Drug Allergy in Hospitalized Patients: Three Years of Consultation Experience in a Tertiary Care Setting
by
, , , , , , , and
Christian P. Ratti
1
,
Alessandra Chiei Gallo
1,*,
Francesca Barei
2,
Alice Botta
1,
Matteo Cavara
1,
Eleonora Bono
1,
Lea Caron
1,
Valeria G. R. Ortolani
1 and
Enrico Iemoli
1 1
Allergy and Clinical Immunology Unit, Sacco Hospital, 20157 Milan, Italy
2
Dermatology Unit, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
BioChem 2025, 5(4), 42; https://doi.org/10.3390/biochem5040042 (registering DOI)
Submission received: 12 August 2025
/
Revised: 31 October 2025
/
Accepted: 27 November 2025
/
Published: 1 December 2025
(This article belongs to the Special Issue Feature Papers in BioChem, 2nd Edition)
Abstract
Background/Objectives: Drug hypersensitivity reactions (DHRs) are an important cause of morbidity in hospitalized patients, but their epidemiology and management in the inpatient setting are not well defined. Mislabeling of drug allergies may lead to inappropriate treatment and reduced antimicrobial stewardship. This study aimed to characterize the clinical profile, diagnostics, and management of inpatients referred for suspected drug allergy in a tertiary care hospital. Methods: We retrospectively reviewed all adult inpatients (≥18 years) at Luigi Sacco Hospital (Milan, Italy) who received allergology consultation between 1 June 2022 and 31 May 2025. Data on demographics, reaction type, culprit drugs, investigations, and management were collected. Immediate reaction severity was graded using the United States Drug Allergy Registry (USDAR) scale; delayed reactions were classified as severe cutaneous adverse reactions (SCARs) or non-SCARs. Logistic regression identified predictors of severity. Results: Among 35,438 admissions, 334 patients (0.9%) were evaluated; median age was 65 years, 51.2% were female, 67.4% had atopic comorbidities, and 55.1% reported prior drug allergy. Immediate reactions occurred in 49.1%, delayed in 43.7%. Cutaneous involvement was present in 86.8%, anaphylaxis in 6.6%, and SCARs in 3.9%. Antibiotics—particularly β-lactams—were most often implicated. In multivariate analysis, antibiotic exposure and older age were linked to more severe immediate reactions, while the absence of atopy predicted SCARs. Desensitization was successfully performed in 16.2% of patients. Conclusions: DHRs in inpatients are frequent and often involve high-risk drugs. Structured inpatient allergology services and an “allergy stewardship” approach may reduce DHR-related risks, support optimal therapy, and improve antimicrobial use strategies in tertiary care settings.
1. Introduction
The World Health Organization’s (WHO) stated definition of an adverse drug reaction (ADR) is a response to a drug that is noxious and unintended and occurs at doses normally used in man for prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function [1].
In hospitalized patients, ADRs—encompassing both allergic and non-allergic mechanisms—are reported in 10–20% of cases [2]. Among these, drug hypersensitivity reactions (DHRs) represent a clinically significant subset due to their association with severe manifestations, including anaphylaxis and Severe Cutaneous Adverse Reactions (SCARs), prolonged hospital stays, and increased reliance on broader-spectrum or costlier medications [2,3]. Mislabeling of drug allergies, particularly antibiotics, exacerbates these issues by limiting appropriate antimicrobial use and contributing to antimicrobial resistance [4].
The true burden of drug allergy remains poorly defined, despite being frequently reported in clinical settings. Approximately 10% of patients accessing healthcare services report a drug allergy, most commonly to penicillin [5]. However, the majority of these self-reported allergies lack confirmatory evaluation, resulting in the unnecessary avoidance of first-line therapies and contributing to suboptimal treatment strategies.
While Allergy and Immunology (A/I) is often considered an outpatient subspecialty, A/I specialists also provide crucial support in inpatient and emergency settings, where their expertise is essential for the accurate diagnosis and management of suspected DHRs. Nevertheless, studies specifically addressing inpatient allergy consultations remain limited [6,7,8,9,10,11,12], and available data frequently focus predominantly on pediatric cohorts or do not distinguish between general A/I referrals and those related to drug hypersensitivity.
Given the growing global emphasis on antimicrobial stewardship and the clinical consequences of inaccurate drug allergy labeling [13], a deeper understanding of inpatient allergy referrals is warranted. The aim of this study is to characterize the clinical features of inpatients referred for allergology consultation due to suspected drug allergy at Luigi Sacco Hospital, a tertiary care center in Milan, over a three-year period, and to detail the allergist’s approach to reaction management, diagnostic evaluation, and guidance for subsequent therapeutic planning.
2. Materials and Methods
2.1. Patients and Data Collection
Luigi Sacco Hospital is a 558-bed facility, ranking among the five largest hospitals in Milan. It also functions as a major teaching institution affiliated with a medical school. This retrospective descriptive study included all patients aged 18 years or older who were hospitalized at Luigi Sacco Hospital between 1 June 2022 and 31 May 2025, and who received an A/I consultation for a suspected drug allergy.
Data were retrospectively extracted from electronic medical records using a standardized collection form. For each patient, the following variables were recorded: demographic characteristics, reason for admission, requesting department, referral question, type of reaction, implicated drugs, and inpatient management. Patients with an inconclusive diagnosis and/or an urgent need for home therapy were promptly re-evaluated after discharge in an outpatient setting, where they underwent diagnostic procedures including skin testing and drug provocation tests (DPTs), performed either with the suspected drug or with suitable therapeutic alternatives.
Although latex is not a pharmaceutical agent, consultations related to suspected hypersensitivity to latex were also included in the study, as latex is commonly used in medical devices and these reactions frequently fall under the scope of hospital-based drug allergy consultations [14].
DHRs were categorized as either immediate (onset within 1–6 h of drug exposure) or delayed (onset after more than 1 h), following a pragmatic binary classification [15]. Reactions occurring between 1 and 6 h were classified as immediate or delayed based on their clinical phenotype (e.g., urticaria, angioedema, bronchospasm for immediate-type; maculopapular rash for delayed-type), acknowledging the overlapping nature of reaction timing in some cases. Reactions for which latency could not be determined were classified in the “latency undetermined” group.
The severity of immediate reactions was graded using the United States Drug Allergy Registry (USDAR) Grading [16]. For statistical analysis, reactions of grades 1–2 (mild) and 3–4 (severe) were combined.
Anaphylaxis was defined according to the criteria outlined in the 2021 position paper by the European Academy of Allergy and Clinical Immunology (EAACI) [17].
Delayed reactions were further classified into SCARs and non-SCARs. SCARs were defined in accordance with EAACI criteria [18] and included Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Acute Generalized Exanthematous Pustulosis (AGEP). Other delayed reactions such as Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) and Erythema Multiforme Majus (EMM) were also classified using the same EAACI definitions.
For each suspected ADR, the likelihood of a causal relationship between the drug and the reaction was assessed using the Naranjo Adverse Drug Reaction Probability Scale [19].
Hospital-wide statistics, including the total number of annual admissions during the study period, were obtained from institutional records and used to contextualize consultation incidence.
2.2. Statistical Analyses
Descriptive statistics are reported as mean and standard deviation (SD) or median and quartiles (Q1–Q3) for quantitative variables based on the distribution of the population. Absolute numbers (n) and frequencies (%) are used for categorical variables. Categorical variables were analyzed using a chi-square test or Fisher’s exact test as appropriate. We performed univariate regression and multivariate regression analyses to evaluate a potential predominant factor affecting the determination of the USDAR score of 3–4 in immediate reactions and the determination of SCAR in the delayed reactions. As covariates, we considered age, sex, current outpatient therapy, previous drug reaction, atopic comorbidities, receiving antibiotics, beta-lactams, NSAIDs, iodine-based contrast media, or opioids. Multicollinearity was assessed using the Variance Inflation Factor (VIF), variance proportions, and the condition index in SPSS. Thresholds of VIF < 10, condition index < 30, and absence of high shared variance proportions were considered acceptable. Considering a chi-square test, with a significance level of 0.05 and 80% power, a degree of freedom of 3, and assuming an effect size of 0.5, we determined that a minimum sample size of 44 patients was necessary. All statistical analyses were two-tailed with an alpha error set at 0.05, considering a p-value < 0.05 as significant. Statistical analyses were carried out using SPSS-IBM software (version 29.0; IBM Corp., Armonk, NY, USA). To calculate the sample size, G*Power software (version 3.1, Heinrich Heine University Düsseldorf, Düsseldorf, Germany) was used.
3. Results
3.1. Study Population
During the study period, 35,438 patients were admitted to Luigi Sacco Hospital. Among them, 334 (0.9%) underwent an allergology consultation for suspected drug allergy and were included in this study. Of these patients, 171 (51.2%) were female and 163 (48.8%) male, with a median age of 65 years (18–96 years). A history of atopic comorbidities was reported in 225/334 patients (67.4%), and previous drug allergy was documented in 184/334 cases (55.1%). Additional atopic conditions are listed in Table 1. Most patients (268/334; 80.2%) were on polypharmacy at home, defined as the use of more than three concomitant medications. The most frequent reason for hospitalization was infectious disease (105/334; 31.4%), followed by surgical procedures (92/334; 27.5%) and cardiovascular conditions (84/334; 25.1%). Consequently, the departments most frequently requesting allergology consultations were Cardiology (93/334; 27.8%), Infectious Diseases (82/334; 24.6%), and General Surgery (54/334; 16.2%).
3.2. Allergological Characteristics of Patients
Consultations were categorized based on the reason for referral as follows: ongoing reactions (163/334; 48.8%), previous reactions (139/334; 41.6%), and suspected latex allergy (35/334; 10.5%) (Table 2). In our population, immediate reactions were identified in 164/334 cases (49.1%), delayed reactions in 146/334 (43.7%), while latency could not be determined in 24/334 patients (7.2%).
Cutaneous involvement was observed in the majority of cases (290/334; 86.8%), with erythematous rash in 39.0%, urticaria in 19.7%, maculopapular exanthema in 18.7%, angioedema in 15.5%, and enanthem in 9.0% (Table 3). Anaphylaxis occurred in 22/334 (6.6%) patients, and 5.7% experienced hypotension or loss of consciousness. One case of Kounis syndrome with cardiac involvement was documented.
The severity of immediate reactions was assessed using the USDAR grading scale in 131/334 (39.2%) patients: 95/131 (72.5%) of them were grade 1, 4/131 (3.1%) grade 2, 20/131 (15.3%) grade 3, and 12/131 (9.2%) grade 4.
Among the delayed reactions, 13/334 (3.9%) cases were classified as SCARs, including 5 SJS (38.5%), 3 DRESS (23.1%), and 5 AGEP (38.5%). Additionally, 1 case of SDRIFE and 6 cases of likely drug-induced EMM were recorded. ACE inhibitor-induced angioedema was diagnosed in 4/334 (1.2%) patients.
Blood tests were performed in 164/334 patients, revealing eosinophilia (eosinophil count in the peripheral blood > 500/μL) in 48 cases (29.3%).
3.3. Drugs Involved
The data regarding the drug involved are reported in Table 3. At the time of the reaction, 291/334 (87.1%) patients were receiving multiple medications. Antibiotics were the most frequently implicated drug class (149/334; 44.6%), particularly beta-lactams (122/334; 36.5%) (Table 3). The most common route of administration was oral (157/334; 47%), followed by intravenous (137/334; 41%) and subcutaneous (24/334; 7.2%).
To assess the likelihood of drug causality, the Naranjo algorithm was applied in 288/344 (86.2%) cases (Table 3). The median score was 5, and most patients (275/288; 95.5%) fell into the “possible” (score 1–4) or “probable” (score 5–8) categories.
3.4. Reaction Management
The data regarding the reaction management are reported in Table 3. The majority of reactions were managed with corticosteroids (171/334; 51.2%) and antihistamines (133/334; 39.8%). Epinephrine was administered in 11/334 (3.3%) cases, while inhalation therapy or oxygen supplementation was used in 10/334 (3.0%) patients. In 75/334 (22.5%) patients, the reaction resolved without pharmacological intervention.
Regarding therapeutic decisions (Table 3), the ongoing treatment was maintained in 41/334 (12.3%) patients, and 15/334 (4.5%) received premedication and comedication with antihistamines. These were mainly patients who had experienced mild, predominantly cutaneous reactions, and for whom there was an urgent need to continue the ongoing therapy. Alternative therapies were recommended in 171/334 (51.2%) patients to ensure treatment continuation. In 25/334 (7.5%) cases, the alternative drug was administered using an incremental dosing protocol (1/1000, 1/100, 1/10, and full dose at 30 min intervals), while 9/334 (2.7%) patients received premedication. The incremental protocol was mainly used when the alternative drug was potentially cross-reactive with the culprit agent, particularly in patients with moderate to severe reactions—for example, cephalosporins in those with a history of penicillin hypersensitivity. Only 2/334 (0.6%) patients failed to tolerate the alternative drug.
Desensitization to the suspected culprit drug was performed in 54/334 (16.2%) patients. The majority of these involved acetylsalicylic acid (ASA) (49/54; 90.7%) for antiplatelet therapy, followed by beta-lactam antibiotics (4/54; 7.4%) and prasugrel (1/54; 1.9%). Seven patients (13%) had previously undergone ASA desensitization but required a repeat procedure due to treatment discontinuation. In 4/54 (7.4%) cases, ASA desensitization was not tolerated, and an alternative treatment with indobufen was required.
Most patients (274/334; 82.0%) required a single consultation; however, 60 (18.0%) needed two or more follow-up evaluations during hospitalization. After discharge, re-evaluation in an outpatient setting to complete the diagnostic process was recommended for 95/334 (28.4%) patients, but follow-up assessment was performed in only 41 (12.3%).
3.5. Allergological Work-Up
Specific IgE testing for beta-lactams (penicillin G, penicillin V, amoxicillin, ampicillin, and cefaclor) was performed in 39/334 (11.7%) patients, with positive results in 2 (0.6%). Latex-specific IgE was measured in 22/334 (6.6%) patients, with 3 positive cases (0.9%).
Skin testing was carried out in 40/334 (12.0%) patients across various drug classes: beta-lactams (22/334; 6.6%), with 1 patient testing positive for aminopenicillins and 4 for cephalosporins; iodinated contrast media (9/334; 2.7%) with 2 positivities; local anesthetics (5/334; 1.5%); general anesthetics (9/334; 2.7%) with 3 positivities; heparins (3/334; 0.9%); and vancomycin (3/334; 0.9%) with 1 positive case. For suspected latex allergy, 33/334 (9.9%) patients underwent skin testing, with 2 positive results. It should be noted that in many cases it was not possible to perform skin testing within the optimal time window for its execution, further underscoring the crucial role of specialist consultation in the diagnostic pathway.
Following diagnostic evaluation, 21/334 (6.3%) patients underwent drug provocation testing with alternative medications in a controlled setting, all of which yielded negative results. Additionally, 14/334 (4.2%) patients were re-exposed to the suspected drug, and only 1/334 (0.3%) patient developed a mild cutaneous reaction.
Among the 35 patients with suspected latex allergy, a latex-free surgical protocol was recommended in only 2/35 (5.7%) cases based on clinical history and testing.
3.6. Final Diagnosis and Follow-Up
Following allergology consultation, an ADR was confirmed in 240/334 (78%) patients. In 78/334 (23.4%) cases, a drug-related cause was excluded, and in 16/334 (4.8%) cases, the diagnosis remained uncertain. Only 5/334 (1.5%) patients experienced new reactions after the conclusion of the allergological assessment and required subsequent evaluation.
3.7. USDAR Grading Scale and Naranjo Score in Immediate Hypersensitivity Reactions
An USDAR scale of 3–4 was significantly associated with antibiotic use (p = 0.029; χ2 = 4.783) and with beta-lactam antibiotic use (p = 0.045; χ2 = 4.014) (Table 4). No significant differences were found for NSAIDs, opioids, general anesthetics, and iodine MC. This result was confirmed by the univariate logistic regression analysis (Table 5), where antibiotics and beta-lactams were associated with an increased risk of having an USDAR score of 3–4 (antibiotics: OR = 2.449, 95% CI 1.085–5.530, p = 0.031; beta-lactams: OR = 2.267, 95% CI 1.008–5.097, p = 0.048). In the multivariate analysis, the antibiotic use remained significant (OR = 3.635, 95% CI 1.471–8.985, p = 0.005) together with age (OR = 1.039, 95% CI 1.007–1.071, p = 0.017). As for the Naranjo score, most patients receiving beta-lactams had a score of 1–4 or 5–8 (p = 0.021).
3.8. SCARs and Naranjo Score in Delayed Hypersensitivity Reactions
For delayed reactions (Table 6), with severity defined by the occurrence of SCAR, the only significant association was between antibiotic use and causality (p = 0.019). No other statistically significant results were observed for the remaining drug classes.
The univariate logistic regression analysis (Table 7) showed that the absence of atopic comorbidities was significantly associated with a higher risk of developing SCARs (OR = 9.500, 95% CI 1.200–75.239, p = 0.033), while no other variables reached statistical significance. In the multivariate model, the absence of atopic comorbidities remained significantly associated with the development of SCARs (OR = 10.400, 95% CI 1.273–84.999, p = 0.029).
4. Discussion
This study presents a comprehensive analysis of inpatient allergology consultations for suspected drug allergy at Luigi Sacco Hospital over a three-year period. Our findings underscore the relevance and complexity of DHRs in hospitalized patients, with an incidence of 0.9% among all admissions, comparable to previous reports from tertiary care centers worldwide [8,9,10].
The demographic profile of our cohort (median age 65 years; 51.2% female) reflects a predominance of elderly, polymedicated individuals—a well-recognized risk group for adverse drug reactions (ADRs) [5]. Notably, for immediate reactions, increasing patient age was significantly associated with a greater risk of reaction severity in multivariate analysis, with an OR of 1.039 for each additional year of age. The high prevalence of atopic comorbidities (67.4%) and prior drug allergy history (55.1%) further underscores the clinical complexity of this population. Our findings are consistent with previous reports indicating that inpatient allergology services frequently manage patients with multiple comorbidities and a high baseline drug exposure [9,11].
Immediate-type reactions accounted for 49.1% of cases, with cutaneous manifestations being the most frequent clinical presentation (86.8%), echoing the results of Thong et al., who observed similar trends in Singapore [8]. This also aligns with the 94.3% skin involvement reported by Büyük Yaytokgil et al. in children [10], confirming the skin as the primary target organ of DHRs regardless of age. Anaphylaxis occurred in 6.6% of our cohort—higher than in some previous inpatient studies (e.g., 0% in Thong et al.) but consistent with reports from European centers [5,8]. This likely reflects the overall rise in anaphylaxis incidence, both drug-induced and from other causes, since the publication of the Thong et al. study in 2003 [5].
Notably, 13 patients developed SCARs, including SJS, DRESS, and AGEP—conditions associated with significant morbidity and mortality, especially in older adults [5,20]. In both univariate and multivariate analyses, the absence of atopic comorbidities was significantly associated with an increased likelihood of developing a SCAR. To the best of our knowledge, this finding has not been previously reported in the literature. A plausible explanation lies in the distinct immunopathogenesis of atopic comorbidities, which are typically IgE-mediated and therefore classified as type I hypersensitivity reactions, compared with SCARs, which are type IV reactions [20,21]. Accordingly, a predisposition to type I reactions may act as a protective factor against the development of type IV reactions such as SCARs.
Eosinophilia, a known marker of delayed hypersensitivity, was detected in nearly 30% of tested patients in our study, further corroborating the immune-mediated nature of many of these reactions.
In our cohort, antibiotics were the most frequently implicated drug class (44.6%), with β-lactams predominating (36.5%). This distribution is consistent with global epidemiological trends, in which penicillin allergy labels remain disproportionately common and β-lactams—particularly aminopenicillins and aminocephalosporins—account for a substantial proportion of severe antimicrobial hypersensitivity reactions [4,22]. Notably, antibiotic use was significantly associated with greater reaction severity, a finding confirmed in both univariate and multivariate analyses. This association was also observed for β-lactams alone in univariate analysis. These findings align with prior multicenter data indicating that penicillins and cephalosporins are among the leading culprits in antimicrobial-associated anaphylaxis, and that β-lactam exposure is linked to a significant proportion of ICU admissions for severe reactions [22]. The predominance of β-lactams in our setting may reflect both their widespread use in tertiary care—particularly in the management of severe infections and in perioperative prophylaxis—and their intrinsic allergenic potential.
A statistically significant association was also identified between immediate reactions to β-lactam antibiotics and Naranjo score categories ranging from 1 to 8. This observation may be explained by the difficulty of determining definitive causality for a specific drug in a polytreated inpatient population. A similar association was also observed for delayed reactions when considering antibiotics as a whole, suggesting that this challenge is not limited to immediate hypersensitivity events. Consistent with these findings, the causality assessment using the Naranjo algorithm classified most reactions as “possible” or “probable” (median score: 5), reflecting the diagnostic uncertainty frequently encountered in the inpatient setting, where multiple concurrent therapies and complex comorbidities often confound causal attribution.
In agreement with the findings reported by Doña et al. regarding the general population [5], nonsteroidal anti-inflammatory drugs (NSAIDs) also represent the second most frequently implicated drug class in our cohort, followed by iodinated contrast media, whose incidence has been increasing in recent years [5].
Pharmacological treatment (mostly corticosteroids and antihistamines) was necessary in about 80% of patients, while epinephrine use was limited to severe cases. Interestingly, although 5.7% of patients experienced hypotension, only 3.3% received epinephrine, suggesting a possible underuse or hesitation in its administration. This finding aligns with previously reported trends and underscores the need to strengthen awareness and adherence to guidelines recommending early epinephrine use in anaphylaxis [23]. Notably, 16.2% of patients underwent desensitization, primarily to aspirin and beta-lactams—a proportion significantly higher than in studies from Kuwait or pediatric centers [9,10,11], likely reflecting the infrequent use of antiplatelet-dose aspirin in pediatric practice.
Interestingly, the success rate of desensitization in our adult cohort was high, reinforcing the safety of this strategy when performed under specialist supervision—a position strongly supported by Doña et al. and recent EAACI recommendations [5], and the consensus statement by Cernadas et al. [24].
Our approach to maintaining essential therapy through alternative drugs or graded challenge protocols proved largely successful, with only two patients (0.6%) unable to tolerate the alternative. These results underscore the importance of allergist-guided interventions to avoid unnecessary discontinuation of first-line therapies [5].
Notably, in only two out of the 35 patients evaluated for suspected latex allergy was the diagnosis confirmed, and a latex-free perioperative pathway was recommended. This suggests that the perception of latex allergy in the general population may be greater than its actual prevalence, which is approximately 1% [25].
Compared to other international experiences (e.g., 0.008% incidence in Kuwait, 0.42–0.87% in broader literature), our higher referral rate likely reflects institutional awareness and the availability of an in-hospital allergology service [9,12]. As Weber et al. highlighted, centers with well-integrated A/I services see more frequent and timely consultations [12].
The variety of clinical departments requesting consultations—most notably Cardiology, Infectious Diseases, and Surgery—also mirrors patterns seen in academic centers, as described by Kempe et al. [11]. The demand for rapid diagnostic clarification in patients needing critical medications (e.g., antibiotics, antiplatelets) emphasizes the indispensable role of allergology in inpatient care.
5. Limitations
This was a retrospective single-center study, and despite the structured data collection, underreporting of minor or self-resolving reactions may have occurred. Moreover, the availability of in vivo tests (e.g., drug provocation testing) was limited during hospitalization, and a complete diagnostic work-up was not always feasible. Additional limitations include the fact that many patients did not undergo follow-up evaluation after discharge, and the need for future multicenter studies to confirm and expand upon these findings.
6. Conclusions
Our findings underscore the importance of establishing structured inpatient allergology services in tertiary hospitals, given the complexity of polypharmacy and comorbidities in the admitted population. Where in-house expertise is lacking, the involvement of an external allergist with specific experience in drug hypersensitivity reactions may be crucial to ensuring optimal patient management. A substantial proportion of patients benefited from specific interventions, including desensitization and diagnostic workup, enabling the safe continuation of essential therapies.
In this context, and drawing on the model of antimicrobial stewardship [13], the development of an allergy stewardship approach could enhance the identification and management of DHR. This would promote timely allergist involvement, reduce inappropriate drug avoidance, and support access to diagnostic procedures such as skin testing, graded challenges, and desensitization.
Efforts should focus on standardizing referral criteria, implementing prospective reporting systems, and increasing post-discharge follow-up to complete allergologic evaluations, as suggested in other models [8,10,11]. With an aging population, rising rates of chronic infections and antimicrobial resistance, increasingly complex drug regimens, and inappropriate medication use, the demand for inpatient allergology services is likely to continue increasing. Future studies should assess the impact of structured allergology interventions on patient outcomes, resource utilization, and healthcare system sustainability.
Author Contributions
Conceptualization, C.P.R.; Methodology, C.P.R., F.B., V.G.R.O. and E.I.; Software, F.B.; Validation, V.G.R.O. and E.I.; Formal analysis, F.B.; Investigation, A.C.G., A.B., M.C., E.B. and L.C.; Resources, L.C.; Data curation, C.P.R., A.C.G., F.B., A.B., M.C., E.B., L.C., V.G.R.O. and E.I.; Writing—original draft, C.P.R. and A.C.G.; Writing—review and editing, F.B., L.C., V.G.R.O. and E.I.; Visualization, A.C.G., A.B., M.C. and E.B.; Supervision, C.P.R. and A.C.G.; Project administration, C.P.R. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
Since the study was exclusively observational and based only on routine analyses, formal approval by an external ethical committee was not warranted or requested. The study was conducted following the ethical principles of the 2013 revision of the Declaration of Helsinki and the code of Good Clinical Practice.
Informed Consent Statement
The study was conducted in accordance with the ethical principles for medical research involving human subjects (WMA declaration of Helsinki and its later amendments). Written informed consent was obtained from all patients.
Data Availability Statement
Data supporting the findings of this study are available upon request from the corresponding author due to privacy.
Conflicts of Interest
The authors declare no conflicts of interest.
References
- World Health Organization (WHO). International Drug Monitoring: The Role of National Centres; WHO Technical Report Series 498; World Health Organization: Geneva, Switzerland, 1972. [Google Scholar]
- Gomes, E.R.; Demoly, P. Epidemiology of Hypersensitivity Drug Reactions. Curr. Opin. Allergy Clin. Immunol. 2005, 5, 309–316. [Google Scholar] [CrossRef]
- Sousa-Pinto, B.; Cardoso-Fernandes, A.; Araújo, L.; Fonseca, J.A.; Freitas, A.; Delgado, L. Clinical and Economic Burden of Hospitalizations with Registration of Penicillin Allergy. Ann. Allergy Asthma Immunol. 2018, 120, 190–194.e2. [Google Scholar] [CrossRef] [PubMed]
- Blumenthal, K.G.; Peter, J.G.; Trubiano, J.A.; Phillips, E.J. Antibiotic Allergy. Lancet 2019, 393, 183–198. [Google Scholar] [CrossRef]
- Doña, I.; Torres, M.J.; Celik, G.; Phillips, E.; Tanno, L.K.; Castells, M. Changing Patterns in the Epidemiology of Drug Allergy. Allergy 2024, 79, 613–628. [Google Scholar] [CrossRef] [PubMed]
- England, R.W.; Ho, T.C.; Napoli, D.C.; Quinn, J.M. Inpatient Consultation of Allergy/Immunology in a Tertiary Care Setting. Ann. Allergy Asthma Immunol. 2003, 90, 393–397. [Google Scholar] [CrossRef] [PubMed]
- Otto, H.F.; England, R.W.; Quinn, J.M. Inpatient Allergy/Immunology Consultations in a Tertiary Care Setting. Allergy Asthma Proc. 2010, 31, 244–251. [Google Scholar] [CrossRef]
- Thong, B.Y.; Leong, K.P.; Tang, C.Y.; Chng, H.H. Drug Allergy in a General Hospital: Results of a Novel Prospective Inpatient Reporting System. Ann. Allergy Asthma Immunol. 2003, 90, 342–347. [Google Scholar] [CrossRef]
- Al-Ahmad, M.; Bouza, T.R. Pattern of Inpatient Referrals to a Drug Allergy Unit in Kuwait. Eur. Ann. Allergy Clin. Immunol. 2017, 49, 276–280. [Google Scholar] [CrossRef]
- Yaytokgil, Ş.B.; Selmanoğlu, A.; Kulhas Çelik, I.; Emeksiz, Z.Ş.; Ginis, T.; Karaatmaca, B.; Toyran, M.; Civelek, E.; Misirlioğlu, E.D. Evaluation of the Frequency and Characteristics of Drug Hypersensitivity Reactions in Hospitalized Children: Real Life-Cohort Study. World Allergy Organ. J. 2024, 17, 100893. [Google Scholar] [CrossRef]
- Kempe, E.; Stukus, D.R.; Strothman, K.; Scherzer, R. Allergy and Immunology Inpatient and Emergency Department Consultations at a Pediatric Academic Medical Center. Ann. Allergy Asthma Immunol. 2016, 116, 373–374. [Google Scholar] [CrossRef]
- Weber, R.W. The Allergist as Consultant. Ann. Allergy Asthma Immunol. 2003, 90, 369–370. [Google Scholar] [CrossRef] [PubMed]
- Lanckohr, C.; Bracht, H. Antimicrobial Stewardship. Curr. Opin. Crit. Care 2022, 28, 551–556. [Google Scholar] [CrossRef] [PubMed]
- Preheim, E.A.; Phillips, C.M.; Weant, K.A. Latex Allergy Alerts in the Age of CPOE: Assessing the Risk from Injectable Medications. Hosp. Pharm. 2022, 57, 413–415. [Google Scholar] [CrossRef]
- Brockow, K.; Przybilla, B.; Aberer, W.; Bircher, A.J.; Brehler, R.; Dickel, H.; Fuchs, T.; Jakob, T.; Lange, L.; Pfützner, W.; et al. Guideline for the Diagnosis of Drug Hypersensitivity Reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in Collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J. Int. 2015, 24, 94–105. [Google Scholar] [CrossRef] [PubMed]
- Khan, D.A.; Phillips, E.J.; Accarino, J.J.; Gonzalez-Estrada, A.; Otani, I.M.; Ramsey, A.; Arroyo, A.C.; Banerji, A.; Chow, T.; Liu, A.Y.; et al. United States Drug Allergy Registry (USDAR) Grading Scale for Immediate Drug Reactions. J. Allergy Clin. Immunol. 2023, 152, 1581–1586. [Google Scholar] [CrossRef]
- Muraro, A.; Worm, M.; Alviani, C.; Cardona, V.; DunnGalvin, A.; Garvey, L.H.; Riggioni, C.; de Silva, D.; Angier, E.; Arasi, S.; et al. EAACI Guidelines: Anaphylaxis (2021 Update). Allergy 2022, 77, 357–377. [Google Scholar] [CrossRef]
- Barbaud, A.; Garvey, L.H.; Torres, M.; Laguna, J.J.; Arcolaci, A.; Bonadonna, P.; Hofmeier, K.S.; Chiriac, A.M.; Cernadas, J.; Caubet, J.C.; et al. EAACI/ENDA Position Paper on Drug Provocation Testing. Allergy 2024, 79, 565–579. [Google Scholar] [CrossRef]
- Naranjo, C.A.; Busto, U.; Sellers, E.M.; Sandor, P.; Ruiz, I.; Roberts, E.A.; Janecek, E.; Domecq, C.; Greenblatt, D.J. A Method for Estimating the Probability of Adverse Drug Reactions. Clin. Pharmacol. Ther. 1981, 30, 239–245. [Google Scholar] [CrossRef]
- Hung, S.I.; Mockenhaupt, M.; Blumenthal, K.G.; Abe, R.; Ueta, M.; Ingen-Housz-Oro, S.; Phillips, E.J.; Chung, W.-H. Severe Cutaneous Adverse Reactions. Nat. Rev. Dis. Primers 2024, 10, 30. [Google Scholar] [CrossRef]
- Jutel, M.; Agache, I.; Zemelka-Wiacek, M.; Akdis, M.; Chivato, T.; del Giacco, S.; Gajdanowicz, P.; Gracia, I.E.; Klimek, L.; Lauerma, A.; et al. Nomenclature of Allergic Diseases and Hypersensitivity Reactions: Adapted to Modern Needs: An EAACI Position Paper. Allergy 2023, 78, 2851–2874. [Google Scholar] [CrossRef]
- Hall, V.; Wong, M.; Munsif, M.; Stevenson, B.R.; Elliott, K.; Lucas, M.; Baird, A.J.; Athan, E.; Young, M.; Pickles, R.; et al. Antimicrobial Anaphylaxis: The Changing Face of Severe Antimicrobial Allergy. J. Antimicrob. Chemother. 2020, 75, 229–235. [Google Scholar] [CrossRef]
- Kamath, P.; Rao, R.R.; Kamath, A. Study of Epinephrine-Induced Cardiovascular Adverse Events in Patients with Anaphylaxis Using Two Spontaneously Reported Adverse Event Databases from 2004 to 2024. Sci. Rep. 2025, 15, 37088. [Google Scholar] [CrossRef]
- Cernadas, J.R.; Brockow, K.; Romano, A.; Aberer, W.; Torres, M.J.; Bircher, A.; Campi, P.; Sanz, M.L.; Castells, M.; Demoly, P.; et al. General Considerations on Rapid Desensitization for Drug Hypersensitivity—A Consensus Statement. Allergy 2010, 65, 1357–1366. [Google Scholar] [CrossRef]
- Charous, B.L.; Blanco, C.; Tarlo, S.; Hamilton, R.G.; Baur, X.; Beezhold, D.; Sussman, G.; Yunginger, J.W. Natural Rubber Latex Allergy After 12 Years: Recommendations and Perspectives. J. Allergy Clin. Immunol. 2002, 109, 31–34. [Google Scholar] [CrossRef] [PubMed]
Table 1.
Baseline characteristics of the overall population and of the three subgroups (immediate, delayed, and latency undetermined).
Table 1.
Baseline characteristics of the overall population and of the three subgroups (immediate, delayed, and latency undetermined).
| Baseline Characteristics | Overall Population | n a | Immediate Reactions | n a | Delayed Reactions | n a | Latency Undetermined | n a |
|---|---|---|---|---|---|---|---|---|
| Sex, n (%) | 334 | 164 | 146 | 24 | ||||
| 171 (51.2) | 89 (54.3) | 72 (49.3) | 10 (41.7) | ||||
| 163 (48.8) | 75 (45.7) | 74 (50.7) | 14 (58.3) | ||||
| Age, mean (SD) | 63.8 (16.7) | 334 | 61.1 (16.9) | 164 | 66.7 (16.4) | 146 | 64.2 (14.8) | 24 |
| Age, median | 65 | 62 | 68 | 64 | ||||
| Age, min | 18 | 18 | 18 | 30 | ||||
| Age, max | 96 | 91 | 96 | 89 | ||||
| Age distribution, n (%) | 334 | 164 | 146 | 24 | ||||
| 42 (12.6) | 28 (17.1) | 12 (8.2) | 2 (8.3) | ||||
| 122 (36.5) | 61 (37.2) | 51 (34.9) | 10 (41.7) | ||||
| 59 (17.7) | 30 (18.3) | 23 (15.8) | 6 (25.0) | ||||
| 111 (33.2) | 45 (27.4) | 60 (41.1) | 6 (25.0) | ||||
| Atopic comorbidities, n (%) | 225 (67.4) | 334 | 148 (90.3) | 164 | 62 (42.5) | 146 | 15 (62.5) | 24 |
| 38 (32.3) | 25 (15.2) | 8 (5.5) | 5 (20.8) | ||||
| 21 (6.3) | 17 (10.4) | 1 (0.7) | 3 (12.5) | ||||
| 23 (6.9) | 12 (7.3) | 5 (3.4) | 6 (25.0) | ||||
| 184 (55.1) | 127 (77.4) | 49 (33.6) | 8 (33.3) | ||||
| 6 (1.8) | 2 (1.2) | 2 (1.4) | 2 (8.3) | ||||
| 4 (1.2) | 2 (1.2) | 1 (0.7) | 1 (4.2) | ||||
| 39 (11.7) | 26 (15.9) | 13 (8.9) | 0 (0.0) | ||||
| 2 (0.6) | 2 (1.2) | 0 (0.0) | 0 (0.0) | ||||
| 3 (0.9) | 2 (1.2) | 1 (0.7) | 0 (0.0) | ||||
| Reason for hospitalization, n (%) | 334 | 164 | 146 | 24 | ||||
| 105 (31.4) | 30 (18.3) | 65 (44.5) | 10 (41.7) | ||||
| 92 (27.5) | 62 (37.8) | 25 (17.1) | 5 (20.8) | ||||
| 84 (25.1) | 55 (33.5) | 24 (16.4) | 5 (20.8) | ||||
| 11 (3.3) | 4 (2.4) | 6 (4.1) | 1 (4.2) | ||||
| 7 (2.1) | 2 (1.2) | 4 (2.7) | 1 (4.2) | ||||
| 11 (3.3) | 5 (3.0) | 6 (4.1) | 0 (0.0) | ||||
| 24 (7.2) | 6 (3.7) | 16 (11.0) | 2 (8.3) | ||||
| Current outpatient therapy, n (%) | 334 | 164 | 146 | 24 | ||||
| 43 (12.9) | 26 (15.9) | 13 (8.9) | 4 (16.7) | ||||
| 23 (6.9) | 19 (6.1) | 12 (8.2) | 1 (4.2) | ||||
| 268 (80.2) | 128 (78.0) | 121 (82.9) | 19 (79.2) |
Note: Valid data a.
Table 2.
Features of consultations in the overall population and in the three subgroups (immediate, delayed, and latency undetermined).
Table 2.
Features of consultations in the overall population and in the three subgroups (immediate, delayed, and latency undetermined).
| Consultation | Overall Population | n a | Immediate Reactions | n a | Delayed Reactions | n a | Latency Undetermined | n a |
|---|---|---|---|---|---|---|---|---|
| Reason for request, n (%) | 334 | 164 | 146 | 24 | ||||
| 163 (48.8) | 29 (17.7) | 117 (80.1) | 17 (70.8%) | ||||
| 139 (41.6) | 114 (68.2) | 21 (14.4) | 4 (16.7) | ||||
| 35 (10.5) | 24 (14.6) | 8 (5.5) | 3 (12.5) | ||||
| Timing of previous reaction, n (%) | 174 | 138 | 29 | 7 | ||||
| 18 (10.3) | 13 (9.4) | 4 (13.8) | 1 (14.2) | ||||
| 28 (16.1) | 24 (17.4) | 4 (13.8) | 0 (0.0) | ||||
| 15 (8.6) | 7 (5.1) | 8 (27.6) | 0 (0.0) | ||||
| 68 (39.1) | 58 (42.0) | 7 (24.1) | 3 (42.9) | ||||
| 42 (24.1) | 33 (23.9) | 6 (20.7) | 3 (42.9) |
Note: Valid data a.
Table 3.
Drug reaction characteristics in the overall population and in the three subgroups (immediate, delayed, and latency undetermined).
Table 3.
Drug reaction characteristics in the overall population and in the three subgroups (immediate, delayed, and latency undetermined).
| Overall Population | n a | Immediate Reactions | n a | Delayed Reactions | n a | Latency Undetermined | n a | |
|---|---|---|---|---|---|---|---|---|
| Drug involved | ||||||||
| Type of drugs, n (%) | 334 | 164 | 146 | 24 | ||||
| 149 (44.6) | 60 (36.6) | 82 (56.2) | 7 (29.2) | ||||
| 122 (36.5) | 54 (32.9) | 61 (41.8) | 7 (29.2) | ||||
| 44 (13.2) | 15 (9.1) | 27 (18.5) | 2 (8.4) | ||||
| 80 (24.0) | 57 (34.7) | 20 (13.7) | 3 (12.5) | ||||
| 18 (5.4) | 13 (7.9) | 5 (3.4) | 0 (0.0) | ||||
| 7 (2.1) | 7 (4.3) | 0 (0.0) | 0 (0.0) | ||||
| 14 (4.2) | 13 (7.9) | 1 (0.7) | 0 (0.0) | ||||
| 31 (9.3) | 15 (9.1) | 16 (11.0) | 0 (0.0) | ||||
| 2 (0.6) | 2 (1.2) | 0 (0.0) | 0 (0.0) | ||||
| 17 (5.1) | 2 (1.2) | 14 (9.6) | 1 (4.2) | ||||
| 7 (2.1) | 0 (0.0) | 7 (4.8) | 0 (0.0) | ||||
| 67 (20.0) | 17 (10.3) | 46 (31.5) | 4 (16.7) | ||||
| 17 (5.1) | 7 (4.3) | 5 (3.4) | 5 (20.8) | ||||
| Administration route, n (%) | 334 | 164 | 146 | 24 | ||||
| 137 (41.0) | 55 (33.5) | 75 (51.4) | 7 (29.2) | ||||
| 157 (47.0) | 82 (50.0) | 69 (47.3) | 6 (25.0) | ||||
| 24 (7.2) | 9 (5.5) | 14 (9.6) | 1 (4.2) | ||||
| 36 (10.4) | 23 (14.0) | 11 (7.6) | 2 (8.3) | ||||
| 21 (6.3) | 6 (3.7) | 6 (4.1) | 9 (37.5) | ||||
| Concomitant medications during the reaction, n (%) | 291 (87.1) | 334 | 138 (84.1) | 164 | 133 (91.1) | 146 | 20 (83.3) | 24 |
| Reaction type | ||||||||
| Reaction type, n (%) | 334 | 164 | 146 | 24 | ||||
| 290 (86.8) | 134 (81.7) | 142 (97.3) | 14 (58.3) | ||||
| 57 (17.1) | 40 (24.4) | 13 (8.9) | 4 (16.7) | ||||
| 45 (13.5) | 35 (21.3) | 9 (6.2) | 1 (4.2) | ||||
| 113 (33.8) | 61 (37.2) | 50 (34.2) | 2 (8.3) | ||||
| 54 (16.2) | 0 (0.0) | 54 (37.0) | 0 (0.0) | ||||
| 26 (7.8) | 7 (4.3) | 19 (13.0) | 0 (0.0) | ||||
| 7 (2.1) | 3 (1.8) | 4 (2.7) | 0 (0.0) | ||||
| 13 (3.9) | 0 (0.0) | 13 (8.9) | 0 (0.0) | ||||
| 13 (3.9) | 12 (7.3) | 1 (0.7) | 0 (0.0) | ||||
| 17 (5.1) | 16 (9.8) | 1 (0.7) | 0 (0.0) | ||||
| 8 (2.4) | 2 (1.2) | 0 (0.0) | 6 (25.0) | ||||
| 19 (5.7) | 19 (11.7) | 0 (0.0) | 0 (0.0) | ||||
| 22 (6.6) | 22 (13.4) | 0 (0.0) | 0 (0.0) | ||||
| 1 (0.3) | 1 (0.6) | 0 (0.0) | 0 (0.0) | ||||
| 16 (4.8) | 5 (3.0) | 4 (2.7) | 7 (29.2) | ||||
| 5 (1.5) | 0 (0.0) | 0 (0.0) | 5 (20.8) | ||||
| Eosinophilia | 48 (14.4) | 164 | 1 (0.6) | 32 | 41 (28.1) | 116 | 6 (25.0) | 16 |
| Naranjo Score | ||||||||
| Naranjo Score, n (%) | 288 | 141 | 136 | 11 | ||||
| 5 (1.5) | 1 (0.6) | 1 (0.7) | 3 (12.25) | ||||
| 120 (35.9) | 52 (31.7) | 61 (41.8) | 7 (29.2) | ||||
| 155 (46.4) | 85 (51.8) | 69 (47.3) | 1 (4.2) | ||||
| 8 (2.4) | 3 (1.8) | 5 (3.4) | 0 (0.0) | ||||
| Patient management | ||||||||
| Continuation of ongoing therapy, n (%) | 41 (12.3) | 334 | 3 (1.8) | 164 | 27 (18.5) | 146 | 11 (45.8) | 24 |
| Suggested alternatives without testing, n (%) | 171 (51.2) | 334 | 72 (43.8) | 164 | 93 (63.6) | 146 | 6 (25.0) | 24 |
| Desensitization, n (%) | 54 (16.2) | 334 | 45 (27.4) | 164 | 9 (6.2) | 146 | 0 (0.0) | 24 |
| Allergological work-up, n (%) | 334 | 164 | 146 | 24 | ||||
| 41 (12.3) | 17 (10.4) | 22 (15.1) | 2 (8.3) | ||||
| 39 (11.7) | 26 (15.9) | 11 (7.5) | 2 (8.3) | ||||
| 40 (12.0) | 28 (17.1) | 10 (6.8) | 2 (8.3) | ||||
| 21 (6.3) | 12 (7.3) | 8 (5.5) | 1 (4.2) | ||||
| 14 (4.2) | 10 (6.1) | 4 (2.7) | 0 (0.0) | ||||
Note: Valid data a. Abbreviation: IgE, immunoglobulin E; SCAR, Severe Cutaneous Adverse Reactions; NSAIDs, non-steroidal Anti-inflammatory Drugs.
Table 4.
Severity and Causality of Immediate Hypersensitivity Reactions by Drug Class.
| Immediate Reactions | USDAR Grading Scale (N = 131) | Naranjo Score (N = 141) | ||||||
|---|---|---|---|---|---|---|---|---|
| Grade 1–2 g | Grade 3–4 g | p-Value | Grade < 0 h | Grade 1–4 h | Grade 5–8 h | Grade ≥ 9 h | p-Value | |
| Antibiotics, n (%) | 37/99 (37.4) a | 19/32 (59.4) a | 0.029 (χ2 = 4.783) | 0/60 (0.0) i | 28/60 (46.7) i | 32/60 (53.3) i | 0/60 (0.0) i | 0.050 |
| Beta-lactam, n (%) | 33/99 (33.3) b | 17/32 (53.1) b | 0.045 (χ2 = 4.014) | 0/54 (0.0) j | 27/54 (50.0) j | 27/54 (50.0) j | 0/54 (0.0) j | 0.021 (χ2 = 8.103) |
| NSAIDs, n (%) | 44/99 (44.4) c | 9/32 (28.1) c | 0.102 | 0/56 (0.0) k | 19/56 (33.9) k | 35/56 (62.5) k | 2/56 (3.6) k | 0.714 |
| Opioids, n (%) | 7/99 (7.1) d | 5/32 (15.6) d | 0.165 | 0/13 (0.0) l | 6/13 (46.2) l | 7/13 (53.8) l | 0/13 (0.0) l | 0.701 |
| General anesthetics, n (%) | 7/99 (7.1) e | 6/32 (18.8) e | 0.840 | 0/13 (0.0) m | 6/13 (46.2) m | 7/13 (53.8) m | 0/13 (0.0) m | 0.701 |
| Iodinate contrast media, n (%) | 13/99 (13.1) f | 2/32 (6.3) f | 0.358 | 0/15 (0.0) n | 5/15 (33.3) n | 9/15 (60.0) n | 1/15 (6.7) n | 0.530 |
Note: 56/131 patients received antibiotics a; 50/131 patients received beta-lactams b; 53/131 patients received NSAIDs c; 12/131 patients received opioids d; 13/131 received general anesthetics e; 15/131 received iodinate contrast media f; 99/131 patients had a USDAR Grading Scale of 1–2, 32/131 patients had a USDAR Grading Scale of 3–4 g; 1/141 patient had a Naranjo score of <0, 52/141 patients had a Naranjo score of 1–4, 85/141 patients had a Naranjo score of 5–8 and 3/141 patients had a Naranjo score of ≥9 h; 60/141 patients received antibiotics i; 54/141 patients received beta-lactams j; 56/141 patients received NSAIDs k; 13/141 patients received opioids l; 13/141 received general anesthetics m; 15/151 received iodinate contrast media n. Abbreviations: NSAIDs, non-steroidal Anti-inflammatory Drugs; USDAR, United States Drug Allergy Registry.
Table 5.
Univariate and multivariate regression analyses to assess the potential predominant factor influencing the achievement of an USDAR Score of 3–4 in the immediate reactions.
Table 5.
Univariate and multivariate regression analyses to assess the potential predominant factor influencing the achievement of an USDAR Score of 3–4 in the immediate reactions.
| Univariate Analysis (USDAR Score 3–4) | Multivariate Analysis (USDAR Score 3–4) | |||||
|---|---|---|---|---|---|---|
| Characteristics | OR | 95% CI | p-Value | OR | 95% CI | p-Value |
| Age | 1.018 | 0.992–1.046 | 0.179 | 1.039 | 1.007–1.071 | 0.017 |
| Sex | 0.938 | 0.422–2.083 | 0.874 | 0.713 | 0.300–1.694 | 0.443 |
| Atopic comorbidities | 0.875 | 0.258–2.966 | 0.830 | / | / | / |
| Current outpatient therapy | 0.889 | 0.293–2.696 | 0.836 | 0.462 | 0.124–1.716 | 0.249 |
| Previous drug reactions | 0.655 | 0.226–1.895 | 0.435 | 0.565 | 0.182–1.754 | 0.323 |
| Antibiotics | 2.449 | 1.085–5.530 | 0.031 | 3.635 | 1.471–8.985 | 0.005 |
| Beta-lactams | 2.267 | 1.008–5.097 | 0.048 | / | / | / |
| NSAIDs | 0.489 | 0.206–1.164 | 0.106 | / | / | / |
| Iodinate contrast media | 0.441 | 0.094–2.069 | 0.299 | / | / | / |
| Opioids | 2.434 | 0.715–8.287 | 0.155 | / | / | / |
Note: As covariates, we considered age (as continuous variable), sex (female vs. male), current outpatient therapy (≥3 drugs vs. <3 drugs), previous drug reaction (yes vs. no), atopic comorbidities (at least one vs. none), receiving antibiotics (yes vs. no), receiving beta-lactams (yes vs. no), receiving NSAIDs (yes vs. no), receiving iodinate contrast media (yes vs. no), and receiving opioids (yes vs. no). The drugs were analyzed together only in the univariate analysis, whereas in the multivariate analysis, only antibiotics were included alongside baseline characteristics. The variable “atopic comorbidities” was excluded from the multivariate analysis due to collinearity with the variable “previous drug reaction”. Variables that were significant in the univariable analyses were not all included in the multivariable logistic regression model because their inclusion led to model instability and convergence issues. Abbreviations: NSAIDs, non-steroidal Anti-inflammatory Drugs; USDAR, United States Drug Allergy Registry; CI, confidence interval; OR, odds ratio.
Table 6.
Severity and causality of delayed hypersensitivity reactions by drug class.
| Delayed Reactions | SCAR (N = 142) | Naranjo Score (N = 136) | ||||||
|---|---|---|---|---|---|---|---|---|
| No a | Yes a | p-Value | Grade < 0 b | Grade 1–4 b | Grade 5–8 b | Grade ≥ 9 b | p-Value | |
| Antibiotics, n (%) | 73/129 (56.6) c | 9/13 (69.2) c | 0.379 | 0/82 (0.0) g | 30/82 (37.0) g | 49/82 (60.5) g | 2/82 (2.5) g | 0.019 (χ2 = 8.754) |
| Beta-lactams, n (%) | 58/129 (45.0) d | 3/13 (23.1) d | 0.129 | 0/60 (0.0) h | 25/60 (41.7) h | 33/60 (55.0) h | 2/60 (3.3) h | 0.816 |
| NSAIDs, n (%) | 18/129 (14.0) e | 1/13 (7.7) e | 0.697 | 0/19 (0.0) i | 8/19 (42.1) i | 10/19 (52.6) i | 1/19 (5.3) i | 1.000 |
| Iodinate contrast media, n (%) | 14/129 (10.9) f | 2/13 (15.4) f | 0.642 | 0/16 (0.0) j | 7/16 (43.8) j | 8/16 (50.0) j | 1/16 (6.3) j | 1.000 |
Note: 129/142 did not have a SCAR, 13/142 had a SCAR a; 1/136 patient had a Naranjo score of <0, 61/136 patients had a Naranjo score of 1–4, 69/136 patients had a Naranjo score of 5–8 and 5/136 patients had a Naranjo score of ≥9 b; 82/142 patients received antibiotics c; 61/142 patients received beta-lactams d; 19/142 received NSAIDs e; 16 patients received iodinate contrast media f. 81/136 patients received antibiotics g; 60/136 patients received beta-lactams h; 19/136 received NSAIDs i; 16/136 received iodinate contrast media j. Abbreviations: NSAIDs, non-steroidal Anti-inflammatory Drugs; SCAR, Severe Cutaneous Adverse Reactions.
Table 7.
Univariate and multivariate regression analyses to assess the potential predominant factor influencing the development of SCAR in the delayed reactions.
Table 7.
Univariate and multivariate regression analyses to assess the potential predominant factor influencing the development of SCAR in the delayed reactions.
| Univariate Analysis (SCAR) | Multivariate Analysis (SCAR) | |||||
|---|---|---|---|---|---|---|
| Characteristics | OR | 95% CI | p-Value | OR | 95% CI | p-Value |
| Age | 0.989 | 0.956–1.022 | 0.499 | 0.994 | 0.958–1.031 | 0.740 |
| Sex | 0.898 | 0.286–2.818 | 0.854 | 1.275 | 0.383–4.244 | 0.692 |
| Atopic comorbidities | 9.500 | 1.200–75.239 | 0.033 | 10.400 | 1.273–84.999 | 0.029 |
| Current outpatient therapy | 0.541 | 0.136–2.155 | 0.383 | 0.558 | 0.111–2.813 | 0.480 |
| Previous drug reactions | 0.127 | 0.016–1.010 | 0.051 | / | / | / |
| Antibiotics | 1.726 | 0.505–5.894 | 0.384 | / | / | / |
| NSAIDs | 0.514 | 0.063–4.196 | 0.534 | / | / | / |
| Iodinate contrast media | 1.494 | 0.300–7.438 | 0.624 | / | / | / |
| Opioids | 2.604 | 0.269–25.206 | 0.409 | / | / | / |
Note: As covariates, we considered age (as continuous variable), sex (female vs. male), current outpatient therapy (≥3 drugs vs. <3 drugs), previous drug reaction (yes vs. no), atopic comorbidities (none vs. at least one), receiving antibiotics (yes vs. no), receiving NSAIDs (yes vs. no), receiving iodinate contrast media (yes vs. no), and receiving opioids (yes vs. no). Variables that were significant in the univariable analyses were not all included in the multivariable logistic regression model because their inclusion led to model instability and convergence issues. Abbreviations: NSAIDs, non-steroidal Anti-inflammatory Drugs; SCAR, Severe Cutaneous Adverse Reactions; CI, confidence interval; OR, odds ratio.
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Ratti, C.P.; Chiei Gallo, A.; Barei, F.; Botta, A.; Cavara, M.; Bono, E.; Caron, L.; Ortolani, V.G.R.; Iemoli, E. Drug Allergy in Hospitalized Patients: Three Years of Consultation Experience in a Tertiary Care Setting. BioChem 2025, 5, 42. https://doi.org/10.3390/biochem5040042
AMA Style
Ratti CP, Chiei Gallo A, Barei F, Botta A, Cavara M, Bono E, Caron L, Ortolani VGR, Iemoli E. Drug Allergy in Hospitalized Patients: Three Years of Consultation Experience in a Tertiary Care Setting. BioChem. 2025; 5(4):42. https://doi.org/10.3390/biochem5040042
Chicago/Turabian StyleRatti, Christian P., Alessandra Chiei Gallo, Francesca Barei, Alice Botta, Matteo Cavara, Eleonora Bono, Lea Caron, Valeria G. R. Ortolani, and Enrico Iemoli. 2025. "Drug Allergy in Hospitalized Patients: Three Years of Consultation Experience in a Tertiary Care Setting" BioChem 5, no. 4: 42. https://doi.org/10.3390/biochem5040042
APA StyleRatti, C. P., Chiei Gallo, A., Barei, F., Botta, A., Cavara, M., Bono, E., Caron, L., Ortolani, V. G. R., & Iemoli, E. (2025). Drug Allergy in Hospitalized Patients: Three Years of Consultation Experience in a Tertiary Care Setting. BioChem, 5(4), 42. https://doi.org/10.3390/biochem5040042
