Case Of Hypersensitivity Reaction Research Articles

Cross-reactivity among and between macrolides, lincosamides, and streptogramins: Study on the French pharmacovigilance database.

Hypersensitivity reactions (HSR) are reported for the macrolides, lincosamides, and streptogramins (MLS) antibiotic family. Data about cross-reactivity among and between MLS remain scarce or controversial. The aim of this study was to provide an overview of hypersensitivity cross-reactions among MLSs based on data extracted from the French National Pharmacovigilance Database (FPVD). Cases of HSR to MLSs reported between January 1985 and December 2019 were extracted from the FPVD using standardized MedDRA queries (SMQ). Cases including an allergological test involving multiple MLSs and giving at least one positive result were included. Of the 8394 cases reviewed, 149 were included. HSR mainly involved pristinamycin (n= 83; 53.2%) and spiramycin (n= 31; 19.9%). HSR to MLS was immediate in 54 cases and delayed in 94 cases. Skin tests represented the majority of the allergological tests performed (n= 728; 84.7%), followed by reintroduction tests (n= 79; 9.2%). Eighty-six cross-reactivities among MLS were identified in 62 cases (41.6%). All the 25 explorations performed for streptogramins showed cross-reactivities, but only 30/253 among macrolides (11.9%). Cross-reactivities between the three MLS were observed in 31/322 (9.6%) of the allergological explorations. This study highlights the possibility of cross-reactivity among and between MLSs. Dermatologists and allergologists managing patients with HSR to MLSs should be aware of a risk of cross-reactivity among the macrolides and between the different classes of MLS and to perform MLSs allergological testing before recommending an alternative antibiotic, especially in severe drug hypersensitivity from the MLS family.

Dermal Hypersensitivity Reaction to Semaglutide: Two Case Reports.

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of antidiabetic agents that work by inducing insulin secretion and inhibiting release of glucagon in a glucose-dependent manner. They are especially promising given their long duration of action, decreased risk of hypoglycemia, and added benefit of weight loss. Semaglutide is a GLP-1 receptor agonist that has been approved for type II diabetes and chronic weight management in obese adults. Cases of hypersensitivity reactions have been previously reported in patients taking GLP-1 receptor agonists dulaglutide and liraglutide. However, to our knowledge, there have been no reports of hypersensitivity reactions to semaglutide. Here, we present two cases of dermal hypersensitivity reactions in patients taking semaglutide for type II diabetes. In the first case, a 75-year-old woman who had been taking semaglutide for 10 months presented with an eruption on her legs, back, and chest for 3 months duration. Histology showed a subepidermal blister with eosinophils, suggestive of a drug hypersensitivity reaction. In the second case, a 74-year-old white man who had been taking semaglutide for 1 month presented with an eruption on the bilateral flanks and lower abdomen for 3 weeks duration. Histology revealed perivascular inflammatory cell infiltrate with eosinophils, also suggestive of a drug hypersensitivity reaction. Both patients began experiencing resolution of their symptoms within 1 month of discontinuing semaglutide. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.6550 Citation: Ouellette S, Frias G, Shah R, et al. Dermal hypersensitivity reaction to semaglutide: Two case reports. J Drugs Dermatol. 2023;22(4):413-415. doi:10.36849/JDD.6550.

Hypersensitivity reactions to metals in spine surgery.

Hypersensitivity to orthopedic devices is a rare condition with an underestimated incidence due to the lack of diagnostic guideline and ambiguous clinical manifestations. Although hypersensitivity to metal is common, a few cases of hypersensitivity reactions have been reported after spinal instrumentation. Spinal fusion and stabilization require a wide range of devices such as screws, wires, bands, and artificial disk replacement devices. Spinal instrumented surgeries are different from total joint arthroplasty in several aspects such as degree and pattern of motion, loading environment, and adjacent tissues with distinct characteristics. The interval for hypersensitivity reactions to occur after spinal metallic implantation is usually weeks to months. The present review covers the topic of hypersensitivity reactions that have been reported after spinal surgeries with the focus on cutaneous presentations.

Efficacy of an oral CRTH2 antagonist (AZD1981) in the treatment of chronic rhinosinusitis with nasal polyps in adults: A randomized controlled clinical trial.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease of the upper airways. AZD1981 is a selective antagonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 and other type 2 cells, including innate lymphoid cells type 2, eosinophils, and basophils. To evaluate the efficacy of AZD1981 in reducing nasal polyp size when added to intranasal corticosteroids in adult patients with CRSwNP. Eighty-one subjects (18-70years of age) with CRSwNP were recruited and screened for trial eligibility from allergy and otolaryngology clinics from a single tertiary care site between June 2016 and August 2019. Eligible patients were randomized in a double-blind fashion to receive either AZD1981 (n=22) or placebo (n=21) orally three times a day for 12weeks, added to intranasal corticosteroids. The primary endpoint was a change in nasal polyp score (NPS) at 12weeks. Secondary endpoints included improvement in sinus computed tomography using Lund Mackay scoring, symptoms using visual analog scale, quality of life using Sino Nasal Outcome Test-22, and the Brief Smell Identification Test. Forty-three patients met the inclusion criteria and were enrolled. At 12weeks, there was no difference in NPS change in the AZD1981 arm (mean 0, standard error 0.34, n=15) compared with placebo (mean 0.20, standard error 0.36, n=17); mean difference -0.20 (95% confidence interval: -1.21, 0.81; p=.69). No significant differences were observed for Lund Mackay score, symptoms, quality of life, or smell test. AZD1981 was well tolerated except for one case of hypersensitivity reaction. In patients with CRSwNP, the addition of AZD1981 to intranasal corticosteroids did not change nasal polyp size, radiographic scores, symptoms, or disease-specific quality of life.

Dermal Fillers and COVID-19: Angioedema With Urticaria in a Patient Post COVID-19 Infection

Hyaluronic acid dermal fillers are a very popular choice for patients wanting to undergo non-invasive facial rejuvenation. Its prevalence is predicted to continue to rise. We report a case of delayed angioedema and associated urticaria to hyaluronic acid dermal fillers post COVID-19 infection. To our knowledge, this is an unusual case of hypersensitivity reaction of eight-month latency. Although the aetiology warrants further research, the author suggests utilisation of a four-week time window between dermal filler injections and COVID-19 vaccination.

РЕДКОЕ НАБЛЮДЕНИЕ РЕАКЦИИ ГИПЕРЧУВСТВИТЕЛЬНОСТИ НА ПРЕПАРАТЫ ДЛЯ ФЕРМЕНТНОЙ ЗАМЕСТИТЕЛЬНОЙ ТЕРАПИИ У РЕБЕНКА С БОЛЕЗНЬЮ ГОШЕ 3-го ТИПА

Gaucher disease (GD) is an autosomal recessive disease that leads to excessive accumulation of glucocerebroside in the cells of the reticuloendothelial system, which leads to multiple organ damage with the development of cytopenia, hepatosplenomegaly, bone and neurological pathology. An effective and safe enzyme replacement therapy has been developed for the treatment of GD. However, there are rare cases of hypersensitivity reactions presented in the literature, requiring individualization of patient management with the search for alternative ways to continue therapy and prevent side effects. We present a rare clinical case of intolerance to imiglucerase and velaglucerase alfa in a child with GD type 3 and possible methods for continuing treatment, taking into account the hypersensitivity reaction.

Allergic-like Hypersensitivity Reactions to Gadolinium-based Contrast Agents: An 8-year Cohort Study of 154 539 Patients.

Background With the widespread use of gadolinium-based contrast agents (GBCAs), the incidence of allergic-like hypersensitivity reactions (HSRs) to GBCAs is increasing. Research on the incidence and risk factors for HSRs to GBCAs is needed for their safe use. Purpose To determine the incidence of acute and delayed reactions to GBCAs and to discuss the risk factors and strategies for the prevention of HSRs to GBCAs. Materials and Methods All cases of HSRs to contrast media that occurred at the Seoul National University Hospital from July 1, 2012, to June 30, 2020, were assessed. Information including age, sex, GBCA type, onset, and severity of HSRs was retrospectively analyzed. Results Among the 331070 cases of GBCA exposure in 154539 patients, 1304 cases of HSRs (0.4%) were reported. Acute HSRs accounted for 1178 cases (0.4%), while 126 cases (0.04%) were delayed HSRs. While both premedication (odds ratio [OR] = 0.7, P = .041) and changing the type of GBCA (OR = 0.2, P < .001) showed preventative effects in patients with a history of acute HSRs, only premedication (OR = 0.2, P = .016) significantly reduced the incidence of HSRs in patients with a history of delayed reactions. The risk of an HSR to GBCA was higher in those with a history of an HSR to iodinated contrast media (OR = 4.6, P < .001). Conclusion The rate of hypersensitivity reactions (HSRs) to gadolinium-based contrast agents (GBCAs) was 0.4%. The absence of premedication, repeated exposures to the culprit GBCA, and a history of HSRs to iodinated contrast media and GBCAs were risk factors for HSRs to GBCAs. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kallmes and McDonald in this issue.

Hypersensitivity reactions after femtosecond laser small incision lenticule extraction: a case report of corneal infiltrates

BackgroundFemtosecond laser corneal refractive surgery is generally considered safe and effective; however, this procedure is rarely associated with severe allergic reactions. We reported a rare case of hypersensitivity reactions which caused bilateral peripheral corneal infiltrates after femtosecond laser small incision lenticule (SMILE) surgery in a man with a history of fruits allergy.Case presentationHere we report the case of a young man who developed white, ring-shaped bilateral peripheral infiltrates that appeared 1 day after an uneventful SMILE surgery. The overlying corneal epithelium was intact; the infiltrate was negative for bacterial culture, but high titers of immunoglobulin E was demonstrated in the blood. Symptomatically, a clinical diagnosis of sterile corneal infiltrates was made, and the patient was treated with topical and systemic steroids. The infiltrates were immunogenic in origin, which may be caused by the contact lenses used for suction duration in surgery. It resolved without corneal scarring in the subsequent months following steroid treatment. The patient’s visual acuity improved.ConclusionsWhen patients with a history of allergy who aim to perform corneal refractive surgery, surgeons must consider possible hypersensitivity reactions after treatment. More studies are needed to clarify the relationship between contact glass used in femtosecond laser corneal refractive surgery and IgE mediated hypersensitivity reactions.

Incidence Rate of Hypersensitivity Reactions to Bee-Venom Acupuncture.

IntroductionBee-venom acupuncture (BVA) has been widely applied to various disorders including pain-related diseases; however, patients are often warned of adverse reactions such as anaphylaxis. This study aimed to estimate the risk of hypersensitivity reactions to BVA and to determine their clinical features.MethodsWe retrospectively surveyed the medical records of patients treated by BVA between January 2010 and April 2019 in Dunsan Hospital of Daejeon University, and all cases of allergic reactions and their clinical symptoms were analyzed.ResultsA total of 8,580 patients (males 4,081 and females 4,499) were treated with BVA which amounts to a total of 60,654 treatments (average 7.1 ± 14.8 times). A total of fifteen patients (7 males and 8 females) reported an allergic reaction (0.175%, 95% CI, 0.086–0.263) of type 1 hypersensitivity, indicating a rate of allergic reaction in 0.025% (95% CI, 0.012–0.037) of the total BVA treatments. The average number of BVA treatments in those patients was 6.9 ± 6.5 (males: 4.1 ± 3.4 and females: 9.3 ± 7.9). Among the cases of hypersensitivity reactions, 4 involved anaphylactic shock; therefore, the incidence rate of anaphylaxis was 0.047% (95% CI, 0.001–0.092) for the 8,580 subjects and 0.007% (95% CI, 0.000–0.013) for the 60,654 treatments. All grade 1 cases were recovered within 1 day, whereas others took up to 30 days for complete recovery.ConclusionOur results may emphasize paying attention to unforeseeable risks of anaphylaxis after bee-venom acupuncture. This study could be essential reference data for the guidelines of appropriate use of bee-venom acupuncture and bee-venom-derived interventions in clinical applications.

Vancomycin Hypersensitivity Reactions Documented in Electronic Health Records

Vancomycin, the most common antimicrobial used in US hospitals, can cause diverse adverse reactions, including hypersensitivity reactions (HSRs). Yet, little is known about vancomycin reactions documented in electronic health records. To describe vancomycin HSR epidemiology from electronic health record allergy data. This was a cross-sectional study of patients with 1 or more encounter from 2017 to 2019 and an electronic health record vancomycin drug allergy label (DAL) in 2 US health care systems. We determined prevalence and trends of vancomycin DALs and assessed active DALs by HSR phenotype determined from structured (coded) and unstructured (free-text) data using natural language processing. We investigated demographic associations with documentation of vancomycin red man syndrome (RMS). Among 4,490,618 patients, 14,426 (0.3%) had a vancomycin DAL with 18,761 documented reactions (2,248 [12.0%] free-text). Quarterly mean vancomycin DALs added were 253 ± 12 and deleted were 12 ± 2. Of 18,761 vancomycin HSRs, 7,903 (42.1%) were immediate phenotypes and 3,881 (20.7%) were delayed phenotypes. Common HSRs were rash (32% of HSRs) and RMS (16% of HSRs). Anaphylaxis was coded in 6% cases of HSRs. Drug reaction eosinophilia and systemic symptoms syndrome was the most common coded vancomycin severe cutaneous adverse reaction. RMS documentation was more likely for males (odds ratio, 1.30; 95% CI, 1.17-1.44) and less likely for blacks (odds ratio, 0.59; 95% CI, 0.47-0.75). Vancomycin causes diverse adverse reactions, including common (eg, RMS) and severe (eg, drug reaction eosinophilia and systemic symptoms syndrome) reactions entered as DAL free-text. Anaphylaxis comprised 6% of documented vancomycin HSRs, although true vancomycin IgE-mediated reactions are exceedingly rare. Improving vancomycin DAL documentation requires more coded entry options, including a coded entry for RMS.

Ketoprofen hypersensibility and idiosyncratic response – a case report

Context: Ketoprofen is widely used to remove pain. A steady increase on allergic reactions and photoallergic contact dermatitis related to ketoprofen has been reported when there is topical use. However, there are few documented cases of hypersensitivity when it is administered systemically.Objective: Present a case of hypersensitivity reaction after systemic administration of ketoprofen for pain control in nephritis crisis.Case description: A 43-years-old Caucasian man diagnosed with renal colic (kidney lithiasis), who was initially treated with 100 mg of tramadol (IV), followed by 4 mg of thiocolchicoside (IM) which caused no relief. Then 100 mg of ketoprofen was administered (IV). Right after the patient began to show hypersensitivity reaction type I characterized by intense coughing, rhinitis, angioedema, periorbital edema, rash, and scleral jaundice.Discussion and conclusion: Maybe it was a case of drug-induced liver disease, however therapeutic dosages of all administered drugs only once. The mechanisms involved were not investigated, but may be the result of allergic and immunologic aspects caused by ketoprofen and facilitated by a history of hypersensitivity to other NSAIDs as reported by the patient. As for jaundice can be attributed to drug toxicity since laboratory parameters did not reveal any evidence of liver disease.

Hypersensitivity reaction with metformin: a case report

Metformin is a biguanide derivative widely used for treatment of diabetic patients. The most common toxic effects of metformin are gastrointestinal (anorexia, nausea, vomiting, abdominal discomfort and diarrhoea). As with other drugs, allergic reactions can occur with metformin also, but these are very rare. A case of hypersensitivity reaction with metformin was reported in adverse drug monitoring centre. A 59-year-old female, newly diagnosed case of diabetes mellitus II, started on metformin tablet 500 mg twice daily, developed purpuric skin lesions on her arms, legs and back few days after starting the drug. metformin was stopped and patient was put on glimepiride tablet. The lesions slowly started subsiding after stopping metformin.

Two Cases of Hypersensitivity Reactions Caused by Human Serum Albumin During Therapeutic Plasma Exchange

Two Cases of Hypersensitivity Reactions Caused by Human Serum Albumin During Therapeutic Plasma Exchange

Clinical analysis of hypersensitivity reaction of platinum in ovarian cancer and cervical cancer patients

Objective: To investigate the incidence, risk factors, management and prognosis of hypersensitivity reaction (HSR) of platinum-based chemotherapy in patients of ovarian cancer and cervical cancer. Methods: Cases from Peking Union Medical College Hospital from Jan. 2013 to Jan. 2016 were checked for patients' data of epithelial ovarian cancer treated with carboplatin/paclitaxel (every 3 weeks) and patients of cervical cancer treated with concurrent radiochemotherapy using cisplatin (every week). General characters, pathological features, treatment and prognosis of patients were analyzed to determine the severity, symptoms, outcomes and risk factors of HSR. Results: (1) Prevalence of HSR: there were 860 cases of ovarian cancer and 580 cases of cervical cancer, among which HSR occurred in 8.8% (76/860) and 5.9% (34/580) patients, respectively. (2) Grading for HSR: most HSR were grade 1 or 2, with 78.9%(60/76) in ovarian cancer and 82.4%(28/34) in cervical cancer patients. In ovarian cancer patients, there were 7 cases of grade 1 HSR and 53 cases of grade 2 HSR, and in cervical cancer patients, there were 11 cases of grade 1 HSR and 17 cases of grade 2 HSR. (3) Symptoms of HSR: most of HSR happened during intravenous infusion of platinum agents, with 98.7% (75/76) in ovarian cancer and 97.1% (33/34) in cervical cancer patients. In ovarian and cervical cancer patients, most common symptom were tight chest and dyspnea, which happened in 92.1% (70/76) and 97.1% (33/34) patients, respectively. Secondary common symptom were skin reactions, which happened in 53.9% (41/76) and 88.2% (30/34) patients respectively. (4) Treatment after HSR: of 76 ovarian cancer cases with HSR, there were no significant difference in the ratio of HSR recurrence among patients of different treatment after HSR (χ2=0.517, P=0.915): 1 of 4 patients applying prior chemotherapy, 4 of 13 cases receiving desensitization, 3 of 11 cases separating medicine, 2 of 11 patients switching to cisplatin. In 34 cervical cancer cases of HSR, there were also no significant difference in the ratio of HSR recurrence among patients of different treatment after HSR (χ2=0.079, P=1.000): 2 of 9 patients applying prior chemotherapy, 3 of 17 cases receiving desensitization. (5) Risk factors of HSR and patients prognosis: in ovarian cancer patients of HSR, risk factors included relapse (P=0.010), courses of chemotherapy reaching seven or nine for patients of primary treatment or reaching six or seven for recurrent patients (all P<0.05). There were no significant risk factors for cervical cancer patients of HSR (all P>0.05). HSR had no impact on the progression- free survival for ovarian cancer (P=0.144) or cervical cancer (P=0.782). Conclusions: In ovarian cancer patients treated with carboplatin and cervical cancer patients treated with concurrent radiochemotherapy using cisplatin, most HSR of platinum are mild and favorable outcomes. Relapse and longer chemotherapy courses are risk factors for HSR of carboplatin for epithelial ovarian cancer.

Hypersensitivity reactions to racemic calcium folinate (leucovorin) during FOLFOX and FOLFIRI chemotherapy administrations

Hypersensitivity reactions to racemic calcium folinate (leucovorin) during FOLFOX and FOLFIRI chemotherapy administrations

Dolutegravir: Clinical and Laboratory Safety in Integrase Inhibitor–Naive Patients

Background:The efficacy of dolutegravir (DTG) has been demonstrated in 5 randomized studies in integrase inhibitor (INI)–naive adult populations. To date, a detailed safety review of DTG has not been provided in the literature. Objective: To describe the safety and tolerability profile of DTG in adults based on 5 randomized, controlled trials and comparison with drugs in 3 major antiretroviral (ARV) classes. Methods: Safety data from phase IIb/III/IIIb trials in ART-naive and ART-experienced, INI-naive adults were integrated. Results: In 4 ART-naive (SPRING-1, SPRING-2, SINGLE, FLAMINGO) and 1 ART-experienced, INI-naive study (SAILING), 1,579 individuals received a DTG-containing regimen. The proportion of individuals from DTG treatment arms who withdrew due to adverse events (AEs) was low (≤2%) compared to raltegravir (RAL; 2% SPRING-2, 4% SAILING), efavirenz (EFV)–containing comparator arm (10% SINGLE), and darunavir + ritonavir (DRV/r; 4% FLAMINGO). The most frequently observed AEs (diarrhea, nausea, headache), typically grade 1 or 2 in severity, did not lead to study discontinuation. Psychiatric and nervous system disorders with DTG were comparable to RAL- and DRV/r-containing regimens and favorable to EFV-containing regimens. In hepatitis B and/or C coinfected ART-naive individuals, the incidence of transaminase elevations was lower with DTG versus RAL and EFV comparators, but was similar to DRV/r. In SAILING, transaminase elevations were more commonly observed with DTG, particularly in the setting of inadequate hepatitis B therapy or immune reconstitution. On DTG treatment, mild creatinine elevations occurred and stabilized early. Few cases of hypersensitivity reaction and/or severe rash were seen. Rates of these events were comparable to or lower than with RAL-, EFV-, and DRV/r-containing regimens. Conclusions: The safety profile for DTG 50 mg once daily in INI-naive individuals was comparable to RAL- and DRV/r-containing regimens and generally favorable compared with EFV-containing regimens.

A large prospective European cohort study of patients treated with strontium ranelate and followed up over 3 years

Strontium ranelate has been available as an osteoporosis treatment in Europe since 2004. This article describes a large European observational survey of the use of strontium ranelate in clinical daily practice. A retrospective observational registry included 32,446 women consulting for postmenopausal osteoporosis in seven countries. Within the registry, 12,046 women were receiving strontium ranelate and were followed up over 3 years. The baseline characteristics of the follow-up cohort were similar to those of the whole registry cohort (age, 68.9 ± 10.3 years; body mass index, 25.6 ± 4.3 kg/m(2); lumbar spine T-score, -2.57 ± 0.85 SD; femoral neck T-score, -2.11 ± 0.86 SD). At baseline, 77 % of patients had at least one risk factor for osteoporosis, and 46 % had a previous history of osteoporotic fracture. Mean duration of follow-up was 32.0 ± 9.7 months, and treatment duration was 25.2 ± 13.7 months (24,956 patient-years of treatment). Persistence with strontium ranelate was 80 % at 1 year, 68 % at 2 years, and 64 % at 32 months; most patients (about 80 %) reported rarely omitting a dose. At least one emergent adverse event was reported in 2,674 (22 %) patients, most frequently gastrointestinal side effects. The crude incidence of venous thromboembolic events was 2.1/1,000 patient-years. No cases of hypersensitivity reactions, such as drug rash with eosinophilia and systemic symptoms (DRESS), Steven-Johnson syndrome, or toxic epidermal necrolysis, were reported. During follow-up, a fracture occurred in 890 patients (7 %); 429 of the fractures were nonvertebral fractures. Our observational survey over 32 months indicated good rates of adherence with strontium ranelate and confirmed its good safety profile in the management of postmenopausal osteoporosis.

Recognizing and Managing Eczematous Id Reactions to Molluscum Contagiosum Virus in Children

Molluscum contagiosum (MC) is a self-limiting cutaneous viral eruption that is very common in children. MC infection can trigger an eczematous reaction around molluscum papules known as a hypersensitivity or an id reaction. In addition, a hypersensitivity reaction can occasionally occur at sites distant from the primary molluscum papules. These eczematous reactions are often asymptomatic or minimally pruritic. We believe that id reactions represent an immunologically mediated host response to MC virus and a harbinger of regression. Therefore, these reactions often do not require treatment other than emollients. Moreover, topical steroids or immunomodulators may suppress this process and potentiate the spread of the primary MC infection. However, in symptomatic patients, treatment should not be withheld and short-course treatments of topical corticosteroids may be used. In this case series, we describe 3 cases of hypersensitivity reactions in otherwise healthy children with MC. We hope that our report will make clinicians more aware of this common eczematous response to MC and will improve the management and counseling of these patients and their parents.

A Retrospective Review of the Frequency and Nature of Acute Hypersensitivity Reactions at a Medium-Sized Infusion Center: Comparison to Reported Values and Inconsistencies Found in Literature

To evaluate acute hypersensitivity reactions at the UCSD Moores Cancer Center in San Diego, compare our findings to those reported previously in the literature, and examine the effectiveness of the objective grading scale as represented by the Common Terminology Criteria for Adverse Events (CTCAE). Using the available pharmacy and electronic medical record data from 2006-2010, we examined our reported hypersensitivity reactions (HSRs) using the CTCAE v.3.0 and v.4.0. A thorough literature review was also performed to compare our findings with those previously reported. We found 222 cases of HSRs, of which 50% were due to immunotherapeutics. Most were grade 1 or 2 by any CTCAE criteria. The clinical presentation of HSRs varied between drug classes. Using different versions of grading schema led to inconsistencies in ~50% of all HSRs. Fifty-two percent of all cases not due to blood products were rechallenged on the same day. The reported literature HSR frequencies for each causative agent showed a striking variability, possibly indicating that previous studies used a wide variety of grading and reporting systems for adverse events. HSRs are common in clinical practice, and most are mild or moderate. There are inconsistencies in reporting HSRs between studies. The existence of several grading schema and subjective definitions of hypersensitivity could be contributing to poor clinical generalizability. Along with an improved system of reporting HSRs to minimize underreporting, a standard system of objectively assessing HSRs is necessary for purposes of research and clinical practice.

Oxaliplatin-Free Interval as a Risk Factor for Hypersensitivity Reaction among Colorectal Cancer Patients Treated with FOLFOX

Background: Hypersensitivity reaction (HSR) and sensory neuropathy are major complications of oxaliplatin-based chemotherapy. Preplanned withdrawal of oxaliplatin after the first six cycles and reintroduction at the time of disease progression (stop-and-go strategy) may reduce neurotoxicity. However, the effect of an oxaliplatin-free interval on HSR occurrence remains poorly understood. Patients and Methods: Data on patients with colorectal cancer who received FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) treatment between June 2005 and June 2009 were retrieved from the prospective cohort database of the Outpatient Oncology Unit of the Kyoto University Hospital. Factor analysis was performed. Results: Among patients who received six or fewer cycles of FOLFOX, the incidence of HSR was low (7/99, 7.1%). For patients who received more than six cycles, the incidence of HSR was higher among patients treated with stop-and-go FOLFOX than among patients treated with continuous FOLFOX (25/61, 41.0% vs. 13/63, 20.6%; p = 0.019). Interestingly, most cases of HSR during stop-and-go FOLFOX occurred during the second or third cycle of the reintroduction phase (21/25, 84%). Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (p = 0.016). Conclusions: An oxaliplatin-free interval may increase the risk of HSR. Special vigilance is needed during the second and third cycles after reintroduction of oxaliplatin.