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.

Multicenter prospective observational study of dupilumab-induced ocular events in atopic dermatitis patients.

BACKGROUND: Although ocular adverse events are frequent in AD patients treated with dupilumab, their characterization remains limited due to a lack of prospective studies with a systematic ophthalmological examination. OBJECTIVE: To examine the incidence, characteristics and risk factors of dupilumab-induced ocular adverse events. METHODS: A prospective, multicenter, and real-life study in adult AD patients treated with dupilumab. RESULTS: At baseline, 27 out of 181 patients (14.9%) had conjunctivitis. At week 16 (W16), 25 out of 27 had improved their conjunctivitis and 2 remained stable and 34 out of 181 patients (18.7%) had dupilumab-induced blepharoconjunctivitis: either de novo (n = 32) or worsening of underlying blepharoconjunctivitis (n = 2). Most events (27/34; 79.4%) were moderate. A multivariate analysis showed that head and neck AD (OR = 7.254; 95%CI [1.938-30.07]; p = 0.004), erythroderma (OR = 5.635; 95%CI [1.635-21.50]; p = 0.007) and the presence of dry eye syndrome at baseline (OR = 3.51; 95%CI [3.158-13.90]; p = 0.031) were independent factors associated with dupilumab-induced blepharoconjunctivitis. LIMITATIONS: Our follow-up period was 16 weeks and some late-onset time effects may still occur. CONCLUSION: This study showed that most dupilumab-induced blepharoconjunctivitis cases are de novo. AD severity and conjunctivitis at baseline were not found to be associated risk factors in this study.

What is the optimal duration for a ROAT? The experience of the French Dermatology and Allergology group (DAG).

BACKGROUND AND OBJECTIVES: The repeated open application test (ROAT) is an adjuvant investigation measure to patch testing in the diagnosis of allergic contact dermatitis. ESCD recommends a 15 days duration but its overall duration varies according to publications and patients hardly adhere to prolonged ROAT duration beyond 1 week. MATERIALS AND METHODS: The Dermatology and Allergy Group of the French Society of Dermatology performed a prospective study with the aim of determining the best duration for the ROAT. RESULTS: A total of 328 ROAT results were collected for topical products, including cosmetics (60%) and topical medications (31.1%). Fifty-nine (18%) ROATs were positive, and 16 (5%) were doubtful. All the positive ROATs occurred within 10 days, with a median time to positivity of 3 days. CONCLUSION: According to our results, a minimum duration of 10 days is necessary to achieve a positive ROAT to a topical product.

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.

DRESS and AGEP Reactions to Iodinated Contrast Media: A French Case Series.

BACKGROUND: Drug reactions with eosinophilia and systemic symptoms (DRESSs) and acute generalized exanthematous pustulosis (AGEP) are potentially severe cutaneous adverse drug reactions. OBJECTIVE: To describe the clinical findings and sensitization profiles of DRESS and AGEP patients who had been administered iodinated contrast media (ICM). METHODS: All adult patients in the dermatologist's French Investigators for Skin Adverse Reactions to Drugs (FISARD) network diagnosed with a DRESS or AGEP highly suspected to have been caused by an ICM were included retrospectively. RESULTS: Thirteen DRESS patients and 19 AGEP patients who had been administered ICM were included, and the median delay in DRESS and AGEP occurrence after ICM administration was short, 4 and 1 days, respectively. Five AGEP patients had systemic involvement. A high cosensitization rate (46%) was observed among the DRESS patients, mainly with beta-lactam antibiotics. Overall, 77% of our patients were sensitized to several ICM. Patch tests identified the suspected ICM for 21 cases (72%). The retrospective nature, the limited number of subjects, the absence of a control group of healthy individuals, and the lack of detailed information on previous exposure to sensitizing drugs are limitations of this study. CONCLUSIONS: We report a large series of DRESSs and AGEPs related to ICM administration. Skin tests appear useful for diagnosis and potentially to identify alternative ICM.

Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort.

BACKGROUND: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. OBJECTIVE: We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort. METHODS: We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up. RESULTS: We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10-9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10-9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10-6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs. LIMITATIONS: No control group, missing data. CONCLUSION: This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.

Higher Frequency of Dipeptidyl Peptidase-4 Inhibitor Intake in Bullous Pemphigoid Patients than in the French General Population.

Dipeptidyl peptidase-4 inhibitors have been suspected to induce bullous pemphigoid (BP). The objective of this study was to compare the observed frequency of gliptin intake in a large sample of 1,787 BP patients diagnosed between 2012 and 2015 in France, with the expected frequency after indirect age standardization on 225,412 individuals extracted from the database of the National Healthcare Insurance Agency. The secondary objective was to assess the clinical characteristics and the course of gliptin-associated BP, depending on whether gliptin was continued or stopped. The observed frequencies of intake of the whole gliptin class and that of vildagliptin in the BP population were higher than those in the general population after age standardization (whole gliptin class: 6.0%; 95% confidence interval = 4.9-7.1% vs. 3.6%, observed-to-expected drug intake ratio = 1.7; 95% confidence interval = 1.4-2.0; P < 0.0001; vildagliptin = 3.3%; 95% confidence interval = 2.5-4.1% vs. 0.7%, ratio = 4.4; 95% confidence interval = 3.5-5.7; P < 0.0001). The association of any gliptin+metformin was also higher than in the general population, ratio = 1.8 (95% confidence interval = 1.3-2.4; P < 0.0001). Gliptin-associated BP had no specific clinical characteristics. Gliptin was stopped in 48 (45.3%) cases. Median duration to achieve disease control, rate, and delay of relapse were not different whether gliptin was stopped or continued. This study strongly supports the association between gliptin intake, particularly vildagliptin, and the onset of BP.

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.

Methotrexate Versus Cyclosporine in Adults with Moderate-to-Severe Atopic Dermatitis: A Phase III Randomized Noninferiority Trial.

BACKGROUND: Methotrexate is currently used to treat atopic dermatitis but has never been assessed versus cyclosporine in adults. OBJECTIVE: This study evaluated the efficacy and safety of methotrexate versus cyclosporine in patients with moderate-to-severe atopic dermatitis. METHODS: Patients were randomized to receive either oral methotrexate (15 mg/wk) or cyclosporine (2.5 mg/kg/d) for 8 weeks. The primary end point was a patient achieving 50% improvement in the SCORing Atopic Dermatitis index (SCORAD 50) at week 8. When the primary end point was not achieved, methotrexate was increased to 25 mg and cyclosporine to 5 mg during the next 16 weeks. The secondary end points were a patient achieving a 50% reduction in the Eczema Area Severity Intensity index (EASI 50) and SCORAD 50 at each visit (ClinicalTrials.gov no. NCT00809172). RESULTS: A total of 97 patients received methotrexate 15 mg (n = 50) or cyclosporine 2.5 mg (n = 47). Regarding the primary end point at week 8, methotrexate was inferior to cyclosporine because the proportion of patients with SCORAD 50 was 8% (4 of 50) in the methotrexate arm versus 42% (18 of 43) in the cyclosporine arm. The difference in percentages for the 2 treatment groups (2-sided 90% CI) was -34% (-48% to -20%). At week 8, methotrexate and cyclosporine dosages were increased in 56% and 49% of the patients, respectively. Regarding EASI 50, the noninferiority end point was reached at week 20 in 92% (22 of 24) of patients in the methotrexate arm and 87% (26 of 30) of patients in the cyclosporine arm. The treatment-related adverse events were more frequent with cyclosporine (P < .0001). CONCLUSIONS: Methotrexate 15 mg/wk was inferior to cyclosporine 2.5 mg/kg/d at week 8. Increasing the doses of methotrexate to 25 mg/wk induced a significant improvement versus cyclosporine at week 20.

Alkyl Glucosides in Contact Dermatitis.

Ecologically sound because they are synthesized from natural and renewable sources, the mild surfactants alkyl glucosides are being rediscovered by the cosmetic industry. They are currently found in rinse-off products such as shampoos, liquid cleansers, and shower gels, but also in leave-on products that include moisturizers, deodorants, and sunscreens. During the past 15 years, numerous cases of allergic contact dermatitis have been published, mostly to lauryl and decyl glucosides, and these compounds are considered emergent allergens. Interestingly, the sunscreen Tinosorb M contains decyl glucoside as a hidden allergen, and most cases of allergic contact dermatitis reported to this sunscreen ingredient are probably due to sensitization to decyl glucoside. This article will review the chemistry of alkyl glucosides, their sources of exposure, as well as their cutaneous adverse effects reported in the literature and encountered in various patch testing centers.

Azo pigments and quinacridones induce delayed hypersensitivity in red tattoos.

BACKGROUND: Induction of delayed hypersensitivity reactions by red tattoos has been occasionally reported. Little is known about the inks used. Azo pigments have been implicated in some instances, but there is only one reported case involving quinacridones. OBJECTIVES: To describe the clinical and pathological features and outcome of skin reactions induced by red tattoo pigments. PATIENTS, MATERIALS, AND METHODS: Six patients with a cutaneous reaction induced by a red tattoo pigment underwent biopsy and prick and patch testing with the inks supplied. RESULTS: We observed seven reactions in the 6 patients. Histology showed various patterns: three lichenoid, two eczematous, and two pseudolymphomatous. Five reactions occurred with azo pigments, and two with quinacridones, in both cases with Violet 19 and Red 122. Four inks were tested. Only one patch test gave a positive result at a late reading (day 7). Prick tests gave negative results. The reactions required various treatments, including laser treatment for 2 patients. Activation of the reaction in 1 case was transient. CONCLUSION: Azo pigments and quinacridones both triggered reactions with similar clinical aspects but with varying histological findings. Patch and prick test results were disappointing with both. Reactions occurred following laser use in 1 case.

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.