Fever as the only manifestation of hypersensitivity reactions associated with oxaliplatin in a patient with colorectal cancer Oxaliplatin-induced hypersensitivity reaction

Hypersensitivity reactions （HSR） to oxaliplatin in patients with colorectal cancer include facial flushing, erythema, pruritis, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. We report a patient with fever as the sole manifestation of initial HSR, review the literature and discuss the management of HSR. A 57-year-old female with T3N2M0 rectal adenocarcinoma received modified FOLFOX-6. She tolerated the first 8 cycles without any toxicities except grade 1 peripheral neuropathy and nausea. During 9th and 10th infusions, she developed fever to a maximum of 38.3℃ with stable hemodynamic status despite medications. During 11th infusion, she developed grade 3 HSR consisting of symptomatic bronchospasm, hypotension, nausea, vomiting, cough, and fever. On examination, she was pale, cyanotic, with a temperature of 38.8℃, BP dropped to 95/43 mm Hg, pulse of 116/min and O2 saturation of 88%-91%. She was hospitalized for management and recovered in 24 h. Fever alone is not a usual symptom of oxaliplatin HSR. It may be indicative that the patient may develop serious reactions subsequently, as did our patient who developed hypotension with the third challenge. Treatment and prevention consists of slowing the infusion rate, use of steroids and antagonists of Type 1 and 2 histamine receptor antagonists, whereas desensitization could help to provide the small number of patients who experience severe HSR with the ability to further receive an effective therapy for their colorectal cancer.

Clinical Features of Oxaliplatin-induced Hypersensitivity Reactions in Chinese Patients: A Retrospective Multicenter Analysis

Objective The characteristics of oxaliplatin-induced hypersensitivity reactions(HSRs)in Chinese patients were investigated to provide a reference for patients treated with oxaliplatin.Methods The study reviewed the records of patients who developed oxaliplatin-induced HSRs in 17 hospitals from May 2016 to May 2017.We collected and analyzed the basic information,history of oxaliplatin administration and premedication treatments,chemotherapy cycles,HSR symptoms,and the management and outcomes of these patients.Results Oxaliplatin-induced HSRs were recorded in 137 patients who had been treated with oxaliplatin-containing regimens.Five different chemotherapy regimens were applied.The median infusion cycle when oxaliplatin-induced HSRs occurred was 7,and HSRs occurred during or shortly after oxaliplatin infusion.Most of the patients experienced grade 1 or grade 2 HSRs with mild symptoms of pruritis(49.64%),flushing(46.72%),chest discomfort(26.28%),and urticaria(25.55%).The majority of the patients completely recovered from HSRs following treatment with antihistamines and dexamethasone.Seven patients completed chemotherapy with oxaliplatin after the symptoms resolved with proper management.Conclusion The results indicate that oxaliplatin-induced HSRs remain an important issue in safely and successfully fulfilling oxaliplatin-containing chemotherapy.Further studies are needed to analyze the risk factors and establish prophylaxis for such reactions.

Hypersensitivity Reaction Caused by Intravenous Gadolinium-based MRI Contrast Agents

Objective To present a rare case of skin allergic reaction to gadobutrol,a magnetic resonance imaging(MRI)contrast agent,in a 37-year-old man.Methods The adverse reactions of gadobutrol were analyzed combined with the instructions and related literatures.Results and Conclusion The presence of this patient is consistent with the adverse reactions in the instructions of gadobutrol.The incidence of ADR in gadobutrol is considered to be low,although sometimes patients report a hypersensitivity reaction when undergoing MRI.There are only a few cases of immediate adverse reactions to gadobutrol.However,we should improve the ability of medical staff to use drugs safely and take preventive measures.

Studies on abacavir-induced hypersensitivity reaction:a successful example of translation of pharmacogenetics to personalized medicine

Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected patients.Its main side effect is hypersensitivity reaction(HSR).The incidence of the HSR is associated with ethnicity among patients exposed to abacavir,and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen(HLA)-B*57:01-carrying patients.Immunological studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire,leading to a systemic autoimmune reaction.HLA-B*57:01 screening,combined with patch testing,had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the population.Therefore,the US Food and Drug Administration(FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR.The studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.

Oral Cadmium Intake Enhances Contact Allergen-induced Skin Reaction in Rats

Objective The effect of oral cadmium(Cd)intake to influence contact skin allergies was examined,since it is known that Cd is a heavy metal that affects many tissues,including the skin,in which it disturbs homeostasis,thus resulting in inflammation and injury.Methods Male rats were evoked with experimental contact hypersensitivity reaction(CHS)to hapten dinitrochlorobenzene(DNCB),after prolonged(30 day)oral exposure to an environmentally relevant Cd dose(5 ppm).The ear cell population was analyzed with flow cytometry.Cytokine production by ear skin cells and the activity of skin-draining lymph node(DLN)cells were measured using enzyme-linked immunosorbent assay(ELISA).Results Orally acquired Cd(5 ppm)increased CHS intensity only in Dark Agouti(DA)rats by affecting inflammatory responses in both the sensitization(an increase of IFN-γ and IL-17 cytokine production)and challenge(an increase of CD8^(+)and CD4^(+)cell number and TNF,IFN-γ and IL-17 cytokine production)phases.An increased CHS reaction was seen in Albino Oxford(AO)rats only at a high Cd dose(50 ppm),during the challenge phase(an increase of CD8^(+)and CD4^(+)cell number and TNF,IFN-γ and IL-17 cytokine production).Conclusion These novel data indicate that oral Cd intensifies the skin response to sensitizing chemicals such as DNCB.

Intervention for oxaliplatin-induced hypersensitivity in China:a cross-sectional internet-based survey

Objective This cross-sectional study aimed at investigating the intervention status and the influence of oncologists on oxaliplatin-induced hypersensitivity reactions(OIHR).Methods Snowball sampling was used to send questionnaires to oncologists in various provinces and cities in China,via the internet,to collect data on their socio-demographic characteristics,the occurrence of OIHR,and the current status of interventions.One-way ANOVA and T-test of geographic samples were used to explore the relationship between the incidence of OIHR and intervention measures.Results A total of 401 valid questionnaires were collected,most respondents were 30–40 years old,and most oncologists had 5 years of working experience.The proportions of glucocorticoid and H1 receptor antagonist use for OIHR prevention were 67.83%and 38.65%,respectively.The proportion of oncologists with longer working years and higher professional titles who used glucocorticoids for OIHR prevention was higher,and the observed OIHR incidence was lower.Pretreatment with glucocorticoids may be an effective preventive measure and can reduce the incidence of the OXA allergic reactions(P<0.05).Conclusion The risk awareness of junior oncologists to OIHR prevention should be strengthened,and clinical efficacy evaluation of glucocorticoids in OIHR prevention should be further promoted.

Severe chest pain in a pediatric ulcerative colitis patient after 5-aminosalicylic acid therapy

Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.

Atezolizumab-induced anaphylactic shock in a patient with hepatocellular carcinoma undergoing immunotherapy:A case report

BACKGROUND Atezolizumab is a programmed death ligand 1(PD-L1)inhibitor,and its combination with bevacizumab has been proven an effective immunotherapy for unresectable hepatocellular carcinoma(HCC).Treatment with immune checkpoint inhibitors(ICIs)can lead to hypersensitivity reactions;however,anaphylactic shock is rare.We present a case of life-threatening anaphylactic shock during atezolizumab infusion and performed a relevant literature review.CASE SUMMARY A 75-year-old man was diagnosed with HCC recurrence after hepatectomy.He was administered immunotherapy with atezolizumab plus bevacizumab after an allergy to a programmed death-1(PD-1)inhibitor.The patient showed a sudden onset of dizziness,numbness,and lack of consciousness with severe hypotension during atezolizumab infusion.The treatment was stopped immediately.The patient’s symptoms resolved after 5 mg dexamethasone was administered.Because of repeated hypersensitivity reactions to ICIs,treatment was changed to oral targeted regorafenib therapy.CONCLUSION Further research is necessary for elucidating the hypersensitivity mechanisms and establishing standardized skin test and desensitization protocols associated with PD-1 and PD-L1 to ensure effective treatment with ICIs.

Investigation of possible risk factors in the development of seasonal allergic conjunctivitis

AIM： To analyze the possible risk factors in the development of seasonal allergic conjunctivitis（SAC） through an evaluation of skin allergy tests and data obtained from questionnaires.METHODS： The study included a total of 75 SAC patients and 71 control subjects without SAC diagnosis who were admitted to the Abant Izzet Baysal University Medical Faculty Ophthalmology Clinic between March 2016 and December 2016. Skin prick tests were performed for all participants. Serum levels of total IgE and 25-OH vitamin D were also measured. In the tear, total IgE levels were measured. Moreover, possible risk factors for the onset of SAC（smoking, paracetamol exposure, vitamin D supplementation and environmental factors etc.） were examined for all patients by both prenatal and postnatal aspects.RESULTS： The patients with SAC were found to have a history of maternal paracetamol exposure during the prenatal period. Likewise, in the same patient group, the duration of postnatal vitamin D supplementation was shorter（P〈0.001）. However, no significant correlation was found between SAC and maternal antibiotic exposure, maternal smoking, the mode of delivery and birth weight, as well as presence of pets. Moreover, patients with SAC were more likely to have asthma, allergic rhinitis and oral allergy syndrome. We have also found that SAC patients＇ mothers and siblings were more likely to have allergic conjunctivitis. Likewise, their fathers were more likely to have allergic rhinitis. CONCLUSION： Prenatal maternal paracetamol exposure and shorter duration of vitamin D supplementation in the postnatal period may play a role in development of SAC. Therefore prevention of unnecessary gestational paracetamol intake and vitamin D supplementation during infancy could potentially reduce the onset and development of SAC.

Differentiation of xanthomonads causing the bacterial leaf spot of poinsettia in China from the pathotype strain of Xanthomonas axonopodis pv. poinsettiicola

In October 2003, a new bacterial disease with symptoms similar to those caused by Xanthomonas axonopodis pv. poinsettiicola was observed on poinsettia leaves at a flower nursery in Zhejiang Province of China. Three Xanthomonas strains were isolated from infected plants and classified as X. axonopodis. They were differentiated from the pathotype strain LMG849 of X. axonopodis pv. poinsettiicola causing bacterial leaf spot of poinsettia by comparison of pathogenicity, substrate utilization and BOX-PCR genomic fingerprints.

Drug Reaction with Eosinophilia and Systemic Symptoms： Retrospective Analysis of 104 Cases over One Decade

Background： Drug reaction with eosinophilia and systemic symptoms （DRESS） is a severe, life-threatening disorder caused by drugs. In the present study, we tried to explore the types of DRESS-inducing drugs, incubation period, features of skin rashes, accompanying visceral damage, and effectiveness of glucocorticoid therapy so as to inform clinical practice. Methods： Patients diagnosed with a drug-induced rash, dermatitis, and DRESS admitted to our hospital from January 2006 to December 2015 were included in the study. The diagnosis followed the criteria and scoring system set by the European Registry of Severe Cutaneous Adverse Reactions. Statistical analyses were carried out using SPSS version 17.0 （IBM, Armonk, NY, USA）, and a value ofP 〈 0.05 was considered statistically significant. Results： Among 104 patients, 38 were male and 66 female （aged 18-83 years）. The latent period was 13 （interquartile range [IQR]： 10-17） days. The most common allergy-inducing drugs were antibiotics （n = 37, 35.6%）, followed by antiepileptic drugs and traditional Chinese medicines （TCMs）. Eighty-two cases （78.8%） had rash with area 〉50% body surface area （BSA）. Liver damage occurred in 90% of cases. Patients were divided into oral antihistamine group and glucocorticoid/immunosuppressive agent/intravenous immunoglobulin （IVIG） group. Sex, age, incubation period, duration of hospital stay, and the number of patients with body temperature 〉38.5℃ were not significantly different between the two groups. However, the number of patients meeting the criteria of＂definite＂ and ＂probable＂ （X2 =5.852, P = 0.016）, with an eosinophilic granulocyte count of〉1.5 x10^9/L 0,2 7.129, P = 0.008）, and with rash area of〉50% BSA （X2 = 4.750, P = 0.029）, was significantly different. Conclusions： Antibiotics were associated with allergic reactions, but TCMs also had an important role. Allergy resulting from repeat use of the same drug was more severe with a shorter incubation period. The most typical rash was widespread erythematous papules. Liver damage accounted for 〉90% of cases.

Pharmacogenetics of asparaginase in acute lymphoblastic leukemia

Asparaginase is a key component in leukemias and lymphomas treatment protocols and is suggested as a treatment for other malignancies in which an amino acid depletion strategy is indicated.Asparaginase intolerance is subject to inter-individual variability and can manifest as hypersensitivity reactions,pancreatitis,thrombosis,as well as metabolic abnormalities,and may affect treatment outcome.Pharmacogenetics aims at enhancing treatment efficacy and safety by better understanding the genetic basis of variability and its effect on the pharmacological responses.Many groups tried to tackle the pharmacogenetics of asparaginase but the potential implementation of such findings remains debatable.In this review,we highlight the most important findings reported in studies of the pharmacogenetics of asparaginase related complications and treatment outcome in acute lymphoblastic leukemia.

Genetic diversity of Harpins from Xanthomonas oryzae and their activity to induce hypersensitive response and disease resistance in tobacco

Three hrfA (hypersensitive response-functioning faction A) homologues (hrf1, hrf2 and hrf3) are cloned from 12 strains of Xanthomonas oryzae using PCR based techniques. Hrf1, hrf2 and hrf3 are derived from strains belonging to X. o. pv. oryzae, X. o. pv. oryzicola and X. o. pv. oryzae respectively. Sequence analysis shows that all three genes encode glycine-rich pro-teins with various numbers of GGG-GG motifs. They all share a conserved cysteine residue at position 45 or 47. Hrf1 and hrf3 encode HarpinXoo while hrf2 encodes Harpinxooc. Hrf1 and hrf3 encodes two different types of HarpinXoo proteins. Hrf1 from X. o. pv. oryzae strains ( JxoIII, JxoIV, Jxov, Pxo61, Pxo76, Pxo79, Pxo99, Pxo99 and Pxo124) encodes a 15.6 kD HarpinXoo with 3 GGG-GG motifs while Hrf3 from strain Pxo86 and Pxo112 encodes a 15.9 kD Harpinxoo with 4 GGG-GG motifs. Harpinxooc encoded by hrf2 from X. o. pv. oryzicola (strain RS105) has the mo-lecular weight of 15.3 kD and contains 2 GGG-GG motifs. Cluster analysis is performed using deduced sequences of hrf1, hrf2 and hrf3 as well as previously reported Hpa1 and XopI protein sequence. The results indicated that Harpinxoo and Harpinxooc belong to two closely related sub-groups. Hrf, hrf2 and hrf3 are expressed in E. coli strain BL21 successfully. Under the same condition, hrf1, hrf2 and hrf3 are expressed at the level of 0.389, 0.530 and 0.083 mg/mL re-spectively. All expressed hrf1, hrf2 and hrf3 proteins (Harpins) are shown to be able to induce hypersensitive reaction and TMV resistance on tobacco. Among the three proteins, Hrf2 has the highest activity while Hrf3 has the lowest activity.