Angiomyomatous hamartoma of subglottic tracheal wall in a 12-year-old adolescent: a case report

Background Allergic rhinitis is the most common allergic disease encountered in a primary care setting. Diagnosis is often made clinically based on response to empiric therapy. However, with long-term treatment failure and/or atypical disease presentation, a differential diagnosis should be considered. The following is a report of an unusual and rare presentation of a subglottic tracheal angiomyomatous hamartoma in an adolescent, treated for many years as allergic rhinoconjunctivitis and asthma. Case presentation A 12-year-old Caucasian was referred to the allergy clinic with a lifetime history of bronchospasms and rhinoconjunctivitis symptoms, treated for many years for asthma and environmental allergies. Cough, posterior nasal drainage, self-described “choking on phlegm,” and a sensation of “a flap in the throat,”, worsened 5 months prior to the initial evaluation. Puncture skin testing for common environmental allergens was negative. Spirometry, performed due to history of chronic cough, showed blunting of the forced expiratory phase. A chest X-ray, immediately ordered to rule out possible extrapulmonary obstruction, showed bilateral bibasilar infiltrates. A noncontrast computerized tomographic scan of the chest, ordered to further elucidate X-ray findings, revealed a subglottic tracheal mass. Following a subsequent transfer and admission to a tertiary hospital center, microlaryngoscopy, bronchoscopy, and microsuspension laryngoscopy were performed to remove the tracheal mass. Pathology confirmed squamous mucosa with polypoid angiomyomatous changes and chronic inflammatory features consistent with angiomyomatous hamartoma. Surgical intervention was successful, and follow-up 1 year postoperatively revealed a healthy, asymptomatic adolescent child with normal lung function. Conclusions Although posterior nasal drainage and cough are typical presenting symptoms in the general patient population, they may be clinically impactful as they could disguise more serious medical conditions. A detailed history and careful physical examination may provide a high index of suspicion of disease, and can help work the differential diagnosis. This case presentation is the first documentation of subglottic hamartoma reported in the pediatric literature with clinical manifestation of environmental allergy and asthma symptoms.

Blood parasites in sympatric lizards: what is their impact on hosts’ immune system?

Assessment of parasites and their pathogenicity is essential for studying the ecology of populations and understanding their dynamics. In this study, we investigate the prevalence and intensity of infection of haemogregarines (phylum Apicomplexa) in two sympatric lizard species, Podarcis vaucheri and Scelarcis perspicillata, across three localities in Morocco, and their effect on host immune response. We used the Phytohaemagglutinin (PHA) skin testing technique to relate the level of immune response with parasite infection. Prevalence and intensity levels were estimated with microscopy, and 18S rRNA gene sequences were used to confirm parasite identity. All parasites belong to the haemogregarine lineage found in other North African reptiles. There were differences in prevalence between localities and sexes. Overall, infected lizards were larger than uninfected ones, although we did not detect differences in parasitaemia across species, sex or locality. The swelling response was not related to the presence or number of haemogregarines, or to host body size, body condition, sex or species. We found no evidence of impact for these parasites on the circulating blood cells or the hosts’ immune system, but more data is needed to assess the potential impact of mixed infections, and the possibility of cryptic parasite species.

Delayed systemic urticarial reactions following mRNA COVID-19 vaccination

Background: As the vaccination campaign in response to the coronavirus disease 2019 (COVID-19) pandemic continues, concerns with regard to adverse reactions to the vaccine remain. Although immediate hypersensitivity reactions have received much attention, delayed systemic urticarial reactions after vaccination can occur. Objective: To describe the clinical presentation, vaccine excipient skin testing results, and outcomes of subsequent COVID-19 vaccination in patients who experienced delayed systemic urticarial reactions after messenger RNA (mRNA) COVID-19 vaccination. Methods: This was a retrospective case series of 12 patients referred to the Mayo Clinics in Rochester, Minnesota, and Jacksonville, Florida, between January 19, 2021, and April 30, 2021, for evaluation of delayed systemic urticarial reactions after mRNA COVID-19 vaccination. Demographics, medical and allergic history, reaction details, vaccine excipient skin testing results (when performed), and the outcome after subsequent vaccination were collected for each patient. Results: The mean age of the patients was 52 years, all were white, and 9 (75%) were women. Half of the patients had a history of drug allergy, and one had a history of chronic spontaneous urticaria. Seven patients reacted to the Pfizer-BioNTech vaccine and five reacted to the Moderna vaccine. Seven patients developed symptoms between 8 and 24 hours after vaccination. Nine patients required antihistamines for treatment. The median time to symptom resolution was 4 days. Nine patients underwent allergist-directed COVID-19 vaccine excipient skin testing, all of which were negative. Ten patients chose to receive their next mRNA COVID-19 vaccine dose, and four patients experienced recurrent delayed urticaria. Conclusion: Delayed systemic urticarial reactions after mRNA COVID-19 vaccination were not life-threatening, could be treated with antihistamines, and were not predicted with vaccine excipient skin testing. They were not a contraindication to subsequent vaccination, although patients should be counseled with regard to the possibility of recurrence.

Tuberculosis detection in nonhuman primates is enhanced by use of testing algorithms that include an interferon-γ release assay

OBJECTIVE To develop a testing algorithm that incorporates multiple assays to evaluate host cellular and humoral immunity and antigen detection concerning Mycobacterium tuberculosis complex (MTBC) infection in captive nonhuman primates. ANIMALS Cohorts of captive-bred and wild-caught macaques from 5 different geographic regions. PROCEDURES Macaques were tested for MTBC infection by use of a γ interferon tuberculosis (GIFT) assay, an interferon-γ release assay, and other assays. In the first 2 cohorts (n = 15 and 181), initial validation of the GIFT assay was performed by use of experimentally infected and unexposed control macaques. In the next 3 cohorts (n = 59, 42, and 11), results were obtained for opportunistically collected samples from macaques exposed during spontaneous outbreaks. RESULTS Sensitivity and specificity of the GIFT assay in the control cohorts were 100% and 97%, respectively, and were variable but enhanced by incorporating results from multiple assays in spontaneous outbreaks. CLINICAL RELEVANCE The detection and management of MTBC infection in captive nonhuman primate populations is an ongoing challenge, especially with animal imports and transfers. Despite standardized practices of initial quarantine with regular intradermal tuberculin skin testing, spontaneous outbreaks continue to be reported. Since infection encompasses a range of disease manifestations over time, a testing algorithm that incorporates multiple assays, such as the GIFT assay, to evaluate host cellular and humoral immunity in addition to agent detection is needed. Testing a combination of samples from controlled studies and spontaneous outbreaks of MTBC infection in nonhuman primates would advance the development and validation of a functional algorithm that incorporates promising tools such as the GIFT assay.

AstraZeneca ChAdOx1-S COVID-19 Vaccine Can Be Safely Administered in Patients with EDTA Allergy

Background: Immediate hypersensitivity reactions to COVID-19 vaccines have been postulated to be linked to their excipients, such as polyethylene glycol (PEG) in Pfizer Comirnaty, or polysorbate 80 and ethylenediaminetetracetic acid (EDTA) in AstraZeneca ChAdOx1-S [recombinant] (Vaxzevria). These excipients are potentially found in a range of other products, including injectable and oral medications as well as intravenous radiocontrast media (RCM) and various cosmetic products.Currently patients with proven excipient allergy may be advised to avoid a COVID-19 vaccine containing that excipient and/or potentially cross-reactive excipients. We present two cases of previously confirmed EDTA anaphylaxis, who had negative Vaxzevria vaccine in-vivo testing and subsequently tolerated the vaccine.Case 1: A patient with history of anaphylaxis to RCM and local anaesthetics (LA) had positive intradermal test (IDT) to EDTA nine years earlier. Skin testing to Vaxzeria vaccine (up to 1:10 IDT), Comirnaty vaccine (up to 1:10 IDT) and EDTA 0.3mg/mL IDT were negative. However, following EDTA 3mg/ml IDT, he developed immediate generalised urticaria without anaphylaxis. Basophil activation testing was negative to disodium EDTA, Vaxzevria and Cominarty vaccines. Given the negative in-vitro and in-vivo testing to Vaxzevria vaccine, he proceeded to Vaxzevria immunisation and tolerated both doses.Case 2: A patient with history of anaphylaxis to RCM had positive skin testing to EDTA and RCM containing EDTA six years earlier. Following referral to COVID19 vaccine clinic, Vaxzevria vaccine (1:10 IDT) and Cominarty vaccine (1:10 IDT) were negative whilst EDTA was positive at 0.3mg/mL IDT. He subsequently tolerated both Vaxzevria vaccinations.Conclusion: Excipient allergy does not necessarily preclude a patient from receiving a vaccine containing that excipient. Allergy testing can help identify excipient-allergic patients who may still tolerate vaccination, which is important in situations where COVID-19 vaccination options are limited.

COVID-19 Vaccine Anaphylaxis: Current Evidence and Future Approaches

Vaccine anaphylaxis is rare; however, severe allergic reactions after administration of a coronavirus disease 2019 (COVID-19) vaccines have been reported. Excipients in the vaccine may play a role in severe allergic reactions post-vaccination. Various mechanisms, including IgE-mediated pathways, direct mass cell stimulation via the Mas-related G protein-coupled receptor-X2, and complement pathway activation, have been proposed to cause the anaphylaxis. Skin testing, using the basophil activation test, has been used to clarify the mechanism of the anaphylaxis and provide safety information for the next injection. Here, we review the current evidence and suggested approaches for patients who experienced an immediate severe allergic reaction to the first dose of a COVID-19 vaccine.

Immediate and Delayed Hypersensitivity Reactions to Antibiotics: Aminoglycosides, Clindamycin, Linezolid, and Metronidazole

Hypersensitivity reactions including IgE-mediated and delayed cell-mediated reactions to aminoglycosides, clindamycin, linezolid, and metronidazole are rare. For aminoglycosides, allergic contact dermatitis is the most frequent reaction for which patch testing can be a useful step in evaluation. For clindamycin, delayed maculopapular exanthems are the most common reactions. There are case reports of clindamycin associated with drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), acute febrile neutrophilic dermatosis, and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). For linezolid, cases of hypersensitivity were exceedingly rare and included urticaria, angioedema, anaphylaxis, delayed rashes, and DRESS. For metronidazole, only rare cases were found across a broad spectrum of reactions including allergic contact dermatitis, fixed drug eruption, angioedema, anaphylaxis, serum sickness-like reaction, SJS/TEN, AGEP, SDRIFE, and a possible case of DRESS. IgE-mediated reactions and anaphylaxis to these types of antibiotics are uncommon, and reports of skin testing concentrations and desensitization protocols are largely limited to case reports and series. Non-irritating skin testing concentrations have been reported for gentamycin, tobramycin, and clindamycin. Published desensitization protocols for intravenous and inhaled tobramycin, oral clindamycin, intravenous linezolid, and oral and intravenous metronidazole have also been reported and are reviewed.

Refractory cytokine release reaction to Nivolumab: Following desensitization algorithms to optimize the management of drug hypersensitivity

Introduction Nivolumab is a fully human IgG4 monoclonal antibody (moAb) against programmed cell death protein 1, approved for the treatment of over ten types of cancer. The use of this and other moAbs has augmented considerably in recent years and this in turn has caused an increase of hypersensitivity reactions (HSR). Case report We present the case of a patient with metastatic renal cell cancer (RCC) who developed a grade 3 cytokine release reaction (CRR) to nivolumab. The maintenance of the symptoms despite of the administration of symptomatic treatment and slowing down the infusion rate of nivolumab during the 1st and 2nd reaction required an allergy evaluation of our patient. Management and outcome Skin testing to Nivolumab with negative results and baseline tryptase within the normal range were observed during the allergy workout. A desensitization protocol with specific premedication was applied to reintroduce the moAb, with no further issues. Moreover, a follow up of the patient in the oncology setting was done showing disease stabilization. Discussion The CRR should be treated by desensitization, in contrast to infusion reactions. The diagnosis of CRR phenotype is based on the clinical presentation and recently, and elevation of IL-6 levels has been shown to be a useful biomarker along with negative skin testing. We can conclude that after a HSR and an appropriate allergy diagnosis of CRR, nivolumab can be safely reintroduced by desensitization without reducing the target dose or the appropriate dilution concentration.