Tuscany consensus for the treatment of moderate-severe psoriasis: update and focus on practical guidelines for place in therapy of anti-IL-17 and anti-IL-23 biologics.

Psoriasis is a common chronic skin disease characterized by a worldwide distribution and a natural tendency towards progression. According to the many clinical forms, the extension of the disease and the many comorbidities, almost the 20% of the patients require a systemic treatment. Biologics have greatly changed the ongoing of psoriasis and the quality of life of psoriasis patients. After the anti-TNF-alpha, which were the first biologics in use for psoriasis, the improvement in knowledge of the pathogenetic mechanisms underlying the disease has led to the development of a series of more specific therapies for psoriasis. This "second generation" of biologics includes the interleukin (IL)-12/23 inhibitor ustekinumab, IL-17 inhibitors (secukinumab and ixekizumab), the IL-17 receptor A (IL-17RA) antagonist brodalumab, and the IL-23 inhibitors guselkumab, risankizumab and tildrakizumab. This study represents an update of the Tuscany consensus focused on the use of new drugs, such as anti-IL-17 and anti-IL-23 in moderate-to-severe psoriasis and their correct place in therapy according to specific clinical requests and in full respect of the current financial restrictions.

Efficacy and safety of dimethylfumarate in elderly psoriasis patients: a multicentric Italian study.

The number of psoriatic elderly patients is steadily increasing in the Western world, nevertheless they are frequently excluded from clinical trials and described as a high-risk group for adverse events.We conducted a retrospective multicentric study of DMF use in elderly (>65 years) psoriatic patients. DMF efficacy was evaluated up to 24 weeks by Psoriasis Area and Severity Index (PASI) score. We also evaluated drug maintenance and safety.Our study population included 81 elderly psoriatic patients treated with DMF up to 24 weeks. The PASI score at the baseline (week 0) ranged from 3,7-24 (mean ± SD, 9,8 ± 4,1), which changed after DMF administration to 4,3 ± 3,2 at week 16 and 2,7 ± 3,2 at week 24. Among 81 elderly psoriatic patients 59 (72,8%) adverse events were reported during the observation period. The most common were gastrointestinal complaints (n = 24, 29,6%) and flushes (n = 10, 12,3%). Lymphocytopenia (n = 10, 12,35%) was frequently observed.In daily practice, DMF seems to be efficacy and well tolerated in elderly psoriatic patients. DMF may be a first-line systemic treatment option to manage elderly psoriasis, provided that also the long-term safety data are closely monitored, in particular lymphocytopenia.

Tuscan Consensus on the diagnosis, treatment and follow up of adult atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory disease with a chronic-relapsing course that is intensely itchy. A correct diagnosis of AD in adults and consequently appropriate clinical therapeutic management is a critical issue for extreme clinical expression heterogeneity and various grades of disease severity. In order to ensure high levels of care and standardization of clinical therapeutic management of Adult AD, the decision was taken to create an AD Tuscan Consensus Group (the Group), to work on and validate a consensus based regional clinical-therapeutic management model. The aims of the Group were to find agreement on the criteria for diagnosis, scoring of severity, multidisciplinary approach and treatment of adult atopic dermatitis and to create an easier way for patients to access specialized dermatology outpatient services and importantly to reduce waiting lists and costs related to the management of AD. The Tuscan Consensus Group adopted a simplified Delphi method, in three principal steps: 1) literature metanalysis and critical review of patient's clinical experience to identify the main areas considered questionable or uncertain; 2) discussion of those areas requiring consensus and statement definition through four different sub-committees (diagnosis, severity evaluation, scoring and comorbidities); 3) a consensus based simplified process with final approval of each statement by plenary vote with approval >80% of the participants. The Group here presents and discusses the consensus based recommendation statements on adult atopic dermatitis.

Fractional CO2 laser: a novel therapeutic device for refractory necrobiosis lipoidica.

Necrobiosis lipoidica diabeticorum is a granulomatous skin disease of uncertain pathogenesis. Many therapeutic approaches have been reported in the literature, but none of them can be considered the gold standard. Fractional CO(2) laser treatment shows peculiar effects in the skin, mainly due to its ability of modulating cytokine pathways of tissue-repairing mechanisms. Thus, we propose fractional CO(2) laser in the management of refractory necrobiosis lipoidica in selected recalcitrant patients.

Treatments of vitiligo: what's new at the horizon.

Vitiligo is a manageable disease. However, current vitiligo treatments can be considered suboptimal as they do not guarantee high efficacy and cannot be standardized for most patients. Recently, combination therapies have been introduced in order to obtain better results and reduce risks in the management of the disease. Novel efficacious products are hereunder discussed to improve the therapeutic options for vitiligo patients.

Clinical efficacy of a novel topical formulation for vitiligo: compared evaluation of different treatment modalities in 149 patients.

Current vitiligo treatments are not always satisfactory for both patients and dermatologists. Recently, combination therapies have been introduced in order to obtain better results and reduce risks in the management of the disease. Novel efficacious products are needed to improve the therapeutic possibilities of dermatologists in the respect of safety for the patients. The objective of the present study was to evaluate the effects of a novel topical in a gel formulation containing phenylalanine, cucumis melo extract, and acetyl cysteine in vitiligo. The present study used an open observational study to evaluate the efficacy and safety of the investigated product, given alone or in combination with 311-nm narrow band microphototherapy. Results were compared with those obtained treating a matched patient population with microphototherapy alone and with clobetasol propionate 0.05% ointment alone. One hundred forty-nine patients suffering from symmetrical vitiligo affecting less than 10% of the skin surface were evaluated. Patients affected by acral vitiligo only were excluded from the analysis. Treatment duration was scheduled for 12 weeks. Excellent repigmentation (>75%) was achieved by 38-73% of patients, depending on the treatment regimen. Mild to moderate side effects were observed only in patients treated with clobetasol 0.05% ointment. The tested gel formulation showed a good efficacy in improving vitiligo repigmentation. No side effects were observed.

Cutaneous necrotizing vasculitis: a rational therapeutic approach.

Cutaneous necrotizing vasculitis is a heterogeneous group of disorders characterized clinically by palpable purpura, and histologically by a segmental angiocentric inflammatory condition with fibrinoid necrosis of the vessel wall, endothelial swelling, and nuclear dust of the post capillary venules. Often, the skin seems the only organ apparently damaged, but systemic involvement may occur. In up to 60% of cases of cutaneous necrotizing vasculitis, the cause remains unknown; in others, it may be due to a variety of underlying conditions such as drugs, chemicals, food allergens, infections, chronic inflammatory systemic disorders, or malignant neoplasms. A rational therapeutic approach of vasculitis begins with the identification and stoppage of any suspected underlying condition. This may be all that is required for the treatment, because it is usually followed by the clearing of cutaneous lesions, and systemic signs and symptoms. In other cases, local and/or systemic anti-inflammatory and/or immunosuppressive therapy is recommended.

Paraneoplastic vasculitis and paraneoplastic vascular syndromes.

Paraneoplastic syndromes are localized or diffuse pathologic manifestations that may occur in subjects affected by neoplastic diseases, even occult ones. Among the many clinical manifestations of paraneoplastic syndromes, cutaneous ones are quite common. It is estimated that skin manifestations may represent the very first diagnostic sign of a neoplastic disease in about 1% of patients. Many paraneoplastic syndromes with skin manifestations are caused by vascular alterations. In case of solid tumors, migrant thrombophlebitis and blood hypercoagulability can be seen, whereas in case of hematological neoplasms, vasculitis, and erythromelalgia can occur. Paraneoplastic vasculitis and paraneoplastic vascular syndromes are challenging issues in dermatology and general medicine. The present article will review the actual knowledge in the argument, together with providing hints for its diagnosis and management.

Clinical evaluation of topical tacalcitol efficacy in extending the remission period between nb-UVB phototherapy cycles in psoriatic patients.

Psoriasis is a very common dermatological disease affecting a large part of the world population. In its most common form, psoriasis vulgaris, many topical drugs are available to treat the localized forms, and the recurrence of the dermatosis. Among topicals, tacalcitol has been proven to be effective and devoid of side effects which are typical of Vitamin-D3 analogues or derivates. The aim of this retrospective study was to evaluate the efficacy of topical tacalcitol vs. calcipotriol and emollient treatment of the first recurring lesion in order to induce a longer remission period before the retreatment with nb-UVB phototherapy in a population of 90 psoriatic patients. In this trial, the time between the first relapsing plaque appearance and retreatment with nb-UVB resulted in 25, 16 and 11 days for tacalcitol, calcipotriol and emollient respectively, with a statistically significant difference for tacalcitol (p < 0.0001). These results proved that tacalcitol treatment is effective in increasing the time interval in consecutive phototherapy cycles and in reducing the total amount of UV exposure.

Focused UV-B narrowband microphototherapy (Biopsorin). A new treatment for plaque psoriasis.

Skin irradiation with ultraviolet light B (UV-B) and in particular the emission peak at 311 nm represents an effective therapeutic regimen for psoriasis. Excessive tanning, photoaging, and skin cancerization do occur mainly in subjects with skin phototype I to III. The possibility of developing skin cancer is parallel to the skin surface area under treatment and to the overall irradiation dose. We report here on a new focused phototherapy method releasing UV-B with a peak at 311 nm, which consists in the selective irradiation of single psoriatic patches with a new device equipped with a special optic fiber. The treatment is effective, safe and well tolerated. Psoriasis Area and Severity Index 75 is achieved in 64% of patients after 12 sessions of treatment. The Physician Global Assessment evaluation significantly improves in all treated patients.

Efalizumab in the treatment of psoriasis: when comorbidity is an issue.

Psoriasis is a common dermatosis affecting the skin, mucosal surfaces, and cutaneous adnexa, and joints and bones can be involved at some degree in the clinical features of the disease, configuring psoriatic arthritis. Moderate to severe psoriasis has a high impact on quality of life and requires an integrated and long-term treatment schedule. However, management of psoriasis in patients affected by other systemic diseases can be challenging because of the possible side effects or contraindications of various treatments in accordance with patients' medical history. In recent times, the therapeutical approaches have changed a lot, thanks to biologicals. The current authors present some cases of psoriatic patients with comorbidities successfully treated with efalizumab, an anti-T lymphocyte biological.

Targeted and combination treatments for vitiligo. Comparative evaluation of different current modalities in 458 subjects.

The current treatment of vitiligo is not satisfactory according to the opinions of both the patient population and the dermatologists. Recently, combination therapies have been introduced, which are both systemic and targeted (microphototherapy). To evaluate the effects of topical treatments given alone or in combination with 311-nm narrow-band microphototherapy. We evaluated the efficacy and safety of: (1) 311-nm narrow-band microphototherapy;(2) tacrolimus 0.1% ointment twice a day; (3) pimecrolimus 1% cream twice a day; (4) betamethasone dipropionate 0.05% cream twice a day; (5) calcipotriol ointment 50 microg/g twice a day; and (6) 10%l-phenylalanine cream twice a day, for the treatment of exclusively vitiligo patches. A 311-nm narrow-band microphototherapy (Bioskin) was given alone or in combination with the above-mentioned popular local treatments. Four hundred and seventy patients suffering from vitiligo that affected less than 10% of the skin surface were evaluated. The patients were divided into 11 groups according to the selected treatment modalities. Four hundred and fifty-eight patients completed the study period of 6 months. Excellent repigmentation (> 75%) was achieved by 72% of the patients in group 1, 76.5% in group 2, 76.1% in group 3, 90.2% in group 4, 75.6% in group 5, 74.8% in group 6, 61% in group 7, 54.6% in group 8, 71.2% in group 9, 59.1% in group 10, and 29.3% in group 11. Marked repigmentation (50-75%) was evident in 19.8% of the patients in group 1, 18.2% in group 2, 20.1% in group 3, 6.7% in group 4, 14.1% in group 5, 11.3% in group 6, 16.1% in group 7, 18.4% in group 8, 25% in group 9, 10.6% in group 10, and 8.1% in group 11. Moderate results (25-50% repigmentation) were seen in 4.6% of the patients in group 1, 3.3% in group 2, 2.7% in group 3, 2.2% in group 4, 7.4% in group 5, 10.1% in group 6, 18.4% in group 7, 21.7% in group 8, 2.1% in group 9, 27.1% in group 10, and 55% in group 11. Finally, minimal (< 25%) or no response was achieved in 3.6% of the patients in group 1, 2% in group 2, 1.1% in group 3, 0.9% in group 4, 2.9% in group 5, 3.8% in group 6, 4.5% in group 7, 5.3% in group 8, 1.75% in group 9, 3.2% in group 10, and 7.6% in group 11. Side effects were skin atrophy (76% in group 4 and 81% in group 9), stinging and burning (groups 2, 3, 7, and 8). Targeted combination therapies in vitiligo are remarkably more effective than single treatments. When single treatments are considered alone, 311-nm narrow-band UVB microfocused phototherapy and 0.05% betamethasone dipropionate cream are the most effective treatments in our study. When combined therapies are chosen, 0.05% betamethasone dipropionate cream plus 311-nm narrow-band UVB microfocused phototherapy apparently give the highest repigmentation rate. In the short term, the only side-effects registered have been cutaneous atrophy with corticosteroid cream, and stinging and burning with 0.1% tacrolimus ointment and, less frequently, with 1% pimecrolimus cream.

Therapy of environmental mycobacterial infections.

Environmental mycobacteria are the causative factors of an increasing number of infections worldwide. Cutaneous infections as a result of environmental mycobacteria are often misdiagnosed, and their treatment is difficult because these agents can show in vivo and in vitro multidrug resistance. The most common environmental mycobacteria that can cause cutaneous infections are Mycobacterium fortuitum and Mycobacterium marinum. All mycobacteria are characterized by low pathogenicity and they can contaminate affected or traumatized skin only in immunocompetent subjects (mainly in fishermen, swimming-pool attendants, and aquarium owners) whereas medical and esthetic procedures are at risk for the infections because of the quick-growing mycobacteria. Immunocompromised subjects can instead easily develop environmental mycobacterial infections of differing degrees of severity.

Atopic dermatitis.

Atopic dermatitis (AD) is a common dermatologic disease that can occur at different ages with different clinical manifestations. The etiologic factors and the pathogenetic pathways of AD have been thoroughly investigated but as often happens, something more has to be yet elucidated before the statement, that we possess the overall comprehension of the disease, could be considered the truth. Treatment of AD is often challenging, because of the chronic course of the disease and the fact that even the best of therapies is affected by adverse events, intolerances, or the possible occurrence of contraindications resulting from a sudden change in the overall health status of the patient (e.g., the onset of some comorbidities). Hence, the need to know "how, when, with what, and why" to treat AD patients with the many therapeutic modalities is now in the hands of the dermatologists.

Prurigo nodularis and lichen simplex chronicus.

Emotional tensions in predisposed subjects may play a key role in inducing a pruritic sensation, leading to a scratching that, becoming a self-perpetuating pathomechanism, may represent the main feature of two distinct cutaneous clinical entities: prurigo nodularis and lichen simplex chronicus. Psychogenic factors play a relevant role in both conditions, and they are often associated with depression and dissociative experiences. Hence, the importance of the evaluation of these patients from the point of view of psychodermatology, which may analyze the relationship between skin disease and psychological factors. Patients with real or perceived imperfections in particular areas of the body (face, scalp, hands, and genital area) are more prone to psychologic distress, whereas cutaneous diseases may lead to experience a heightened level of distress. As psychosomatic factors have been estimated to be present in at least one-third of dermatologic patients, effective management of skin conditions involves consideration of the associated emotional factors.

Therapeutical approaches in melasma.

Melasma (cloasma) is a typical hypermelanosis and a common dermatologic skin disease that involves sun-exposed areas of the skin. It mostly affects women of reproductive age. Solar and ultraviolet exposure are the most crucial etiologic factors. Pregnancy, certain endocrine disorders and hormonal treatments, cosmetics, phototoxic drugs, and antiseizure medications are well-known inducing and exacerbating factors. A classification of melasma is based on Wood's light examination, classifying it in four major clinical types and patterns: epidermal, dermal, mixed, and indeterminate. Different treatment options are currently available for melasma. The choice of proper treatment should take into account the type of melasma to be treated, the skin complexion of the patient, possible previous treatments, the expectations and compliance of the patient, and the season in which the treatment is started.

A rational approach to the treatment of vitiligo and other hypomelanoses.

A rational approach to hypopigmented disorders needs a clear and widely accepted classification and meta-analysis of the literature to position the medical, physical, surgical, and combined treatments available in terms of safety and effectiveness profiles. Best available scientific evidence must be rationally adapted to the patient's expectations and to the clinical presentation of the hypopigmentary disease, to reach the most valid final results.

New and experimental treatments of vitiligo and other hypomelanoses.

This article deals with new and experimental treatments that can be used to treat various forms of depigmenting disorders. Ultraviolet B-focused therapies and new surgical approaches are analyzed in this article. These therapies were mainly or only developed to treat vitiligo, which is the most studied and probably the most challenging of all the hypomelanoses, but the results obtained in trials and clinical experiences about vitiligo sometimes can be referred to other depigmenting disorders.