Management of Ocular Manifestations of Atopic Dermatitis: A Consensus Meeting Using a Modified Delphi Process.

There is a need for unified guidance on the management of ocular manifestations of atopic dermatitis and ocular manifestations associated with dupilumab in the Nordic region (Denmark, Finland, Norway and Sweden). This initiative gathered Nordic dermatologists and ophthalmologists to identify consensus in this area using a modified Delphi process. The initiative was led by a Nordic expert panel who developed a questionnaire that was circulated to a wider group. The results informed an agenda consisting of 24 statements to be voted on using a 5-point Likert scale at a meeting in Copenhagen on 24 April 2019. A facilitator moderated discussion and revised statements according to expert feedback for a second vote when required to reach consensus. Consensus was reached for 23 statements regarding the diagnosis, treatment and referral of these patients, which we hope will improve patient management in the Nordic region.

The Value of FLG Null Mutations in Predicting Treatment Response in Atopic Dermatitis: An Observational Study in Finnish Patients.

The contribution of filaggrin null mutations to predicting atopic dermatitis (AD) treatment response is not clear, nor have such mutations been studied in the Finnish population. This study tested the association of the 4 most prevalent European FLG null mutations, the 2 Finnish enriched FLG null mutations, the FLG 12-repeat allele, and 50 additional epidermal barrier gene variants, with risk of AD, disease severity, clinical features, risk of other atopic diseases, age of onset, and treatment response in 501 patients with AD and 1,710 controls. AD, early-onset AD, palmar hyperlinearity, and asthma showed significant associations with the combined FLG null genotype. Disease severity and treatment response were independent of patient FLG status. Carrier frequencies of R501X, 2282del4, and S3247X were notably lower in Finns compared with reported frequencies in other populations. This data confirms FLG mutations as risk factors for AD in Finns, but also questions their feasibility as biomarkers in predicting treatment response.

Long-term efficacy and tolerability of tacrolimus 0.03% ointment in infants:* a two-year open-label study.

BACKGROUND: Tacrolimus ointment is effective for treatment of moderate to severe atopic dermatitis (AD) in children aged ≥2 years (Br J Dermatol, 2004; 150: 554). Here, efficacy and tolerability of tacrolimus 0.03% ointment were evaluated in 50 infants aged <2 years at start of treatment. METHODS: Infants with AD previously enrolled in a tacrolimus ointment pharmacokinetics trial were eligible for a 24-month open-label phase II study. Tacrolimus 0.03% ointment was applied to affected areas until clearance. In cases of exacerbation or clinical worsening, patients restarted treatment. RESULTS: Mean ± SD Eczema Area and Severity Index (EASI) score improved, from 11.2 ± 10.5 baseline to 2.6 ± 4.1 at endpoint (24 months); mean affected body surface area decreased from 25.2 ± 21.1% to 5.1 ± 9.0%, with improvement on all items of the Physicians' Assessment of Individual Signs. The Physicians' Global Evaluation of Clinical Response showed a result of "cleared"/"excellent" for 63.3% of patients; 85.7% of parents/guardians assessed symptoms as "much better." Treatment was well tolerated, with common, nonserious respiratory infections and gastroenteritis the most frequently reported adverse events. The most common application-site events were infections and pruritus. Over 98% of blood samples showed tacrolimus concentrations <1.0 ng/ml; >40% showed concentrations below the lower limit of quantification (0.0250 ng/ml). CONCLUSIONS: Over a period of two years, tacrolimus 0.03% ointment was associated with substantial clinical improvement of AD in infants aged <2 years. Treatment tolerability was similar to that seen in older children.

A 10-year open follow-up of eczema and respiratory symptoms in patients with atopic dermatitis treated with topical tacrolimus for the first 4 years.

OBJECTIVES: To examine the 10-year outcome of affected body surface area (BSA), respiratory symptoms, and serum IgE in adult AD patients 6 years after a 4-year intervention with topical tacrolimus. METHODS: Patients who 10 years ago participated in a 4-year, open tacrolimus study (n = 65) were contacted for assessment of affected BSA, bronchial hyper-reactivity (BHR), respiratory symptoms, skin prick tests and serum IgE. RESULTS: Altogether, 50 (77%) patients attended the follow-up visit. The median affected BSA decreased from 19% to 1.6% during the 10-year follow-up (p < 0.0001). Patients with active asthma and rhinitis symptoms at baseline reported a significant decrease at the follow-up (p = 0.02 andp = 0.01). In patients with BHR at baseline, the provocative dose of inhaled histamine producing a 15% decrease in FEV(1) increased. Responders (>or= 60% improvement of affected BSA) to tacrolimus treatment at the 1-year visit had a significantly smaller affected BSA at the 4- and 10-year visits than non-responders (< 60% improvement). Responders also showed a significant decrease in serum IgE at the follow-up visit compared to baseline (p = 0.002). CONCLUSIONS: The long-term, effective treatment of patients with AD may have a beneficial effect on affected BSA, respiratory symptoms, and serum IgE.

One-year treatment with 0.1% tacrolimus ointment versus a corticosteroid regimen in adults with moderate to severe atopic dermatitis: A randomized, double-blind, comparative trial.

A one-year, randomized, double-blind study was conducted in 80 patients with atopic dermatitis treated with tacrolimus ointment or a corticosteroid regimen (hydrocortisone acetate 1% ointment for head and neck, hydrocortisone butyrate 0.1% ointment for trunk and limbs) to compare efficacy and safety, and effects on Th2-reactivity. The study was completed by 36/40 patients in the tacrolimus group, and 31/40 patients in the corticosteroid group. In both groups affected body surface area, eczema area and severity index, and transepidermal water loss decreased at months 6 and 12. Tacrolimus was superior for all efficacy scores at month 6, and in the head and neck area at month 12. Recall antigen reactivity increased at month 12 in both groups. Adverse events were reported by 40/40 patients in the tacrolimus, and by 34/40 patients in the corticosteroid group. Long-term treatment with topical tacrolimus or a corticosteroid regimen improves atopic dermatitis and recall antigen reactivity, suggesting an improvement in the Th1/Th2-balance.

The pharmacokinetics of tacrolimus after first and repeated dosing with 0.03% ointment in infants with atopic dermatitis.

BACKGROUND: In adults and children aged > 2 years, systemic absorption of tacrolimus from tacrolimus ointment is very low. In this study, the pharmacokinetics of tacrolimus 0.03% ointment were investigated in infants aged 3-24 months. METHODS: The pharmacokinetics of tacrolimus after first and repeated topical application of tacrolimus 0.03% ointment were evaluated in 53 infants (age, 3-24 month) with atopic dermatitis requiring treatment with mid-potency topical corticosteroids. Patients were grouped according to percentage of body surface area affected (Group 1: 5-20%; Group 2: > 20-40%; Group 3: > 40%). After stratification, patients were randomized (double-blind) to receive once-daily or twice-daily tacrolimus 0.03% ointment. RESULTS: Blood samples taken on days 1 and 14 (first and last application) showed minimal systemic tacrolimus exposure. Overall, 97% of blood samples assayed contained tacrolimus concentrations < 1 ng/ml, and 20% were below the lower limit of quantification (0.025 ng/ml). Systemic tacrolimus exposure was variable, but tended to increase as the treated body surface area increased. Mean apparent half-life of tacrolimus was 80 +/- 35 h (range: 25-175 h). Most patients experienced substantial clinical improvement in their atopic dermatitis. There were no clinically significant changes in laboratory values, and the most frequently reported adverse events were minor infections and local skin irritations. CONCLUSIONS: Tacrolimus 0.03% ointment in infants is associated with very low systemic exposure to tacrolimus. Treatment was well tolerated and led to considerable clinical improvement.