Secondary Immunodeficiency and Vaccine Response in Rheumatoid and Psoriatic Arthritis on Immunosuppressive Medicines.

Background Rheumatoid arthritis and psoriatic arthritis patients have dysregulated immune system parameters that may increase infection risk at baseline. In addition, treatment of these conditions with immunosuppressive medications may lead to the development of secondary immunodeficiency (SID). Our objective was to assess SID in a cohort on immunosuppressive medications. We hypothesized that SID is clinically detectable by assessing immune parameters and polysaccharide and protein-based vaccination responses. Methodology A prospective cohort study of 42 subjects on immunosuppressive medications was assessed. Analysis included immunoglobulin levels, lymphocyte subsets, and two-step response to diphtheria, tetanus, and 23-valent Streptococcus pneumoniae vaccinations. Exclusions included primary immunodeficiency, malignancy, pregnancy, neutropenia, immunoglobulin replacement, prior B-cell-depleting medication or chemotherapy, use of non-immunosuppressive medication, or recent use of glucocorticoids. Suboptimal vaccine response was defined as an abnormal response based on standard criteria for each vaccine. Results Low IgM levels (below 50 mg/dL) occurred in seven (17%) subjects and IgG (below 650 mg/dL) in three (7%) subjects. Impaired lymphocyte subsets were uncommon. In total, 33 (78%) subjects completed the two-step vaccination assessment. Overall, 29 of 33 (88%) subjects demonstrated suboptimal response to pneumococcal vaccination, 10 (30%) demonstrated suboptimal response to diphtheria, and four (12%) to tetanus. Two (6%) subjects demonstrated suboptimal response to all vaccinations. Finally, 31 (94%) subjects demonstrated suboptimal response to at least one vaccination. Conclusions SID may develop, is clinically detectable, and most notably demonstrated in suboptimal responses to polysaccharide vaccinations, especially against S. pneumoniae.

Transitions of Care in Patients With Inborn Errors of Immunity.

Inborn errors of immunity (IEI) are a group of inherited conditions caused by damaged monogenic variants that result in impairment and/or dysregulation within the immune system. IEI are typically diagnosed in infancy or early childhood, with clinical presentations that include increased susceptibility to infections, immune dysregulation, autoinflammation, bone marrow failure, and/or malignancy. Historically, transitions of care experienced by patients with IEI have not been well described in the literature. However, with treatment advances extending the long-term survival of patients, this has become a primary area of research. It is crucial to establish guidelines and recommendations specific to the transition of patients with IEI. Transitions may include patients who naturally progress from pediatric to adult care, from inpatient to outpatient settings, or from their established health care team to a new team (ie, moving from one geographic area to another). This narrative review summarizes the current data on transitions of care and describes the health care challenges and patient-related barriers impacting transitions of care. Frameworks with practical guidance on how health care practitioners can better manage care transitions faced by patients with IEI are presented.

A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

Drug Allergy in Women.

Across all settings, women self-report more drug allergies than do men. Although there is epidemiologic evidence of increased drug allergy labeling in postpubertal females, the evidence base for female sex as a risk factor for true immune-mediated drug hypersensitivity reactions (DHRs), particularly in fatal drug-induced anaphylaxis, is low. A focus on the known immunologic mechanisms described in immediate and delayed DHR, layered on known hormonal and genetic sex differences that drive other immune-mediated diseases, could be the key to understanding biological sex variations in DHR. Particular conditions that highlight the impact of drug allergy in women include (1) pregnancy, in which a drug allergy label is associated with increased maternal and fetal complications; (2) multiple drug intolerance syndrome, associated with anxiety and depression; and (3) female-predominant autoimmune medical conditions in the context of mislabeling of the drug allergy or increased underlying risk. In this review, we describe the importance of drug allergy in the female population, mainly focusing on the epidemiology and risk, the mechanisms, and the associated conditions and psychosocial factors. By performing a detailed analysis of the current literature, we provide focused conclusions and identify existing knowledge gaps that should be prioritized for future research.

United States Drug Allergy Registry (USDAR) grading scale for immediate drug reactions.

BACKGROUND: There is no accepted grading system classifying the severity of immediate reactions to drugs. OBJECTIVE: The purpose of this article is to present a proposed grading system developed through the consensus of drug allergy experts from the United States Drug Allergy Registry (USDAR) Consortium. METHODS: The USDAR investigators sought to develop a consensus severity grading system for immediate drug reactions that is applicable to clinical care and research. RESULTS: The USDAR grading scale scores severity levels on a scale of 0 to 4. A grade of no reaction (NR) is used for patients who undergo challenge without any symptoms or signs, and it would confirm a negative challenge result. A grade 0 reaction is indicative of primarily subjective complaints that are commonly seen with both historical drug reactions and during drug challenges, and it would suggest a low likelihood of a true drug allergic reaction. Grades 1 to 4 meet the criteria for a positive challenge result and may be considered indicative of a drug allergy. Grade 1 reactions are suggestive of a potential immediate drug reaction with mild symptoms. Grade 2 reactions are more likely to be immediate drug reactions of moderate severity. Grade 3 reactions have features suggestive of a severe allergic reaction, whereas grade 4 reactions are life-threatening reactions such as anaphylactic shock and fatal anaphylaxis. CONCLUSION: This proposed grading schema for immediate drug reactions improves on prior schemata by being developed specifically for immediate drug reactions and being easy to implement in clinical and research practice.

Drug allergy in older adults: A study from the United States Drug Allergy Registry.

BACKGROUND: Older adults have an increased risk of adverse drug reactions and negative effects associated with alternative antibiotic use. Although the number of antibiotic allergies reported increases with age, the characteristics and outcomes of older adults receiving drug allergy assessment are unknown. OBJECTIVE: To assess the characteristics and outcomes of drug allergy evaluations in older adults. METHODS: We considered patients aged above or equal to 65 years enrolled in the United States Drug Allergy Registry (USDAR), a US multisite prospective cohort (January 16, 2019 to February 28, 2022). Data were summarized using descriptive statistics. RESULTS: Of 1678 USDAR participants from 5 sites, 406 older adults aged above or equal to 65 years (37% 65-69 years, 37% 70-74 years, 16% 75-79 years, and 10% ≥80 years) received 501 drug allergy assessments. USDAR older adults were primarily of female sex (69%), White (94%), and non-Hispanic (98%). Most USDAR older adults reported less than or equal to 1 infections per year (64%) and rated their general health as good, very good, or excellent (80%). Of 296 (59%) penicillin allergy assessments in USDAR older adults, 286 (97%) were disproved. Other drug allergy assessments included sulfonamide (n = 41, 88% disproved) and cephalosporin (n = 20, 95% disproved) antibiotics. All 41 drug allergy labels in USDAR participants aged above or equal to 80 years and all 80 penicillin allergy labels in USDAR men aged above or equal to 65 years were disproved. CONCLUSION: Older adults represented a quarter of USDAR participants but were neither racially nor ethnically diverse and were generally healthy without considerable antibiotic need. Most older adults presented for antibiotic allergy assessments, the vast majority of which were disproved. Drug allergy assessments may be underutilized in the older adults who are most vulnerable to the harms of unconfirmed antibiotic allergy labels.

Outcomes of oral food challenges in a real-world setting, with predictors of outcomes.

BACKGROUND: Oral food challenge (OFC) remains the reference standard for food allergy (FA) diagnosis. OBJECTIVE: This study reports a single-center observational experience with all OFCs conducted over 3 years. METHODS: All OFCs performed at an outpatient office were tracked. The OFCs were conducted without strict prespecified inclusion or exclusion criteria. Demographic information along with results of diagnostic testing and results of the OFCs were recorded. RESULTS: A total of 1132 OFCs were performed, with a median age of 4 years (interquartile range = 2.0-10.0). Of the 1132 OFCs, 862 (76.1%) tolerated the food, whereas 232 (20.5%) experienced a reaction, and 38 (3.4%) did not complete the OFC because of food refusal. The highest percentage of tolerated food was shellfish (91.1%), with the lowest percentage of tolerated food being baked egg (66.1%). There were 66 (5.8%) OFCs that were deemed to be high risk, of which 35 (53.0%) tolerated the food. More than 50% of reactions occurred on the first or second dose, with the most common clinical symptom being urticaria or angioedema, with 29.2% of reactions treated with epinephrine. There were several factors that predicted tolerating an OFC, including the food challenge, the reason for food avoidance, older age at the time of OFC and less reactive skin prick testing, and lower food-specific immunoglobulin E levels. CONCLUSION: Certain factors can predict tolerating an OFC, and even those considered to be high risk can be safely completed in an outpatient setting, with most tolerating the food, and most reactions not requiring treatment with epinephrine.

Direct challenges are the gold standard for most antibiotic allergy evaluations.

Antibiotic allergies are frequently encountered in clinical practice, and delabeling of these allergies has individual and public health benefits. This review focuses on the evidence supporting graded challenges without preceding skin testing in adult and pediatric patients to the major groups of antibiotics including penicillins, cephalosporins, sulfamethoxazole, fluoroquinolones, tetracyclines, macrolides, metronidazole, carbapenems, and aztreonam. The cost savings, time savings, and evidence for performing graded challenges outside of an allergy/immunology office are also reviewed for graded challenges to penicillins.

Teleallergy: Where Have We Been and Where Are We Going?

Telemedicine uptake in allergy/immunology was slow before the coronavirus disease 2019 pandemic, but has accelerated since. This review examines where telemedicine has been in allergy/immunology and where it is headed in the future. Focus is placed on patient, physician, and health care professional satisfaction with telemedicine, capacity to expand access to allergy/immunology care, cost considerations, the regulatory environment, and future applications of telemedicine including adherence monitoring, wearable biosensors, artificial intelligence, and machine learning addressed.