Anaphylaxis From Ethylene Oxide-Sterilized Dialysis Tubing and Needles: A Case Report.

Hypersensitivity reactions to ethylene oxide-sterilized dialyzers have been well described. Although ethylene oxide is no longer used to sterilize most dialyzers, it is used on other pieces of dialysis equipment. We present a case of a 78-year-old man who experienced dialysis-related anaphylaxis attributed to an IgE-mediated allergy to dialysis tubing and needles sterilized with ethylene oxide. Shortly after transitioning from a tunneled catheter to an arteriovenous fistula, he developed multiple episodes of intradialytic hypotension and syncope within minutes of starting dialysis. Laboratory evaluation revealed marked leukocytosis, eosinophilia, and elevated anti-ethylene oxide IgE antibody. After pretreatment with corticosteroids and antihistamines, the rinsing of dialysis tubing, and transition of access back to a tunneled catheter, he tolerated subsequent dialysis treatments. Review of his history revealed chronic eosinophilia since the time of hemodialysis initiation. We hypothesize his eosinophilia and mast cell degranulation began upon initial exposure to ethylene oxide and hemodialysis equipment. When use of the arteriovenous fistula was resumed, he was exposed to a higher "dose" of ethylene oxide due to the use of needles. The higher antigenic stimuli triggered a memory immune response, leading to mast cell degranulation and repeated anaphylactic episodes that were overcome by minimization of ethylene oxide-sterilized equipment, corticosteroid pretreatment, and the anti-IgE Fc monoclonal omalizumab.

Direct oral amoxicillin challenge without preliminary skin testing in adult patients with allergy and at low risk with reported penicillin allergy.

Introduction: Ten percent of hospitalized patients report penicillin allergy; however, recent studies indicate that ∼98% of these patients are not acutely hypersensitive. Unconfirmed penicillin allergy poses public health risks, and an evaluation of penicillin allergy labels is recommended to improve antibiotic stewardship. Although the most widely accepted protocol is penicillin skin testing, followed by oral amoxicillin challenge, time constraints and resources may preclude this. Recent literature supports the safety and efficacy of direct oral amoxicillin challenge in individuals at low risk. Methods: We retrospectively evaluated direct oral challenge acceptance and outcomes in eligible adult outpatients with allergy and with a penicillin allergy label over a 6-month period. Direct oral amoxicillin challenge was recommended in patients with a history of benign rash, benign somatic symptoms, or unknown history associated with the last penicillin exposure >12 months ago. Those with severe reactions or reactions within 12 months of evaluation were not challenged. The patients were monitored for 60 minutes after challenge and were discharged with instructions to call in the event of a delayed reaction. Results: There were 50 of 355 adults (14%) with a penicillin allergy label seen by a single allergist; of these patients, 38 (76%) met our criteria for a direct oral challenge. The index penicillin associated reactions were mostly remote, and 44 subjects (88%) reported reactions >10 years earlier. Four patients (8%) were de-labeled based on history alone. Twenty subjects (40%) consented to challenge in the clinic, and none developed immediate, or to our knowledge, delayed hypersensitivity reactions. Three of 20 patients (15%) developed self-limited subjective symptoms that were not deemed to constitute true immunoglobulin E mediated hypersensitivity. A total of 24 patients (48%) had the penicillin allergy label removed from their medical record. Conclusion: This study added to the accumulating body of evidence that supports the safety and efficacy of direct provocative challenge without preliminary skin testing to exclude penicillin allergy in individuals at low risk. Larger prospective studies are necessary to confirm these observations.

Refractory Status Epilepticus Associated With a Pathogenic Variant in TNFRSF13B.

Febrile infection-related epilepsy syndrome (FIRES) is a rare epileptic syndrome characterized by new-onset refractory status epilepticus preceded by a febrile illness. Limited literature exists regarding the relationship between primary immunodeficiencies and immune-mediated epilepsy, and the relationship between new-onset refractory status epilepticus and common variable immunodeficiency (CVID) is not well-understood. We present a case of a 21-year-old female with a history of recurrent sinus infections, asthma, thrombocytopenia, atrioventricular nodal reentrant tachycardia, and neonatal seizures who presented with fever and new-onset status epilepticus. She was ultimately diagnosed with a heterozygous variant in TNFRSF13B c.311G>A (p.Cys104Tyr), which encodes for a tumor necrosis factor receptor implicated in CVID.

Immune Responses to SARS-CoV-2 in Solid Organ Transplant Recipients.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is caused by a complex interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics and host immune responses. Hosts with altered immunity, including solid organ transplant recipients, may be at increased risk of complications and death due to COVID-19. A synthesis of the available data on immune responses to SARS-CoV-2 infection is needed to inform therapeutic and preventative strategies in this special population. RECENT FINDINGS: Few studies have directly compared immune responses to SARS-CoV-2 between transplant recipients and the general population. Like non-transplant patients, transplant recipients mount an exuberant inflammatory response following initial SARS-CoV2 infection, with IL-6 levels correlating with disease severity in some, but not all studies. Transplant recipients display anti-SARS-CoV-2 antibodies and activated B cells in a time frame and magnitude similar to non-transplant patients-limited data suggest these antibodies can be detected within 15 days of symptom onset and may be durable for several months. CD4+ and CD8+ T lymphopenia, a hallmark of COVID-19, is more profound in transplant recipients, but SARS-CoV-2-reactive T cells can be detected among patients with both mild and severe disease. SUMMARY: The limited available data indicate that immune responses to SARS-CoV-2 are similar between transplant recipients and the general population, but no studies have been sufficiently comprehensive to understand nuances between organ types or level of immunosuppression to meaningfully inform individualized therapeutic decisions. The ongoing pandemic provides an opportunity to generate higher-quality data to support rational treatment and vaccination strategies in this population.

The Role of Systems Vaccinology in Understanding the Immune Defects to Vaccination in Solid Organ Transplant Recipients.

Solid organ transplant recipients (SOTRs) are at increased risk for many infections, whether viral, bacterial, or fungal, due to immunosuppressive therapy to prevent organ rejection. The same immune defects that render transplanted patients susceptible to infection dampen their immune response to vaccination. Therefore, it is vital to identify immune defects to vaccination in transplant recipients and methods to obviate them. These methods can include alternative vaccine composition, dosage, adjuvants, route of administration, timing, and re-vaccination strategies. Systems biology is a relatively new field of study, which utilizes high throughput means to better understand biological systems and predict outcomes. Systems biology approaches have been used to help obtain a global picture of immune responses to infections and vaccination (i.e. systems vaccinology), but little work has been done to use systems biology to improve vaccine efficacy in immunocompromised patients, particularly SOTRs, thus far. Systems vaccinology approaches may hold key insights to vaccination in this vulnerable population.

Brief Report: Enhanced Allogeneic Cellular Responses to Mismatched HLA-B Antigens Results in More Efficient Killing of HIV Infected Cells.

Epidemiologic studies have demonstrated that HIV-1 discordant couples who share HLA-B alleles were more likely to transmit HIV-1. These data lead us to hypothesize that individuals who match at both HLA-B alleles should have a reduced allogeneic response than those who are not matched. We observed diminished killing of CD4 target cells only when HLA-B alleles were matched. We propose that for cell-associated HIV-1 transmission, the ability of the recipient to eliminate infected cells from a donor partner may be enhanced when HLA-B alleles are different between partners. These findings suggest a novel mechanism for protection against HIV infection.