Real-Life Effectiveness and Safety of Guselkumab in Patients with Psoriasis Who Have an Inadequate Response to Ustekinumab: A 3-Year Multicenter Study.

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment.

A single-operator experience using EchoLaser SoracteLiteTM for focal laser ablation of prostate cancer: One more arrow in the quiver for the conservative management of the disease.

BACKGROUND: The aim of this study was to evaluate the outcomes of patients suffering prostate cancer (PCa) treated conservatively using 1064 nm laser energy for focal laser ablation (FLA). The patients included in the study were unsuitable for surgery or unwilling to receive external beam radiotherapy because they were afraid of the possible side effects of whole-gland therapies. METHODS: This study included patients with a diagnosis of nonmetastatic PCa who underwent FLA using SoracteLiteTM system. Tissue ablation was performed at a fixed power of 5 W by the diode multichannel laser system EchoLaser X4 that uses laser light transmitted through optical fibres causing the target tissue to undergo irreversible thermal damage. Functional outcomes were evaluated with the International Prostatic Symptoms Score (IPSS) and 5-item version of the International Index of Erectile Function (IIEF-5) before the treatment and one year later. RESULTS: Ten patients suffering non-metastatic PCa were included. Four decided upon a conservative treatment because of reduced performance status and for six patients the procedure was chosen electively. All patients underwent multiparametric magnetic resonance imaging at 3 and 12 months and eight out of ten patients underwent prostate biopsy at 6 months. Persistent disease was detected in 3 patients who underwent a second ablation. In these patients at the biopsy following the second ablation none harbored residual disease. At follow-up, no patient suffered urinary incontinence requiring the use of pads. No significant worsening in sexual potency measured with IIEF-5 (p = 0.356) or prostatic symptoms measured at IPSS (p = 0.462) were recorded comparing pre-treatment condition vs one-year follow-up. Compared with baseline, prostate-specific antigen was significantly reduced at one-year follow-up (3.7 ± 1.1 vs 7.9 ± 4.1 ng/mL; p = 0.008). CONCLUSIONS: Although whole gland therapies remain the gold standard treatment for PCa, our results indicate that the SoracteLiteTM system for focal laser ablation, as a very preliminary step, appears to offer a short-term oncologic control of PCa with negligible side effects.

The Efficacy and Safety of Abrocitinib as a Treatment Option for Atopic Dermatitis: A Short Report of the Clinical Data.

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease that predominantly affects children. However, it can persist in adulthood and/or start at older ages. Both dysfunction of the epidermal barrier and immune dysregulation are known to play a role in the pathogenesis of AD. In the last years, numerous studies showed that Janus kinase (JAK) enzymes have a key role in AD pathogenesis. Therefore, oral and topical JAK inhibitors are new emerging treatments for AD. We report the data relating to abrocitinib, an oral JAK1 inhibitor. For this purpose, we examined articles already published concerning, in particular, concluded clinical trials. Furthermore, we also report the design of current ongoing clinical trials. The search was carried out considering the main search engines relating to medical literature and clinical trials. From all the data we collected, abrocitinib proved to be an effective drug in significantly reducing the severity of moderate-to-severe AD when compared to placebo. Furthermore, the efficacy was similar to other well-established treatment for AD, such as dupilumab. Adverse events were generally mild; indeed, the drug was definitively suspended only in few patients.

Dermoscopic patterns of intradermal naevi.

BACKGROUND: Intradermal naevi represent a benign histopathological variant of common melanocytic naevi. Studies describing dermoscopic criteria of dermal naevi are very limited. OBJECTIVES: To identify dermoscopic features of dermal naevi in order to facilitate differential diagnosis from malignant lesions. METHODS: A 15-year retrospective study was performed to evaluate the dermoscopic characteristics of 202 dermal naevi, histopathologically diagnosed through the analysis of digital dermoscopic images performed with polarised light dermoscopy. For each lesion, vascular pattern, pigment pattern and other dermoscopic clues were evaluated. RESULTS: 147 Unna naevi and 55 Miescher naevi were included in the study. Brown pigment (37.1%) was the pigment pattern most frequently observed in both Unna and Miescher naevi, followed by cobblestone pattern (30.6%) in Unna naevi and white areas (23.6%) and dotted/globule pattern (20%) in Miescher naevi. As regards the vascular patterns, the polymorphic one was the most frequently observed (34.6%). The combination between comma-shaped and arborising vessels was the most common among all naevi. CONCLUSIONS: Our study describes the dermoscopic features of dermal naevi that may help to differentiate them from malignant lesions such as basal cell carcinoma, amelanotic melanoma and Spitz naevi.

The pharmacology of antibiotic therapy in hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, inflammatory, and debilitating skin disease. Several pharmacologic agents have been described to reduce lesion activity and inflammation in HS. In this study, we have reviewed the available antibiotic therapies for HS, analyzing the pharmacologic aspects of these kind of treatments. AREAS COVERED: The role of bacteria, infections, and superinfections in HS is still debated and controversial. Antibiotics are recognized as first-line treatments for hidradenitis suppurativa, but the data on their efficacy are limited. Antibiotics should not be replaced by new biological therapies and it is not necessary to make an efficacy classification: it is important for dermatologists to recognize the right patient and the right moment to prescribe an antibiotic therapy, together or in a rotational way with other therapeutic options. EXPERT OPINION: The HS treatment process for the physicians is often complicated by the disease's severity and several comorbidities. Fortunately, a better understanding of HS pathogenesis has been used to improve treatment strategies. Antibiotic therapy is an effective treatment of patients with HS but probably, in the next five years, many therapeutic options will be available, which will change the way we manage the disease, especially the moderate-to-severe forms of HS.

Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency.

Celiac disease (CD) and selective IgA deficiency (IgAD) are frequently associated, and share the same genetic background. The aim of the present study was to evaluate both Type 1 and 2 plasma cytokine levels in CD and in CD-IgAD. IL-2, TNF-alpha, IL-10, IL-4 and IL-13 plasma levels were measured both at diagnosis and after a gluten-free diet (GFD) in 32 CD patients, in 27 CD-IgAD patients and in 30 healthy controls. IFN-gamma levels were significantly higher in CD and CD-IgAD than in controls, TNF-alpha displayed significantly higher levels in CD-IgAD when compared both with controls and with CD, and IL-2 was in CD-IgAD significantly increased respect to controls. Kinetics of the Type 1 cytokine plasma levels did not show a clear relationship with the GFD in both groups of CD patients, and particularly in those with IgAD. IL-4 and IL-13, both at diagnosis and after a GFD, were not significantly different in controls and in celiac patients (with and without IgAD). IL-10, whose production is stimulated by the TNF-alpha, had significantly higher plasma levels in CD-IgAD, but not in CD patients, with a significant decrease after a GFD. CD and especially CD-IgAD patients display persistently higher pro-inflammatory cytokine levels, suggesting a persistent state of activation of pro-phlogistic signals in CD, particularly when IgAD coexists. Serial measurement of serum IL-10 may be an adjunctive evaluating criterion in the follow-up of CD-IgAD patients.

IL-10 and TNF-alpha polymorphisms in a sample of Sicilian patients affected by tuberculosis: implication for ageing and life span expectancy.

Human longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses, in particular cytokine gene polymorphisms. In fact, modification of cytokine network is a constant report in studies on age related modification of immune response. Moreover cytokine polymorphisms studies are indicating their involvement in the reshaping of cytokines network as an integral part of the scenario related to a successful ageing. A particular role might be attributed to the influence of cytokine polymorphisms on the efficiency of immune response against infectious diseases that have been the principal selection in oldest old. Here are reported data on the evaluation of the frequency of the functional polymorphisms at genes coding for TNF-alpha (-308G-->A) and IL-10 (-1082G-->A), analysed by ARMS-PCR, in a group of Sicilian patients affected by chronic lung tuberculosis (TBC) compared to that from a group of healthy individuals living in the same region. Data obtained demonstrated a reduction of -308GG TNF homozygous individuals in TBC affected subject group. In the same group a reduction of IL-10 -1082A/* carriers was found. Our results seem to suggest that multiple genetic traits may affect the capacity to cope with an infectious agents and this might predispose to an overt disease. Moreover these data are in agreement with previous reports suggesting that a balanced interaction among pro- and anti-inflammatory molecules it is a key point for conditioning the life span expectancy.

Increased prevalence of autoimmune diseases in first-degree relatives of patients with celiac disease.

BACKGROUND: The prevalence of autoimmune disorders is increased in patients with celiac disease (CD), and it is unknown whether their first-degree relatives also have a high risk of autoimmune disorders. METHODS: To assess the prevalence of autoimmune diseases in first-degree relatives of CD patients, the authors looked for autoimmune disorders in 225 first-degree relatives of 66 children with CD (group A) and in 232 first-degree relatives of 68 healthy children (group B). For both groups, serologic screening for CD was performed through antiendomysium (EMA) and tissue transglutaminase autoantibodies (tTGAA). EMA- and tTGAA-positive subjects were offered an intestinal biopsy. The age at onset of autoimmune diseases was also recorded in group A. RESULTS: The prevalence of autoimmune disorders was significantly (P = 0.028) higher in group A (11 of 225, 4.8%) than in group B (2 of 232, 0.86%). In relatives of CD patients, the prevalence increased with age (chi2 for trend, 43.5; P < 0.0001). Serologic screening for CD was only positive in group A (15 of 225 subjects). An intestinal biopsy was performed in 13 of these 15 relatives (2 refused biopsy). Eleven of 13 had flat mucosa, with subclinical or silent forms of CD. The prevalence of autoimmune diseases in the EMA- and tTGAA-positive relatives of CD patients was significantly higher (3 of 15, 20%; P = 0.028; odds ratio, 6.3; 95% CI, 1/0.21-1/0.11, 4.9-7.6) than in those who were EMA and tTGAA negative (8/210, 3.8%). CONCLUSIONS: The first-degree relatives of CD patients have an increased risk of autoimmune diseases, most likely connected with unrecognized subclinical or silent forms of CD.