Oral Drug Provocation Test Research Articles

Development of anaphylaxis upon oral food challenge and drug provocation tests in pediatric patients.

Background: The drug provocation test (DPT) and the oral food challenge (OFC) are considered as the criterion standard for the diagnosis of drug hypersensitivity reactions and food allergy. Severe allergic reactions may develop during these tests. Objective: To evaluate the frequency and features of anaphylaxis in pediatric patients undergoing OFCs and DPTs. Method: OFCs and DPTs performed in an open method in the pediatric allergy clinic of our institution between January 2014 and January 2021 were reviewed retrospectively. The characteristics of anaphylaxis that developed during these tests were evaluated. Results: A total of 3631 OFCs and/or DPTs were performed on 2588 pediatric patients. Reactions were recorded in 317 challenges (8.7%), including 42 (1.2%) in the form of anaphylaxis. Of the patients with anaphylaxis, 31 developed anaphylaxis during OFC and 11 during DPT. Anaphylaxis during OFCs was mostly triggered by yogurt (n = 8), hen's egg (n = 6), baked milk (n = 5), and baked egg (n = 4). Cases with anaphylaxis during DPT were recorded mostly with ibuprofen (54.5% [n = 6]). All patients who developed anaphylaxis during OFC had cutaneous manifestations, and 90.3% had respiratory symptoms. Gastrointestinal involvement was present in 32.3% of the patients. During DPT, cutaneous manifestations were observed in 90.9% in the patients who developed anaphylaxis and the respiratory tract was involved in 81.8%. In terms of concomitant allergic diseases, 51.6% of the patients who developed anaphylaxis during OFC had atopic dermatitis and 38.7% had asthma. All the patients with anaphylaxis triggered by nonsteroidal anti-inflammatory drug DPT had asthma. Of the anaphylaxis, 54.8% were mild, 35.7% were moderate, and 9.5% were severe. Severe anaphylaxis was recorded with baked milk (n = 2), baked egg and trimethoprim-sulfamethoxazole (n = 1, each). The patients did not require intensive care, and no death occurred. Conclusion: Anaphylaxis may develop during OFCs and DPTs. These tests should be carried out by experienced allergists in an appropriate setting where emergency equipment and medications, including epinephrine, are readily available.

Can clarithromycin be used without testing in patients with penicillin allergy?

BackgroundPenicillin hypersensitivity is a common cause of suspected and proven drug allergy and drug-induced anaphylaxis in medical records and causes social and economic burdens. ObjectiveSince the rate of clarithromycin hypersensitivity is low in the general population, we aimed to investigate whether clarithromycin can be prescribed to patients with penicillin allergy without a provocation test. MethodsThe medical records of 186 patients referred to our clinic between 2015 and 2021 with a history of penicillin allergy were evaluated retrospectively. Patients having a history of at least two immediate-type hypersensitivity reactions with penicillin antibiotics or having a history of immediate-type hypersensitivity with penicillin and diagnosed by positive penicillin V/G specific IgE and/or penicillin skin tests were included in the study. Penicillin skin tests were performed according to the manufacturer's instructions. Concentrations of serum specific IgE against phenoxymethylpenicillin (penV) and benzylpenicillin (pen G) were determined using The Phadia CAP System FEIA method. An oral drug provocation test with clarithromycin was performed in all patients. ResultsThe data of 64 patients diagnosed with penicillin allergy and who underwent clarithromycin oral provocation test were analyzed. Oral provocation test with clarithromycin was positive in only two of these patients (3%). These two patients had a history of multidrug hypersensitivity, and one of them also had food and venom allergies. ConclusionWe suggest that clarithromycin can be given without an oral provocation test when an alternative antibiotic is required in patients with penicillin allergy and without multidrug hypersensitivity.

Cardiovascular Changes during Oral Food Challenge and Drug Provocation Test in Children Detected by Noninvasive Hemodynamic Monitoring

The prompt recognition of allergic reactions during oral food and drug challenge (OFC/DPT) in children is crucial. Non-invasive hemodynamic monitoring may help in early detection of the reactions. We sought to describe cardiovascular changes and test their performance in predicting the reaction during OFC/DPT.

Diagnostic Value of Oral Provocation Tests in Drug Hypersensitivity Reactions Induced by Nonsteroidal Anti-Inflammatory Drugs and Paracetamol.

Oral drug provocation tests (DPT) are the basic diagnostic tool for the detection of hypersensitivity to non-opioid analgesics and for selecting a safe alternative for a patient. They are of great practical importance due to their common use, but the data on the follow-up of patients after negative DPT are still very scarce. We examined the further fate of 164 such adult patients after negative NSAID or paracetamol tests and analyzed which excipients in the studied drugs they could be exposed to after the diagnostic workup. A structured medical interview was performed 32.9 months (mean) after the provocation tests. Of the 164 patients, 131 (79.9%) retook the tested drug and 12 developed another hypersensitivity reaction, giving the estimated negative predictive value of 90.8%. These reactions were induced by acetylsalicylic acid, paracetamol, meloxicam, and diclofenac, and were clinically similar to the initial ones (most commonly urticaria and angioedema). There are 93 generics of these drugs on the local market, containing a total of 33 excipients for which hypersensitivity reactions have been reported. All available generics contain such excipients. Thirty-one patients (20.1%) did not take the previously tested drug again, most often because it was not needed or because they were afraid of another reaction. DPT with analgesics has a high diagnostic performance. A minority of patients had relapsed after reexposure. One of the underestimated reasons for this may be drug excipients provoking a reaction, so it is advisable to use exactly the same medical product that has been negatively tested. Many patients avoid reexposure to a given drug, despite negative tests, therefore very reliable patient education in connection with DPT is highly needed.

Safe De-Labeling of Patients at Low Risk of Penicillin Allergy in Denmark

Introduction: Penicillin allergy is suspected in 10% of hospital inpatients but can be disproved in 90% of cases. Direct oral provocation without preceding tests among low-risk patients has proven to be safe in studies of both children and adults and is gaining use across the world. The aims of this study were to investigate the rate of severe allergic reactions to direct oral drug provocation, without preceding tests, in penicillin allergy patients stratified to be at low risk, as well as to examine if these patients have barriers to penicillin allergy de-labeling and future use of penicillins. Methods: Adult patients referred to a university hospital allergy clinic with a suspected penicillin allergy were prospectively risk evaluated. Patients stratified to be at low risk were offered a direct oral provocation with a single-dose amoxicillin followed by 4 days of continued treatment. The same risk stratification criteria were applied to a larger retrospective cohort. Results: In the prospective study population, 202 patients had a direct oral drug provocation and 20 (10%) were positive. There were no cases of anaphylaxis or severe delayed hypersensitivity. Fifteen reactions were benign rashes with onset >1 day after initial dosing, and 13 of these were maculopapular rashes. The same low-risk criteria were applied retrospectively to patients in a drug provocation database, and 1,759 patients fulfilled the criteria; of these, 10% had positive provocations, and there were no cases of anaphylaxis or severe delayed hypersensitivity. De-labeled patients in the prospective study reported not to fear future penicillin intake, after prolonged provocation. Conclusion: The risk stratification criteria for identifying low-risk patients for the oral drug provocation test without prior skin testing were safe in terms of avoiding anaphylaxis or severe delayed hypersensitivity. Benign delayed skin reactions still occurred, and access to allergy advice and follow-up is necessary.

Antibiotic oral provocation challenge in children.

The main objective of this study was to see how many of the children, with a suspected antibiotic allergy, developed an allergic or adverse reaction to a drug provocation test. Data on children that had undergone a drug provocation test for a suspected antibiotic allergy were compiled retrospectively for the period from 2007-2018. The median age at the first provocation was 2.25years (1.5-5.7). Standardised questionnaires, the children's parents had answered before the provocation, were used to evaluate the originally suspected allergic reaction, previous health, atopic diseases and family history. Ninety-two (6.4%) of the 1440 children showed a possible mild allergic reaction. Sixty-four of the 92 children underwent a second drug provocation test 1-2years later. At that time, only eleven developed a positive- or a possible-delayed reaction. An immediate moderate or severe allergic reaction was excluded in all cases of suspected antibiotic allergy in this study. Our study indicates that an oral drug provocation test is safe. It may be appropriate to wait for 6months or more after the initialevent of ADRbefore these tests are performed.A second oral provocation 1-2years after the first oneshowsthatADRsare outgrown inmostchildren.

Meloxicam and/or Etoricoxib Could Be Administered Safely in Two Equal Doses during an Open Oral Challenge in Patients with Nonsteroidal Anti-Inflammatory Drug Hypersensitivity

Background: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are common. These patients require an effective and safe analgesic alternative. Objective: The aim of the study was to demonstrate the safety of meloxicam and etoricoxib administered by open oral challenge in 2 equal steps in patients with NSAID hypersensitivity. Methods: A cross-sectional, descriptive study of patients with a diagnosis of NSAID hypersensitivity who underwent an oral drug provocation test (DPT) with meloxicam or etoricoxib between January 2011 and August 2017 was conducted. The analysis was performed from a database in BD Clinic. Results: Two hundred and twenty-eight oral provocations were performed with an alternative NSAID (203 with meloxicam and 25 with etoricoxib) in 217 patients with hypersensitivity to NSAIDs. The median age was 38 years. Ninety-eight percent of meloxicam and 100% of etoricoxib DPTs were performed in 2 steps (without previous placebo), and 52% and 64% of meloxicam and etoricoxib DPTs, respectively, were performed with 50% of the therapeutic dose in each step. Tolerance to meloxicam was demonstrated in 192 patients (94.5%) and in 100% of patients receiving etoricoxib. Conclusions: Open oral provocation with meloxicam and etoricoxib carried out in 2 steps without placebo seems to be safe and implies less costs and less time expenditure. Also, it could be performed with 2 equal doses.

Hypersensitivity reactions to multiple anti-tuberculosis drugs.

This study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs. We retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs). Twenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2-73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0-3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543). Multiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.

Parental anxiety and depression levels associated with challenge tests in children with suspected drug and food allergies

Aim: Oral food challenges (OFCs) and drug provocation tests (DPTs) are currently the gold standards for evaluating food and drug hypersensitivity, respectively; however, use of these tests on children may generate anxiety and depression among their parents. Our aim was to explore depression and anxiety level among parents of children who were undergoing clinical evaluation via a DPT or OFC. Methods: This cross-sectional study included parents of patients diagnosed with food or drug hypersensitivity reactions in the pediatric allergy clinic between September 2018 and October 2019. Children in Group 1 were subjected to DPT, Group 2 underwent OFC, and Group 3 were healthy controls. Before a child underwent an OFC or DPT, all parents (one parent per child) completed the Hospital Anxiety and Depression Scale, which is a serial assessment for symptoms of depression and anxiety. Results: The study included parents of 105 children, among which Group 1 (n=50 children) were subjected to DPT, Group 2 (n =35 children) underwent OFC, and Group 3 (n=20 children) were healthy controls. In all three Groups, parents were primarily female (62.9%). Anxiety and depression scores were significantly higher among the parents of children in Groups 1 and 2 vs. those of children in Group 3 (P=0.002 and P=0.028, respectively). Anxiety scores were significantly higher among parents of children in Group 2 than those of children in Group 1 (P=0.017). Conclusions: DPTs and OFCs have a significant impact on the emotional status of parents. Parents of children with suspected or documented food allergy experience particularly elevated levels of anxiety and depression before an OFC.

EARLY BIRD CATCHES THE SPOT: ACUTE FIXED DRUG ERUPTION

Introduction Fixed drug eruption (FDE) is a recurring cutaneous reaction that characteristically occurs in the same location(s) upon re-exposure to the same drug. Lesions normally appear 8 hours and up to 2 weeks after drug administration. Case Description A 48-year-old female with a history of primary ciliary dyskinesia and bronchiectasis, lung transplant candidate, came into the Allergy Clinic after developing a hyperchromic macule on her left 4th finger two weeks after being put on trimethoprim-sulfamethoxazole (160 mg/800 mg) for a MDR Achromobacter infection. The lesion resolved within a month after suspending treatment with TMP-SMX. She denies similar episodes while off this antibiotic and with other drugs. An oral drug provocation test was performed with trimethoprim-sulfamethoxazole (160 mg/800 mg). Thirty minutes after receiving the antibiotic, the patient developed a flat, non-pruritic, erythematous macule on her 4th left finger. A biopsy of the lesion demonstrated changes consistent with early fixed drug eruption:focal interface dermatitis, papillary dermal eosinophils, and dermal pigment incontinence. Given the patient's history, she was not a candidate for desensitization. Therefore, she was recommended to avoid TMP-SMX and to use equally efficacious alternatives. Discussion FDE is a delayed hypersensitivity reaction mainly associated with CD8+ T cells. The lesions are typically round to oval, dusky, red to brown/black macules, plaques, or bullae that can appear anywhere on the body; however, hands, feet, lips, and genitalia are sites of predilection. While FDE is a delayed hypersensitivity reaction, there are some cases reported that occur as acutely as within 30 minutes. This is a documented case of such time-variation in presentation.

Drug eruption by antihistamine mistaken for chronic urticaria in a child.

Although rare, antihistamines can cause adverse effects, including drug-induced eruptions or anaphylaxis. A 4-year-old child visited the pediatric department of a hospital for skin eruptions after administration of antihistamines, (e.g., ucerax [hydroxyzine] or leptizine [levocetirizine]), for cholinergic rashes; he did not have pruritus. Skin prick, intradermal, and drug provocation tests were performed to determine the relationship between the antihistamines and eruptions. Levocetirizine induced wheals in the skin prick test and a rash in the oral drug provocation test. In contrast, ketotifen induced no reaction in the skin prick test but showed a positive reaction in the oral provocation test. Our case report highlights that children can experience the same types of adverse reactions as seen in adults, and cross-reactivity between various antihistamines can occur.

P1.10 - Patient with Multiple Drugs Intolerance: Oral Drug Provocation Test

P1.10 - Patient with Multiple Drugs Intolerance: Oral Drug Provocation Test

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs and tolerance to alternative drugs

Abstract Introduction Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) are the most common reactions to drugs. The prevalence varies from 0.6 to 5.7% in the general population, but there are no data available in children. The aim of this study is to determine the frequency of patients diagnosed with hypersensitivity to NSAIDs, and describe their clinical characteristics, type of hypersensitivity, and tolerance to alternative drugs. Methods A retrospective study was conducted on children with suspected hypersensitivity to NSAIDs from January 2012 to December 2013. The diagnosis was confirmed by oral drug provocation test (DPT) to the drug involved in the group with a history of one episode, while in the group with a history of more than one episode with the same drug the diagnosis was based on clinical data. Subsequently, a DPT with acetylsalicylic acid (ASA) was done in order to classify hypersensitivity into selective or multiple. In those cases with a positive result, a DPT was performed with alternative drugs. Results Out of a total of 93 children studied, 26 were diagnosed with hypersensitivity to NSAIDs: 7 confirmed by oral DPT, and 19 based on clinical data. Multiple hypersensitivity was diagnosed in 50% of patients. Ibuprofen was involved in all reactions. The most common clinical manifestation was angioedema (44%). Acetaminophen was the best tolerated alternative drug. Conclusions More than one quarter (28%) of the population studied was diagnosed with hypersensitivity to NSAIDs, and 50% had multiple hypersensitivity. Acetaminophen is a safe alternative in children with hypersensitivity to NSAIDs. Meloxicam may be an alternative in cases that do not tolerate acetaminophen.

Reacciones de hipersensibilidad a antiinflamatorios no esteroideos y su tolerancia a fármacos alternativos

IntroductionHypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) are the most common reactions to drugs. The prevalence varies from 0.6 to 5.7% in general population, but there are no data available in children. The aim of this study is to determine the frequency of patients diagnosed with hypersensitivity to NSAIDs, and describe their clinical characteristics, type of hypersensitivity, and tolerance to alternative drugs. MethodsRetrospective study was conducted on children with suspected hypersensitivity to NSAIDs from January 2012 to December 2013. The diagnosis was confirmed by oral drug provocation test (DPT) to the drug involved in the group with a history of one episode, while in the group with a history of more than one episode with the same drug the diagnosis was based on clinical data. Subsequently, a DPT with acetylsalicylic acid (ASA) was done in order to classify hypersensitivity into selective or multiple. In those cases with a positive result, a DPT was performed with alternative drugs. ResultsOut of a total of 93 children studied, 26 were diagnosed with hypersensitivity to NSAIDs: 7 confirmed by oral DPT, and 19 based on clinical data. Multiple hypersensitivity was diagnosed in 50% of patients. Ibuprofen was involved in all reactions. The most common clinical manifestation was angioedema (44%). Acetaminophen was the best tolerated alternative drug. ConclusionsMore than one quarter (28%) of the population studied was diagnosed with hypersensitivity to NSAIDs, and 50% had multiple hypersensitivity. Acetaminophen is a safe alternative in children with hypersensitivity to NSAIDs. Meloxicam may be an alternative in cases that do not tolerate acetaminophen.

Moxifloxacin hypersensitivity: Uselessness of skin testing

Moxifloxacin hypersensitivity: Uselessness of skin testing

Post exposition to etoricoxib in patients with negative oral drug provocation tests

Results Forty-one patients were tested, all with negative results. Thirty seven of them (90%) were contacted and 28 (76%) remembered the tested drug’s name. Twelve of them (32%) had used the drug again without any reaction. Twenty five patients were not re-exposed: 18 did not need, 4 were afraid of a new reaction and 3 used another alternative. Of the 4 patients who were afraid to use the drug again, 3 of them had presented anaphylaxis symptoms with other NSAIDs.

Determinants of nocebo effect during oral drug provocation tests

BackgroundA “nocebo” effect is defined as troublesome symptoms after the administration of placebo. The aim of this study was to determine characteristics of nocebo responses and related factors. MethodsPatients with a reliable history of drug-induced hypersensitivity reactions subjected to placebo-controlled oral drug provocation tests and reacted to placebo, were consecutively included in this case–control study. Controls consisted of the randomly selected subjects who had a history of drug hypersensitivity reaction but did not react to placebo. A structured questionnaire was performed by an allergy specialist. ResultsThere were 137 subjects (mean age: 43.10±12.65 years), with nocebo and 91 subjects (42.38±12.18 years) without any reaction to placebo. Most nocebo reactions (71.5%, n=98) were classified as subjective, with local pruritus as the most common finding. A minority of nocebo reactions (11.7%, n=16) were objective as cutaneous reactions including flushing and urticaria. Factors related with nocebo risks were university graduation (OR: 2.96, 95% CI: 1.27–6.93, p=0.012) and non-atopy (OR: 2.12, 95% CI: 1.02–4.40, p=0.043). In terms of the time of first and last historical reaction to drugs, each 1-unit (a month) increase in first reaction time (OR: 1.008, 95% CI: 1.00–1.02, p=0.001) and last reaction time (OR: 1.019, 95% CI: 1.01–1.03, p<0.001) were associated with increased nocebo risk. ConclusionIn conclusion, subjects with high education, non-atopy, and older drug hypersensitivity reactions history seem to be more likely to experience nocebo effect during oral drug provocation tests. These risk factors should be considered and managed accordingly to complete the drug provocation procedure successfully.

Tolerance to COX-2 inhibitors in children with hypersensitivity to nonsteroidal anti-inflammatory drugs

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) can affect children, with the mechanism proposed being inhibition of the cyclooxygenase enzyme-1 (COX-1). In these patients nonchemically related NSAIDs, including COX-2 inhibitors, can induce the reaction, hampering treatment of fever and inflammatory processes. To analyse retrospectively tolerance to etoricoxib, a selective COX-2 inhibitor, and to meloxicam, a preferential COX-2 inhibitor, in children with hypersensitivity to NSAIDs. Clinical records of children (aged 1-14 years) diagnosed with hypersensitivity reactions to NSAIDs from January 2006 to January 2013 were included. The diagnosis was confirmed by oral drug provocation test (DPT) with the culprit NSAIDs and acetylsalicylic acid (ASA). Tolerance to paracetamol, etoricoxib and meloxicam was also evaluated. The study included 41 children with a positive DPT with ASA and the culprit NSAID. DPT with paracetamol and etoricoxib was negative in all children, although two (4.9%) children developed a reaction after the administration of meloxicam. These data indicate that both etoricoxib and meloxicam are good alternatives for treatment in older children with hypersensitivity to NSAIDs.

A Case of Immunoglobulin E Mediated Anaphylaxis to Levodropropizine

We experienced a case of immunoglobulin E (IgE) mediated anaphylaxis to levodropropizine. The patient was an 18-year old Korean woman. After taking the common cold medication including acetaminophen, domperidone, and levodropropizine, skin rash, angioedema and anaphylaxis were developed immediately. As she was tolerable to acetaminophen alone, we thought the culprit agent was maybe a levodropropizine tablet. To confirm the culprit, she underwent skin prick test and oral drug provocation test with the suspected one. Finally we detected levodropropizine specific IgE and confirmed the specificity by inhibition enzyme-linked immunosorbent assay (ELISA).

Oral drug provocation test to generate a list of safe drugs: Experience with 100 patients

Following a drug eruption, patients and their doctors need to know which drugs can be safely administered for subsequent illnesses. Currently available laboratory tests are unable to answer this question in a clinically meaningful manner. To describe our use of oral provocation tests to provide a list of safe drugs to patients. We studied the records of 100 patients who underwent oral provocation testing in our department between 2003 and 2009. All patients were admitted to hospital and drugs were administered under supervision, one drug per day. A dermatologist evaluated all symptoms and signs that developed following drug intake. Sixty nine women and 31 men underwent provocation testing. There were 96 reactions in 61 patients, of which 44 reactions in 34 patients were judged to be true reactions. All reactions could be controlled, with treatment or spontaneously. A list of safe drugs was provided to the patient along with written instructions to avoid any drug(s) that had produced a reaction. Oral provocation tests are safe and effective in providing patients with a list of drugs they can take safely. These tests should preferably be undertaken after admitting the patient to hospital.