Pain Control during the Treatment of Primary Palmar Hyperhidrosis with Botulinum Toxin A by a Topical Application of Liposomal Lidocaine: Clinical Effectiveness.

Primary palmar hyperhidrosis (PPH) constitutes a debilitating condition that profoundly impacts the social, functional, and occupational aspects of individuals. The intradermal administration of botulinum toxin type A (BoNT-A) stands as an established therapeutic approach for PPH, albeit one frequently accompanied by considerable pain, posing challenges for patient tolerance. Our study aimed to assess the efficacy of combining cryoanalgesia spray (CA) with topical anesthesia utilizing a cream containing liposomal lidocaine at a concentration of 40 mg/g, with the objective of mitigating the pain associated with intradermal BoNT-A injection for PPH treatment. Nineteen participants, aged ≥18 years and afflicted with severe PPH, were enrolled in a double-blind randomized vehicle-controlled trial. Patient-perceived pain during the procedure was quantified using the Numeric Rating Scale (NRS). Statistical analysis was applied to the collected data. The combination of CA and the topical application of liposomal lidocaine during BoNT-A treatment for PPH resulted in diminished pain compared to CA alone and the combination of CA with the application of a basic cream. Topical anesthesia through the application of a liposomal lidocaine-containing cream emerged as a facile, secure, and efficacious approach for alleviating the pain associated with intradermal BoNT-A injection in PPH treatment. Furthermore, it demonstrated compatibility with CA, thereby offering a comprehensive strategy for pain management during BoNT-A administration.

Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art.

Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition.

Latest combination therapies in psoriasis: Narrative review of the literature.

Biological therapies revolutionized the treatment of many chronic inflammatory skin diseases, first of all psoriasis, thanks to their high efficacy and the reduced number of side effects. However, the use of a single biologic drug does not always provide complete control of the disease or associated comorbidities over time. The first biological drugs used for the treatment of psoriasis, tumor necrosis factor alpha inhibitors, have long been used in combination with traditional topical and systemic therapies to induce a complete remission of the disease that could not be achieved with innovative drug alone. Even with the advent of new biological therapies with more precise molecular targets, the challenge of using combination therapies remained. Psoriatic patients often have major comorbidities, such as arthritis, inflammatory bowel disease, uveitis or have other concomitant conditions such as chronic spontaneous urticaria and atopic dermatitis, which may require different biologic treatments than those indicated in psoriasis. The objective of this article is, through a comprehensive revision of the literature, to analyze in which cases the use of the combination of the latest therapies for psoriasis may be useful.

Botulinum Toxin Type A for Treatment of Forehead Hyperhidrosis: Multicenter Clinical Experience and Review from Literature.

Among the forms of idiopathic hyperhidrosis, those involving the forehead have the greatest impact on patients' quality of life, as symptoms are not very controllable and are difficult to mask for patients. Although the local injection therapy with Incobotulinum toxin type A (IncoBTX-A therapy) can be considered a rational treatment, data from the literature describing both efficacy and safety of the treatment over the long term are poor. The aim of this report is to describe the single-center experience of five patients seeking treatment, for forehead hyperhidrosis with IncoBTX-A. To evaluate the benefits, safety profile and duration of anhidrosis, patients were treated following a standardized procedure and then followed until clinical relapse. The amount of sweating was measured by gravimetric testing, the extension of hyperhidrosis area was measured through Minor's iodine starch test, and response to the treatment was evaluated using the Hyperhidrosis Disease Severity Scale (HDSS) and the Dermatology Life Quality Index (DLQI). In all treated patients, a significant anhidrotic effect was observed 4 weeks after the treatment and lasted for approximately 36 weeks. The reduction in sweat production was associated with significant amelioration of symptoms and quality of life for all treated patients. No serious side effects occurred; one patient complained of a mild transient bilateral ptosis. Although further wider studies are required, our preliminary results seem to encourage the use of IncoBTX-A in forehead hyperhidrosis.

The Role of Nutrition in Immune-Mediated, Inflammatory Skin Disease: A Narrative Review.

Immune-mediated inflammatory skin diseases are characterized by a complex multifactorial etiology, in which genetic and environmental factors interact both in genesis and development of the disease. Nutrition is a complex and fascinating scenario, whose pivotal role in induction, exacerbation, or amelioration of several human diseases has already been well documented. However, owing to the complexity of immune-mediated skin disease clinical course and breadth and variability of human nutrition, their correlation still remains an open debate in literature. It is therefore important for dermatologists to be aware about the scientific basis linking nutrition to inflammatory skin diseases such as psoriasis, atopic dermatitis, hidradenitis suppurativa, bullous diseases, vitiligo, and alopecia areata, and whether changes in diet can influence the clinical course of these diseases. The purpose of this narrative review is to address the role of nutrition in immune-mediated inflammatory skin diseases, in light of the most recent and validate knowledge on this topic. Moreover, whether specific dietary modifications could provide meaningful implementation in planning a therapeutic strategy for patients is evaluated, in accordance with regenerative medicine precepts, a healing-oriented medicine that considers the whole person, including all aspects of the lifestyle.

Real-world evidence of biologic treatments in moderate-severe psoriasis in Italy: Results of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional longitudinal study of real-life clinical practice) study.

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate-severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate-severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow-up visit at 6 months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%-89%) at 16 weeks, 90% (87%-93%) at 24 weeks, and 91% (89%-94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%-79%) and 53% (49%-57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%-82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients.

Psoriatic patients treated with secukinumab reach high levels of minimal disease activity: results from the SUPREME study.

BACKGROUND: Achieving minimal disease activity (MDA) represents an ambitious and sustainable therapeutic goal in psoriasis. Clear criteria for defining MDA in psoriasis are lacking. OBJECTIVES: The primary outcome was to evaluate the effect of 300 mg secukinumab in achieving MDA in patients with psoriasis and identify the most useful criteria to define MDA in such patients. The secondary outcome was to identify clinical factors influencing MDA. MATERIALS & METHODS: In this post hoc analysis of the SUPREME study, in which 433 patients were enrolled, MDA was assessed using established criteria: ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) and Dermatology Life Quality Index 0/1 (MDA-1), PASI score ≤1 or body surface area (BSA) <3% (MDA-2), or Investigator Global Assessment x BSA (MDA-1a and MDA-2a), for which cut-off values were obtained in patients achieving MDA-1 and MDA-2, respectively. RESULTS: After 16 weeks of secukinumab, 65% and 76% of the evaluable population achieved MDA-1 and MDA-2, respectively; at Week 24, this was 70% and 83%. Factors that positively influenced MDA at Week 16 were younger age, lower weight and body mass index, absence of depression and anxiety, and lower serum levels of complement C3 and high-sensitivity C-reactive protein. MDA-1a and MDA-2a were achieved by 64% and 74% of patients at Week 16 and by 70% and 81% at Week 24, respectively. CONCLUSION: Patients treated with secukinumab achieved high levels of MDA at Weeks 16 and 24, regardless of the method used to calculate MDA.

A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. METHODS: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). RESULTS: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time. CONCLUSION: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Novel Therapeutic Approaches and Targets for the Treatment of Neutrophilic Dermatoses, Management of Patients with Neutrophilic Dermatoses and Future Directions in the Era of Biologic Treatment.

Neutrophilic dermatoses are a heterogeneous group of inflammatory skin disorders characterized by the presence of a sterile, predominantly neutrophilic infiltrate on histopathology. Universally accepted and validated guidelines for the management of neutrophilic dermatoses do not exist, also given the paucity of randomized controlled study and high-quality data. However, the literature on the effective use of biologic therapies is rapidly expanding. This article reviews the epidemiology, clinical characteristics, histopathologic features, and management of pyoderma gangrenosum as well as Sweet's syndrome, sub-corneal pustular dermatoses and bowel-associated dermatosis arthritis syndrome. The use of biologic agents, including tumor necrosis factor α-inhibitors, anti-IL1, anti-IL-17, and IL-23 are discussed in detail.

Novel Therapeutic Approaches and Targets for Treatment of Chronic Urticaria: New Insights and Promising Targets for a Challenging Disease.

BACKGROUND: Chronic Spontaneous Urticaria (CSU) is a disease characterized by the onset of wheals and/or angioedema over 6 weeks. The pathophysiology for CSU is very complex, involving mast cells and basophils with a multitude of inflammatory mediators. For many years the treatment of CSU has been based on the use of antihistamines, steroids and immunosuppressive agents with inconstant and frustrating results. The introduction of omalizumab, the only licensed biologic for antihistamine- refractory CSU, has changed the management of the disease. OBJECTIVE: The aim of this article is to review the current state of the art of CSU, the real-life experience with omalizumab and the promising drugs that are under development. METHODS: An electronic search was performed to identify studies, case reports, guidelines and reviews focused on the new targets for the treatment of chronic spontaneous urticaria, both approved or under investigation. The search was limited to articles published in peer-reviewed journals in the English Language in the PubMed database and trials registered in Clinicaltrials.gov. RESULTS: Since the advent of omalizumab, the search for new therapies for chronic spontaneous urticaria has had a new impulse. Anti-IgE drugs will probably still be the cornerstone of therapy, but new targets may prove effective in syndromic urticaria or refractory cases. CONCLUSION: Although omalizumab has been a breakthrough in the treatment of CSU, many patients do not completely get benefit and even require more effective treatments. Novel drugs are under investigation with promising results.

Bullous Sweet's syndrome in a patient with ulcerative colitis: a rare case report.

Bullous Sweet's syndrome is an uncommon clinical presentation of classical Sweet's syndrome, often associated with various kinds of tumors, infections, and active inflammatory bowel diseases (IBDs), namely Crohn's disease and ulcerative colitis. Only a few cases of bullous Sweet's syndrome associated with ulcerative colitis are described in the literature. We report a case of a 62-year-old female patient with acute exacerbation of ulcerative colitis associated with infiltrating purple-erythematous skin plaques, which were partly vesicular, and oral ulcerative stomatitis. Biopsy was consistent with bullous Sweet's syndrome. Treatment with betamethasone sodium phosphate, starting at 5.5 mg, followed by gradual dose tapering for 12 weeks, resulted in improvement of the ulcerative colitis and disappearance of the cutaneous lesions. Bullous Sweet's syndrome most commonly occurs in the setting of hematologic malignancies, suggesting that physicians should perform long-term screening for early diagnosis of hematological and solid malignancies.

Global coronavirus pandemic (SARS-CoV-2): Past, present, and future of pediatric dermatology.

Two months have passed since the World Health Organization (WHO) declared the pandemic of the Coronavirus Disease 19 (COVID-19), caused by the SARS-CoV-2 virus, on 11 March 2020. Medical and healthcare workers have continued to be on the frontline to defeat this disease, however, continual changes are being made to their working habits which are proving to be difficult. Although the skin is not the main target of the SARS-CoV-2 infection, it is strongly involved both directly and indirectly, in many aspects of dermatological disease management, and particularly in pediatric dermatology. In this manuscript, our goal was to provide a "up-to-date" account on this topic, through analysis of current literature and sharing our experiences during this pandemic.

Efficacy and Safety of Topical Calcipotriol 0.005% Versus Topical Clobetasol 0.05% in the Management of Alopecia Areata: An Intrasubject Pilot Study.

INTRODUCTION: Alopecia areata (AA) is a chronic inflammatory non-scarring type of hair loss. Current therapies for alopecia areata are rather limited and mainly involve the use of topical, intra-lesional or systemic steroids and topical immunotherapy, with variable benefit. Recent studies have demonstrated that vitamin D analogues could potentially promote hair growth in patients with patchy AA. METHODS: We investigated the efficacy and safety of treatment with calcipotriol, a synthetic derivative of vitamin D (calcipotriol 0.005% ointment), versus treatment with the corticosteroid clobetasol (topical clobetasol 0.05% formulation), in a series of 35 patients with scalp AA, using an intrasubject design. RESULTS: Patches treated with calcipotriol ointment showed greater and faster response rates than did those treated with topical clobetasol, although the differences were not statistically significant. The main strength of the study is its prospective design; the main limitation is the small number of participants. CONCLUSIONS: Treatment with the calcipotriol would appear to be reasonably effective in patients with mild to moderate patchy AA and was associated with only limited and reversible side effects.

Buschke-Ollendorff syndrome in a 6-year-old patient: clinical and histopathological aspects of a rare disease.

Buschke-Ollendorff syndrome (BOS) is a rare genetic hereditary genodermatosis characterized by benign skeletal and cutaneous lesions. Skeletal alterations known as osteopoikilosis (OPK) or "spotted bone disease" are asymptomatic areas of sclerosing dysplasia. Two skin lesion patterns have been described because they may be of either elastic tissue (juvenile elastoma) or collagenous composition (dermatofibrosis lenticularis disseminata). We present the case of a 6-year-old male patient with yellowish papules that coalesced to form plaques localized on both thighs and on the upper limbs consistent with a connective tissue nevus (CTN) diagnosis. X-ray examination of the skeletal system revealed the presence of multiple small areas (measuring between 1 and 7 mm) of increased bone density (OPK) bilaterally. A skin biopsy was performed and did not show striking alterations in the number or dimension of the extracellular matrix fibers, but it showed mucin deposition between them, which is compatible with a CTN. This study reports on the clinical presentation and histological examination of this unusual disease.

Safety update of etanercept treatment for moderate to severe plaque psoriasis.

Introduction: Conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) for patients with psoriasis are often linked to inadequate outcomes and risk of multiple adverse effects. Biologic agents such as etanercept (ETN) have revolutionized the therapeutic management of psoriasis, allowing the treatment of most difficult cases, and fragile patients.Areas covered: The authors searched PubMed using the term 'psoriasis,' 'etanercept,' and 'safety.' Articles considered by the authors to be most relevant, such as randomized controlled studies, cohort studies, and review articles placing emphasis on studies of efficacy and safety were selected. Case reports and letters relating to safety were also included. The main sources of data referenced by these articles were also included in the review. Besides, to get the relevant studies, the reference lists were examined to identify the potentially available studies. The aim of this review is to describe the safety profile of ETN, used for psoriasis treatment, focusing on related clinical implications.Expert opinion: ETN has a favorable safety profile, and its use should be largely considered in psoriatic patients. Caution should be recommended in case of chronic heart failure, autoimmune disease, previous malignancies, familial history of demyelinating diseases, latent TBC infection, chronic HBV and HCV infection or HIV.

Pharmacodynamics OF TNF α inhibitors for the treatment of psoriasis.

Introduction: The treatment of psoriasis with conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) is often linked to unsatisfactory outcomes and the risk of serious adverse events. Over the last decades, research advances in understanding the role of tumor necrosis factor alpha (TNF α) and other cytokines in the pathogenesis of psoriasis have driven the introduction of biologic agents targeting specific immune mediators in everyday clinical practice. TNF α inhibitors are a consolidated treatment option for patients with moderate-to-severe disease with remarkable efficacy and a reassuring safety profile.Areas covered: The PubMed database was searched using combinations of the following keywords: psoriasis, TNF α inhibitors, biologic therapy, pharmacodynamics, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects. The aim of this review is to describe the pharmacodynamic profile of anti-TNF α inhibitors, currently approved by the European Medicines Agency (EMA) for the treatment of psoriasis, focusing on related clinical implications, also in comparison to the new generation biological therapies targeting the interleukin 23/interleukin 17 axis.Expert opinion: Pharmacodynamics of TNF α inhibitors should be fully considered in planning patient's therapy strategies, especially in case of secondary failures, poor adherence to treatment, instable psoriasis, high risk of infection, pregnant or lactating women, metabolic comorbidities, coexistence of other immune-mediated inflammatory diseases.

Metabolic, pharmacokinetic, and toxicological issues surrounding dapsone.

INTRODUCTION: In their 70-year history, dapsone and other sulfones have been used as both antibacterial and anti-inflammatory agents. Dapsone has been the main active principle in the multidrug regimen recommended by the World Health Organization for the treatment of leprosy. In addition, dapsone has been successfully used to treat a wide range of dermatological and systemic disorders, mostly characterized by neutrophilic and eosinophilic accumulation and infiltration. Areas covered: The PubMed database was searched using combinations of the following keywords: dapsone, sulfones, pharmacodynamics, pharmacology, adverse events, pharmacokinetics, drug interaction, dermatologic uses, and antimicrobial uses. This article reviews and updates the chemistry, pharmacokinetics, mechanism of action, adverse effects, drug interactions, and clinical application of sulfones. Expert opinion: Dapsone exhibits clinical efficacy in several cutaneous and systemic conditions and is now generally accepted as the therapy of choice for leprosy and for rare dermatosis, as dermatitis herpetiformis. Careful patient selection and close monitoring during treatment are mandatory to provide safe and effective use of dapsone. Familiarity with sulfones and dapsone is crucial because of this agent retains its niche in the clinician's therapeutic armamentarium.