Polyethylenglycol–allergy

Allergic reactions to systemically or topically administered polyethylene-containing drugs.

PEG(s) are given different names depending on the molecular size:

• Macrogols (INN): PEGs used as ointments (see macrogol ointment) as well as laxatives in medicine. They are neither absorbed by the skin nor broken down by the intestine. Their molecular weight serves as a more detailed description; e.g. macrogol 400 = molecular weight of 380-420. PEGs in cosmetics correspond to macrogols in medicine. The term "macrogol 400" is synonymous with "PEG-9", a PEG consisting of 9 EO units.
• PEG Beeswax: gel former in oleogels. The degree of ethoxylation is indicated with a hyphen after the PEG and may range from about 3 to 20.
• PEG esters: are produced by the ethoxylation of carboxylic acids. They are used e.g. in shampoos.
• Polysorbates: These are e.g. surface-active substances like Tween.
• PPG: Polypropylene glycols are produced analogously to PEG from propylene oxide (PO). They are used as a substitute for mineral and vegetable oils.
• Sodium Laureth Sulfate: Used mainly in shampoos and detergents.
• Sodium Laureth Phosphate: Sodium Laureth-4 Phosphate is used in detergents and as an emulsifier in creams.
• Higher molecular weight PEGs form moisturizing films on the skin surface which have only little influence on the skin barrier layers due to their lack of penetration.

Polyethylene glycols or macrogols (PEGS; also known as macrogol when used as a drug), are non-toxic, hydrophilic polymers found in everyday products such as food, cosmetics and drugs (ointments, creams, vaccines). Thus, covalent modification with polyethylene glycol (PEG) can profoundly affect the pharmacokinetic, pharmacological, and toxicological profile of protein- and peptide-based therapeutics.Polyethylene glycols are, depending on chain length, variably consistent (liquid or solid), chemically inert, water-soluble, and nontoxic polymers with the general molecular formula C2nH4n + 2On + 1, formed by polymerization of ethylene oxide. Depending on the chain length, PEGs have different properties. Polyethylene glycols with an average molecular mass between 200 and 400 Da are non-volatile liquids at room temperature. Higher molecular masses lead to wax-like solid consistencies. The most important property of all polyethylene glycols is their solubility in water, their long shelf life (they are not subject to the usual biodegradation processes) and their good general and especially good skin compatibility. Monomethoxypolyethylene glycol (mPEG) is frequently used as an adjuvant in vaccines.

There is extensive and long-term clinical experience with pegylated system therapeutics with regard to their tolerability, e.g. with vaccines as well as with hyposensitizations (HS) with pollen and wasp venom allergens. Polyethylene glycol electrolyte lavage solutions (PEG-ELS) are regularly used for colon cleansing before colonoscopy. Remarkably, cross-sectional studies in pediatric patients with acute lymphoblastic leukemia (ALL) who received pegylated asparaginase (PEG-ASP) intravenously revealed hypersensitivities in the low double digits (10-15%) Browne EK et al (2018).

In case of local (topical) application of macrogolexterna it is of decisive importance that only the low-molecular polyethylene glycols can penetrate through the skin. Only these are likely to be of allergological significance. Allergic reactions after topical application to skin and mucous membranes lead remarkably preferentially to contact urticaria.

With systemic application of polyethylene glycols (oral, intramuscular, intravenous), allergic reactions of the IgE-mediated type (immediate-type allergy) have been described in isolated cases (Giavina-Bianchi P et al. 2019). Clinically, the symptoms of this ADR are manifested in palmoplate itching, generalized urticaria, and angioedema. Severe, even fatal anaphylactic reactions have also been described (Sellaturay P et al. (2020).

A complement factor C3-dependent complement activation is discussed, whereby even small amounts can lead to severe reactions. Furthermore, the induction of a specific IgE-mediated immune reaction (Hyry H et al. 2006) is suspected, although the detection of specific IgE has not been possible so far.

In addition to history and clinic, positive reactions are frequently found in intradermal and prick tests.

Procedure: Systemic reactions of the immediate type: prick or intradermal test for PEGs with different molecular weights. Experience has shown that about 60% of clinically clearly allergic patients respond with a positive skin prick test result.

Alternatively, intradermal testing can be performed. Without knowledge and informed planning, these tests carry a risk that should not be underestimated. They should therefore only be performed in a specialist drug allergy centre (Wylon K et al 2016).

Contact allergic reactions: If a contact allergy is suspected, a polyethylene glycol ointment, test concentration 100 % can be used (Block Hermal cooling lubricants I, ointment bases and emulsifiers).

The general awareness of the allergenic potential of PEG is considered to be low. This is due to a widespread lack of scepticism towards excipients and insufficient product labelling (Wenande E et al. 2016). Information on immediate-type reactions to PEG is limited to anecdotal reports. Also, the potential for PEG sensitization and cross-sensitization to PEG-ylated drugs and structurally related derivatives is likely underestimated (Wenande E et al. 2016). An increase in IgE-mediated allergic adverse events due to the incipient vaccinations with pegylated COVID vaccines can be expected.

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