Evaluation of the impact of night shift work on disease severity in psoriatic patients: a case-control study with clinical, hormonal, and immunological evaluation.

INTRODUCTION: Night shift work disrupts circadian rhythms and has been associated with immune system alterations and various health conditions. However, there is limited data regarding its impact on psoriasis. The aim of our study was to compare psoriasis severity and the hormonal and immunological profile in patients with a night shift work to those with a daytime occupation. METHODS: In this case-control study, we enrolled psoriatic patients aged >18 years engaged in night shift work and a control group of psoriatic patients with a daytime occupation. A further categorization was performed by the duration of nightshift work: < or ≥ 7 days a month and < or ≥ 8 years. Disease severity was evaluated by PASI, BSA and DLQI and blood samples were taken to measure various hormonal and immunological markers. Univariable and multivariable analysis were performed to assess differences between the two groups. RESULTS: A total of 40 night shift workers were included, along with 36 patients in the control group. Patients who worked nightshifts at least 7 days a month had significantly higher PASI scores (11.2 ± 6.6 vs 8.5 ± 6.6; p 0.04) and higher IL-8 serum (115.33 ± 463.65 pg/ml vs 19.98 ± 29.78 pg/ml; p = 0.006) compared to patients who didn't. Night shifts workers for at least 8 years had higher BMI (28.65±4.56 versus 25.32±5.50, p=0.010), and females had higher testosterone levels (0.46±0.53 ng/mL vs. 0.23±0.13 ng/mL; p = 0.055). CONCLUSION: Night shift might increase psoriasis severity and have an impact on chronic inflammation, obesity and hormonal imbalances.

Tildrakizumab in moderate-to-severe plaque psoriasis: A multicenter, retrospective, real-life study.

New biologic agents targeting interleukin (IL)23/T-helper17 axis, such as tildrakizumab, have been developed for the treatment of plaque psoriasis. To analyze the efficacy and safety of tildrakizumab in a real life setting of patients affected by moderate-to-severe psoriasis over a 28-week treatment period. A multicentric retrospective study was conducted in patients who initiated tildrakizumab between February 2020 and March 2021. Psoriasis Area and Severity Index-PASI was measured at baseline and after 4, 16 and 28 weeks. The percentage change in PASI value from baseline to the considered time-points, proportion of patients with absolute PASI <3 at week 28 and the percentages of achieving a PASI75 or PASI90 response were assessed. Data about potential safety issues and adverse events (AEs) were collected. Statistical analysis were performed for establish clinical efficacy and for variables predicting clinical response. Fifty nine patients with psoriasis were included. Overall mean PASI percentage reduction was of 88% from baseline to week 28 and 47 out of 59 patients (79.7%) at week 28 had an absolute PASI <3. PASI75 and PASI90 responses at week 28 were achieved by 48 (81.40%) patients and 38 (64.4.0%) patients, respectively. No substantial associations between gender, body mass index - BMI, PASI at baseline and prior exposition to biological therapies and the efficacy endpoints were retrieved. No serious safety issues or discontinuations related to adverse events were reported. In our real-life study, tildrakizumab showed high efficacy and a favorable safety profile, regardless of patient- and disease-related factors.

Risankizumab for the treatment of moderate-to-severe psoriasis: A multicenter, retrospective, 1 year real-life study.

Several new biologic agents targeting IL23/Th17 axis, such as risankizumab, have been developed for the treatment of psoriasis. The aim of the present study was to analyze the efficacy and safety of risankizumab in patients with moderate-to-severe psoriasis over a 52-week period. A multicentric retrospective study was conducted in patients who initiated risankizumab between July 2019 and December 2020. Psoriasis Area and Severity Index-PASI was measured at baseline and after 4, 16, 28 and 52 weeks. Clinical responses were evaluated by PASI75, PASI90 and PASI100 at the same timepoints. Potential safety issues and adverse events (AEs) were collected. Univariable and multivariable logistic regressions were performed for variables predicting clinical response. One hundred and twelve patients with psoriasis were included. PASI90 response was achieved by 17.86% of patients at week 4, 72.22% at week 16, 91.0% at week 28 and 95.24% at week 52 (as observed analysis). No associations between the considered variables and the efficacy endpoints were retrieved, influence of variables such as Body Mass Index (BMI), baseline PASI or previous biologics were not shown. No serious safety issues or discontinuations related to adverse events were reported. Risankizumab showed high efficacy and a favorable safety profile, regardless of patient- and disease-related factors.

Therapeutic Impact and Management of Persistent Head and Neck Atopic Dermatitis in Dupilumab-Treated Patients.

BACKGROUND: Localization of atopic dermatitis (AD) in exposed areas such as the hands, head, and neck has been considered as a negative factor impacting on dupilumab response, although a comparison of exposed versus unexposed areas is not currently available. OBJECTIVES: The aim of this study is to evaluate the clinical response to dupilumab depending on the presence or persistency of AD skin manifestations in specific body areas. METHODS: The study retrospectively collected clinical and demographic data of adult patients affected by moderate to severe AD. Based on the anatomical sites involved, 5 subcohorts of patients were identified. RESULTS: A total of 41 patients were included in the study. Disease amelioration was detected during the study period, although baseline head/neck and hand localization was associated with a significantly lower likelihood of achieving an Eczema Area Severity Index (EASI) ≤1. In addition, patients with head/neck persistency showed a significantly lower response when compared to patients without persistency of head/neck AD in terms of both mean EASI and Dermatology Life Quality Index (DLQI) reduction. CONCLUSION: AD localization in exposed areas at the baseline and AD persistency at the head/neck may have a negative impact on certain treatment response parameters to dupilumab therapy.

Successful Combination of Systemic Agents for the Treatment of Atopic Dermatitis Resistant to Dupilumab Therapy.

BACKGROUND: Dupilumab, a monoclonal antibody inhibiting the signaling pathway of IL-4/IL-13, was shown to be safe and effective in the treatment of moderate/severe atopic dermatitis (AD) in several clinical trials and real-life experiences, with only a small percentage of patients showing to be resistant or to lose disease control. OBJECTIVES: In this study, we investigated the effectiveness and safety in combining dupilumab with systemic agents or phototherapy in patients experiencing an inadequate response to dupilumab. METHODS: This retrospective, monocentric, observational study consecutively included patients aged >18 years, with moderate-severe AD, under treatment with dupilumab. In this cohort of patients, we analyzed data of subjects who experienced an inadequate response to dupilumab, even when combined with topical corticosteroids, and for whom an additional systemic treatment or phototherapy was combined to dupilumab. RESULTS: In this study, we included a total population of 69 patients treated with dupilumab. In 12/69 patients (17.4%) showing an inadequate response to dupilumab, a combined treatment consisting of dupilumab plus methylprednisolone (n = 5), cyclosporine (n = 4), methotrexate (n = 2), or narrow band-UVB (n = 1) was administered. Overall, after 8 weeks of combined therapy, the majority of patients (11 of 12) obtained an improvement of signs and symptoms of AD. Patients treated with combined therapy did not experience any adverse events, neither did they withdraw treatment because of the occurrence of adverse events. CONCLUSIONS: This study suggests that the combination of dupilumab with a conventional drug or phototherapy may represent a valid therapeutic choice, maintaining a good safety profile in AD patients recalcitrant to dupilumab monotherapy.

Clinical and Ultrasonographic Profile of Adalimumab-treated Hidradenitis Suppurativa Patients: A Real-life Monocentric Experience.

Ultrasonography has proven useful for diagnosis and treatment monitoring in patients with hidradenitis suppurativa. The aim of this study was to assess the clinical response to adalimumab using ultrasound findings. This prospective study collected data on demographic features, disease severity, and hidradenitis suppurativa findings from patients with hidradenitis suppurativa treated with adalimumab. Generalized estimating equations investigated relationships between disease severity measures and clinical/demographic variables. The study included a total of 41 patients with hidradenitis suppurativa who were treated with adalimumab for a mean period of 50.8 ± 32.2 weeks; range 6-108 weeks). Clinical improvement was observed during adalimumab therapy, with a progressively greater number of patients achieving HiSCR50 response (36.4% at week 52). Disease duration was identified as the most relevant clinical variable affecting disease severity and treatment response. Treatment response was also influenced by treatment duration, with a 4% greater likelihood of achieving HiSCR50 response at each time-point. At the ultrasound examination, subcutaneous involvement of hidradenitis suppurativa lesions was identified as a predictive negative factor for clinical response to adalimumab (HiSCR50 achievement).

Untreated Psoriasis Impairs Male Fertility: A Case-Control Study.

BACKGROUND: Recent evidence indicates that a systemic state of inflammation may impair fertility, but data about psoriatic males are scarce. OBJECTIVES: The aim of this study was to assess gonadal function in psoriatic males implementing our knowledge about fertility in these subjects. METHODS: Male psoriatic patients, aged between 18 and 55 years, and a group of healthy subjects matched for age, BMI and geographic origin were enrolled. All subjects underwent a complete physical and andrological examination, standard semen analysis, complete microbiological analysis and ultrasound evaluation of sexual glands. Seminal levels of soluble urokinase-type plasminogen activator receptor (suPAR) and serum levels of testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone and follicle-stimulating hormone were also assessed. RESULTS: Fifty patients and 50 controls fulfilled the inclusion criteria and were enrolled in our study. Testosterone and SHBG were found to be significantly decreased in patients with psoriasis compared with the control group. Higher levels of E2 were also reported in psoriatic patients. Total sperm count, sperm motility and percent of spermatozoa with normal morphology were significantly reduced in patients compared to controls. suPAR levels were significantly increased in patients compared to controls and found to be above the reference limits. Ultrasound signs of inflammation of the accessory glands were observed in 35/50 patients with psoriasis and in none of the controls. CONCLUSION: Our study suggests that untreated psoriasis may impair male fertility. We also found that this might be due to an impact of systemic inflammation on the hormonal profile and on sexual accessory gland inflammation.

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.

HLA-Cw6 allele, NFkB1 and NFkBIA polymorphisms play no role in predicting response to etanercept in psoriatic patients.

OBJECTIVE: This retrospective study aimed to evaluate the role of NFKB1-94 insertion/deletion ATTG (rs28362491) and NFkBIA 2758 A>G (rs696) polymorphisms and HLA-Cw6 allele in predicting the response to etanercept, a TNF-α blocker, in a population of psoriatic patients naive to biologics. METHODS: Genomic DNA was extracted from whole blood in a series of 96 psoriatic patients who received etanercept for at least 3 months. Patients were classified as responders if they achieved a Psoriasis Area and Severity Index improvement of at least 75% after 12 weeks of etanercept treatment and as nonresponders if Psoriasis Area and Severity Index improvement was less than 75%. Genotyping was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: We did not find any significant role of NFKB1-94 insertion/deletion ATTG (rs28362491) and NFkBIA 2758 A>G (rs696) polymorphisms and the HLA-Cw6 allele in predicting the response to etanercept. CONCLUSION: Our findings suggest that NFKB1 and NFkBIA polymorphisms are not related to the response to etanercept. They also indicate that the therapeutic response to etanercept is not influenced by the presence of the HLA-Cw6 allele, in contrast with previous evidence on ustekinumab, suggesting that such an association is related more to drug than to disease characteristics.

Clinical predictors of nonresponse to anti-TNF-α agents in psoriatic patients: A retrospective study.

Although the heterogeneity of the therapeutic response to TNF-α blockers seems to be mainly due to genetic factors, several studies showed that a range of factors may influence it. The aim of our study was to investigate the impact of patients' demographic and clinical characteristics on primary response to an anti-TNF-α therapy in psoriatic patients. We retrospectively examined the relationship between various clinical and demographic features and response to treatment with etanercept, adalimumab, and infliximab, evaluated as PASI75 and average PASI improvement at weeks 12, 16, and 14, respectively. We analyzed data obtained from 199 patients. A better response to the treatment was significantly associated with male gender (OR = 2.59), coexistence of psoriatic arthritis (OR = 1.97), and PASI ≤15 at baseline (OR = 0.91). The present study supports that some clinical factors may be potential predictors of response to anti-TNF-α agents in psoriatic patients.

A possible role of polycystic ovary syndrome for pregnancy complications in women with psoriasis.

Psoriasis is a common, chronic, relapsing immune-mediated inflammatory disease (IMID) of the skin. IMIDs are multifactorial diseases characterized by common molecular pathways leading to a systemic inflammation. Patients with an IMID are also at higher risk of developing co-morbidities, such as adverse pregnancy outcomes, than the general population. A higher rate of pregnancy complications have been seen in inflammatory bowel disease and rheumatoid arthritis. The data for psoriasis are inconsistent but it appears that women with moderate-to-severe psoriasis may also have an increased risk of poor pregnancy outcomes. The cause of this association is unknown, although it may be related to elevated proinflammatory cytokines such as IL-6 and TNF-α, the high prevalence of comorbidities and other unhealthy behaviours, or the high prevalence of polycystic ovary syndrome (PCOS). In a recent study, PCOS prevalence in a psoriatic cohort (n = 51) was higher than in non-psoriatic women (n = 102) (47% versus 11%), and women with PCOS and psoriasis had a greater probability of insulin resistance, hyperinsulinaemia, and dyslipidaemia as well as a more severe skin condition, than those with psoriasis alone. Further studies are necessary to clarify the impact of psoriasis on pregnancy and in particular if these effects are mediated by concomitant PCOS.

Drug survival of biologics and non-biologics in patients affected by palmoplantar psoriasis: a "real-world", mono-center experience.

BACKGROUND: Data on the treatment of palmoplantar psoriasis (PP) are very limited as these patients are often excluded from clinical trials. Moreover, this form of psoriasis is often resistant to treatment, making its clinical management complex. METHODS: Primary endpoint was to evaluate the clinical and demographic characteristics and the drug survival of both biological and non-biological drugs in a population affected by PP. Secondary endpoint was to highlight any differences between the hyperkeratotic and pustular variant. We analyzed data from 233 psoriasis patients with palmoplantar involvement, with or without chronic plaque psoriasis. We performed a drug-survival analysis with the aid of Kaplan-Meier survival and a multivariate analysis to highlight the influence of certain variables on treatment persistence using a Cox regression model. RESULTS: The drug-survival analysis revealed that biologic drugs compared to non-biologic drugs are associated with a higher persistence in treatment (59.73 vs. 43.56%); in particular, anti-IL23 drugs were found to be the drugs with the best drug-survival overall (67.94% of patients at 60 months are still on these drugs). Furthermore, our multivariate analysis shows that when compared with biological drugs, non-biological drugs are associated with an increased risk of treatment discontinuation (HR = 1.95 [95% CI: 1.41-2.68], P = 0.001). CONCLUSIONS: Our study confirms the difficulty of treating PP and shows that biologic drugs are associated with longer persistence in treatment than non-biologics in both PP's variants, not because of their higher effectiveness but because of their better safety profile.

Rapid response on facial psoriasis to bimekizumab: case series.

Psoriasis is a chronic inflammatory disease that can affect any part of the body but, when it appears in certain areas, like the face, it can have a very significant psychological impact. Biologics, in particular IL-17 and IL-23 drug inhibitors, have shown relevant clinical efficacy in the management of psoriatic lesions in difficult-to-treat areas. In post hoc analysis of phase III trials in plaque psoriasis, bimekizumab has shown safety and complete clearance of high-impact areas. However, these studies did not focus on the effect of bimekizumab on facial lesions. Therefore, this case series represents the first clinical real-life experience of rapid and successful management of facial psoriasis with bimekizumab in six patients.