Psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferation of keratinocytes and immune dysregulation. The advent of biologic therapies has revolutionized its management; however, challenges such as loss of efficacy over time, treatment-resistant areas like the nails and scalp, and comorbid conditions complicate treatment strategies. Bimekizumab, a monoclonal antibody targeting interleukin (IL)-17A and IL-17F, has demonstrated superior efficacy in managing moderate to severe plaque psoriasis. In the BE RADIANT phase 3b trial, patients receiving bimekizumab achieved higher rates of skin clearance compared to those treated with secukinumab, another IL-17A inhibitor. At Week 48, 74.8% of patients treated with bimekizumab achieved complete skin clearance (PASI 100), compared to 52.8% of those receiving secukinumab [1]. This superiority was maintained over a three-year period, indicating sustained long-term benefits [2]. The dual inhibition of IL-17A and IL-17F by bimekizumab is believed to contribute to its enhanced effectiveness. A significant concern with biologic treatments is the potential loss of efficacy over time, necessitating changes in therapy. Studies have reported diminished responses with agents like secukinumab, another anti-IL-17 blocker, leading to treatment discontinuation or modification. If there has been a secondary loss of efficacy during treatment, i.e., the drug with the same target was effective previously, it is worth trying another molecule with the same target. The sustained efficacy of bimekizumab over extended periods offers a potential solution to this issue, providing consistent disease control and reducing the need for frequent therapeutic adjustments [3]. Psoriasis affecting the nails and scalp presents unique treatment challenges due to the difficulty of delivering therapies effectively to these sites. These areas often exhibit resistance to standard treatments and significantly impact patients' quality of life. While specific studies on bimekizumab's efficacy in nail and scalp psoriasis are limited, its robust anti-inflammatory effects suggest potential benefits in these difficult-to-treat regions [4]. Systemic treatment of psoriasis patients with comorbidities is always a challenge for the treating physician. Traditional systemic agents, such as methotrexate and cyclosporine, are often contraindicated in chronic kidney disease due to nephrotoxicity or because the drugs are eliminated through the kidneys. Biologic therapies, including bimekizumab, offer a safer alternative for psoriasis patients with renal impairment, as the kidneys do not primarily metabolize them and have a favorable safety profile [5]. Bimekizumab represents a superior therapeutic option for patients with moderate to severe plaque psoriasis, offering sustained efficacy and addressing challenges associated with traditional biologic therapies. Its potential benefits in treatment-resistant areas and suitability for patients with comorbidities further underscore its value in comprehensive psoriasis management. The author declares no conflicts of interest.

The diagnosis of severe dermatological infections is usually not the pathologist’s task, but sometimes the pathological diagnosis enables the beginning of the targeted or even lifesaving therapy. An infectious disease is considered unusual when it is rare in the given climate or the causative agent normally not cause human illness, or when the disease itself is very rare. In the case of an uncommon disease with generalized skin symptoms and possibility of infectious origin skin biopsy is easily feasible, and the relatively quick and precise „bed-side” histological diagnosis could be lifesaving. Authors present such rare infectious diseases diagnosed by dermatolpathologist.

In the psoriatic non-lesional (PS-NL) skin, the tissue environment potentially influences the development and recurrence of lesions. Therefore, we aimed to investigate mechanisms involved in regulating tissue organization in PS-NL skin. Cytokine, chemokine, protease, and protease inhibitor levels were compared between PS-NL skin of patients with mild and severe symptoms and healthy skin. By comparing mild and severe PS-NL vs. healthy skin, differentially expressed cytokines and chemokines suggested alterations in hemostasis-related processes, while protease inhibitors showed no psoriasis severity-related changes. Comparing severe and mild PS-NL skin revealed disease severity-related changes in the expression of proteases, cytokines, and chemokines primarily involving methyl-CpG binding protein 2 (MECP2) and extracellular matrix organization-related mechanisms. Cytokine and chemokine expression in clinically resolved versus healthy skin showed slight interleukin activity, differing from patterns in mild and severe PS-NL skin. Immunofluorescence analysis revealed the severity-dependent nuclear expression pattern of MECP2 and decreased expression of 5-methylcytosine and 5-hydroxymethylcytosine in the PS-NL vs. healthy skin, and in resolved vs. healthy skin. Our results suggest distinct cytokine-chemokine signaling between the resolved and PS-NL skin of untreated patients with varying severities. These results highlight an altered inflammatory response, epigenetic regulation, and tissue organization in different types of PS-NL skin with possibly distinct, severity-dependent para-inflammatory states.

This review outlines the novel therapies and their effects in lymphedema, lipedema and chronic wounds. So far compression therapy represents the cornerstone of all treatment modalities in these disoders and recent reports demonstrated compression-related systemic cardiovascular effects. Furthermore, we are able to determine responsiveness of venous leg ulcers to therapy and with application of autologous blood their healing can be ameliorated.

Psoriasis vulgaris is one of the most common immune-mediated skin diseases with characteristic skin symptoms. Authors provide an overview of the advancement in the psoriasis treatment over the past twenty years. They discuss the therapeutic options and the latest developments in the field of topical therapy, phototherapy, small-molecule systemic drugs and revolutionary biological treatments.

The psoriatic skin resembles wound healing, and it shows abnormalities at the basement membrane (BM), also in the non-lesional skin. Fibroblast-derived dermal periostin has well-known functions in wound healing and Th2-mediated diseases, such as atopic dermatitis. Here we show that serum periostin level was elevated in psoriatic patients, remarkably in the systemically treated ones. Obvious periostin positivity was detected in basal keratinocytes of the non-lesional, lesional, and previously-lesional psoriatic vs. healthy skin. Ex vivo skin models were generated to examine how different skin injuries affect periostin expression during wound healing. Our newly developed cultured salt-split model demonstrated that BM-injury induced periostin expression in basal keratinocytes, and periostin levels in the supernatant were also increased upon healing. In wound healing models, β1-integrin expression was similarly induced. β1-integrin blocking caused reduced periostin expression in in vitro scratch assay, indicating that β1-integrin can mediate periostin production. In contrast to atopic dermatitis, psoriatic basal keratinocytes are in an activated state and show a stable wound healing-like phenotype with the overexpression of periostin. This abnormal BM-induced wound healing as a potential compensatory mechanism can be initiated already in the non-lesional skin present in the lesion and keratinocytes can remain activated in the healed skin.

Psoriasis is a chronic, relapsing disease. Topical treatment with local corticosteroids plays a significant role in the management of psoriasis. In the current medical practice, the so called reactive treatment approach, which treats active symptoms is used. However, using this method, the relapse of the symptoms is inevitable. Relapses may affect unfavourably the quality of life of the patients, therefore reducing the frequency of the relapses is an important therapeutic target. A proactive treatment approach means that previously symptomatic areas of the skin are treated at specific times to maintain remission. Clinical studies with a high level of evidence using a fixed combination of calcipotriol and betamethasone dipropionate foam have shown that proactive treatment administered two times weekly can prolong the time until the first relapse. Furthermore, this treatment method may reduce the frequency of the relapses and may increase the number of days spent in remission without any major side effects.

The autologous platelet-rich blood derivatives have been used in bioregenerative medicine for decades in various indications including the facilitation of wound healing. Leukocyte- and platelet-rich fibrin (PRF) is a second-generation autologous blood-derived product, which can be obtained relatively easily and at low cost. PRF is rich in growth factors and antimicrobial proteins that are released by activated platelets and leukocytes. The authors present a successful treatment of a venous leg ulcer providing a detailed presentation of the PRF method.

The dry and scaly skin of psoriatic patients decreases the efficacy of ultraviolet B (UVB) phototherapy. Different agents are used to facilitate the transmission of light, but most of these preparations are cosmetically unfavorable. We have tested a novel preparation containing sodium hyaluronate and nicotinic acid (UV Fotogel®; Pernix Ltd.) with the double aim to improve the efficacy of UVB phototherapy and assess the cosmetic acceptability of the preparation. Ninety patients with plaque psoriasis were enrolled in the study, of whom 44 received narrow-band UVB (NB-UVB) phototherapy. Prior to phototherapy, one side of the patient’s body was treated with UV Fotogel while the other side served as a control. The other 46 patients used the preparation at their homes before regular sunbathing. The Local Psoriasis Severity Index (L-PSI), cosmetic acceptability and tolerability were recorded. The median values with the 25th and 75th percentiles (25p and 75p, respectively) were determined for the UV Fotogel-treated and control sites and then compared. The sides of the body to which UV Fotogel was applied prior to NB-UVB phototherapy had a significantly lower median L-PSI score than the non-treated control sides at the end of the treatment (1.0 [25p–75p: 0.0–2.0] vs. 2.0 [1.0–3.0], respectively). The application of UV Fotogel prior to sunbathing also led to a significant decrease in L-PSI score. There was a significant reduction in the median L-PSI score of patients at the final visit compared to baseline (2.5 [25p–75p: 1.5–3.5] vs. 6.0 [6.0–7.0], respectively). Use of the preparation was not accompanied by considerable adverse effects, and the patients found it cosmetically acceptable. Application of UV Fotogel prior to sunbathing was well tolerated by the patients, and the cosmetic acceptability was also good. UV Fotogel is potentially a useful device for enhancement of the efficacy of phototherapy in patients with psoriasis.

A szerzők összefoglalják a psoriasis vulgaris és a hidradenitis suppurativa új kezelési lehetőségeit.Az általános kezelési elvek leírását követően részletesen bemutatják a két betegség kezelésében jelenleg elérhető készítmények jellemzőit, terápiás hatékonyságát, valamint a mindennapi klinikai gya

Ez az áttekintés a krónikus sebek és a nyiroködéma patomechanizmusának és kezelésének legfrissebb ismereteivel foglalkozik, kiemelve azt is, hogy a nyirokkeringési zavar mindkét esetben jelentős szereppel bír a két betegség kialakulásában.Habár továbbra is a kompresszió terápia képviseli a legalapvetőbb konzervatív kezelési módszert mind a vénás lábszárfekély, mind pedig a nyiroködéma esetén, az elmúlt időszakban néhány olyan új eredmény látott napvilágot, amelyek reménnyel kecsegtetnek a terápia eredményességének javításában

Most studies on psoriasis focus on lesional skin, however healthy looking non-lesional skin already carries alterations that could be a basis of the manifestation of the disease. These include extracellular matrix defects that have been observed in psoriatic non-lesional skin, such as the disruption of laminin networks, which may lead to impaired keratinocyte adhesion to the basement membrane. This process is also associated with aberrant expression of the α5β1 integrin complex and the extradomain-A-containing fibronectin (EDA+FN) around basal keratinocytes. We set out to examine further the basement membrane alterations by focusing on type VII collagen and laminin 332 (LAMA3) proteins in non-lesional skin of psoriatic patients. We compared protein expression from samples derived near and far from lesions using immunfluorescent staining. Type VII collagen and LAMA3 are uniformly expressed in psoriatic lesional skin, as well as in healthy skin, but not in non-lesional skin. We found that the type VII collagen and LAMA3 expression in non-lesional skin corresponded with the PASI score of the patients and the distance of the sample from the lesion. High PASI scores were typically coupled with intensive type VII collagen staining in lesional and in non-lesional skin. In contrast, patients with low PASI score showed nearly no detectable type VII collagen protein in the NL skin. Also, NL samples taken further from lesions expressed less type VII collagen and LAMA3. In psoriatic NL skin changes in basal membrane proteins create a damaged, unstable dermal-epidermal junction zone that could manifest in a chronic inflammatory phenotype (lesional skin).

A STAT (signal transducer and activator of transcription) jelátviteli útvonalak kulcsfontosságú szerepet töltenek be a pikkelysömör patomechanizmusában.Kutatócsoportunk megállapította, hogy a STAT1 aktivált állapotban van egészséges és tünetes bôrben, ellentétben a tünetmentes bôrrel, ahol jórészt inaktív.Tünetmentes bôrben a csökkent mértékû STAT1 aktiváció független a lézióktól való távolságtól.Az aktivált STAT1 korrelációt mutat a PASI (psoriasis area and severity index) értékével, minél magasabb a beteg PASI-ja, annál erôsebb az aktivált STAT1 kifejezôdése a bôrben.Korábbi vizsgálataink azt mutatták, hogy a STAT1 abnormálisan regulálódik a pikkelysömörös fibroblasztokban

Antidrug antibodies have been shown to be associated with a loss of response during biologic therapy. Despite the potential association, there has been no report on the simultaneous monitoring of the following parameters in psoriasis: presence of neutralizing antibodies, plasma tumor necrosis factor (TNF)-alpha concentration, TNFi concentration and disease activity. Plasma concentrations of adalimumab, infliximab, etanercept and their respective antidrug antibodies, as well as plasma concentrations of TNF-alpha were measured in 77 psoriasis patients receiving biologic therapy, and the values were correlated with the clinical activity of the skin disease. Antidrug antibodies were identified in the plasma of 25% of infliximab-treated patients and 29.6% of adalimumab-treated patients, but not in the etanercept group. Clinical severity scores were significantly higher in the antibody-positive patients. In patients receiving infliximab or adalimumab therapy, the presence of antidrug antibodies was directly associated with reduced plasma TNF-inhibitor concentration and elevated plasma TNF-alpha level.

Alteration of the extracellular matrix (ECM) is a likely participant in the pathomechanism of psoriasis. ECM defects have been observed in non-lesional (NL) psoriatic skin, including disruption of the laminin, possibly leading to impaired keratinocyte adhesion to the basement membrane. This is associated with aberrant expression of a5b1 integrin in, and extradomain-A containing fibronectin (EDA+FN) around basal keratinocytes. In our previous work, we found that in NL psoriatic skin, the expression of KGFR and KGF were also increased compared to healthy controls. Because fibronectin can specifically bind to type VII collagen, we aimed to examine the putative connection between EDA+FN and collagen VII expression in non-lesional and lesional psoriatic skin. We found that collagen VII expression was decreased to a variable degree in psoriatic NL skin, while in lesional skin its expression was comparable to healthy skin. The antibody clone LH7.2 (Novocastra) was used for visualizing collagen VII. Samples from 6 patients were stained. Collagen VII expression in NL skin seems to correlate with PASI score. High PASI scores (e. g. 19.6) were typically coupled with intensive collagen VII staining in the lesional skin and a weak collagen VII staining in NL skin. In contrast, patients with lower PASI scores (e. g. 9.8) showed no collagen VII expression in NL skin. Collagen VII expression was always present in lesional skin. Also, the further the biopsy was taken from the lesions, the less collagen VII expression was detected in NL skin. This is an unexpected finding and has to be confirmed in larger NL samples. We speculate that increased EDA+FN production may be a compensation mechanism for the reduced collagen VII expression in non-lesional skin.

This study was carried out to examine the possible role of interleukin-1 (IL-1) in the functional insufficiency of regulatory T cells in psoriasis, by comparing the expression of IL-1 receptors on healthy control and psoriatic T cells. Patients with moderate-to-severe chronic plaque psoriasis and healthy volunteers, matched in age and sex, were selected for all experiments. CD4+CD25−effector and CD4+CD25+CD127lowregulatory T cells were separated and used for the experiments. Expression of the mRNA of IL-1 receptors (IL-1R1, IL-1R2, and sIL-1R2) was determined by quantitative real-time RT-PCR. Cell surface IL-1 receptor expression was assessed by flow cytometry. Relative expression of the signal transmitting IL-1 receptor type 1 (IL-1R1) mRNA is higher in resting psoriatic effector and regulatory T cells, and activation induces higher IL-1R1 protein expression in psoriatic T cells than in healthy cells. Psoriatic regulatory and effector T cells express increased mRNA levels of the decoy IL-1 receptors (IL-1R2 and sIL-1R2) upon activation compared to healthy counterparts. Psoriatic T cells release slightly more sIL-1R2 into their surrounding than healthy T cells. In conclusion, changes in the expression of IL-1 receptors in psoriatic regulatory and effector T cells could contribute to the pathogenesis of psoriasis.

AIM: To assess tumor necrosis factor-alpha (TNF-alpha), infliximab (IFX) concentrations, and antibodies against IFX molecules in patients with inflammatory bowel disease (IBD) who develop loss of response, side effects, or allergic reaction during anti TNF-alpha therapy.METHODS: Blood samples of 36 patients with response loss, side effects, or hypersensitivity to IFX therapy (Group.) and 31 patients in complete clinical remission (Group.) selected as a control group were collected to measure trough serum TNF-alpha level, IFX, and anti-IFX antibody (ATI) concentration. We examined the correlation between loss of response, the development of side effects or hypersensitivity, and serum TNF-alpha, IFX trough levels, and ATI concentrations.RESULTS: The serum TNF-alpha level was shown to be correlated with the presence of ATI; ATI positivity was significantly correlated with low trough levels of IFX. ATIs were detected in 25% of IBD patients with loss of response, side effects, or hypersensitivity, however no association was revealed between these patients and antibody positivity or lower serum IFX levels. Previous use of IFX correlated with the development of ATI, although concomitant immunosuppression did not have any impact on them.CONCLUSION: On the basis of the present study, we suggest that the simultaneous measurement of serum TNF-alpha level, serum anti TNF-alpha concentration, and antibodies against anti TNF-alpha may further help to optimize the therapy in critical situations. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Costmary (Tanacetum balsamita L.) has been used as a food, food flavoring, and medicinal plant since ancient times; however, nowadays its importance has remarkably diminished. Extensive studies of phytochemicals biosynthesized in costmary during last few decades resulted in the identification and quantification of several compounds possessing various bioactivities. On average, aerial costmary parts accumulate 0.8–1.2% of essential oil, containing R-carvone as a main constituent. Although numerous bioactivities were reported for carvone, including antimicrobial effects, the uses of costmary preparations are rather limited, most likely because developments of broader applications require more systematic studies focused on various activities and beneficial health effects of costmary oils and their valuable constituents. In conclusion, costmary may be considered as a forgotten plant with some potential in the future for development of functional ingredients for foods and other products.

Introduction: Infliximab is effective for the treatment of refractory inflammatory bowel disease (IBD). Nevertheless, up to 40% of patients lose response to infliximab and 10% develops severe side effects or allergic reaction. The aim of this study was to assess the clinical value of measuring infliximab trough levels (TL) and antibodies to infliximab (ATI) concentrations in IBD patients who lost response or developed adverse reaction to infliximab therapy.