A Prospective, Multicenter, Open-label Study to Evaluate the Safety and Efficacy of a Cream Containing Xyloglucan, Pea Protein, and Opuntia ficus-indica Extract Versus Calcipotriol/Betamethasone in Adult Patients with Mild-to-moderate Psoriasis.

Objective: Psoriasis is a chronic, inflammatory skin disease, requiring local and systemic drugs according to disease severity. This study aims to investigate the efficacy and safety of a topical treatment containing xyloglucan, pea proteins and Opuntia ficus-indica extracts (XPO) compared to calcipotriol 50mcg/betamethasone 0.5mg ointment (CB). Methods: Forty-two patients diagnosed with mild-to-moderate plaque psoriasis were assigned 1:1 to XPO treatment or CB for 28 days. Disease status was assessed at baseline (V1), monitored every two weeks (V2, V3), and at follow-up (V4). Disease severity was assessed by PASI (Psoriasis Area and Severity Index), PGA (Physician's Global Assessment), and VAS (Visual Analog Scale for itching). Photos were taken before and after XPO treatment. Treatment efficacy was determined by comparing psoriasis severity at baseline to V3. Tolerability was assessed by monitoring the occurrence of adverse events. Results: Both groups showed a statistically significant difference in PASI score from V1 to V2 (p=0.001, XPO; p=0.008, CB) and to V3 (p=0.001, XPO; p=0.004, CB). XPO achieved a PASI 50 score of 24 percent at V2 and 52 percent at V3 compared to CB (0% at V2 and 19% at V3). At V3, PGA was significantly reduced in both groups (p=0.003, XPO; p=0.001 CB). Both treatments significantly reduced itching at V2 (p=0.001, XPO; p=0.003, CB) and V3 (p=0.001, XPO; p=0.0005, CB). Conclusion: XPO showed similar efficacy to CB, significantly reducing disease severity, erythema, itching, induration, and scaling with an excellent tolerability profile.

Prevalence of metabolic syndrome and chronic inflammation in psoriasis before and after biologic therapy: a prospective study.

Background: As a chronic inflammatory disease, psoriasis affects not only the skin but also the metabolic profile of the patients. Biologic therapies, including tumor necrosis alpha (TNF-a) inhibitors and interleukin (IL)-12/23 and IL-17 antagonists, have proven effective in the reduction of psoriasis severity; however their impact on the metabolic and chronic inflammatory profiles of the patients remains incompletely elucidated. Methods: We performed a longitudinal case-control study on 106 psoriasis patients and an equal number of controls without the disease, as well as a prospective study on the patient group with the end point being 6 months of biologic therapy. Patients received either ixekizumab, secukinumab, guselkumab, certolizumab, ustekinumab, risankizumab, or adalimumab. Abdominal circumference, serum fasting glucose, triglycerides (TG), high-density lipoproteins (HDL), erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured for both patients and controls, with an additional measurement for patients after 6 months. Results: At baseline, the number of psoriasis patients suffering from obesity, metabolic syndrome, and chronic inflammation significantly outnumbered controls (p<0.05), with the calculated odds ratio being 1.88, 6.83, and 81.84 for these conditions in psoriasis, respectively. Biologic therapies increased the abdominal circumference of patients in a slight but significant fashion (p<0.05), as well as significantly improved HDL, CRP, ESR levels at 6 months (p<0.05). Moreover, after 6 months, the number of patients meeting the diagnostic criteria for metabolic syndrome and chronic inflammation was significantly lower than at baseline (p<0.001). Conclusions: According to our results, biologic therapies improve the overall metabolic and inflammatory profiles of psoriasis patients, the most significant ameliorations being noticed for serum HDL, CRP, and ESR.

Association between IL-17F, IL-17RA Gene Polymorphisms and Response to Biological Drugs in Psoriasis and Beyond.

Psoriasis is a systemic inflammatory disease that associates with multiple comorbidities. It involves complex interactions between environmental factors and polygenic predisposition. The IL-17 family is one of the main actors in the pathogenesis of psoriasis. Secondary nonresponse is common, especially during the long-term use of TNF-α inhibitors, but it is not uncommon even for newer biologics, such as IL-17 inhibitors. Identification of clinically useful biomarkers of treatment efficacy and safety would enable optimal treatment selection, improve patient quality of life and outcome, and reduce healthcare costs. To our knowledge, this is the first study to evaluate the relationship between genetic polymorphism of IL-17F (rs763780) and IL-17RA (rs4819554) and response to biological treatment and other clinical data in bio-naive and secondary non-responders psoriasis patients in Romania and Southeastern Europe. We performed a prospective, longitudinal, analytical cohort study of 81 patients diagnosed with moderate-to-severe chronic plaque psoriasis who received biological treatments for the first time. Of the 79 patients treated with TNF-α inhibitors, 44 experienced secondary nonresponse. All patients were genotyped for the two SNPs in IL-17F and IL-17RA genes. The rs763780 polymorphism in the IL-17F gene could be an attractive candidate biomarker for predicting which patients will respond to anti-TNF-α therapies. Another emergent association of rs4819554 in IL-17RA with the risk of nail psoriasis and a higher BMI in moderate-to-severe plaque psoriasis patients is described.

Biologic Therapies Decrease Disease Severity and Improve Depression and Anxiety Symptoms in Psoriasis Patients.

BACKGROUND: Psoriasis is an immune-mediated chronic skin disease that is associated with a significant psychological burden. A newer line of therapy is represented by biologic agents. Our study aimed to evaluate the effect of biologic therapies in the treatment of psoriasis concerning both disease severity and psychological comorbidity. MATERIAL AND METHODS: We performed a prospective case-control comparison to evaluate the prevalence of depression and anxiety in psoriasis patients and unaffected individuals. All patients were recruited between October 2017 and February 2021. Baseline depression (PHQ-9), anxiety (GAD-7), PASI, and DLQI scores were noted. Then, we evaluated the efficacy of biologic treatment in reducing these scores at 6 months of therapy. Patients were treated with either ixekizumab, secukinumab, guselkumab, certolizumab, ustekinumab, risankizumab, or adalimumab. RESULTS: 106 bio-naïve patients with psoriasis and 106 controls without the disease were included in this study. Depression and anxiety were significantly more common among psoriasis patients than in unaffected individuals (p < 0.0001). Female patients presented both depression and anxiety more frequently than men in both case and control groups. Disease severity was significantly associated with worsened depression and anxiety symptoms. Biologic therapy resulted in a significant decrease in all four scores at the 6-month mark for each patient (p < 0.0001). Only an improved PASI correlated significantly with lower depression and anxiety scores (p < 0.005), whereas a decreased DLQI did not (p > 0.955). None of the seven biologic agents used was discovered to be superior. CONCLUSION: biologic therapies are effective in decreasing both disease severity and alleviating depression and anxiety symptoms in psoriasis.

Treatment of psoriasis - unburdened by fear during SARS-CoV2 menace.

In a matter of mere months, humanity was unexpectedly struck by the appearance of SARS-CoV-2, shifting our perception as medical practitioners regarding our day-to-day activity. One especially disconcerting change was patient addressability to medical facilities, as well as access to proper healthcare in various fields. As these changes occurred rapidly, dermatologists too had to adapt by means of teledermatology, giving us back the ability to reach, treat, and comfort our patients. Among the individuals requiring special dermatological attention are those suffering from psoriasis, especially considering that the biological therapies employed in treating this debilitating disease become questionable in the circumstance of the current pandemic. As more evidence surfaces concerning the pathophysiology of SARS-CoV-2, we become closer to understanding which therapies may interfere with its clearance, and which are actually safe to use. This review aims to answer the question, are biological therapies warranted in the treatment of psoriasis during the COVID-19 outbreak, or should they be discontinued?

An updated guide in the management of psoriasis for every practitioner.

BACKGROUND: Psoriasis is one of the most common chronic cutaneous skin disorders, having genetic and immunological components. It is currently unknown what exactly triggers it, or how far reaching are the etiological factors, although great strides have been made in uncovering the pathophysiological cascade. Presently, there is a wide diversity of treatment methods for psoriasis, yet not all are applicable for each patient. Selection of both drug and dosage depends on both the knowledge and experience of the treating dermatologist and also on the specific characteristics of each patient. Therefore, the treating physicians should be made aware of the management possibilities, their advantages and their side effects. METHODS: We have performed a non-systematic literature review on the current treatment methods for psoriasis. We have included the studies, articles, and prescription information that provided the most relevant information regarding each therapeutic agent. Afterward, we divided the treatment methods according to delivery and illustrated the management protocols for adult, paediatric, and pregnant patients. DISCUSSION AND CONCLUSIONS: Current therapies are divided into topical drugs, phototherapy, systemic and biological agents. Topical therapies and phototherapy are generally the first and second line of management respectively, being typically effective in treating mild to moderate forms of psoriasis. On the other hand, the chronic moderate to severe forms usually benefit from systemic drugs, whereas biologic agents are reserved for severe or unremitting cases, especially those suffering from psoriatic arthritis. Also of importance is the understanding of the pathophysiological mechanisms in psoriasis and how the selected drugs interfere in the pathological cascade. Furthermore, physicians should be able to recommend the appropriate therapy not only for adults but also for paediatric and pregnant patients as well. In the following manuscript, we present an updated version of these management options, alongside their indications, posology and most common side effects, a guide that may be useful for every practitioner in this field.

Psoriasis: Association of interleukin-17 gene polymorphisms with severity and response to treatment.

Psoriasis is a chronic, inflammatory disease with a complex pathogenesis that is not yet fully understood. Although it is a multifactorial disease, the genetic factor has a major role in the pathogenesis of psoriasis. Genome wide association studies have identified over 50 genetic loci associated with psoriasis risk. Beside TNF-α or IL-23, the IL-17 family is a newer group that has proven implications in the pathogenesis of psoriasis. The most important members of the family, with pro-inflammatory qualities, are IL-17A and IL-17F. These interleukins are produced by a varied number of cells, but by far the most important are Th17 cells. Of the patients 20-30% present moderate-to-severe psoriasis, therefore, systemic medication (phototherapy, methotrexate, cyclosporine, acitretin or biologic agents) is mandatory. The necessity of an individualized treatment plan, for each patient, is imperative in order to establish the best strategy for non-responders to classical treatment or to other biologic treatments. The discovery of Th17 pathway improved the treatment and prognosis of psoriasis. Anti-psoriatic agents against IL-17 or its receptors are a novel group of biologic agents; these include ixekizumab, secukinumab and brodalumab. Polymorphisms of IL-17 family have been correlated with the severity and response to treatment in psoriasis, and also with the risk of inflammatory, infectious, autoimmune or neoplastic pathologies. The significant difference in the presence or absence of susceptibility loci in different population is due to genetic background and environmental factors that have a major impact on disease predisposition. In this study, we reviewed the importance and influence of the IL-17 polymorphisms as predictors of response to treatment and severity of the disease.

Immunohistochemical study of psoriatic plaques and perilesional skin in psoriasis vulgaris patients: A pilot study.

Psoriasis vulgaris, a chronic inflammatory skin disorder, is the result of immune mediated processes, genetic background and environmental factors. Prolactin and the vascular endothelial growth factor seem to play a key role in psoriasis pathogenesis regarding hyperproliferation of epidermal keratinocytes and dermal vascular ectasia. The aim of the study was to investigate the expression of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor receptor 2 (VEGFR2) and prolactin receptor (PRLR) in psoriatic skin by immunohistochemical analysis and to evaluate the correlation with disease severity. Two skin biopsies, psoriatic lesion and perilesional skin, obtained by punch biopsy from 19 nontreated psoriasis patients were examined in hematoxylin and eosin staining and immunohistochemistry (IHC) for TNF-α, VEGFR2 and PRLR. The indirect IHC reaction was carried out automatically and visualized by 3,3-diaminobenzidine (DAB) technique. The average number of DAB-positive cells and the intensity of cell staining were quantified on a predefined scale. The results show a significant difference in the quantity and distribution of TNF-α positive cells in the two sample groups. In psoriatic plaque skin, an increased expression of TNF-α was found in the perivascular dermis and epidermic keratinocytes. In perilesional skin the immunostaining was predominant in the basal layer keratinocytes, while in psoriatic plaque, all the layers were positively marked, with stronger expression at the base. A statistically significant difference was found between the intensity of the immunostaining in the two types of tissue. Positive cells for VEGFR2 and PRL were identified in the basal layer keratinocyte cells (VEGFR2), sweat glands and hair outer shaft sheath (PRLR), without significant differences between the two types of samples. Our findings confirm the importance of TNF-α in psoriasis pathogenesis and a positive correlation with lesions severity. No significant differences were found for VEGFR2 and PRLR, but additional studies are necessary to establish their role.

Understanding psoriasis: Role of miRNAs.

Psoriasis is a chronic, immune-mediated inflammatory skin disease, with a multifactorial etiology and important immunologic, genetic and environmental components. Psoriasis vulgaris represents its most common form, with a variable prevalence across the globe. Although its pathogenesis remains to be fully elucidated, a lack of balance in the epigenetic network has been shown to trigger certain elements of this disease, possibly altering its outcome. MicroRNAs are small non-coding RNA molecules involved in RNA-silencing and the post-transcriptional regulation of gene expression, which also appear to mediate the immune dysfunction in psoriasis. Although microRNA research is a new field in dermatology and psoriasis, there is rapidly accumulating evidence for its major contribution in the pathogenesis of chronic inflammatory conditions, including psoriasis and other dermatological disorders. Furthermore, circulating miRNAs identified in patients' blood samples have been identified as promising biomarkers of diagnosis, prognosis or treatment response. Extended investigations in this field are required, as until now, the exact involvement of miRNAs in psoriasis have remained to be entirely elucidated. This short review highlights a number of the roles of miRNAs found in different stages of psoriasis.

Relationship between etanercept and thyroid function in patients with psoriasis vulgaris.

BACKGROUND AND AIM: Psoriasis vulgaris, a chronic inflammatory skin disease, requires a long term medication, in order to avoid relapsing episodes. TNF-alpha, one of the targeted molecule in psoriasis therapy, seems to be also involved in thyroid disorders etiopathogenesis. The aim of this study was to evaluate the relationship between anti TNF-alpha therapy and thyroid parameters: serum level of triiodothyronine (T3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and antithyroidperoxidase antibody (AbTPO) in psoriasis treated population. METHODS: The study was performed on 44 patients with psoriasis vulgaris (20 patients under antiTNF-alpha treatment (etanercept), 24 patients with no previous systemic therapy). Serum concentrations of hormones, AbAntiTPO and TNF-alpha were measured and a thyroid ultrasonographic evaluation was performed for each patient. RESULTS: The mean serum level of FT4 was significantly higher in patients with no systemic treatment (p<0.05). The patients treated with etanercept had a significantly higher level of TNF-alpha (p<0.05). No significant difference was observed for the other evaluated parameters. Also, we found a significant negative correlation between TNF-alpha and TSH levels (r=-0.366, p=0.015). CONCLUSIONS: We only found that the mean level of FT4 was significantly higher in patients with no systemic treatment. Also, a negative strong correlation was seen between serum level of TSH and TNF-alpha. Based on our data, comparison with other anti TNF-alpha therapies might be of interest in future studies.

Hair loss and regeneration performed on animal models.

Research in the field of reversal hair loss remains a challenging subject. As Minoxidil 2% or 5% and Finasteride are so far the only FDA approved topical treatments for inducing hair regrowth, research is necessary in order to improve therapeutical approach in alopecia. In vitro studies have focused on cultures of a cell type - dermal papilla or organ culture of isolated cell follicles. In vivo research on this topic was performed on mice, rats, hamsters, rabbits, sheep and monkeys, taking into consideration the advantages and disadvantages of each animal model and the depilation options. Further studies are required not only to compare the efficiency of different therapies but more importantly to establish their long term safety.

The role of hormones in the pathogenesis of psoriasis vulgaris.

Psoriasis vulgaris is a chronic, common skin disease, which affects the patient's quality of life to the highest degree. Several exogenous factors and endogenous hormonal changes may act as triggers for psoriasis. The skin possesses a true endocrine system, which is very important in multiple systemic diseases. A number of conditions are associated with psoriasis, and its severity can also be influenced by hormones. Even though the sex hormones and prolactin have a major role in psoriasis pathogenicity, there are a lot of other hormones which can influence the psoriasis clinical manifestations: glucocorticoids, epinephrine, thyroid hormones, and insulin.