Hypersensitivity reactions to excipients contained in drugs are rare but can be severe or confusing. With regard to generic versus brand drug, often the ingredients are different; for each DHR, we recommend that the physician exercises caution in considering which brand drug or generic was administered and in listing all medicine components and not only the active drug.
Drug skin tests can reproduce delayed hypersensitivity to drugs and entail a moderate reexposure of patients to offending drugs. Drug patch tests (DPTs) and prick tests can be done with any commercialized form of a drug. In non-severe delayed non-IgE-mediated reactions to drugs, intradermal tests (IDT) with delayed readings have a greater value, but their techniques lack standardization. A negative drug skin test does not exclude the responsibility of a drug, and the drug must be rechallenged in non-severe cases. DPTs are useful in maculopapular rashes, flexural exanthemas, and if done in situ, also in fixed drug eruption. Their best indication is in acute generalized exanthematous pustulosis or drug reaction with eosinophilia and systemic symptoms (DRESS). They should be carried out cautiously, following strict guidelines. Prick tests have a low value but they can sometimes be positive on delayed readings. In non-severe delayed reactions to drugs, intradermal tests with delayed readings are the most sensitive skin tests especially for beta-lactam antibiotics, radiocontrast media, heparins but also some biological agents. The value of patch testing varies according to the implicated drug and the non-immediate adverse drug reaction. In DRESS, DPTs have a good value in testing carbamazepine or proton pump inhibitors but remain negative in testing with allopurinol or salazopyrin. In toxic epidermal necrolysis, DPTs are safe but positive in only 9 to 23 % of the reported cases.
This study has two purposes:--to know whether the European standard series is still the key reference when it comes to contact dermatitis, i.e., are its components still the most frequently involved allergens in contact dermatitis nowadays?--to assess the results of the European standard series among French and Belgian dermatologists/allergists as, so far, most of them have failed to provide statistical data within the European community of allergists/dermatologists. 18 participants from 2 dermatology and allergy centres in Belgium and 11 centres in France collected their results from 3,073 patients tested in 2011. They assessed the relevance of some tests as well as that of the standard series and additional series to establish an etiological diagnosis of contact dermatitis. These results, together with the history of the European standard series, have shown that some allergens are obsolete and that others should be included in a new standard series for which we are making a few suggestions.
Drug patch tests (DPTs) with medicaments suspected of causing an allergic reaction represent a method of diagnostic testing that is low risk; DPTs can reproduce delayed hypersensitivity to drugs, and entail only a moderate re-exposure of patients to potential offending drugs. We assessed the non-irritating concentrations of DPTs and determined the amounts of active ingredient (AI) contained in the drugs used in the tests.
The preservative methylisothiazolinone (MI) is used in combination with methylchloroisothiazolinone (MCI), but the MCI/MI mixture has been identified as highly allergenic. MI is considered to be less allergenic, and since the mid-2000s has been widely used alone, but is now clearly identified as a contact allergen. The French Vigilance Network for Dermatology and Allergy of the Study and Research Group on Contact Dermatitis (REVIDAL-GERDA) added MI to its baseline patch testing series in 2010.
Some patients with drug reaction with eosinophilia and systemic symptoms (DRESS) are probably admitted in intensive care unit (ICU), but data concerning their clinical features at admission are scarce. Therefore, in the present study, we used a clinical network of French intensivists to study the clinical features and evolution of DRESS patients hospitalized in ICU. A national, retrospective, multicenter study collected DRESS cases hospitalized in ICU for DRESS from 2000 to end of 2011. All files were analyzed through the RegiSCAR scoring system as "no," "possible," "probable," or "definite" DRESS. Patients were included only if they had a probable or definite DRESS. Demographic, hemodynamic, biological, and infectious data were recorded. Twenty-one patients were included. Hospital mortality was 10 (47%) of 21, and 16 of 21 patients had on admission a shock state necessitating vasopressor agents. Echocardiographic ejection fraction in shock patients was depressed (47% ± 13%). Mechanical ventilation was required in 13 of 21 cases. Hepatic failure was observed in 11 of 21 cases, acute renal failure in 18 of 20 cases, and lactic acidosis in 12 of 20 patients. Initial bacteriology was negative in all patients. Human herpesvirus reactivations were found in five of 15 cases. In conclusion, shock without bacteriological documentation associated with multiple organ failure is the most common presentation of DRESS at admission in ICU and is associated with a higher mortality than previously described.
Nicorandil, a nicotinamide ester, was first reported to be involved in the induction of oral ulcers in 1997. Since then, many reports of single or multiple nicorandil-induced ulcerations (NIUs) have been reported. We hypothesised that in the case of high-dosage nicorandil or after an increased dosage of nicorandil, nicotinic acid and nicotinamide (two main metabolites of nicorandil) cannot appropriately merge into the endogenous pool of nicotinamide adenine dinucleotide/phosphate, which leads to abnormal distribution of these metabolites in the body. In recent or maintained trauma, nicotinamide increases blood flow at the edge of the raw area, inducing epithelial proliferation, while nicotinic acid ulcerates this epithelial formation, ultimately flooding the entire scar. We demonstrate, by comparison to a control patient non-exposed to nicorandil, an abnormal amount of nicotinic acid (×38) and nicotinamide (×11) in the ulcerated area in a patient with NIUs. All practitioners, especially geriatricians, dermatologists and surgeons, must be aware of these serious and insidious side effects of nicorandil. It is critical to rapidly reassess the risk-benefit ratio of this drug for any patient, and not only for those with diverticular diseases.
Allergic reactions to vaccines can be classified as sensitivity to one of the vaccine components, pseudo-allergic reactions, often after hyperimmunization, and exacerbation of atopic symptoms or vasculitis. Pseudo-allergic reactions, some possibly due to hyperimmunization, are probably more common than true allergies. Atopic reactions should not be confused with the "flash" phenomenon, defined as an exacerbation of an allergic reaction due to a reduction in the allergic reactivity threshold following the vaccine injection. BCGitis occurs frequently, and for this reason, guidelines for Bacillus Calmette-Guérin (BCG) have been modified. The vaccine is now reserved for people at risk of exposure to Mycobacterium tuberculosis. This review provides an update on the vaccination modalities for people allergic to eggs, on the assessment that should be performed when a reaction occurs due to tetanus vaccination, on the urticaria after hepatitis vaccination, on an aluminum granuloma, which is more and more frequent in young children, and vasculitis after flu vaccination and BCGitis. The side effects associated with new, recently released vaccines, such as anti-influenza A H1N1 or anti-human papilloma virus (HPV) will also be presented.
Reactivations of human herpesviruses (HHVs) contribute to the development of drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of HHV reactivation is conventionally based on quantitative real-time polymerase chain reaction (PCR) analysis of blood samples, but these viruses are present in the oropharynx and are shed in saliva.
Biological agents induce cutaneous adverse drug reactions (CADR) different from those observed with xenobiotics. Type alpha is the cytokine release syndrome, type beta are hypersensitivity reactions and type gamma is a cytokine imbalance syndrome. Infusion-reactions, anaphylactoid reactions occur with various biological agents administered intravenously. In non-severe cases the infusion rate has to be reduced, in severe reactions, the treatment must be stopped and resuscitation carried out with corticosteroids and epinephrine. Reactions may be due to an alpha syndrome but a true allergy could be involved as demonstrated in some patients with IgE antibodies to the galactose-alpha-1,3-galactose portion of the cetuximab or anti infliximab-IgE. Some desensitisation protocols have been published. Non allergic itching and eczema-like lesions are frequent with epidermal growth factor receptor inhibitors. Rash or desquamation was observed in 40% of cases with antiangiogenic agents, 90% of patients treated with imatinib have rashes, oedema or pruritus and a non-allergic periorbital oedema. Severe CADR, such as Stevens-Johnson syndrome, can be provoked. Delayed readings of intradermal tests could be of value in managing patients with a maculopapular rash due to interferon. Anaphylaxis attributed to omalizumab seems to be rare (0.2%) and skin rashes occur in 7% of cases. Anaphylactoid reactions occur in 1% of patients treated with natalizumab. In the case of anti-natalizumab antibody-mediated reactions, treatment should be stopped. These allergic-like side effects of new biological agents must be known and reported to Pharmacovigilance agency networks.
Fluindione is an oral vitamin K antagonist (indanedione derivative) exclusively marketed in France and Luxembourg, known to have immuno-allergic adverse effects such as hepatitis, fever or interstitial nephritis. A few cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with fluindione. The aim of the present study was to investigate fluindione-induced DRESS cases reported in France and to describe their characteristics.
Fixed drug eruption (FDE) is one of the most typical cutaneous drug adverse reactions. This localized drug-induced reaction is characterized by its relapse at the same sites. Few large series of FDE are reported. The aim of this study was to retrospectively collect and analyse well informed cases observed in a hospital setting. This study involved 17 academic clinical centers. A French nation-wide retrospective multicentric study was carried out on a 3-year-period from 2005 to 2007 by collecting data in seventeen departments of dermatology in France. Diagnosis of FDE was based essentially on clinical findings, at times confirmed by pathological data and patch-testing. Records were reviewed for demographics, causative drugs, localization, severity, and patch-tests, when available. Fifty nine cases were analysed. Patients were 59-years-old on average, with a female predilection. The most common drug was paracetamol, followed by the non-steroidal anti inflammatory drugs. The time between drug intake and skin symptoms was, on average, two days. Beside these classical characteristics, some original findings were found including, a frequent non pigmentation course and a sex-dependent pattern of distribution. Women often had lesions on the hands and feet, and men on the genitalia. Given the fact that skin pigmentation is an inconstant feature of FDE, its French name (erythème pigmenté fixe) should be reconsidered. The sex-dependent distribution could help our understanding of the pathophysiology of fixed drug eruption.
Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma?
Amoxicillin is known to induce exanthema in patients with EBV-induced infectious mononucleosis. It is widely recognized that the reactivation of herpesviruses, including HHV-6 (Human Herpesvirus 6) and EBV (Epstein Barr virus) is associated with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms). We report 7 cases of amoxicillin-induced flare in patients with DRESS induced by other drugs and investigate whether amoxicillin may have a direct effect on HHV-6 replication in vitro. 7 cases of DRESS with amoxicillin-induced flare were retrospectively analysed. The influence of amoxicillin on HHV-6 HST strain replication was studied in vitro in a human T lymphoblastoid MT4 cell line. The viral replication was quantified by immunofluorescence assay and by real-time polymerase chain reaction (PCR). Comparisons were performed using the Students t test. Amoxicillin-induced flare was observed in 7 patients with DRESS induced by other drugs. In two cases HHV-6 reactivation was studied and was demonstrated by PCR. Amoxicillin neither modified cell viability nor cell proliferation for the range of tested concentrations. Amoxicillin increased the replication of HHV-6 at 25 microg*mL-1 and 50 microg*mL-1. Amoxicillin may induce a flare of DRESS, possibly by acting directly on herpesvirus replication.
Drug skin tests (eg, patch tests, prick tests with delayed readings, intradermal tests [IDT], especially with delayed readings) are used to investigate cutaneous adverse drug reactions (CADR) in delayed hypersensitivity reactions caused by a particular drug. Their value depends on the clinical features of the CADR and on the drug tested. In maculopapular rash (MPR), drug skin tests are of value, beginning with patch tests, and followed: 1) if negative by prick tests (with delayed readings at 24 hours); and, 2) if the injectable form of the drug is available, with IDT with immediate and delayed readings. This article discusses details of the use of patch tests as they apply to patients with various drug reactions. Drug skin tests are useful to study cross-reactivity between suspected drugs. False positive results can occur. The negative predictive value of drug skin tests is approximately 90%.
Nicorandil is an original vasodilatator used to control angina by decreasing cardiac preload and afterload. Since 1997, many reports of single or multiple nicorandil-induced ulcerations have been published. To date, eight cases of nicorandil-induced fistula into adjacent organs have been described. The pathogeneses of nicorandil-induced ulceration and fistula into adjacent organs are not yet elucidated. The two main hepatic biotransformation pathways of nicorandil are denitration and reduction of the alkyl chain leading to nicotinamide and niconitic acid which merge into the endogenous pool of nicotinamide adenine dinucleotide/phosphate. This merging which is known as saturable, may contribute to a slow and abnormal distribution of nicotinamide and nicotinic acid out of the endogenous pool. Under these special conditions, providing these two molecules in situ, nicotinic acid associated with nicotinamide may ulcerate rather recent or maintained trauma. Ulcers and fistulae induced by nicorandil heal after withdrawal. Surgical intervention is unnecessary and inappropriate as it is ineffective and exacerbates morbidity. All practitioners should be correctly informed about these serious but preventable nicorandil side effects, which mostly occur in the elderly and fragile population. In the absence of corrective measures, withdrawal of this original and active drug should be considered.
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