Probiotics and Prebiotics Orally Assumed as Disease Modifiers for Stable Mild Atopic Dermatitis: An Italian Real-Life, Multicenter, Retrospective, Observational Study.

The role of the skin-gut axis in atopic dermatitis (AD) remains a subject of debate, limiting non-pharmacological interventions such as probiotics and prebiotics. To improve understanding of their potential as a monotherapy for stable mild cases, we conducted a real-life, multicenter, retrospective observational study in Italy. We administered three selected bacteria (Bifidobacterium animalis subsp. lactis BS01, Lactiplantibacillus plantarum LP14, and Lacticaseibacillus rhamnosus LR05) orally to patients with mild atopic dermatitis without a placebo control group, following up for 12 weeks. Clinical assessments using the Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), and Three-Item Severity (TIS) score were conducted on 144 enrolled patients (average age: 25.1 ± 17.6 years). Notably, both pruritus and AD-related lesions (erythema, edema/papules, excoriation) exhibited significant clinical and statistical improvement (p < 0.001) after 12 weeks of exclusive probiotic and prebiotic use. These preliminary results suggest a potential link between the skin-gut microbiome and support the rationale for using specific probiotics and prebiotics in mild AD, even for maintenance, to reduce flares and dysbiosis.

A consensus-based approach on the management of patients with both psoriasis and psoriatic arthritis in the dermatological and rheumatological settings in Italy: The ADOI PSO-Amore Project.

Psoriasis is a complex disease often needing a multidisciplinary approach. In particular, the collaboration between dermatologist and rheumatologist is crucial for the management of patients suffering from both psoriasis (PSO) and psoriatic arthritis (PsA). Here we report a series of recommendations from a group of experts, as a result of a Consensus Conference, defining the circumstances in which it is preferable or even mandatory, depending on the available settings, to rely on the opinion of the two specialists, jointly or in a deferred manner. Indications are given on how to organize a 3rd level joint Dermatology- Rheumatology care unit, in connection with 1st and 2nd level clinicians of both specialties, GPs, and other specialists involved in the management of psoriasis. A potential patient journey is suggested, that can be used as a basis for future design and validation of national and/or local diagnostic therapeutic and assistance pathways.

Patient satisfaction with calcipotriol/betamethasone dipropionate cutaneous foam for the treatment of plaque psoriasis: The LION real-life multicenter prospective observational cohort study.

Topical treatment is the mainstay for mild or moderate psoriasis, but patients are generally little satisfied. Calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam has shown to improve signs and symptoms in plaque psoriasis patients. This study assessed patient's satisfaction with Cal/BD foam in a real-life Italian dermatological clinical practice. A multicenter, 4-week observational prospective cohort study enrolled, in 17 Italian dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM-9 median (25th-75th percentile) scores were 83.3 (66.7-88.9) for effectiveness, 77.8 (66.7-88.9) for convenience, and 78.6 (64.3-92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real-life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI.

Gut microbiome profile in psoriatic patients treated and untreated with biologic therapy.

There are increasing data about the role of the gut microbiome in various autoimmune diseases, including psoriasis, a chronic inflammatory and immune-mediated disease. Current treatment strategies in psoriasis include immunomodulating biologic agents. A variable response to this type of therapy has been reported in psoriatic patients. A possible effect of biologic therapy on the gut microbiome composition has been suggested, but data are still limited. The aim of this study was to compare the gut microbiome composition between psoriatic patients treated and untreated with biologic drugs in order to identify differences which may highlight the potential impact of the treatment on the gut microbiome. 16S rRNA sequencing and bioinformatic analyses were performed on the fecal samples of 30 psoriatic patients with similar clinicopathological features, 10 of whom were undergoing biologic therapy and 20 not receiving systemic therapy. Alpha and beta diversity significantly differed between the two groups of patients. A reduced bacterial biodiversity in the group of treated patients compared with the group of untreated patients was observed. Differential relative abundances of key gut microbial communities, including Akkermansia muciniphila and Bacteroides plebeius, were identified between the two groups of patients. This study showed that biologic therapy may have an impact on the composition of the gut microbiome of psoriatic patients. Gut microbiome composition could be used as an indicator of response to therapy and the modulation of the microbial composition could help to restore the intestinal symbiosis in psoriatic patients.

PsA-Disk, a novel visual instrument to evaluate psoriatic arthritis in psoriatic patients: an Italian derma-rheuma multicentre study.

BACKGROUND: Consensus among dermatologists and rheumatologists in the diagnosis and assessment of musculoskeletal diseases in psoriasis (PsO) patients is needed. This study assesses characteristics of musculoskeletal pain in patients with PsO for the presence of psoriatic arthritis (PsA) and evaluation of a novel 16-item visual instrument (PsA-Disk). METHODS: Data were collected from eight dermatological/rheumatological centres across Italy. Patients with PsO completed PEST (Psoriasis Epidemiology Screening Tool) and PsA-Disk questionnaires during the first visit. A rheumatological visit was performed to confirm the presence of PsA. Both validity and reliability of PsA-Disk were assessed. RESULTS: A total of 573 patients with PsO were examined at the first visit, and 120 (21%) were diagnosed with PsA. Patients with PsA compared with patients with PsO (n = 119) presented statistically significant differences for: nail involvement, PEST score ⩾3, higher erythrocyte sedimentation rate (ESR), Nail Psoriasis Severity Index (NAPSI)-feet, NAPSI-(hands + feet) and PsA-Disk scores (73.9 ± 32.1 versus 58.1 ± 39.8, p < 0.001). Patients with PsA with knee arthritis had higher PsA-Disk scores (98.4 ± 26 versus 71.5 ± 31.9, p = 0.006) that were also correlated with number of swollen (r = 0.2, p < 0.05) and tender joints (r = 0.24, p = 0.021), patient (r = 0.4, p < 0.001) and physician-pain-visual analogue scale (VAS; r = 0.33, p < 0.001), patient global assessment (PGA)-VAS (r = 0.23, p = 0.025), physician-health assessment questionnaire (HAQ; r = 0.38, p = 0.011), Disease Activity Score (DAS)-44 (r = 0.25, p = 0.023) and Disease Activity in Psoriatic Arthritis (DAPSA; r = 0.31, p = 0.005). The instrument had excellent reliability in terms of internal consistency (Cronbach's alpha = 0.90) and stability (intraclass correlation = 0.98). Moderate agreement between PsA-Disk and PEST (Cohen's kappa = 0.46) was observed, while construct validity appeared appropriate [PsA + patients: PsA-Disk score (interquartile range; IQR) =71 (50-96); PsA-patients: PsA-Disk score (IQR)=50 (20-90); p < 0.001]. CONCLUSION: PsA-Disk may be considered a valid novel instrument aiding both dermatologists and rheumatologists in the rapid detection and assessment of musculoskeletal disease characteristics.

From patients' needs to treatment outcomes in psoriasis: Results from the 'pSORRIDI' experience.

OBJECTIVE: To evaluate results of the 'pSORRIDI' experience (which is a prevention campaign to evaluate the prevalence of comorbidities, multidisciplinary needs and appropriateness of the therapeutic approach for comorbidities) in patients already being treated for psoriasis. METHODS: Telephone interviews were conducted in patients with psoriasis, who then underwent comprehensive evaluation and investigation of comorbidities. If necessary, patients were referred to specialist cardiology, endocrinology and/or rheumatology services. RESULTS: Overall, 72.0% (54/75) of patients required a multidisciplinary consultation. Among patients referred to cardiology, therapeutic adjustment was needed in 33.3% (five of 15) patients and a redefined diagnosis in 26.7% (four of 15) cases. Among patients undergoing endocrinology evaluations, therapeutic adjustment and a redefined diagnosis were needed in 61.1% (11/18) and 33.3% (six of 18) patients, respectively; for rheumatology evaluations, therapeutic adjustment and a redefined diagnosis were needed in 76.2% (16/21) and 19.0% (four of 21) of patients, respectively. CONCLUSIONS: Among patients with psoriasis, there may be a need for an improvement in the diagnosis of underlying comorbid conditions, and in disease management of both psoriasis and any comorbid conditions.

Psoriasis awareness among Italian patients: results of a nationwide survey.

BACKGROUND: This was a prospective, multicentre study conducted in 14 Italian psoriasis referral centres (January-June 2014) with the objective of identifying factors associated with different levels of patient awareness on psoriasis. METHODS: Overall, 298 patients (119 females, mean age 49.4 years, range 20-88) with a diagnosis of psoriasis (median of 14.1 years) were enrolled. Patients were more knowledgeable about the pathogenic nature of their condition compared with the other parameters (diagnosis, clinical course, prognosis, effect on QoL). Variables associated with significantly higher awareness, included years of education (the higher the educational levels the greater awareness), internet usage, other family member with the disease, diet rich in fruit/vegetables, cigarette smoking and bone and joint involvement. RESULTS: Older age, diabetes, and alcohol abuse were inversely associated. CONCLUSIONS: Having established factors that affect awareness in our patients we can now go on to devise educational interventions to address these needs.

Clinical markers predictive of primary inefficacy: a "real life" retrospective study in psoriatic patients treated with etanercept.

Overexpression of tumor necrosis factor alpha (TNF-α) has been demonstrated to play a pivotal role in the pathogenesis of both plaque-type psoriasis and psoriatic arthritis. TNF-α blockers, including etanercept, a human protein that acts as a TNF-α soluble receptor, are effective in the treatment of psoriasis. This retrospective study investigated the impact of psoriasis patients' demographic and clinical characteristics on primary inefficacy to etanercept. Our findings suggest that the presence of psoriatic arthritis is a risk factor for primary inefficacy to etanercept in the treatment of psoriasis. However, etanercept efficacy appears to be independent of patient age, gender, or previous biologic treatments.

Efficacy and maintenance strategies of two-compound formulation calcipotriol and betamethasone dipropionate gel (Xamiol® gel) in the treatment of scalp psoriasis: results from a study in 885 patients.

BACKGROUND: Previous studies showed the efficacy of a formulation containing calcipotriol and betamethasone dipropionate for the treatment of psoriasis. OBJECTIVE: To investigate maintenance strategies of a formulation containing calcipotriol (50 µg/g) and betamethasone dipropionate (0.5 mg/g) for the treatment of scalp psoriasis. MATERIALS AND METHODS: Nine-hundred and four patients were screened and randomised on a 1:1 basis in two groups: maintenance of two applications per week (group A) versus on-demand therapy (group B). Clinical evaluation was performed at weeks 0, 2, 4, 8 and 12. RESULTS: Eight-hundred and eighty-five patients were randomised: 441 in group A and 444 in group B. From week 2, both groups showed a significant clinical improvement compared with baseline; at weeks 8 and 12, group A demonstrated a higher clinical response compared with group B (p < 0.05). This difference was statistically significant (OR 0.47, 95% CI 0.37, 0.60). CONCLUSIONS: The maintenance of twice-weekly application versus on-demand treatment of calcipotriol/betamethasone dipropionate gel is more effective and is associated with a lower rate of relapse.

Efficacy and safety of systemic treatments for psoriasis in elderly patients.

Management of psoriasis in elderly patients can be challenging, because of the impairment of immune system efficiency and the presence of comorbidities that contra-indicate systemic therapies. We studied the safety and efficacy of systemic traditional and biological treatments in 187 consecutive psoriatic patients aged > 65 years. At week 12 of therapy, Psoriasis Area and Severity Index 75 was achieved by 49%, 27%, 46% and 31% of patients who received methotrexate, acitretin, cyclosporine or PUVA, and 64.1%, 64.7%, 93.3%, 57.1% and 100% of patients who received etanercept, adalimumab, infliximab, efalizumab and ustekinumab. The rate of adverse events was 0.12, 0.32, 1.4 and 0.5 per patient-year in the methotrexate, acitretin, cyclosporine and PUVA groups and 0.11, 0.35, 0.19, 0.3 and 0.26 in the etanercept, adalimumab, infliximab, efalizumab and ustekinumab groups. Traditional drugs were less effective than biologics in our elderly population. Etanercept was associated with a lower rate of adverse events compared with other treatments.

The cooccurrence of interictal discharges and seizures in pediatric sleep-disordered breathing.

Studies in the literature data have shown that the prevalence of obstructive sleep apnea (OSA) in children with epilepsy is high and that treatment for OSA leads to a reduction in the number of seizures; by contrast, few studies have demonstrated an increased prevalence of interictal epileptiform discharges (IEDs) or epilepsy in children with sleep-disordered breathing (SDB). The aim of the present study was to confirm the high prevalence of IEDs or epilepsy in a large sample of children with SDB and to collect follow-up data. Children were recruited prospectively and underwent their first video-polysomnography (video-PSG) for SDB in a teaching hospital sleep center. Of the 298 children who fulfilled the diagnostic criteria for sleep-disordered breathing, 48 (16.1%) children were found to have IEDs, three of these 48 children were also found to have nocturnal seizures (two females diagnosed with rolandic epilepsy and a male diagnosed with frontal lobe epilepsy). Only 11 subjects underwent a second video-PSG after 6months; at the second video-PSG, the IEDs had disappeared in six subjects, who also displayed a reduced AHI and an increased mean overnight saturation. Thirty-eight of the 250 children without IEDs underwent a second video-PSG after 6months. Of these 250 children, four, who did not display any improvement in the respiratory parameters and were found to experience numerous stereotyped movements during sleep, were diagnosed with nocturnal frontal lobe epilepsy. Our study confirms the high prevalence of IEDs in children with SDB. Follow-up data indicate that they may recede over time, accompanied by an improvement of sleep respiratory parameters.

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.

Detection and management of latent tuberculosis infections before biologic therapy for psoriasis.

The biologic agents can be highly efficacious in the treatment of psoriasis and psoriatic arthritis; however, their use is associated with an increased risk of developing active TB. In particular, TNF-α plays critical role in preventing TB infection and reactivation of latent TB infection (LTBI). Therefore, it is critical that all patients be screened for LTBI prior to initiating therapy. An expert panel of Italian dermatologists met recently with the goal of producing a consensus paper on screening and chemoprophylaxis for LTBI in Italian psoriasis patients treated with biologics. Current recommendations for the screening algorithm include medical history, chest x-ray, and tests that evaluate immunologic response to the presence of Mycobacterium tuberculosis. Patients with positive screening results and without active disease are to be treated with a full course of chemoprophylaxis; however, if the patient is compliant and tolerating the regimen, biologic therapy for psoriasis may be started after at least 1 month on prophylactic therapy when prompt control of disease is required.

TNF-α antagonists and nail psoriasis: an open, 24-week, prospective cohort study in adult patients with psoriasis.

INTRODUCTION: Treatment of nail psoriasis can be challenging and unsatisfactory. The aim of this study was to compare the efficacy of three different anti-TNF-α agents on nail psoriasis in patients affected by psoriasis. MATERIALS AND METHODS: Seventy-two patients with nail psoriasis were evaluated in this open, 24 weeks, prospective study. Patients were enrolled in three groups of treatment: adalimumab, etanercept or infliximab. Severity of nail psoriasis was assessed by the Nail Psoriasis Severity Index (NAPSI) at baseline, week 14, and 24. RESULTS: Sixty patients were included in the study. The mean NAPSI was 33.77. In the adalimumab group, the mean NAPSI score was 33.1 (± 14.9) at baseline, 21 (± 8.91) at week 14 and 11.4 (± 4.6) at week 24 (p < 0.0002). In the etanercept group, the mean NAPSI was 34.8 (± 12.38) at baseline, 23.6 (± 10.43) at week 14, and 10.6 (± 5.25) at week 24 (p < 0.0016). In the infliximab group, the mean NAPSI was 33.3 (± 9.76) at baseline, 14.9 (± 4.20) at week 14 (p < 0.001) and 3.1 (± 3.27) at week 24 (p < 0.00001). At week 14 efficacy was higher in infliximab group compared to adalimumab and etanercept groups (p < 0.05). CONCLUSIONS: Among the three agents, in the infliximab group a significant improvement in nail psoriasis was observed as early as week 14 of therapy whereas in the adalimumab and etanercept groups at week 24.

Efficacy and safety of subcutaneous anti-tumor necrosis factor-alpha agents, etanercept and adalimumab, in elderly patients affected by psoriasis and psoriatic arthritis: an observational long-term study.

BACKGROUND: In elderly patients the management of psoriasis is challenging due to contraindications and a higher risk of side effects. OBJECTIVE: Our retrospective study aimed to evaluate the long-term efficacy and safety profile of subcutaneous anti-tumor necrosis factor (anti-TNF) agents in elderly psoriatic patients. METHODS: The study included 89 patients (aged ≥65 years) with plaque-type psoriasis and psoriatic arthritis treated with the subcutaneous anti-TNF-α agents etanercept or adalimumab as monotherapy for a long-term continuous period. RESULTS: Efficacy results were consistent and stable over long-term observation, as expressed by mean Psoriasis Area and Severity Index (PASI) score variation, percentage of patients achieving PASI50 and PASI75 and by the improvement of articular indices, pain visual analogue scale (Pain-VAS) and 44-Joint Disease Activity Score (DAS44-ESR). The proportion of patients achieving PASI50 was 91.80 and 82.14% at week 156 with etanercept and adalimumab treatment, respectively, while the proportion of patients achieving PASI75 was 83.61 and 71.43% at week 156 when treated with etanercept and adalimumab, respectively. The mean DAS44-ESR score decreased from 5.80 to 0.89 and from 3.43 to 1.44 at week 156 and the mean Pain-VAS score decreased from 75.10 to 3.15 and from 71.30 to 18.26 at week 156 with etanercept and adalimumab treatment, respectively. Both treatment adherence and safety profile were good. CONCLUSIONS: Our study demonstrates that subcutaneous anti-TNF-α agents are appropriate in the long-term management of elderly patients.

IL-21 promotes skin recruitment of CD4(+) cells and drives IFN-γ-dependent epidermal hyperplasia.

Psoriasis is a chronic inflammatory disorder of the skin characterized by epidermal hyperplasia and infiltration of leukocytes into the dermis and epidermis. T cell-derived cytokines, such as IFN-γ and IL-17A, play a major role in the psoriasis-associated epidermal hyperplasia, even though factors/mechanisms that regulate the production of these cytokines are not fully understood. We have recently shown that IL-21 is synthesized in excess in psoriatic skin lesions and causes epidermal hyperplasia when injected intradermally in mice. Moreover, in the human psoriasis SCID mouse model, neutralization of IL-21 reduces both skin thickening and expression of inflammatory molecules, thus supporting the pathogenic role of IL-21 in psoriasis. However, the basic mechanism by which IL-21 promotes skin pathology remains unknown. In this study, we show that CD4(+) cells accumulate early in the dermis of IL-21-treated mice and mediate the development of epidermal hyperplasia. Indeed, IL-21 fails to induce skin damage in RAG1-deficient mice and CD4(+) cell-depleted wild-type mice. The majority of CD4(+) cells infiltrating the dermis of IL-21-treated mice express IFN-γ and, to a lesser extent, IL-17A. Studies in cytokine knockout mice show that IFN-γ, but not IL-17A, is necessary for IL-21-induced epidermal hyperplasia. Finally, we demonstrate that IFN-γ-producing CD4(+) cells infiltrating the human psoriatic plaque express IL-21R, and abrogation of IL-21 signals reduces IFN-γ expression in cultures of psoriatic CD4(+) cells. Data indicate that IL-21 induces an IFN-γ-dependent pathogenic response in vivo, thus contributing to elucidate a mechanism by which IL-21 sustains skin-damaging inflammation.

Long-term experience with etanercept in psoriatic arthritis patients: a 3-year observational study.

OBJECTIVE: To evaluate the clinical efficacy and tolerability of etanercept in the treatment of active and progressive psoriatic arthritis (PsA) in patients who have previously demonstrated an inadequate response to standard treatments, such as disease-modifying anti-rheumatic drugs (DMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: An open-label, non-controlled, prospective study was conducted including 32 patients affected by PsA with variable skin involvement who had responded inadequately to at least two DMARDs. Patients received etanercept subcutaneously administered as monotherapy at the dosage of 50 mg twice weekly for 12 weeks followed by 25 mg twice weekly. Clinical response was evaluated using the EULAR (European League Against Rheumatism) disease activity score (DAS) in 28 joints (DAS-28) and the Psoriasis Area and Severity Index (PASI). The percentage improvement in DAS-28 and the proportion of patients achieving a PASI improvement from baseline of between 50% and 75% (PASI 50), > 75% (PASI 75) and > 90% (PASI 90) were analysed as primary endpoints. RESULTS: Twenty-seven (27/32) patients (84.3%) completed 3 years (144 weeks) of continuous treatment, while 5/32 (15.6%) patients were withdrawn from the study. At week 144, a significant improvement in DAS-28 was registered with a reduction in mean DAS-28 from 5.3 at baseline to 1.8, while 25/27 patients (92.5%) achieved PASI 75 with a mean PASI score of 0.7; the mean pain visual analogue scale (pain-VAS) score decreased from 64.2 at baseline to 2 at week 144, corresponding to an improvement of 94.7%. CONCLUSIONS: Etanercept is a safe and effective agent in the long-term management of PsA patients. After 3 years of continuous treatment, symptoms were under control in the majority of patients and there was a low level of disease activity.

Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis.

T cells are crucial mediators of the skin damage in psoriasis. We here show that interleukin-21 (IL-21), a T cell-derived cytokine, is highly expressed in the skin of individuals with psoriasis, stimulates human keratinocytes to proliferate and causes epidermal hyperplasia when injected intradermally into mice. In the human psoriasis xenograft mouse model, blockade of IL-21 activity resolves inflammation and reduces keratinocyte proliferation. Blocking IL-21 may represent a new therapeutic strategy in psoriasis.