Moderate Hypersensitivity Reactions Research Articles

Hypersensitivity Reactions to Taxanes: A Multicenter Study for Outcomes and Safety of Rapid Drug Desensitization.

Taxanes can cause hypersensitivity reactions (HSRs), which pose a significant challenge in the treatment of malignancies. Patients who are eligible for rapid drug desensitization (RDD) can continue treatment; however, some patients experience breakthrough reactions (BTRs). Data about risk factors for BTRs during RDDs in patients with HSRs to taxanes are limited. This was a multicenter, retrospective study of patients with immediate-HSRs to taxanes. Initial HSRs were classified as grade 1, 2, or 3 based on severity. Prick/intradermal skin tests were performed with implicated taxanes. A 12-step protocol was used during RDD. The study comprised 75 patients (F/M: 63/12, mean age 49.92 ± 11.72 years, 43 HSRs to paclitaxel, 32 HSRs to docetaxel). The majority of reactions (86.7%) occurred during the first or second exposure. The prevalence of drug allergy history was higher in patients with paclitaxel HSR than in those with docetaxel HSR, although it was not statistically significant (23.3% vs. 6.3%). The initial HSRs were mostly grade 2 (n = 50, 66.7%) or grade 3 (n = 22, 29.3%). Skin tests with implicated taxanes were done on 48 patients, and the rate of positive response in patients with grade 1, 2, and 3 initial HSRs were 50%, 17.6%, and 16.7%, respectively. . A total of 255 RDDs were completely performed, although BTRs occurred in 27 (grade 1, 55.6%; grade 2, 40.7%; grade 3, 3.7%). There were no statistically significant correlations between the risk of BTR and age, drug cycle, gender, positivity of skin test or atopy. The step reduction was successfully done on 9 eligible patients with mild or moderate HSRs during the 12-step RDDs. Our experience demonstrates a 100% success rate in completing the 255 RDDs for taxanes, affirming the safety and efficacy of the RDD within the study population.

A Survey of Practicing Radiologists on the Use of Premedication Before Intravenous Iodinated Contrast Medium Administration

ObjectiveTo determine whether updated guidance by the ACR in 2017 advocating use of intravenous (IV) premedication in emergency department (ED) patients and inpatients with reported iodinated contrast allergy was associated with a change in clinical practice. MethodsAn anonymous survey was distributed via e-mail in October 2020 to practicing radiologist members of the ACR interrogating use of corticosteroid premedication for two clinical vignettes: an indicated routine (perform within 24 hours) inpatient contrast-enhanced CT (CE-CT) and an indicated urgent (perform within 6 hours) ED CE-CT. In both scenarios, the patient had a prior moderate hypersensitivity reaction to iodinated contrast media. Clinical management was evaluated. Data were compared to historical controls from 2009. ResultsThe response rate was 11% (724 of 6,616). For the inpatient scenario, 72% (518 of 724) would use corticosteroid premedication with CE-CT, and 28% (200 of 724) would perform noncontrast CT. For the ED scenario, 67% (487 of 724) would use corticosteroid premedication with CE-CT, and 30% (217 of 724) would perform noncontrast CT. Oral premedication (85%, 439 of 518) was preferred for routine inpatients, and rapid IV premedication (89%, 433 of 487) was preferred for urgent ED patients. Of those who provided rapid IV dosing data in the ED, two doses of corticosteroids were used by 53% (216 of 410) and one dose was used by 45% (185 of 410), with academic radiologists more likely than private or hybrid practice radiologists to administer two doses (74% [74 of 100] versus 48% [151 of 312], P < .001, odds ratio, 3.03; 95% confidence interval, 1.84-5.00). Rapid IV premedication was more commonly used in 2020 than in 2009 (60% [433 of 724] versus 29% [20 of 69], P < .001, odds ratio, 3.65; 95% confidence interval, 2.12-6.26). Antihistamine use was common in both inpatient (93%, 480 of 518) and ED settings (92%, 447 of 487). Only 32% (229 of 721) of radiologists practiced in accordance with ACR guidelines, suggesting no need for routine premedication before CE-CT in patients with prior severe hypersensitivity reaction to gadolinium-based contrast media. Nonetheless, most (93%, 670 of 724) said the ACR Manual on Contrast Media was a major determinant of their practice. ConclusionsUse of rapid IV premedication in urgent settings has increased since 2009, following updated ACR guidelines, but there is disagreement over whether one or two corticosteroid doses is required. Despite reported high reliance on ACR guidelines, deviations from those guidelines remain common. In general, when ACR guidelines were not followed, it was in a risk-averse direction.

Hypersensitivity reactions to paclitaxel: The Mexican experience of rapid desensitization.

Taxanes adjuvant therapy is recommended in certain high risk or metastatic tumors, particularly in lung and breast cancer, but also in other types of cancer like ovarian. The incidence of severe adverse drug reactions to paclitaxel is of approximately 10%. Analyze type I hypersensitivity reactions to paclitaxel and their management in the Mexican population. It is a retrospective, observational and descriptive study that included type I hypersensitivity reactions to paclitaxel reported from our database. Symptoms of hypersensitivity reactions to paclitaxel were classified and skin testing was performed with a 6 mg/mL paclitaxel concentration. The desensitization procedure consisted of a 12-steps, 3-bags of 250 mL protocol with a 6-7-hour duration. A total of 60 desensitization procedures were performed and were all completed successfully. All participants in our group were female, their median age was 44.5 years.All of our patients had hypersensitivity adverse drug reaction to paclitaxel during their first exposure and within the first 10 minutes of infusion. 63.6% of the patients had a moderate hypersensitivity reaction to paclitaxel and 36.4% had a severe reaction. Paclitaxel continues to be a common use drug and has a high rate of adverse drug reactions. This is the first study of hypersensitivity to paclitaxel in a Mexican population.

Safety of Intravenous Iron Following Infusion Reactions

Where an ongoing requirement for intravenous iron replacement exists after an index infusion reaction, current recommendations are limited to expert opinion and isolated case reports. To evaluate the safety of recommencing an infusion or subsequent rechallenge following an infusion reaction to intravenous iron. Infusion reactions to intravenous iron occurring between January 1, 2010, and December 31, 2019, at a metropolitan health network were identified. Patient characteristics, reaction type (mild, moderate, or severe hypersensitivity, delayed, or Fishbane: transient flushing and truncal myalgias), and outcomes of recommencing the index infusion or subsequent rechallenge were examined. Among 13,509 iron infusions, 195 infusion reactions occurred in 195 patients (1.4% of infusions). Recommencement of the index infusion (generally with a reduced infusion rate and premedication) was tolerated in 33 of 33 patients with Fishbane (20 of 20) or mild (9 of 9) and moderate (4 of 4) hypersensitivity reactions. Subsequent rechallenge (generally at standard infusion rates to an alternative formulation, ferric carboxymaltose) was successful in 68 of 69 patients with Fishbane (23 of 23), mild (26 of 26), moderate (16 of 17), and severe (3 of 3) hypersensitivity, or delayed (2 of 2) reactions. All 9 patients rechallenged to the original formulation (iron polymaltose) completed the infusion. Following an infusion reaction to intravenous iron infusion, recommencement of the index infusion is safe for Fishbane or mild and moderate hypersensitivity reactions. Subsequent rechallenge to an alternative formulation is tolerated, including in severe hypersensitivity reactions (albeit based on limited numbers). Where alternative formulations are not available, rechallenge to the same formulation could be considered, depending on the risk-benefit profile.

Reduced iodinated contrast media dose and injection speed for CT: how much does this decrease the risk of a hypersensitivity reactions?

Adverse reactions developing after administration of iodinated contrast media (ICM) can either constitute hypersensitivity reactions, toxic reactions, or even events unrelated to ICM exposure, such as acute spontaneous or infection-induced urticaria (1). Toxicity-related reactions (also called “physiologic” or “chemotoxic” reactions) are more common than hypersensitivity reactions and often manifest with mild unspecific symptoms, such as pruritus, heat sensation, transient erythema, dizziness, nausea, sneezing, chest tightness, arrhythmia, hypertension, and vasovagal signs (i.e., hypotension and bradycardia). Immediate hypersensitivity reactions (IHR) (acute hypersensitivity reactions) occur within 1 hour after ICM administration and either present with full anaphylaxis, involving skin, gastrointestinal, respiratory and/or cardiovascular organ systems simultaneously, sometimes with bronchospasm and/or hypotension, but may also manifest as fractions of anaphylaxis, such as urticaria, or angioedema only (2,3). Fatalities do occur (4). Among IHR, there is growing evidence that particularly severe reactions may be immunoglobulin E (IgE)-mediated and skin test- positive, whereas mild to moderate hypersensitivity reactions are mostly non-allergic (5-7). IHR have been reported in a frequency of about 0.3–3% of ICM injections (1).

Hypersensitive adverse drug reactions to glucosamine and chondroitin preparations in Australia between 2000 and 2011

Purpose of the studyThis study investigates spontaneous adverse drug reactions (ADRs) to glucosamine and chondroitin in the Australian population between 2000 and 2011, with a primary focus on hypersensitivity reactions.Study...

Mild to moderate hypersensitivity reactions to beta-lactams in children: a single-centre retrospective review

ObjectiveBeta-lactam (BL) antibiotics are the most reported drugs in hypersensitivity reactions in children. More than 90% of these children tolerate the suspected drug after diagnostic work-up. Skin tests (STs) show...

Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin

ObjectiveThe primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). MethodsThis was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment with 4-step, one-solution desensitization protocols in the outpatient infusion center were included. Patients with delayed HSRs or immediate high-risk, moderate or severe HSRs were excluded. The primary end point was the rate of successful administrations of each course of platinums. ResultsFrom January 2011 to June 2013, eighteen eligible patients were evaluated for outpatient 4-step, one-solution desensitization. Thirteen patients had a history of HSRs to carboplatin and 5 with HSRs to cisplatin. All of 18 patients successfully completed 94 (98.9%) of 95 desensitization courses in the outpatient infusion center. Eight of 8 (100%) patients with initial mild HSRs completed 29/29 (100%) desensitization courses, and 9 of 10 (90%) of patients with initial moderate HSRs completed 65/66 (94%) desensitization courses. In total, 65/95 (68%) desensitizations resulted in no breakthrough reactions, and mild, moderate and severe breakthrough reactions were seen in 19%, 12% and 1% desensitizations, respectively. No patients were hospitalized during desensitization. ConclusionsThe outpatient rapid, 4-step, one-solution desensitization protocol was effective and appeared safe among gynecologic oncology patients who experienced mild to low-risk, moderate HSRs to carboplatin/cisplatin.

Outpatient rapid desensitization for gynecologic oncology patients with mild to moderate hypersensitivity reactions to platinums

Objectives: Platinums (carboplatin and cisplatin) are associated with hypersensitivity reactions (HSR). While 50% of HSR to carboplatin are mild, re-challenge is often associated with earlier onset and more severe HSR. Most published desensitization protocols were implemented in the inpatient settings. The objective of study is to assess the safety and efficacy of outpatient rapid desensitization in gynecologic oncology patients with a history of mild to moderate HSR to platinums.

The Risk of Toxicities from Trastuzumab, Alone or in Combination, in an Elderly Breast Cancer Population

Background: Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab-based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. Patients and Methods: Medical records of consecutive HER2-positive breast cancer patients aged ≥70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). Results: Among 59 patients identified, 51 patients were evaluable (median age 76 years). The rate of any adverse event was 20% (10/51). The most relevant cardiac adverse event consisted of symptomatic congestive heart failure (CHF; n = 1, 2%) followed by asymptomatic decreases of left ventricular ejection fraction (LVEF; n = 6, 12%). Other toxicities included moderate hypersensitivity reactions during trastuzumab infusions (n = 3, 6%). Hypertension, obesity, prior anthracyclines exposure and concurrent chemotherapy were associated with a higher incidence of toxic events. Previous radiotherapy, concurrent endocrine therapy and different trastuzumab-based regimens did not seem to influence toxicity. Conclusions: Our data suggest that trastuzumab has a good safety profile in nonfrail women aged 70 years and older. These favorable findings may be related to a limited number of anthracycline pretreatments, patient selection and a close cardiologic monitoring.

Rituximab hypersensitivity reactions (HSR): Predictors of recurrent and severe reactions based on severity of reaction, NHL histologic subtype, and burden of disease.

e18520 Background: Rituximab is an anti-CD20 monoclonal antibody with efficacy in B-cell malignancies. Grade II-IV HSR occur in 5-10% of patients. There are no data to predict which patients are at risk for more severe rituximab HSR as well as no data on eventual successful rituximab administration in this population. Methods: We analyzed all rituximab HSR in patients at Massachusetts General Hospital between 2006-2010. Patients included had documented HSR on the chemotherapy infusion sheet on our electronic medical record or via referral to allergy for desensitization. Control rituximab-treated patients were identified from tumor registry data. ICD3 codes were used to determine the histologic subtypes. Rates of HSR were analyzed by logistic regression and Fisher's exact test. Severity of HSR was based on an established classification system. Results: Immediate HSR occurred in 9% of patients (79/901) treated with rituximab and premedications. A majority of patients with a HSR developed symptoms on their initial infusion (76%); however, 46% of moderate or severe HSR occurred on subsequent infusions. Severity of HSR was directly correlated to the risk of a recurrent reaction where all patients with severe HSRs and 56% of patients with moderate HSRs had a recurrent reaction in contrast to only 36% of patients with mild reactions (p = 0.005). Advanced stage of disease increased the risk of a moderate or severe HSR (HR = 4, p = 0.02). Waldenstrom’s Macroglobulinemia (WM) accounted for 10% of all HSR while representing only 1% of rituximab treated pts (p &lt; .003 adjusting for multiple comparisons) and 70% of these patients had a HSR. All patients with complex HSR who were referred to allergy for desensitization (n=14) were able to complete therapy safely. Conclusions: Severe rituximab HSR commonly occurs after the initial infusion. Severity of the HSR predicted recurrent HSR and an advanced stage of disease predicted more severe reactions. WM had a disproportionately higher risk for HSR. Despite HSR, we found that all patients were able to tolerate the recommended number of infusions without severe adverse events utilizing medical management and/or desensitization.

Safety of trastuzumab, alone or in combination, in elderly patients with HER2-positive breast cancer: A 5-year case series.

e11056 Background: Breast cancer (BC) is frequent in the elderly and is burdened by high recurrence and death rates, due mostly to undertreatment. Trastuzumab (T), in combination with chemotherapy (CT) or hormonotherapy (HT), is a well-established treatment strategy for early and advanced HER2-positive (HER2+) breast cancer, but has been poorly studied in the elderly setting due to its infrequency. The aim of our study is to assess the safety of T in elderly patients with HER2+ BC. Methods: Between 2005 and 2010, consecutive HER2+ breast cancer patients of ≥70 years of age referred to two oncology centers and that received T-based therapy were retrospectively reviewed. All patients were treated according to multidimensional geriatric assessment (MGA) and clinical criteria. Results: Of 59 patients, 51 were evaluable with a mean age of 76 years (range 70-86). Trastuzumab was well tolerated overall. Median left ventricular ejection function (LVEF) at baseline was 61% and at the end of treatment was 55%. The most relevant adverse events consisted of only one case (2%) of symptomatic congestive heart failure, which required treatment withdrawal and six (12%) asymptomatic decreases of LVEF (3 pts &gt;15% and 3 pts &gt;10% versus baseline). Mild to moderate hypersensitivity reactions associated with T-containing infusions occurred in 3 patients (5.8%). Hypertension, obesity and previous anthracycline-based treatment and combination with CTs gave a trend towards a higher incidence of toxic events. Previous radiotherapy, concurrent HT and the different T schedules did not influence toxicity. Conclusions: Our data shows a good trastuzumab safety profile in non-frail women age 70 and older. These favourable findings may be related to the limited number of anthracycline pre-treatments, a substantial patient selection by MGA and close cardiologic monitoring. [Table: see text]

Paclitaxel plus carboplatin (PC) in patients with metastatic melanoma (MM): Experience in a single institution

e20019 Background: The number of agents active in patients with metastatic melanoma is limited and cure is not an objective for treatment at this stage, so that clinical benefit in these patients is the most important. The aim of the study was to evaluate the efficacy and safety of combination regimen consisting of paclitaxel and carboplatin as second-line chemotherapy, in patients with MM. Based on reports of responses to PC, 17 patients with MM was treated at the National Cancer Institute of Mexico. Methods: We evaluated retrospectively the combination of PC in patients with MM. Data regarding patient characteristics and outcomes were abstracted from medical records of NCI of Mexico from 01/05 to 12/08. The regimen was weekly paclitaxel (at a dose of 80 mg/m2) received on days 1, 8, and 15 of a 21-day cycle and carboplatin (AUC 5) on day 1. Response evaluation was using RECIST and toxicity was according to National Cancer Institute Common Toxicity Criteria. This study was approved by the hospital ethics committee. Results: Seventeen patients with MM were treated with PC. All patients were previously treated (and failed) with dacarbazine (DTIC). Sixteen were assessable for response with three cycles of chemotherapy and seventeen for toxicity. One patient was deemed to be ineligible because they presented severe hypersensitivity reaction to paclitaxel at beginning. Objective partial response were obtained in 4 patients (25%); 8 stable disease (50%) at least four months. No patient had a complete response to therapy. Progression disease was in 4 patients (25%). In 12 (75%) we noted clinical benefit. The median time to disease progression for the entire group was 4.2 months (range, 1–11 mos), with a median overall survival of 8.1 months (range, 5.6–10.5 mos). The toxicity grade 3 reported was thrombocytopenic in 2 patients (11%) and anemia in one patient (6%). Additional patients had reversible toxicities grade 3 including alopecia, nausea and fatigue; 2 of them presented moderate hypersensitivity reactions to paclitaxel. No toxic death was noted. Conclusions: The PC combination appears to be safety and well tolerated in second line chemotherapy in MM, however we need more patients to demonstrate a true clinical benefit, we outcomes are according with other clinical reports. No significant financial relationships to disclose.

Docetaxel in Combination with Dacarbazine in Patients with Advanced Melanoma

Objectives: The number of agents that are active in patients with metastatic melanoma is limited and cure is not a realistic objective for treatment at this stage. The aim of the study was to evaluate the efficacy and safety of new combination regimen cosisting of docetaxel and dacarbazine (DTIC), as first-line chemotherapy, in patients with advanced melanoma. Patients and Methods: Patients with advanced melanoma (including cerebral metastases) were eligible. Docetaxel 80 mg/m², i.v. over 1 h infusion on day 1, and DTIC 400 mg/m², i.v. over 45 min on days 1 and 2, were given every 21 days, for six cycles. All patients were premedicated, prior to each course, with methylprednisolone per os. Results: Forty-one patients entered the study. Thirty-nine were assessable for response and 40 for toxicity. Objective responses were seen in 10 patients (24% of the eligible; 95% CI = 12.4–40.3%, 26% of the assessable and 28% of patients with cerebral metastases were excluded). Three of them achieved a complete response (7%; 95% CI = 1.5–19.9) and 7 a partial response (17%; 95% CI = 7.1–32.0), while 8 patients demonstrated stabilization of their disease (20%; 95% CI = 8.8–34.9). After a median follow-up of 20 months, the median time to progression was 7 months (range 0.5–22) and the median survival was 10 months (1–24+). The main toxicity (G3–4) was neutropenia which occurred in 8/40 (20%) patients. Additional patients had reversible G3–4 toxicities including alopecia, nausea and vomiting and fatigue; 3 of them presented mild to moderate hypersensitivity reactions to docetaxel. No toxic death was noted. Conclusions: The combination of docetaxel and DTIC is active and well tolerated in patients with advanced melanoma. While this combination is at least as effective as various combination regimens, it does not differ from that reported for single-agent DTIC.

Phase I study of paclitaxel (Taxol™) and ifosfamide in previously untreated patients with advanced non-small-cell lung cancer : A study of the National Cancer Institute of Canada Clinical Trials Group

Paclitaxel (Taxol) and ifosfamide are among the most active single agents for the treatment of non-small-cell lung cancer. We undertook this phase I dose escalation study to determine the maximum tolerated doses of these drugs which could be administered without growth factors to untreated patients with tumours of this type. Forty patients with advanced non-small-cell lung cancer were treated with a 3-hour infusion of paclitaxel and a 1-hour infusion of ifosfamide every 3 weeks. Groups of 3 patients were entered at escalating dose levels in traditional phase I design. Starting doses were paclitaxel, 100 mg/m2, and ifosfamide 3 g/m2, and all patients received premedication with dexamethasone, diphenhydramine and a 5-HT3 blocker. Dose escalation occurred only after full toxicity assessment for 2 cycles for all patients in the dose level. Dose escalation of paclitaxel continued to 225 mg/m2 without dose-limiting toxicity, but further escalation was not attempted because of the known likelihood of neuro-toxicity above this level. Instead, ifosfamide was increased to 4 g/m2 for the final level. At these doses, dose-limiting myelosuppression was not seen, and there was only 1 episode of febrile neutropenia in 164 treatment cycles. Drug-related toxicities of ifosfamide included gross hematuria and confusion in 1 patient each, and paclitaxel-related symptoms included flu-like syndrome in most patients, mild to moderate arthralgia and/or myalgia in 8 and 25 patients, respectively, parasthesiae in 15 patients and mild to moderate hypersensitivity reactions in 15 patients each. Partial response was seen in 20.5% of patients (CI 9.3%-36.5%). Out-patient paclitaxel given over 3 hours and single-dose ifosfamide over 1 hour may be combined safely without the need for hematopoietic growth factors for the treatment of patients with non-small-cell lung cancer. The recommended doses for phase II study are paclitaxel, 225 mg/m2 and ifosfamide, 4 g/m2 every 3 weeks.

Dyazide-Induced Reversible Acute Renal Failure Associated With Intracellular Crystal Deposition

Acute interstitial nephritis due to Dyazide therapy, ie, a combination of hydrochlorothiazide (25 mg) and triamterene (50 mg), has been recently reported in the literature. This had been characterized by nonoliguric renal failure after a long latent period (weeks) following exposure to the drug. Pathologic data have indicated a drug-induced hypersensitivity reaction. We report here one case of oliguric acute renal failure after a massive Dyazide intoxication. Based on the results of the renal biopsy and clinical course, we propose that the oliguria was secondary to a direct toxic effect on the tubules, and intrarenal obstruction was secondary to triamterene crystals and crystal-laden cells. In addition, pathologic findings also suggested a moderate hypersensitivity reaction. After hemodialysis and short-term steroid therapy, the patient achieved complete recovery of renal function within 12 days. Recent knowledge of triamterene-induced nephrolithiasis helps to explain the pathogenesis of acute renal failure in this patient, and is briefly reviewed here.