A Case of Acrodermatitis Dysmetabolica in a Child Affected by Citrullinemia Type I: When Early Diagnosis and Timely Treatment Are Not Enough.

An infant with a prenatal diagnosis of citrullinemia, who started standard treatment at birth (L-arginine; sodium benzoate and a personalized diet characterized by a low protein intake and supplementation of essential nutrients and amino acids), presented at 4 months of age with extended, progressive, and severe skin lesions consistent with acrodermatitis dysmetabolica. Guidelines for the diagnosis and management of urea cycle disorders underline that a low-protein diet places patients at risk of essential fatty acids, trace elements, and vitamin deficiency. At hospital admission, our patient had normal levels of zinc and alkaline phosphatases. The plasmatic amino acid profile revealed a severe and generalized deficiency. In particular, the serum levels of arginine, valine, and isoleucine were very low and the dermatitis did not improve until the blood levels of these amino acids increased. In our patient, skin lesions happened despite an early diagnosis of citrullinemia and timely treatment due to compliance issues as a consequence of linguistic barriers.

Promoting Integrated Care in Eczematous Dermatitis and Dry Sensitive Skin.

Sensitive skin exposed to external insults (i.e., allergens, chemicals, and radiation) becomes erythematosus, and with repeated aggravations may become chronically dry. This is often observed in atopic dermatitis and allergic contact dermatitis, two skin conditions that display key pathogenic components: barrier dysfunction, skewed inflammatory immune response, and pruritus. Recent studies have evidenced that oxidative stress is a possible fourth component of the pathogenesis of sensitive skin. In patients with persistent disease, new agents and combination therapies that target oxidative stress along with other hallmarks of dry and sensitive skin have depicted positive effects on clinical outcomes in infants with dry and sensitive skin. In this paper, we reviewed clinical registration studies of products that have been observed to reduce skin dryness with cosmetically acceptable effects. Overall, similar approaches may be explored to improve the management of dry skin across all age groups for better consistency in achieving treatment goals. (SKINmed. 2022;20:414-419).

Update on the Management of Pediatric Psoriasis: An Italian Consensus.

INTRODUCTION: Psoriasis affects children with a considerable burden in early life. Treating pediatric psoriasis is challenging also because of the lack of updated specific guidelines. With the recent approval of several biologics for pediatric psoriasis and the ongoing COVID-19 pandemic, the management of young psoriatic patients is facing major changes. A revision of treatment recommendations is therefore needed. METHODS: In September 2021, a board of six Italian dermatologists convened to update treatment recommendations. The board issued evidence- and consensus-based statements covering relevant areas of pediatric psoriasis, namely: assessment of psoriasis severity, management of children with psoriasis, and treatment of pediatric psoriasis. To reach consensus, the statements were submitted to a panel of 24 experts in a Delphi process performed entirely via videoconference. A treatment algorithm was produced. RESULTS: There was full consensus that psoriasis severity is determined by the extension/severity of skin lesions, site of lesions, and impact on patient quality of life. Agreement was reached on the need for a multidisciplinary approach to pediatric psoriasis and the importance of patient/parents education. The relevance of vaccinations, including COVID-19 vaccination, for psoriatic children was acknowledged by all participants. Management issues that initially failed to reach consensus included the screening for psoriasis comorbidities and early treatment with biologics to prevent them and the use of telemedicine to facilitate patient follow-up. There was full consensus that topical corticosteroids are the first choice for the treatment of mild pediatric psoriasis, while phototherapy and systemic therapy are used in children with moderate-severe psoriasis. According to the proposed treatment algorithm, biologics are the first line of systemic therapy. CONCLUSIONS: Targeted systemic therapies are changing the treatment of moderate-severe pediatric psoriasis, while topical corticosteroids continue to be the first choice for mild disease. Children-centered research is needed to further improve the treatment of pediatric psoriasis.

Treatment of severe psoriasis in children: recommendations of an Italian expert group.

This article provides comprehensive recommendations for the systemic treatment of severe pediatric psoriasis based on evidence obtained from a systematic review of the literature and the consensus opinion of expert dermatologists and pediatricians. For each systemic treatment, the grade of recommendation (A, B, C) based on the treatment's approval by the European Medicines Agency for childhood psoriasis and the experts' opinions is discussed. The grade of recommendation for narrow-band-ultraviolet B phototherapy, cyclosporine, and retinoids is C, while that for methotrexate is C/B. The use of adalimumab, etanercept, and ustekinumab has a grade A recommendation. No conventional systemic treatments are approved for pediatric psoriasis. Adalimumab is approved by the European Medicines Agency as a first-line treatment for severe chronic plaque psoriasis in children (≥ 4 years old) and adolescents. Etanercept and ustekinumab are approved as second-line therapy in children ≥ 6 and ≥ 12 years, respectively. CONCLUSION: A treatment algorithm as well as practical tools (i.e., tabular summaries of differential diagnoses, treatment mechanism of actions, dosing regimens, control parameters) are provided to assist in therapeutic reasoning and decision-making for individual patients. These treatment recommendations are endorsed by major Italian Pediatric and Dermatology Societies. What is Known: • Guidelines for the treatment of severe pediatric psoriasis are lacking and most traditional systemic treatments are not approved for use in young patients. Although there has been decades of experience with some of the traditional agents such as phototherapy, acitretin, and cyclosporine in children, there are no RCTs on their pediatric use while RCTs investigating new biologic agents have been performed. What is New: • In this manuscript, an Italian multidisciplinary team of experts focused on treatment recommendations for severe forms of psoriasis in children based on an up-to-date review of the literature and experts' opinions.

Randomized, controlled, double-blind clinical study evaluating the safety and efficacy of MD2011001 cream in mild-to-moderate atopic dermatitis of the face and neck in children, adolescents and adults.

INTRODUCTION: This mono-center randomized, controlled, double-blind study evaluates the safety and efficacy of MD2011001 cream versus placebo, in mild-to-moderate atopic dermatitis (AD). MD2011001 is a nonsteroidal topical cream containing vitamin E, epigallocatechin gallate and grape seed procyanidins. METHODS: Patients with AD (corresponding to an IGA score of 2 or 3), involving the face, the perioral/periocular area and/or the neck, were enrolled. Patients were randomized 1:1 ratio to receive MD2011001 or placebo before the start of the study (D0), then evaluated after 7 days, and after 28 days. The study was approved by the Local Independent Ethics Committee and conducted according to the Declaration of Helsinki and local regulations. The statistical tests used were the Wilcoxon test and the Mann-Whitney U-test. RESULTS: Forty-four patients (29F and 15M) were enrolled. The IGA values showed a statistically significant reduction during the treatment period obtaining a favorable safety profile and local tolerance for both the products. The reduction in the surface area affected by AD was significantly faster with MD2011001. DISCUSSION: This study focuses on very sensitive areas known to be particularly susceptible to local complications. CONCLUSIONS: These results suggest the usefulness of an emollient treatment for mild/moderate AD.

A novel HPLC-electrochemical detection approach for the determination of D-penicillamine in skin specimens.

D-penicillamine is a thiol drug mainly used for Wilson's disease, rheumatoid arthritis and cystinuria. Adverse effects during normal use of the drug are frequent and may include skin lesions. To evaluate its toxic effects in clinical cases an original method based on high performance liquid chromatography coupled to amperometric detection in a specific biological matrix such as skin has been developed. The chromatographic analysis of D-penicillamine was carried out on a C18 column using a mixture of acid phosphate buffer and methanol as the mobile phase. Satisfactory sensitivity was obtained by oxidizing the molecule at +0.95 V with respect to an Ag/AgCl reference electrode. A chemical reduction of D-penicillamine-protein disulphide bonds using dithioerythritol combined with microwaves was necessary for the determination of the total amount of D-penicillamine in skin specimens. A further solid-phase extraction procedure on C18 cartridges was implemented for the sample clean-up. The whole analytical procedure was validated: high extraction yield (>91.0%) and satisfactory precision (RSD<6.8%) values were obtained. It was successfully applied to skin samples from a patient who was previously under a long-term, high-dose treatment with the drug and presented serious D-penicillamine-related dermatoses. Thus, the method seems to be suitable for the analysis of D-penicillamine in skin tissues.

Plaque stage mycosis fungoides treated with bexarotene at low dosage and UVB-NB.

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL), a non-Hodgkin lymphoma characterized by proliferation of atypical epidermotrophic helper/memory T cells in the skin. Therapeutic management includes topical therapy such as topical corticosteroids, topical chemotherapy or phototherapy; or systemic therapy such as photochemotherapy (psoralen and ultraviolet A [PUVA]), extracorporeal phototherapy, radiation, and mono or polychemotherapy. Herein we report one case of MF unresponsive to conventional therapy, subsequently treated with bexarotene and narrow-band ultraviolet B (UVB-NB). Bexarotene belongs to a new subclass of retinoids, binding primarily the nuclear hormone receptors RXRs. Bexarotene has the same effect as its natural counterpart: 9-cis-retinoic acid. Bexarotene may be used alone or in association with interferon alfa, interferon gamma, extracorporeal photophoresis and PUVA. We utilized 75 mg/day of bexarotene associated with 0.3 J/cm(2) UVB-NB as an initial dose. The sessions were three times weekly and the irradiation was increased by 30% at each session to reach a maximum of 1.6 J/cm(2). After 8 week treatment, clinical lesions markedly improved without recording hypercholesterolemia or hypothyroidism. During the follow-up no relapses were detected. We suggest that the combined therapy UVB-NB and bexarotene may be considered as an alternative treatment to PUVA and bexarotene.

A double-blind, randomized, vehicle-controlled clinical study to evaluate the efficacy and safety of MAS063DP (ATOPICLAIR) in the management of atopic dermatitis in paediatric patients.

A multicenter, randomized, double-blind, vehicle-controlled clinical study was conducted to evaluate the efficacy and safety of MAS063DP in 60 paediatric patients affected by atopic dermatitis (AD), aged between 2 and 17 years. Using the Investigator's Global Assessment (IGA) score for AD, patients with a score of 2 (mild) or 3 (moderate) were enrolled in the study. Patients were randomly selected to receive MAS063DP (20 patients), MAS060 (20 patients, a similar formulation with lower key ingredients' concentration and no preservatives) or vehicle (20 patients).The study consisted in a treatment period of 43 days, with clinical evaluations at baseline (day 1), days 8, 15, 22, 29 and 43, at which time the treatment was stopped. MAS063DP showed nearly 80% improvement in IGA score at day 22, compared with 16.6% and 26.3% with the MAS060 and vehicle respectively. A statistically significant difference was found by comparing MAS063DP with MAS060 (p < 0.0001); a similar result was evidenced comparing MAS063DP and vehicle (p = 0.001). By contrast, no significant difference was found between MAS060 and vehicle. A statistically significant difference was sustained until the end of the study. MAS063DP may therefore be considered as one of the available regimens effective in the treatment of mild-to-moderate AD in children and adolescents.