Methylisothiazolinone allergic contact dermatitis: Assessment of relapses in 139 patients after avoidance advice.

BACKGROUND: Methylisothiazolinone (MI) is a preservative that is responsible for an epidemic of allergic contact dermatitis (ACD). Few studies have been published on the prognosis of patients with MI-induced ACD. OBJECTIVES: To evaluate relapses of MI-induced ACD and difficulties in avoiding MI in patients who had received avoidance advice. METHODS: A retrospective study of patients with MI-induced ACD diagnosed in two specialized dermato-allergology units between 2010 and 2015 was performed. The median follow-up was 3 years. RESULTS: Relapses were observed in 64% of 139 included patients, and were severe in 18%. Rinse-off cosmetics were responsible for the largest proportion of relapses (27%). The median time to relapse was 5 months. Sixty-nine per cent of relapses were on the hands, and 29% were on the face. Risk factors for relapsing were hand eczema and a personal history of atopy. The main difficulties encountered in the avoidance strategy were hidden sources of MI, the lack of labelling on industrial products, the complexity of cosmetic labelling, and remembering the name of the allergen. CONCLUSION: MI-induced ACD has a poor prognosis. Its high rate of relapse is mainly attributable to the difficulties of avoidance. Management needs to be improved. Specialized follow-up in the year following diagnosis is essential to educate patients.

Is a specific eyelid patch test series useful? Results of a French prospective study.

BACKGROUND: Eyelids are frequent sites of contact dermatitis. No prospective study focused on eyelid allergic contact dermatitis (EACD) has yet been published, and this topic has never been studied in French patients. OBJECTIVES: To prospectively evaluate the usefulness of an eyelid series in French patients patch tested because of EACD, and to describe these patients. METHODS: We prospectively analysed standardized data for all patients referred to our departments between September 2014 and August 2016 for patch testing for suspected EACD as the main reason. All patients were patch tested with an eyelid series, the European baseline series (EBS), the French additional series, and their personal products. Patch testing with additional series and repeated open application tests (ROATs) or open tests were performed if necessary. A standardized assessment of the relevance was used, and the analysis of the results was focused on patients having positive test results with a current certain relevance. RESULTS: Two-hundred and sixty-four patients (238 women and 26 men) were included. Three-hundred and twenty-two tests gave positive results in 167 patients, 84 of whom had currently relevant reactions: 56 had currently relevant positive test reactions to the EBS, 16 had currently relevant positive test reactions to their personal products, 8 had currently relevant positive test reactions to the French additional series, and 4 had currently relevant positive test reactions to the eyelid series. Sixty-seven per cent of all relevant cases were related to cosmetic products. The most frequent allergens with current relevance were methylisothiazolinone (10.2%), fragrance mix I (3%), nickel (2.7%), hydroxyperoxides of linalool (2.7%) and limonene (2.3%), and Myroxylon pereirae (2.3%). Current atopic dermatitis was found in 9.5% of patients. The duration of dermatitis was shorter (23.2 vs 34.2 months; P = .035) in patients with currently relevant test reactions. The percentage of currently relevant tests remained the same when atopic patients or dermatitis localized only on the eyelids were taken into account. CONCLUSION: In French patients, testing for EACD with the extended baseline series and personal products, also including ROATs and use tests, appears to be adequate, considering the currently relevant positive test reactions. The regular addition of an eyelid series does not seem to be necessary.

Airborne allergic contact dermatitis caused by isothiazolinones in water-based paints: a retrospective study of 44 cases.

BACKGROUND: Airborne allergic contact dermatitis caused by paints containing isothiazolinones has been recognized as a health hazard. OBJECTIVES: To collect epidemiological, clinical and patch test data on airborne allergic contact dermatitis caused by isothiazolinone-containing paints in France and Belgium. METHODS: A descriptive, retrospective study was initiated by the Dermatology and Allergy Group of the French Society of Dermatology, including methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI)- and/or MI-sensitized patients who developed airborne allergic contact dermatitis following exposure to isothiazolinone-containing paint. RESULTS: Forty-four cases were identified, with mostly non-occupational exposure (79.5%). Of the patients, 22.5% of also had mucosal symptoms. In several cases, the dermatitis required systemic corticosteroids (27.3%), hospitalization (9.1%), and/or sick leave (20.5%). A median delay of 5.5 weeks was necessary to enable patients to enter a freshly painted room without a flare-up of their dermatitis. Approximately one-fifth of the patients knew that they were allergic to MI and/or MCI/MI before the exposure to paints occurred. CONCLUSION: Our series confirms that airborne allergic contact dermatitis caused by paints containing isothiazolinones is not rare, and may be severe and long-lasting. Better regulation of isothiazolinone concentrations in paints, and their adequate labelling, is urgently needed.

Genetic Predictors of Drug Hypersensitivity.

Our knowledge of genetic predisposing factors of drug hypersensitivity reactions (DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2, LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the single replicated GWAS performed so far. The HLA-DRA variants are predictors of allergy to penicillins, but not to cephalosporins and they influence also the sensitization against prevalent allergens. The predictors of DHRs against NSAIDs are mostly linked to metabolism of eicosanoids (ALOX5, ALOX5AP, TBXAS1, PTGDR, CYSLTR1). Single nucleotide polymorphisms (SNPs) in genes involved in histamine biosynthesis and antigen presentation, HLA, could also have a role in DHRs against NSAIDs. The intriguing association of DHRs to NSAIDs with atopy should deserve further attention. Predictors of DHRs against asparaginase and other biological agents relate to antigen presentation (HLA-DRB1 and HLA-A alleles, respectively). The potential relationship of genetic predictors of DHRs with pathomechanisms also involved in environmental exposure and atopy highlights the need to perform GWAS in contrasted populations, taking into account world-wide variations of allele frequencies and contrasted situations of environmental exposure.

Systemic Allergy to Corticosteroids: Clinical Features and Cross Reactivity.

Systemic hypersensitivity (HS) to corticosteroids (CS) is paradoxical but does exist. Some patients with a previous contact allergy to topical CS may develop a systemic contact dermatitis (SCD) while receiving CS orally or intravenously. However, a previous contact sensitization is not mandatory for developing a systemic HS to CS. Acute or delayed urticaria can occur in immediate HS. Immediate HS can be due to excipients, mainly carboxymethylcellulose or to CS themselves. Delayed reactions, mainly maculopapular rash and acute generalized exanthematous pustulosis can occur. Skin tests with systemic CS have to be standardized. It is necessary to determine if IDT with CS frequently induce skin atrophy or not and if such skin atrophy is transient by doing prospective studies using an standardized method and a limited injected volume (0.02 ml). Patch tests can be done in delayed HS, with readings at day 2, 4 and 7. In SCD, the Baeck's classification of CS in 3 chemical groups could explain cross reactivity between systemic CS. However, this classification is not applicable to explain cross-reactions between in systemic HS. According to the literature, 52/79 patients had a HS reaction to a group confirmed by a positive allergological investigations, but had a negative provocation test with another CS belonging to the same group. In case of non-severe cutaneous adverse reactions and when skin tests are negative, provocation tests have to be performed to find an alternative CS, even if it belongs to the same chemical group as those responsible for the initial reaction.

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 low concentrations 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.

IgE antibodies and skin tests in immediate hypersensitivity reactions to infliximab in inflammatory bowel disease: impact on infliximab retreatment.

BACKGROUND: Infliximab (IFX) is used for the treatment of inflammatory bowel diseases (IBD). Immediate hypersensitivity reactions (HR) to IFX are frequently reported. OBJECTIVES: We investigated immunoglobulin E (IgE)-mediated mechanisms underlying immediate HR to IFX. We also evaluated the clinical utility of allergological tests as well as the tolerability of IFX retreatment in these patients. METHODS: This was a prospective single-center study including IBD patients with previous immediate HR to IFX. Skin tests to IFX, including prick tests and intradermal tests, and measurement of anti-IFX IgE antibodies were performed at least 4 weeks after HR. In case of negative skin tests and absence of IgE antibodies, readministration of IFX was performed with a twice-reduced infusion rate. In case of positive tests or recurrence of HR during readministration of IFX, a 12-step desensitization or induction of tolerance protocol was proposed. RESULTS: A total of 24 IBD patients were included (Crohn's disease: n=20). Prick tests to IFX were all negative. Intradermal test was positive in one patient. Anti-IFX IgE antibodies were not detected in 21 patients and were detected in three patients (significant level in one patient and intermediate level in two patients). No relationship was observed between positive skin tests and the presence of anti-IFX IgE antibodies. Switch to adalimumab was well tolerated in 10/11 patients. The readministration of IFX was well tolerated in 4/11 patients. Desensitization to IFX was successful in three out of four patients. CONCLUSION: The vast majority of immediate HR to IFX is not IgE-mediated. Allergological tests are of poor clinical utility. Desensitization or induction of tolerance protocol may allow continuation of IFX therapy in IBD patients with a history of immediate HR.

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

BACKGROUND: 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. OBJECTIVES: To determine the rate of sensitization (contact allergy) to MDs and substances present in dressings. PATIENTS AND METHODS: A prospective multicentre study was carried out in patients with CLUs at five French dermatology departments; patch tests were performed with the European baseline series and with an additional 27 individual allergens and 10 MDs. RESULTS: Among 354 patients (226 women and 128 men) with CLUs, 59.6% had at least one positive patch test reaction to an MD and 19% had at least one sensitization to an MD. The number of positive test reactions per patient was correlated with the duration of ulcerative disease, but not with ulcer duration, the cause of the ulcer, or the presence of surrounding eczematous lesions. For 11 of 45 patients sensitized to Ialuset cream®, more detailed information could be obtained with sensitization to sodium dehydroacetate (5 cases) or Lanette SX® (3 cases). CONCLUSIONS: Sensitization to MDs is not rare. It is absolutely necessary to label all components of MDs on their packaging and to avoid some sensitizing molecules, such as colophonium derivatives or any strong sensitizers.

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

BACKGROUND: 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. OBJECTIVES: The objectives were to assess the non-irritating concentration of DPTs and determine the amounts of active ingredient (AI) contained in the drugs used in the tests. METHODS: From a retrospective, single-centre study of all patients investigated during a 6-year period with a drug eruption, each potentially responsible drug was tested with the commercially available preparation diluted to 30% in water, petrolatum, or alcohol. Data collection was performed with a customized computer database. For each type of DPT studied, the numbers of positive and negative test results were recorded. The amount of AI contained in the DPT (as a percentage) was then calculated after weighing of each tablet. RESULTS: Of the 5558 DPTs studied, all were non-irritant. The average concentration of AI was 9.8%; 25% of DPTs had an AI concentration of < 2%, and 25% had an AI concentration of > 16%. The AI concentration ranged from 0.05% (digoxin) to 30% (paracetamol lyophilisate). CONCLUSION: These data provide thresholds for the non-irritating concentration of AI of 68 different drugs, and thresholds for the non-irritating dilution for 82 drugs, and will help to standardize DPT methods.

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

BACKGROUND: 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. OBJECTIVE: To evaluate the change in the proportion of MI-positive tests in France between 2010 and 2012. PATIENTS/MATERIALS/METHODS: We conducted a nationwide, multicentre, retrospective study of all MI-tested patients between 2010 and 2012. RESULTS: Sixteen centres participated in the study (7874 patients were tested). Patch tests were performed mainly at a concentration of MI 200 ppm aq. We observed a significant increase in the proportion of MI-positive tests in 2012 and 2011 as compared with 2010 (5.6%, 3.3%, and 1.5%, respectively; p < 0.001). CONCLUSIONS: We report a significant increase in the number of MI-positive tests. MI is confirmed to be a rapidly emerging allergen, as also observed in other European countries.

The European Standard Series and its additions: are they of any use in 2013?

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.

Hypersensitivity and vaccines: an update.

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.

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.