Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

Real-life applicability of the Euroarray dermatomycosis kit in the diagnosis of onychomycosis.

BACKGROUND: Traditionally, KOH microscopy and fungal culture are the two preferred tests as gold standard for diagnosis of onychomycosis. Recently, other diagnostic methods have been developed to improve the microbiological diagnosis. The EUROArray dermatomycosis kit is a PCR-based microarray test system for the detection and direct identification of species that are most frequently involved in skin and nail infections. OBJECTIVES: Our primary aim was to evaluate the real-life applicability of the EUROArray dermatomycosis kit in the diagnosis of onychomycoses. In addition, we compared the aetiology of onychomycoses found in our patients with those described in the literature. PATIENTS/METHODS: We prospectively studied consecutive 100 patients with suspected onychomycoses. Samples of suspect toenails were taken as part of routine medical management. Nail specimens were evaluated by means of three diagnostic methods: KOH preparation, culture and EUROArray dermatomycosis kit. RESULTS: Onychomycosis was diagnosed in 47/100 patients who proved positive on at least one reference diagnostic test and in 49/100 patients who proved positive on PCR. The combination of microscopy and PCR had better sensitivity than microscopy (p = .0397), fungal culture (p = .0061) and PCR alone (p = .0117). Moulds were more frequently positive in culture than in PCR (p = .033). Dermatophytes proved positive more frequent than moulds and yeasts in both culture and PCR; in particular, Trichophyton interdigitale was the most frequent pathogen. CONCLUSIONS: In conclusion, introducing EUROArray dermatomycosis kit into the diagnostic algorithm of onychomycosis increases the sensitivity of direct microscopy and yields more rapid results than culture.

DECISA Project (DErmatology Clinics in Italy: Survey on Alitretinoin): A real-life retrospective cohort multicenter study on 438 subjects with chronic hand eczema.

Alitretinoin is the only systemic agent approved to treat moderate-severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. No nationwide Italian data regarding real-life efficacy, safety, and tolerability of treatment are available. The DECISA project (DErmatology Clinics in Italy: Survey on Alitretinoin) retrospectively examined data from a registry including 15 Dermatology Clinics authorized to prescription of alitretinoin for CHE patients. Disease severity was assessed at baseline, and after 3 and 6 months of treatment, using the 5-point Physician Global Assessment (PGA) and the modified Total Lesion-Symptoms-Severity (mTLSS) scores. Between November 2010 and July 2018, data of 248 male and 190 female patients (mean age 49.71 ± 13.20 years) treated with alitretinoin were collected. Of them, 43.2% had irritant contact dermatitis, 22.2% allergic contact dermatitis, 18.0% atopic dermatitis, 16.7% mixed (irritant/allergic) type of eczema. At 3 months, the 420 re-evaluated patients showed significantly reduced mTLSS and PGA (P < .0000001 vs baseline for both); PGA was clear/almost clear in 35.6% of cases. At 6 months, the 341 re-evaluated patients showed significant (P < .0000001) improvement of mTLSS and PGA vs baseline and 3 months (PGA clear/almost clear: 41.4%). Relapses occurred in 125 patients; 58 underwent an additional course of alitretinoin, with similarly good results. No relevant safety issues were reported; 86 patients experienced adverse effects, which forced 40 to prematurely stop treatment. The DECISA project results confirm the real-life efficacy, safety and tolerability of alitretinoin in the treatment of moderate to severe CHE refractory to standard topical therapies.

Real-life experience on effectiveness and tolerability of topical ivermectin in papulopustular rosacea and antiparasitic effect on Demodex mites.

Ivermectin is a drug approved for the treatment of papulopustular rosacea (PPR). Although clinical guidelines recommend the use of ivermectin as the first-line treatment in patients with almost clear and mild rosacea, studies concerning its use on them are lacking. This study investigated the effectiveness and the tolerability of ivermectin in almost clear to severe rosacea and assessed the antiparasitic effect on Demodex mites. This is a retrospective study based on 50 patients affected by PPR and treated with topical ivermectin 1% once daily over 16 weeks. The disease severity, the patient-examined improvement, and the safety assessment of patients were evaluated. Demodex mites were studied with the standardized skin surface biopsy. PPR to all severity achieved a therapeutic success. The number of inflammatory lesions was significantly decreased in almost clear (p < .0001), mild, moderate, and severe (p < .001) forms. A complete remission of inflammatory lesions was achieved by almost clear (p < .001) and mild (p = .005) with 82% with none-to-mild cutaneous adverse events. Thirty-two percent were positive for Demodex mites, and all of them turned negative after 16 weeks. Ivermectin is an effective treatment not only in moderate to severe PPR but also in almost clear/mild rosacea.

Follicular scales, scalp and ocular involvement in patients with papulopustular rosacea: prevalence and association with Demodex mite proliferation.

Facial follicular scales, dandruff, scalp itching and ocular alterations are lesser-known signs of rosacea and demodicosis. The aim of this prospective original study was to investigate the presence of these signs and symptoms in patients with almost-clear, mild and moderate papulopustular rosacea (PPR) and to study the differences between Demodex-positive (D+) and Demodex-negative (D-) rosacea. Twenty-seven out of 60 patients (45%) presented follicular scales, 24 (40%) ocular involvement and 22 (36.67%) scalp involvement. Follicular scales were more frequently observed in mild and moderate than in almost-clear rosacea (P<0.001). Itching of the scalp was more frequently reported in patients with moderate rosacea than in those with mild disease (P=0.05). Follicular scales (P=0.002) and scalp itching (P=0.05) were more frequently reported in D+ than in D- patients. Among D+ patients, scalp itching was more frequently reported in mild than in almost clear rosacea (P=0.01) and ocular symptoms associated to scalp itching were more frequently reported in moderate than in almost-clear rosacea (P=0.05). We suggest looking for these signs and symptoms in all patients with PPR, because they can be a sign of a more severe form of rosacea or of demod-icosis.

The impact of occlusive vs non-occlusive application of methyl aminolevulinate on the efficacy and tolerability of daylight photodynamic therapy for actinic keratosis.

BACKGROUND: Conventional photodynamic therapy (c-PDT) is an effective treatment for actinic keratoses (AKs) and nonmelanoma skin cancer which exploits the photosensitizing properties of methyl aminolaevulinate (MAL). Daylight photodynamic therapy (DL-PDT) is an alternative to c-PDT which does not require the application of MAL in occlusion and that is better tolerated by patients. The impact of occlusion on the efficacy of DL-PD has not been investigated by previous studies. OBJECTIVE: To compare the efficacy and tolerability of occlusive and non-occlusive DL-PDT. METHODS: We conducted a prospective intraindividual left/right comparison study. AKs of the face or scalp were marked in two symmetrical treatment areas. The two target areas were randomly assigned to DL-PDT with occlusive and non-occlusive application of MAL. The efficacy and cosmetic outcome were determined by a "blinded" investigator. RESULTS: Lesions in occluded areas showed a better response in the clearance rate of the lesions (65.5% vs 35.0 %, p < 0.001 %), and cosmetic outcome (P < 0.001). There was no difference in phototoxicity or pain between occluded and non-occluded areas. CONCLUSION: The occlusive application of MAL improves the efficacy of DL-PDT in clearing AKs and does not increase the incidence of side effects.

The new Italian SIDAPA Baseline Series for patch testing (2023): an update according to the new regulatory pathway for contact allergens.

Allergic contact dermatitis (ACD) is a common inflammatory skin disease caused by delayed hypersensitivity to chemical and biotic contact allergens. ACD significantly affects the patients' quality of life negatively impacting both occupational and non-occupational settings. Patch testing is the gold standard diagnostic in vivo test to precise the ACD etiology and to correctly perform prevention. According to the Italian Medicines Agency (AIFA) legislative decree no. 178 of 29th May 1991, allergens are defined as medicines and therefore they are subject to strict regulation. In 2017, AIFA (decree no. 2130/2017) started a procedure to regulate contact allergens on the Italian market and actually the contact allergens temporarily authorized are reported in AIFA decree no. 98/2022, valid until November 2023. The availability on the market of contact allergens to diagnose ACD and continuous updating on the basis of new epidemiological trends are mandatory, jointly with the continuous update of the baseline and integrative series for patch testing. For this reason, the scientific community represented in Italy by the Skin Allergies Study Group of SIDeMaST (Italian Society of Dermatology and Venereology) and SIDAPA (Italian Society of Allergological, Occupational and Environmental Dermatology) are constantly working, in close relationship with the European scientific communities with large expertise in this important sector of the modern Dermatology. Herein, we report the setting up of regulatory legislation by AIFA and the new Italian Adult Baseline Series for patch testing.