Tolerability of sublingual versus vestibular allergy immunotherapy tablet administration: A randomized pilot study.

BACKGROUND: Local application site reactions are common with sublingual allergy immunotherapy (AIT)-tablets for the treatment of allergic rhinitis/conjunctivitis (AR/C) and occasionally lead to treatment discontinuation. Because of the lower mast cell density in the vestibular mucosa than the sublingual area, vestibular AIT-tablet administration may result in fewer adverse events (AEs). This pilot study evaluated the tolerability of the vestibular administration route of AIT-tablets compared with the sublingual route in adult subjects with AR/C. METHODS: Adults (n = 164) aged 18-65 years with AR/C treated with daily birch pollen, grass pollen, ragweed pollen or house dust mite AIT in tablet form were randomized 1:1 to vestibular or sublingual administration for 28 days, followed by 28 days of sublingual administration only. The primary endpoint was the severity (mild, moderate, severe) of local treatment-related adverse events (TRAEs) during the first 28 days of treatment. RESULTS: During the first 28 days, the percentage of subjects in the vestibular and sublingual groups reporting mild TRAEs were 55.6% versus 50.6%, respectively; moderate TRAEs were 27.2% versus 30.1%; and severe TRAEs were 12.3% versus 6.0% (p = .16). In the vestibular group, 95.1% of the subjects experienced at least one TRAE during the first period versus 81.9% in the sublingual group (p = .01) and discontinuation rates due to AEs were higher (12.3% vs. 3.6%). CONCLUSION: The frequencies of subjects experiencing severe TRAEs, at least one TRAE, and discontinuations due to AEs at the initiation of AIT-tablets were numerically higher with vestibular administration than sublingual administration. Sublingual administration should remain the standard of care for subjects treated with AIT-tablets for AR/C.

Safety of Direct Drug Provocation for the Evaluation of Penicillin Allergy in Low-Risk Adults.

BACKGROUND: About 10% of patients have a penicillin allergy label, but less than 5% of them are actually allergic. Unnecessary penicillin avoidance is associated with serious medical consequences. Given the growing number of these labels, it is imperative that our diagnostic strategy for penicillin allergy be as efficient as possible. The validity of traditionally used skin tests (STs) has been questioned, whereas drug provocation testing (DPT), the criterion standard, without previous ST appears very safe in most cases. OBJECTIVE: To evaluate the safety of direct DPT without consideration for ST results and the validity of ST in the diagnosis of penicillin allergy. METHODS: In this prospective cohort study without a control group, we recruited patients consulting an allergist for penicillin allergy. Patients underwent ST followed by DPT regardless of ST results. Patients with anaphylaxis to penicillin within the past 5 years or a severe delayed reaction were excluded, as were those with significant cardiorespiratory comorbidity. RESULTS: None of the 1002 recruited patients had a serious reaction to DPT. Ten (1.0%) had a mild immediate reaction, of whom only 1 (0.1%) was considered likely IgE-mediated. The positive and negative predictive values of ST for an immediate reaction were 3.6% and 99.1%, respectively. CONCLUSIONS: In a low-risk adult population reporting penicillin allergy, ST has very poor positive predictive value. Direct DPT without ST is safe and appears to be an ideal diagnostic strategy to remove penicillin allergy labels that could be implemented in first-line practice.

Revaccination outcomes among adolescents and adults with suspected hypersensitivity reactions following COVID-19 vaccination: A Canadian immunization research network study.

BACKGROUND: COVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations. METHODS: Individuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied. RESULTS: The analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis. All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms. CONCLUSIONS: Most individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination.

Multicentric castleman disease in a child with primary immunodeficiency.

Multicentric Castleman disease is a rare lymphoproliferative disorder mostly seen in adults with HIV. It presents with fever and systemic symptoms and is extremely uncommon in children. We describe a novel case of multicentric Castleman disease associated with primary immunodeficiency (common variable immunodeficiency) and discuss pathophysiologic mechanisms and recent advances in understanding this disease.

Rate of Recurrence of Adverse Events Following Immunization: Results of 19 Years of Surveillance In Quebec, Canada.

BACKGROUND: While adverse events following immunization (AEFI) are frequent, there are limited data on the safety of reimmunizing patients who had a prior AEFI. Our objective was to estimate the rate and severity of AEFI recurrences. METHODS: We analyzed data from the AEFI passive surveillance system in Quebec, Canada, that collects information on reimmunization of patients who had a prior AEFI. Patients with an initial AEFI reported to the surveillance system between 1998 and 2016 were included. Rate of AEFI recurrence was calculated as number of patients with recurrence/total number of patients reimmunized. RESULTS: Overall, 1350 patients were reimmunized, of which 59% were 2 years of age or younger. The AEFI recurred in 16% (215/1350) of patients, of whom 18% (42/215) rated the recurrence as more severe than the initial AEFI. Large local reactions extending beyond the nearest joint and lasting 4 days or more had the highest recurrence rate (67%, 6/9). Patients with hypotonic hyporesponsive episodes had the lowest rate of recurrence (2%, 1/50). Allergic-like events recurred in 12% (76/659) of patients, but none developed anaphylaxis. Of 33 patients with seizures following measles mumps rubella with/without varicella vaccine, none had a recurrence. Compared with patients with nonserious AEFIs, those with serious AEFIs were less often reimmunized (60% versus 80%; rate ratio: 0.8; 95% confidence interval: 0.66-0.86). CONCLUSIONS: Most patients with a history of mild or moderate AEFI can be safely reimmunized. Additional studies are needed in patients with serious AEFIs who are less likely to be reimmunized.

Clinical Approach Used in Medical Consultations for Allergic-Like Events Following Immunization: Case Series Report in Relation to Practice Guidelines.

BACKGROUND: The Joint Task Force on Practice Parameters (JTFPP) guidelines for the investigation and reimmunization of patients who experienced allergic-like events (ALEs) after immunization are predicated on the likelihood of anaphylaxis, assessed through the time to symptom onset (≤ or >4 hours) and number of systems involved. OBJECTIVE: The objectives of this study were to compare the management of a series of patients with ALE in actual practice relative to JTFPP guidelines and to discuss key concepts and considerations in their use. METHODS: This retrospective study was based on a chart review of patients who consulted for suspected vaccine-associated ALEs at a large allergy department in Canada. RESULTS: Only 3 of the 135 patients who presented ALEs after immunization were referred for suspected anaphylaxis. There was no significant difference in the frequency of skin testing or reimmunization of patients whatever the time to symptom onset or number of systems involved in the ALE. Eight patients whose initial ALE occurred within 1 hour after immunization had a recurrence on reimmunization. Another patient whose initial ALE occurred 10 hours after influenza immunization had throat tightening and difficulty swallowing without objective signs. CONCLUSIONS: Most ALEs after immunization are not suggestive of anaphylaxis and should not be managed as such. The definition of anaphylaxis in the JTFPP guidelines is nonspecific and may need to be revisited. Restricting skin testing and graded dose reimmunization to patients whose ALE onset is ≤1 hour (compatible with IgE-mediated reaction) and to those meeting specific clinical criteria for anaphylaxis (whatever the timing) is likely a sufficiently sensitive and cautious approach.

Distance to faults as a proxy for radon gas concentration in dwellings.

This research was done to demonstrate the usefulness of the local structural geology characteristics to predict indoor radon concentrations. The presence of geologic faults near dwellings increases the vulnerability of the dwellings to elevated indoor radon by providing favorable pathways from the source uranium-rich bedrock units to the surface. Kruskal-Wallis one-way analyses of variance by ranks were used to determine the distance where faults have statistically significant influence on indoor radon concentrations. The great-circle distance between the 640 spatially referenced basement radon concentration measurements and the nearest fault was calculated using the Haversine formula and the spherical law of cosines. It was shown that dwellings located less than 150 m from a major fault had a higher radon potential. The 150 m threshold was determined using Kruskal-Wallis ANOVA on: (1) all the basement radon measurements dataset and; (2) the basement radon measurements located on uranium-rich bedrock units only. The results indicated that 22.8% of the dwellings located less than 150 m from a fault exceeded the Canadian radon guideline of 200 Bq/m(3) when using all the basement radon measurements dataset. This percentage fell to 15.2% for the dwellings located between 150 m and 700 m from a fault. When using only the basement radon measurements located on uranium-rich bedrock units, these percentages were 30.7% (0-150 m) and 17.5% (150 m-700 m). The assessment and management of risk can be improved where structural geology characteristics base maps are available by using this proxy indicator.

Thalidomide in Refractory Tuberculomas and Pseudoabscesses.

Paradoxical immune reconstitution inflammatory syndrome is a well-described entity even in immunocompetent children, principally in association with Mycobacterium tuberculosis infections. Central nervous system involvement is a potential life-threatening form, sometimes refractory to standard treatment. We report the case of an HIV-negative refugee teenager, who presented with brain tuberculomas and pseudoabscesses responsive only to thalidomide.

Methodology developed to make the Quebec indoor radon potential map.

This paper presents a relevant approach to predict the indoor radon potential based on the combination of the radiogeochemical data and the indoor radon measurements in the Quebec province territory (Canada). The Quebec ministry of health asked for such a map to identify the radon-prone areas to manage the risk for the population related to indoor radon exposure. Three radiogeochemical criteria including (1) equivalent uranium (eU) concentration from airborne surface gamma-ray surveys, (2) uranium concentration measurements in sediments, (3) bedrock and surficial geology were combined with 3082 basement radon concentration measurements to identify the radon-prone areas. It was shown that it is possible to determine thresholds for the three criteria that implied statistically significant different levels of radon potential using Kruskal-Wallis one way analyses of variance by ranks. The three discretized radiogeochemical datasets were combined into a total predicted radon potential that sampled 98% of the studied area. The combination process was also based on Kruskal-Wallis one way ANOVA. Four statistically significant different predicted radon potential levels were created: low, medium, high and very high. Respectively 10 and 13% of the dwellings exceed the Canadian radon guideline of 200 Bq/m(3) in low and medium predicted radon potentials. These proportions rise up to 22 and 45% respectively for high and very high predicted radon potentials. This predictive map of indoor radon potential based on the radiogeochemical data was validated using a map of confirmed radon exposure in homes based on the basement radon measurements. It was shown that the map of predicted radon potential based on the radiogeochemical data was reliable to identify radon-prone areas even in zones where no indoor radon measurement exists.

Risk factors associated with anaphylaxis and other allergic-like events following receipt of 2009 monovalent AS03-adjuvanted pandemic influenza vaccine in Quebec, Canada.

INTRODUCTION: In Quebec, Canada, receipt of the 2009 AS03-adjuvanted pandemic H1N1 vaccine was associated with increased risk of anaphylaxis and other allergic-like events (ALE), especially among women of childbearing age. In response to this safety signal, a case-control study was conducted to identify potential risk factors. METHODS: A total of 435 ALE (50 anaphylaxis) occurring <24h following pandemic vaccination were compared to 849 age-gender matched controls randomly selected from the provincial Pandemic Influenza Vaccination Registry. More than 60 potential risk factors were evaluated through phone interviews and included demographic information, medical history, medication use or acute respiratory illnesses (ARI) concurrent with vaccination and other risk factors associated with general allergy. Odds ratios (ORs) with 95% confidence intervals were estimated with unconditional logistic regression. RESULTS: Factors associated with increased risk of anaphylaxis included concurrent ARI (18% cases vs. 4% controls, ORadj 7.67, 95%CI: 3.04-13.37), food allergy (26% cases vs. 4% controls, ORadj 3.84, 95%CI: 1.51-9.74) and vaccination during the first four weeks of the campaign (66% cases vs. 50% controls, ORadj 2.16, 95%CI: 1.10-4.25) whereas alcohol exposure (≥1 drink/week) was associated with reduced risk (29% cases vs. 42% controls, ORadj 0.26, 95%CI: 0.13-0.57). These factors were also significantly associated with any ALE but the strength of association was weaker. Allergy to components found in the vaccine (e.g., egg, thimerosal) was infrequent and did not significantly differ between cases and controls. CONCLUSION: Increased anaphylaxis and other allergic-like events observed in association with AS03-adjuvanted pandemic H1N1 vaccine remain mostly unexplained despite extensive risk factor review. However, prior to mass vaccination with similar formulations this safety signal warrants further consideration and better understanding. In particular, the predominance among women of childbearing age may be a clue to underlying biological or hormonal influences on adverse immunological responses to vaccine.

Increased risk of anaphylaxis following administration of 2009 AS03-adjuvanted monovalent pandemic A/H1N1 (H1N1pdm09) vaccine.

BACKGROUND: Anaphylaxis after trivalent influenza vaccination is typically reported at a rate of <1 per million doses. In Quebec, Canada, anaphylaxis following administration of the monovalent AS03-adjuvanted H1N1pdm09 vaccine was reported through passive surveillance at a rate of 8 per million doses administered. This was 20 times higher than the reporting rate for non-adjuvanted trivalent vaccines administered during the six previous seasons. However, adequate estimation of the incidence of anaphylaxis is hindered by wide variations in definitions and diagnosis. METHODS: Using the Brighton collaboration case definition of anaphylaxis, all cases with allergic symptoms (AS) reported to public health were reviewed to estimate the incidence of anaphylaxis following AS03-adjuvanted H1N1pdm09 vaccine. RESULTS: Among 752 reports of allergic symptoms, 33 were initially reported as anaphylaxis of which 20/33 (60%) met the Brighton definition (19/20 with certainty levels 1 or 2). A total of 38 additional cases with onset within 1h of vaccination also met the Brighton definition of anaphylaxis (27 (71%) with certainty levels 1 or 2). The 58 cases meeting Brighton Level 1 or 2 criteria for anaphylaxis represent a 75% increase over the 33 passively reported and an incidence of 13 per million doses administered. CONCLUSION: A substantial number of patients with early-onset allergic symptoms met the most specific levels of the Brighton case definition but were not reported as anaphylaxis. Based on this specific case definition, the incidence of anaphylaxis after AS03-adjuvanted H1N1pdm09 vaccine substantially exceeded that reported with seasonal influenza vaccines, a signal that warrants better understanding.

An approach to define potential radon emission level maps using indoor radon concentration measurements and radiogeochemical data positive proportion relationships.

The aim of this paper is to present the first step of a new approach to make a map of radonprone areas showing different potential radon emission levels in the Quebec province. This map is a tool intended to assist the Quebec government in identifying populations with a higher risk of indoor radon gas exposure. This map of radon-prone areas used available radiogeochemical information for the province of Quebec: (1) Equivalent uranium (eU) concentration from airborne surface gamma-ray surveys; (2) uranium concentration measurements in sediments; and (3) bedrock and surficial geology. Positive proportion relationships (PPR) between each individual criterion and the 1417 available basement radon concentrations were demonstrated. It was also shown that those criteria were reliable indicators of radon-prone areas. The three criteria were discretized into 3, 2 and 2 statistically significant different classes respectively. For each class, statistical heterogeneity was validated by Kruskal-Wallis one way analyses of variance on ranks. Maps of radon-prone areas were traced down for each criterion. Based on this statistical study and on the maps of radon-prone areas in Quebec, 18% of the dwellings located in areas with an equivalent uranium (eU) concentration from airborne surface gamma-ray surveys under 0.75 ppm showed indoor radon concentrations above 150 Bq/m3. This percentage increases to 33% when eU concentrations are between 0.75 ppm and 1.25 ppm and exceeds 40% when eU concentrations are above 1.25 ppm. A uranium concentration in sediments above 20 ppm showed an indoor radon concentration geometric mean of 215 Bq/m3 with more than 69% of the dwellings exceeding 150 Bq/m3 or more than 50% of dwellings exceeding the Canadian radon guideline of 200 Bq/m3. It is also shown that the radon emission potential is higher where a uranium-rich bedrock unit is not covered by a low permeability (silt/clay) surficial deposit.