Incidence and risk factors for dupilumab associated ocular adverse events: a real-life prospective study.

BACKGROUND: Dupilumab is approved for use in moderate-to-severe atopic dermatitis (AD) and as an add-on maintenance treatment in patients suffering from severe asthma with type 2 inflammation. Ocular adverse events (OAEs) have been reported with dupilumab almost exclusively in patients treated for AD. OBJECTIVES: The objectives of this study were to describe the incidence and nature of dupilumab-induced OAEs and to assess the potential predisposing factors. PATIENTS AND METHODS: We conducted a prospective, single-centre, real-life study in adult AD patients treated with dupilumab, who were systematically examined by an ophthalmologist before and during treatment. RESULTS: Forty-six patients were included prospectively with a median age of 41.1 years and a median initial SCOring Atopic Dermatitis of 46.0 (IQR: 34.5-55.5). OAEs concerned 34.8% of patients and were mostly of mild to moderate severity. Two patients had to discontinue treatment due to OAE. The majority of patients developed or aggravated dry eye disease, with superficial punctate keratitis (SPK). Six patients developed conjunctivitis. Dupilumab-induced OAEs were associated with the following pre-existing parameters: dry eye disease with SPK (Odds ratio (OR); 6.3 [95% confidence interval (CI): 1.3-31.6]), eyelid eczema (OR: 8.7 [95%CI: 1.8-40.6]), history of food allergy (OR 3.8 (95% CI: 1.002-14,070) and IgE serum level> 1000 kU/L (OR:10.6 [CI 95%: 1.2-91.3]). CONCLUSION: Atopic dermatitis patients with eyelid eczema or dry eye disease symptoms may be referred to an ophthalmologist before starting dupilumab to consider initiating preventive eye hydration measures. Further multicentric and translational studies are warranted to better explain OAEs pathophysiology.

Stepwise approach of development of dermo-cosmetic products in healthy and atopic dermatitis paediatric population: safety evaluation, clinical development and postmarket surveillance.

BACKGROUND/OBJECTIVES: Paediatric skin, considered sensitive, and infant skin, more susceptible to percutaneous toxicity, require specially formulated cosmetic products. As recently shown, early use of emollients in infants "at risk" of developing atopic dermatitis has shown controversial results in reducing the incidence of atopic dermatitis. Development of dermo-cosmetic products for this specific population should especially ensure tolerance and safety. In absence of good clinical practice guideline, we propose here a stepwise approach for the development of paediatric cosmetic skincare products. METHODS: Our stepwise methodology for cosmetics aimed at paediatrics, starts with in vitro assessment of product's ingredients safety, followed by preclinical and clinical evaluations of the final product, including sequentially: (1) Repeated Open Application Test (ROAT), (2) Human Repeated Insult Patch Test (HRIPT), (3) In-use dermatological and ophthalmological tolerance studies (sequentially in 3a: healthy adults, 3b: healthy paediatric subjects and finally 3c: paediatric patients). We also describe the integrated cosmetovigilance-toxicological surveillance during the clinical development phase and postmarketing. RESULTS: As illustrated with one dermo-cosmetic product intended to be used as a preventative/maintenance treatment for atopic dermatitis in paediatric population, we show that using this stepwise methodology to test a product reduces potential risks of irritation and contact dermatitis in this sensitive population. CONCLUSION: Standardized ethical stepwise development approach is needed to ensure the commercialization of safe and well-tolerated dermo-cosmetics for paediatrics. The approach described here could potentially serve as guidance for evaluation of new paediatric cosmetic products.

[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.

Validation of a clinical evaluation score for irritative dermatitis: SCOREPI.

BACKGROUND: Most dermatological conditions can be evaluated using validate clinical scores, no such tool is available for irritant contact dermatitis (ICD). OBJECTIVE: To create and validate a grid-based ICD severity score. METHODS: Three dermatologists developed the SCOre de REparation de l'EPIderme (SCOREPI) grid. Two studies were conducted to validate the SCOREPI. A cross-sectional study assessed the intra- and inter-observer error associated with using the SCOREPI. Each investigator received 15 min of training on proper use of the SCOREPI. A computer displayed a series of 20 photos of ICD, each of which were repeated three times in a randomized order. The prospective study assessed the correlation between SCOREPI with the severity of clinical symptoms as well as the sensitivity of the score to changes in ICD in response to topical treatment. RESULTS: The SCOREPI took an average of 35 ± 5 s to be completed and was characterized by an excellent intra-observer and moderate inter-observer reproducibility (intra-class correlation coefficient = 0.93 and 0.74, respectively). Significant divergence was observed between the physicians' assessment of estimated surface (P = 0.04), the presence of erythema (P < 0.0001) and the number of deep cracks (P = 0.0008). In the prospective analysis of patients, SCOREPI was correlated with tightness (r = 0.45; P < 0.0001), pain (r = 0.45; P < 0.0001), burning (r = 0.42; P < 0.0001), and pruritus (r = 0.28; P = 0.0055). SCOREPI decreased considerably during follow-up from 10.45 ± 4.61 to 4.82 ± 4.15 (P < 0.0001). CONCLUSION: The SCOREPI is easy to use, sensitive to change, and characterized by high intra- and moderate inter-observer reliability.

Contact photoallergy to isothipendyl chlorhydrate.

Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel® (Merck Médication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies. This case confirms the need to keep the phenothiazines in the photopatch test standard series as a diagnostic marker of phenothiazine photoallergy.

[Severe drug hypersensitivity reaction (DRESS syndrome) to doxycycline]. / DRESS syndrome sous doxycycline.

BACKGROUND: While many cases of DRESS reaction to minocycline have been described, few of these involve doxycycline. CASE STUDY: A 59-year-old woman of African origin was repatriated after a journey to Ghana for hyperthermia with infiltrated maculopapular exanthema, facial oedema (no mucosal involvement) and polyadenopathy. Laboratory tests revealed hypereosinophilia, hepatic cytolysis and mononucleosis syndrome. Cutaneous histology was non-specific. The patient had been taking doxycycline as antimalarial prophylaxis for three weeks before the onset of symptoms. DRESS to doxycycline was diagnosed. Patch-tests with doxycycline three months later proved negative. The patient's HLA phenotype was A3/A30 and B39/B42. DISCUSSION: An intrinsic causal relationship with doxycycline was likely in this case (I3). Although patch-test sensitivity and specificity with doxycycline remains unknown in DRESS exploration, a negative result does not necessarily rule out the diagnosis. A number of cases of DRESS to doxycycline have been described recently, possibly as a result of more frequent prescription (malarial prophylaxis, acne). Subjects of African ethnicity or having specific HLA phenotypes are at higher risk of developing drug hypersensitivity. CONCLUSION: This patient is the third case of DRESS to doxycycline described in the literature. The originality of this case lies in the allergological investigation using patch-tests and HLA determination.

Prevalence and risk factors for allergic contact dermatitis to topical treatment in atopic dermatitis: a study in 641 children.

BACKGROUND: There is little information regarding the risk of sensitization associated with topical atopic dermatitis (AD) treatment. OBJECTIVES: To assess the frequency of sensitization to topical treatment of AD in children and to determine risk factors associated with skin sensitization. METHODS: Six hundred and forty-one children with AD were systematically patch tested with seven agents of common topical treatment: chlorhexidine, hexamidine, budesonide, tixocortol pivalate, bufexamac, sodium fusidate and with the current emollient used by the child. The following variables were recorded: age, sex, age at onset of AD, associated asthma, severity of AD, and history of previous exposure to topical agents used in the treatment of AD. Skin prick tests to inhalant and food allergens were used to explore the IgE-mediated sensitization. RESULTS: Forty-one positive patch tests were found in 40 patients (6.2%). Allergens were emollients (47.5%), chlorhexidine (42.5%), hexamidine (7.5%), tixocortol pivalate and bufexamac (2.5% each). Risk factors associated with sensitization to AD treatment were AD severity [OR: 3.3; 95% confidence interval (CI):1.5-7.1 for moderate to severe AD], AD onset before the age of 6 months (OR: 2.7; 95% CI: 1.2-6.1), and IgE-mediated sensitization (OR: 2.5; 95% CI: 1.1-5.9). CONCLUSIONS: Topical treatment of AD is associated with cutaneous sensitization. Antiseptics and emollients represent the most frequent sensitizers and may be included in the standard series in AD children when contact dermatitis is suspected. Risk factors associated with sensitization to AD topical treatments are AD severity, early AD onset and IgE-mediated sensitization.

[Avoidance lists]. / Listes d'éviction.

In the event of contact dermatitis, delivery of avoidance lists is an essential step towards recovery. Lists must be clear enough to be able to be easily understood by the patient, as well as being exhaustive and regularly updated. Recent and complete avoidance lists (allergens from the European Standard Series and others) can be obtained from various sources such as books, scientific publications, CD-ROM and websites, which will be listed in this article.

[Cutaneous hypersensitivity at the site of injection of vitamin K1]. / Hypersensibilité cutanée au point d'injection de vitamine K1.

INTRODUCTION: Skin reactions after vitamin K injections are uncommon and only seen with vitamin K1 (phytomenadione). Possible association with liver disease is debated. The pathophysiological mechanism would be related to hypersensitivity to phytomenadione. CASE REPORT: Two new cases of hypersensitivity reactions at the point of vitamin K1 injection are reported. Neither of the patients had liver disease. DISCUSSION: Injectable vitamin K1 can cause skin reactions whatever the dose and mode of injection. Two clinical presentations have been described: an acute eczematous aspect and a late onset sclerous and atrophic form. The first cases of hypersensitivity to vitamin K were reported in patients with liver disease. Several recent publications did not find such an association. Our two observations would confirm this hypothesis. The pathophysiological mechanism of the acute form would involve type IV allergy to phytomenadione as suggested by the delay between sensitization and reactivation, the histology, the patch tests which are positive with phytomenadione and negative with the carrier and the presence of reaction at rechallenge. However, the lack of the necessary sensitization phase and abnormally slow regression of eczematous lesions are unusual and might be explained by a particularly active antigenic effect of the phytomenadione molecule possibly related to the phytyl moiety.

[Contact eczema induced by propylene glycol. Concentration and vehicle adapted for for patch tests]. / Eczéma de contact au propylène glycol. Concentration et véhicule adaptés pour les tests épicutanés.

INTRODUCTION: Contact dermatitis to propylene glycol, a widely used compound, is often difficult to evidence with skin tests. CASE REPORTS: We observed three cases of contact eczema to a dermal cream (Zovirax) used for labial herpes simplex. Patch-tests were positive in all three cases when the entire product was used but negative for each of the constituent components. The initial diagnosis could be an allergic reaction to the composition between the components as has been described elsewhere. Skin tests were completed with patch-tests using propylene glycol at concentrations over 5 p. 100 or with a vehicle other than vaseline (commercial tests use 5 p. 100 propylene glycol in vaseline). The results of these tests provided evidence allowing the diagnosis of contact dermatitis to the dermal cream due to allergic reaction to propylene glycol. DISCUSSION: Our three cases illustrate the frequency of false negative reactions to propylene glycol on commercial patch-tests. In agreement with data in the literature, these tests show that propylene glycol must be used at concentrations up to 10 to 20 p. 100 to identify allergic reactions with patch-tests.

[Contact allergy to beta blockaders in eye drops: cross allergy?]. / Allergie de contact aux beta bloqueurs des collyres: allergie croisée?

INTRODUCTION: Beta-blockers in eye-drops are widely used for the treatment of glaucoma. The potential allergic effect was only recently recognized. CASE REPORT: A 65-year-old man had been treated with eye-drops containing beta-blockers for bilateral chronic glaucoma for 14 years. During the last two years, he developed eczema localized on the upper and lower eyelids. Allergy screening confirmed the implication of timolol and befunolol which had been used successively. Later prescription of eye-drops containing carteolol led to recurrence of the eczema. DISCUSSION: This case of contact allergy with three different beta-blockers in the same patient is similar to others reported in the literature. All beta-blockers have a similar chemical structure, but it cannot act as a haptene. The proposed hypothesis is a cross-sensitivity which develops after primary metabolism to a common aldehyde. The risk of recurrence is high if another beta-blocker eye-drop compound is prescribed in a sensitized patient. The risk of side effects in such sensitized patients when taking oral beta-blockers is unknown.

[Photoaggravated contact allergy and contact photoallergy caused by ketoprofen: 19 cases]. / Allergies de contact photoaggravées et photoallergies de contact au kétoprofène: 19 cas.

INTRODUCTION: Between September 1994 and September 1999, we observed 19 cases of photoaggraved contact allergy or contact photoallergy to ketoprofen (non steroidal anti-inflammatory derived from arylpropionic acid). We present a clinical and photobiological retrospective study of these 19 cases with investigation of cross-reactivity between benzophenone-containing molecules. PATIENTS AND METHODS: On clinical level, we investigated the type of eruption, the delay of appearance, the initial area of eruption and areas of diffusion. Phototesting included patchtests and photopatchtests performed with the gel containing ketoprofen (17 patients), ketoprofen 2 p. 100 petrolatum (14 patients), fenofibrate 10 p. 100 petrolatum and 10 p. 100 water (15 patients), 3 benzophenones (19 patients): oxybenzone 10 p. 100 petrolatum, mexenone 2 p. 100 petrolatum, sulisobenzone 10 p. 100 petrolatum and the other arylpropionic derivatives (4 patients). Three identical series were applied: one was irradiated with 3/4 polychromatic minimal erythematosus dose, a second was irradiated with UVA 13 J/cm2 until January 1997, then 5 J/cm2, the third series was not irradiated (control series). RESULTS: Patients were 9 men and 10 women with an average age of 41.2 years. The type of eruption was an eczema. The delay of appearance of the eruption was one day to 3 months. For 10 patients, the delay was between 4 and 18 days. The eruption was localized to the application area in 1 case, to the application area then to the same contralateral area in 3 cases, to the application area then to all photoexposed areas in 13 cases, to the application area then to the photoexposed areas and then to non-sun-exposed areas in 2 cases. Evolution showed prolonged photosensitivity in 3 cases after withdrawal of the contact and the contact photoallergy to ketoprofen was severe. Gel-containing ketoprofen photopatchtests showed 9 photoaggravated contact allergy, 6 contact photoallergy and 2 contact allergy. Ketoprofen photopatchtests showed 12 contact photoallergy and 2 photoaggraved contact allergy. Tiaprofenic acid photopatchtests were positive in all performed cases (4/4), but photopatchtests with the other arylpropionic derivatives, without benzophenone structure, were negative. Fenofibrate photopatchtests were always positive (15/15). Benzophenones photopatchtests only showed 4 cases of contact photoallergy to oxybenzone (4/19). In 68 p. 100 of cases, patients presented a contact allergy or photoallergy to fragrances. CONCLUSIONS: This study shows the actual frequency of contact allergy and contact photoallergy to ketoprofen with a higher frequency of contact photoallergy. Thus, photopatchtesting is essential. In cases of contact photoallergy to ketoprofen, ketoprofen, tiaprofenic acid but not the other arylpropionic derivatives, fenofibrate and benzophenones have to be withdrawn.

"Lucky Luke" contact dermatitis from diapers: a new allergen?

"Lucky Luke" contact dermatitis is a particular pattern of diaper dermatitis, reminiscent of a cowboy's gunbelt holsters (1).