Allopurinol is the well-known first-line treatment option for symptomatic hyperuricaemia and gout. It is cost-effective particularly for the management of chronic gout. The common early side effects of allopurinol are skin rashes, diarrhoea and nausea. Meanwhile, a dangerous concerning complication is Stevens–Johnson syndrome, which can cause severe morbidity and mortality. Delayed hypersensitivity to allopurinol is rare but should be one of the differential diagnoses if a patient with underlying gout on chronic allopurinol treatment presents with skin rashes. The present case highlights the importance of a high index of suspicion in at-risk patients with underlying gout along with skin rashes on long-term allopurinol treatment to avoid unnecessary patient management.
Hypersensitivity, Delayed ; Allopurinol ; Exanthema

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.
Biomarkers/blood* ; Child ; Child Health ; Child, Preschool ; Cohort Studies ; Environmental Exposure/adverse effects* ; Environmental Health ; Environmental Pollutants/adverse effects* ; Female ; Fetal Blood/chemistry* ; Follow-Up Studies ; Growth/drug effects* ; Humans ; Hypersensitivity/etiology* ; Infant ; Japan/epidemiology* ; Male ; Neurodevelopmental Disorders/etiology* ; Pregnancy ; Prenatal Exposure Delayed Effects/etiology* ; Prevalence ; Smoking/adverse effects*

Influenza vaccine-associated anaphylaxis is a very rare allergic reaction to vaccines, but the most concerning and life-threatening adverse reaction. Although the safety of influenza vaccines has been well documented, occasional cases of anaphylaxis in vaccinated patients have been reported. In this study, we analyzed the immunoglobulin E (IgE) response to whole influenza vaccines in a pediatric case of delayed-onset anaphylaxis after influenza vaccination. The patient showed elevated specific IgE levels against whole influenza vaccines, especially with split virion from egg-based manufacturing process. Specific IgE levels to influenza vaccines showed decreased over. We evaluated a causal relationship between influenza vaccine and anaphylaxis event by enzyme-linked immunosorbent assay. Delayed-onset anaphylaxis after influenza vaccination can occur in children without predisposing allergic diseases. In addition, the results suggested that formulation and production system of influenza vaccines could affect the probability of severe allergic reaction to vaccines.
Anaphylaxis ; Child ; Drug Hypersensitivity ; Enzyme-Linked Immunosorbent Assay ; Humans ; Hypersensitivity ; Hypersensitivity, Delayed ; Immunoglobulin E ; Immunoglobulins ; Influenza Vaccines ; Influenza, Human ; Vaccination ; Vaccines ; Virion

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.
Animals ; Autoimmune Diseases/pathology* ; Cell Count ; Epididymis/pathology* ; Epididymitis/pathology* ; Histamine H1 Antagonists/pharmacology* ; Hypersensitivity, Delayed ; Immunity, Cellular/drug effects* ; Ketotifen/pharmacology* ; Male ; Mast Cells/pathology* ; Orchitis/pathology* ; Rats ; Severity of Illness Index ; Spermatic Cord Torsion/pathology* ; Testis/pathology* ; Vaccination

Rituximab is a monoclonal antibody used for the treatment of B-cell malignancies, including diffuse large B-cell lymphoma. Infusion-related hypersensitivity reactions to rituximab is well known, and delayed hypersensitivity reactions to rituximab are also reported. Desensitization is commonly used to prevent immediate hypersensitivity reactions, but recently there have been cases of successful desensitization therapy for delayed hypersensitivity reactions. A 66-year-old patient who underwent rituximab treatment for diffuse large B-cell lymphoma showed repeated rituximab-induced delayed hypersensitivity reactions with whole body rashes. Intravenous rapid desensitization was performed by using a 1-bottle, 11-step protocol for 6 cycles and thereafter hypersensitivity reaction did not recur. We herein reported a case of delayed hypersensitivity reaction caused by rituximab, which was successfully desensitized using our 11-step protocol.
Aged ; B-Lymphocytes ; Desensitization, Immunologic ; Exanthema ; Humans ; Hypersensitivity ; Hypersensitivity, Delayed ; Hypersensitivity, Immediate ; Lymphoma, B-Cell ; Rituximab

Hypersensitivity to cholecalciferol (vitamin D3) or its active metabolite, calcitriol, is an exceedingly rare clinical phenomenon, with only 2 previously reported cases of suspected immediate hypersensitivity. Diagnosis of delayed drug hypersensitivity reactions is inherently difficult due to the lack of any robust in vitro diagnostic assay, particularly in those patients for whom provocation testing confers an unacceptable risk. In these situations, diagnosis relies on reproducible clinical manifestations following administration of the culprit agent, resolution upon its withdrawal and exclusion of other potential differential diagnoses. Based on these criteria, we propose the first reported case of delayed hypersensitivity to cholecalciferol successfully managed with a desensitisation protocol to pure cholecalciferol.
Calcitriol ; Cholecalciferol ; Diagnosis ; Diagnosis, Differential ; Drug Hypersensitivity ; Humans ; Hypersensitivity ; Hypersensitivity, Delayed ; Hypersensitivity, Immediate ; In Vitro Techniques

Fluconazole is a triazole-based first-generation antifungal agent and has excellent effects on candidiasis and cryptococcosis. Hypersensitivity has been reported as a side effect of fluconazole. A 76-year-old female patient used fluconazole for consolidation therapy for cryptococcal meningitis, but showed delayed hypersensitivity with skin rashes and itching sensation of the whole body. For desensitization, was attempted by administering 12-step, 1:1 fluconazole solutions were administered intravenously at sequentially increasing infusion rates. After successful quick desensitization to fluconazole, fluconazole was continuously used as a consolidation therapy for cryptococcal meningitis. We herein report a case of delayed hypersensitivity reaction to fluconazole in consolidation therpy with cryptococcal meningitis who successfully completed desensitization.
Aged ; Candidiasis ; Cryptococcosis ; Exanthema ; Female ; Fluconazole ; Humans ; Hypersensitivity ; Hypersensitivity, Delayed ; Meningitis, Cryptococcal ; Pruritus ; Sensation

Pyrazinamide (PZA) is an anti-tuberculosis drug and an essential component of the standard four-drug regimen for tuberculosis. Here, we report a case of immediate angioedema secondary to PZA administration intended for pulmonary tuberculosis treatment. A previously healthy 48-year-old woman was diagnosed with pulmonary tuberculosis and tuberculous lymphadenitis. Thirty minutes after taking the first dose of isoniazid, rifampicin, pyrazinamide, and ethambutol, the patient developed facial edema, generalized rash, and dizziness. An oral provocation test was performed on the four drugs, and 1,000 mg pyrazinamide showed a positive result characterized by 50 minutes of urticaria, angioedema, and hypotension. As the prevalence of tuberculosis increases, prescriptions for anti-tuberculosis drugs may increase as well. Clinicians should be aware of the possibility of immediate hypersensitivity as well as delayed hypersensitivity to anti-tuberculosis drugs.
Angioedema* ; Dizziness ; Drug Hypersensitivity ; Edema ; Ethambutol ; Exanthema ; Female ; Humans ; Hypersensitivity, Delayed ; Hypersensitivity, Immediate ; Hypotension ; Isoniazid ; Middle Aged ; Prescriptions ; Prevalence ; Pyrazinamide ; Rifampin ; Tuberculosis ; Tuberculosis, Lymph Node ; Tuberculosis, Pulmonary ; Urticaria*

The major apple allergen Mal d 1 cross-reacts with the homologous birch pollen allergen Bet v 1 and causes immunoglobulin E (IgE)-mediated immediate-type allergic reactions. In some patients, delayed-type hypersensitivity to apples may develop within 72 hours without evidence of specific IgE or a positive skin prick test (SPT). The aim of the study was to evaluate the concomitance of delayed-type hypersensitivity reactions and immediate IgE-mediated reactions against high- and low-allergenic apple cultivars in patients with birch pollen allergy. Data were obtained from 45 adults with clinical symptoms of birch pollen allergy. Patients were exposed to apple pulp via atopy patch tests (APTs) and SPTs. Levels of IgE specific to Bet v 1 and Mal d 1 were measured with a radioallergosorbent test. Patients allergic to birch pollen showed the highest rate of positive SPT responses to Golden Delicious apples and the lowest rate to low-allergenic cultivar Grey French Reinette. Among these patients, 9% developed delayed hypersensitivity reactions to either Golden Delicious or Grey French Reinette apples; these reactions manifested clinically as erythema with papules (class ++). Fifty percent of APT-positive patients were concomitantly SPT-negative. Here, we show for the first time the clinical relevance of T cell-driven allergic reactions to apples. APTs may reveal type IV sensitization in patients who are negative for the corresponding type I sensitization tests. Thus, utilization of the APT procedure with fresh apple appears to be a valuable tool for the diagnosis of apple allergy and may improve the accuracy of food allergy diagnoses.
Adult ; Betula* ; Diagnosis ; Erythema ; Food Hypersensitivity ; Humans ; Hypersensitivity* ; Hypersensitivity, Delayed ; Immunoglobulin E ; Immunoglobulins ; Incidence* ; Malus* ; Patch Tests ; Pollen* ; Radioallergosorbent Test ; Rhinitis, Allergic, Seasonal ; Skin

PURPOSE: Cefaclor, a second-generation oral cephalosporin, is known to cause IgE-mediated hypersensitivity. Assays of serum-specific IgE (sIgE) to cefaclor are commercially available via the ImmunoCAP system (Thermo Fisher Scientific). While serum levels of sIgE >0.35 kU/L are considered indicative of an allergy, some patients with cefaclor allergy show low serum IgE levels. This study aimed to evaluate the proper cut-off levels of sIgE in the diagnosis of immediate hypersensitivity to cefaclor. MATERIALS AND METHODS: A total of 269 patients with drug allergy history, who underwent assays of sIgE to cefaclor at Ajou University hospital and Dong-A University Hospital, were reviewed retrospectively. Among them, 193 patients exhibited cefaclor-induced immediate hypersensitivity with certain or probable causality of an adverse drug reaction according to the WHO-UMC (the World Health Organization-the Uppsala Monitoring Centre) algorithm, and 76 controls showed delayed hypersensitivity reactions to non-antibiotics. RESULTS: In total, 126 of the 193 patients (65.3%) experienced anaphylaxis; they had higher serum sIgE levels than patients with immediate hypersensitivity who did not experience anaphylaxis (6.36±12.39 kU/L vs. 4.28±13.61 kU/L, p < 0.001). The best cut-off value for cefaclor-induced immediate hypersensitivity was 0.11 kU/L, with sensitivity of 80.2% and specificity of 81.6%. A cut-off value of 0.44 kU/L showed the best sensitivity (75.4%) and specificity (65.7%) for differentiating anaphylaxis from immediate hypersensitivity reactions. CONCLUSION: Patients with cefaclor anaphylaxis exhibit high serum IgE levels. A cut-off value of 0.11 kU/L of sIgE to cefaclor is proper for identifying patients with cefaclor allergy, and 0.44 kU/L may be useful to detect anaphylaxis.
Anaphylaxis ; Cefaclor* ; Diagnosis ; Drug Hypersensitivity ; Drug-Related Side Effects and Adverse Reactions ; Global Health ; Humans ; Hypersensitivity* ; Hypersensitivity, Delayed ; Hypersensitivity, Immediate ; Immunoglobulin E* ; Retrospective Studies ; Sensitivity and Specificity