Human Beta Defensin-2 mRNA and Proteasome Subunit ß Type 8 mRNA Analysis, Useful in Differentiating Skin Biopsies from Atopic Dermatitis and Psoriasis Vulgaris Patients.

(1): Atopic dermatitis and psoriasis vulgaris are chronic, inflammatory diseases. Clinical presentation usually leads to a proper diagnosis, but sometimes neither clinical examination nor histopathological evaluation can be conclusive. Therefore, we aimed to build up a novel diagnostic tool and check it for accuracy. The main objective of our work was to differentiate between healthy skin (C), atopic dermatitis (AD) and psoriasis vulgaris (PV) biopsies on the base of involucrin (IVL) and human ß-defensin-2 (hBD-2) concentrations and their mRNA, as well as mRNA for TPP2 and PSMB8. (2): ELISA for IVL and hBD-2 proteins and Real-time PCR for the relative expression of mRNA for: IVL (IVL mRNA), hBD-2 (hBD-2 mRNA), PSMB8 (PSMB8 mRNA) and TPP2 (TPP2 mRNA), isolated from skin biopsies taken from AD and PV patients and healthy volunteers were performed. (3): hBD-2 mRNA and PSMB8 mRNA correlated with some parameters of clinical assessment of inflammatory disease severity. hBD-2 mRNA expression, exclusively, was sufficient to distinguish inflammatory skin biopsies from the healthy ones. (4): hBD-2 mRNA and PSMB8 mRNA analysis were the most valuable parameters in differentiating AD and PV biopsies.

Does the effectiveness of biological medications in the treatment for psoriasis depend on the moment of starting therapy? A preliminary study.

Introduction: It is well known that biological medications acting on selected elements of the immune response are highly effective in psoriasis treatment. It is a common perception that psoriasis is a seasonal disorder with improvement in warmer months, however it has not been unequivocally confirmed. It is not known whether the time of year of starting systematic therapy for psoriasis influences treatment outcomes. Material and methods: Changes in psoriasis severity scores during treatment with biologics were investigated. The scores were recorded for 62 patients with moderate to severe psoriasis at the beginning, after 1, 4 and 7 months of the therapy. Patients were divided into two groups: those beginning the treatment in the cold period of the year (November-March) and in the warm period (May-September). The seasonal groups were also divided into subgroups according to the type of biologics used: interleukin inhibitors and tumor necrosis factor α (TNF-α) inhibitors. Results of the treatment were analysed using standard statistical tests of differences between samples. Results: After 1 and 4 months of the therapy, better efficacy of interleukin inhibitors was found in patients starting treatment in summer. The course of psoriasis improvement in patients taking TNF-α inhibitors resulted in consistent improvement regardless of the season. The outcome of the treatment after 7 months was similar for both seasonal groups and types of biologics used. Conclusions: Our understanding of the effectiveness of the treatments depending on the time of the year combined with the type of biologics used, may further improve results of the therapy.

Comparative effectiveness of adalimumab versus ustekinumab in the treatment of severe chronic plaque psoriasis: The results based on data from the program "treatment of moderate and severe forms of plaque psoriasis (B.47)" of the National Health Fund in Poland.

Biological agents: TNF-α inhibitors, IL-12, and IL-23 blockers, IL-17 inhibitors are used in the treatment of plaque psoriasis. Adalimumab (ADA) is an antibody that binds to TNF-α. Ustekinumab (UST) blocks IL-12 and IL-23. The data obtained from medical records is of exceptional value. The aim of the study was to evaluate the efficacy of ADA and UST during a single 40-week period of biological treatment of patients under the drug program "Treatment of moderate and severe form of plaque psoriasis." The group of 620 adult patients with moderate to severe form of plaque psoriasis, who were unresponsive or had contraindications to the standard treatment were qualified to the drug program. In the evaluated group, 50.64% patients were treated with UST, 49.36% with ADA. The efficacy of treatment was assessed during weeks 0, 4, 16, 28, and 40. At week 16th, PASI75 reached 80.72% patients in ADA treated group, PASI ≥90 54.88%, PASI100 19.6% of patients. In the UST group (week 16th) PASI75 reached 70.38%, PASI90 44.26%, PASI100 15.6% of patients. At week 28th PASI90 and PASI100 were more pronounced in the ADA group than in UST. In addition, the total percentage of PASI improvement was significantly higher in the ADA group (p = 0.0006). The percentage of PASI improvement in week 40 was statistically higher in ADA group compared to UST (p = 0.015). Compared to UST, ADA was clinically more effective during a 40-week observation. Patients receiving ADA achieved PASI75, PASI90, and PASI100 more frequently and faster than those treated with UST. Additionally, ADA improved the quality of life of psoriatic patients more substantially compared to UST.

Occurrence of IL-1, IL-10, CD25, CD40, and CD69 in the tissue of palatine tonsils.

Introduction: Palatine tonsil disease often coexists with dermatological diseases. Correct diagnosis of inflammation of the palatine tonsil tissue and removal of the diseased palatine tonsils results in remission of the disease. Aim: To determine similarities and differences in the immunohistochemistry profile of the palatine tonsil tissue between tonsillitis and hypertrophy, including location of the immunohistochemistry reactions in specific histological sites. Material and methods: A prospective analysis of 50 palatine tonsils that had undergone tonsillectomy due to tonsillitis (30 cases) and hypertrophy (20 cases) was performed. The collected material underwent immunohistochemistry staining for: IL-1, IL-10, CD25, CD40, and CD69, and subsequently phenotypic expression of the obtained results was performed including their histological location. Results: Statistically significant differences (p < 0.05) between the tonsillitis and hypertrophy groups were found for almost all IHC reactions in the epithelium covering the tonsils for CD-25, CD-69, IL-1, IL-10. Furthermore, significant differences between these groups were found for IL-10 reaction in the subepithelial inflammatory infiltrate and follicular centres of lymphatic follicles as well as for CD-69 reaction between the follicles. When all the locations were summarized, significant (p < 0.05) differences were found for all IHC reactions except for CD-40. Conclusions: The investigated markers and cytokines: CD25 and CD69, and IL-1 and IL-10 are more abundant in tonsillitis than in hypertrophy of the palatine tonsils.

Skin manifestations of neuroendocrine neoplasms: review of the literature.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumours derived from peptidergic neurons and specialized neuroendocrine cells capable of secreting various peptides or amines. These cells may be present in endocrine tissue or diffused in the tissues of the digestive or respiratory system. The article reviews the characteristic features of NENs, with particular emphasis on skin manifestations, such as necrolytic migratory erythema (NME), tongue inflammation, angular cheilitis, venous thrombosis and alopecia in glucagonoma; "flushing", "lion face", pellagra skin symptoms, "scleroderma-like features without Raynaud's phenomenon" in carcinoid tumours. The paper also presents the clinical picture of the neuroendocrine tumour of the skin - Merkel cell carcinoma. The aim of this study was to draw attention to the need for precise and comprehensive diagnosis of the patients, with particular emphasis on skin lesions as a revelator of neuroendocrine tumours. This management allows for the early implementation of appropriate treatment.

Effectiveness of infliximab biosimilars in the treatment of moderate to severe chronic plaque psoriasis: experience of real-world data from the register of the program "Treatment of moderate and severe forms of plaque psoriasis (B.47)" of the National Health Fund in Poland.

Introduction: Infliximab (IFX) is a monoclonal antibody that binds to and neutralizes TNF-α. IFX (Remicade) was approved by the U.S. Food and Drug Administration in 2006 for the treatment of severe plaque psoriasis. In 2013 two infliximab biosimilars: Remsima and Inflectra were also registered. The introduction of biosimilar drugs is associated with a significant reduction in treatment costs. Aim: To evaluate the efficacy of treatment with biosimilar IFX with non-medical switch option in patients with plaque psoriasis under the drug program "Treatment of moderate and severe plaque psoriasis" of the Ministry of Health in Poland. Material and methods: The group of 91 adult patients with moderate to severe plaque psoriasis, unresponsive or with contraindications to the standard treatment were qualified to the drug program (in 2016-2018). Efficacy of treatment with biosimilar IFX was evaluated using the Psoriasis Area and Severity Index, body surface area and Dermatology Life Quality Index scoring performed at week 0, 14, 46 and 94. Results: The mean change in PASI, DLQI, and BSA scores at week 14 was 89.92%, 93.75% and 90.91%, respectively. By week 14, 83.52% of patients achieved PASI75, 49.45% PASI ≥ 90 and 26.37% PASI100. At week 46, 84.62% of patients achieved PASI75, 54.95% PASI ≥ 90, and 21.98% PASI100. At week 94 of therapy, 80.22% of patients achieved PASI75, 48.35% PASI ≥ 90, and 18.68% PASI100. At week 94 of therapy, PASI100 was maintained by 37.5% of patients who achieved PASI100 at week 14. Conclusions: 94-week therapy with biosimilar infliximab results in high and sustained clinical efficacy in patients with moderate to severe psoriasis.

Real-world evidence on time to relapse of plaque psoriasis after discontinuation of biologic treatment in Poland.

The aim of this study is analysis of time to relapse after discontinuation of biologic treatment and identification of factors associated with risk of relapse. The analysis used real-world data of 705 patients treated with biologic drugs (adalimumab [ADA], ustekinumab, infliximab, and etanercept) in Poland in 2013-2019. Time to relapse was analyzed by Kaplan-Meier estimator. Data was stratified by the number of prior relapses. Determinants of risk to relapse were analyzed with Prentice-Williams-Peterson model. Kaplan-Meier estimate of time to the first relapse was 276 days, to the second relapse was 246 days, to the third relapse was 218 days, and to the fourth relapse was 178 days. In multidimensional analysis statistically significant variables affecting risk of relapse were the following: biologic naivety (hazard ratio [HR] 0.707), ADA (HR 0.787), psoriasis area and severity index at the last follow-up visit (HR 1.049), abnormal hemoglobin level (HR 0.794), and abnormal lymphocyte counts (HR 1.278). The findings of this study suggest that periods to relapse after discontinuation of biologic drugs become shorter with the number of prior relapses experienced by the patient. Ninety-five percentage of observed relapses occurred within 613 days of the end of the first treatment cycle, within 478 of the second cycle and within 351 days of the third cycle.

Familial localized scleroderma with paediatric onset: a review.

Localized scleroderma is an inflammatory disease causing sclerosis of the skin. The aetiology and pathogenesis of localized scleroderma remain unclear. Localized scleroderma is considered a genetically driven disease. It is not well understood if genetic factors or environmental exposure individually can cause its development or if their interaction is needed to trigger the disease. Some authors postulate that familial clustering is evidence of a hereditary disease. Familial localized scleroderma has been rarely reported and is a case worth studying. We present the review of literature on this subject with 3 additional cases of familial localized scleroderma with paediatric onset.

Does smoking affect your skin?

Smoking has a negative influence on human beings. Carcinogens detected in smoke can increase the risk of developing chronic disorders, cancer and premature death. Nicotine can also affect dermatological diseases such as psoriasis, hidradenitis suppurativa, chronic dermatoses, alopecia, lupus erythematosus, polymorphous light eruption, skin cancer and tobacco-associated oral lesions. Advanced education at a doctor's surgery in various medical occupations can change the bad habits and protect people from the consequences.

Calcipotriene/betamethasone dipropionate foam: primary evidence supporting its use in patients with psoriasis vulgaris. A narrative review.

Psoriasis vulgaris is a chronic, immune-mediated disorder, which has a substantial impact on all aspects of patients' quality of life. In most patients, the disease is mild to moderate and is successfully treated with topical agents. The most common therapy involves a vitamin D3 analogue (calcipotriene) in combination with a synthetic corticosteroid (betamethasone dipropionate). The aerosol vehicle (foam) with softening properties is another formulation of this combination drug, apart from ointment and gel, expanding the therapeutic options available to patients with psoriasis. The article describes the pharmacokinetic and pharmacodynamic properties of calcipotriene/betamethasone dipropionate foam. The results of the key randomised clinical studies investigating the efficacy, including patients' quality of life and safety of the foam versus ointment, gel and either active ingredient in foam vehicle are presented. In addition, the results of a study on maintenance treatment with calcipotriene/betamethasone dipropionate foam as well as reports on real-world use of this medicine in patients with psoriasis, are discussed.

Adalimumab and methotrexate affect the concentrations of regulatory cytokines (interleukin-10, transforming growth factor-ß1, and interleukin-35) in patients with plaque psoriasis.

Dysfunctional regulatory T lymphocytes are important for the pathogenesis of psoriasis and atherosclerosis. We analyzed the severity of atherosclerosis and the concentration of regulatory cytokines in patients with psoriasis who were administered methotrexate or adalimumab for 12 weeks. We included 34 patients with psoriasis (17 each, administered methotrexate or adalimumab) and eight healthy volunteers. BMI, psoriasis area and severity index (PASI), body surface area (BSA), and at least 75% and 90% improvements in PASI were observed. The 10-year risk of fatal cardiovascular disease was estimated using Systematic Coronary Risk Evaluation charts. The plasma interleukin (IL)-10, IL-35, and transforming growth factor ß1 (TGF-ß1) levels were determined using enzyme-linked immunosorbent assay before and after the 12-week treatment regimen. PASI (P = .0006) and BSA (P = .0001) were positively correlated with the BMI, IL-35 (-0.38), and IL-10 (0.48) levels. Baseline IL-35 concentrations were the highest in healthy volunteers; the IL-10 and TGF-ß1 level were the highest in the methotrexate group. IL-10 concentration decreased in both treatment groups (P = .02 for the methotrexate and P = .09 for adalimumab group), and IL-35 decreased in the adalimumab group (P = .019), consistent with skin lesion recovery. Thus, this study demonstrates the dysregulated secretion of regulatory cytokines in psoriatic patients under systemic treatment.

Methotrexate and Adalimumab Decrease the Serum Levels of Cardiovascular Disease Biomarkers (VCAM-1 and E-Selectin) in Plaque Psoriasis.

Background and objectives: The shared pathogenesis of psoriasis and atherosclerosis may be determined by assaying the levels of endothelial activation molecules. This study aimed at evaluating vascular cell adhesion molecule 1 (VCAM-1) and E-selectin serum concentrations, and atherosclerosis severity in patients with plaque psoriasis. It also aimed to determine the effects of methotrexate/adalimumab treatment for 12 weeks on the plasma levels of the aforementioned molecules. Materials and Methods: The study included 34 psoriasis patients (17 treated with methotrexate and 17 treated with adalimumab) and eight controls. The 10-year risk of a fatal cardiovascular disease, body mass index, Psoriasis Area and Severity Index, and body surface area were calculated for each subject. VCAM-1 and E-selectin levels were determined via an enzyme-linked immunosorbent assay at baseline and after 12 weeks. Results: Baseline E-selectin and VCAM-1 levels were higher in the adalimumab group than in the methotrexate and control groups. VCAM-1 levels decreased in the adalimumab (p = 0.02) and methotrexate groups (p = 0.008), while E-selectin levels decreased in the methotrexate group (p = 0.004). Conclusions: The results indicate a correlation between systemic psoriasis treatment and E-selectin and VCAM-1 plasma concentrations, which may be associated with the risk of cardiovascular disease development.

The use of biological drugs in psoriasis patients prior to pregnancy, during pregnancy and lactation: a review of current clinical guidelines.

INTRODUCTION: Information on the possibility of using biological drugs in psoriasis patients planning to conceive, patients who are pregnant or during lactation is limited. AIM: Presenting recommendations published in clinical guidelines regarding the use of biological drugs - adalimumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab, by psoriasis patients in the period of planning pregnancy, during pregnancy or during lactation. MATERIAL AND METHODS: The paper was based on a comprehensive review of over 40 websites of HTA agencies, dermatological associations worldwide and medical databases (PubMed, Embase), the objective of which was to identify clinical guidelines relating to biological treatment of women of childbearing potential, published after 2018, which used GRADE - a system for rating the quality of a body of evidence. FINDINGS: Certolizumab pegol is recommended in women who are planning to conceive. Furthermore, guidelines indicate other TNF-α inhibitors as possible treatment. Certolizumab pegol is also recommended as first-line treatment in pregnant patients. Furthermore, for trimesters 2 and 3, guidelines allow using other TNF-α inhibitors. Treatment with secukinumab and ustekinumab should be discontinued when planning pregnancy or when pregnancy was diagnosed. Biological treatment during pregnancy and lactation (continuation or initiation of treatment) can be used only after an analysis of risks and benefits has been conducted. CONCLUSIONS: TNF-α inhibitors seem to be the safest and most researched biological drugs used in psoriasis treatment of patients planning to conceive, during pregnancy or lactation. Given its non-existent or minimal placental permeability, most likely the safest alternative is certolizumab pegol.

Secondary failure of TNF-α inhibitors in clinical practice.

Tumor necrosis factor alpha (TNF-α) is a leading inflammatory cytokine that plays a pivotal role in the pathogenesis of psoriasis. In case of a severe course of psoriasis and moderate-to-severe disease in which traditional systemic treatments are ineffective or contraindicated, TNF-α inhibitors (iTNF-α) are used. This class of drugs includes monoclonal antibodies and a fusion protein (etanercept) and can induce a humoral or cell-mediated immune response, leading to formation of anti-drug antibodies (ADAs). The immunogenicity may affect iTNF-α drug pharmacokinetics, which would lead to hampering the clinical response (secondary drug failure), so a need to increase the drug dose arises. Antibodies against monoclonal antibodies (adalimumab, infliximab) have been associated with diminished clinical response, while against etanercept are non-neutralizing and appear to have no significant effect on clinical response and treatment safety. Switching of biologic agents may be one strategy in ADA-associated secondary failure of iTNF-α. However researches are needed to identify risk factors for ADA development and investigate management strategies for optimized treatment response. The authors reviewed the literature on the effectiveness of iTNF-α and pointed out the prevention of secondary failure in clinical practice.

The incidence and management of cutaneous adverse events of the epidermal growth factor receptor inhibitors.

Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and colorectal, cervical, prostate, breast, ovary, stomach, and pancreatic cancer. The EGFR inhibitors are used at present in the treatment of such cancers. Skin lesions that develop during and after cancer treatment may be due to specific cytostatics, molecular-targeted drugs, radiation therapy, complementary therapy, or the cancer itself, and hence knowledge is essential to distinguish between them. The mechanism through which skin toxicity arises during treatment with EGFR inhibitors is not well known, but seems to be due to the modification of the RAS/RAF/MEK/ERK signal path associated with its activation, which results in the similarity between the adverse effects of EGFR inhibitors and the treatment of melanoma with BRAF and MEK inhibitors. The most common side effects are pruritus, xerosis, papulopustular rash, hand-foot skin reaction, alopecia and dystrophy of the hair, and paronychia. This work presents options for prevention and suggestions for managing these adverse events, which are of importance in the care of patients undergoing oncological treatment.

[Clinical usefulness of diagnostic methods for human papilloma virus dependent lesions]. / Przydatnosc kliniczna metod wykorzystywanych w diagnostyce zmian wywolanych zakazeniem wirusem brodawczaka ludzkiego.

Persistent infection of Human Papilloma Virus (HPV) is confirmed necessary factor for development of cervical cancer and anogenital neoplasia. DNA HPV is detected in 96% of cervical cancer, 40% of vulvar and vaginal cancer, 90% of anal cancer and 26% of oral cavity cancer cases in general population. The most common high-risk HPV types observed in anogenital intraepithelial neoplasia or anogenital cancer are HPV 16, 18 and 45. Numerous diagnostic methods of detection of HPV infection and lesions causes by persistent HPV infection are widely used. Epidemiological data reveals correlation of incidence and mortality reduction due to cervical cancer and consequent prosecution and improvement of screening programmes based on morphological assessment of exfoliative smears. In last decade some limitations of conventional smear method were pointed out and a new diagnostic techniques were introduced: liquid-based cytology and HPV DNA testing. Combination of cytological examination and HPV DNA testing seems to be optimal solution to be introduced in large population because of combining high sensitivity of molecular test with high specificity of cytological smear.