Effectiveness of risankizumab for the treatment of psoriatic arthritis: a multicenter, real-world study.

BACKGROUND: IL-23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL-23, has proven effective on PsA in two randomized controlled trials. To date, only a few real-world data are available on this topic. METHODS: Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real-world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28-40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR-OMERACT score. RESULTS: After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1-8) to TP1 (1; range 0-7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). CONCLUSION: We can conclude that risankizumab led to substantial improvement in both skin and joint involvement.

Impact of Body Mass Index on the Efficacy of Biological Therapies in Patients with Psoriasis: A Real-World Study.

BACKGROUND: The efficacy of biological therapies used for the treatment of chronic plaque psoriasis can be influenced by numerous variables including  body mass index (BMI). OBJECTIVE: This study aimed to evaluate the impact of BMI on the short-term and long-term efficacy of biological therapies in clinical practice and to identify the best therapeutic options in obese patients (BMI ≥ 30 kg/m2). METHODS: A multicentric retrospective study was conducted in patients who initiated a biological therapy during the period January 2006-December 2019. The proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index at weeks 12 and 24 was calculated also recording the 12- and 24-month drug survival as a measure of long-term efficacy, performing multivariate analyses to assess the impact of different variables. RESULTS: Five hundred and four patients with psoriasis were included. After 12 and 24 weeks, the proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index response was higher in patients with a BMI < 30 kg/m2 compared with those with a BMI ≥ 30 kg/m2 [54.90% vs 43.45% (p = 0.014) at week 12 and 66.84% vs 56.55% (p = 0.021) at week 24]. The Kaplan-Meier survival curves showed how obese patients had a higher probability of discontinuation due to a lack or loss of efficacy (p = 0.0192) compared with non-obese patients. The drug survival analysis also showed that BMI negatively affected the drug survival of secukinumab (odds ratio 1.27, p < 0.001) and ustekinumab (odds ratio 1.06, p = 0.050), while the long-term efficacy of adalimumab, etanercept, and ixekizumab was not influenced by BMI. CONCLUSIONS: Obesity (BMI ≥ 30 kg/m2) negatively affects the clinical response of biological drugs in psoriatic patients, with anti-interleukin drugs being more affected by BMI than anti-tumor necrosis factor drugs.

Predictive factors of lack of response to adalimumab among bio-naive patients suffering from moderate-to severe psoriasis: analysis of a multicenter data collection in Italy.

INTRODUCTION: Efficacy of anti-TNF-a agents seems inferior to IL-17 and IL-23 inhibitors. Nevertheless, after biosimilars approval, anti TNF-a agents are recommended as first-line for psoriatic patients, for economic reasons. METHODS: Predictive factors of response or non-response to adalimumab in bionaive patients who started adalimumab (originator or biosimilar) over 12 years in 9 dermatologic centers in Italy. Effectiveness was assessed with Psoriasis Area and Severity Index (PASI75 and PASI90) at weeks 12, 24 and 48. Multiple logistic regressions were used for variables predicting clinical response; Kaplan-Meier survival curves and Cox regression for drug survival. RESULTS: The drug survival analysis showed reduced hazard ratio of overall discontinuation with male gender and scalp localization. In contrast, baseline PASI and genital psoriasis were significantly associated with increased risk of overall discontinuation. Predictive factors of non-response seemed elevated in patients with baseline PASI, older age groups, previously treated patients with phototherapy, females or patients with palmo-plantar while scalp psoriasis, previous cyclosporine and acitretin appeared as a positive predictive factor. CONCLUSIONS: This real-life analysis might be useful for clinicians in case of bio-naive patients with moderate-to-severe psoriasis and various comorbidities.

Prevalence of cutaneous comorbidities in psoriatic patients and their impact on quality of life.

In contrast to the evidence for systemic co-morbidities, relatively few studies have examined the prevalence of cutaneous inflammatory co-morbidities in psoriatic patients. We conducted an observational multi-site study to measure the prevalence of cutaneous co-morbidities in adult patients with plaque psoriasis and to assess the relative impact on quality of life (QOL). Each patient attending one of the study clinics over a period of six months was evaluated to assess the presence of any concomitant skin inflammatory disease other than psoriasis at the time of the visit. Patients were also asked to complete QOL surveys at the initial visit, using DLQI, SF36, Skindex 29, and PDI. A total of 118 study participants (21.1%) had a cutaneous comorbidity. The most common cutaneous co-morbidities were rosacea (23 cases; 4.1%) and acne vulgaris (22 cases; 3.9%). Psoriatic patients with co-existing skin diseases had a worse QOL than those without, as evidenced by DLQI, Skindex 29, and PDI scores. Dermatologists should take a global approach to manage psoriatic patients by carefully evaluating the skin for any disorder and providing treatment to achieve "clean" skin.

Moderate-to-severe psoriasis and pregnancy: impact on fertility, pregnancy outcome and treatment perspectives.

Psoriasis affects 2-4% of the world's population, with no difference between men and women and 70% of patients experiencing disease onset before the age of 40, which coincides with the reproductive years. Few data are available from literature on impact of psoriasis on fertility, course and outcome of pregnancy and risk associated with treatments. Recent studies on other immune-mediated inflammatory diseases, among which psoriasis is also included, indicate that rheumatoid arthritis and inflammatory bowel diseases can impact female fertility and pregnancy outcomes especially during active disease episodes. In psoriasis hormonal and metabolic comorbidities, unhealthy lifestyles and systemic inflammation could also influence the ability to conceive, pregnancy course and birth outcomes. In this article we review current knowledge on reproductive function, course and outcome of pregnancy in women affected by moderate-to-severe psoriasis. Systemic treatments are also considered with a special focus on TNF-alpha blocking agents and implication of molecular structure on placental transportation and fetal exposure.

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.

Treatment of psoriasis with etanercept in immunocompromised patients: Two case reports.

Tumour necrosis factor (TNF)-α blocking agents have revolutionized the treatment of psoriasis and psoriatic arthritis. Concerns remain about increased susceptibility to infection and onset of malignancies, and the use of TNF-α agents in patients with HIV infection or undergoing immunosuppressant treatment is debated. We report cases of severe plaque psoriasis in a patient with HIV infection and in a liver transplant recipient who were successfully treated with etanercept, an anti-TNF-α agent, without notable side-effects.

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.

Clinical, histopathological, and immunological evaluation of a series of patients with erythema nodosum.

BACKGROUND: The pathogenesis of erythema nodosum (EN) is still poorly understood, and studies evaluating the involvement of a cytokine network are very scarce. OBJECTIVES: To investigate clinical and pathological features, the cytokine profiles, and the balance of T-regulatory (Treg) and T-helper (Th)17 cells in serum and lesional skin of patients with EN. METHODS: Patients with a diagnosis of EN were consecutively enrolled, and their clinical and histopathological features were recorded. A panel of cytokines was evaluated in both serum and lesional skin using enzyme-linked immunosorbent assay. Real-time polymerase chain reaction was performed to evaluate the Treg/Th17 cell balance. RESULTS: Histopathological examination of skin biopsy specimens from all patients (four women and one man) showed classical features of EN. The most widely expressed cytokines were innate immunity cytokines (mainly tumor necrosis factor alpha, interleukin-8 and -6) and growth factors (mainly granulocyte colony-stimulating factor and monocyte chemoattractant protein-1). The Treg/Th17 balance was highly different between patients. CONCLUSIONS: The present study emphasizes the crucial role of neutrophils in the pathogenesis of EN, as high levels of cytokines and growth factors mainly involved in neutrophil recruitment and activation were detected.

Melanoma and non-melanoma skin cancer in psoriatic patients treated with high-dose phototherapy.

OBJECTIVES: The carcinogenic effect of plus ultraviolet A (PUVA)-therapy in psoriatic patients has been widely demonstrated, while data on the safety of narrow band (311 nm) ultraviolet B (nb-UVB) are scarce. We investigated the occurrence of melanoma and non-melanoma skin cancer (NMSC) in psoriatic patients treated with nb-UVB or PUVA-therapy. METHODS: This retrospective study included patients affected by psoriasis, who had been treated with nb-UVB or PUVA-therapy. Clinical data and phenotypic risk factors were collected and a total body examination was performed at a routine appointment during the study period. RESULTS: We examined 92 patients (60 males and 32 females; mean age: 53.5 years, range: 20-83 years) treated with PUVA-therapy (42/92, 45%) or with nb-UVB (50/92, 55%) for 1-28 years (mean: 7.1 years). Among patients treated with PUVA, nine skin tumors (one melanoma, seven basal cell carcinoma (BCCs) and one squamous cell carcinoma (SCC)) were detected in 2/42 (4.7%) patients, while in the nb-UVB group, 14 skin tumors including two melanomas, four BCCs, and eight SCCs were diagnosed in 6/50 (12%) patients. CONCLUSIONS: A noteworthy number of NMSC were diagnosed in this Mediterranean population of patients exposed to high-dose UV treatment. A thorough risk-benefit evaluation should always be done before UV treatment and patients should be carefully monitored for skin cancer during and after treatment discontinuation.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL): a possible pathogenic role in chronic plaque psoriasis.

BACKGROUND: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine member of the tumour necrosis factor (TNF) family. Its role has been investigated in skin cancers and some inflammatory and/or immune-mediated skin diseases. An involvement of TRAIL in psoriasis pathogenesis has recently been hypothesized. We investigated the expression and localization of TRAIL and its receptors in psoriatic skin and measured serum TRAIL. The intracellular pathways activated by TRAIL were assessed to investigate its potential role in the pathogenesis of psoriasis. METHODS: Twenty-four consecutive patients with plaque psoriasis and age- and sex-matched healthy subjects were recruited. Serum TRAIL was measured by means of an enzyme-linked immunosorbent assay (ELISA). TRAIL and TRAIL receptors were evaluated by reverse transcription - polymerase chain reaction (RT-PCR) (RNA of lesional and non-lesional psoriatic skin) and by immunohistochemistry (lesional skin). Caspase 8 and NF-kB immunoexpression were also evaluated by immunohistochemistry. RESULTS: RT-PCR demonstrated increased synthesis of TRAIL and its receptors in lesional vs. non-lesional skin. Immunohistochemistry showed a strong staining of TRAIL and TRAIL receptors both in the epidermis and in the dermal infiltrate. Finally, a correlation emerged between caspase 8 and TRAIL immunoexpression in the dermis. CONCLUSIONS: Our findings suggest an involvement of TRAIL in psoriasis pathogenesis, probably through an action at the site of the inflammatory infiltrate, likely via caspase 8.

Psoriasis and polycystic ovary syndrome: a new link in different phenotypes.

OBJECTIVE: Women affected by PCOS and psoriasis are more likely to have insulin-resistance, hyperinsulinemia, reduced HDL cholesterol levels and a more severe degree of skin disease than those with psoriasis alone. The mechanism underlying this association between PCOS and psoriasis is currently unknown. The aim of the present study was to evaluate the features of psoriasis and the psoriasis severity scores in the different PCOS phenotypes and in age and body mass index (BMI)-matched psoriatic control patients. STUDY DESIGN: A cross-sectional study was performed on 150 psoriatic patients: 94 PCOS and 56 age- and BMI-matched controls. PCOS patients were diagnosed and divided into four phenotypes according to Rotterdam criteria: A - patients with complete phenotype with hyperandrogenism (H) plus oligoamenorrhea (O) plus polycystic ovary (PCO) on ultrasound examination; B - patients with H plus O (without PCO); C - patients with H plus PCO (ovulatory phenotype); D - patients with O plus PCO (without H). The patient's Psoriasis Area and Severity Index (PASI) as well as the Physician's Global Assessment (PGA) were calculated. A PASI score ≥10 was correlated with common indicator of severe disease. A PGA ≥4 was considered as a condition of moderate to severe disease. RESULTS: Among the four phenotypes investigated, the group with complete phenotype (H plus O plus PCO) had a higher prevalence of patients with patient's PASI ≥10 compared to controls (Odds Ratio (OR) 4.71, 95% confidence intervals (CI) 1.59-13.95). The group with O plus PCO had a higher prevalence of patients with PGA ≥4 compared to controls (OR 26.79, 95% CI 3.40-211.02) while the ovulatory group had a lower prevalence of patients with PGA ≥4 (OR 0.06, 95% CI 0.01-0.51). CONCLUSIONS: The ovulatory phenotype displays a milder psoriasis form than other phenotypes while the phenotypes with oligoamenorrhea presented higher severity scores of disease than other phenotypes and control group.

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.

Dermoscopy of melanocytic lesions in patients affected by oculocutaneous albinism: a case series.

BACKGROUND: Although the majority of skin cancers in albino patients consists of squamous and basal cell carcinomas, malignant melanomas have also been described, albeit less frequently. OBJECTIVE: The aim of our study was to evaluate melanocytic lesions in albino patients to look for any recurrent dermoscopic pattern. METHODS: We enrolled 12 consecutive albino patients presenting to our department and examined each patient for the presence of melanocytic nevi with the unaided eye and then with dermoscopy. Melanocytic lesions with suspicious clinical or dermoscopic features were excised and histopathologically evaluated. RESULTS: Analysis of the recorded images permitted us to find two main dermoscopic patterns in this group of patients. The first one was represented by a homogeneous light-brown yellowish pattern associated with comma-like and dotted vessels; the second one consisted of a classical brown reticular pattern frequently associated with central depigmentation and with comma-like vessels. Moreover, based on some atypical dermoscopic features, in 2 patients we excised 3 melanomas in situ (in the same patient) and a thick melanoma (3.2 mm). CONCLUSIONS: Dermoscopy may represent a useful tool for the evaluation of melanocytic lesions in albino patients, permitting an early diagnosis of melanoma.