Approach For Psoriasis Research Articles

Excimer laser for psoriasis treatment: A case report and short review.

Psoriasis is a common cutaneous disease that has major implications in the quality of life of the patient. It is characterised by a chronic course and in some subtypes, it can be life threatening. Many studies have focused on the pathogenesis concerning this disease therefore improving the therapeutic approaches. Phototherapy represents a well-known treatment option for psoriasis. The depletion of T cells mostly from the epidermis, after exposure to phototherapy, validates the role of this treatment. The 308 nm excimer laser has the ability to treat mild, moderate and even severe but localised psoriasis plaques and plays an important role in the treatment management of psoriasis. In this report, we present the case of a patient diagnosed with plaque psoriasis, resistant to topical ointments, successfully treated with the 308 nm excimer laser. Although further studies are still required to consider the 308 nm excimer laser as a first line therapy, its high response rates have significantly influenced the therapeutic approach in psoriasis.

IL-23 Inhibition in Psoriasis: A Novel Approach to Convenient, Consistent Clearance

Prof Reich outlined our latest understanding of relevant psoriasis pathophysiology. Psoriasis was believed to be a skin disease mediated by T helper cell 1 (Th1 cell) 20 years ago; it has now been shown to be driven by Th17 cells, which are stimulated by a number of proinflammatory cytokines, among which IL-23 is overexpressed. Characteristics of the individual antibodies determine clinical properties. IL-23 inhibitors have long injection intervals, and inhibit more regulatory than effector cytokines. Prof Strober reviewed key clinical data on IL-23 inhibitors including that from VOYAGE 1 and 2, NAVIGATE, and ECLIPSE for guselkumab; reSURFACE 1 and 2 for tildrakizumab; and ultIMMa-1/2 and IMMvent for risankizumab. Taken together, the many comparator studies suggest that the IL-23 inhibitors deliver robust and long-lasting efficacy, with long treatment intervals and with relative safety; there are few contraindications to use an IL-23 inhibitor. Prof Strober said he believes that, over time, this class will replace ustekinumab and become the first-line therapeutic approach in psoriasis. Prof Conrad gave an overview of patients’ needs and the drug, patient, and disease-related factors to be considered when choosing a therapy from the increasing numbers available. He stressed that no single agent or class is appropriate for all patients and that, in many instances, traditional anti-TNF are being superseded in terms of both efficacy and safety by newer drugs. Data on some disease-related factors, e.g., the presence of psoriatic arthritis, however, support the use of anti-TNF. Prof Conrad outlined his considerations regarding drug choice for patients with conditions such as pregnancy, inflammatory bowel disease (IBD), latent tuberculosis (TB), or hepatitis B virus (HBV).

S100A7 in Psoriasis: Immunodetection and Activation by CRISPR technology.

Psoriasis, an inflammatory autoimmune skin disease, is the result of a chronic interaction between hyperproliferative keratinocytes and infiltrating activated immune cells. The mechanisms underlying psoriasis pathogenesis remain largely unknown, although a combination of genetic and environmental factors plays an important role in its development. S100A7 is overexpressed in psoriasis, and there is growing evidence that S100A7 may be involved in the pathogenesis of psoriasis. Since the mechanisms underlying S100A7 regulation and function remain elusive, a better understanding of these mechanisms may be useful to uncover additional treatment approaches for psoriasis. Immunohistology provides invaluable tools for a better understanding of the pathogenetic mechanisms of psoriasis. Here, we describe basic methods for immunofluorescence and immunohistochemistry analysis of S100A7 expression in psoriatic patients as well as in S100A7 CRISPR-activated human keratinocyte cell line.

Rottlerin as a therapeutic approach in psoriasis: Evidence from in vitro and in vivo studies

Rottlerin is a natural polyphenolic compound that was initially indicated as a PKCδ inhibitor. However, it was recently revealed that it may target a number of molecules and have biological effects on various cell types and is considered as a possible agent for tumor and cell proliferative diseases. Psoriasis is a chronic inflammatory cutaneous disorder with undefined etiology and is characterized by abnormal cellular proliferation, angiogenesis, and inflammation. Therefore, this paper investigates the regulatory effects of rottlerin on normal human epidermal keratinocytes (NHEKs) and imiquimod (IMQ)-induced psoriasiform (IPI) lesions. In vitro results showed that rottlerin inhibited cell proliferation in NHEKs through growth arrest and NFκB inhibition. It may also induce apoptosis in an autophagy-dependent pathway. We found that rottlerin inhibited human microvascular endothelial cells tube formation on matrigel. Rottlerin also decreased the cell senescence of keratinocytes and intracellular ROS generation, which indicated its antioxidant effect. We also showed that rottlerin affects the expression of keratinocyte proliferation biomarkers. In 12-O-tetradecanoylphorbol13-acetate (TPA)–induced keratinocytes, rottlerin significantly inhibited the expression of the induced pro-inflammatory cytokines in keratinocytes. An animal experiment provided the corresponding evidence based on this evidence in vitro, by using IPI model, we found that rottlerin could relieve the psoriasiform of BALB/c mice by inhibiting keratinocyte proliferation, inflammatory cell infiltration, and vascular proliferation. In conclusion, our results suggest that rottlerin may prove useful in the development of therapeutic agents against psoriasis. However, the deep mechanism still requires further study.

Evidence and Suggested Therapeutic Approach in Psoriasis of Difficult-to-treat Areas: Palmoplantar Psoriasis, Nail Psoriasis, Scalp Psoriasis, and Intertriginous Psoriasis.

Psoriasis is resistant to treatment and it shows frequent relapse; systemic treatment is often associated with toxicities, and long-term safety data are lacking for most of the newer drugs like biologics. Moreover, some body areas such as hands, feet, intertriginous areas, scalp, and nails are even more resistant. Frequently, systemic treatments are necessary considering the higher psychological impact on the patient. There is a lack of agreement on the best therapeutic modalities in the management of psoriasis involving difficult-to-treat locations. At present, there are no Indian guidelines for these conditions. Available literature has been reviewed extensively on the treatment of psoriasis involving difficult-to-treat locations; level of evidence has been evaluated as per the Oxford Centre for Evidence-Based Medicine 2011 guideline, and therapeutic suggestions have been developed. Best care has been employed to consider socioeconomic, cultural, genetic, and ethnic factors to prepare a therapeutic suggestion that is appropriate and logical to be used among Indian population and people of similar ethnic and socioeconomic background.

IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis

BackgroundAberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial. MethodsForty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks. Post-treatment follow-up was seven weeks. Primary outcome was incidence of adverse events. Secondary, exploratory outcomes included changes in psoriasis area and severity index (PASI). ResultsIMO-8400 across all dose levels did not cause any serious or severe adverse events. The most common treatment-related adverse events were dose-dependent injection-site reactions. All IMO-8400 groups showed clinical improvement, but a clear dose-response relationship and statistically significant differences with placebo were not observed (P=0.26). Eleven (38%) of 29 subjects on IMO-8400 achieved ≥50% PASI-reduction, compared to 1 (11%) of 9 subjects on placebo. Five (17%) and 2 (7%) IMO-8400-treated subjects achieved PASI-75 and PASI-90, respectively, compared to none on placebo. ConclusionsShort-term IMO-8400-treatment was well tolerated and reduced psoriasis severity. These findings warrant further investigation of endosomal TLR-antagonism as a therapeutic approach in psoriasis and other TLR-mediated IMIDs. Trial registrationEudraCT 2013-000164-28 and Clinicaltrials.govNCT01899729.

A novel approach in psoriasis: first usage of known protein oxidation markers to prove oxidative stress.

Oxidative stress may play a pivotal role in the pathogenesis of psoriasis, an inflammatory/hyperproliferative skin disease characterized by the cutaneous accumulation of neutrophils releasing reactive oxygen species, as revealed in a number of studies. This study was performed to demonstrate the presence of oxidative stress in psoriasis, as measured by protein oxidation markers. Twenty-nine psoriasis patients were selected based on disease severity assessment using body surface area as well as the psoriasis area severity index (PASI), and were grouped as mild (PASI≤10) and moderate-to-severe (PASI>10). The measured parameters in psoriatic patients and fourteen healthy volunteers were as follows: erythrocyte sedimentation rate (ESR), high sensitive C-reactive protein (CRP), myeloperoxidase (MPO) activity, neopterin, total lipid hydroperoxides (LHP), pyrrolized protein (PP), protein carbonyl compounds (PCC), advanced oxidation protein products (AOPP), thiol levels, along with complete blood count. Except lower thiols, all parameters were found to be higher in total patients as well as in subgroups, compared to controls. There was no significant difference among the subgroups. In conclusion, protein oxidation in psoriatics, not only in moderate-to-severe, but also in mild patients, may be explained by the findings of inflammation, phagocytic cell oxidation, and MPO-hypochlorous acid-oxidation reactions; as reflected by increased total/differential leucocytes counts, CRP, ESR as well as MPO, neopterin, AOPP, PCC, PP, LHP, and decreased thiol levels. Demonstrating the AOPP and PP formation for the first time, oxidants from active neutrophils/monocytes may play an important role in the pathogenesis of psoriasis, leading to oxidative stress, especially by protein oxidation.

Assessment of serum interferon-γ in psoriasis

Background Psoriasis is a common chronic, recurrent, and immune-mediated disease of the skin and joints that follows a relapsing and remitting course. Psoriasis represents a T-cell-mediated inflammatory skin disease that includes the activation of both Th1, which produces interferon-g (IFN-γ), tumor necrosis factor-α, and interleukin-2 (IL-2), and Th17, which produces IL-17, tumor necrosis factor-α, IL-6, and IL-22. Objective We planned this study to determine probable associations between IFN-γ, Th1 cytokine, in the sera of psoriatic patients and the possible correlation to disease severity. Materials and methods We studied the level of serum IFN-γ in 40 cases of plaque psoriasis, erythrodermic, and guttatepsoriasis using PASI score for assessing the severity, and in the serum of healthy 40 controls. Results There was a statistically significant positive correlation between the PASI score and the level of IFN-γ in all clinical types. This can suggest that serum IFN-g is a psoriasis severity and prognostic marker. Conclusion Serum IFN-γ in psoriatic patients can be used as a severity and prognostic marker, and then anti-IFN-γ may eventually become a useful therapeutic approach in psoriasis.

Fluorescent Imaging for Assessment of the Effect of Combined Application of Electroporation and Rifampicin on HaCaT Cells as a New Therapeutic Approach for Psoriasis

The study aimed to clarify the role of electric pulses in combination with chemotherapy on the viability of keratinocyte cell line HaCaT, in the context of its application as a new therapeutic approach for psoriasis. The data show that electroporation of HaCaT cells in combination with rifampicin induces cytoskeleton disruption and increases permeability of cell monolayer due to cell-cell junctions' interruption, visualized by fluorescent imaging of E-cadherin and actin integrity. This was accompanied with synergistic reduction of cell viability. The study proposes a new opportunity for more effective skin treatment than chemotherapy. The future application of this electrochemotherapeutic approach for combined local treatment of psoriasis may have serous benefits because of a high possibility to avoid side-effects of conventional chemotherapy.

Vitamin D Analog Calcipotriol Suppresses the Th17 Cytokine–Induced Proinflammatory S100 “Alarmins” Psoriasin (S100A7) and Koebnerisin (S100A15) in Psoriasis

The antimicrobial peptides (AMP) psoriasin (S100A7) and koebnerisin (S100A15) are differently induced in psoriatic skin. They act synergistically as chemoattractants and "alarmins" to amplify inflammation in psoriasis. Th17 cytokines are key players in psoriasis pathogenesis and vitamin D analogs feature anti-psoriatic effects; both of these activities could be mediated through epidermal AMP regulation. We show that supernatants of cultured psoriatic T cells induce and release psoriasin and koebnerisin from keratinocytes and the Th17 cytokines IL-17A, tumor necrosis factor-α, and IL-22 differently regulate psoriasin and koebnerisin reflecting their distinct expression pattern in normal and psoriatic skin. IL-17A is the principal inducer of both S100 and their expression is further amplified by cooperating Th17 cytokines in the micromilieu of psoriatic skin. Increased extracellular psoriasin and koebnerisin also synergize as "alarmins" to prime epidermal keratinocytes for production of immunotropic cytokines that further amplify the inflammatory response. Treatment of psoriatic plaques with the vitamin D analog calcipotriol interferes with the S100-mediated positive feedback loop by suppressing the increased production of psoriasin and koebnerisin in psoriatic skin and their Th17-mediated regulation in epidermal keratinocytes. Thus, targeting the S100-amplification loop could be a beneficial anti-inflammatory approach in psoriasis and other inflammatory skin diseases.

Immunohistochemical study of osteopontin, Ki-67, and CD34 of psoriasis in Mansoura, Egypt

Psoriasis is a chronic inflammatory skin disease characterized by hyper-proliferation, abnormal differentiation, and inflammatory infiltration in epidermis and dermis. We planned this study to analyze probable associations between Osteopontin (OPN), Ki-67, CD34, and histopathological features in psoriasis. We studied OPN expression and its correlation with Ki-67 and CD34 expression in lesional, non-lesional skin, and normal skin. Immunoreactivity for OPN and Ki-67 was based on the level of epidermal staining. CD34 expression was scored as mild, moderate, and strong, according to the number of stained dermal capillaries. Our results showed statistically significant differences in the expression of OPN, Ki-67, and CD34 between lesional and non-lesional skin as well as between non-lesional skin and control group (P ≤ 0.001). In addition, there was a significant difference in the expression of OPN, Ki-67, and CD34 between control and lesional group (P=0.02, P=0.02, and P=0.04, respectively). OPN expression seems to be related to Ki-67 (proliferation index) and CD34 expression (angiogenesis marker) confirming its role in the pathogenesis of psoriasis. Then "anti- OPN and anti-angiogenesis" may eventually become a useful therapeutic approach in psoriasis.

Sequential treatment with biologics: switching from efalizumab to etanercept in 35 patients with high‐need psoriasis

Use of biological agents has been shown to be an efficacious approach in psoriasis, when traditional treatments fail. However, there are limited data on the effectiveness and safety of switching from one biological agent to another. We aimed to evaluate the effectiveness and safety of etanercept as a sequential treatment in patients previously treated with efalizumab, and to evaluate different transition strategies from efalizumab to etanercept. We present a retrospective study in patients with high-need plaque psoriasis who were unable to continue efalizumab and were immediately switched to etanercept. We included 35 patients during a 4.5-year period. At 24 weeks of etanercept therapy, 57% of patients had a PASI reduction of 75%, suggesting that alternating between biological agents is feasible. We used three different switching approaches: (i) etanercept in combination with cyclosporine as bridge therapy, (ii) etanercept in combination with methotrexate as bridge therapy, (iii) etanercept monotherapy. Combination therapy was efficacious in all patients, including eight patients with rebound phenomenon with efalizumab. Etanercept was discontinued in two patients as a result of serious adverse events that consisted of an oral squamous cell carcinoma and a diffuse B-cell-non-Hodgkin lymphoma. In our experience, it seems that etanercept alone may not be sufficient when transitioning from efalizumab in high-need patients with severe worsening or rebound of psoriasis. In such patients, combination of etanercept with cyclosporine or methotrexate is a more effective approach. Non-response to efalizumab did not preclude clinical response after switching to etanercept.

Serum leptin levels, skin leptin and leptin receptor expression in psoriasis

Recent studies support the relation of psoriasis with obesity and cardiovascular disease. Leptin, a peptide hormone secreted predominantly from adipose tissue, is involved in the regulation of energy intake and expenditure. Recently, it has been shown to have several immunological effects including induction of proinflammatory cytokine production. To investigate the possible role of leptin in psoriasis pathogenesis. Forty-three patients with psoriasis, 10 diseased and 10 healthy controls with normal body mass index were included. Serum fasting leptin levels of the study group were examined by enzyme-linked immunosorbent assay. Tissue leptin and leptin receptor expression of both patients and controls were investigated by immunohistochemistry. Serum leptin levels, tissue leptin and leptin receptor expression were significantly higher in patients with severe psoriasis than patients with mild-moderate psoriasis and controls (P < 0.05). Serum leptin levels showed a positive correlation with Psoriasis Area and Severity Index and involved body surface area in patients with psoriasis. In addition, serum leptin levels, tissue leptin and leptin receptor expression showed a positive correlation with disease duration in patients with psoriasis (P < 0.01, r = 0.979; P < 0.01, r = 0.691; P < 0.01, r = 0.428, respectively). We assume that leptin might serve as a marker of severity in psoriasis and also may be a pathogenetic cofactor contributing to chronicity of the disease. Consequently, its role in obesity and cardiovascular disease in patients with psoriasis deserves to be studied. In addition, drugs targeting the proinflammatory effects of leptin may be a new adjuvant therapeutic approach in psoriasis.

Monitoring of serologic immune parameters in inflammatory skin diseases.

This paper deals with the correlation of clinical scoring and serologic markers of inflammation in atopic dermatitis and psoriasis. Serum eosinophil cationic protein (ECP), soluble interleukin-2 receptor (sIL-2R), total serum IgE, IgG and IgM anti-IgE antibodies, and IgE immune complexes were evaluated in monitoring inflammatory skin diseases such as atopic dermatitis and psoriasis. Well-established clinical activity scores were used as standards in recording skin improvement under treatment in a clinical setting. Serum ECP was found to be increased in both atopic dermatitis and psoriasis patients compared to normal controls; sIL-2R and IgE immune complexes were increased only in atopics with increased serum IgE. Anti-IgE antibodies did not show any deviation in both groups of patients. There was a significant elevation of sIL-2R and IgE immune complexes and a nonsignificant elevation of ECP in high-IgE atopics in comparison to those with normal serum IgE. In both groups of patients, there was a significant reduction of ECP and sIL-2R accompanying the improving skin condition. Serum IgE and the other immune parameters failed to respond. In contrast to other studies, serum ECP failed to correspond significantly with disease activity in our study. Our results showed measurable changes of ECP and sIL-2R for atopic dermatitis and/or psoriasis under treatment, but comparison to clinical scores remains difficult due to the different basis of the two systems. The only significant correlation was established for relative changes in sIL-2R and psoriasis area and intensity (PASI), a correlation which might be a useful approach in psoriasis.

S009 New therapeutic approaches for psoriasis

S009 New therapeutic approaches for psoriasis

Angiogenesis in Psoriasis: Therapeutic Implications

Within solid neoplasms, the population of tumor cells and the population of capillary endothelial cells constitute a highly integrated ecosystem. Tumor cells release an endothelial mitogen, Tumor-Angiogenesis-Factor (T.A.F.) which continually stimulates new capillaries to grow into the tumor. When T.A.F. is blocked, neovascularization is prevented and tumor nodules stop expanding at a diameter less than 2.5 mm. They enter a dormant phase because they are forced to live by simple diffusion of nutrients and wastes. Thus anti-angiogenesis can force a population of tumor cells to become dormant at a tiny diameter. In this paper an analogy is drawn between tumor angiogenesis and the angiogenesis which accompanies psoriasis. If the relationship between psoriatic epithelium and its capillary endothelium turns out to be similar to the integration of capillaries by solid tumors, then anti-angiogenesis may eventually become a useful therapeutic approach in psoriasis.