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.

Urticaria: recommendations from the Italian Society of Allergology, Asthma and Clinical Immunology and the Italian Society of Allergological, Occupational and Environmental Dermatology.

BACKGROUND: Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12-22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6-16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention. This makes likely that its incidence is underestimated. The epidemiological data currently available on chronic urticaria in many cases are deeply discordant and not univocal, but a recent Italian study, based on the consultation of a national registry, reports a prevalence of chronic spontaneous urticaria of 0.02% to 0.4% and an incidence of 0.1-1.5 cases/1000 inhabitants/year. METHODS: We reviewed the recent international guidelines about urticaria and we described a methodologic approach based on classification, pathophysiology, impact on quality of life, diagnosis and prognosis, differential diagnosis and management of all the types of urticaria. CONCLUSIONS: The aim of the present document from the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) is to provide updated information to all physicians involved in diagnosis and management of urticaria and angioedema.

Living with Chronic Spontaneous Urticaria in Italy: A Narrative Medicine Project to Improve the Pathway of Patient Care.

Chronic spontaneous urticaria (CSU) is perceived as a difficult to manage disease with negative impact on quality of life. The aim of this study was to highlight how to improve the care of people with CSU, using the methodology of narrative medicine. From June 2014 to March 2015, CSU-diagnosed patients and their physicians were asked to record their experiences of the condition in writing. Fourteen healthcare teams participated: 41% considered CSU as a challenge to overcome, while 22% experienced CSU as a big commitment. The number of professional involved was evaluated as insufficient in 11 hospitals. Seventy-five percent of the 190 Italian patients had visited 3 or more physicians before receiving a final diagnosis, with a perceived waste of time and resources. The therapeutic pathways were described as unsatisfactory in 83% of cases. As a result, anger and frustration were life-dominant emotions in 92% of patients. The critical points of the care pathway are related to organizational issues and lack of awareness.

Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids.

BACKGROUND: Little is known about the socio-economic burden of severe chronic hand eczema in patients refractory to treatment with potent corticosteroids. OBJECTIVES: To estimate the socio-economic burden of severe chronic hand eczema refractory to potent topical corticosteroids, and to establish an algorithm for the estimation of the health-related quality of life EuroQol five-dimensional (EQ-5D) utility index from the Dermatology Life Quality Index (DLQI) summary score. METHODS: A multicentre cost of illness study was conducted, adopting the societal perspective. Adult patients with severe and refractory chronic hand eczema were enrolled. Direct (e.g. drug treatment and travel) and indirect (i.e. loss of productivity) mean costs/patient-month were estimated. Health-related quality of life was assessed with the EQ-5D and DLQI questionnaires. An ordinary least square regression model was used to investigate relationships between health-related quality of life scores. RESULTS: One hundred and four valid patients (mean age 44.5 years, 39.4% male) participated. Overall mean costs were €418.3/patient-month: loss of productivity contributed 43.7%, followed by hospitalization (16.1%) and travel (10.3%). Health-related quality of life scores were, on average, 0.50 (EQ-5D utility) and 11.3 (DLQI). Utility and DLQI summary were significantly related to each other. CONCLUSIONS: Wellbeing and loss of productivity are the most important consequences in these patients. Appropriate treatment is necessary to improve patient health and productivity, which will contribute to reducing societal costs.

Dupilumab in real-life settings: a review of adverse events and their pathogenesis.

INTRODUCTION: Dupilumab is a safe and effective biological drug that revolutionized the treatment of atopic dermatitis (AD). Concerning adverse events (AEs), the most commonly reported included ocular involvement, nasopharyngitis, and injection site reactions in clinical trials. Anyway, its use in daily practice is revealing novel dupilumab-induced manifestations. AREAS COVERED: Relevant English literature (real-life studies, case series, reviews, and meta-analyses) regarding real-life adverse events induced by dupilumab were searched for up to 10 June 2023. EXPERT OPINION: Dupilumab is an effective treatment for AD, showing favorable safety profile since no routine laboratory monitoring is recommended. However, several cutaneous and extracutaneous AEs have been reported in real-life setting expanding the pool emerged from clinical trials. In detail, dupilumab may determine de-novo onset or exacerbation of preexisting conditions, whose pathogenesis is still unclear and seems to involve Th1/Th2 and Th2/Th17 immune-response imbalance. Also, the heterogeneity and the variable onset time of AEs with respect to dupilumab initiation warrant a thorough patients' history collection and strict short- and long-term monitoring. Finally, the most appropriate management of patients with AEs related to dupilumab should take into consideration efficacy for AD as well as severity and nature of the AE, available treatment and patients' preferences.

Evaluating the Clinical Meaning of Dermatology Life Quality Index Scores Between Different Phenotypes of Atopic Dermatitis in Patients Before and After Biologic Therapy With Dupilumab.

Background and Objective: Atopic Dermatitis (AD) is the most prevalent inflammatory skin disorder resulting in an intense impact on patients quality of life. The aim of this study is to evaluate the clinical meaning of the DLQI scores documented between different phenotypes of AD patients under biologic therapy with Dupilumab. Method: We conducted a retrospective analysis of 209 patients with AD treated with Dupilumab for 2 years. These patients were categorized into different clinical phenotypes. Severity of the disease was assessed by using the Eczema Area and Severity Index (EASI), Numerical Scale Rating (NRS) for sleep (NRS sleep), pruritus (NRS pruritus) and Dermatology Life Quality Index (DLQI) at baseline and subsequently at 4,12 and 24 months. Results: Our results show that the higher DLQI scores (mean: 18.6, range:9-30) achieved at T0 are associated with a prurigo nodularis AD pattern, while after 24 months (T3) of therapy with Dupilumab, the worst quality of life index results were reported in Flexural and Head-Neck combined clinical phenotypes. Conclusions: Quality of life is probably what matters most as an overall endpoint in AD. Assessing the clinical meaning of DLQI scores across different AD phenotypes could be a further aid when considering decision making factors in patient management.

Reactivation of human polyomavirus JC in patients affected by psoriasis vulgaris and psoriatic arthritis and treated with biological drugs: preliminary results.

Psoriasis vulgaris (PsV) and psoriatic arthritis (PSA) are inter-related heritable inflammatory skin diseases. Psoriatic lesions develop as a result of abnormal immune responses, hyperproliferation and altered differentiation of keratinocytes, and a notable subset of psoriatic patients develops PsA, characterized by joints inflammation. Recently, biological drugs were introduced to treat these diseases. However, this therapy has already been associated with the development of serious life-threatening infections, such as the reactivation of human polyomavirus JC (JCV), responsible for the progressive multifocal leukoencephalopathy (PML), a lethal demyelinating disease caused by oligodendrocytes lytic infection. Therefore, the aims of our study were the investigation of the possible JCV reactivation in PsV and PsA patients treated with adalimumab, etanercept, and methotrexate, performing quantitative real-time PCR in sera and skin biopsies at the time of recruitment (T0) and after 3 (T3) and 6 (T6) months of treatment, and the sequencing analysis of the JCV non-coding control region (NCCR). We found JCV DNA in 5/15 PsV patients and in 2/15 PsA patients and JCV NCCR sequence analysis always showed a structure similar to non-pathogenic CY archetype, with random occurrence of a few irrelevant point mutations. Nevertheless the poor number of patients analyzed, our preliminary data can pave the way for taking into account that the follow-up of JCV DNA detection and the JCV NCCR sequence analysis in psoriatic patients may be important to evaluate the risk of PML onset, considering that patients affected by autoimmune diseases and treated with biologics continue to rise.

Therapy with rituximab for autoimmune pemphigus: results from a single-center observational study on 42 cases with long-term follow-up.

BACKGROUND: Rituximab induces depletion of B cells and has shown efficacy in antibody-mediated autoimmune disorders. In studies on small series of patients with pemphigus, rituximab administration results in significant improvement. However, differences in inclusion criteria, treatment protocols, and follow-up make it difficult to derive uniform conclusions. OBJECTIVES: We sought to test the efficacy and tolerability of rituximab as adjuvant therapy to corticosteroids in the treatment of pemphigus. METHODS: In all, 42 patients with pemphigus were treated with rituximab and followed up for up to 5 years. No additional immunosuppressive agents were used. Steroids were rapidly tapered. Outcomes were the proportion of patients who achieved a complete response on or off therapy, the rate of discontinuation of corticosteroid within 6 months, length of remission, time to relapses, and occurrence of adverse events. RESULTS: In all, 36 of 42 patients (86%; 95% confidence interval 75%-96%) achieved a complete response on or off therapy and discontinued steroids within 6 months from induction therapy. Six patients had a complete response off therapy with an additional infusion of rituximab 6 months after initial treatment. Twenty patients experienced a total of 34 relapses; the time to relapse was 8 to 64 months. Every relapse was treated with rituximab (500 mg) without corticosteroids, which induced a new complete response. No serious adverse events were observed. LIMITATIONS: Lack of a control group is a limitation. CONCLUSIONS: Rituximab therapy induces prolonged clinical remission in patients with pemphigus. Coadministration of other immunosuppressive agents is not necessary. Relapses can be managed with additional infusions administered on demand.

Methotrexate in the therapeutic pathway of patients with psoriasis. Analysis of clinical practice data and comparison with guidelines.

Psoriasis is an inflammatory skin disease with a chronic-relapsing course. It is estimated that the prevalence in Italy is 3%. An adequate model of taking care of the patient with psoriasis allows the patient to benefit from the most suitable treatment option for his health needs. In this position statement the observations, criticalities and proposals for improvement of the Pso-Path Working Group, composed by health economists, clinicians and patients, on the diagnostic-therapeutic pathway of the patient with psoriasis have been collected. In particular, the deviation of clinical practice from the current Guidelines for the management of patients with psoriasis, which recommend the use of biologic drugs in case of non-response, intolerance or contraindication to Methotrexate or Cyclosporine, was evaluated. A Working Group was convened whose participants were asked to express their thoughts on the diagnostic and therapeutic pathway of the patient with psoriasis, bringing out critical elements and proposals for improvement, based on their experiences. This position statement summarizes the experiences and consensus between clinicians and patients on actions to optimize the management of patients with psoriasis undergoing biological treatment. Compared to the epidemiological data currently available, it is believed that only a small percentage of patients with psoriasis are treated with systemic drugs. The perception of clinicians, according to their experience, confirms the data emerging from the National Report "National Observatory on the Use of Medicines" (Osmed) compiled by AIFA in 2015, according to which more than 77% of patients with psoriasis are started to treatment with biological drugs without a previous use of Methotrexate or Cyclosporine for at least 3 months. The Pso-Path Working Group concluded that it would be desirable to incentivize, through the formalization of regional guidelines, the creation of a network system that promotes not only a greater awareness, at the territorial level, of the importance and impact of the disease and the possible paths, but also the collaboration and connection between all the actors involved in the overall care of the patient.

Topical non-pharmacological treatment of eczema: an Italian consensus.

Eczematous diseases (contact dermatitis, atopic dermatitis, hand eczema) are among the most frequent findings in dermatological clinical practice. A large body of evidence exists on structural and functional skin barrier damage in eczematous diseases, and on the importance of interventions aimed to repair such damage. While there is substantial agreement on pharmacological treatment, more sparse data are available on role, indications and usefulness of topical non-pharmacological treatments, despite significant research and progress in the composition and technology of emollients, cleansers and barrier creams significantly changed and expanded the functional activities of these products. This often leads to inadequate prescription and/or use, which increase individual and social costs of the disease and make the products useless or, in some cases, even counterproductive. This consensus document, discussed and compiled in a series of meetings by a group of Italian dermatologists experienced in the field of eczematous diseases, summarizes epidemiology and clinical features of the nosological entities of the "eczema family", illustrates the chemical/biochemical structure of emollients, cleansers and barrier creams, and aims to help physicians to exploit the full potential of available products, by providing a detailed but practical guide on characteristics, indications and correct use of non-pharmacological treatments currently available for eczematous diseases.

Therapeutic management of chronic spontaneous urticaria in clinical practice: results from a pilot survey.

BACKGROUND: The therapeutic approaches to patients with chronic spontaneous urticaria (CSU) differ among health care professionals and may be influenced by many factors. This cross-sectional survey was aimed at evaluating physicians' attitudes regarding therapeutic management of CSU in clinical practice. METHODS: A study-specific questionnaire was administered to a group of physicians (N.=21) with a specialist interest in CSU from different areas of Italy (group A) and also to other physicians (N.=25) who manage CSU only occasionally in their clinical activity (group B). RESULTS: In case of ineffectiveness of second-generation antihistamines at standard doses, higher doses of the same drug were always or frequently prescribed by most physicians in both groups, and 64% in group B and one third in group A usually increased the dose up to twice. Old-generation antihistamines were never used in clinical practice by 14% of survey participants in group A and 24% in group B, with the remaining physicians reporting rare or occasional uses. The prescription of systemic corticosteroids appeared to be more common among physicians in group B. The question concerning the use of alternative drugs in refractory CSU produced different answers between the two groups. Costs and access to specialist reference centers were indicated as the most important barriers to the use of medications different from antihistamines. CONCLUSIONS: These preliminary results suggest that therapeutic approaches to CSU seem to be heterogeneous in clinical practice and could be at least in part conditioned by the different medical settings where physicians usually work.

Usefulness of skin immunofluorescence for distinguishing SLE from SLE-like renal lesions: a pilot study.

Lupus nephritis (LN) may represent a diagnostic problem, particularly in pediatric patients that present with typical histological lesions but do not fulfill the American Rheumatism Association (ARA) criteria for the diagnosis of systemic lupus erythematosus (SLE). Based on the well-described deposition of immunoglobulins (Ig) and complement at the dermoepithelial junction in SLE, we hypothesized that skin biopsies may help in the diagnosis of LN. To test this hypothesis, we carried out a pilot study, performing a skin biopsy in 22 patients with LN and 13 patients with lupus-like lesions, regardless of the time elapsed from onset of renal disease. The latter group of patients was further divided into a purely renal group, designated as isolated full-house nephropathy (FHN), and a dubious cases group, presenting with additional clinical and biological features consistent with SLE but insufficient for diagnosing SLE. None of the 6 isolated FHN patients had positive skin immunofluorescence. Conversely, 5/7 patients in the dubious cases group (p<0.02) and 13/22 in the LN group (p<0.002) had positive staining for C1q, and 5/7 patients in the dubious cases group (p<0.02) and 16/22 patients in the LN group (p<0.001) had positive staining for IgM. No correlation was observed with the time elapsed from the initial diagnosis. These data suggest that skin biopsies may help distinguishing LN from isolated FHN. In addition, they identify an intermediate group of patients with evidence of systemic involvement despite the absence of a sufficient number of ARA criteria to be labeled as SLE.

Efficacy of oral hyposensitization in allergic contact dermatitis caused by nickel.

BACKGROUND: Nickel contact allergy remains common in Western countries, and the dermatitis may require prolonged treatment. The development of new strategies aimed at improving the quality of life of affected individuals is needed. OBJECTIVES: To investigate the efficacy of oral hyposensitization in nickel-allergic individuals and how this affects in vitro T cell responsiveness to the metal. METHODS: Twenty-eight nickel-allergic patients received a daily dose of 50 µg of elemental nickel (given as NiSO(4) ·6H(2) O) in cellulose capsules for 3 months. Severity of clinical manifestations, in vivo nickel responsiveness and in vitro T cell responses to the metal were assessed after 1 and 3 months. RESULTS: Twenty-six patients finished the study. In these patients, oral hyposensitization ameliorated clinical manifestations despite continued nickel exposures, and increased the threshold of skin responsiveness to nickel. The 12 enrolled patients in the immunological study showed decreased in vitro T lymphocyte responsiveness to the metal, in terms of both cell proliferation and cytokine release. In the 1-year follow-up, 50% of the patients experienced relapses of the clinical manifestations at sites of topical exposure to nickel. CONCLUSIONS: Our study suggested therapeutic efficacy of oral hyposensitization in allergic individuals. Placebo-controlled studies are required to confirm the results and determine the optimal therapeutic regimen for prolonged beneficial effects.

Chronic spontaneous urticaria in clinical practice: a pilot survey about attitudes and perceptions on assessment, diagnostic work-up and dietary management.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a heterogeneous condition whose management can be complex and challenging. The aim of this study is to evaluate physicians' attitudes regarding practical aspects of CSU management, including adherence to international guidelines, criteria and instruments for CSU assessment, prescription of laboratory investigations and role of dietary measures. METHODS: A cross-sectional survey was conducted using a study-specific questionnaire. It was administered to a group of physicians with a specialist interest in CSU from different areas of Italy definable as "CSU experts" (group A; N.=21) and subsequently to other physicians who managed CSU only occasionally in their clinical activity (group B; N.=25). RESULTS: The EAACI/GA2LEN/EDF/WAO guidelines were considered very or moderately useful by the majority of participants. Significantly more physicians in group A reported that such guidelines were always followed in clinical practice (P=0.0008). Instruments for the assessment of CSU severity/activity and quality of life were used in clinical practice significantly more often by CSU experts as compared to group B. Dietary measures were frequently suggested for CSU patients by nearly three quarters of group B members and by only 5% of CSU experts (P<0.00001). When physicians were asked to indicate the type of laboratory examinations that were commonly performed in patients with longstanding and/or uncontrolled CSU, regardless of history, the investigations most frequently reported were full blood count and thyroid autoantibodies, followed by erythrocyte sedimentation rate and/or C-reactive protein and thyroid function tests. CONCLUSIONS: The results of the present pilot survey seem to suggest the heterogeneity of the approaches used for CSU management in clinical practice.

Clinical activity of pemphigus vulgaris relates to IgE autoantibodies against desmoglein 3.

Pemphigus vulgaris (PV) is a severe autoimmune bullous skin disease and is primarily associated with IgG against desmoglein 3 (dsg3), a desmosomal adhesion protein. In light of the recent association of autoreactive T helper (Th) 2 cells with active PV, the present study sought to relate the occurrence of Th2-regulated dsg3-specific autoantibody subtypes, i.e. IgE and IgG4, in 93 well-characterized PV patients. Patients with acute onset PV (n=37) showed the highest concentrations of serum IgE and IgG4 autoantibodies, which were significantly lower in PV patients in remission (n=14). Furthermore, there was a strong correlation between dsg3-reactive IgE and IgG4 in acute onset, but not in chronic active (n=42) or remittent patients. Additionally, intercellular IgE deposits were detected in the epidermis of acute onset PV. Thus, dsg3-specific IgE and IgG4 autoantibodies are related to acute onset disease which provides additional support to the concept that PV is a Th2-driven autoimmune disorder.

Suppressor of cytokine signaling 1 inhibits IFN-gamma inflammatory signaling in human keratinocytes by sustaining ERK1/2 activation.

IFN-gamma is a pleiotropic cytokine importantly involved in the development of skin inflammatory responses. Epidermal keratinocytes are extremely susceptible to IFN-gamma action, but, once transduced with the suppressors of cytokine signaling (SOCS)1 molecule, they can no longer express a number of IFN-gamma-inducible signal transducer and activator of transcription (STAT)1-dependent genes. Extracellular-signal-regulated kinase (ERK)1/2 pathway is also involved in the protection of keratinocytes from the proinflammatory effect of IFN-gamma. Here we show that, after IFN-gamma stimulation, SOCS1 inhibited IFN-gamma receptor and STAT1 phosphorylation but maintained ERK1/2 activation. SOCS1 was also necessary for the IFN-gamma-induced RAS and Raf-1 activities in keratinocytes. The enhanced ERK1/2 pathway in SOCS1-overexpressing keratinocytes was in part responsible for their inability to respond to IFN-gamma, in terms of CXCL10 and CCL2 production, and for the high production of CXCL8. Moreover, SOCS1 interacted with the RAS inhibitor p120 RasGAP and promoted its degradation after IFN-gamma stimulation. We hypothesize that SOCS1 functions as suppressor of IFN-gamma signaling, not only by inhibiting STAT1 activation but also by sustaining ERK1/2-dependent antiinflammatory pathways.

Low-frequency low-intensity ultrasounds do not influence the survival and immune functions of cultured keratinocytes and dendritic cells.

Low-frequency ultrasounds (US) are used to enhance drug transdermal transport. Although this phenomenon has been extensively analyzed, information on US effects on the single skin cell components is limited. Here, we investigated the possible effects of low-frequency US on viability and immune functions of cultured human keratinocytes and dendritic cells (DC), skin cells involved in the regulation of many immune-mediated dermatoses. We demonstrated that US, employed at low-frequency (42 KHz) and low-intensity (0.15 W/cm(2)) values known to enhance drug and water transdermal transport, did not affect extracellular-signal-regulated-kinase (ERK)1/2 activation, cell viability, or expression of adhesion molecules in cultured keratinocytes. Moreover, US at these work frequency and intensity did not influence the keratinocyte expression and release of immunomodulatory molecules. Similarly, cultured DC treated with low-frequency low-intensity US were viable, and did not show an altered membrane phenotype, cytokine profile, nor antigen presentation ability. However, intensity enhancement of low-frequency US to 5 W/cm(2) determined an increase of the apoptotic rate of both keratinocytes and DC as well as keratinocyte CXCL8 release and ERK1/2 activation, and DC CD40 expression. Our study sustains the employment of low-frequency and low-intensity US for treatment of those immune skin disorders, where keratinocytes and DC have a pathogenetic role.