Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Atopic Dermatitis in the Elderly Population.

Atopic dermatitis is a common inflammatory disease with a chronic and relapsing course. Although considered a childhood disease, it is now evident that atopic dermatitis is also common in adulthood and in the elderly population. Atopic dermatitis typically manifests with bilateral and symmetrical eczematous lesions on the face, trunk and skin folds. Itch is invariably present and may be very severe, markedly  affecting daily life and sleep. In older adults, atopic dermatitis may have a high level of impact on quality of life, frequently burdening an already complex comorbid situation. The full assessment of disease burden (localizations, itch severity, sleep alterations, impact on quality of life, disease history, comorbidities) is crucial to identify the most appropriate treatment. In many cases, moderate-to-severe atopic dermatitis in the elderly population can be successfully and safely treated with biological agents inhibiting the interleukin-4/-13 pathway, whereas the use of Janus kinase inhibitors may pose concerns about the safety profile.

IL-17A inhibitors in patients with chronic plaque psoriasis and history of malignancy: A case series with systematic literature review.

The treatment of moderate to severe plaque psoriasis in patients with history of malignancy is challenging. To review the studies reporting the experience with IL-17A inhibitors in patients with psoriasis and history of malignancy; secondly, to investigate cancer recurrence in a series of patients with a prior malignancy and plaque psoriasis treated with IL-17A inhibitors. A systematic literature review and an observational retrospective analysis of patients with history of malignancy and plaque psoriasis treated with IL-17A inhibitors was performed. About 5 original articles out of 601 were retrieved, reporting a total of 10 patients with a median age of 59 years, interquartile range (IQR) 50-63. Seven patients were treated with secukinumab, one with ixekizumab and two with both sequentially. Although the stage ranged from in situ to IV stage, most of the cases were early-stage neoplasm. The IL-17A inhibitor was initiated after a median of 10 months, interquartile range (IQR) 5-30 (range 0-144) from the diagnosis of malignancy. In addition, a series of 12 patients with history of malignancy were identified from the University Hospital of Verona, including 9 cases with cancer in clinical remission and 3 with advanced disease at time of initiating IL-17 inhibitor. No malignancy recurrence was reported within a median of 12 (IQR 6-23) and 46 (IQR 36-48) months follow up in case series from literature and our experience, respectively. Data on use of IL-17A inhibitors in patients with chronic plaque psoriasis and history of malignancy are limited. Registries and proactive pharmacovigilance activities are needed to guide clinical practice.

Milia-like calcinosis cutis in Down syndrome: a new case with a review of the literature.

We report an 11-year-old girl who presented with white papules on the dorsal and palmar region of the hands bilaterally. The parents reported that the lesions had appeared four months before and some had resolved spontaneously. The girl was suffering from celiac disease, Down syndrome, and alopecia areata treated with topical corticosteroids. At the first visit, the girl presented with alopecia areata, corticosteroid acne, and a dozen white papules located on the hands. On dermoscopy, a whitish structureless area was seen. Histological examination showed the presence of calcium deposits without tissue damage, thus confirming the diagnosis of milia-like idiopathic calcinosis cutis. At 6-month follow up, the lesions had completely disappeared. Milia-like idiopathic calcinosis cutis is a benign cutaneous disorder consisting of calcium deposits in an apparently undamaged dermis and is typically associated with Down syndrome. Up to a quarter of patients have coexisting syringomas. The milia-like papules tend to self-resolve as patients reach adulthood, so a wait-and-see approach is recommended.

Dupilumab improves clinical manifestations, symptoms, and quality of life in adult patients with chronic nodular prurigo.

BACKGROUND: Chronic nodular prurigo (CNPG) is a multifactorial skin disease characterized by itchy papules and nodules, usually resistant to standard treatment and associated with markedly impaired quality of life. OBJECTIVE: To describe dupilumab effectiveness and tolerability in treating adult patients with CNPG refractory to both topical and systemic therapies. METHODS: Retrospective, multicenter study including adult patients affected by CNPG, who were treated with dupilumab for at least 16 weeks. RESULTS: Twenty-seven CNPG patients showed clinical improvement in terms of skin lesions, itch, sleeplessness, and quality of life. A consistent proportion of patients (24/27; 88.9%) had at least 16-week continuous treatment and achieved Investigator Global Assessment score 1 (11/24; 45.8%). An increased number of patients achieved at least a 2-grade reduction in Investigator Global Assessment score (19/24; 79.2%). Numeric rating scale values for itch and sleeplessness decreased from 8.9 to 2.7 and from 8.2 to 1.7, respectively (P < .001) after 16-week therapy. Ten patients achieved 36 weeks of continuous treatment while maintaining clinical efficacy. LIMITATIONS: Major limitations included lack of validated assessment tools at the initial data collection, a limited cohort of treated patients, and a short-term observation period. CONCLUSION: Dupilumab was proven effective in reducing itch and improving CNPG skin lesions.

Drug survival of dupilumab compared to cyclosporin in moderate-to-severe atopic dermatitis patients.

Dupilumab and cyclosporin are recommended treatments for moderate-to-severe atopic dermatitis (AD). The objective of this study was to investigate drug survival of dupilumab in comparison with CsA, reasons of drug discontinuation, and predictive parameters of drug survival in daily practice. Retrospective study including patients with moderate-to-severe AD treated with dupilumab or cyclosporin (CsA) from January 1, 2019 to April 30, 2020. Drug survival analysis was performed using the Kaplan-Meier method and predictive factors were analyzed using multivariate Cox regression analyses. Adult patients with AD (n = 251) treated with dupilumab (n = 149) or CsA (n = 102) were included. Sixteen months from baseline, 82% of patients receiving dupilumab were still on treatment vs 11% of those treated with CsA. Reason for withdrawing dupilumab were primary inefficacy in 4.7% of patients, persistent clinical remission in 7.4%, and cutaneous adverse effects in 2.0%. Older age at diagnosis and shorter AD duration predicted shorter dupilumab survival. Reasons for CsA withdrawal included adverse effects in 23.5% of patients, persistent clinical remission in 15.6%, and a minimal or absent improvement in 11.7%. Dupilumab has a longer drug survival compared to CsA. Only a limited number of dupilumab patients discontinued treatment due to adverse effects and/or ineffectiveness.

Clinical features and treatments of transient acantholytic dermatosis (Grover's disease): a systematic review.

Grover's disease (GD) is an itchy acantholytic disorder occurring on the trunk of middle-aged men. Based on the best evidence, this study aimed to provide a summary of the clinical characteristics, disease course and treatments of GD. A systematic review was performed according to PRISMA guidelines for original articles published between 01.01.1970-08.15.2019, assessing clinical features and/or any type of intervention for GD. A total of 263 articles were retrieved, and 116 original reports that were deemed relevant and satisfied the inclusion criteria were included in the analysis (88 case reports, 26 case series and two retrospective reviews). From these articles, 317 patients were identified, with a male-to-female ratio of 3.95. The mean age was 59 years (range 11-92). Typical lesions were itchy papules and vesicle-papules, generally located on the trunk. Spontaneous resolution within one week to eight months was described in 42 % of cases. Topical corticosteroids (TCSs) were the most frequent treatment (response rate of 70 %) followed by systemic retinoids and corticosteroids with response rates of 86 % and 64 %, respectively. According to the results of this review, TCS appears to be the most frequently employed treatment, and we suggest TCS as first-line therapy. Second-line treatments could include systemic retinoids or systemic corticosteroids.

Advanced Glycation End Products are Increased in the Skin and Blood of Patients with Severe Psoriasis.

Psoriasis is frequently associated with metabolic comorbidities. Advanced glycation end products (AGEs) are highly oxidant, biologically active compounds that accumulate in tissues in association with hyperglycaemia, hyperlipidaemia and oxidative stress. This is a cross-sectional case-control study involving 80 patients with mild/severe psoriasis and 80 controls matched for age, sex and body mass index (40 with severe eczema, 40 healthy individuals). Patients and healthy individuals with a smoking habit, diabetes, dyslipidaemia, hypercholesterolaemia, hypertension or who were under systemic treatment were excluded from the study. Skin AGEs were measured in normal-appearing skin by a standard fluorescence technique, and blood AGEs (total AGEs, pentosidine and AGEs receptor) by enzyme-linked immunosorbent assay. Levels of cutaneous AGEs (p < 0.04), serum AGEs (p < 0.03) and pentosidine (p <0.05) were higher in patients with severe psoriasis. Cutaneous AGEs correlated well with serum AGEs (r = 0.93, p < 0.0001) and with Psoriasis Area and Severity Index score (r = 0.91, p < 0.0001). Receptor levels were lower (p < 0.001) in severe psoriasis, and inversely correlated with disease severity (r = -0.71, p < 0.0002). Patients with severe psoriasis have accumulation of skin and serum AGEs, independent of associated metabolic disorders.

Primary Cutaneous CD4+ Small/Medium Pleomorphic T-Cell Lymphoproliferative Disorder: A Case Series.

BACKGROUND: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+ PCSM-LPD) is defined by a predominance of small- to medium-sized CD4+ pleomorphic T cells and a favorable clinical course. OBJECTIVE: We performed a retrospective analysis of 6 patients with CD4+ PCSM-LPD and reviewed the literature to address questions about its diagnosis, treatment, and prognosis. METHODS: Patients were 3 men and 3 women with a median age of 50 years. All patients presented with a single erythematous nodule, localised on the head in 4 patients and the upper trunk in 2 cases. No patients showed extracutaneous disease at any evaluation. Histopathologic features were characterised by nodular, diffuse, or, in 1 case, a superficial dense infiltrate of small/medium-sized pleomorphic CD4+/PD1+ T lymphocytes. T-cell receptor clonality was demonstrated in 5 cases. Treatment was surgical excision in 5 cases and radiotherapy in 1 case. RESULTS: All patients achieved complete resolution without relapses, during a median follow-up of 3 years. A review of the literature confirmed that CD4+ PCSM-LPD presents predominantly with a solitary nodular lesion on the face, neck, or upper trunk in adult patients. Surgical excision is the preferred treatment. Spontaneous resolution after biopsy may occur. CONCLUSIONS: CD4+ PCSM-LPD is a rare disorder with a favorable course.

Advanced Glycation End Products in the Pathogenesis of Psoriasis.

Advanced glycation end products (AGEs) are extremely oxidant and biologically reactive compounds, which form through oxidation of sugars, lipids and amino acids to create aldehydes that bind covalently to proteins. AGEs formation and accumulation in human tissues is a physiological process during ageing but it is enhanced in case of persistent hyperglycemia, hyperlipidemia and oxidative or carbonyl stress, which are common in patients with moderate to severe psoriasis. Exogenous AGEs may derive from foods, UV irradiation and cigarette smoking. AGEs elicit biological functions by activating membrane receptors expressed on epithelial and inflammatory cell surface. AGEs amplify inflammatory response by favoring the release of cytokines and chemokines, the production of reactive oxygen species and the activation of metalloproteases. AGEs levels are increased in the skin and blood of patients with severe psoriasis independently of associated metabolic disorders. Intensified glycation of proteins in psoriasis skin might have a role in fueling cutaneous inflammation. In addition, AGEs released from psoriatic skin may increase metabolic and cardiovascular risk in patients with severe disease.

Managing the Patient with Psoriasis and Metabolic Comorbidities.

Epidemiological data demonstrate strong associations between psoriasis and metabolic comorbidities, including obesity, hypertension, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease. The presence of metabolic comorbidities significantly influences the selection and effectiveness of pharmacological treatments. Some drugs should be prescribed with caution in patients with metabolic comorbidities because of an increased risk of adverse events, while others could have a reduced effectiveness. The aim of this narrative review is to highlight the challenges that healthcare professionals may face regarding the management of psoriasis in patients with metabolic comorbidities. In the first part of the article, the epidemiological association between psoriasis and metabolic comorbidities and their pathogenetic mechanisms is summarized. The second part describes the efficacy and safety profile of conventional and biologic drugs in patients with selected metabolic comorbidities including obesity, non-alcoholic fatty liver disease/hepatic steatosis, and diabetes. Finally, the role of pharmacological and non-pharmacological interventions, such as diet, alcohol abstinence, physical activity, and smoking avoidance is discussed. In conclusion, the choice of the best approach to manage patients with psoriasis with metabolic comorbidities should encompass both tailored pharmacological and individualized non-pharmacological interventions.

Long-Term Effectiveness and Safety of Ixekizumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: A Five-Year Multicenter Retrospective Study-IL PSO (Italian Landscape Psoriasis).

INTRODUCTION: The introduction of biological therapies has revolutionized the treatment of moderate-to-severe plaque psoriasis. In particular, ixekizumab, an inhibitor of interleukin-17A, has shown great results in terms of efficacy and safety in both clinical trials and real-world experiences. However, there is a lack of long-term real-world data available for ixekizumab. METHODS: We conducted a multicenter real-life study to evaluate the effectiveness and safety of ixekizumab in patients with moderate-to-severe plaque psoriasis. Psoriasis Area and Severity Index score (PASI) was collected at baseline and after 1, 2, 3, 4, and 5 years. The occurrence of any adverse events was recorded at each time point. RESULTS: We enrolled 1096 patients treated with ixekizumab for at least 1 year. At week 52, the percentages of PASI 90 and PASI 100 were 85.04% and 69.07%, respectively. After 5 years of treatment with ixekizumab, out of 145 patients, a PASI 90 response was achieved by 86.90% of patients, while complete skin clearance was reached by 68.28% of patients. We did not observe any new significant safety findings throughout the study period. CONCLUSION: This study supports the long-term effectiveness and safety of ixekizumab in a real-world setting.

Effectiveness, Tolerability, and Drug Survival of Risankizumab in a Real-World Setting: A Three-Year Retrospective Multicenter Study-IL PSO (ITALIAN LANDSCAPE PSORIASIS).

BACKGROUND: Risankizumab is a humanized monoclonal antibody that selectively inhibits interleukin-23. It has been approved for moderate-to-severe plaque psoriasis and has shown efficacy and safety in clinical trials and real-world experiences. This study aimed to evaluate the long-term effectiveness, safety, and drug survival of risankizumab in a real-life setting. MATERIALS AND METHODS: We included patients treated with risankizumab from January 2019 to February 2023. A Psoriasis Area and Severity Index score (PASI) was collected at weeks 0, 16, 28, 52, 104, and 156, when available. The occurrence of any adverse events was recorded at each visit. RESULTS: We enrolled 1047 patients. At week 52, a ≥90% improvement in PASI was observed in 81.44% of patients, with a continuous improvement throughout the study (88.99% and 99.07% at weeks 104 and 156, respectively). After three years of treatment, all patients involving the scalp, palms/soles, and genitalia and 95% of patients with nail psoriasis achieved a complete or almost complete skin clearance. No significant safety findings were observed, and 90.73% of the patients were still on treatment after 36 months. CONCLUSIONS: This study supports the long-term effectiveness and safety of risankizumab in a real-world setting, even in patients involving difficult-to-treat areas.