Voelker, Dayne

Purpose of review Anaphylaxis is a severe type 1 hypersensitivity reaction which is the result of mast cell degranulation causing multiorgan dysfunction. Currently, the most accepted biomarker measurement for mast cell mediated anaphylaxis is serum tryptase measurement. Serum tryptase measurement has limitations including an ideal window of collection during anaphylaxis and must be obtained by venipuncture collection. Urinary mast cell mediators are emerging mast cell biomarkers that can be used for evaluation of mast cell mediated anaphylaxis and mast cell activation. This review will highlight biomarker measurement with urinary mast cell mediators in anaphylaxis. Recent findings This review will highlight biomarker measurement of urinary mast cell mediators including N-methylhistamine, leukotriene E4, and 2,3-dinor-11beta-prostaglandin F2 alpha and their role in anaphylaxis. Summary Urine mast cell mediator collection obtained during acute anaphylaxis and compared to baseline measurements are emerging biomarkers for the detection of mast cell mediated anaphylaxis. Further research is needed to validate the utility of urinary mast cell mediators in anaphylaxis.

Pollen exposure drives allergic disease in millions of Americans, yet no standardized, publicly available national pollen dataset has existed until now. We describe the first nationally standardized and publicly available dataset of pollen season timing and airborne pollen concentrations. The data were derived from the National Allergy Bureau™ (NAB™), the only pollen and mold measuring network in the United States certified by the American Academy of Allergy, Asthma & Immunology (AAAAI), and curated, processed, and disseminated by the U.S. Centers for Disease Control and Prevention (CDC). The 2003–2024 dataset provides standardized measures of (1) taxa-specific historical average main pollen season (MPS) concentrations and timing (e.g., start dates, peak dates, end dates, season length); (2) taxa-specific yearly MPS concentrations and timing; (3) grouped weekly MPS concentrations, levels, and timing; and (4) grouped daily pollen levels and MPS timing. Pollen concentrations are reported as pollen grains per cubic meter (PPCM). MPS timing is computed using a 3-day consecutive method: season start occurs after the first occurrence of three consecutive days with concentrations > 1.0 PPCM; season peak is the day of maximum concentration; and season end occurs after the first occurrence of three consecutive days with concentrations < 1.0 PPCM after the peak. Historical average timing is calculated in a 365-day-of-year format and converted to calendar dates using 2024 as a reference year for display and consistency. By combining long-term data from monitoring sites across the country, this dataset shows how pollen levels vary over time and across geographic locations. This resource supports tracking pollen trends, linking pollen with weather and climate factors, and informing public health action, clinical care, and communication about population exposure and the impact to allergic diseases such as asthma and hay fever.

Background: One in five Americans turn to TikTok before calling their own physician. Objective: With social media on the rise as a source of health-related information, we aimed to investigate and evaluate popular content about mast cell activation syndrome (MCAS) on TikTok. Methods: Between June 14 and 16, 2024, four different MCAS-relevant phrases were searched on TikTok, and the top 50 most watched videos were analyzed independently by three subinvestigators. The global quality score (GQS) (range from 1 to 5) was applied to assess the value of the educational videos. The profession of the content creator, use of MCAS Vienna diagnostic criteria, association with postural orthostatic syndrome (POTS)/Ehlers Danlos syndrome (EDS), and information trends were also analyzed. Results: The 50 most watched MCAS-related videos collectively had > 6.5 million views, and the average number of views per video was 131,500. Most videos were created by health-care professionals (58%), including physicians (26%) and other health-care professionals (32%), whereas the minority were created by non‐health-care professionals (42%). Only one video included the MCAS Vienna criteria (2%), and 12 videos associated MCAS with POTS and/or EDS (24%). The average GQS was 1.94 (SD 0.34). Common MCAS misinformation trends included the following: inaccuracy of symptoms, diagnostic criteria, triggers, and treatment options. Conclusion: Most MCAS videos on TikTok contained misinformation, did not include key diagnostic criteria, and had poor GQS. The most viewed videos were primarily created by health-care professionals. Patients and health-care providers need to be aware of the quality of health-care information on social media.

Abstract: Background: Fragrances/botanicals are ubiquitous allergens. Patients allergic to one fragrance/botanical are frequently sensitive to other fragrances/botanicals and are typically counseled to avoid all fragrances/botanicals. However, broad avoidance of all fragrances/botanicals may not be clinically necessary. Objectives: We examined copositivity patterns in fragrance/botanical patch testing. Methods: The Mayo Clinic patch test database was queried for pairwise copositivity rates for fragrances/botanicals between 1997 and 2022, representing a total of 43 allergens. Data analyzed included 4706 positive reactions out of 252,485 total patches applied to 15,864 patients. After background correction for general positivity, copositivity rates were organized through unsupervised hierarchical clustering to determine copositivity subgroups and then evaluated through network analysis. Results: After background correction, clustering revealed distinct copositivity subgroups: Fragrance Mix I– Myroxylon pereirae –limonene hydroperoxides–linalool hydroperoxides; Compositae Mix–sesquiterpene lactone–parthenolide; Fragrance Mix II–Lyral; lichen acid mix–treemoss extract; menthol– Mentha piperita ; narcissus–dandelion; and Santalum album –trans-anethole–tea tree–lemongrass–clove–turpentine– Rosa damascena – Lavandula – Geranium – Cananga odorata –neroli–bergamot. In addition, there were further isolated intergroup copositivity reactions seen in network analysis. Conclusions: Background correction followed by hierarchical clustering demonstrated the fragrance/botanical group can be divided into multiple copositivity subgroups. Combined with network analysis, patients with a positive patch test to one fragrance/botanical allergen may be preferentially guided to use specific other fragrances/botanicals.

Background Cytokines play an important role in Th1 and Th2 inflammation. Both Th1 and Th2 cytokines can be utilized for evaluation and treatment response in many different disorders, including inborn errors of immunity. The role of broad cytokine panel testing in inborn errors of immunity is not well described. Objective To analyze broad cytokine panel testing in clinical practice. Methods A retrospective review of cytokine panel testing performed at Mayo Clinic was performed. Data were collected from patients at Mayo Clinic Rochester, Mayo Clinic Jacksonville, and Mayo Clinic Health System. Serum cytokine panel testing included the following cytokines: tumor necrosis factor (TNF), IL-6, IFN-β, IL-10, monocyte chemoattractant protein-1 (MCP-1), IL-1β, IFN-γ, macrophage inflammatory protein-1 alpha (MIP-1α), granulocyte-monocyte colony-stimulating factor (GM-CSF), IL-2 receptor α soluble, IFN-α, and IL-18. Data collection ranged from 03/2021 to 09/2024. The study was funded by Mayo CCaTS grant number UL1TR002377. Results A total of 88 cytokine panel tests were performed during the study period on 80 total patients. There was at least 1 elevated cytokine level in 70/88 (80%) tests performed. There was elevation in each individual cytokine level as follows: TNF (49), IL-2 receptor α soluble (40), IFN-α (0), IL-18 (26), IL-6 (33), IFN-β (4), IL-10 (13), MCP-1 (18), IL-1β, IFN-γ (11), MIP-1α (12), and GM-CSF (6). 18 patients that underwent cytokine panel testing had common variable immune deficiency (CVID), and 10 of those patients had granulomatous lymphocytic interstitial lung disease. 6 patients with early onset inflammatory bowel disease, 5 patients with autoimmune lymphoproliferative syndrome, 2 patients with Myhre syndrome, 2 patients with Hyper IgE syndrome, 1 patient with hypereosinophilic syndrome, 1 patient with autoimmune polyglandular syndrome type 1, 1 patient with XIAP deficiency, 1 patient with X-linked chronic granulomatous disease, and 1 patient with STAT 1 gain of function were tested. Other patients tested had other medical diagnoses or were undergoing immunodeficiency evaluation. There was no significant increase noted in any individual cytokine level when compared with the whole cohort. Conclusion Cytokine panel testing could be a potential diagnostic tool in evaluation of inborn errors of immunity. Further research is needed to better characterize the importance of cytokine panel testing in inborn errors of immunity.

ImportancePatients are frequently copositive for multiple allergens simultaneously, either due to chemical similarity or simultaneous sensitization. A better understanding of copositivity groups would help guide contact avoidance.ObjectiveTo use patient data to systematically determine copositivity groups in the Mayo Clinic Standard Series.Design, Setting, and ParticipantsIn this retrospective cross-sectional analysis, the Mayo Clinic patch test database was queried for pairwise copositivity rates in the 80 allergen Mayo Clinic Standard Series between 2012 and 2021. Data were collected from 3 tertiary care sites of the Mayo Clinic Contact Dermatitis Group and a total of 5943 patients were included, comprising all patients undergoing patch testing to the Mayo Clinic Standard Series allergens.Main Outcomes and MeasuresCopositivity rates between every 2 allergens in the 80-allergen Mayo Clinic Standard Series were estimated. After background correction, copositivity rates were analyzed using unsupervised hierarchical clustering to systematically identify copositivity groups in an unbiased manner.ResultsOverall, 394 921 total patches were applied to 5943 patients (4164 [70.1%] women, 1776 [29.9%] men, with a mean [SD] age of 52.3 [18.8] years ), comprising 9545 positive reactions. After background correction based on overall positivity rates, hierarchical clustering revealed distinct copositivity groups. Many were supported by prior literature, including formaldehyde releasers, cobalt-nickel-potassium dichromate, acrylates, 3-dimethylaminopropylamine-amidoamine-oleamidopropyl dimethylamine, alkyl glucosides, budesonide-hydrocortisone-17-butyrate, certain fragrances, compositae-sesquiterpene lactone mix, mercapto mix-mercaptobenzothiazole, carba mix-thiuram mix, and disperse orange-p-phenylenediamine. However, novel associations were also found, including glutaraldehyde-sorbitan sesquioleate, benzalkonium chloride-neomycin-bacitracin, bronopol-methylchloroisothiazolinone-methylisothiazolinone, and benzoic acid-iodopropynyl butylcarbamate.Conclusions and RelevanceThis retrospective cross-sectional analysis found that copositivity rates varied between allergens; allergens with extremely high positivity rates demonstrated nonspecific copositivity to multiple other allergens. Background correction based on positivity rates followed by hierarchical clustering confirmed prior known copositivity groups, contaminants and/or excipients leading to copositivity, and novel associations to guide contact avoidance.

Background: Penicillin is the most common reported drug allergy. Previous literature suggests that there is increased prevalence of penicillin drug allergy in female patients in the outpatient setting. However, this is poorly described in the inpatient setting. Objective: This study was performed to determine whether female sex is an independent risk factor for penicillin allergy in the inpatient setting. Methods: A retrospective review of electronic medical records (January 1, 2001-December 31, 2017) was performed for patients with a history of penicillin allergy who underwent penicillin skin testing (PST). Each chart review included the age at initial skin testing, sex, medications, and medical co-morbidities. The study was approved by the institutional review board. Results: 30,883 patients underwent PST with 29,354 and 1,529 occurring in the outpatient and inpatient setting respectively. 170 patients tested positive with a ≥ 5x5 wheal. Of the 170 positive patients, 122 were female (72%) and 48 were male (28%). 15 patients tested positive in the inpatient setting. Of the 1506 adult patients tested in the inpatient setting, 809 were female and 697 were male. 12 females (92.3%) and 1 one male (7.7%) tested positive with a ≥ 5x5 wheal (OR-10.5; 95% CI-1.4-80.8; p-value=0.02). 23 pediatric patients were tested in the inpatient setting. Two pediatric male patients were positive and no female pediatric patients tested positive (OR-1.7; 95% CI-0.5-5.9; p-value=0.5). Conclusion: In the inpatient setting, adult females are 10 times more likely to have a positive PST compared to males. Female sex may be a potential risk factor for objective penicillin drug allergy in the inpatient setting.

Introduction Fat embolism (FE) induced by iv injection of triolein (T) causes vasculitis, septal inflammation and fibrosis in rat lungs at 48 hrs that is mitigated by two drugs acting on the renin‐angiotensin system (RAS): captopril and losartan (1). The histopathological changes found at this time are also ameliorated by treatment with the renin inhibitor aliskiren as the associated increase in mast cell numbers (2). This study examines whether captopril and losartan also prevent the increase in mast cell number at this time. Methods Sprague‐Dawley rats (280–300g) were treated with 0.2 ml iv (T) n=31 or saline n=7. One hour later 0.2 ml of saline (n=7) ip, aliskiren (50 mg/kg n=6), (100 mg/kg n=6), captopril (150 mg/kg n=6) or losartan (10 mg/kg n=6) were given. Saline treated rat (n=7) receive ip, one hour later, the same dose of saline. 48 hours later all the rats were necropsied after isofluorane anesthesia, lungs fixed in 10% formalin and H&E stained for morphology, Masson trichrome for fibrosis and CD 117 for mast cells. Two pathologists unaware of slides identity took at random 10 photographs of all the slides at 400× and separately counted the mast cells. Results As previously reported, 48 hours after triolein the lungs showed severe histopathological damage that was prevented by all three of the RAS drugs (1–3) and was associated with an increase in the number of mast cells (3). Aliskiren treatment reduced their numbers confirming previous findings (3,4). A significant reduction was also induced by losartan but not by captopril despite its protective effects on lung histopathology. Conclusions Mast cells may be involved in the pathological damage found after FE as suggested by their increase in number in the lungs after T and their reduction during protective treatment with aliskiren. Aliskiren and losartan also reduced their number. However, the lack of effect of captopril on mast cell number at this acute time period may suggest that some other pathways are involved in the time course of mast cell recruitment, such as angiotensin (1–7). Support or Funding Information Supported by the Catherine T Geldmacher Foundation, St. Louis, MO This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .