Prognosis in early stage cutaneous T-cell lymphoma treated with psoralen plus ultraviolet A irradiation and low-dose interferon-α: Long-term efficacy and survival according to conventional and emerging clinical endpoints.

Patients with early stage cutaneous T cell lymphoma (CTCL) usually have a benign and chronic disease course, characterized by temporally response to conventional skin directed therapies and intrinsic possibility to evolve. Using the combination of psoralen plus ultraviolet A irradiation (PUVA) and low-dose interferon-α (INF), the principal treatment goal is to keep confined the disease to the skin, preventing disease progression. Among 87 patients with early stage IA to IIA MF treated with low-dose IFN-α2b and PUVA in our center, complete remission (CR) were reported in 70 patients (80.5%) and the overall response rate (ORR) was 97.8% (n = 85), with a median time to best response to therapy of 5 months (range, 1-30). Among the responders, only the 8% of patients had a relapse with major event. The median follow-up was 207 months (range, 6-295). Survival data showed a median overall survival (OS) not reached (95% CI; 235-NR months), a disease free survival (DFS) of 210 months (95% CI; 200-226 months) and a median time to next treatment (TTNT) of 38.5 months (95% CI, 33-46 months). The long follow up of this study verifies our preliminary results already published in 2006 and confirms the efficacy of INF-PUVA combination therapy in a real world setting, according conventional (OS and DFS) and emerging (TTNT) clinical endpoint of treatment efficacy.

The pharmacological treatment and management of hyperhidrosis.

INTRODUCTION: Idiopathic hyperhidrosis is a dysfunctional disorder involving eccrine sweat glands, and its impact on patients' daily quality of life is well known. Unlike some years ago, when only poor effective and safe therapeutic alternatives were available, nowadays, several emerging pharmacological active substances have gained significant space as treatment options. AREAS COVERED: The authors report on, in this narrative review, the emerging data from the literature focusing on the pharmacological treatments to draw up a drug treatment flow chart for patients with idiopathic hyperhidrosis, taking into consideration specific differences among axillary, palmoplantar, and craniofacial hyperhidrosis. EXPERT OPINION: Idiopathic hyperhidrosis, regardless of the site of involvement, remains a functional disorder that places a significant burden on patients. After balancing efficacy against adverse events, systemic therapy, although off-label for all forms of hyperhidrosis, can be an added therapeutic option for patients with insufficient response to topical treatment. Until the pathophysiological mechanisms underlying hyperhidrosis are clear and the etiological therapeutic approach becomes realistic, the greatest challenge in the therapeutic management of hyperhidrotic patients seems to be the search for the most convenient combination between different therapeutic modalities (topical and systemic agents, and botulinum toxins) to achieve long-term control of the disease symptoms.

Long-term proactive management of psoriasis with calcipotriol and betamethasone dipropionate foam: an Italian consensus through a combined nominal group technique and Delphi approach.

BACKGROUND: Although long-term management of psoriasis is paramount, this approach is challenging in clinical practice. In the recent PSO-LONG trial, a fixed-dose combination of betamethasone dipropionate (BD) and calcipotriol (Cal) foam applied twice a week on non-consecutive days for 52 weeks (proactive treatment) reduced the risk of relapse. However, the role of Cal/BD foam in the long-term management of psoriasis needs further clarifications. The ProActive Management (PAM) program, a nationwide Italian project, aims at reaching a consensus on the role of proactive management of psoriasis. METHODS: A steering committee generated some statements through the nominal group technique (NGT). The statements were voted by an expert panel in an adapted Delphi voting process. RESULTS: Eighteen statements were proposed, and the majority of them (14/18) reached a consensus during the Delphi voting. The need to provide long-term proactive topical treatment to reduce the risk of relapse for the treatment of challenging diseases sites or in patients where phototherapy or systemic therapies are contraindicated/ineffective was widely recognized. A consensus was reached about the possibility to associate the proactive treatment with systemic and biological therapies, without the need for dose intensification, thus favoring a prolonged remission. Moreover, the proactive treatment was recognized as more effective than weekend therapy in increasing time free from relapses. Approaches to improve adherence, on the other hand, need further investigation. CONCLUSIONS: The inclusion in guidelines of a proactive strategy among the effective treatment options will be a fundamental step in the evolution of a mild-moderate psoriasis therapeutic approach.

Deferred time of delivery of biologic therapies in patients with stabilized psoriasis leads to a 'perceived satisfaction': a multicentric study.

OBJECTIVE: Thanks to their specificity of action, biologic drugs often lead to complete clearance of psoriatic lesions. In order to maintain its effectiveness, biological therapies cannot be discontinued. The aim of the study was to investigate the effect of widening the administration window of four biologic drugs, thus improving the quality of life of psoriatic patients and satisfying their desire to feel free from the disease, without loss of effectiveness. METHODS: We performed a multicentric cohort study considering patients with moderate-severe plaque psoriasis and/or arthropathic psoriasis treated with infliximab, adalimumab, etanercept or ustekinumab. The study group included patients with stabilized psoriasis in which the administration regimen of the biologic drug was deferred. The control group included psoriatic patients treated according the product monograph. RESULTS: The percentage of relapses in case of deferred administration intervals was comparable to that of standard administration intervals. The delayed administration modality got a good psychological consensus from the patients themselves, that reported a greater 'perceived satisfaction'. A consistent economic advantage was reported in case of prolonged administration intervals. CONCLUSIONS: The administration of biologic drugs with prolonged intervals maintains the same effectiveness as standard administration and produces a 'perceived satisfaction' in psoriatic patients.

Effects of in vivo application of an overnight patch containing Allium cepa, allantoin, and pentaglycan on hypertrophic scars and keloids: Clinical, videocapillaroscopic, and ultrasonographic study.

Several therapeutic approaches have been described for their treatment of hypertrophic scars and keloids, but to date, the optimal treatment has not been established yet. Our in vivo study was conducted to evaluate the effect of a medical device consisting in an adhesive patch containing onion extract (Allium cepa) 10%, allantoin 1%, and pentaglycan 4% (Kaloidon patch) on hypertrophic scars and keloids. Thirty-nine patients with hypertrophic scars and seven patients with keloids were asked to apply an adhesive patch containing Allium cepa, allantoin, and pentaglycan once/day for at least 8 h consecutively, for 24 weeks. Patients were reevaluated 6 weeks (T6), 12 weeks (T12), and 24 weeks (T24) after starting the treatment through POSAS scale v 2.0, ultrasonographic, and videocapillaroscopic assessment. The investigated medical device was able to induce a significant improvement of POSAS starting from T12, with a positive amelioration trend until T24. However the patient-assessed POSAS sub-items showed improvement already after 6 weeks, whereas a significant improvement of the observer-assessed POSAS sub-items was observed only after 12 weeks (P < .001). Ultrasonography and intravital videocapillaroscopy confirmed a significant improvement of skin scars thickness (P < .001) and vascularization (P < .001) after 12 weeks of medical device application at least, with increasing improvement until T24. Applying an adhesive patch containing Allium cepa, allantoin, and pentaglycan once a day for at least 8 consecutive hours seems to be able to improve the clinical and morphological characteristics of the scars of the skin in 24 weeks.

Metabolic, pharmacokinetic, and toxicological issues of biologic therapies currently used in the treatment of hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa is a chronic, relapsing, debilitating inflammatory dermatologic disease of the terminal hair follicles at intertriginous sites clinically characterized by painful inflammatory nodules, abscesses, draining sinus tracts, and dermal fibrosis. The management of hidradenitis suppurativa is a challenge and usually consists of both medical and surgical approaches, which must often be combined for best outcome. The introduction of biological therapies, specifically TNFα-inhibitors such as adalimumab, has profoundly changed the therapeutic armamentarium of the disease. AREAS COVERED: The PubMed database was searched using combinations of the following keywords: hidradentis suppurativa, biologic therapy, TNF-α inhibitors, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects, pharmacodynamics, pharmacology, adverse events, pharmacokinetics, drug interaction. This article reviews and updates the chemistry, pharmacokinetics, mechanism of action, adverse effects, drug interactions of on-label and off-label use of TNF-α inhibitors in HS. EXPERT OPINION: Biologic agents, particularly adalimumab, exhibit clinical efficacy in patients with hidradenitis suppurativa. Careful patient selection and close monitoring during treatment are mandatory to provide safe and effective use of the TNF-α inhibitor. Familiarity with biologic agents is crucial because these agents could become a consolidated treatment option in the clinician's therapeutic approaches.

Ixekizumab for treatment of moderate to severe plaque psoriasis: real world clinical experience.

BACKGROUND: Data concerning clinical experience in real world setting with ixekizumab for psoriasis are still exiguous. So, the aim of this report was to provide our experience in the use of ixekizumab in outpatient setting. METHODS: Fifteen Caucasian individuals (10 male, 5 females; mean age: 58.1; range: 30-75 years) affected by moderate to severe plaque psoriasis (PASI≥10 and/or DLQI≥10 and/or BSA≥10) were treated with ixekizumab, following dosing regimen of technical data sheet and clinically evaluated after 4 weeks (T4) and 12 weeks (T12) after. At baseline median PASI was 16.3 (range: 10-30, SD=6.0). The median BSA was 21.3 (10-35, SD=7.0), the median PGA was 3.4 (2-6, SD=1.2), the median DLQI was 18.6 (14-25, SD=3.6), the median m-NAPSI was 42.0 (30-56, SD=13.11). The median absolute value of PASI, BSA, PGA, DLQI and m-NAPSI showed a statistically significant decrease (P<0.05) already after 4 weeks of treatment, in order to testify treatment effectiveness. RESULTS: At T4, 93.3% of the patients reached PASI50, 6.9% reached PASI75; at T12, 100% of the patients reached PASI50, 80% reached PASI75, 13% reached PASI90 and 6.9% reached PASI100. One-third of observed patients reached MDA after 12 weeks of treatment. Injection site reactions were the only side effects occurring during the first 12 weeks of treatment. CONCLUSIONS: Our preliminary results seem to confirm the efficacy and safety profile provided through the UNCOVER pivotal trials (UNCOVER 1-3) although further larger observational studies are needed.

Switching from a biological therapy to another biologic agent in psoriatic patients: the experience of PsOMarche group.

BACKGROUND: Switching is a "hot" topic and the main reasons for switching prior biologic agent are for a primary failure, a secondary failure or drug intolerance, patient's dissatisfaction, physician decision. The aim of the study was to assess the optimization of the switching from a biologic agent to another. METHODS: Five Dermatological Units have participated to PsOMarche working group have studied thirty-eight patients affected moderate to severe chronic plaque psoriasis at time 0 (patient recruitment at time of switching from biological therapy to another), 8 weeks (T8), 16 weeks (T16). RESULTS: Twenty-eight males and 10 females were included in the study. At T0, 18 of 22 patients treated with etanercept had been switched to adalimumab and 4 to ustekinumab. Among 10 patients treated with adalimumab, 5 had been switched to ustekinumab, 2 to golimumab and 3 to certolizumab pegol. One patient treated with Infliximab and 5 patients treated with ustekinumab had been switched to adalimumab. Switching had been performed for primary inefficacy in 9 patients (23.6%) and a secondary failure was evidenced in 29 patients (73.4%). PASI75 was achieved in 53% and in 89.4% of patients after 8 weeks and 16 weeks of switching to the second biologic agent respectively; similarly, PsoDISK score significantly decreased at T8 and T16. CONCLUSIONS: The experience of PsOMarche group have shown that the switching to a biologic agent to another is a valuable treatment choice in patients with moderate to severe psoriasis experiencing a treatment failure with one biologic therapy, leading to a good improvement in skin disease and in patient's quality of life.

Biologic Therapy in Psoriasis (Part II): Efficacy and Safety of New Treatment Targeting IL23/IL-17 Pathways.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disorder that is estimated to affect 2-3% of the general population. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. METHODS: Biologics licensed for psoriasis include the TNFα inhibitors (infliximab, adalimumab, etanercept), the interleukin (IL)-12/23 monoclonal antibody (ustekinumab), and IL-17 inhibitor (secukinumab, ixekizumab). RESULTS: In this section, we analyse the role of IL-12, IL-23, and IL-17 in psoriasis and evaluated the efficacy and safety of biologic therapies targeting this cytokine. CONCLUSION: Dosing regimens, administration modality, and pharmacodynamics profiles of currently available anti-IL-12/IL-23 and IL-17 inhibitors are also examined.

Biologic Therapy in Psoriasis (Part I): Efficacy and Safety of Tumor Necrosis Factor- α Inhibitors.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disorder, with an estimated global prevalence of 2-3%. Psoriasis is associated with an impaired health-related quality of life and a substantial economic burden. Biologics, which target the pathways involved in the pathogenesis of psoriasis, represent an established therapeutic approach for moderate-to-severe plaque psoriasis, with remarkable efficacy and safety profile extensively examined and monitored. METHODS: Biological therapies currently available can be divided into three main categories: the TNFα antagonists (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol), the interleukin (IL)- 12/23 monoclonal antibody (ustekinumab), and IL-17 inhibitor (secukinumab, ixekizumab). RESULTS: In this section, we explore the complex role of TNFα in psoriasis as well as the efficacy and safety of TNFα inhibitors largely used in the management of the cutaneous disease. CONCLUSION: Dosing regimens, administration, pharmacodynamics profiles, efficacy, and safety of licensed anti-TNFα are here discussed in detail.

Efficacy and Safety of Topical Pidobenzone 4% as Adjuvant Treatment for Solar Lentigines: Result of a Randomized, Controlled, Clinical Trial.

BACKGROUND/OBJECTIVE: This study aims at the evaluation of the efficacy and safety of a combination therapy based on pidobenzone 4% and fractional CO2 laser or cryotherapy in the treatment of solar lentigines and the prevention of eventual posttreatment hyperchromia. METHODS: Efficacy was clinically evaluated by grading the pigmentation level with the Skin Tone Color Scale (STCS), and by grading patients' impression through a Visual Analog Scale (VAS). RESULTS: Our study shows that the associated treatment was safe and that it improves the therapeutic results on solar lentigines and prevents postiatrogenic hyperpigmentation compared with physical therapy alone. CONCLUSION: The combination of cryotherapy and pidobenzone 4% has been found to be the most useful treatment.

The transitioning from conventional therapy to biological treatment in psoriatic patients: STRATOS, a project of Marche Region.

BACKGROUND: STRATOS is the acronym of the "STRuctured Approach to the Treatment of psOriatic patientS". The optimization of the psoriasis's therapeutic management is one of the most important goals for dermatologists. According to Mrowietz's consensus report, the transitioning from conventional therapy to biological therapy is mainly due to the lack/loss of efficacy and/or for safety reasons. The aim of the manuscript was to describe the principal results obtained by the Dermatologic Clinic of Polytechnic University of Marche Region and the Units of Dermatology of the Marche Region applying, in our regional reality, Mrowietz's protocol for the daily management of patients with moderate-to-severe plaque. METHODS: Forty-seven patients with moderate to severe chronic plaque psoriasis have been monitored during the six-months study period. RESULTS: Psoriatic patients with diabetes showed further concomitant comorbidities compared to non-diabetics, as hypertension and hypercholesterolemia. Moreover, based on WHO classification, overweight was diagnosed in female patients, whereas obesity was prevalent in male patients. This aspect confirms the strict link between the multifaceted aspects of psoriatic patient which is primarily related to the persistent low-grade inflammation. In our psoriatic group, 10% of monitored patients were affected by Crohn disease or ulcerative colitis. CONCLUSIONS: The Mrowietz's transitioning protocol is a useful, reliable and feasible tool to manage the therapeutic iter of psoriatic patients in an Italian clinical setting also at regional level.

Biologic Therapy in Inflammatory and Immunomediated Skin Diseases: Safety Profile.

Biologic treatments have modified the therapeutic armamentarium in the treatment of many dermatological and non- dermatological diseases and data on literature have widely focused on the efficacy and safety of TNF-alpha inhibitors in psoriasis. Although the etiopathogenesis has not completely elucidated, inflammation appears the lait motif unifying the immune-pathogenesis of diverse skin disease, as atopic dermatitis, alopecia areata and hidradenitis suppurativa. Actually, data on the off-label use of biologics in cutaneous immune-mediated inflammatory diseases are scarce and restricted to anecdotal cases and case series. The present review aims to evidence the major off- label use of TNF-alpha inhibitors in dermatology.

Biologic Therapy in Psoriasis: Safety Profile.

This review focuses on the emerging concepts concerning the efficacy profile of biological drugs in psoriasis ranging from moderate to severe, and attempts to provide the most recent individual positioning of biologics in treating psoriasis. Biologic agents targeting towards specific immune mediators have emerged as treatment options for patients with moderate to-severe plaque psoriasis unresponsive or intolerant to traditional systemic agents. Data on the safety of biologics are available for up to 5 years in psoriasis and are on the whole reassuring. National registries are still evolving and will provide data on safety, to help the long-term monitoring of patients with psoriasis ongoing biological treatment. Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third line therapies due to relative lack of long-term safety data, especially for those who have been commercialized recently. Here, we have reviewed the long-term safety data obtained from National Registries, randomized controlled trials, open-label extension studies and meta-analyses on etanercept, infliximab, adalimumab, and ustekinumab in the treatment of adults with moderate to severe plaque psoriasis.

Helicobacter pylori infection in psoriasis: results of a clinical study and review of the literature.

BACKGROUND: Data from the literature concerning the role of Helicobacter pylori (H. pylori) infection in psoriasis are still conflicting. This study was carried out to evaluate prevalence of H. pylori in patients with mild to severe psoriasis, correlation between H. pylori infection and severity of psoriasis, and effect of H. pylori eradication on the clinical course of psoriasis. METHODS: Two hundred and ten patients with psoriasis and 150 healthy controls were screened for H. pylori through [(13) C] urea breath test at baseline (T0). All patients with psoriasis received standardized phototherapy treatment, and those infected by H. pylori were also treated with a 1-week triple therapy, then they were all re-evaluated four weeks later at the end of therapy (T5). RESULTS: The prevalence of H. pylori was not higher in psoriasis than in the control group (20.27 vs. 22%; P > 0.05). Patients infected by H. pylori showed more severe psoriasis than uninfected patients (psoriasis area and severity index score 17.9 ± 7.1 vs. 13.7 ± 6.9; P = 0.04), and patients who received successful eradication of H. pylori infection showed a greater improvement of psoriasis than the others (psoriasis area and severity index score at T5 in patients infected by H. pylori was 8.36 ± 3.76, in uninfected patients was 10.85 ± 3.49; P = 0.006). CONCLUSIONS: Patients with mild to severe psoriasis do not show a greater prevalence of H. pylori infection; however, H. pylori seems able to affect the clinical severity of psoriasis.

Elastosis perforans serpiginosa: a case successfully treated with intralesional steroids and topical allium cepa-allantoin-pentaglycan gel.

Elastosis perforans serpiginosa is a rare skin disease in which abnormal elastic fibers, other connective tissue elements, and cellular debris are expelled from the papillary dermis through the epidermis. Three clinical variants of EPS can be detected: idiopathic, reactive, and drug-induced. Clinically it consists of small horny or umbilicated papules arranged in a linear, arciform, circular, or serpiginous pattern. It usually occurs in young adults and shows a predilection for the head and neck. The lesions are generally asymptomatic or slightly itching. Several treatments have been reported with poor long-term success; these include intralesional and topical corticosteroids, tazarotene, imiquimod, and cryotherapy. We report a case of 40-year-old black woman affected by elastosis perforans serpiginosa that was referred to our department and treated with intralesional injections of triamcinolone acetonide and topical application of allium cepa-allantoin-pentaglycan gel.

Effect of allium cepa-allantoin-pentaglycan gel on skin hypertrophic scars: clinical and video-capillaroscopic results of an open-label, controlled, nonrandomized clinical trial.

BACKGROUND: Hypertrophic scar formation is a process in which prolonged angiogenesis sustained by vascular endothelial growth factor cutaneous expression plays an important role. OBJECTIVE: This in vivo study was conducted to evaluate the clinical effect of a topical gel containing onion extract, allantoin, and pentaglycan on hypertrophic scars and keloids. MATERIALS AND METHODS: Thirty people with hypertrophic scars or keloids were examined. Fifteen patients received a topical application of a gel containing allium cepa, allantoin, and pentaglycan twice a day for 24 weeks, the remaining 15 patients received no topical treatments. A clinical evaluation and an intravital videocapillaroscopy were performed on every patient at baseline (T0) and 24 weeks (T24) after the treatment. RESULTS: Only the patients who received the topical treatment showed a significant reduction in neoangiogenetic features, demonstrated through an improvement of erythema and all videocapillaroscopic markers of neoangiogenesis. These changes induced by therapy led to a general improvement of the lesions. CONCLUSION: Topical applications of a gel containing allium cepa, pentaglycan, and allantoin twice a day for 24 weeks seems to be useful in reducing neoangiogenesis in hypertrophic scars and keloids, resulting in clinical improvement of skin lesions. The authors have indicated no significant interest with commercial supporters.