Impact of dupilumab on patch test results and allergic contact dermatitis: A prospective multicenter study.

BACKGROUND: Limited and conflicting data have been reported on the impact of dupilumab (DUPI) on patch test (PT) results and its efficacy against allergic contact dermatitis (ACD). OBJECTIVE: This study was undertaken to analyze PT reactivities and relevance during treatment with DUPI to determine whether they could detect ACD in patients with uncontrolled or worsened atopic dermatitis (AD) who were receiving this agent. METHODS: This prospective, multicenter study examined 76 DUPI-treated patients who had undergone PTs. The relevant information was collected during 3 visits. RESULTS: Overall, 36 patients (47%) had ≥1 positive PT reaction, and 142 PT results were positive. Twenty-three patients (30%) had ≥1 positive and clinically relevant PT result. Five of them had clinical eczema improvement after allergen avoidance. We compared the PT results of 36 patients before and during DUPI therapy, representing 1230 paired PT allergens, of which 1022 were the same, 34 were positive, 44 were lost, and 130 were uninterpretable. LIMITATIONS: Because the number of patients included remains limited, our findings should be confirmed with a larger sample. CONCLUSION: Our results confirmed the usefulness of PTs for patients receiving DUPI, with good PT reproducibility. We suggest that all DUPI-treated patients with AD developing partial responses or experiencing symptom worsening should undergo PTs to look for contact sensitization.

Hand eczema in glove-wearing patients.

BACKGROUND: Allergic contact dermatitis to gloves is mostly induced by rubber accelerators. The European baseline series (EBS) appears insufficient to detect glove allergy. Since 2017, it is recommended to use the European rubber series (ERS) and to test the patients' own gloves. OBJECTIVES: To investigate the clinical profile of glove-wearing patients with hand eczema (HE) and to evaluate their sensitisation profile to glove allergens and the value of testing the patients' own gloves. METHODS: We conducted a French multicentre study of patients evaluated for HE between 2018 and 2020 and tested with the EBS, the ERS and their own gloves in patch tests and semi-open (SO) tests. RESULTS: A total of 279 patients were included; 32.6% of patients had positive tests to their own gloves or to glove allergens. Almost 45% of the sensitisations to glove allergens were detected only by the ERS. Among the patients tested both in patch tests and SO tests with their own gloves with positive results, 28% had positive SO tests only. Polyvinylchloride (PVC) gloves were positive in four patients. CONCLUSION: Our series confirms the need to test the ERS. All the patients' gloves must also be tested including PVC gloves. SO tests with gloves are useful as a complement to patch tests.

Contribution of phototesting in the diagnosis of photodermatoses: Retrospective study of 100 cases.

BACKGROUND: Photodermatoses are sun-related inflammatory skin diseases. They usually require phototesting in diagnosis. However, fewer and fewer medical centers in France are equipped with photobiological equipment. OBJECTIVES: The main purpose was to evaluate the relevance of phototesting in photodermatosis diagnosis. The second goal was to study the proportions of the different kinds of photodermatosis found in this particular study. METHODS: This study was descriptive, retrospective, and mono-centric. It was based on 100 consecutive patients, who have been phototested in a French University Hospital from 2014 to 2018. Phototesting included determination of the minimal erythematous dose (MED), UVA and UVB phototests, and photopatch testing. RESULTS: The use of phototesting led to 60% of photodermatosis diagnosis and formally eliminated the latter in 13% of the cases. The diagnosis remained undetermined in 27% of the cases. Nineteen cases of polymorphous light eruption (PLE), 14 cases of photocontact dermatitis (PCD), 10 cases of solar urticaria, 8 cases of photo-aggravated atopic eczema, 5 cases of chronic actinic dermatitis, and 2 cases of systemic photosensitization were diagnosed. The allergens involved in PCD were topical non-steroidal anti-inflammatory drug (NSAID) in 9 cases, sunscreens in 3 cases, and fragrance in 2 cases. The average amount of time between the first symptoms and actual phototesting was about 7,5 years. CONCLUSION: This study confirms phototesting is truly useful. PLE was the most common form of photodermatosis, followed by PCD and solar urticaria. As photodermatosis could imply severe diseases sometimes requiring hospitalization, it is critical to maintain this expertise.

Preparations of exploration of immediate hypersensitivity to antineoplastic agents: An oncology pharmacy perspective.

BACKGROUND: Cancer patients are being exposed to antineoplastic drugs more frequently and for longer periods, resulting in a higher risk of hypersensitivity reactions. The aim of this study was to assess the pharmaceutical time and direct cost of drug allergy explorations following immediate hypersensitivity reactions to antineoplastic agents. METHODS: A micro-costing method was used to collect data on consumption of human and material resources for allergy exploration preparations. The monetisation was carried out on the basis of prices and hourly wage costs applied in 2018. The number and type of allergy explorations prepared by the pharmacy as well as nature of antineoplastic drugs tested, and the number of culprit drugs reintroductions were collected. RESULTS: Almost 1.5 h is required to realise allergy tests for one patient including pharmacist time for prescription analysis and pharmacy technician's time for tests preparation. The mean manufacturing cost of these tests is estimated at €62.87 (€57.82-65.49) per culprit drug for one patient. Programming patients according to culprit drugs tested allows rationalising healthcare provider time and increasing efficiency. From January 2010 to December 2018, 277 patients were tested and 490 allergy explorations were performed, corresponding to more than 5000 preparations. Mostly, the culprit drug could be reintroduced (n = 383, 78.2%) allowing patients to receive the best possible treatment. CONCLUSION: Management of hypersensitivity reactions is constantly progressing, as it contributes to improving patient care in oncology. This activity is time-consuming for the pharmacy team but allows patients with previous hypersensitivity reaction to continue effective treatment.

Multiple cases of sensitization to an antiseptic containing chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol with different profiles of sensitization in adults and children.

BACKGROUND: An aqueous antiseptic containing "chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol" (CBB) is widely used in France. The only previous documented study dealing with allergic contact dermatitis (ACD) to this antiseptic is one small case series in children. The French Vigilance Network for Dermatology and Allergy (REVIDAL-GERDA) has collected many cases in the last few years. OBJECTIVES: To evaluate the clinical and sensitization profiles of patients diagnosed with ACD to CBB. METHODS: We performed a retrospective study of patients with contact dermatitis to CBB and positive tests to CBB and/or at least one of its components. All patients had to be tested with all components of CBB. RESULTS: A total of 102 patients (71 adults and 31 children) were included. The lesions were extensive in 63% of patients and 55% had delayed time to diagnosis. CBB patch tests were positive in 93.8% of cases. The allergen was identified in 97% of patients, mainly benzyl alcohol in adults (81.7%) and chlorhexidine digluconate in children (54.8%). About 32.4% of the patients were sensitized to several components. CONCLUSION: CBB is a cause of ACD at all ages. The components of the antiseptic should be tested. The sensitization profile seems to be different between adults and children.

Unique molecular signatures typify skin inflammation induced by chemical allergens and irritants.

BACKGROUND: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic. METHODS: To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants. RESULTS: A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation. CONCLUSION: These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.

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.

The basophil activation test: a sensitive test in the diagnosis of allergic immediate hypersensitivity to pristinamycin.

Immediate hypersensitivity (IHS) reactions to macrolides and to macrolide-derived antibiotics like pristinamycin are uncommon. In this context, there is little data available to appreciate the true value of biological tools regarding the diagnosis of immediate allergy to pristinamycin. Here we assess the clinical usefulness of the basophil activation test (BAT) to differentiate allergic from nonallergic IHS to pristinamycin. Thirty-six patients were tested with skin tests as the gold standard and BAT. The BAT achieved a sensitivity of 76% and a specificity of 100%, implying an absence of false positive results. Multicenter studies remain to be performed to better define the sensitivity, specificity and interlaboratory variation of BAT in the diagnosis of allergy to pristinamycin and macrolides.

Discrepancies in the management of acquired cold contact urticaria: Results of a French-speaking urticaria experts questionnaire survey.

Acquired cold contact urticaria (ACU) is a putatively serious condition, because of the risk of anaphylactic shock whenever patients are massively exposed to cold atmosphere/water, raising the question of the prescription of an "emergency kit" with oral antihistamines and epinephrine auto-injector. We performed an online survey to evaluate how French-speaking urticaria experts manage ACU. According to the 2016 consensus recommendations on chronic inducible urticarias, all the participants perform at least 1 of the available provocation tests and 84.2%, 77.8%, and 88.9% prescribe on-label use of second generation anti-H1 antihistamines (2GAH1) as a first line treatment, updosed 2GAH1 as a second line treatment, and omalizumab as a third line treatment, respectively. Interestingly, 44.4% of the practitioners always prescribe a continuous background treatment, versus 11.1% prescribing only on-demand therapy. Also, 11.7% of participants always prescribe an epinephrine auto-injector, 70.6% sometimes do, and 17.6% never do. Finally, 89.5% authorize swimming under strict conditions but 36.8% and 68.4% contra-indicate other water sports and occupational cold exposure, respectively.

Improvement of patient outcomes following therapeutic optimization of chronic urticaria: two-year data from France as part of the international real-life AWARE study.

BACKGROUND: It is important to assess the burden of chronic urticaria (CU) with real-life studies. The AWARE study was performed in 36 countries over two years in CU patients resistant to H1-antihistamines. OBJECTIVES: To correlate patient-reported outcomes and available therapeutic options in CU patients. MATERIALS & METHODS: The AWARE study was a prospective, non-interventional, international study that included adult patients who have had H1-antihistamine-resistant CU for at least two months. The primary endpoints were the evolution of disease activity (UAS7), urticaria control (UCT), dermatological quality of life (DLQI) and treatment satisfaction (visual analogic scale) during a two-year follow-up. The data from French centres are reported. RESULTS: Ninety-two patients were included (mean age: 47.8 years; women: 70.7%; mean disease duration: 6.5 years; angioedema: 34.1%). The percentage of patients with CU treatment increased from 56.5% at inclusion to 86.0% after two years (for patients with non-sedative H1-antihistamines from 52.2% to 74.4%, and omalizumab from 2.2% to 25.6%). During the follow-up, the percentage of patients with UAS7 score <6 increased from 12.5% to 60.9%, and patients with well-controlled CU (UCT score >12) increased from 11.1% to 62.2%. The negative impact on quality of life (DLQI >10) decreased from 34.1% to 10.5%. The mean score of patient satisfaction for treatment increased from 4.6 to 7.6. CONCLUSION: The management of CU patients resistant to H1-antihistamines was not optimal at inclusion with uncontrolled disease, impaired quality of life and insufficient treatment. After a two-year follow-up, disease symptoms and quality of life improved, but the therapeutic management could be further optimized.

The burden of chronic urticaria: French baseline data from the international real-life AWARE study.

BACKGROUND: The AWARE study is an ongoing international study of patients with chronic urticaria refractory to H1-antihistamines. The aim of this study is to evaluate the burden of disease and the use of healthcare resources in real-life conditions. OBJECTIVES: To analyse the baseline data of French patients included in the AWARE study. MATERIALS & METHODS: AWARE is a prospective, non-interventional, international study that includes adult patients who have had chronic urticaria, refractory to at least one H1-antihistamine, for at least two months. RESULTS: Ninety-four patients (mean age: 47.9 years; 71.3% women) with chronic urticaria (50.0% spontaneous only, 9.6% inducible only, and 40.4% both) were included in French centres. The median duration from diagnosis was three years and angioedema was present in 31.5% of patients for the past six months. In 63.8% of cases, the patients received at least one treatment for urticaria (H1-antihistamine for 66.0%). Chronic urticaria was poorly controlled (UCT score <12) in 88.9% of patients and quality of life was severely impaired (mean DLQI score: 8.6). The use of healthcare resources was significant with frequent visits to general practitioners (80.8% of patients; mean: 8.1 visits). However, more than half of patients had not previously consulted a dermatologist. CONCLUSION: These baseline data of French patients in the AWARE study show that patients suffering from chronic urticaria, refractory to H1-antihistamines for a median of three years, are insufficiently treated and that their quality of life is impaired. Despite the significant use of healthcare resources, access to specialised consultations remains insufficient.

Antituberculosis Drug-Associated DRESS: A Case Series.

BACKGROUND: Although antituberculosis drug-associated drug reaction with eosinophilia and systemic symptoms (DRESS) is rarely reported, its diagnosis should not be dismissed. Its management implies an early withdrawal of suspected drugs. OBJECTIVE: The objective of this study was to describe the characteristics of antituberculosis drug-associated DRESS and to identify the most likely involved drugs. METHODS: We searched for potential cases of DRESS with rifampicin, isoniazid, pyrazinamide, and ethambutol reported from January 1, 2005, to July 30, 2015, in the French pharmacovigilance database. A literature review was also performed. RESULTS: Sixty-seven cases of antituberculosis drug-associated DRESS were analyzed (40 women and 27 men, median age of 61 years). Liver and kidneys were the most frequently involved organs. Two patients died from DRESS. Skin tests were performed in 11 patients and were positive in 8 cases. Discrepancies between epicutaneous tests and reintroduction of the culprit drugs were observed for 2 patients with a premature reintroduction of antituberculosis drugs in 1 case. Antituberculosis drugs were the only suspects in 20 cases. As for the literature data, rifampicin was the most suspected drug because of its larger indications, but in case of tuberculosis infections, isoniazid was the most suspected drug. CONCLUSIONS: We described the largest case series of first-line antituberculosis drug-associated DRESS in the literature. All antituberculosis drugs pose a risk of DRESS. An early withdrawal of the culprit drugs is essential. A drug allergy evaluation must be performed to optimize the second-line treatment of tuberculosis infection.

Diagnosis and treatment of upper airway oedema caused by acute angio-oedema in the emergency department: a French consensus statement.

Angio-oedema is a transitory, localized, noninflammatory oedema of subcutaneous tissue or mucous. When the oedema affects the mouth, lips, tongue or larynx, it can result in fatal asphyxiation in the absence of specific treatment. Oedema secondary to plasma extravasation is usually mediated by either histamine or bradykinin. As laboratory tests are not available in an emergency setting, the implicated mediator cannot be readily determined. The challenge for the emergency physician is to determine the aetiological type, evaluate severity and initiate adapted treatment by means of a structured approach. A team of experts from the French Reference Centre for Angio-oedema reached a consensus for recommendations for the diagnostic and therapeutic strategy to be adopted by emergency departments faced with angio-oedema of the upper airways in adults. The experts defined 11 important questions. Responses were rated using a two-round Delphi methodology. The 11 recommendations were related to triage on admission, a step-by-step diagnostic protocol, definition of attack severity, discouragement of instrumental examination, prioritization of treatment for severe attacks according to clinical signs and anticipation of access to specific treatments by the hospital. Angio-oedema of the upper airways can be fatal and requires anticipation by the emergency department. A search for the aetiology, an evaluation of clinical symptoms and the availability of the treatments are challenges justifying these recommendations.