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Inhibitory effect of Yunbutang on mast cell-dependent allergic reactions.

Yunbutang (YB) is an Oriental herbal prescription, which has been successfully applied for the treatment of allergic disorders, mainly atopic dermatitis in clinical medicine. However, its effect in experimental models remains unknown. Here, we report inhibitory effects of YB on mast cell-dependent immediate-type allergic reactions. YB inhibited systemic allergic reaction induced by compound 48/80. YB dose-dependently inhibited the histamine release from the mast cells activated by compound 48/80. YB also showed an inhibitory effect of anti-dinitrophenyl IgE antibody-induced passive cutaneous anaphylaxis reaction by oral administration. Furthermore, YB inhibited tumor necrosis factor-alpha secretion from stimulated mast cells. These findings provide evidence that YB inhibits the mast cell-dependent allergic reactions.

Animals↗

Allergic reaction to intranasal midazolam HCl: a case report.

An acute allergic reaction in a 5-year-old healthy male, after receiving midazolam by intranasal atomizer for sedation purposes in the dental clinic, was reported. Shortly after the midazolam was provided, the child developed urticaria in both ankles, which rapidly progressed to the lower extremities, stomach, back, arms, neck, and face. The periorbital skin also became edematous. In the emergency room, the diagnosis of an urticaria allergic reaction was confirmed. The child was treated with intramuscular diphenylhydramine, discharged from the emergency room after 5 hours, and prescribed oral diphenylhydramine (Benadryl) and prednisolone (Orapred). Children who receive sedatives such as midazolam in the dental clinic should be carefully monitored from the moment they receive the sedative, in order to disclose and treat undesirable side effects of the sedative agents as early as possible. The implications of allergic reactions to sedative agents in the dental clinic are reviewed.

Administration, Intranasal↗

IgE binding to unique hazelnut allergens: identification of non pollen-related and heat-stable hazelnut allergens eliciting severe allergic reactions.

BACKGROUND: Usually hazelnut allergic patients suffer from the tree pollen associated oral allergy syndrome (OAS) caused by cross-reactive structures. Anaphylactic reactions elicited by hazelnuts happen rarely but are of high clinical significance. Considering that hazelnuts are ingredients in processed foods, hazelnuts may play an important role as hidden allergens for these high risk patients. Therefore, we analyzed the IgE reactivity of a young woman with severe allergic reactions after ingestion of hazelnuts without any association to tree pollen allergy. AIM OF THE STUDY: The aim of this study was to identify and characterize these potent hazelnut-specific allergens. We compared these allergens to structures displayed by sera from patients with a completely or partially non pollen-related hazelnut allergy and with birch pollen-related hazelnut allergy. None of the sera had a clinical history of anaphylaxis. Special emphasis was placed on the heat stability and cross-reactivity of these allergens. METHODS/RESULTS: Using Western blotting with extract from birch pollen and EAST inhibition techniques we were able to show that the allergens in the serum sample of the young woman were not cross-reactive with birch pollen. Immunoblot experiments with extracts from native and heated hazelnuts and EAST inhibition tests further characterized these allergens to be heat-stable. Unlike the IgE binding pattern of the sera from the patients with pollen-related hazelnut allergy, low molecular weight proteins below 10 kDa were identified by the sera from the patients without pollinosis. CONCLUSIONS: Since the binding pattern of the serum sample of the young woman was different from that of the sera from patients without pollen allergy but less severe symptoms, we assume an association between single non pollen-dependent hazelnut allergens in the low molecular range and severe allergic reactions. These results enable us to approach a subgroup of hazelnut allergens which we believe to be responsible for anaphylactic reactions in hazelnut allergic patients after ingestion of heat-stable hazelnut structures in processed food stuff, independent of pollinosis.

Allergens↗

Artemisia iwayomogi inhibits immediate-type allergic reaction and inflammatory cytokine secretion.

The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. The discovery of drugs for the treatment of immediate-type allergic diseases is a very important subject in human health. In this study, we investigated the effect of Artemisia iwayomogi (AIAE) on mast cell-mediated allergic reaction and inflammatory cytokine secretion. AIAE inhibited compound 48/80-induced systemic reactions in mice. AIAE decreased the passive cutaneous anaphylaxis (PCA) reaction activated by antidinitrophenyl (anti-DNP) IgE antibody. AIAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, AIAE attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 secretion in human mast cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.

Animals↗

[Transfusion-induced severe allergic reaction--report of one case].

Recently, improved cross-matching techniques have reduced the frequency of adverse reactions of blood transfusion less the 2%, but allergic reactions (non-hemolytic) occur in about 3% of patients receiving properly typed and crossmatched blood. Allergic reactions to blood or drugs administered during anesthesia represent an unpredictable and occasionally life-threatening event. When a severe allergic reaction develops, an aggressive and prompt treatment, including intravenous epinephrine, is necessary to minimize morbidity and mortality. We experienced a case of intraoperative shock due to blood transfusion. The case manifested with hypotension, tachycardia, cutaneous rash and bronchospasm during blood transfusion and then the aggressive treatment was given to resume normal vital signs. The rest of anesthesia and surgery as well as the recovery was uneventful and the patient was discharged on the 18th postoperative day.

Adult↗

Langerhans cells are not damaged in contact allergic reactions in humans.

Fifteen biopsies from contact allergic reactions in sensitized patients were taken at different time intervals after application of simple chemicals. Two different procedures for electron microscopy were done. No signs of damage were ever seen in Langerhans cells. The authors are therefore of the opinion that there is still no proof for a target role of Langerhans cells in contact allergic reactions in humans.

Cobalt↗

Incidence of allergic reactions with fresh frozen plasma or cryo-supernatant plasma in the treatment of thrombotic thrombocytopenic purpura.

Plasma replacement for thrombotic thrombocytopenic purpura (TTP) is accomplished with various plasma products. This study sought to determine the incidence of allergic reactions with FFP or CPP as replacement in therapeutic plasma exchange (TPE). Forty-one TTP patients were identified retrospectively who received TPE replacement with either FFP (n=21) or CPP (n=20). Anti-histamine was administered prophylactically following the initial occurrence of an allergic reaction (urticaria, respiratory distress, or anaphylaxis with hypotension). Fifty-one allergic reactions occurred in 65.8% of patients. Urticaria comprised 49 of 51 (96%) of reactions and respiratory distress the remaining 4%. No anaphylaxis occurred. Nineteen urticarial reactions occurred in 50% of CPP recipients compared to 71% of FFP recipients (P=0.28). Anti-histamine breakthrough occurred in 36.3% of patients who experienced a previous allergic reaction with CPP and 37.5% with FFP (P=1.0). The overall risk of allergy per unit of plasma was 1.37% (1.23 % CPP, 1.48% FFP), comparable to estimates in non-TTP recipients. The median number of donor exposures preceding the first allergic reaction was 35 and 32, CPP and FFP, respectively (P=0.63). The mean volume of plasma transfused prior to reaction was 9,883 mL for CPP and 9,348 mL for FFP (P=0.85). Neither product was advantageous in preventing allergic complications. Because of the large volume, the number of donor exposures, and prolonged duration of therapy, allergic reactions to plasma are common (65.8%) in the treatment of TTP.

Blood Preservation↗

Out-of-hospital provider use of epinephrine for allergic reactions: pilot program.

OBJECTIVE: To describe experience with an out-of-hospital provider program for the recognition and field management of allergic reactions by advanced life support (ALS) and basic life support (BLS) providers. METHODS: Data sheets completed between June 1, 1988, and August 31, 1993, and records from receiving sites (physicians' offices or EDs) were reviewed for information regarding the presentation of the allergic reaction, the time course and treatment provided out of hospital, and the clinical outcome at the receiving health care facility. RESULTS: Thirty-seven data sheets were completed during the study period. Fourteen (38%) of the providers were BLS providers. The epinephrine was supplied from the emergency medical services (EMS) provider's personal kit in 35% of the cases, from an EMS vehicle in 57% of the cases, and by the patient in 8% of the cases. Availability of the kits allowed administration of epinephrine prior to the arrival of the first EMS vehicle in 41% of the instances and prior to physician on-line medical command in 65% of all the instances (predominantly by BLS providers). Overall, 77% of the patients experienced alleviation of their symptoms of respiratory difficulty, swelling, or rash after epinephrine administration, while 20% were unchanged and 3% worsened. All patients receiving epinephrine had an ED diagnosis of allergic reaction, and no adverse event was encountered on follow-up of the patients treated. CONCLUSIONS: Severe allergic reactions can be reliably identified and safely managed by out-of-hospital providers, including BLS providers. Providing personal anaphylactic treatment kits and increasing the pool of providers trained to manage allergic reactions (including BLS providers) can often decrease the time to treatment.

Adrenergic Agonists↗

Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based study.

BACKGROUND: Emergency department visits for acute allergic reactions are common. Although the diagnosis and classification of these allergic reactions is primarily empiric, it is not always clear whether certain signs and symptoms constitute systemic mediator release syndromes, such as anaphylaxis, and thus may warrant more aggressive therapy or follow-up. OBJECTIVE: We sought to determine associations between various clinical signs and symptoms with both plasma histamine levels and serum tryptase levels in adult patients presenting to an emergency department with acute allergic syndromes. The clinical correlates of raised beta-tryptase levels were also investigated. METHODS: Ninety-seven adult emergency department patients were prospectively studied by using a questionnaire, physical examination, and serum-plasma sampling. Plasma histamine and serum total and beta-tryptase levels were determined. Clinical groupings were compared for mediator levels by using simple and multivariate analysis. RESULTS: Elevated levels of plasma histamine (>10 nmol/L) and serum total tryptase (>15 ng/mL) were observed in 42 and 20 patients, respectively. Detectable beta-tryptase (>/=1 ng/mL) was observed in 23 patients, including 15 of the patients with elevated total tryptase levels. Suspected food allergy incidences and the duration of reaction were similar in patients with increased histamine levels and in patients with increased tryptase levels. Increased total tryptase levels, histamine levels, or both were observed in some patients who did not have airway, cardiovascular, or abdominal signs. Histamine levels correlated better with clinical signs than tryptase levels. Histamine elevations (>10 nmol/L) were observed more frequently in patients characterized by the following clinical signs in univariate analysis: the presence of urticaria, more extensive erythema, abnormal abdominal findings, and wheezing. Total tryptase increases were observed more frequently only in patients with urticaria. Histamine levels correlated with initial heart rates. In multivariate analysis the extent of urticaria was the best single predictor of plasma histamine levels and of either an elevated histamine or tryptase level. Detectable beta-tryptase levels were observed in some patients who had neither elevated total tryptase nor elevated histamine levels. Unlike patients without detectable beta-tryptase levels, patients who had detectable beta-tryptase levels had a significant correlation between total tryptase and histamine levels (P <.05). CONCLUSIONS: Raised histamine and, less commonly, raised tryptase levels are observed in almost 50% of patients presenting to emergency departments with acute allergic reactions. Some cases associated with systemic mediator release do not have classical features of severe anaphylaxis, such as hypotension or tachycardia. The lack of total tryptase elevations in many patients with elevated plasma histamine levels suggests basophil involvement. The clinical utility of beta-tryptase determinations in the evaluation of acute allergic reactions needs further study.

Adult↗

Pharmacological studies of N-(2-mercapto-2-methylpropanoyl)-L-cysteine (SA96) (3). Effects of SA96 on experimental allergic reactions.

The effects of an antirheumatic agent, N-(2-mercapto-2-methylpropanoyl)-L-cysteine (SA96), were investigated on allergic reactions in rats and guinea pigs. The effects of SA96 were compared with those of D-penicillamine (D-Pc). SA96 given twice orally at the doses of 10 to 50 mg/kg significantly caused inhibitions of 28%, 29% and 44% against passive cutaneous anaphylaxis (PCA), reversed cutaneous anaphylaxis (RCA) and reversed passive Arthus (RPA) reactions, which are classified as Type I, Type II and Type III allergic reactions, respectively. D-Pc also showed inhibitions of 30%, 23% and 18% on Type I, Type II and Type III reactions, respectively, and inhibitions on Type II and Type III reactions were not significant. On the other hand, SA96 (10 to 50 mg/kg twice) had no influence on the Type IV allergic reaction, delayed hypersensitivity, while D-Pc (20 mg/kg twice) showed an enhancement of 27% on the Type IV reaction. In the in vitro study, SA96 inhibited the hemolytic complement activity at 10(-4) to 10(-2) M and the macrophage migration at 1 X 10(-4) to 5 X 10(-3) M in a dose-dependent manner. These in vitro activities of SA96 were more potent than those of D-Pc. These results showed that SA96 had some different immunopharmacological properties on experimental allergic reactions as compared with those of D-Pc.

Anaphylaxis↗

Post-marketing surveillance of immediate allergic reactions: polygeline-based versus polygeline-free pediatric TBE vaccine.

Scattered cases of immediate allergic reactions occurred in the nineties after widespread use of the original (polygeline-based) pediatric tick-borne encephalitis (TBE) vaccine and were reported to Pharmacovigilance, Chiron Vaccines. Although, still indicating a very rare frequency of about two cases per 100,000 doses sold, the benefit/risk assessment resulted in its withdrawal from the market in early 1998. An intensive evaluation revealed that polygeline used as a vaccine stabilizer was the most probable cause of the reported allergic reactions. Consequently, an improved pediatric TBE vaccine, free of polygeline and other protein-derived vaccine stabilizers, was developed. A post-marketing surveillance analysis covering the first two vaccination seasons after the introduction of this new pediatric TBE vaccine in early 2002 reveals a very low reporting rate of immediate allergic reactions post immunization (within the range as noted for other widely used vaccines for childhood immunization), i.e., 0.08-0.24 cases per 100,000 doses sold depending on case definition and medical assessment. In conclusion, this analysis provides post-marketing surveillance evidence that the change in the vaccine formulation, with regards to the potential risk of immediate allergic reactions, has led to an intended improvement in the vaccine's safety profile.

Adverse Drug Reaction Reporting Systems↗

Allergic reactions to cyclophosphamide: delayed clinical expression associated with positive immediate skin tests to drug metabolites in five patients.

BACKGROUND: Cyclophosphamide (CP) is one of the relatively few drugs implicated in systemic allergic reactions for which the metabolites are well known. Formation of CP metabolites is a multistep, time-dependent process (hours) with significant interindividual differences. Although allergic reactions to CP have been recorded in 17 previous reports, skin testing with CP or its metabolites has been included in only five. We now describe five patients receiving monthly cycles of intravenous CP whose allergic reactions included clinical features of type I hypersensitivity but were atypical in their markedly delayed onset (i.e., 8 to 16 hours in patients 1 to 4 and 10 days in patient 5). OBJECTIVE: The objective was to investigate these late-developing clinical reactions by skin testing with CP and two of its major metabolites. METHODS: The five patients and a control group receiving intravenous CP uneventfully were studied by the same skin test protocol. RESULTS: The four individuals in the control group were unreactive to CP or its metabolites. All five patients with late-onset allergic reactions had positive immediate skin test results to CP metabolites but not to CP itself. We propose that the allergic reactions in patients 1 to 4 were mediated, wholly or in major part, by IgE antibodies reactive with allergens derived from time-dependent drug metabolites. The 10-day lag time in patient 5 is unexplained. Immunomodulation by the underlying malignancies or by the immunosuppressive drugs could have contributed. CONCLUSION: IgE-mediated allergic drug reactions may have a delayed onset if the allergen is a time-dependent drug metabolite, illustrated in this study by CP.

Adult↗

Type I allergic reactions of the middle ear and eustachian tube: an experimental study.

To clarify the role of type I allergic reactions in etiology and pathogenesis of otitis media with effusion and to determine whether or not the middle ear is an allergic "shock" organ, we made animal models of nasal allergy in guinea pigs by passive sensitization with serum of homologous animals containing specific IgE antibodies. We also examined the eustachian tube, tympanic cavity (histologically), and tubal function after the induction of type I allergic reactions of the nose. However, the involvement of histologic changes was limited only up to the area near the pharyngeal orifice. The tubal dysfunction evoked by nasal allergic reactions was transient, culminating in no middle ear effusion. Upon direct antigen-challenge into the tympanic cavity, allergic changes were observed in the mucosa lining the tympanic bulla, even though no microscopic effusion was present. Findings of the present study suggest that type I allergic reactions of the nose are not an etiologic factor for otitis media with effusion, although the middle ear is potentially an allergic shock organ.

Animals↗

Severe allergic reactions to guinea pig.

BACKGROUND: Allergic sensitization and reactions to guinea pig (Cavia porcellus) have been well documented in laboratory animal handlers, primarily manifesting as rhinitis, conjunctivitis, and asthma. Severe allergic reactions, however, are rare. METHODS: We report two patients with severe allergic reactions following non-occupational exposure to guinea pigs. The first patient, an 11-year-old female, developed ocular, nasal, skin and laryngeal edema symptoms immediately after handling a guinea pig. The second patient, a 24-year-old female, developed symptoms of isolated laryngeal edema after cleaning a guinea pig cage. Percutaneous skin testing, RAST, ELISA and ELISA inhibition testing with guinea pig extract were performed. RESULTS: Both patients had IgE-mediated allergy to guinea pig confirmed by ELISA and either RAST or skin testing. ELISA inhibition studies confirmed the specificity of the IgE reactivity to guinea pig. CONCLUSION: Severe IgE-mediated reactions can occur following non-occupational guinea pig exposure. Physicians should be aware of this possibility.

Journal Article↗

Anti-allergic effects of Sanguisorba officinalis on animal models of allergic reactions.

We investigated the effect of aqueous extract of Sanguisorba officinalis L.(Rosaceae) root (SOAE) on the immediate-type allergic reactions in vivo and in vitro. SOAE (0.01 to 1 g/kg) inhibited systemic allergic reaction induced by compound 48/80. When SOAE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. SOAE (0.001 to 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE. SOAE (0.001 to 1 mg/mL) also dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP (cAMP) in RPMC, When SOAE was added, significantly increased compared with that of normal control. Moreover, SOAE (0.01 to 1 mg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production. These results suggest that SOAE may be beneficial in the regulation of immediate-type allergic reaction.

Animals↗

Fluorouracil for allergic reactions to capecitabine.

OBJECTIVE: To report the safe use of fluorouracil in a patient with breast cancer who had allergic reactions to capecitabine. CASE SUMMARY: A 42-year-old African American woman with metastatic breast cancer developed progressive disease. Capecitabine 1500 mg taken by mouth twice daily was prescribed as the salvage chemotherapy. She developed a generalized rash and itching, sore throat, and dizziness approximately 4 hours after the first dose of capecitabine. These reactions recurred immediately after the second dose. Capecitabine was discontinued and the allergic reactions resolved after the woman took diphenhydramine for 1 week. In view of limited therapeutic options for her progressive disease, a trial of fluorouracil 300 mg/m(2)/d continuous intravenous infusion over 5 days was initiated without any premedications. She did not experience any reactions. The dose of fluorouracil in the second cycle was increased to 400 mg/m(2)/d continuous infusion over 5 days. DISCUSSION: Capecitabine is not intrinsically cytotoxic, but is converted to fluorouracil in tumor tissues via a 3-step enzymatic pathway. Capecitabine reaches peak blood concentrations in about 1.5 hours, with peak fluorouracil concentrations occurring at 2 hours. The elimination half-life of both drugs is 0.5-0.7 hours. The patient tolerated the rechallenge with fluorouracil without complications. Objective causality assessment revealed that the adverse event was probably drug induced. It was postulated that the allergic reaction was most likely caused by capecitabine or the intermediate metabolites based on the immediate reappearance of symptoms from the rechallenge, pharmacokinetic data, and well-tolerance of fluorouracil. CONCLUSIONS: The use of fluorouracil treatment with careful monitoring can be considered in a patient with mild allergic reactions to capecitabine.

Adult↗

Effect of cetirizine, a new H1 antihistamine, on the early and late allergic reactions in a bronchial provocation test with allergen.

BACKGROUND: Cetirizine is a highly sensitive H1 antihistamine with particular antiallergic properties, which has been shown to be effective in the treatment of allergic rhinitis, urticaria, and hay-fever-associated asthma. METHODS: To assess the effect of cetirizine on the late allergic reaction to a specific bronchial provocation test (BPT) with allergen, we selected 25 patients with allergic asthma as determined by history, skin tests, and specific IgE levels. They were challenged with increasing doses of a cat or mite extract until a 20% drop in forced expiratory volume in 1 second (FEV1) was recorded. Sixteen patients (11 men and 5 women with a mean age of 22 years; range, 18 to 48 years) exhibited a dual response (early and late allergic reactions). These 16 patients underwent a second BPT 2 weeks later, and each again showed a dual response. They were then randomized to receive either a placebo (8 patients) or cetirizine, 15 mg twice daily (8 patients) in a double-blind fashion. After 7 days of treatment, they underwent a third BPT with the same allergen dose as given in the second BPT. RESULTS: The intensity and duration of early allergic reaction were not affected by cetirizine, whereas all parameters of late allergic reaction were statistically significantly improved in the cetirizine group when compared with those of the placebo group (maximum FEV1 decrease, p = 0.046; FEV1 [area above the curve], p = 0.027; maximum airway resistance increase, p = 0.021; airway resistance [area under the curve], p = 0.036). CONCLUSIONS: Cetirizine produced a significant protective effect against an allergen-induced late allergic reaction in a BPT. Cetirizine might therefore be effective in the treatment of asthma.

Adolescent↗