Predictive factors of lack of response to adalimumab among bio-naive patients suffering from moderate-to severe psoriasis: analysis of a multicenter data collection in Italy.

INTRODUCTION: Efficacy of anti-TNF-a agents seems inferior to IL-17 and IL-23 inhibitors. Nevertheless, after biosimilars approval, anti TNF-a agents are recommended as first-line for psoriatic patients, for economic reasons. METHODS: Predictive factors of response or non-response to adalimumab in bionaive patients who started adalimumab (originator or biosimilar) over 12 years in 9 dermatologic centers in Italy. Effectiveness was assessed with Psoriasis Area and Severity Index (PASI75 and PASI90) at weeks 12, 24 and 48. Multiple logistic regressions were used for variables predicting clinical response; Kaplan-Meier survival curves and Cox regression for drug survival. RESULTS: The drug survival analysis showed reduced hazard ratio of overall discontinuation with male gender and scalp localization. In contrast, baseline PASI and genital psoriasis were significantly associated with increased risk of overall discontinuation. Predictive factors of non-response seemed elevated in patients with baseline PASI, older age groups, previously treated patients with phototherapy, females or patients with palmo-plantar while scalp psoriasis, previous cyclosporine and acitretin appeared as a positive predictive factor. CONCLUSIONS: This real-life analysis might be useful for clinicians in case of bio-naive patients with moderate-to-severe psoriasis and various comorbidities.

Emergency dermatology: Three-month experience from an Italian academic outpatient clinic during lockdown for COVID-19 pandemic.

Dermatology is a field of medicine where urgent cases occur commonly. However, access to specialized emergency dermatology services is very limited. Following the declaration of the COVID-19 pandemic, the cessation of all elective dermatology visits was widely urged. Accordingly, in Italy, a country severely affected by the pandemic, various measures were applied and the care at university clinics was limited to urgent cases. Here we retrospectively analyzed data of patients who presented at an Italian academic outpatient clinic reserved only for emergency cases. In total, 252 patients (109 males and 143 females) with a mean age of 55.25 ± 20.99 years were cared for at our clinic during a three-month period. We classified 10 patients (4%) as real emergency cases. Pityriasis rosea was diagnosed in three patients. Many patients sought care for skin cancer screening. In 131 patients (52%) dermoscopic skin examinations were performed. In 39 patients (15%), actinic keratosis or nonmelanoma skin cancer was detected, while melanoma was diagnosed in three patients, two of which were proven later as in situ melanoma. About 111 patients (44%) visited our clinic for other, nonurgent skin diseases. Our results imply that many patients felt that their skin problems required immediate attention, even if this could not be justified. Melanoma care may be considered an emergency care for its highly malignant potential and the possibility of rapid spreading. Adequately taken photos with a dermoscope may be readily read without the presence of specialist in the emergency room to prevent unnecessary delay in diagnosing oncologic skin diseases.

Nonmelanoma skin cancer associated with Hydroxyurea treatment: Overview of the literature and our own experience.

Nonmelanoma skin cancer is the most common malignant tumor in the fair skin population, with each year several millions of diagnosed cases. Their most common risk factors are fair skin, a history of excessive ultraviolet light exposure, chronic inflammatory skin conditions, exposure to radiation, and contact with arsenic. Certain drugs can also be associated with a higher risk of nonmelanoma skin cancer. These include hydroxyurea, which acts as a metabolic inhibitor of ribonucleotide reductase and a potent nonalkylating myelosuppressive agent. It is used for the treatment of various myeloproliferative disorders, including chronic myeloid leukemia, polycythemia vera, and essential thrombocytopenia. Several publications describe an increased occurrence of skin manifestations following hydroxyurea treatment. A growing body of evidence indicates a possible role of hydroxyurea in skin cancer progression. In this review article, we summarize some relevant observations about the association of hydroxyurea and skin cancer, and we describe our own clinical experiences to provide up to date recommendations about the care of patients on hydroxyurea therapy.

Type I leucocyte adhesion deficiency in Yemenian family managed with appropriate treatment: A case series.

Primary immunodeficiencies are rare, inherited diseases, characterized by altered function or absence of immune cells. Among them is leukocyte adhesion deficiency Type I (LAD-I), an autosomal recessive disorder characterized by primary immunodeficiency, caused by mutations in the ITGB2 gene which produces inability of leucocytes to migrate toward the area of inflammation and is associated with recurrent life-threatening bacterial and fungal infections. Pyoderma gangrenosum (PG) is an uncommon noninfectious neutrophilic dermatosis, characterized by recurrent, necrotic ulcers. It is a diagnosis of exclusion and can be challenging and its management is empirical, with local (topical tacrolimus or intralesional triamcinolone) or systemic immunosuppressive therapy (oral or intravenous glucocorticoids, sulfasalazine, especially in cases associated with Crohn's disease, cyclosporine and, recently, anti-tumor necrosis factor drugs such as Infliximab, Etanercept, and Adalimumab). Though skin ulcerations are common, predominant clinical presentation as PG can often mimic other diseases. It is unusual in children even more in LAD-I. Here, we present a Yemenian family with LAD-I from consanguineous relatives. All patients had history of chronic recurrent skin ulcerations without any bleeding tendency, associated with persistent neutrophilia and requiring steroids and antibiotics. There was no history of delayed cord separation and the condition was initially diagnosed as epidermolysis bullosa, but successively as PG. LAD-I should be kept in mind while evaluating patients with PG especially in children with persistent neutrophilia in the absence of other rheumatological disorders. Its diagnosis is extremely important from the management perspective, as treating these patients without adequate antibiotic cover may be fatal, as happened to one of our patient, and these patients often require hematopoietic stem cell transplantation for permanent cure. Therefore, genetic counseling especially in population with high consanguinity is mandatory.

Treating psoriasis with etanercept in italian clinical practice: prescribing practices and duration of remission following discontinuation.

BACKGROUND: 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 >or=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 >or=50% (PASI50) and a PASI score <10 at the end of treatment. Etanercept treatment was restarted if the PASI score reached >or=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 >or=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 re-treatment 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.