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Hereditary angioedema (HAE) is frequently misdiagnosed as drug allergy. It is essential to differentiate HAE from allergy. Diagnosing HAE-normal-C1INH (conventional HAE type III), presenting normal C1-INH, is even more difficult. Here, we report a case of a 17-year-old female diagnosed with HAE and having labeled wheat and multiple drug allergies. She had been suffering from skin edema and abdominal symptoms since childhood. After taking wheat at 13 years old, she had multiple episodes of the same symptoms. Wheat allergy was suspected, and she started eliminating wheat. Multiple attacks were observed after several drug use, and drug allergy was labeled. However, her attacks did not improve after eliminating wheat and the suspected drugs. Her C4 and C1-INH activity was normal, but we diagnosed her with HAE-normal-C1INH based on her family history, multiple attacks after dental procedures, ineffective antihistamines, and significant efficacy of C1-INH infusion. A double-blind, placebo-controlled wheat challenge test at our hospital was negative, and wheat removal was lifted. Drugs could be de-labeled by allergic tests and history. Repeated attacks of unexplained edema and abdominal pain should be differentiated from HAE and lead to an appropriate diagnosis.

Background: Avoidance of suspect drugs based solely on a history of drug allergy is detrimental to disease outcomes. Many antimicrobial allergy labels are not usually true allergy. Some studies have demonstrated that antimicrobial allergy assessments can be safely performed on pregnant women. The purpose of this study was to examine the usefulness of antibiotic allergy assessment during pregnancy in Japan., Methods: We reviewed pregnant women who reported antimicrobial allergies and were referred to the allergy center. Allergists conducted an interview and skin test and selected antibiotics that could be used at delivery., Results: Twenty-four pregnant women were referred to as having antimicrobial allergies. Most of the suspected antimicrobials were cephalosporin (13 cases, 52%) and penicillin (9 cases, 36%). Five women were ruled out only by our interviews. Of the remaining 20 cases, 10 were immediate type, 6 were non-immediate type, and 4 were unknown. All 21 pregnant women who needed antimicrobials were able to use the first-line drugs (β-lactam antimicrobials) at the time of delivery. No surgical site infections or allergic reactions were observed., Conclusion: Pregnant women with antimicrobial allergy labels could be evaluated by antimicrobial allergy assessment during pregnancy, and first-line antimicrobials were safely and properly used at delivery.

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug induced hypersensitivity syndrome (DIHS) are severe cutaneous adverse reactions, which can be life-threatening and lead to severe sequelae. Antiepileptic drugs frequently cause severe adverse reactions in the form of. It is important to understand the characteristics of each disease and attempt at early diagnosis.

Three stages of the pathogenic mechanism of drug allergies can be considered: antigen formation, immune reaction and inflammation/disorder reaction. Drugs are thought to form 4 types of antigens: drug only, polymers, drug-carrier conjugates, and metabolite-carrier complexes. Antigens are recognized by B cell receptors and T cell receptors. Helper T cells (Th) are differentiated into four subsets, namely, Th1, Th2, Th17 and regulatory T cells (Treg). Th1 produces interleukin (IL)-2 and interferon (IFN)-γ, and activates macrophages and cytotoxic T cells (Tc). Macrophages induce type IV allergies, and Tc lead to serious type IV allergies. On the other hand, Th2 produces IL-4, IL-5, and IL-6, etc., and activates B cells. B cells produce IgE antibodies, and the IgE antibody affects mast cells and induces type I allergies. Activated eosinophil leads to the chronic state of type I allergy. Diagnostic testing for allergenic drugs is necessary for patients with drug allergies. Because in vivo diagnostic tests for allergenic drugs are associated with a risk and burden to the patient, in vitro allergy tests are recommended to identify allergenic drugs. In allergy tests performed in vitro, cytological tests are more effective than serological tests, and the leukocyte migration test (LMT) presently has the highest efficacy. An LMT-chamber is better than LMT-agarose in terms of usability and sensitivity, and it can detect about 80% of allergenic drugs.

Multiple drug hypersensitivity (MDH) is an allergy to two or more chemically unrelated drugs. We present a case of MDH caused by antituberculosis agents during the treatment of tuberculous meningitis (TBM). A 64-year-old man without a history of drug allergy developed fever and severe headache. Examination of cerebrospinal fluid showed lymphocytosis, a low glucose level, and a high ADA activity, suggestive of TBM. The patient was treated with isoniazid, rifampicin, pyrazinamide, and ethambutol, and his symptoms resolved quickly. However, 20 days after the initiation of therapy, he developed remittent fever without mucocutaneous lesions. A drug-induced lymphocyte stimulation test was positive for isoniazid, rifampicin, and pyrazinamide, which was consistent with a diagnosis of MDH. All the antituberculosis drugs were replaced with levofloxacin and ethionamide, both of which have excellent cerebrospinal fluid penetration, and the fever subsided. The patient made a full recovery from TBM. Because standard antituberculosis regimens include three or four antituberculosis drugs, it is difficult to determine the culprit drug when hypersensitivity occurs. Moreover, there can be multiple causative drugs as illustrated by the present case. During a time-consuming desensitization therapy, TBM could flare up, leading to permanent neurological damage. Thus, treatment with suitable alternative drugs should be started immediately.

Passive smoking causes a wide range of diseases from membrane irritation such as sore throat or nasal symptom, to fatal diseases such as lung cancer or heart attack. Extensive epidemiological studies have revealed that passive smoking at home or at workplaces raises the all cause mortality of nonsmoking family members by 14-75%. Moreover, many people in Japan are suffered from chemical hypersensitivity due to chronic persistent passive smoking at workplaces. Most critical diagnostic clue of passive smoking caused disease is the temporal relationship of tobacco smoke exposure and disease onset. One hundred percent smoke free workplace or environment is the only effective measure for curing and preventing illnesses caused by passive smoke exposure.

A 43-year-old man developed fever, systemic erythema, and hepatic dysfunction approximately 1 month after initiating treatment with oral allopurinol and anti-TB drugs. The high fever, skin rash, headache, vomiting, and general malaise aggravated even after discontinuation of the anti-TB drugs and allopurinol, and they continued for more than 2 weeks. Hence, the patient was diagnosed with atypical drug-induced hypersensitivity syndrome. Oral prednisolone was introduced at a dosage of 65 mg, and the systemic symptoms rapidly subsided. Drug lymphocyte stimulation test was positive for isoniazid and oxypurinol, a metabolite of allopurinol. The prednisolone dosage was gradually reduced with 3-7 day intervals, and the patient was discharged on day 31 without any recurrence of the symptoms. Although high fever and erythema occurred again upon resumption of isoniazid, the symptoms gradually improved with oral prednisolone. Finally, the patient was diagnosed with atypical drug-induced hypersensitivity syndrome caused by isoniazid.

Oxaliplatin (L-OHP), a platinum-containing antineoplastic agent, is a key drug for the treatment of colorectal cancer. However, it is often difficult to continue with its treatment because of the expression of allergic reactions. This study was an investigation of the expression of allergic reactions resulting from administration of L-OHP. A retrospective analysis was performed on patients undergoing therapeutic regimens including L-OHP, from April 2009 to November 2010 in Juntendo University Urayasu Hospital. The results showed that allergic reactions were expressed in 15 out of 81 patients (18. 5%). A high correlation was found between the time from administration until expression of the allergic reaction, and the number of treatment courses (r=-0. 521, p=0. 047). When patient characteristics were compared between the allergic reaction group and the no-reaction group, it was suggested that differences due to the regimen or the presence or absence of liver metastasis, which is considered to be related to drug metabolism, had no effect. Items showing significant differences were sexual difference(p=0. 022)and the effect of changes depending on the dose form of L-OHP(p=0. 003). It was possible to continue treatment with L-OHP in six patients even after expression of allergic reactions. Anti-allergy measures such as additional administration of steroids or antihistamines were suggested to be useful for continuing treatment.

This article reviews recent progresses on the treatment, prevention and management of drug allergy. Life-threatening drug reactions, also referred to as severe cutaneous adverse reactions (SCARs), include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug-induced hypersensitivity syndrome (DIHS) and anaphylactic type drug reaction. Accurate evaluation of the severity of drug reaction in early period must be critical to minimize the mortality. Japanese SCAR research group advocated the criteria for diagnosis and the guideline for the treatment of SJS and TEN with systemic steroid in early stage. For prevention, studies on the prevalence of the HLA genotype in SCARs due to each medicine are in progress. A financial relief system for patients by PMDA (pharmaceuticals and medical devices agency) is introduced.

Background: Although adverse reactions to local anesthetics are often diagnosed as local anesthetic allergy, there is evidence that most of these reactions occur via non-allergic mechanisms., Methods: To evaluate allergic reactions to local anesthetics, challenge tests were performed in 20 patients who had a history of adverse events to local anesthetics for whom dental treatment was planned. The diagnostic protocol of this challenge test consisted of skin prick and intracutaneous tests, as well as subsequent incremental subcutaneous challenge tests with local anesthetics such as lidocaine., Results: 17 patients (85%) showed no immediate allergic response to lidocaine, which could then be used for dental treatment. Three patients (15%) reacted positively to lidocaine: one had local erythema at the site of the skin prick, and two reacted to subcutaneous challenge., Conclusion: The proportion of immediate-type reactions to local anesthetics is small but not rare in patients suspected of having local anesthetic allergy. This result suggests that the diagnostic approach to confirm allergy to local anesthetics is clinically important and requires further study in a larger population.

We experienced a case of drug-induced hypersensitivity syndrome (DIHS) for salazosulfapyridine (SASP). After we started administration of SASP in a 26-year old man with ulcerative colitis (UC), he had symptoms resembling infectious mononucleosis, high fever, skin eruption, cervical lymphadenopathy, elevate white blood cell count with atypical lymphocyte, and liver dysfunction. We diagnosed the illness as drug-induced hypersensitivity syndrome (DIHS) due to SASP. We halted SASP and started administration of methylprednisolone and prednisolone but his condition deteriorated. We changed to administration of betamethasone and he recovered. In cases of DIHS accompanied by UC, we should administer drugs carefully and recognize serious complications.

There have been several reports on anesthesia for a patient with a history of multiple drug allergies. We present here anesthesia for a 33-year-old woman with histories of multiple drug allergies. She was scheduled to undergo total abdominal hysterectomy. We could not perform preoperative screening of the drugs using a dermal test because of a high risk of anaphylactic shock. Anesthesia was induced and maintained with sevoflurane and nitric oxide. The operation was finished without complications and her postoperative course was uneventful. It is important preoperatively to obtain histories of allergies adequately for recognition of allergens.

A 30-year-old female with paroxysmal supraventricular tachycardia (PSVT) underwent catheter ablation. About 30 minutes later, urticaria and dyspnea occurred suddenly. Blood pressure decreased to 62/41 mmHg, and she fell into the state of anaphylactic shock. She recovered within one hour following treatment. We initially suspected the onset of anaphylaxis was caused by either the local anesthetic or the intravenous antibiotic administered. Following thorough investigation (skin tests and challenge tests), we concluded that the anaphylaxis was not drug induced. Subsequently, we suspected latex allergy. Skin prick test showed a positive reaction to rubber gloves. The specific test for IgE antibody against latex was positive at 10.8 UA/ml. From these results, anaphylactic shock caused by latex (probably medical gloves) was diagnosed. Doctors should take preventive measures against latex allergy not only in operating rooms but also during minor treatments. It is possible that latex allergy is responsible for some cases of anaphylaxis of unknown origin.

Although hypersensitivity reactions to the anticancer drug are rare, since the reactions occasionally are clinical problems enough, that measure is important. The backgrounds (the etiologic mechanisms, the frequency, and etc) differ by each, therefore the knowledge for each medicine is required for measures including prediction and the prevention. This paper reviews the sensitivity reactions of various anticancer drugs (especially, paclitaxel, cisplatin and carboplatin) also including the molecular targeting drugs (trastuzumab, rituximab).

To avoid serious adverse reactions, especially anaphylactic shock, a skin test to detect allergy is recommended prior to the administration of antimicrobial drugs. Japanese pharmaceutical companies provide skin test kits appropriate for each drug, specifying how to administer and interpret the skin test in a package insert for physicians. However, procedures are not consistent between products. We therefore examined package inserts accompanying skin tests for allergies to antimicrobial drugs in use at the Hiroshima University Hospital, including five penicillin, 13 cephalosporin, and four carbapenem preparations. Preparation of test solutions followed five different protocols. Positive responses were defined by four different criteria, and three different intervals between inoculation and reading times were specified. Such differences in procedures between skin test kits appear likely to confuse physicians when using and interpreting the tests. These results suggest that standardization of skin tests would promote more rational and effective use of antimicrobial drugs.

We clinically investigated 19 cases of antituberculous drug-induced allergy. The results of the challenge tests were positive in 30 out of the 55 drugs tested. The results of the lymphocyte stimulation tests were positive in 19 out of the 55 drugs tested. In 84.2% of the cases with positive lymphocyte stimulation test findings, the challenge test was also positive. It can be concluded from these results that the lymphocyte stimulation test may be useful in the detection of the causes of drug induced allergies in patients undergoing drug therapy for tuberculosis.

To elucidate the usefulness in prediction of hypersensitive reactions of L-asparaginase (L-asp), anti-L-asp IgG antibody was measured by two kinds of enzyme-linked immunosolvent assay (ELISA) with improved microplate method and original immunobeads method. The correlation coefficient of both methods matched very well (R = 0.949). Nine out of the 10 patients who were treated with L-asp for the first time showed the elevation of the anti L-asp IgG antibody and returned to normal range within 9 months thereafter. Twenty-two out of 26 patients (84.6%) who had ever developed hypersensitive reactions showed the positive anti-L-asp antibody. There was no positive correlation between the anti-L-asp titer and the severity of the hypersensitive reactions. We concluded that the ELISA with microplate was simple and useful methods to determined the anti-L-asp IgG antibody.

Response of murine lymphnode cells (LNC) sensitized with sulfhydryl drugs to recombinant interleukin 2 (rIL-2) was studied in antigen-specific lymphocyte proliferation test (LPT). Mice were primed with tiopronin (TP) and gold sodium thiomalate (GTM) and the secondary response to LNC was measured in a proliferative assay in vitro. Rapid fluorochromasia assay with propidium iodide (RFP) was used for the quantitative measurement of LPT instead of 3H-thymidine uptake. There was no difference in proliferative response to specific antigen between TP or GTM-primed LNC and control ones. In contrast, a significant proliferation was observed when LNC from sensitized mice were cultured with sensitizing antigen and rIL-2. The strength of response was dependent on the concentration of rIL-2. It was considered that adding rIL-2 to LPT of TP or GTM-sensitized mice enhanced antigen-specific lymphocyte proliferative response and the measurement of IL-2 responsiveness using RFP method might be useful to detect sulfhydryl drug allergy in man.

Commercially available antibiotics for injection are supplied with test ampules. Users are instructed to dissolve them to make 300 micrograms/ml solution for intradermal pretests to avoid allergic reactions. Sometimes this concentration is too low to prevent anaphylactic reactions. In the present study, we tried to find the maximum concentration for the intradermal tests which would have high sensitivity without giving nonspecific, false positive reactions. We investigated intradermal tests with cephalothin (CET) in a patient who suffered from anaphylaxis after drip infusion with CET, although she was judged to be negative to CET by the usual intradermal test prior to the infusion. Her CET skin test was negative at a concentration of 150 micrograms/ml and positive at 300 micrograms/ml 6 weeks after anaphylaxis, but negative at 300 micrograms/ml and positive at 1000 micrograms/ml 4 and 7 years after anaphylaxis. Prick tests were always negative, even with the maximum soluble concentration of CET, 200 mg/ml. Nonspecific reactions to intradermal tests at concentrations as high as 1000 micrograms/ml were examined with 20 kinds of penicillins and cephems in 51 healthy subjects without histories of drug allergies. Very few false positive reactions were observed, except in 5 out of 24 cases with cefotiam. Intradermal tests at 3000 micrograms/ml, however, frequently resulted in nonspecific reactions. We conclude that 1000 micrograms/ml, not 300 micrograms/ml solutions should be used for intradermal tests to prevent allergic reactions to the injection of antibiotics.