do you suggest for a reasonable approach in such situation?

A:

Is the timing of the urticaria consistent with an IgE-mediated food reaction? Does the baby eat and tolerate fresh banana? Is the banana flavored milk a commercially purchased product or homemade? If the timing fits (within minutes up to 2 hours), I suggest further evaluation with prick skin testing to the commercial product and reviewing its ingredient label. If skin test positive to that product, then pursue testing to ingredients that seem possible based upon the infant's dietary history.

Regarding the possibility of allergy to propylene glycol, please see the previous question below.

Allergy to macrogols (polyethylene glycol)
Q: 3/6/2013
I have a patient who is allergic to Macrogols. (positive skin prick). My question is this. Is it possible to desensitize such a patient? This patient requires laxatives due to a bowel problem and is feeling that surgery is her only option if she can’t take laxatives.

A: Allergy to macrogols (polyethylene glycol) have been reported in the literature on occasion. Please see the previous question posted on 10/7/2011.

I have a 57y/o pt. who had anaphlaxis requiring ICU care during a bowel prep with polyethylene glycol. Subsequently, PEG was avoided, but she went into shock during colonoscopy due to unlisted PEG in the lubricant. She required an IV epi drip and glucagon (because she is on a Beta blocker for ASHD) and was hospitalized for 2 days. She then stopped taking Multaq and Aldactone because they contain PEG, although she had not reacted to them. I'm aware of previous case reports regarding bowel preps, but don't know how to advise her about other meds with PEG.

A: Thank you for your recent inquiry.

Anaphylaxis to polyethylene glycol ingestion is well recognized. Copied below for your convenience is a very extensive case report as well as a reference to another such report.

Unfortunately as you can see from reading the first case, polyethylene glycols are somewhat ubiquitous and very difficult to avoid. Evidently, based upon your patient's ability to ingest small amounts contained in excipients, the phenomenon in her case is dose related. Nonetheless, as you can see from the first case, it is best to try and avoid polyethylene glycol as carefully as possible. This is a difficult task given the ubiquitous nature of these substances, but it is clearly the safest strategy to employ.

Thank you again for your inquiry and we hope this response is helpful to you.

ALLERGY 62 (1) pages 92,3 2007

We reported an anaphylaxis after oral intake and contact urticaria due to polyethylene glycols.

Polyethylene glycols (PEGs) or macrogols are hydrophilic substances used in many drugs and cosmetics. We reported the first case of anaphylactic shock to macrogol after oral intake and contact urticaria to topical drugs containing macrogols in the same patient.

A 58-year-old man consulted for an anaphylactic shock in 2002 30 min after oral intake of citrate de betaine UPSA® effervescent tablets (UPSA, Agen, France) for dyspepsia. He reported also several reactions of immediate contact urticaria after using corticosteroid creams betneval® (betamethasone valerate; GlaxoSmithKline, Marly-le-Roi, France) and nerisone® (diflucortolone valerate; Schering SA, Lys-lez-Cannoy, France) in 2005 for an eczema. In 1995, he presented a maculopapulous exanthema after oral intake of penglobe® (bacampicillin; AstraZeneca, Rueil-Malmaison, France). He was considered to be allergic to aminopenicillins.

Patch testing with the European standard series, corticosteroid series and the used topical drugs were all negative at 30 min, 48 and 72 h (except Myroxylon Pereirae and fragrance mix with a past relevance).

Then, we performed prick tests. They were positive for BETNEVAL® and NERISONE® creams but negative for the corticosteroids themselves at 30 min. The only two common ingredients of these creams were macrogol (cetomacrogol 1000 in BETNEVAL® cream and macrogol stearate 40 in NERISONE® cream) and stearylic alcohol.

Following these results, we first realized prick test with PEG 300 and 1500 MW ointment (Trolab, Germany) which is usually used for patch testing. It was positive at 30 min. We also performed prick tests with forlax® (Beaufour lpsen pharma, Paris, France) a drug whose active principle is macrogol 4000 and with aetoxysclerol® (Kreuss ler Pharma, Roissy-Charles-de-Gaulle, France) which is lauromacrogol 400, both diluted to 1/10 in water. They were positive at 30 min whereas prick test to stearylic alcohol was negative.

Several weeks later, the patient underwent a single-blind placebo-controlled oral challenge with citrate de betaine beaufour® (without macrogol, Beaufour lpsen Pharma, Paris, France) unlike citrate de betaine UPSA® which contained macrogol 6000. This test was negative. Our patient was probably not allergic to bacampicillin but to macrogol 6000 present in penglobe® (not available nowadays) because allergological tests to penicillins (including oral challenge to ampicillin) were negative.


We concluded to an immediate hypersensitivity to macrogol or PEG. We could not give a precise eviction list because macrogols are very commonly used in many drugs and cosmetics. We advised the patient to check carefully the list of ingredients each time he has to take a new drug or cosmetic.

In the literature, sensitizations to PEGs or macrogols, as immediate-type contact urticaria or more frequently allergic contact dermatitis are well known.

Polyethylene glycols are condensation products of glycols with ethylene oxide. Their chemical formula is HO (CH2 CH2)× OH. Their molecular weights varied from 200 to 700 Da in a liquid form to 1000–6000 Da in a solid form, according to the condensation degree. Polyethylene glycols of weak molecular weight (200–400 Da) have a greater sensitization capacity (1). Our patient had immediate reactions both to weak and high-molecular weight PEGs, which is not usual.

Polyethylene glycols are used as solvent and excipient in topical or systemic drugs, as active principle of drugs, in electrodes gels, insect repulsives, cosmetic and hygiene products, cutting fluids, glue and epoxy hardeners (plasticizers; 1). There are many PEGs derivatives, such as cetomacrogol, lauromacrogol, nonoxynol.

One case of anaphylaxis to macrogol after an intra-articular injection of corticoid has been reported (2). We found rare reports of bronchospasm, anaphylaxis, urticaria or angioedema after ingestion of PEGs solutions for preparation before coloscopy but no allergological exploration was made (3).

This observation underlined that allergy to excipients even if it is a rare event should be considered, a fortiori if there are multiple allergic reactions. To our knowledge, it is the first case of anaphylactic shock to macrogol after oral intake and contact urticaria to topical drugs containing macrogols in the same patient.

We reported an anaphylaxis after oral intake and contact urticaria due to polyethylene glycols.

Polyethylene glycols (PEGs) or macrogols are hydrophilic substances used in many drugs and cosmetics. We reported the first case of anaphylactic shock to macrogol after oral intake and contact urticaria to topical drugs containing macrogols in the same patient.

A 58-year-old man consulted for an anaphylactic shock in 2002 30 min after oral intake of citrate de betaine UPSA® effervescent tablets (UPSA, Agen, France) for dyspepsia. He reported also several reactions of immediate contact urticaria after using corticosteroid creams betneval® (betamethasone valerate; GlaxoSmithKline, Marly-le-Roi, France) and nerisone® (diflucortolone valerate; Schering SA, Lys-lez-Cannoy, France) in 2005 for an eczema. In 1995, he presented a maculopapulous exanthema after oral intake of penglobe® (bacampicillin; AstraZeneca, Rueil-Malmaison, France). He was considered to be allergic to aminopenicillins.

Patch testing with the European standard series, corticosteroid series and the used topical drugs were all negative at 30 min, 48 and 72 h (except Myroxylon Pereirae and fragrance mix with a past relevance).

Then, we performed prick tests. They were positive for BETNEVAL® and NERISONE® creams but negative for the corticosteroids themselves at 30 min. The only two common ingredients of these creams were macrogol (cetomacrogol 1000 in BETNEVAL® cream and macrogol stearate 40 in NERISONE® cream) and stearylic alcohol.

Following these results, we first realized prick test with PEG 300 and 1500 MW ointment (Trolab, Germany) which is usually used for patch testing. It was positive at 30 min. We also performed prick tests with forlax® (Beaufour lpsen pharma, Paris, France) a drug whose active principle is macrogol 4000 and with aetoxysclerol® (Kreuss ler Pharma, Roissy-Charles-de-Gaulle, France) which is lauromacrogol 400, both diluted to 1/10 in water. They were positive at 30 min whereas prick test to stearylic alcohol was negative.

Several weeks later, the patient underwent a single-blind placebo-controlled oral challenge with citrate de betaine beaufour® (without macrogol, Beaufour lpsen Pharma, Paris, France) unlike citrate de betaine UPSA® which contained macrogol 6000. This test was negative. Our patient was probably not allergic to bacampicillin but to macrogol 6000 present in penglobe® (not available nowadays) because allergological tests to penicillins (including oral challenge to ampicillin) were negative.

We concluded to an immediate hypersensitivity to macrogol or PEG. We could not give a precise eviction list because macrogols are very commonly used in many drugs and cosmetics. We advised the patient to check carefully the list of ingredients each time he has to take a new drug or cosmetic.

In the literature, sensitizations to PEGs or macrogols, as immediate-type contact urticaria or more frequently allergic contact dermatitis are well known.

Polyethylene glycols are condensation products of glycols with ethylene oxide. Their chemical formula is HO (CH2 CH2)× OH. Their molecular weights varied from 200 to 700 Da in a liquid form to 1000–6000 Da in a solid form, according to the condensation degree. Polyethylene glycols of weak molecular weight (200–400 Da) have a greater sensitization capacity (1). Our patient had immediate reactions both to weak and high-molecular weight PEGs, which is not usual.

Polyethylene glycols are used as solvent and excipient in topical or systemic drugs, as active principle of drugs, in electrodes gels, insect repulsives, cosmetic and hygiene products, cutting fluids, glue and epoxy hardeners (plasticizers; 1). There are many PEGs derivatives, such as cetomacrogol, lauromacrogol, nonoxynol.

One case of anaphylaxis to macrogol after an intra-articular injection of corticoid has been reported (2). We found rare reports of bronchospasm, anaphylaxis, urticaria or angioedema after ingestion of PEGs solutions for preparation before coloscopy but no allergological exploration was made (3).

This observation underlined that allergy to excipients even if it is a rare event should be considered, a fortiori if there are multiple allergic reactions. To our knowledge, it is the first case of anaphylactic shock to macrogol after oral intake and contact urticaria to topical drugs containing macrogols in the same patient.

We reported an anaphylaxis after oral intake and contact urticaria due to polyethylene glycols.

Polyethylene glycols (PEGs) or macrogols are hydrophilic substances used in many drugs and cosmetics. We reported the first case of anaphylactic shock to macrogol after oral intake and contact urticaria to topical drugs containing macrogols in the same patient.

A 58-year-old man consulted for an anaphylactic shock in 2002 30 min after oral intake of citrate de betaine UPSA® effervescent tablets (UPSA, Agen, France) for dyspepsia. He reported also several reactions of immediate contact urticaria after using corticosteroid creams betneval® (betamethasone valerate; GlaxoSmithKline, Marly-le-Roi, France) and nerisone® (diflucortolone valerate; Schering SA, Lys-lez-Cannoy, France) in 2005 for an eczema. In 1995, he presented a maculopapulous exanthema after oral intake of penglobe® (bacampicillin; AstraZeneca, Rueil-Malmaison, France). He was considered to be allergic to aminopenicillins.

Patch testing with the European standard series, corticosteroid series and the used topical drugs were all negative at 30 min, 48 and 72 h (except Myroxylon Pereirae and fragrance mix with a past relevance).

Then, we performed prick tests. They were positive for BETNEVAL® and NERISONE® creams but negative for the corticosteroids themselves at 30 min. The only two common ingredients of these creams were macrogol (cetomacrogol 1000 in BETNEVAL® cream and macrogol stearate 40 in NERISONE® cream) and stearylic alcohol.

Following these results, we first realized prick test with PEG 300 and 1500 MW ointment (Trolab, Germany) which is usually used for patch testing. It was positive at 30 min. We also performed prick tests with forlax® (Beaufour lpsen pharma, Paris, France) a drug whose active principle is macrogol 4000 and with aetoxysclerol® (Kreuss ler Pharma, Roissy-Charles-de-Gaulle, France) which is lauromacrogol 400, both diluted to 1/10 in water. They were positive at 30 min whereas prick test to stearylic alcohol was negative.

Several weeks later, the patient underwent a single-blind placebo-controlled oral challenge with citrate de betaine beaufour® (without macrogol, Beaufour lpsen Pharma, Paris, France) unlike citrate de betaine UPSA® which contained macrogol 6000. This test was negative. Our patient was probably not allergic to bacampicillin but to macrogol 6000 present in penglobe® (not available nowadays) because allergological tests to penicillins (including oral challenge to ampicillin) were negative.

We concluded to an immediate hypersensitivity to macrogol or PEG. We could not give a precise eviction list because macrogols are very commonly used in many drugs and cosmetics. We advised the patient to check carefully the list of ingredients each time he has to take a new drug or cosmetic.

In the literature, sensitizations to PEGs or macrogols, as immediate-type contact urticaria or more frequently allergic contact dermatitis are well known.

Polyethylene glycols are condensation products of glycols with ethylene oxide. Their chemical formula is HO (CH2 CH2)× OH. Their molecular weights varied from 200 to 700 Da in a liquid form to 1000–6000 Da in a solid form, according to the condensation degree. Polyethylene glycols of weak molecular weight (200–400 Da) have a greater sensitization capacity (1). Our patient had immediate reactions both to weak and high-molecular weight PEGs, which is not usual.

Polyethylene glycols are used as solvent and excipient in topical or systemic drugs, as active principle of drugs, in electrodes gels, insect repulsives, cosmetic and hygiene products, cutting fluids, glue and epoxy hardeners (plasticizers; 1). There are many PEGs derivatives, such as cetomacrogol, lauromacrogol, nonoxynol.

One case of anaphylaxis to macrogol after an intra-articular injection of corticoid has been reported (2). We found rare reports of bronchospasm, anaphylaxis, urticaria or angioedema after ingestion of PEGs solutions for preparation before coloscopy but no allergological exploration was made (3).

This observation underlined that allergy to excipients even if it is a rare event should be considered, a fortiori if there are multiple allergic reactions. To our knowledge, it is the first case of anaphylactic shock to macrogol after oral intake and contact urticaria to topical drugs containing macrogols in the same patient.

Allergy. 2006 Aug;61(8):1021.
Two cases of anaphylaxis to macrogol 6000 after ingestion of drug tablets.
Hyry H, Vuorio A, Varjonen E, Skyttä J, Mäkinen-Kiljunen S.

Sincerely,
Phil Lieberman, M.D.

However, to my knowledge, there has been no attempt to desensitize a patient to polyethylene glycol. I could not find any reference to a desensitization procedure in the literature. The closest thing to a desensitization protocol that I could find was an oral challenge procedure (1). In this article, the authors performed an oral challenge to macrogol 4000.

“After a negative labial test, the oral test was started with a dose of 1 mg of macrogol 4000 and the dose was increased at 30 minute intervals.”

Thirty minutes after the ingestion of a cumulative dose of 7.1 grams (equivalent to the minimal dose contained in some osmotic laxatives) the patient developed a reaction.

Conceivably, one could modify this protocol to attempt a desensitization reaction in your patient. However, as noted above, I am not aware of, and could find no reference to, a successful desensitization to macrogol.

Thank you again for your inquiry and we hope this response is helpful to you.

Reference:
1.Sohy C, et al. Usefulness of oral macrogol challenge in anaphylaxis after intra-articular injection of corticosteroid preparation. Allergy 2008; 63(4):478-487.

Sincerely,
Phil Lieberman, M.D.


Jacqueline A. Pongracic, MD, FAAAAI



UPDATE
Thank you! Appreciate it the efforts and sorry for the typo error in the email.
 
Yes, the urticarial timing is consistent with IgE mediated reaction.
 
I had the discussion with mother about oral challenge with the same product but she did not want to do it. I will consider skin testing if she is willing to do so.
 
The milk though it is banana flavored it does not contain banana. So, did not get information about the banana for this reason. The milk is “ Shattoo banana milk “with ingredient as follows:
 
Whole Milk, Sugar, Annatto color, Natural Flavor, Propylene Glycol, Natural Turmeric Color, Sodium Benzoate, Polysorbate 80, Znthan Gum, Citric Acid, Vitamin D3
 
I thought possible evaluation for Annatto allergies but Propylene Glycol was the common between the two.
 
My question was allergy to “Propylene Glycol “not to “polyethylene glycol”. I thought they are different???
 

Response:
I suggest that the identity of the natural flavor be investigated. This might reveal the culprit. I apologize for the mix-up regarding propylene glycol and polyethylene glycol. Propylene glycol has been associated with contact reactions and allergic contact dermatitis, which was not the issue in this patient.

Jacqueline A. Pongracic, MD, FAAAAI

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