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.

Allergic contact dermatitis from essential oil in consumer products: Mode of uses and value of patch tests with an essential oil series. Results of a French study of the DAG (Dermato-Allergology group of the French Society of Dermatology).

OBJECTIVE: To analyse the clinical characteristics and sensitivity of an essential oil patch test series (EOS) in patients sensitized to their own essential oils (EOs). METHOD: We analysed the clinical data and patch test results obtained with the European baseline series (BSE) and an EOS, as well as the mode of use of EOs, through a questionnaire included in the patient file. RESULTS: The study included 42 patients (79% women, average age 50 years) with allergic contact dermatitis (ACD), 8 patients required hospitalization. All patients were sensitized to the EO they used, primarily lavender (Lavandula augustifolia, 8000-28-0), tea tree (Melaleuca alternifolia leaf oil, 68647-73-4), ravintsara (Cinnamomum camphora oil, 92201-50-8), and 2 cases were attributed to helichrysum (helichrysum italicum flower absolute, 90045-56-0). 71% had positive patch tests to fragrance mix I or II, 9 only to the EOS and 4 only with their personal EO. Interestingly, 40% of patients did not spontaneously mention the use of EOs, and only 33% received advice on their use at the time of purchase. CONCLUSION: Patch tests with the BSE, limonene and linalool HP, and oxidized tea tree oil is sufficient to detect most EO-sensitized patients. The most important is to test the patient's own used EOs.

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.

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.

Tacrolimus 0.1% versus ciclopiroxolamine 1% for maintenance therapy in patients with severe facial seborrheic dermatitis: A multicenter, double-blind, randomized controlled study.

BACKGROUND: No long-term maintenance therapy has been tested in patients with seborrheic dermatitis (SD). OBJECTIVE: We sought to compare the efficacy and tolerance of tacrolimus 0.1% ointment versus ciclopiroxolamine 1% cream as maintenance therapy for severe SD. METHODS: This double-blind randomized controlled study was conducted from 2014 to 2017 in 5 Dermatology Departments and 15 dermatology practices in France. Consecutive patients with severe and chronic facial SD were included. Patients were initially treated with desonide 0.05% cream twice daily for 7 days. Patients cleared after this open phase were randomized to receive tacrolimus 0.1% or ciclopiroxolamine 1% cream 2 times a week 24 weeks. The primary endpoint was disease-free-duration, defined as the time from randomization to first relapse. RESULTS: One hundred fourteen patients were randomized (tacrolimus, n = 57; ciclopiroxolamine, n = 57). Twelve patients relapsed in the tacrolimus group after a median delay of 91.5 days (range 15-195 days) versus 23 patients in the ciclopiroxolamine group (median delay, 27 days [range 13-201 days]). Comparison of disease-free duration curves showed that patients in the tacrolimus group had a longer duration of complete remission than those in the ciclopiroxolamine group (P = .018), corresponding to a hazard ratio of relapse of 0.44 (95% confidence interval 0.22-0.89; P = .022). LIMITATIONS: The theoretical sample size was not reached. CONCLUSION: Tacrolimus 0.1% is more effective than ciclopiroxolamine 1% as maintenance therapy for patients with facial SD.

Drug-induced linear immunoglobulin A bullous dermatosis: A French retrospective pharmacovigilance study of 69 cases.

AIMS: Linear immunoglobin A (IgA) bullous dermatosis is a rare autoimmune dermatosis considered spontaneous or drug-induced (DILAD). We assessed all DILAD cases, determined the imputability score of drugs and highlighted suspected drugs. METHODS: Data for patients with DILAD were collected retrospectively from the French Pharmacovigilance network (from 1985 to 2017) and from physicians involved in the Bullous Diseases French Study Group and the French Investigators for Skin Adverse Reactions to Drugs. Drug causality was systematically determined by the French imputability method. RESULTS: Of the 69 patients, 42% had mucous membrane involvement, 20% lesions mimicking toxic epidermal necrolysis (TEN), 21% eosinophil infiltrates and 10% keratinocytes necrosis. Direct immunofluorescence, in 80%, showed isolated linear IgA deposits. Vancomycin (VCM) was suspected in 39 cases (57%), 11 had TEN-like lesions, as compared with three without VCM suspected. Among the 33 patients with a single suspected drug, 85% had an intrinsic imputability score of I4. Among them, enoxaparin, minocycline and vibramycin were previously unpublished. For all patients, the suspect drug was withdrawn; 15 did not receive any treatment. First-line therapy for 31 patients was topical steroids. Among the 60 patients with available follow-up, 52 achieved remission, 10 without treatment. Four patients experienced relapse, four died and five had positive accidental rechallenges. CONCLUSIONS: There is no major clinical difference between DILAD and idiopathic linear IgA bullous dermatosis, but the former features a higher prevalence of patients mimicking TEN. VCM, suspected in more than half of the cases, might be responsible for more severe clinical presentations. We report three new putative drugs.

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.

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.

Cutaneous Adverse Drug Reactions with Antimalarials and Allergological Skin Tests.

BACKGROUND: Currently used antimalarial drugs (AM) are hydroxychloroquine and chloroquine, which are prescribed for many autoimmune disorders. The value of skin tests on cutaneous adverse drug reactions (CADR) with AM remains unknown. OBJECTIVE: The main objective of this retrospective study is to know whether skin tests for AM are useful and how to manage the recovery of AM therapy in these patients. METHODS: All patients referred for suspected CADR secondary to AM between 2001 and 2014 in eight French dermatology centers were retrospectively reviewed. RESULTS: We report herein a retrospective series of 20 patients with CADR and AM involvement. Skin tests, performed in 14/20 patients, were negative in all cases. Six patients had an oral provocation test with recurrence of CADR in 1 case. CONCLUSION: We encourage dermatologists to perform oral provocation tests in nonsevere CADR in order to allow AM rechallenge at progressive doses.