Featured CDSI Research of Dr. Cosby Stone
Dr. Cosby Stone focuses on the “right amount of testing,” which has involved identifying and delabeling low-risk penicillin allergies in the hospital and clinic. His efforts have saved lives and allowed patients to receive the “right drug at the right time.”
Cosby Allen Stone, Jr., MD, MPH, is an Assistant Professor of Medicine in the Division of Allergy, Pulmonology, and Critical Care Medicine within the Department of Medicine at Vanderbilt University Medical Center.
Expertise:
Dr. Stone has expertise in epidemiology, clinical drug allergy, and translational mechanistic projects in drug and vaccine allergy. He is engaged in pioneering clinical/translational research on beta-lactam antibiotic allergies with a secondary interest in immediate excipient allergies to alpha-gal and polyethylene glycols/polysorbates.
Current Focus:
At CDSI, Dr. Stone’s work is currently culminating in a study on understanding and monitoring drug-induced anaphylaxis. Dr. Stone and CDSI researchers are collecting DNA information from individuals who have anaphylactic reactions from medications and/or foods to determine if certain genetic sequences are predisposed to certain reactions. This study, defined below, utilizes the knowledge and information Dr. Stone and his colleagues have developed through their research on beta-lactam allergies and their previous work identifying and delabeling low-risk penicillin allergies at VUMC.
Learn more about Dr. Stone's research projects below.
The objective of this study, led by Dr. Stone and co-investigated by Dr. Elizabeth Phillips, is to contribute to the scientific knowledge of the ecological and genetic risk factors that predispose individuals to experience anaphylaxis. Drug-induced anaphylaxis appears randomly, is life-threatening, and has a significant impact on patient outcomes and receipt of safe healthcare.
The present study will contribute to the literature on whether and how long affected individuals remain at risk of symptoms and the natural history and progression of reductions in drug-induced anaphylaxis in affected individuals over time. Finally, understanding the underlying cellular and molecular mechanisms that separate a patient at risk for anaphylaxis from someone who is not at risk is another critical objective of this study.
The specific aims of Dr. Stone's study are to test two hypotheses:
- Both genetic (human leukocyte antigens, HLA) and ecological risk factors are critical to the development of true immunoglobulin E (IgE) mediated reactions associated with medications, foods, or other allergens
- True IgE-mediated reactions to medications, foods, or other allergens decrease predictably over time.
Consenting patients are enrolled during a clinic visit at Vanderbilt Asthma Sinus and Allergy (VASAP), as an inpatient being treated for a reaction to a drug, food, or other allergens in question at Vanderbilt University Medical Center, and through referring physicians at outside clinics with patients that meet study criteria.
For participants referred to the study by external providers, consent is obtained via the study webpage, which may be accessed by clicking the study title above. Study procedures involve the collection of blood samples, saliva samples, and skin tests. Saliva samples can be collected without an accompanying blood draw when needed.
The AAAAI Foundation recognized Dr. Stone with a 2021 Faculty Development Award for his research defining the key epidemiologic and immunogenetic risk features of true IgE-mediated cephalosporin allergy. Between 1% and 2% of the general population is labeled as cephalosporin allergic. Yet, specific and validated management for cephalosporin allergy has yet to be well defined, even though cephalosporins are widely used in the community and hospital setting.
A recent retrospective cohort study published by Dr. Stone and his colleagues in the Journal of Allergy and Clinical Immunology in Practice titled "Testing Strategies and Predictors for Evaluating Immediate and Delayed Reactions to Cephalosporins" (PMCID: PMC7855229) revealed that only 8.9% of patients with a history of immediate hypersensitivity to a cephalosporin demonstrated a positive skin testing result, that positive skin testing result was side chain-specific, and that there was a decreased probability of both positive immediate skin testing result and drug challenges over time since the index reaction.
Dr. Stone’s work, recognized by AAAAI, proposed to validate a risk stratification approach to identify low-risk cephalosporin and penicillin allergies, to assess ecological and immunogenetic risk factors of patients with skin test-positive cefazolin allergy, and to study the natural history of skin test positive cephalosporin allergy.
Dr. Stone has developed and validated risk stratification tools utilizing data from patients tested for penicillin allergy to identify patients with low-risk penicillin allergy labels. Patients qualifying as having low-risk penicillin allergy labels include more than 60% to 70% of patients. The tools utilized by Dr. Stone, Dr. Elizabeth Phillips, and their colleagues have a 99% negative predictive value (NPV 95% CI, 96.4-99.9) for excluding true penicillin allergy. These diagnostic tools have been successfully administered to inpatients at Vanderbilt University Medical Center (VUMC) and to outpatients at the Vanderbilt Asthma, Sinus, and Allergy Program (VASAP) to safely remove their penicillin allergy label via amoxicillin challenge without preceding skin testing.
Penicillin Allergy Risk Stratification*
This schema has been retrospectively and prospectively validated to have a >99% NPV for any symptoms after a challenge when the patient has been assessed as having a low-risk history. The main observed risk in low-risk patients who are challenged is a 0.5% chance of mild-moderate delayed onset rash (typically morbilliform type)
* Koo G, Stollings JL, Lindsell C, Dear ML, Kripalani S, Nelson GE, McCoy AB, Rice TW, Phillips EJ, Stone CA Jr; Vanderbilt University Medical Center Learning Healthcare System. "Low-risk penicillin allergy delabeling through a direct oral challenge in immunocompromised and/or multiple drug allergy labeled patients in a critical care setting." J Allergy Clin Immunol Pract. 2022 Jun;10(6): PMID: 35131513; PMCID: PMC9188986.
Cephalosporin allergy risk stratification**
This schema has been retrospectively validated to have (so far) 100% NPV for any symptoms after a challenge when the patient is assessed as having a low-risk cephalosporin allergy history.
** Koo G, Yu R, Phillips EJ, Stone CA Jr. "Retrospective stratification of cephalosporin allergy label risk using validated penicillin allergy frameworks." J Allergy Clin Immunol Pract. 2022 Sep;10(9):2472-2475.e1. doi: 10.1016/j.jaip.2022.05.032. Epub 2022 Jun 9. PMID: 35690369.