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Immunogenicity of anti-TNFα therapy in psoriasis: a clinical issue?

Introduction: Immunogenicity of antitumor necrosis factor-alpha (TNFα) agents has been proven to play a significant role in the variability of clinical responses among patients with chronic inflammatory diseases. However, its clinical impact on the outcome of patients with psoriasis and psoriatic arthritis receiving anti-TNFα treatment is not yet fully clear. Despite the high rates of efficacy of anti-TNFα agents in psoriasis, a substantial proportion of patients remain who experience a primary or secondary failure or significant side effects, which are potentially ascribable to immunogenicity. Areas covered: Topics include immunologic response elicited by anti-TNFα agents, the impact of immunogenicity on treatment response to anti-TNFα and the role played by immunogenicity in the lack of efficacy of anti-TNFα agents (infliximab, adalimumab and etanercept) in psoriasis. Expert opinion: Based on data available in the literature and the clinical experience of the authors, this article suggests the optimal approach to drug monitoring and antidrug antibody assay and the most effective use of biologic immunotherapies in this setting. Immunogenicity should be taken into account in the adoption of therapeutic choices in psoriatic patients, such as anti-TNFα agent intensification, or switching to another anti-TNFα agent or a drug with a different mechanism of action.

Correlations between Psoriasis and Inflammatory Bowel Diseases

For a long time the relationship between inflammatory bowel diseases (IBDs) and psoriasis has been investigated by epidemiological studies. It is only starting from the 1990s that genetic and immunological aspects have been focused on. Psoriasis and IBD are strictly related inflammatory diseases. Skin and bowel represent, at the same time, barrier and connection between the inner and the outer sides of the body. The most important genetic correlations involve the chromosomal loci 6p22, 16q, 1p31, and 5q33 which map several genes involved in innate and adaptive immunity. The genetic background represents the substrate to the common immune processes involved in psoriasis and IBD. In the past, psoriasis and IBD were considered Th1-related disorders. Nowadays the role of new T cells populations has been highlighted. A key role is played by Th17 and T-regs cells as by the balance between these two cells types. New cytokines and T cells populations, as IL-17A, IL-22, and Th22 cells, could play an important pathogenetic role in psoriasis and IBD. The therapeutic overlaps further support the hypothesis of a common pathogenesis.

Topical immunomodulator therapy with squaric acid dibutylester (SADBE) is effective treatment for severe alopecia areata (AA): Results of an open‐label, paired‐comparison, clinical trial

Severe alopecia areata (AA) may have a chronic relapsing course and is often resistant to current treatments. Objectives: The aim of our study was to evaluate whether topical immunotherapy with squaric acid dibutylester (SADBE) is able to improve the course of severe AA and to reduce the severity of relapses. Methods: Fifty‐four patients affected by severe AA treated with SADBE who were followed for a period of at least 2 years were selected as the study group. Data collected were compared with those of a matched control group of 54 patients who did not receive any treatment. Students t‐test, analysis of variance (ANOVA) and Pearsons chi‐squared test were utilized for data analysis. Results: At the end of therapy, in comparison with the control group, the treatment group showed a statistically significant (p<0.001) improvement. At follow‐up, there was no significant change in relapse rate (treated 44% vs control 52%). However, relapses in the treated group were significantly less severe compared with the control group (p<0.001). Conclutions: Our data suggest that topical SADBE represents a valid therapeutic option in severe AA, and may prove to be disease modifying.

BRAF and NRAS Mutations are Heterogeneous and Not Mutually Exclusive in Nodular Melanoma

Inhibitors of RAF inhibit the MAPK pathway that plays an important role in the development and progression of those melanoma carrying the V600E BRAF mutation, but there’s a subset of such patients who do not respond to the therapy. Various mechanisms of drug resistance have been proposed which include the clonal heterogeneity of the tumor. We have studied a population of nodular melanoma to investigate the intratumor and intertumor heterogeneity by Laser Capture Microdissection (LCM) analysis. Our results showed that BRAF and NRAS mutations were detected in 47% and 33% of nodular melanoma, respectively, and that there is a discrepancy in mutational pattern of tumoral sample because in the 36% of patients a different mutation, in at least 1 area of the tumor, was found by LCM analysis, giving evidence of the presence of different clonal cells populations. Moreover, we found that mutations in BRAF and NRAS are not mutually exclusive because they were simultaneously present in the same tumor specimens and we observed that when the 2 different mutations were present one is a high-frequency mutation and the other is a low-frequency mutation. This was more evident in lymphonodal metastasis that resulted from wild type to mutational analysis, but showed different mutations following LCM analysis. Therefore, we believed that, when primary tumoral sample results negative to mutational analysis, if it is possible, metastases should be investigated to verify the presence of mutations. Generally, it should be searched for other mutations, in addition to BRAF V600E, so as to better understand the mechanism of drug resistance.

Mediterranean diet and familial dysmetabolism as factors influencing the development of acne

Aim: To investigate the effects of adherence to the Mediterranean diet and familial dysmetabolisms on acne development. Methods: A community-based case–control study was carried out in Italy enrolling cases as acneic outpatients of a dermatological ambulatory service and controls as clinically healthy acne-free subjects. Food consumption were evaluated with a validated food-frequency questionnaire, exploring the consumption of pasta, meat, cheese, fish, fruit, vegetables, and olive oil. Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean diet scale that incorporated the main characteristics of this diet. A logistic regression analysis estimated the variables who predicted the odds of being case, using those variables that at the univariate analysis yielded a p-value <0.25. Results are presented as odds ratio (OR) or adjusted OR (AOR). Results: The study included 93 cases (36.6% males, median age 17 years) and 200 controls (32% males, median age 16 years). The Mediterranean diet score ≥6 revealed a protective effect towards acne (crude OR 0.22, 95% CI 0.08–0.64). Logistic regression analysis showed that familial hypercholesterolaemia, diabetes, and hypertension are strong risk factors for acne (AOR 8.79, 95% CI 1.67–46.22; 3.32, 95% CI 1.27–8.63; and 2.73, 95% CI 1.07–6.96, respectively), while the Mediterranean diet represents a protective factor (score ≥6, AOR 0.31, 95% CI 0.11–0.89). Conclusions: The odds for familial dysmetabolisms was higher in cases than in controls, confirming their role in determining or maintaining acne. Moreover, this is the first study demonstrating a protective role of the Mediterranean diet in the pathogenesis of acne.

Psodisk, a new visual method for assessing the burden of psoriasis on patients

Background  The last decades have witnessed an increasing interest for the psychosocial aspects of chronic skin diseases, such as psoriasis. Nonetheless, systematic assessments of the impact of psoriasis on patients’ lives are rarely done in daily clinical practice. The existing instruments are mostly meant to be completed by patients alone, and rarely comprise a graphical representation of the results.

Treating psoriasis with etanercept in Italian clinical practice: Prescribing practices and duration of remission following discontinuation

AbstractBackground: Conventional antipsoriatic therapies are often administered until remission, with treatment resumed in the case of relapse, in order to reduce the likelihood of cumulative, dose-dependent toxicities. Biological agents have been safely used in continuous therapy. Objective: To assess the use of etanercept for psoriasis in clinical practice in Italy. Methods: This was an observational study carried out in 13 dermatological centres across Italy in patients with plaque psoriasis (with a Psoriasis Area and Severity Index [PASI] score ≥10) treated with etanercept. The study comprised a treatment and subsequent discontinuation period. Patients were eligible if they had plaque psoriasis and had begun treatment with etanercept between 1 September 2007 and 1 April 2008. Patients were evaluable for the duration of discontinuation analysis if they achieved a PASI reduction ≥50% (PASI50) and a PASI score <10 at the end of treatment. Etanercept treatment was restarted if the PASI score reached ≥10 or the patient had a clinical relapse. Data were collected retrospectively up to June 2008 and prospectively between July 2008 and January 2009. Patients received etanercept during the treatment period, followed by no etanercept treatment (other psoriasis treatment permitted) during the discontinuation period, and etanercept again during re-treatment. The main outcome measures were: PASI scores (type A responders: PASI reduction ≥75% [PASI75]; type B responders: PASI50 and PASI final score <10), Dermatology Life Quality Index (DLQI) scores and body surface area (BSA) involvement. Time from discontinuation to retreatment was evaluated. Use of other antipsoriatic medications was recorded throughout. Results: Eighty-five patients were evaluable for the treatment period. Overall, 55 (64.7%) of these patients were prescribed etanercept 50 mg twice weekly. The mean treatment duration was approximately 25 weeks. In total, 79 patients (92.9%) were considered type B responders and 77 of these patients were evaluable for the duration of discontinuation analysis. Overall, 68/85 (80%) were type A responders. During the treatment period, 7/85 (8.2%) patients received other antipsoriatic therapies. Improvements in mean DLQI score (−71.5%) and mean BSA involvement (−79.2%) were also observed. Etanercept was well tolerated. During the discontinuation period, 40/77 (51.9%) patients used other antipsoriatic medications (group 1) and 37/77 (48.1%) did not (group 2). The mean duration of discontinuation was significantly longer in group 1 (174 days) than in group 2 (117 days, log-rank test: p = 0.0013). Conclusion: In clinical practice, the duration of discontinuation from etanercept was in accordance with previously reported data, and was longer in patients who received other antipsoriatic drugs during discontinuation of etanercept than in those who did not. High rates of PASI50 and PASI75 response were obtained with etanercept, and these rates were higher than those observed in controlled clinical studies. Etanercept treatment was flexible, effective and well tolerated, and was associated with improved quality of life.

The impact of psoriasis on work‐related problems: a multicenter cross‐sectional survey

Psoriasis can have cumulative physical and psychosocial effects preventing sufferers from achieving their full‐life potential. Few studies have addressed the impact of psoriasis on work‐related characteristics.

Adalimumab in the treatment of plaque-type psoriasis and psoriatic arthritis

Introduction: Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated diseases, and TNF-α (tumor necrosis factor) is a pro-inflammatory cytokine that plays a critical role in the pathogenesis of these conditions. Adalimumab is an anti-TNF-α drug widely used for the treatment of both psoriasis and PsA. Controlled clinical trials demonstrated that adalimumab is characterized by a high degree of clinical response. The aim of this review is to report the safety, efficacy, and recent findings in the treatment of psoriasis and PsA with adalimumab. Areas covered: This article reviews the results of Phase II, III, controlled, and observational clinical studies on adalimumab in the treatment of psoriasis and PsA. A systematic search was conducted using the Pubmed Medline database for primary articles. Expert opinion: Treatment of psoriasis and PsA represents a therapeutic challenge for dermatologists and rheumatologists. The efficacy, tolerability, and safety profiles suggest adalimumab as a suitable anti-psoriatic drug in the long-term treatment of psoriasis and PsA. Management of long-term treatment, loss of efficacy, and comorbidities has been described.

Acitretin in management of diffuse common warts: a case report

Warts are among the most commonly observed dermatological diseases, caused by human papilloma virus (HPV), usually HPV1‐2 subtypes; HPV4‐7 are rarely found and mostly related to professional exposure (butchers and dairy workers). Different therapeutical approaches are possible, depending on extension and severity of lesions. The present authors describe the case of 32‐year‐old Caucasian man, who came to our attention for the presence of numerous exophytic papules on the back of both hands and over periungual regions, which appeared about 6 months before. Histological examination confirmed the clinical suspicion of common warts (HPV4). The patient underwent therapy by acitretin for 12 weeks, obtaining during the 8th week of therapy complete resolution of skin lesions. The present authors present this case for the unusual local aggressiveness of viral warts in an immunocompetent patient successfully treated with acitetrin.