J. Waton

A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions

Background  Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re‐exposure of patients to offending drugs.

Contact urticaria from Emla® cream

We report the first case of immediate‐type hypersensitivity caused by Emla® cream. A 55‐year‐old woman, after using Emla® cream, went on to develop urticaria. An open test was positive to Emla® cream. Patch tests and prick tests were performed with Emla® cream, the components of Emla® cream (lidocaine, prilocaine and castor oil) and other local anaesthetics. The patch test with lidocaine and the prick test with Emla® cream were both positive. An intradermal test and subcutaneous administration of 3 anaesthetics that had negative patch tests and prick tests were performed and well tolerated, allowing their use. In the literature, anaphylactic reactions to lidocaine injections, delayed‐type hypersensitivity after lidocaine subcutaneous injections and contact dermatitis from Emla® cream have all been described. This first case of contact urticaria from Emla® cream was due to lidocaine and did not show any cross‐reaction with other local anaesthetics.

Outbreak of contact sensitization to methylisothiazolinone: an analysis of French data from the REVIDAL‐GERDA network

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.

How to manage hypersensitivity reactions to biological agents

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.

Contact sensitization to modern dressings: a multicentre study on 354 patients with chronic leg ulcers

Modern dressings (MDs) may have a low sensitization rate, but there is a lack of prospective studies in patients with chronic leg ulcers (CLUs) to evaluate this.

Occupational protein contact dermatitis

Occupational contact dermatitis is generally caused by haptens but can also be induced by proteins causing mainly immunological contact urticaria (ICU); chronic hand eczema in the context of protein contact dermatitis (PCD). In a monocentric retrospective study, from our database, only 31 (0.41%) of patients with contact dermatitis had positive skin tests with proteins: 22 had occupational PCD, 3 had non-occupational PCD, 5 occupational ICU and 1 cook had a neutrophilic fixed food eruption (NFFE) due to fish. From these results and analysis of literature, the characteristics of PCD can be summarized as follows. It is a chronic eczematous dermatitis, possibly exacerbated by work, suggestive if associated with inflammatory perionyxix and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have negative results. In case of multisensitisation revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. A history of atopy, found in 56 to 68% of the patients, has to be checked for. Most of the cases are observed among food-handlers but PCD can also be due to non-edible plants, latex, hydrolysed proteins or animal proteins. Occupational exposure to proteins can thus lead to the development of ICU. Reflecting hypersensitivity to very lowconcentrations of allergens, investigating ICU therefore requires caution and prick tests should be performed with a diluted form of the causative protein-containing product. Causes are food, especially fruit peel, non-edible plants, cosmetic products, latex, animals.

Analysis of cross-reactivity among radiocontrast media in 97 hypersensitivity reactions

Results Ninety-seven patients were included. CR occurred between ionic monomers (IMs) in 2 cases, between non-ionic monomers (NIMs) in 93 cases, between an ionic dimer (ID) and an IM in 1 case, between NIMs and IMs in 38 cases, between NIMs and IDs in 29 cases, between non-ionic dimers (NIDs) and IMs in 9 cases, between IDs in 13 cases, and between NIMs in 65 cases. Multiple correspondence analyses identified two subgroups of RCM in which CR was frequent: Group A (iodixanol, iopamidol, iomeprol, iohexol, ioversol), which share two identical N-(2, 3-dihydroxypropyl) carbamoyl side chains that could be the antigen determinant (also present in other drugs), and Group B (ioxaglate, iobitridol). Conclusion From this largest study of CR between RCM, we demonstrate that frequent CR between RCM does not follow the current chemical classification. Thus, we propose reclassifying RCM, and also suggest re-challenging sensitized patients with RCM from a different CR subgroup than that of the RCM initially involved.

Is 500 ppm a better concentration than 200 ppm for diagnosing contact allergy to methylisothiazolinone

Two commercial products are available for peforming patch tests for sensitivity to methylisothiazolinone (MI): one diluted to 200ppm MI (Laboratory Chemotechnique, Velinge, Sweden) and the other to 500ppm (Laboratory Stallergene, Antony, France). The sensitivity and specificity of these tests are not known, and the authors discuss which one is best to use.

La polysensibilisation médicamenteuse systémique existe-t-elle ?

BACKGROUND Multiple-drug hypersensitivity (MDH) in the literature concerns different entities. Our objective was to define its frequency and characteristics in patients examined for cutaneous adverse drug reaction (CADR) before studying genetic predisposition. MATERIALS AND METHODS From a database comprising all patients referred for CADR between 2000 and 2010, we selected those meeting the following criteria: sensitisation to at least two chemically unrelated substances, as confirmed by positive skin tests or challenge tests. The following were excluded: patients with haematological diseases, HIV or chronic wounds and sensitization to the excipients. RESULTS Of the 1925 patients included, 11 (0.6%) were classed as polysensitized: eight women and three men, of mean age 62 years, presenting 2.5 episodes of drug hypersensitivity per patient. Four cases of DRESS were noted. DISCUSSION The strict criteria stipulated for this study enabled us to select patients with MDH, and to affirm that while it does in fact exist, it seems rare. Compared to polysensitized patients described in the literature, we preferred to distinguish between three groups of MDH: one occurring with different substances in separate episodes of CADR, one occurring with different substances during the same episode of CADR, and one occurring during DRESS and correlating with viral replication. CONCLUSION MDH exists and genetic predisposition could be investigated by studying cytokine polymorphism in such patients. However, because of its rarity, it is impossible to rule out fortuitous association of two episodes of CADR in the same patient.

Non-irritant concentrations and amounts of active ingredient in drug patch tests

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.