Efficacy and safety of biologics and small molecules for psoriasis in pediatric and geriatric populations. Part II: focus on elderly patients.

INTRODUCTION: The management of moderate-to-severe forms of psoriasis is becoming a frequent concern in geriatric age due to the higher risk to develop treatment adverse events, logistic issues, vulnerability to immune-related diseases and cancer, presence of comorbidities and the risk of drug interactions. In this context, traditional systemic treatments are often contraindicated, and biologic drugs and small molecules seem to be a valuable option. However, data on their effectiveness and safety in elderly patients are scant. AREAS COVERED: The aim of this review is to analyze the current literature in order to point out data on the efficacy and safety of biologic drugs and small molecules for the management of psoriasis in elderly patients in order to put the basis for universally shared treatment algorithm following available evidence. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used for the literature research. EXPERT OPINION/COMMENTARY: Our review suggests biologics and small molecules as an effective and safe option for the management of moderate-to-severe forms of psoriasis in elderly patients.

Efficacy and safety of biologics and small molecules for psoriasis in pediatric and geriatric populations. Part I: focus on pediatric patients.

INTRODUCTION: Psoriasis management is challenging, especially in pediatric age for different factors. The introduction of biologic drugs and oral small molecules (OSM) revolutionized the armamentarium of available weapons in psoriasis treatment. Despite the use of these drugs in adult patients has been widely investigated, pediatric patients have often been unconsidered in clinical trials and real-life studies. However, the high efficacy and speed of action, the safety profile and the ease-to-use administration make these innovative drugs an invaluable therapeutic opportunity. AREAS COVERED: The aim of this manuscript is to perform a review of the current literature examining data on the effectiveness and safety of biologic drugs and OSM for the management of psoriasis in pediatric patients in order to put the basis for universally shared treatment algorithm following available evidence. PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines were used for the literature research. EXPERT OPINION/COMMENTARY: Our review based on currently available evidence suggests biologics and OSM as an ideal treatment option for pediatric patients, with an excellent profile in terms of efficacy and safety as compared to traditional systemic drugs.

New Developing Treatments for Molluscum Contagiosum.

A large variety of treatments for molluscum contagiosum (MC) are available, but none are Food and Drug Administration (FDA) approved and there is no consensus on the optimal approach, mainly owing to a lack of high-level data. Physical modalities are widely used, but require repeated outpatient visits for administration, are painful and difficult to perform in children, and are associated with the possibility of residual scarring and post-inflammatory hypo- or hyperpigmentation. Two experimental topical drugs, a new standardized preparation of topical cantharidin, called VP-102, and a topical nitric oxide (NO)-releasing product containing berdazimer, called SB206, represent promising products that have been designed to overcome the limitations of current treatments. They have recently shown good results in terms of safety and efficacy in large cohorts of patients in phase III studies and have the potential to be the first FDA-approved therapies for the treatment of MC.

An Unusual Case of Pemphigus Vulgaris.

Introduction: Pemphigus is a potential life-threatening skin disorder belonging to the group of the autoimmune bullous diseases affecting the skin and mucosa. The most common subtypes are pemphigus foliaceus (PF) and pemphigus vulgaris. Case Presentation: We present the case of a young woman with scalp manifestations diagnosed as seborrhiasis who came to our office where a more careful history and clinical examination directed us toward another diagnostic suspicion. The histological examination confirmed our suspicion of pemphigus and therefore we believe it is important to report our experience to avoid misdiagnosis. Discussion/Conclusion: Our case may be useful in the literature to identify cases of PF with atypical manifestations that may mimic other diseases.

Tetracyclines and photosensitive skin reactions: A narrative review.

Tetracyclines are a group of broad-spectrum antibiotics largely employed in infectious, dermatological and surgical fields. Some adverse events may occur during treatment, including photosensitivity reactions, which are divided in phototoxic or photoallergic. We performed a systematic search on Pubmed, Cochrane and Embase from database inception to August 9, 2020 aim to summarize all available papers on photosensitive reactions related to tetracyclines in all clinical settings where they are used on human being. On the basis of our inclusion criteria, we selected only randomized controlled trials, open comparative trials and prospective cohort studies performed on both volunteers and patients, moreover we included a pharmacovigilance register. Thirty-eight articles met inclusion criteria, describing photo-sensitive effects due to doxycycline, minocycline, tetracycline, lymecycline, sarecycline, demethylchlortetracycline, chlortetracycline and metacycline, across six diagnoses (acne, Lyme disease, Gulf Veteran Illness, adbominal aortic aneurysms, traveler's diarrhea and pterygium) and several volunteers who were deliberately exposed to natural or artificial light sources. Not all drugs belonging to tetracyclines class are available to date, moreover the studies included lacked a homogeneous design and most of them involved a scarce number of patients, including reactions induced in volunteers during photo-testing. Available data on incidence, severity and clinical relevance of tetracyclines-related photo-sensitive reactions are scarce, heterogeneous and weak. What we can extrapolate is that some tetracyclines are more often related to phototoxic skin reactions than others and some of those seem to have a very low risk of phototoxicity.

Ultraviolet radiation, vitamin D, and COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become pandemic on March 11th, 2020. COVID-19 has a range of symptoms that includes fever, fatigue, dry cough, aches, and labored breathing to acute respiratory distress and possibly death. Health systems and hospitals have been completely rearranged since March 2020 in order to limit the high rate of virus spreading. Hence, a great debate on deferrable visits and treatments including phototherapy for skin diseases is developing. In particular, as regards phototherapy very few data are currently available regarding the chance to continue it, even if it may be a useful resource for treating numerous dermatological patients. However, phototherapy has an immunosuppressive action possibly facilitating virus infection. In the context of COVID-19 infection risk it is important to pointed out whether sunlight, phototherapy and in particular ultraviolet radiation (UV-R) constitute or not a risk for patients. In this review we aimed to focus on the relationship between UV-R, sunlight, phototherapy, and viral infections particularly focusing on COVID-19.

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

Impact of sun exposure on adult patients affected by atopic dermatitis.

BACKGROUND: Atopic dermatitis management is challenging and usually requires intermittent or continuous, long-term treatment with topical and/or systemic anti-inflammatory agents and appropriate skin care. Most patients affected by atopic dermatitis improve during sun exposure. It has been reported that the change from a subartic/temperate to a subtropical climate for 4 weeks improved significantly skin symptoms and quality of life in children, even for 3 months after return. However, until now the effect of sun exposure on adult patients with atopic dermatitis has never been investigated. METHODS: We conducted a retrospective study to assess the short-term effect of sun exposure during summer holidays on skin symptoms of adults affected by AD. RESULTS: One hundred and fourteen patients were enrolled in the study (62 males; aged 18-72 years, mean age 35.3±12.6). Seventy-three out of 114 patients (64%) spent their holidays at the seaside, and 41/114 (36%) in the mountains; 38/41 (92.7%) subjects from the latter group reported that during their holidays they frequented outdoor swimming pools or solariums almost every day of their vacation. The sunlight effect was considered beneficial by 68/114 (59.6%) of patients. In particular, 38/114 patients (33.3%%) reported the improvement of AD and 30/114 (26.3%) the complete resolution of the disease during summer holiday. CONCLUSIONS: Our data seem to suggest that sun exposure is beneficial in most patients, but not in all patients. In fact, sun exposure does not appear to improve skin symptoms or even aggravate them in about 4 out of 10 patients. This could be particularly important also considering ongoing climate changes that may affect the clinical history of several skin diseases, among which AD.

A Critical Reappraisal of Off-Label Use of Photodynamic Therapy for the Treatment of Non-Neoplastic Skin Conditions.

BACKGROUND: In the past 30 years, topical photodynamic therapy (PDT) has been investigated for the treatment of a broad spectrum of cosmetic, inflammatory, and infectious skin conditions with variable, and often contrasting, results. However, the non-expert clinician may be in difficulty evaluating these results because different sensitizers, concentrations, formulations, light sources, and irradiation protocols have been used. In addition, many of these studies have poor quality design being case reports and uncontrolled studies of few cases. SUMMARY: With the aim to clarify the potential usefulness of PDT for the treatment of infectious and inflammatory skin diseases as well as selected cosmetic indications, we searched for randomized controlled clinical trials, non-randomized comparative studies, retrospective studies, and case series studies with a number of at least 10 patients, published since 1990. Later, we reappraised the results in order to give a simple critical overview. Key Messages: Evidence from the literature seems to strongly support the use of ALA- and MAL-PDT for the treatment of common skin diseases such as acne, warts, condylomata, and Leishmania skin infection and for photorejuvenation, i.e., the correction of selected cosmetic changes of aging and photoaging. For other disorders, the level of evidence and strength of recommendation are lower, and controlled randomized studies with prolonged follow-ups are necessary in order to assess the clinical usefulness and other potential advantages over current treatment options.

Hidradenitis Suppurativa in a Patient Affected by Mayer-Rokitansky-Küster-Hauser Syndrome: Insight into the Role of Hormones in HS.

INTRODUCTION: Hidradenitis suppurativa (HS) is an inflammatory skin disease, which usually occurs after puberty. Even if the pathogenesis of HS is still unproven, numerous studies hypothesized that the disease is triggered by genetic and environmental factors, with hormones playing a central role. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital malformation in which a failure of Müllerian duct development results in absent uterus and fallopian tubes and malformations of the vagina. CASE PRESENTATION: A 38-year-old Caucasian female referred at our outpatient clinic affected by HS. Before the appearance of HS manifestations, the patient referred to a gynecologist due to difficulties in getting pregnant. The sonographic findings were consistent with MRKH syndrome. An ovarian stimulation for in vitro fertilization was started. However, after 3 months the patient showed the first HS onset. After the hormonal treatment ended, a combined treatment with rifampicin and clindamycin was started, showing a great clinical improvement at week 10. DISCUSSION/CONCLUSION: HS usually appears after puberty, exhibits premenstrual flare, improves in pregnancy, and worsens postpartum, which indicates a role of hormones and particularly of androgens in its pathophysiology. Contrasting data are reported in the literature. Our case wants to strengthen the idea that hormones could play an important role, probably with other endogenous or exogenous factors. Multidisciplinary investigations will clarify which part is played by each factor in the pathogenesis of HS.

Effectiveness of a combination of salicylic acid-based products for the treatment of mild comedonal-papular acne: a multicenter prospective observational study.

BACKGROUND: The most common therapeutic approach to acne is a combined treatment of retinoid and benzoyl peroxide, with oral antibiotics recommended for moderate-to-severe cases. These kinds of therapies often lead to adverse reactions, leading to the request for new therapeutic options. Recently, the combined use of three salicylic acid-based products for the topical treatment of acne has been related to a significant improvement in acne lesions. METHODS: A multicenter prospective observational study was carried out on patients with a diagnosis of mild comedonal-papular facial acne to provide new evidence on the clinical effectiveness, tolerability and acceptability of three salicylic acid-based products for the topical treatment of acne in the daily clinical practice. Clinical effectiveness on lesions improvement, the evaluation of personal discomfort related to acne and the assessment of overall clinical outcome were the primary endpoints. Treatment acceptability and tolerability were also evaluated. RESULTS: The treatment with the three salicylic acid-based products has been related to a significant improvement on acne lesions over 8 weeks of treatment, along with a reduction of personal discomfort related to acne and an improvement on lesions appearance. The products have also shown good acceptability and tolerability. CONCLUSIONS: The results of this observational study support the effective and well-tolerated use of a combined treatment with three salicylic acid-based products for the topical treatment of acne.

Milk thistle and olive extract: old substances with a new mission against sun-induced skin damage.

BACKGROUND: Natural antioxidants represent an effective option in the prevention and/or improvement of ultraviolet radiations (UVR)-induced/aggravated skin conditions. UVR cause DNA damage in keratinocytes, directly, in the form of cyclobutane pyrimidine dimers (CPDs), or indirectly, through oxidative stress production. Failure of the repair system can result in genetic mutations primarily responsible for the initiation of NMSCs. The aim of our study was to evaluate the in vitro protective effect of milk thistle and olive purified extracts on cultured keratinocytes after solar simulator irradiations (SSR). METHODS: Immortalized keratinocytes were pre-incubated with different concentrations of milk thistle and olive purified extracts, and irradiated with increasing doses of SSR. Thereafter, CPDs and p53 expression were evaluated to assess DNA damage, whereas cellular antioxidants consumption and lipid membranes peroxidation were measured to analyze oxidative stress. RESULTS: The study substances were well tolerated by cells and displayed good cytoprotective and antioxidant activities, being milk thistle dry extract more effective in limiting the direct DNA damage, and olive extract particularly able to reduce lipid membrane peroxidation and to increase cellular antioxidants. CONCLUSIONS: Both study substances can be defined as safe compounds, showing differential cytoprotective and antioxidant activities and might represent interesting options for NMSCs chemoprevention.

Melanoma frequency among symmetrical Spitzoid-looking lesions: a retrospective study.

BACKGROUND: Many efforts have been spent attempting to define clinical, histopathological and molecular markers for differential diagnosis of Spitz nevus and melanoma. Dermoscopy has been widely used but it may be not always sufficient. METHODS: A retrospective study was performed evaluating Spitzoid-looking lesions showing symmetry at clinical and dermoscopic examination in patients ≥12 years attending our Clinic from 2004 to 2014. Demographic, clinical and dermoscopic data were assessed for each lesion in order to highlight the most common characteristics which could help the differential diagnosis between Spitz nevus and melanoma when clinical or dermoscopic asymmetry is lacking. RESULTS: A total of 760 lesions were excised. 690/760 (90.8%), were identified as typical Spitz nevi, whereas 70/760 lesions (9.2%) consisted of malignant melanocytic lesions. Our study showed that almost 9.2% of clinically and dermoscopically symmetric Spitzoid lesions revealed to be malignant melanocytic lesion. For symmetric Spitzoid looking lesions female sex, clinical palpability, the presence of an inverse network at dermoscopic examination and the involvement of lower limbs were observed as the main factors, which were linked to a higher possibility of being malignant lesions. CONCLUSIONS: In order to avoid missing diagnoses for malignant melanocytic lesions, this study remarked the importance of preventive excision for all Spitzoid-looking lesions in patients ≥12 years, even if they show symmetry at both clinical and dermoscopic level.