Pre-vaccination allergy testing with COVID-19 mRNA vaccines predicts tolerance

Background: The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy, or with an allergic-like reaction after the first dose remains to be defined. Methods: We studied two cohorts of individuals: one pre-vaccination, the second post-vaccination. Skin testing was performed with COVID-19 mRNA vaccines. Upon negative skin test, a two-step (10%-90%) vaccination protocol was performed. Positive skin tests were confirmed with basophil activation tests (BAT). Vaccine-sensitized patients were offered a five-step induction protocol. Results: We identified 187 patients with high-risk profiles for developing anaphylaxis. In parallel, among 385’926 doses of vaccine, 87 allergic-like reactions were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% in the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced acute asthma exacerbation during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism. Finally, 13 sensitized patients were successfully vaccinated with a five-step vaccination protocol. Conclusion: A two-step 10%-90%-vaccination protocol can be safely administered upon negative skin testing. Yet, it should be delayed in individuals with poorly controlled asthma. Importantly, mRNA vaccine sensitized individuals may receive a five-step vaccination protocol.

Assessment of immediate and non-immediate hypersensitivity contrast reactions by skin tests and provocation tests: A review

Introduction: Allergic and nonallergic hypersensitivity reactions to iodinated contrast media (ICM) and gadolinium-based contrast media are classified as immediate or non-immediate hypersensitivity reactions (IHR and NIHR), respectively. Skin tests and provocation tests are recommended for the evaluation of hypersensitivity reactions to contrast agents; however provocations are not common in clinical practice. Methods: A MEDLINE search was conducted to investigate studies comprising both skin tests and provocation tests that evaluated hypersensitivity reactions to ICM. Results: Nineteen studies were identified that reported on skin tests, followed by provocations. In the case of IHR to ICM, 65/69 (94%) patients with a positive skin test for the culprit media tolerated a challenge with a skin-test-negative alternative ICM. In IHR to ICM with a negative skin test for the culprit media, provocations were positive in 3.2%–9.1% patients. In the case of a NIHR to ICM with a positive skin test, provocation with a skin-test-negative agent was tolerated in 75/105 (71%) of cases. In NIHR with a negative skin test for the culprit agent, re-exposure to the culprit or an alternative was positive in 0%–34.6% patients. Provocations with the same ICM in skin test positive patients with IHR or NIHR were positive for a majority of the patients, although such provocation tests were rarely performed. Data on hypersensitivity reactions, skin tests and provocations with gadolinium-based contrast media were limited; however, they exhibited a pattern similar to that observed in ICM. Conclusion: In both ICM and gadolinium-based contrast media, the risk of an immediate repeat reaction is low when skin tests are negative. In contrast, a provocation with a skin-test-positive contrast medium showed a high risk of an immediate repeat hypersensitivity reaction. Therefore, a thorough medical history is necessary, followed by skin tests. A provocation is recommended, for diagnostic work-up, when the diagnosis is uncertain.

The use of topical zinc in tuberculin test

with under-diagnosis or over-diagnosis commonly occurring. The tuberculin test as a supporting examination for tuberculosis infection has a false negative value rate of 10-25%. Also, a majority of children with tuberculosis have lower plasma zinc levels than healthy children. Zinc deficiency may impair the immune response, leading to more false negative skin-test results.Objective To evaluate the effectiveness of topical zinc for augmenting the diameter of tuberculin induration in children with tuberculosis.Methods This unblinded, clinical trial was performed from October to December 2012 in subjects matched with themselves. Subjects were children with tuberculosis aged 2-18 years at the Department of Child Health at Cipto Mangunkusumo Hospital and Persahabatan Hospital. Every subject was injected tuberculin in volar region of left and right arm. Test sites then were covered with topical zinc cream on the right arm and placebo cream on the left arm. Indurations were measured after 72 hours. The difference of tuberculin diameter of 3 mm was considered as clinically significant. Data analysis was performed with Wilcoxon signed rank test.Results There were 47 subjects in this study. The majority of subjects were well-nourished (53%). Subjects’ median treatment duration was < 6 months, median age was 72 months and 47% of subjects were under the age of five years. Sixteen subjects had a median 1 mm difference in tuberculin induration diameter between the zinc arm and placebo arm (P<0.001), but this was clinically insignificant. Twenty-two subjects (43%) had Koch reaction after zinc cream application, but the placebo cream did not cause Koch reaction.Conclusion Application of topical zinc does not increase tuberculin induration compared to placebo.

Cephalosporin Induced Disulfiram-Like Reaction: A Retrospective Review of 78 Cases

Concomitant ingestion of alcohol and cephalosporin may cause a disulfiram-like reaction; however its fatal outcomes are not commonly known. We retrospectively reviewed 78 patients who had cephalosporin induced disulfiram-like reaction (CIDLR). The patients who had a negative skin test to cephalosporin prior to intravenous antibiotics were included, and those who were allergic to either alcohol or antibiotics were excluded. The average age of 78 patients was 37.8±12.2 (21–60) years. Of the 78 patients, 93.58% of the patients were males, 70.51% of the patients consumed alcohol after use of antibiotics, and 29.49% patients consumed alcohol initially, followed by intravenous antibiotics; however, no significant difference of morbidity was observed in these two groups. All patients were administered antibiotics intravenously. Five of 78 patients (6.41%) developed severe CIDLR too urgently to be rescued successfully. In conclusion, it is important for clinicians to educate patients that no alcohol should be used if one is taking cephalosporin. Also, clinicians should keep in mind that cephalosporin should not be prescribed for any alcoholics.

The Differences and Similarities between Allergists and Non-Allergists for Penicillin Allergy Management

The purpose of this study was to compare the management of patients with a history of penicillin allergy between allergists and non-allergists in Thailand. A questionnaire was distributed to Thai physicians by online survey. The answers from 205 physicians were analyzed. The discrepancy of penicillin allergy management between allergists and non-allergists was clearly demonstrated in patients with a history of an immediate reaction in the presence of penicillin skin test (P<0.01) and in patients with a history of Stevens-Johnson syndrome (P<0.05) from penicillin. Allergists are more willing to confirm penicillin allergic status, more likely to carefully administer penicillin even after negative skin test, but less concerned for the potential cross-reactivity with 3rd and 4th generation cephalosporins, compared to non-allergists. The lack of penicillin skin test reagents, the reliability of penicillin allergy history, and medicolegal problem were the main reasons for prescribing alternate antibiotics without confirmation of penicillin allergic status. In summary, the different management of penicillin allergy between allergists and non-allergists was significantly demonstrated in patients with a history of severe non-immediate reaction and in patients with a history of an immediate reaction when a penicillin skin test is available.