Effectiveness and safety of dupilumab in the treatment of atopic dermatitis in children (6-11 years): data from a French multicentre retrospective cohort in daily practice.

BACKGROUND: Dupilumab is the first biotherapy available for the treatment of moderate-to-severe childhood atopic dermatitis (AD). OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of dupilumab in daily practice. METHODS: Patients aged 6-11, who had received a first dose of dupilumab, were included in this multicentre retrospective cohort study. The primary endpoint was change in SCORAD after 3 months of treatment. Secondary endpoints were change in IGA score at 3 months, proportion of patients with SCORAD50 and SCORAD75, description of adverse events and proportion of children in our cohort who would be excluded from pivotal phase 3 clinical trial. RESULTS: Eighty patients were included. After 3 months of treatment, there was a significant decrease in SCORAD (mean: 21.8 ± 13.8 vs 53.9 ± 18.5; P < 0.0001) and IGA (1.3 ± 0.8 vs 3.5 ± 0.7; P < 0.0001). Conjunctivitis was observed in 11.3% (n = 9/80); three patients experienced dupilumab facial redness (DFR); 17.5% (n = 14/80) reported injection site reactions; 6.3% (n = 5/80) discontinued treatment. 61.2% (n = 49/80) children were ineligible in the phase 3 trial. LIMITATIONS: There is no control group. Because it was a real life study based on information from patient medical records in a French multicentre cohort, we cannot rule out the presence of reporting bias generated by the use of patient reported characteristics and missing information. CONCLUSION: These real-life data confirm the efficacy and safety of dupilumab in children with moderate to severe AD extended to dyshidrosis and atopic prurigo, but it also revealed a lower frequency of DFR and conjunctivitis. However, administration in injectable form may be a barrier in this age group.

[Recommendations for patients on preparing for dermatology-allergology consultations: Evaluation of the information notice of the French Society for Dermatology]. / Recommandations au patient avant les tests cutanés : évaluation de la fiche d'information du groupe dermato-allergologie de la Société française de dermatologie.

BACKGROUND: Skin patch-tests in dermatology-allergology practice require good preparation. To this end, the dermatology-allergology group of the French Society of Dermatology introduced an information notice informing patients about patch testing procedures. The aim of this study was to evaluate the utility and understanding of the notice. PATIENTS AND METHODS: The information notice was sent out to patients before testing. On the day of the test, a questionnaire was submitted to patients to evaluate their comprehension of the notice. Another questionnaire was submitted simultaneously to the dermatology-allergology practitioner to evaluate whether the patient had complied with the guidelines given in the information notice. Paired questionnaires were analyzed for this study. RESULTS: Eight dermatology-allergology hospital departments participated in the study and collected 921 paired questionnaires over a period of 18months. Among the vast majority (96.2%) of patients who had read the information notice, most found it useful (98.8%), easy to read (97.4%), and appropriate (91.5%). Ten percent of patients had difficulty understanding. CONCLUSION: This study shows that the information notice was clear and explicit for the immense majority of patients. Thanks to the feedback of a number of patients, the information notice was further improved to enhance patient understanding.

Long-lasting allergic contact blepharoconjunctivitis to phenylephrine eyedrops.

Allergic contact dermatitis due to mydriatic eyedrops is rare despite extensively used by ophthalmologists. Phenylephrine is responsible for most of the cases in the literature. We reported two other cases due to phenylephrine eyedrops with an unusual evolution characterized by chronic debilitating blepharoconjunctivitis.

[Patch-test methods: materials and allergens]. / Méthodologie des patch-tests : supports et allergènes.

We describe the methods used in patch-testing: various kinds of chamber tests, the standard and additional series of patch-tests, mix of allergens, information about allergens comprising the European Standard Series.

[A new case of systemic contact eczema to nickel in a peripheral venous catheter]. / Eczéma de contact systémique au nickel d'un cathéter périphérique : un nouveau cas.

BACKGROUND: Nickel-elicited systemic contact dermatitis is a rare event seen in previously skin sensitized patients. We report a case of systemic contact dermatitis due to nickel released into the bloodstream from a metal section of a catheter during infusion. CASE REPORT: A 39-year-old woman presented papular and vesicular flexural dermatitis and pompholyx 72h after cervical spine surgery. She received numerous treatments during the perioperative period. A challenge test with one of the suspected treatments, cefazolin, was performed by intravenous infusion over a six-hour period using the same Optiva) peripheral catheter (Johnson & Johnson, USA). Six hours after withdrawal of the catheter, an eruption occurred. A further cefazolin challenge test performed later under identical conditions but using a different type of catheter (nickel-free) was negative. Nickel-elicited systemic contact dermatitis due to nickel release from a catheter was diagnosed. The patient's medical history was notable for contact dermatitis with jewellery. Patch tests confirmed marked nickel sensitization. DISCUSSION: A little-known way of systemic nickel absorption is through insertion of a venous catheter with a metal section containing nickel and a metallic eyelet containing nickel can in fact remain in place after catheter placement. Nickel can thus be released into the circulation during infusion and an eruption may occur during the postoperative period. This diagnosis is noteworthy as such eruptions can easily be mistakenly diagnosed as cutaneous drug eruptions.

Recombinant proteins and peptides as tools for studying IgE reactivity with low-molecular-weight glutenin subunits in some wheat allergies.

Two genes of wheat low-molecular-weight glutenin subunits (LMW-GS), B16 and P73, were cloned and expressed in E. coli. They were homologous to proteins encoded respectively at Glu-B3 and Glu-D3 loci. The N-terminal and C-terminal halves of B16 (NB16 and B16C) and the two chimeras combining the halves of the two genes (B16-P73 and P73- B16) were also expressed. All these constructs were compared for their reactivity with IgE from 24 patients suffering from different forms of wheat allergies. The results confirmed that LMW-GSs bound IgE in all adult allergies tested. Strong differences in reactivity between all the constructs were observed. They were disease-dependent. In wheat-dependent exercise-induced anaphylaxis (WDEIA), the reactivity of the constructs depended partly on common epitopes with omega-5 gliadins but also on differences in molecule conformation. The presence of NB16 in the constructs greatly influenced their IgE reactivity.

[Connubial contact dermatitis to an inhaled corticosteroid]. / Eczéma de contact par procuration à un corticoïde inhalé.

BACKGROUND: Inhaled corticosteroids are widely used in allergic asthma and rhinitis. They are most often used alone or sometimes in association. Allergic side-effects of inhaled corticosteroids are less frequent than those of topical corticosteroids. We report a case of a connubial dermatitis to a budesonide spray. OBSERVATION: A 3-year old boy was treated for asthma by budesonide (Pulmicort) and terbutaline (Bricanyl) aerosols with an inhalation chamber (Babyhaler). From the fourth day of treatment onwards, his mother had swollen and itchy lesions on the face with conjunctivitis several hours after the administration of the corticosteroids using the inhalation chamber. The last eruptions were marked by extensive lesions. The patient reported a worsening of her eruption when she was treated with a desonide cream (Tridesonit). Prick-tests conducted later on confirmed the contact allergy to budesonide and Pulmicort spray. They were also positive for Tridesonit cream and triamcinolone acetonide. Repeated open application tests with a 17-butyrate hydrocortisone cream (Locoid) for three weeks remainded negative. DISCUSSION: Our observation is original: allergic contact dermatitis to inhaled corticosteroids is rare, the clinical presentation mimicked angioedema although it was a delayed-type hypersensitivity, hypersensitivity was limited to group B corticosteroids and it was in fact a connubial contact dermatitis.

[Contact allergy to antiseptics: 75 cases analyzed by the dermato-allergovigilance network (Revidal)]. / Allergie de contact aux antiseptiques: 75 cas analysés par le réseau Revidal de dermato-allergovigilance.

AIM: To determine the clinical features of contact dermatitis caused by antiseptics and to ascertain whether the substance responsible is the antiseptic itself or the excipients. PATIENTS AND METHODS: A multicenter, retrospective study based on analysis of all cases reported over a 2-year period to the Dermato-Allergology Vigilance network known as Revidal. Each dossier contained details of the clinical characteristics of lesions, the incriminated antiseptic, the mode of exposure and the results of patch tests done with the antiseptic in question. RESULTS: 75 patients (mean age: 44 years) were sensitized to chlorhexidine (14 cases), hexamidine (20 cases), povidone iodine (14 cases), mercuric antiseptics (3 cases), triclocarban (Septivon, 17 cases), hexamidine-chlorhexidine-chlorocresol (Cytéal, 4 cases), or chlorhexidine surfactant (Hibiscrub), cetrimide or chlorhexidine digluconate (Diaseptyl) (1 case each). Exposure was therapy-related (68 cases), work-related (6 cases; 5 in health workers and 1 in a cattle farmer due to povidone-iodine) or related to cosmetics (1 case, hexamidine). The clinical features consisted mainly of localized contact dermatitis, although generalized eczema occurred in 9 cases due to hexamidine contact. Sensitization was due to the antiseptic itself (53 cases) or to the excipients alone (22 cases), particularly in the 17 cases caused by Septivon. In 27/75 cases (35%), patients exhibited polysensitization to antiseptics belonging to different chemical classes or to other topical drugs. CONCLUSION: Sensitization to antiseptics is probably not rare, with various sources of exposure being present in everyday life. Patch tests are essential for diagnosis in order to distinguish between antiseptic-related and excipient-related sensitization and to screen for polysensitization to topical drugs.

Phenotypic characterization of human CD4+ regulatory T cells obtained from cutaneous dinitrochlorobenzene-induced delayed type hypersensitivity reactions.

In this study, we describe the generation and characterization of cloned human CD4+ T lymphocyte populations that have infiltrated into cutaneous, 2,4-dinitrochlorobenzene-induced delayed type hypersensitivity reactions in healthy human subjects. It is shown that, in addition to T helper type 1 clones, elevated numbers of regulatory T clones, producing high levels of interleukin-10 and interleukin-5, but no measurable interleukin-4, were isolated from delayed type hypersensitivity reactions in four of six donors. A subsequent challenge with 2,4-dinitrochlorobenzene of two donors from whom only few interleukin-10-producing T cell clones had been generated after primary challenge, resulted in a decrease in the frequency of T helper type 1 clones and a strong increase in the number of interleukin-10-producing T helper type 2 and regulatory T clones. Culture supernatants from the latter cells, activated with anti-CD3 and anti-CD28 monoclonal antibody, inhibited alloantigen-mediated T cell proliferation which was, partly dependent on interleukin-10, and independent of transforming growth factor-beta. In addition, dendritic cells generated in vitro in the presence of these culture supernatants were impaired in their ability to induce alloantigen-induced proliferative responses. Differential expression of transcripts for the T1/ST2 molecule enabled a phenotypic distinction between resting regulatory T cells and T helper type 2 cells, but not between regulatory T cells and T helper type 1 cells. This experimental model provides a useful tool to isolate human inflammatory and anti-inflammatory T cell subpopulations and, furthermore, enables the study of the kinetics of their appearance into delayed type hypersensitivity reactions.