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Background: Most studies investigating steroid allergy have been performed with tixocortol pivalate, hydrocortisone butyrate and budesonide. Betnovate and Dermovate are widely prescribed in the U.K. but little is known about the frequency of sensitization to them., Objectives: To determine the optimum method to detect contact allergy to betamethasone valerate (BV) and clobetasol propionate (CP)., Methods: Seven centres tested consecutive patients attending for investigation of suspected allergic contact dermatitis to these steroids at a range of concentrations in different vehicles., Results: Of 1562 patients tested, 16 (1%) reacted to either BV or CP. Ten patients (0.7%) reacted to BV and 13 (0.8%) to CP. Two patients of a further centre were included in analysis of dilutions and vehicles. Sixteen of a total of 25 reactions (64%) were identified with a 1% dilution in ethanol., Conclusions: Consideration should be given to adding BV and CP to a standard allergy series, given that both are frequently used in the treatment of eczema and that most patients sensitized to them are not identified with currently used markers of steroid allergy. If patch tests to BV and CP are initially negative, but an allergy is suspected, the patient should be further investigated. Further studies are required to identify the ideal patch test material.

Physicians often must select antibiotics for patients who are reported to have an antibiotic allergy. For penicillins, the sensitivity of penicillin skin testing for predicting serious allergic reactions is excellent. For other beta-lactam antibiotics, penicillin skin testing is useful for excluding the possibility of sensitivity to the beta-lactam ring. For other antibiotics, the patient history remains the most useful tool for determining whether a serious reaction is likely to occur with further drug exposure. The cross-reactivity between penicillins and second- or third-generation cephalosporins (excluding cefamandole) is probably no higher than is the cross-reactivity between penicillins and other classes of antibiotics. When a patient has a suspected immunoglobulin E-mediated antibiotic allergy, desensitization therapy should be considered, if the efficacy of alternate antibiotics is in doubt. For the treatment of serious infections, it is usually possible to safely administer the antibiotic of choice despite a history of possible antibiotic allergy.

Infliximab, a chimeric human/murine monoclonal antibody directed against the proinflammatory cytokine tumor necrosis factor alpha, is an effective therapy for Crohn's disease (CD) and rheumatoid arthritis refractory to standard medical treatment. We report a case of adult respiratory distress syndrome associated with infliximab therapy. A 33-year-old white male presented with an exacerbation of CD and was treated with his second infliximab infusion (15 months following the first infusion). Within 7 days he developed arthralgias, myalgias, and fever, followed by respiratory failure. He required intubation and mechanical ventilation. Open lung biopsy demonstrated eosinophilic pneumonia. Human antichimeric antibodies were present at high concentrations. An extensive investigation for infectious etiologies was negative. The patient was treated with intravenous corticosteroids, and fully recovered after a prolonged hospitalization. We review the infectious and immunologic complications of infliximab.

A hypersensitivity reaction occurs in association with initiation of abacavir therapy as part of combination antiretroviral therapy in approximately 3.7% of patients. The reaction is possibly the result of a combination of altered drug metabolism and immune dysfunction, which is poorly understood. White patients appear to be at higher risk and patients of African descent at lower risk of abacavir hypersensitivity. Clinical management involves supportive measures and discontinuation of abacavir therapy. Rechallenge with abacavir in a hypersensitive patient should be avoided because it might precipitate a life-threatening reaction.

Omeprazole is a potent proton pump inhibitor and usually is well tolerated. Adverse effects of this drug have been reported in up to 5% of patients, most of which are trivial and disappear rapidly on discontinuation of the drug. Skin adverse reactions attributed to omeprazole are uncommon and include rashes, urticaria, angio-oedema, acute disseminated epidermal necrolysis, lichen spinulosus, and contact dermatitis. Cutaneous leucocytoclastic vasculitis (CLV) has not been previously reported in association with omeprazole. The development of CLV in an elderly patient four weeks after starting treatment with omeprazole is described.

Recently, it has been proposed that viral infection is involved in the pathogenesis of hypersensitivity syndrome. Cytomegalovirus (CMV), one of the aetiological agents of infectious mononucleosis, has never been reported as an organism associated with hypersensitivity syndrome. We describe a 64-year-old man with severe phenytoin-induced hypersensitivity syndrome associated with CMV infection. Twenty-five days after the patient was started on phenytoin, he developed high fever and a generalized erythematous rash followed by jaundice, renal failure and disseminated intravascular coagulopathy (DIC). CMV-specific IgG antibodies were significantly increased 7 weeks after the onset of clinical symptoms and the increase was associated with the appearance of CMV-specific IgM. CMV DNA was detected in the serum of the patient. Coinfection with other viruses, such as Epstein-Barr virus and human herpesviruses 6 and 7, could be excluded because antibody titres to those viruses did not increase during the clinical course of his illness. We suggest that reactivation of CMV may contribute, at least in some cases, to the development of hypersensitivity syndrome.

The purpose of this retrospective study was to assess cross-hypersensitivity between imipenem/cilastatin and penicillin in patients with reported penicillin allergies. Medical records of febrile neutropenic, penicillin-allergic bone marrow transplant recipients who received imipenem/cilastatin treatment were retrospectively reviewed. The findings of this study indicate the incidence of cross-reactivity between imipenem/cilastatin and penicillin among patients with a history of penicillin allergy may be lower than previously reported.

The toxic effects of paracetamol in overdose quantities are well recognised but the occurrence of anaphylactoid reactions to paracetamol is infrequently identified by consumers and health care professionals. Nevertheless adverse reactions to this drug, even in therapeutic doses, can have fatal or near fatal consequences. A case of an anaphylactoid reaction to paracetamol is described.

Twenty-five patients with mucous membrane pemphigoid (MMP), whose oral lesions were unresponsive to topical steroid treatment, were treated with 1 g daily of sulphamethoxypyridazine (SMXP), a long-acting sulphonamide antibiotic, in an open prospective clinical trial. Lesion severity was assessed objectively in a semiquantitative fashion before treatment and after 14 weeks of treatment. The patient's subjective assessment of the associated pain or discomfort, using a visual analogue scale, was also recorded at these times. Three patients (12%) were withdrawn from the study owing to side-effects or complications, one due to an allergic reaction, the other two because of significant haemolysis. For the remainder there was a significant improvement in the mean objective clinical scores for desquamative gingivitis, other oral lesions, conjunctival inflammation, nasal, vulvovaginal and skin involvement, after 14 weeks treatment with SMXP (all P < 0.001, except skin P < 0. 01). Only conjunctival scarring showed no improvement. In addition, there was a significant improvement (P < 0.001) in the pain scores for the mouth, eyes, nose, vulvovaginal region and skin. The results indicate that with appropriate monitoring SMXP is an effective treatment for MMP and compares favourably with other systemic agents used in the management of this condition.

The cost-effectiveness of different approaches to antimicrobial prophylaxis for cardiovascular surgery patients labeled penicillin allergic was studied. A decision-analytic model was used to examine the cost-effectiveness of six strategies for antimicrobial prophylaxis in cardiovascular surgery patients at a tertiary care hospital. The strategies consisted of (1) giving vancomycin to all patients labeled penicillin allergic, (2) giving cefazolin to all patients labeled penicillin allergic, (3) giving vancomycin to all patients with a history suggesting an immunoglobulin E (IgE)-mediated reaction to penicillin and cefazolin to patients without such a history, (4) administering a penicillin skin test to patients with a history suggesting an IgE-mediated reaction to penicillin and giving vancomycin to patients with positive results and cefazolin to all others, (5) skin testing all patients labeled penicillin allergic and giving vancomycin to those with positive results and cefazolin to those with negative results, regardless of history, and (6) skin testing all patients and giving vancomycin to those with positive results or a history suggesting an IgE-mediated reaction to penicillin and cefazolin to all others. Giving cefazolin to all patients labeled penicillin allergic was the least expensive strategy but was associated with the highest rate of both anaphylactic and non-life-threatening serious reactions. Selective use of vancomycin in patients with a history suggesting an IgE-mediated reaction to penicillin was associated with an added cost and a slightly lower rate of anaphylaxis. Although skin-testing strategies may decrease both non-life-threatening and anaphylactic reactions, the incremental cost was high. When vancomycin was given to all patients labeled penicillin allergic, the incremental cost was very high. A decision-analytic model indicated that selective use of vancomycin is more cost-effective than indiscriminate use of vancomycin for surgical prophylaxis in cardiovascular surgery patients labeled penicillin allergic.

The phenytoin (hydantoin) hypersensitivity syndrome is rare but potentially fatal. Often, as in this case, it presents with non-specific symptoms and signs, requiring a high degree of clinical suspicion for diagnosis.

Background: Remarkable overlap exists in symptoms between asthma and chronic obstructive pulmonary disease (COPD), and the symptoms of the patients with mild asthma are often falsely thought to be caused by smoking. The objective of the study was to determine the prevalence of doctor-diagnosed asthma, asthmatic symptoms and doctor-diagnosed COPD in an adult population. The prevalence and relation to asthma of aspirin intolerance, nasal polyposis, allergic rhinitis and smoking habits were also examined., Methods: Postal questionnaire survey of a population-based random sample (4300) of adult women and men aged 18-65 years served by the Päijät-Häme Central Hospital in southern Finland (a region with 208 000 inhabitants) was performed., Results: The non-response-adjusted prevalence (Drane's linear method) of doctor-diagnosed asthma was 4.4% (95% CI: 3.3-5.5%) and of COPD 3.7% (95% CI: 2.7-4.8%). The prevalence of allergic rhinitis was 37.3% (95% CI: 33.3-41.2%), and of overall aspirin intolerance 5.7% (95% CI: 4.4-7.1%). The observed prevalence of aspirin intolerance causing shortness of breath or attacks of asthma was 1.2% and it was higher in patients with doctor-diagnosed asthma than without (8.8% versus 0.8%, relative risk [RR] = 11.4, P < 0.0001), and higher in those with allergic-like rhinitis than without (2.6% versus 0.3%, RR = 7.7, P < 0.0001). The prevalence of nasal polyposis was 4.3% (95% CI : 2.8-5.8%)., Conclusions: The current prevalence of doctor-diagnosed asthma among adults is 4.4%, and allergic rhinitis, nasal polyposis and aspirin intolerance are associated with an increased risk of asthma. There is also association between aspirin-induced asthma and allergic-like rhinitis.

Allopurinol is a xanthine oxidase inhibitor widely used to control plasma uric acid levels. Episodes of hypersensitivity to the drug are not rare. A severe form of this with a generalized exanthem, fever and liver involvement has been termed the allopurinol hypersensitivity syndrome (AHS). Patch testing and lymphocyte stimulation testing (LST) are not helpful in confirming this sensitivity. Allopurinol works as a substrate of xanthine oxidase, and is rapidly oxidized into oxypurinol in vivo. Therefore, the biological half-life of oxypurinol is markedly longer than that of allopurinol. In addition, conspicuous pre-existing renal impairment has been noted in many AHS patients. Thus, it is possible that AHS is a manifestation of hypersensitivity to oxy-, not allopurinol. Here, we now report three cases of AHS in which there were significant lymphoproliferative reactions to oxypurinol but not allopurinol.

Viral infections are thought to play a part in some cutaneous drug reactions. Human herpesvirus 6 (HHV6), which is the agent of exanthema subitum (sixth disease), has never been implicated in a drug reaction. We report a patient with severe phenobarbital-induced anticonvulsant hypersensitivity syndrome in whom a fulminant haemophagocytic syndrome was associated with HHV6 infection. We discuss the possible role of HHV6 in this reactive condition.

Design of Study: Two groups of patients undergoing long-term dialysis were studied in order to evaluate the importance of ethylene oxide (EtO) in causing allergic reactions during dialysis. The first group of 50 subjects had never shown any hypersensitivity reactions related to dialysis, whereas the second group of 20 subjects had previously complained of reactions. All the patients underwent a prick test with a standard kit of aeroallergens in order to assess the presence of atopy (in doubtful cases a RAST test was carried out with the same aeroallergens). A blood sample for the investigation of EtO specific IgE antibodies was taken from all the patients; the immunoenzymatic method was used., Results: Sensitivity to EtO is significantly higher in the group of patients with previous allergic reactions during dialysis (55 vs 6% in the control group).

We report a patient who developed an acute symmetrical polyarthropathy, orbital myositis and posterior scleritis following inoculation with the 1993 Fluvirin (inactivated influenza vaccine: surface antigen) vaccine. We believe that this represents a hypersensitivity reaction to the vaccine as extensive investigations revealed no underlying infective, inflammatory or systemic cause. We review the current indications for vaccination against the influenza virus and the known adverse reactions to the vaccine.

The Jarisch-Herxheimer reaction (JHR) observed after antibiotic treatment of relapsing fever caused by Borrelia recurrentis is associated with the systemic appearance of cytokines. The decrease of cytokine production and block of JHR was attempted by administering pentoxifylline prior to antibiotic treatment. Fifteen patients with confirmed relapsing fever were infused intravenously with pentoxifylline 90 min before intramuscular injection of penicillin; 4 patients were not treated with pentoxifylline. All patients developed JHR to varying degrees. Treatment with pentoxifylline failed to prevent fever, increase in pulse, respiration, or blood pressure, or decrease in white blood cell count. No reduction of circulating levels of tumor necrosis factor, interleukin 6, or interleukin-8 was observed with pentoxifylline treatment. Pentoxifylline did not prevent clearance of the B. recurrentis spirochetes. Thus, pentoxifylline treatment of patients with relapsing fever fails to prevent or diminish JHR or the associated cytokine release observed after appropriate antibiotic treatment.

Medication misadventures resulting in visits to the emergency department of a health maintenance organization (HMO) were studied. The records of patients who visited the emergency department at a California HMO between August 1992 and August 1993 were evaluated for evidence of medication misadventures brought to the department. The definition of misadventure included noncompliance and inappropriate prescribing but excluded intentional overdoses and substance abuse. If it seemed probable that a misadventure occurred, a pharmacist interviewed the patient by telephone. During the 12-month study, 1,074 (1.7%) of 62,216 visits to the emergency department were due to medication misadventures. The patients who had had a misadventure were predominantly female (62%); 38% were 15-44 years of age and 33% were 65 or older. Interviews were possible with 962 patients. Only 30.6% of the patients had a good understanding of the potential adverse effects of their regimen, and only 29.0% had a good understanding of the potential interactions. Misadventures were most often due to allergies or medication underuse among patients < or = 14 years of age and to adverse effects and inappropriate dosage in elderly patients. Of the 1,074 misadventures, 152 (14.1%) resulted in hospital admission. Three areas of particular concern were identified (1) noncompliance with respiratory agents in the young, (2) nonsteroidal anti-inflammatory use leading to hospital admission, and (3) the frequency of problems in the elderly. Medication misadventures accounted for 1.7% of emergency department visits and 1.0% of hospital admissions at an HMO medical center.

Although fulminating non-cardiogenic pulmonary edema following cardiopulmonary bypass is not a new phenomenon, the exact cause and pathogenesis are still unknown. The causative agent of this potentially lethal syndrome was hypothesized to be either protamine or blood products. There was no evidence that an antibody-mediated reaction plays a role and patients were reported to have negative skin tests. We report, for the first time, a patient who presented with fulminating non-cardiogenic pulmonary edema after repeated protamine administration with a subsequent positive skin test to protamine. Specific IgG antibodies to protamine were also found; however, the level was in the range of that of exposed non-reacting controls. IgE antibodies could not be detected.

Azathioprine is used in a variety of dermatological conditions. However, because of its side-effect profile, azathioprine is limited for use in patients with severe disease. An unpredictable, rare and potentially fatal side-effect of azathioprine is the development of a hypersensitivity reaction, often consisting of fever, hypotension and oliguria. We describe a 17-year-old patient with leucocytoclastic vasculitis who was placed on azathioprine; within 15 days of start of therapy, she developed a fever. Azathioprine was discontinued and an evaluation for sepsis was undertaken; all cultures were negative and the fever abated. Azathioprine was restarted 5 days later. After a single dose, fever, nausea and vomiting, diarrhoea, hypotension, tachycardia and oliguria developed and the patient was admitted to an intensive care unit. Azathioprine was discontinued and investigations revealed no sign of an infection. All the above signs and symptoms abated within 24 h and the patient was discharged from hospital in 7 days. A review of 28 case reports in the literature of azathioprine-induced hypersensitivity reactions suggest that most commonly a fever and gastrointestinal symptoms occurred on initial presentation. In addition, a maculopapular rash, urticaria, vasculitis, erythema multiforme or erythema nodosum may occur. Hepatotoxicity and nephritis have also been reported. The aetiology of the reaction is unknown but sudden onset of fever and hypotension suggests that this reaction may be due to cytokine or mediator release induced by azathioprine. As azathioprine is metabolized to 6-MP, rechallenges to both should be avoided in patients who experienced an azathioprine hypersensitivity-like reaction.

Background: Treatment with the immune system modulator interleukin 2 (IL-2) can result in a number of immunologic abnormalities ranging from suppression of delayed-type hypersensitivity responses and neutrophil activity to autoimmune thyroiditis and hypersensitivity reactions against iodine-containing radiographic contrast media. There are a number of published reports of chemoimmunotherapy using IL-2 in combination with various chemotherapeutic agents to treat patients with certain cancers, but none have described hypersensitivity responses to the chemotherapeutic agents given., Purpose: In the early stages of an ongoing clinical trial of the efficacy of combination chemoimmunotherapy for the treatment of patients with metastatic melanoma, we discovered that a number of the patients experienced unexpected hypersensitivity reactions after receiving chemotherapy. We therefore decided to examine these hypersensitivity reactions in detail., Methods: During the period of March 1993 through February 1994, 31 patients with metastatic melanoma were treated either by chemotherapy (dacarbazine, cisplatin, and tamoxifen) or by chemoimmunotherapy (the same drug regimen plus interferon alfa and high-dose IL-2). Twelve patients were treated in a non-randomized pilot study, with six receiving chemotherapy and six receiving chemoimmunotherapy. The six patients who received chemotherapy also received carmustine (BCNU). Nineteen subsequent patients were treated in a prospective, randomized study to compare the two therapeutic approaches. In total, 15 of the 31 patients were treated by chemotherapy alone, and 16 were treated by combination chemoimmunotherapy. Overall, the patients in the two groups were balanced in terms of age, sex, and stage of disease., Results: Ten of 16 chemoimmunotherapy patients exhibited type I hypersensitivity reactions during chemotherapy administration, ranging from pruritus, erythema, and edema to hypotension with hemodynamic instability that required pressor therapy. None of the 15 patients on the chemotherapy regimen exhibited hypersensitivity reactions. All patients in the chemoimmunotherapy group gained weight and had elevated white blood cell and eosinophil counts during chemotherapy; these effects were more prominent in those with hypersensitivity reactions., Conclusions: Hypersensitivity reactions occurred within several hours after chemotherapy administration in patients who had previously received one to two cycles of high-dose IL-2, suggesting that prior IL-2 therapy sensitized patients to cisplatin or dacarbazine. This is the first report of IL-2-induced hypersensitivity to chemotherapy agents.

Hypersensitivity to zidovudine is an uncommon complication of antiretroviral therapy. Manifestations range from isolated fever to anaphylaxis. Fever and rash are the most common features. Diagnosis is made by rechallenge, although some patients have antibodies to zidovudine. Treatment is supportive, and symptoms resolve on withdrawal of the medication.

Local reactions have been frequently reported following repeated injections of human menopausal gonadotrophins (HMG) for the treatment of infertility. Also immunoglobulin (Ig) E-mediated systemic reactions have sporadically been observed. Since most HMG preparations contain significant amounts of non-hormonal urine-derived proteins, it was suggested that these contaminating proteins are responsible for the various allergic reactions. In order to verify this hypothesis, different human follicle stimulating hormone (HFSH) and HMG preparations (Metrodin and Pergonal from Ares-Serono, and Humegon from Organon), were compared with a highly purified preparation (Metrodin HP from Ares-Serono) for the frequency and severity of allergic reactions induced in laboratory animals. The occurrence of anaphylactic shock or related symptoms was studied in sensitized guinea-pigs. The production of specific IgE was evaluated in serum from mice sensitized with the test drugs by the induction of passive cutaneous anaphylaxis in rats. In both models, two different schedules of sensitization were used. Severe allergic reactions were found in 20 of 7% of the guinea-pigs receiving highly purified FSH (Metrodin HP) in the two schedules, respectively, compared to 90 and 88% with the other preparations. Similarly significantly lower IgE titres were induced by highly purified FSH in respect to the other preparations. It can be concluded that the elimination of contaminating proteins significantly reduces the allergenicity of urine-derived HFSH preparations.

Antibodies to streptokinase (SK) are widespread in the population, but reports of their effect on the action of SK are conflicting. Specific anti-SK IgG was purified from the sera of 10 patients, five with low titres of anti-SK IgG and five with high titres. The effect of increasing specific anti-SK IgG antibodies on the action of SK was evaluated in vitro using a fluorimetric assay for plasmin and by a fibrin plate lysis assay. The inhibition of SK by whole plasma from a further group of patients was also assessed by the fibrin plate assay. There was a positive correlation between the serum antibody concentration and the quantity of specific anti-SK eluted (r = 0.797; P < 0.005). The addition of specific anti-SK IgG caused a dose-related decrease in SK activity (fluorimetric assay r = -0.93; P = 0.02; fibrin plate assay r = -0.98; P < 0.001). The addition of patient plasma to the fibrin plate assay also resulted in decreased lysis, which was dependent upon antibody titre (r = -0.95; P < 0.0001). Significant in vitro reduction of the activity of SK by specific antibody was demonstrated, and this was similar with plasma containing comparable amounts of antibody. The findings suggest that treatment with SK would be unlikely to induce an effective thrombolytic state when antibody titres are high (such as those seen within 2 years of an initial dose of SK).