Biosimilars for psoriasis: clinical studies to determine similarity.

Biosimilars are drugs that are similar, but not identical, to originator biologics. Preclinical analytical studies are required to show similarity on a molecular and structural level, but efficacy and safety studies in humans are essential to determining biosimilarity. In this review, written by members of the International Psoriasis Council, we discuss how biosimilars are evaluated in a clinical setting, with emphasis on extrapolation of indication, interchangeability and optimal clinical trial design.

Biosimilars for psoriasis: worldwide overview of regulatory guidelines, uptake and implications for dermatology clinical practice.

The introduction of biological drugs for the treatment of patients with psoriasis has revolutionized treatment paradigms and enabled numerous patients to achieve disease control with an acceptable safety profile. However, the high cost of biologics limits access to these medications for the majority of patients worldwide. In recent years, the introduction of biosimilars for inflammatory diseases has become a fast evolving field. The future use of biosimilars offers the potential for decreased cost and increased access to biologics for patients with psoriasis. For approval of biosimilars, different regulatory agencies use highly variable methods for definition, production, approval, marketing and postmarketing surveillance. Due to potential interchangeability between biologics and biosimilars, traceability and pharmacovigilance are required to collect accurate data about adverse events in patients with psoriasis; spontaneous reporting, registries and use of 'big data' should facilitate this process on a global basis. The current article describes biosimilar regulatory guidelines and examples of biosimilar uptake in clinical practice in several countries around the world. As it is apparent that biological therapy treatment decisions may become more physician independent, the International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies.

Real-life 9-year experience with adalimumab in psoriasis and psoriatic arthritis: results of a single-centre, retrospective study.

BACKGROUND: Observational studies in daily practice are an essential complement to pivotal randomised controlled trials because their findings refer to larger and more diverse patient populations with common comorbidities, complex medical history, concomitant medications and longer follow-up periods. OBJECTIVES: To evaluate long-term clinical outcomes of the anti-TNF-α monoclonal antibody, adalimumab, in patients with psoriasis (PsO) or psoriatic arthritis (PsA) referring to an Italian dermatological centre. METHODS: Single-centre retrospective real-world investigation with an observation period of up to 9 years. RESULTS: We reviewed the records of 316 patients (117 with PsO and 199 with PsA) treated with adalimumab and followed for up to 9 years. Safety and efficacy of adalimumab were consistent with those described in randomised controlled trials (RCTs) and other observational studies. A rapid and sustained improvement of skin lesions (evaluated as Psoriasis Area and Severity Index (PASI) 75, PASI 90 and PASI 100 response rates) was observed in the majority of patients, including those with body mass index (BMI) >30 and with prior experience of biologic therapies (including other anti-TNFs). The safety profile of adalimumab was confirmed also in elderly patients (>65 years). CONCLUSION: Our real-life experience shows that the long-term treatment with adalimumab is effective and well tolerated in psoriatic patients, including overweight/obese, elderly and anti-TNF-experienced subjects.

Quality of life and patient benefit following transition from methotrexate to ustekinumab in psoriasis.

BACKGROUND: TRANSIT (NCT01059773) compared immediate and gradual transition from methotrexate to ustekinumab in psoriasis patients via multiple measures, including patient-reported outcomes. OBJECTIVE: To evaluate patient perception of treatment benefits in TRANSIT. METHODS: A total of 489 psoriasis patients received ustekinumab, with immediate cessation of methotrexate (Arm 1) or 4 weeks' overlap with decreasing methotrexate dose (Arm 2). Ustekinumab was administered at weeks 0, 4, 16, 28 and 40. Dermatology Life Quality Index (DLQI), EuroQol 5-item (EQ-5D), visual analogue scale (VAS) valuation technique and patient benefit index (PBI) were employed. Mean global PBI and sub-scores were calculated from the sum of the benefit items weighted by their respective relevance at baseline. Patient-relevant benefit was defined as PBI ≥1 (scale: 0 [no benefit] to 4 [maximum benefit]). Correlations of global PBI with Psoriasis Area and Severity Index (PASI) and DLQI were examined. RESULTS: Relationships between PBI and clinical data were evaluable in 340 patients. The most important treatment goals at baseline included: 'be healed of all skin defects', 'have confidence in therapy', 'get better skin quickly' and 'regain control of the disease'. Benefit in PBI global score was achieved at week 4 by 93% of patients in Arm 1 and 91% in Arm 2. Global PBI scores increased in both Arms between weeks 4 and 52. Global PBI correlated weakly with PASI change from baseline (correlation coefficient range: -0.22 to -0.40), and moderately with DLQI (-0.29 to -0.54). Overall DLQI score was lower than baseline at all times; and the percentage of patients with an overall score of 0 or 1 increased with time. Correspondingly, EQ VAS scores increased with time. DLQI and EQ VAS results were similar between arms. CONCLUSIONS: Regardless of the strategy for transitioning from methotrexate, ustekinumab was associated with rapid and sustained improvement in patient-reported outcomes. PBI appears a suitable tool for assessing patient-relevant treatment benefits in psoriasis patients.

Dose adjustment of biologic therapies for psoriasis in dermatological practice: a retrospective study.

INTRODUCTION: Despite the large routine use of biologic drugs in psoriasis treatment, the majority of studies do not take into consideration dose-adjustment practice in 'real-life' dermatological setting. In routine clinical practice, the disease management may include a large number of conditions requiring non-standard dosage regimens, including dose escalation, dose reduction and/or off-label treatment interruption. OBJECTIVE: The ONDA (Outcome of non-standard dosing regimen in Psoriasis and Psoriatic Arthritis) study aim was to retrospectively analyse dose-adjustment strategies among biologic therapies for psoriasis in dermatological practice during a 3-year period. RESULTS: This retrospective, observational, multicentre study was carried out in 350 patients (68% male, 32% female) affected by plaque-type psoriasis (Pso) with a coexistence of psoriatic arthritis in 164 patients (46.9%). At baseline mean PASI score was 14.9 (SD 7.2). Dose adjustment was demonstrated to be a common practice with 70/350 patients (20%) who needed a dose variation during the treatment time, in particular a dose increase in 20/70 patients (28.6%) and a dose reduction in 50/70 patients (71.4%). Dose increase was due to inefficacy on Pso parameters in 60% of cases and to inefficacy of PsA parameters in 40% of cases, while dose reduction (or temporary off-label treatment interruption) was due to prolonged remission in 54% of cases, other reason in 18% of cases, patient choice or request in 14% of cases, occurrence of concomitant event in 12% of cases. CONCLUSION: Dose adjustment is a common clinical practice, consisting of frequent dose reduction when a disease prolonged remission is obtained or dose increase to improve efficacy on Pso and PsA disease parameters.

Latent tuberculosis infection in patients with chronic plaque psoriasis: evidence from the Italian Psocare Registry.

BACKGROUND: The nationwide prevalence of latent tuberculosis infection (LTBI) in Italian patients with psoriasis has never been investigated. OBJECTIVES: To estimate the nationwide prevalence of LTBI in Italian patients with psoriasis who are candidates for systemic treatment. METHODS: Data were obtained from the Psocare Registry on those patients (n = 4946) with age > 18 years, systemic treatment at entry specified and tuberculin skin test (TST) performed according to the Mantoux method. LTBI diagnosis was based on a positive TST result in the absence of any clinical, radiological or microbiological evidence of active tuberculosis. RESULTS: Latent tuberculosis infection was diagnosed in 8·3% of patients with psoriasis (409 of 4946). The prevalence of LTBI was lower in patients on biologics than in those on conventional systemic treatments, ranging from 4·3% (19 of 444) of patients on adalimumab to 31% (eight of 26) of those on psoralen-ultraviolet A (P < 0·05). Independent factors associated with LTBI were male sex [odds ratio (OR) 1·30, 95% confidence interval (CI) 1·04-1·62; P = 0·02], age over 55 years (OR 2·93, 95% CI 2·18-3·93; P < 0·001) and being entered into a conventional treatment (OR 3·83, 95% CI 3·10-4·74; P < 0·001). Positive history of tuberculosis was seen in 1% of patients (n = 49). CONCLUSIONS: The nationwide prevalence of LTBI in Italian patients with psoriasis candidate to systemic treatment is high, and screening is recommended prior to biological treatment.

Dermoscopic variability of basal cell carcinoma according to clinical type and anatomic location.

BACKGROUND: Correctly diagnosing basal cell carcinoma (BCC) clinical type is crucial for the therapeutic management. A systematic description of the variability of all reported BCC dermoscopic features according to clinical type and anatomic location is lacking. OBJECTIVES: To describe the dermoscopic variability of BCC according to clinical type and anatomic location and to test the hypothesis of a clinical/dermoscopic continuum across superficial BCCs (sBCCs) with increasing palpability. METHODS: Clinical/dermoscopic images of nodular BCCs (nBCCs) and sBCCs with different degrees of palpability were retrospectively evaluated for the presence of dermoscopic criteria including degree of pigmentation, BCC-associated patterns, diverse vascular patterns, melanocytic patterns and polarized light patterns. RESULTS: We examined 501 histopathologically proven BCCs (66.9% sBCCs; 33.1% nBCCs), mainly located on trunk (46.7%; mostly sBCCs) and face (30.5%; mostly nBCCs). Short fine telangiectasias, leaf-like areas, spoke-wheel areas, small erosions and concentric structures were significantly associated with sBCC, whereas arborizing telangiectasias, blue-white veil-like structures, white shiny areas and rainbow pattern with nBCCs. Short fine telangiectasia, spoke-wheel areas and small erosions were independently associated with trunk location, whereas arborizing telangiectasias with facial location. Scalp BCCs had significantly more pigmentation and melanocytic criteria than BCCs located elsewhere. Multiple clinical/dermoscopic parameters displayed a significant linear trend across increasingly palpable sBCCs. CONCLUSIONS: Particular dermoscopic criteria are independently associated with clinical type and anatomic location of BCC. Heavily pigmented, scalp BCCs are the most challenging to diagnose. A clinical/dermoscopic continuum across increasingly palpable sBCCs was detected and could be potentially important for the non-surgical management of the disease.

The impact of biologic therapy in chronic plaque psoriasis from a societal perspective: an analysis based on Italian actual clinical practice.

OBJECTIVE: Psoriasis is one of the most common forms of chronic dermatitis, affecting 2-3% of the worldwide population. It has a serious effect on the way patients perceive themselves and others, thereby prejudicing their quality of life and giving rise to a significant deterioration in their psycho-physical well-being; it also poses greater difficulties for them in leading a normal social life, including their ability to conduct a normal working life. All the above-mentioned issues imply a cost for the society. This study proposes to evaluate the impact on societal costs for the treatment of chronic plaque psoriasis with biologics (etanercept, infliximab and adalimumab) in the Italian clinical practice. METHOD: A prospective observational study has been conducted in 12 specialized centres of the Psocare network, located throughout Italy. Direct and indirect costs (as well as the health-related quality of life of patients with plaque psoriasis undergoing biologic treatments) have been estimated, while the societal impact has been determined using a cost-utility approach. RESULTS: Non-medical and indirect costs account for as much as 44.97% of the total cost prior to treatment and to 6.59% after treatment, with an overall 71.38% decrease. Adopting a societal perspective in the actual clinical practice of the Italian participating centres, the ICER of biologic therapies for treating plaque psoriasis amounted to €18634.40 per QALY gained--a value far from the €28656.30 obtained by adopting a third-party payer perspective. CONCLUSION: Our study confirms that chronic psoriasis subjects patients to a considerable burden, together with their families and caregivers, stressing how important it is to take the societal perspective into consideration during the appraisal process. Besides, using data derived from Italian actual practice, treatment with biologics shows a noteworthy benefit in social terms.

One-year safety and efficacy of ustekinumab and results of dose adjustment after switching from inadequate methotrexate treatment: the TRANSIT randomized trial in moderate-to-severe plaque psoriasis.

BACKGROUND: There are limited long-term, 'real-world' data on ustekinumab, or the effect of dose adjustment in suboptimal responders. OBJECTIVES: We describe 52-week data from TRANSIT, which initiated ustekinumab by licensed regimen and investigated exploratory dose adjustment. METHODS: Patients with moderate-to-severe psoriasis and inadequate methotrexate response received ustekinumab, with immediate or gradual methotrexate withdrawal. Outcomes were similar between treatment arms at week 12 (primary endpoint), so week 52 data were pooled. Patients weighing ≤ 100 kg or > 100 kg were administered ustekinumab 45 or 90 mg, respectively. Patients weighing ≤ 100 kg without 75% improvement in Psoriasis Area and Severity Index (PASI 75) response at weeks 28 or 40 received a dose adjustment to 90 mg. The primary analysis used observed data. RESULTS: Overall, 391 and 98 patients received ustekinumab 45 and 90 mg, respectively. Forty-four patients (9%) discontinued before week 52 (0·4% due to adverse events). At week 52 (in the overall population), 369 patients (83%) achieved a PASI score ≤ 5, and 341 patients (77%) achieved PASI 75; the median PASI score decreased from 15 at baseline to 1·8. At weeks 28 and 40, 84 and 31 patients, respectively, did not achieve PASI 75 and received a dose adjustment; by week 52, 35/82 (43%) and 15/31 (48%) of these patients, respectively, achieved PASI 75 (two discontinued between weeks 28 and 40). CONCLUSIONS: Ustekinumab showed sustained 1-year efficacy and was well tolerated when initially administered according to label. Adjusting the ustekinumab dose to 90 mg may result in clinically meaningful improvement in response in patients weighing ≤ 100 kg with suboptimal initial response.

Transition to ustekinumab in patients with moderate-to-severe psoriasis and inadequate response to methotrexate: a randomized clinical trial (TRANSIT).

BACKGROUND: Limited data exist on transitioning patients with psoriasis from conventional systemic agents to biologics. OBJECTIVES: The TRANSIT study aimed to assess the efficacy and safety of two methotrexate-to-ustekinumab transition strategies. METHODS: Patients with moderate-to-severe psoriasis and inadequate methotrexate response were randomized 1 : 1 to receive ustekinumab with immediate (arm 1) or 4-week gradual (arm 2) methotrexate withdrawal. Patients weighing ≤ 100 kg or > 100 kg received ustekinumab 45 mg or 90 mg, respectively. The primary endpoint was the frequency of adverse events (AEs) at week 12. Secondary endpoints included additional safety, efficacy and patient-reported outcomes. We report the 12-week efficacy and safety results. RESULTS: Overall, 244 patients in arm 1 and 245 in arm 2 were randomized and received ustekinumab. Four patients per arm discontinued the trial by week 12. At week 12 in arms 1 and 2, respectively, 61% and 65% of patients experienced an AE, 2·9% and 2·4% had a serious AE, and 1·2% and 0·4% had an AE leading to ustekinumab discontinuation. In arms 1 and 2, respectively, median Psoriasis Area and Severity Index (PASI) score decreased from 15·2 and 15·4 at baseline to 2·9 and 2·8 at week 12; 58% and 62% of patients achieved a 75% reduction from baseline in PASI score (PASI 75) at week 12; median baseline Dermatology Life Quality Index fell from 8 and 9 at baseline to 1 (both arms) at week 16. CONCLUSIONS: Ustekinumab was well tolerated and effective in patients who had an inadequate response to methotrexate. Both transition strategies resulted in similar week 12 safety and efficacy outcomes.

Management of non-melanoma skin cancer in solid organ transplant recipients.

Non-melanoma skin cancer (NMSC) is the most frequent cancer observed in solid organ transplant recipients (SOTR). Early diagnosis, patient education, and modification of immunosuppression are effective measures for reduction of NMSC incidence. Many risk factors have been identified, including age at transplantation, fair skin, type of immunosuppressive drugs, cumulative sun exposure, viral infections, and various genetic markers. Skin self-examination and photoprotection should be encouraged in all transplanted patients. Long-term skin surveillance, early diagnosis and aggressive treatment of any suspicious lesion, reduction of immunosuppressive therapy, and conversion to mammalian target-of-rapamycin (m-TOR) inhibitors can be also effective measures for reduction of NMSC incidence.

Cutaneous manifestations in patients with chronic renal failure on hemodialysis.

Patients with chronic renal failure (CRF) may exhibit various cutaneous abnormalities, including changes in skin colour, pruritus, xerosis, hair, nail and oral changes, metastatic calcinosis, and bullous dermatosis. These changes have a considerable negative effect on the patient's quality of life. Early recognition of cutaneous signs and prompt initiation of treatment can dramatically alter their course and decrease morbidity.

The role of tumour necrosis factor in the pathogenesis of immune-mediated diseases.

Immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthropathies, Crohn's disease, ulcerative colitis and juvenile idiopathic arthritis, comprise a group of chronic disorders characterized by an immune-mediated pathogenesis. Although at clinical presentation these diseases appear unrelated, they have been recognized to share similar pathogenic mechanisms. Data from epidemiological and genetic studies further support the concept that IMIDs are interrelated, as they can co-occur in the same patient and share a similar genetic susceptibility. The specific aetiologies of IMIDs remain unknown, but all are known to involve dysregulation of the immune system, including an over-expression of the pro-inflammatory cytokine tumour necrosis factor (TNF). The pivotal role played by TNF in the pathogenesis and pathophysiology of IMIDs has been documented by extensive preclinical and clinical investigations, and confirmed by the efficacy of anti-TNF biotechnological drugs, such as etanercept, infliximab and adalimumab, in the therapeutic management of these disorders. In this narrative review, we discuss the available data on the TNF-dependent pathogenesis of IMIDs and associations among the different disorders. Although much remains to be discovered about the pathogenesis and aetiology of IMIDs, their common inflammatory pathological features may explain why they can be successfully targeted by anti-TNF drugs. Among these, adalimumab, a fully human monoclonal antibody, has been approved for treatment of nine distinct IMID indications and it is likely to become a valuable therapeutic tool for this complex cluster of chronic inflammatory disorders.

anti-TNF agents as therapeutic choice in immune-mediated inflammatory diseases: focus on adalimumab.

The complex pathogenesis of immune-mediated inflammatory diseases (IMIDs) has been extensively investigated and dysregulation of cytokines, such as tumour necrosis factor (TNF) has been shown to play a dominant role in the pathogenesis of various IMIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. The subsequent development of biological agents capable of blocking TNF has led to important advances in the pharmacotherapy of such diseases and confirmed the concept of a common pathophysiology among IMIDs with TNF having a predominant role. Five TNF inhibitors have currently been approved for treatment of one or more IMIDs; these include infliximab, etanercept, adalimumab, golimumab and certolizumab pegol. Given the similarities in the pathogenic background of IMIDs, one could expect that anti-TNF agents be similarly effective and with comparable tolerability profiles; however, this may not be the case. Structural and pharmacological differences among the anti-TNF drugs are likely to result in differences in efficacy and tolerability among the agents in the different IMIDs, together with differences in potency, therapeutic dose ranges, dosing regimens, administration routes, and propensity for immunogenicity. Among the five TNF inhibitors approved for treatment of IMIDs, adalimumab has the widest range of indications. Data from controlled clinical trials of adalimumab, showing its excellent efficacy and tolerability in a wide range of indications, are supported by real-world long-term data from observational studies, which confirm the value of adalimumab as a suitable choice in the management of IMIDs.

Adalimumab in the treatment of immune-mediated diseases.

Tumour necrosis factor (TNF) plays an important role in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). TNF inhibition results in down-regulation of abnormal and progressive inflammatory processes, resulting in rapid and sustained clinical remission, improved quality of life and prevention of target organ damage. Adalimumab is the first fully human monoclonal antibody directed against TNF. In this article, we review the role and cost effectiveness of adalimumab in the treatment of IMIDs in adults and children. The efficacy and tolerability of adalimumab has been demonstrated in patients with a wide range of inflammatory conditions, leading to regulatory approval in rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis, inflammatory bowel diseases (Crohn's disease, ulcerative colitis, paediatric Crohn's disease, and intestinal Behçet's disease), ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and juvenile idiopathic arthritis. The major tolerability issues with adalimumab are class effects, such as injection site reactions and increased risk of infection and lymphoma. As with all anti-TNF agents, adalimumab is immunogenic, although less than infliximab, and some patients receiving long-term adalimumab will develop anti-drug antibodies, causing a loss of response. Comparisons of its clinical utility and cost effectiveness have shown it to be a valid treatment choice in a wide range of patients. Recent data from Italian economic studies show the cost effectiveness of adalimumab to be below the threshold value for health care interventions for most indications. In addition, analysis of indirect costs shows that adalimumab significantly reduces social costs associated with RA, PsA, AS, Crohn's disease and psoriasis. The fact that adalimumab has the widest range of approved indications, many often presenting together in the same patient due to the common pathogenesis, may further improve the utility of adalimumab. Current clinical evidence shows adalimumab to be a valuable resource in the management of IMIDs. Further research, designed to identify patients who may benefit most from this drug, will better highlight the role and cost-effectiveness of this versatile TNF inhibitor.

Immunologic biomarkers for clinical and therapeutic management of psoriasis.

BACKGROUND: The therapeutic management of psoriasis includes conventional treatments as well as the new generation of highly effective TNF-α inhibitors. However, psoriasis has proven to be a complex therapeutic challenge and treatment failures are not uncommon. Thus, laboratory biomarkers of disease progression/therapeutic efficacy may greatly help in the clinical management of psoriasis. AIMS: To identify laboratory biomarkers for clinical management and therapeutic monitoring of psoriasis. METHODS: An observational study performed on 59 patients, presenting moderate to severe psoriasis, undergoing treatment with anti-TNF-α agents (etanercept, adalimumab, and infliximab). Soluble and cellular immune/inflammatory parameters were assessed at baseline and after 12 and 24 weeks of treatment. RESULTS: Clinical efficacy was achieved in 88% of the subjects at 12 weeks, reaching 90% after 24 weeks. IL-6 and IL-22, which were elevated at baseline, were significantly reduced, in association with a significant decrease of CLA+ T cells and an increase of Treg lymphocytes. T, B, and NK cell subsets and T cell response to recall antigens did not show any evidence of immune suppression. CONCLUSIONS: Immune/inflammatory parameters including IL-6 and IL-22, CLA+ T cells, and Treg lymphocytes may prove to be valuable laboratory tools for the clinical and therapeutic monitoring of psoriasis.

Betamethasone valerate dressing is non-inferior to calcipotriol-betamethasone dipropionate ointment in the treatment of patients with mild-to-moderate chronic plaque psoriasis: results of a randomized assessor-blinded multicentre trial.

BACKGROUND: A ready-to-use betamethasone valerate 0.1% (BMV) dressing was found to be superior to placebo dressing and a reference 0.1% BMV cream in the treatment of patients with chronic plaque psoriasis (CPP). METHODS: This multicentre, prospective, randomized, investigator-blinded, controlled, non-inferiority trial compared the efficacy and safety of the BMV dressing to the calcipotriol-betamethasone dipropionate (CBD) ointment during a 4-week treatment of patients with mild to moderate CPP. The primary efficacy endpoint was the 4-item psoriasis total severity score (TSS-4) at week 4, and the associated non-inferiority margin was 1 point. Secondary outcome measures included the psoriasis global assessment (PGA) score and patients' quality of life (QoL). Safety was assessed through adverse events (AE) reporting in each treatment group. RESULTS: Of 325 screened patients, 324 were randomized to BMV (N = 165) or CBD (N = 159), and were considered evaluable for the safety and intention-to-treat (ITT) efficacy analyses. Per protocol (PP) populations included 133 and 131 patients in the BMV and CBD groups respectively. The mean adjusted TSS-4 significantly decreased through the study from baseline in both groups. The PP (primary) analysis of week 4 data revealed a -0.288 (95% CI: -0.610 to 0.034) not significant between-group difference in adjusted means, demonstrating non-inferiority of BMV to CBD. Non-inferiority was also demonstrated in the ITT analysis. The PGA and other secondary outcomes were significantly improved from baseline in both groups at week 4. The QoL score was slightly better in the CBD group at week 4, but no difference was observed at follow-up. No safety or tolerability concerns were observed in either group. CONCLUSIONS: BMV dressing is non-inferior to CBD ointment in patients with mild to moderate CPP. Both treatments significantly improve patients' psoriasis and QoL.

Benign dermoscopic features in melanoma.

BACKGROUND: Various dermoscopic features are usually associated with benign melanocytic lesions. Our objective was to determine frequency and extension of benign dermoscopic features (BDF) in melanoma. METHODS: Retrospective review of dermoscopic images of a consecutive series of 516 histopathologically proven melanomas collected in 6 years in Graz. Correlation of BDF with mean Breslow thickness, with presence/absence of associated benign nevus component and with the pre-operative clinico-dermoscopic diagnosis, as reported on the original histopathologic reports. RESULTS: In addition to melanoma specific criteria, 42% of melanomas showed BDF. In 12.3% cases, the benign features occupied more than the half of the lesion. The BDF typical pigment network, homogeneous pattern and regular globules/cobblestone pattern had the highest frequency. BDF were associated with relatively thinner melanomas (mean Breslow thickness of 0.51 mm). The presence of BDF was observed in 67.1% of histopathologically documented nevus-associated melanoma and in 35.7% of melanoma de novo. A pre-operative clinico-dermoscopic diagnosis of melanoma was achieved in only 54.1% of cases displaying BDF. CONCLUSION: A significant proportion of melanomas may exhibit BDF. Clinicians should be aware of the presence of BDF in melanoma as possible diagnostic pitfall.

Topical lactoferrin can improve stable psoriatic plaque.

AIM: Lactoferrin (LF), a non-haem iron binding glycoprotein, shares antimicrobial properties with innate immune system components influencing proinflammatory release of cytokines involved in psoriatic plaque development. The objective of the study was to verify if LF could provide a therapeutic application in psoriasis. METHODS: An open-label, two arms, 4-week trial was designed on 30 subjects affected by mild to moderate plaque psoriasis. All patients received oral bovine LF 100 mg. Fifteen patients (group A) were topically treated with 10% LF ointment, 15 patients (group B) with 20% LF ointment. All patients applied only ointment vehicle on contra lateral target lesion as intra-patient side to side control. Efficacy was assessed by Target Lesion Score. RESULTS: Twenty-two patients completed the study. Improvement in elevation, redness and scaling was observed on LF treated psoriatic target lesions comparing to the controlateral controls (P<0.05). There was no additional efficacy for 20% versus 10% topical applications. Oral drug alone did not exert any improvement on the control plaques receiving topical placebo. CONCLUSION: Our clinical results suggest that LF could be included as a possible safe topical therapeutic option in the treatment of psoriatic plaque.

Relapsed actinic keratosis evaluation: an observational Italian multicenter prospective study. Does gender have a role?

AIM: Relapsed actinic keratoses evaluation study (RAKE) was performed in nine Italian centers of dermatology in order to observe the outcome of the treatments of these common skin neoplasms. METHODS: A total of 182 patients were enrolled in 2 cohorts: the first included 144/182 patients (79.1%) evaluated after 6 months from clinical remission, and the second 116/182 (63.7%) evaluated for at least 12 months after clinical remission. Patients were previously treated with topical diclofenac 3% in hyaluronic acid, cryotherapy, photodynamic, curettage or imiquimod cream. RESULTS: Subjects with history of malignant skin diseases showed an increased number of new lesions at 16 months from baseline (12 months from remission) compared to patients without history of cancers (mean 1.58 versus 1.17). Hyperkeratotic lesions healed more rapidly but relapsed at 6 months more frequently than non-hyperkeratotic ones (32.9% versus 20.7%). The results showed gender-related differences: male patients recovered better and independently from the treatment used; in contrast, men showed a higher recurrence (32% at 6 months and 6.6% between 6 and 12 months versus 16% at 6 months and 5.9% between 6 and 12 months for females) and a higher average number of new lesions after 12 months from remission (1.6 versus 0.88 for females). CONCLUSION: The results may suggest a lower adherence to photoprotection in male patients. Hyperkeratotic lesions recurred mostly at 6 months in comparison to non-hyperkeratotic lesions.