ABSTRACT
Background: Polyethylene glycol (PEG) and polysorbate are two commonly used excipients in cosmetics, therapeutics, and processed foods. They are used not just to stabilize and preserve but also to influence the pharmacokinetics and bioavailability of the active ingredients of these products. Numerous reports have described patients with recurrent urticaria self-reporting multiple unrelated products hypersensitivities. We aim to describe a case series of sensitization to PEG in patients with recurrent urticaria and its implications to the currently available COVID-19 vaccines in Malaysia. Method(s): Data of all patients during the peak vaccination period (March 2021 -May 2021) who had positive intradermal test to surrogate PEG and polysorbate 80 were retrieved and analyzed. They were tested with PEG 4000 (macrogol), PEG 400 (Systane Ultra eye drop) and polysorbate 80 (Tween 80). Result(s): A total of eight patients were skin test positive to PEG and/ or polysorbate 80. The mean age was 35.1 +/- 10.5 years. Only one patient was male. Everyone reported history of multiple product reactions with recurrent urticaria as the major symptom. Majority (75%) had multiple unrelated products hypersensitivities. Four of them had urticarial reactions after the first dose of mRNA vaccine. Two patients were skin test negative to the lower molecular weight PEG 400. Cross sensitization between PEG 4000 and polysorbate 80 was 100%. All patients were subsequently inoculated with two doses of inactivated virus COVID-19 vaccine without any serious sequalae. Conclusion(s): The validity of skin testing towards PEG is not yet clear. Nonetheless it is a promising tool in diagnosing PEG sensitization in selected patients reporting recurrent urticaria with multiple unrelated products. Pretesting of this select group may be considered before the inoculation of PEG-containing COVID-19 vaccine.
ABSTRACT
A 46-year-old man with no known allergies or history of atopy was referred for the investigation of a severe anaphylactic reaction following root canal dental treatment. The procedure had been done under local anaesthetic and involved drilling the tooth, removal of dental pulp, cleaning and insertion of a temporary filling. Preliminary skin prick tests (SPTs) and intradermal tests were negative to natural rubber latex, articaine (the local anaesthetic used for his procedure), lidocaine and chlorhexidine. He had negative specific IgE to chlorhexidine and latex, and a negative lidocaine challenge, confirming that he was not allergic to lidocaine. He returned for further dental treatment, which was done without local anaesthetic. As the procedure was completed, he developed severe anaphylaxis again. He made a full recovery and his dentist was asked for detailed information and samples of all the materials used during the procedure. Subsequent SPT showed a positive weal of 12 x 6 mm to the dental lubricant, Glyde, which was used on both occasions. Its ingredients included polyethylene glycol (PEG) 4253. SPT to other high-weight macrogol-containing products showed positive reactions to a 5% lidocaine ointment, Movicol, EMLA cream and Depomedrone. On further questioning he recalled minor immediate irritation after using a brand of children's shampoo, but a SPT to the shampoo was negative. An open test, closed test and SPT to a lower-molecular-weight patch-test allergen (PEG400 in petrolatum) were negative. PEGs or 'Macrogols' are hydrophilic polymers used in food, cosmetics and pharmaceutical reagents. They have recently attracted attention as they are excipients in several COVID-19 vaccines and have been suggested as a possible cause of anaphylaxis. Anaphylaxis to higher-molecular-weight PEGs has been reported from the use of bowel preparations and parenteral steroids. There are a handful of reports of contact urticaria to PEG-containing medicaments. We report this case to raise awareness of severe immediate hypersensitivity to these apparently innocuous ingredients and a novel source of exposure. A low index of suspicion, lack of standardized nomenclature and commercial reagents for testing are current barriers to diagnosis.
ABSTRACT
Background: Delayed local reactions due to mRNA vaccines or COVID arm have been reported. COVID arm commonly presents as an itchy and painful erythematous plaque with swelling and is characterized by a delayed onset of 7 to 10 days after vaccination. New excipients used in mRNA vaccines (polyethylene glycol (PEG)-2000, tromethamol and 1,2-distearoyl-sn-glicero-3-phosphocholine) have increased the awareness about their role in such cutaneous adverse reactions. Objectives: To define the excipient accountability in COVID arm through specific skin provocation testing. Methods: Health workers of a tertiary level hospital suffering COVID arm were patch, skin prick (SP) and intradermal (ID) tested with PEG-400, PEG-2000, tromethamol and 3-phosphocholine at different concentrations (0.001%, 0.01%, 0.1% and 1%). Positive long standing ID reactions were biopsied. Results: Eleven patients were included. Patch tests were always negative. PEG-2000 presented positive SP at 1% (4 patients) and 0.1% (1 patient). PEG-2000 ID was positive at 1% (10 patients), 0.1% (7 patients) and 0.01% (6 patients). Three showed long standing positive reactions to ID of PEG-2000 on day 2, whose biopsies depicted perivascular lymphocytes, occasional eosinophils and dermal edema. In addition, 6 patients reacted to PEG-400, all of which also reacted to PEG-2000. SP and ID for the other excipients were negative. Conclusions: The presence of immediate and delayed reactions to PEG-2000 in patients. with COVID arm poses a challenge on whether PEG-2000 acts as a delayed sensitizer or. these infrequent reactions are irritative.
ABSTRACT
Background: A 41 y/o woman diagnosed with betalactam hypersensitivity without any other medical condition or treatment was referred to our Allergy Service because of a large local reaction after the application of an Influenza vaccine. She showed a large local reaction, from elbow to shoulder, some hours after the inoculation of an Influenza vaccine in 2005. The reaction disappeared after a week treatment with oral and topical corticosteroids. As a consequence of the present pandemic situation she asked about (the possibility of) getting the SARS-CoV-2 vaccine administered. Methods and results: We performed the prick and intradermal (ID) tests with the available Influenza vaccine and prick and ID (1/100, 1/10 and 1/1) tests with the available SARS-CoV-2 vaccine. Tests with Influenza vaccine were negative and positive 1/10 ID with SARS-CoV-2 vaccine. 1/1 ID test was also positive but in later studies this concentration seemed to be irritating and it wasn't taken into account. Some of the Influenza vaccines commercialized in Spain contain polysorbate 80 and it has shown cross reactivity with other preservatives as polyethylene glycol (PEG), used in the latest SARS-CoV-2 vaccines. As we didn't know the exact Influenza vaccine administered to our patient, and being suspicious that it could have contained polysorbate 80, we performed epicutaneous tests with both polysorbate 80 and PEG-400 7 days after the neutralization of the first tests. Polysorbate 80 was negative but PEG-400 was positive 96 hours later and it reactivated the 1/10 and 1/1 ID tests of the SARS-CoV-2 vaccine, which is known as a flare-up phenomenon. Conclusions: We present a singular case of a flare-up phenomenon of intradermal tests to SARS-CoV-2 vaccine after an epicutaneous test with PEG-400. According to our present experience, this is the first documented report of this type involving PEG and SARS-CoV-2 vaccine.
ABSTRACT
Background: Vaccines represent an efficient means to control the pandemic of Coronavirus Disease 2019 (COVID-19). Two mRNA-based emergency vaccines have recently been licensed for mass administration: BNT162b2 and mRNA-1273 COVID-19 vaccine. Delayed hypersensitivity reactions these new vaccines can range widely from localized skin symptoms to disseminated exanthemas. Locally confined reactions can be caused by the active component or the excipients in the vaccine. Both mRNA vaccines contain polyethylene glycol (PEG) 2000 lipid conjugate as excipient. PEG and its derivatives with clinical cross-reactivity (polysorbates, laureth-9) are ubiquitous in many drugs. The mRNA-1273 COVID-19 vaccine also contains trometamol, an organic amine used extensively. Method: We reported a series of 14 patients referred to our Allergy Department with suspected delayed large local reactions (DLLR): erythematous and edematous plaques ≥10 cm in diameter accompanied by pain or pruritus, after the administration of BNT162b2 or mRNA-1273 COVID-19 vaccine between January to February 2021. We describe cutaneous manifestations,latency time, treatment and duration of the lesions. We performed patch test in the upper back with PEG 400 1% in petrolatum (pet), PEG 3350 10% pet, PEG 3350 in aqueous solution (aq), PEG 4000 10% pet, polysorbate 80 1% pet, polysorbate 80 10% pet, laureth-9/ sodium lauril sulphate 1%, trometamol 0.50% aq (only in mRNA-1273 vaccinated patients), with readings at day 2 and day 4. Results: We collected 14 patients: 13 received mRNA-1273 and only one BNT162b2 COVID-19 vaccine. Most patients (13/14) reacted to the first dose. 42.9% had detectable serum specific IgG antibodies against SARS-CoV-2 in the last 3 months. The mean size of DLLR was 11.9 ± 1.6 cm and the latency time was 4.4 ± 1.8 days. Ten patients (71.4%) not receive any treatment, and four (28.6%) received topical corticosteroids. The mean duration of the reactions was 4.75 ± 2.7 days when treated and 4.5 ± 0.60 days without treatment, with no significant differences (p = 0.79). All patients completed vaccination with the second dose and 69.2% developed DLLR again. PT were negative in the 100% cases Conclusion: We didn't found any sensitization to excipients in our 14 cases series. We thought that DLLR may occur due to a non-specific inflammatory response or represent the normal immune response to the vaccination, and in our experience, this should not be a contraindication to receive further doses of mRNA vaccines.
ABSTRACT
Background: Vaccination has become increasingly relevant to prevent the global pandemic from coronavirus disease 2019 (COVID-19). Two mRNA-based emergency vaccines have recently been licensed for mass administration: BNT162b2 and mRNA-1273 COVID-19 vaccine. Delayed vaccines hypersensitivity reactions can be caused by residual proteins, or most frequently by excipients. Both mRNA vaccines contain polyethylene glycol (PEG) 2000 lipid conjugate as excipient. PEG and its derivatives with clinical cross-reactivity (polysorbates, laureth-9) are ubiquitous in many drugs. mRNA-1273 COVID-19 vaccine also contains trometamol, an organic amine used extensively. Method: We collected the patients referred to our Allergy Department with systemic skin delayed reaction after the administration of BNT162b2 or mRNA-1273 COVID-19 vaccine between January to February 2021. We recorded age, sex, personal history of allergies and previous SARS-CoV-2 infection. We describe cutaneous manifestations, latency time, treatment, and duration. We performed patch test (PT) in the upper back with PEG 400 1% in petrolatum (pet), PEG 3350 10% pet, PEG 3350 in aqueous solution (aq), PEG 4000 10% pet, polysorbate 80 1% pet, polysorbate 80 10% pet, laureth-9/ sodium lauril sulphate 1%, trometamol 0.50% aq (only in mRNA-1273 vaccinated patients), with readings at day 2 and day 4. Results: The study population comprised 11 patients: 6 (54.5%) received BNT162b2 and the rest received mRNA-1273 COVID-19 vaccine. Most patients (10/11, 90.9%) reacted to the first dose. Almost half of them (5/11, 45.4%) had detectable serum specific IgG antibodies against SARS-CoV-2 in the last 3 months. The most frequent manifestation was generalized maculopapular exanthema (6/11, 54.5%), 2 flaking palms, 1 acute generalized exanthematous pustulosis (AGEP), 1 micropapular exanthema accompanied by a 7-centimeter blister, and 1 multiple fixed drug eruption (MFDE). PT were negative in the 100% cases. We contraindicate the second dose of the vaccine in patients with severe skin reactions (MFDE, AGEP) after the first dose (2/10, 20%). The remaining patients received the second dose, reappearing systemic skin lesions in 1/8 (12.5%), having a maculopapular exanthema again. Conclusion: In our experience, mild exanthemas should not be a contraindication to receive further doses of mRNA vaccines. However, we recommended an exhaustive allergy workout in all patients with systemic skin delayed reaction.