Etiopathogenesis Of Psoriasis Research Articles

Methylenetetrahydrofolate Reductase C677T Gene Polymorphism as Risk Factor for Psoriasis in Saudis.

Methylenetetrahydrofolate reductase (MTHFR) has been linked with the etiopathogenesis of psoriasis with inconsistent results. Methylenetetrahydrofolate reductase C677T polymorphism was evaluated in 106 Saudi psoriasis vulgaris patients and 280 matched healthy controls using PCR-RFLP (restriction fragment length plymorphism) technique. The cardiovascular risk factors were also compared in cases and controls. Allele T and genotypes CT and TT were found to be increased while allele C and genotype CC significantly decreased in psoriasis patients as compared with controls (P < .001). These results showed that the T-allele and T-containing genotypes (TT, CT) of MTHFR C677T are significantly linked with psoriasis susceptibility while C-allele and CC genotype are protective for it. Body mass index, fasting glucose, total cholesterol, low-density lipoprotein, triglycerides, and C-reactive protein, known markers for cardiovascular diseases, were found to be significantly elevated in the patient group as compared with the controls. It is concluded that the MTHFR C677T polymorphism increases psoriasis risk in Saudi patients.

The role of epigenetics and immunological imbalance in the etiopathogenesis of psoriasis and psoriatic arthritis.

Psoriasis (Ps) and psoriatic arthritis (PsA) represent a clinical and immunopathogenic continuum, called psoriatic disease, cumulatively affecting approximately 3% of the general population. Psoriatic disease is a chronic inflammatory disorder affecting the skin and musculoskeletal system. The immuno-pathogenesis is characterized by an activation of the TNF/IL-23/IL-17 cytokine axis, leading to an immunologic imbalance of T-cells resident in all affected tissues, mainly entheses. In the majority of cases, skin Ps predates rheumatological manifestations. Secondary to the higher incidence and the availability of mouse models, there is stronger data available on skin Ps, and data are, in most cases, relevant also to PsA. In a widely accepted model, environmental trigger factors like infections or trauma are capable of initiating an inflammatory cascade, ultimately creating a sustained state of chronic inflammation in genetically susceptible individuals. Besides well-known genetic susceptibility loci, epigenetic DNA modifications, which are associated with Ps development have been characterized recently and will be discussed in this article. The current evidence is promising in the possibility to provide new therapeutic avenues and fill the unmet need of patients, for whom current treatments either do not allow the disease to be controlled or must be continued for life.

Serum Concentrations of Interferon Gamma (IFN-γ) in Patients with Psoriasis: Correlation with Clinical Type and Severity of the Disease.

Introduction: The etiopathogenesis of psoriasis is still unclear but there is evidence that many of cytokines released by keratinocytes and inflammatory leukocytes may contribute to the induction or persistence of the inflammatory process in psoriasis. Aim: The aim of the study was to evaluate serum concentrations of Interferon gamma (IFN-γ) in patients with psoriasis and the healthy subjects and also to assess a possible association between IFN-γ, clinical type and severity of disease. Material and Methods: The study included a total of 60 patients with psoriasis and 20 healthy subjects in the control group. According to the clinical type of disease, patients with psoriasis were divided into four groups: psoriasis vulgaris (PV), psoriasis erythrodermica (PE), psoriasis pustulosa (PP) and psoriasis arthropatica (PA). Blood samples were collected from all psoriasis patients and from healthy control subjects. Serum IFN-γ levels were measured by an enzyme-linked immunosorbent assay (ELISA) technique. The severity of PV was assessed by Psoriasis Area and Severity Index (PASI) score. Results: The serum concentration of IFN-γ in patients with psoriasis was significantly higher than that in the control group (1.91±1.79 pg/mL vs 0.91±0.38 pg/mL, respectively). Significantly elevated serum IFN-γ concentrations were noticed in patients with PV (2.15±0.30 pg/mL). There was no statistically significant difference between the mean values of IFN- γ compared to the clinical type of psoriasis (p>0.05). In the group of patients with PV 36 (85.71%) patients had mild form of disease with PASI <50, and 6 (14.29%) patients had severe disease with PASI >50. It was not found statistically significant correlation between serum IFN-γ level and PASI score in the group of PV. Conclusions: The results of our study indicate that psoriasis is associated with significant changes in the serum concentration of IFN-γ. There was no significant correlation between serum IFN-γ concentrations, clinical type of psoriasis and severity of PV evaluated with the use of PASI score.

Psychosis and psoriasis, the skin talks the truth

IntroductionIt is well known about relation between skin and mind, not only due to their mutual origin, but also by their illness expression parallelism. We report a case to show that reciprocity.Personal antecedentsWoman, 42-year-old, single. She only suffers from a skin disease; mild psoriasis guttata placed in both elbows and knees. She treated it with local treatment (cortisone cream) during seasonal prutius and the lesions did not grow or expand. She was hospitalized due to psychotic symptoms (paranoid delusions with her colleagues) and started antipsychotics treatment (risperidone 12 mg per day and olanzapine 10 mg per night). By the same time, she suffered a psoriasis crisis. Her psoriatic plaques increased their sizes and her chest and both thighs were affected too. She complained about grave pruritus. All her medical test results were normal. After that, the patient improved her psychotics’ symptoms, but she started with agoraphobic signs and seclusion at home. Psoriasis were even worse than before and she needed metrotexate to treat it. Being introduced to escitalopram 15 mg per day, anxiety and depression symptoms disappeared and her grave psoriasis became the mild one that she knew.ConclusionSchizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Studies found evidence for a shared genetic etiology between schizophrenia and psoriasis. Despite that, we think that the study of psychopathology can amplify our understanding about the etiopathogenesis of psoriasis and associated mental disorders.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Components of the alternative complement pathway in patients with psoriasis.

Psoriasis is a chronic inflammatory skin disease. Adipose tissue plays important roles in the events that regulate body metabolism. This study determined the levels of complement 3 ( C3), acylation-stimulating protein (ASP), and adipsin, which take part in the alternate complement pathway, and are synthesized in and secreted by adipose tissue. Thirty-two patients with psoriasis were matched with 22 controls in terms of age, sex, body mass index, and lipid profiles. Serum C3, ASP, and adipsin levels were measured in both groups. The serum C3 level was higher and ASP and adipsin levels were lower in the patient group, but these differences were not significant (p = 0.708, p = 0.628, and p = 0.218, respectively). ASP and adipsin levels were correlated positively in patients with psoriasis (p = 0.029). To our knowledge, this study is the first to evaluate ASP and adipsin levels in patients with psoriasis. The roles of ASP and adipsin in the etiopathogenesis of psoriasis are unclear. Although not statistically significant, the lower ASP and adipsin levels in the patient group suggest a potential anti-inflammatory role of these proteins in psoriasis. Further studies should examine the relationships between ASP/adipsin and psoriasis.

Selected psychological aspects of psoriasis: case study analysis

Aim: The aim of the study is to define selected psychological aspects of psoriasis. For analysis there are taken such factors as: stress, social stigma, cognitive processes, social support, mood, acceptance of disease and subjective assessment of life quality. Method: Two persons took part in the study. Following questionnaire methods were used: Polish version of 6-gradual scale of social sigma, E. Hrehorów, J. Szepietowski, A. Reich; Polish version of the questionnaire to assess quality of life dependent skin ailments, J. Szpietowski; General Health Questionnaire GHQ-28, D. Goldberg. The method of qualitative analysis was also used, i.e. psychobiographical method. Results: The emergence of the disease is closely associated with the experience of stress. The large surface of affected areas influences on the level of stigma, what causes worse assessment of life quality. The duration of symptoms affects the acceptance of the disease. Family support helps the tested person to think positively. When it comes to women, psoriasis does not affect noticeably on the quality of cognitive processes. In turn, taking men into account, this disease causes concentration difficulties. This person feels low social support, that the level of his mood and the assessment of life quality are strongly reduced. Conclusion: Due to the participation of psychological factors in the etiopathogenesis of psoriasis, an important part of psoriasis should become a psycho-education, and an individual psychotherapy and system psychotherapy for patient’s all family should play an important role in the treatment of the patient.

G-231A and G+70C Polymorphisms of Endothelin Receptor Type-A Gene could Affect the Psoriasis Area and Severity Index Score and Endothelin 1 Levels.

Background:The etiopathogenesis of psoriasis has not been clearly elucidated although the role of chronic inflammation, imbalance between pro- and anti-inflammatory cytokines, and many immunological events have been established. Endothelin 1 (EDN1) and endothelin receptor type-A (EDNRA) are implicated in the inflammatory process. The relationships between EDN1 and EDNRA polymorphisms with several diseases have been found.Aims and Objectives:This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (G-231A and G + 70C) single nucleotide polymorphisms (SNPs) with the occurence of psoriasis, and evaluated the relationship between genotypes and clinical/laboratory manifestation of psoriasis.Materials and Methods:We analyzed genotype and allele distributions of the above-mentioned polymorphisms in 151 patients with psoriasis and 152 healthy controls by real-time PCR combined with melting curve analysis.Results:We did not find significant differences in the genotype and allele distributions of EDN1 T-1370G, EDNRA G-231A, and EDNRA G+70C polymorphisms between patients with psoriasis and healthy controls. Psoriasis area and severity index (PASI) score of EDNRA –231 polymorphic A allele carrying subjects (AA and AA + AG) was higher than that of wild homozygotes (P = 0.044 and P = 0.027, respectively). In addition, EDN1 levels in EDNRA+70 polymorphic C allele carriers (CC + CG) were elevated when compared with GG genotype; however, the difference was at borderline significance (P = 0.05).Conclusion:Although there were no associations between studied polymorphisms and psoriasis susceptibility, the PASI score and EDN1 levels seem to be affected by EDNRA G-231A and G + 70C polymorphisms.

Serum prolactin levels in psoriasis and its association with disease activity: a case-control study.

Background:Psoriasis is a T-cell-mediated autoimmune chronic skin disorder in which an environmental factor, perhaps a viral antigen, induces T cells to produce cytokines. These cytokines stimulate keratinocyte proliferation and production of antigenic adhesion molecules in the dermal blood vessels. Several mediators and hormones have been implicated in keratinocyte hyperproliferation and among these hormones, prolactin (PRL) has been found to have an effect on epithelial cells, lymphocytes and keratinocytes, thus an effect on the etiopathogenesis of psoriasis.Aim:The present study was designed to compare serum PRL levels in psoriatic patients with a control group.Settings and Design:This study was a hospital-based case control study, conducted in the department of Dermatology, STD and Leprosy, SMHS Hospital (Associated teaching hospital of Government Medical College Srinagar) over a period of 1 year, from September 2012 to 2013.Materials and Methods:The present study included 60 patients of psoriasis (42 males and 18 females) and 60 controls matched for age and sex. Serum PRL levels of patients and controls were measured by ECLIA and inferences were drawn.Statistical Analysis Used:Statistical significance of the results was carried out by the Chi-square test and the independent samples t-test. Statistical significance was determined at a level of P < 0.05.Results:Serum PRL levels were significantly increased in patients as compared to the control group (P value: 0.002). There was a positive correlation between pretreatment serum PRL levels and PASI score (r value: 0.379; P value: 0.003). An insignificant association was found between the pretreatment PRL level and serum PRL level after treatment (P value: 0.22). Also, a negative correlation between the duration of psoriasis and serum PRL was seen (r value: -0.008; P value: 0.954).Conclusion:PRL may have a role to play in the etiopathogenesis of psoriasis. However, further studies with large sample size should be carried out so as to validate this hypothesis.

Trace elements homeostatic imbalance in mild and severe psoriasis: a new insight in biomarker diagnostic value for psoriasis

Introduction: The pathogenesis of psoriasis remains elusive and is a subject of interest to clinicians and scientists. Many studies have thrown light on the etiopathogenesis of psoriasis at both molecular and tissue concentrations. Of these, the role of trace metals has been of interest. Objective: To evaluate the possible role of trace elements in mild and severe psoriasis. Patients: Sixty patients suffering from psoriasis were included in the study and 30 healthy subject served as a control. Methods: Serum sample analysis for some trace elements namely Na, K, Ca, P, Cu, Zn, and Fe using inductively coupled plasma-atomic emission spectroscopy (ICP-AES). In psoriatic patients and control, the severity of psoriasis was assessed by psoriasis area severity score (PASI score). Results: In psoriatic patients the level of serum calcium and zinc were diminished while the level of serum copper, iron and organic phosphorous were increased. These changes were significantly evident in severe psoriasis compared to control and mild psoriasis (P<0.05). Conclusions: There may be a role for trace elements in the etiopathogenesis of psoriasis.

Comment on “Serum methylglyoxal level and its association with oxidative stress and disease severity in patients with psoriasis”

Dear Editor,We have read the article ‘‘Serum methylglyoxal leveland its association with oxidative stress and diseaseseverity in patients with psoriasis’’ written by Kaur et al.[3]. The authors aimed to compare the systemic levels ofoxidative stress (OxS) markers such as total peroxide count(TPX), total antioxidant capacity (TAC), OxS index (OSI)in patients with psoriasis vulgaris (PV) and healthy controlsand to investigate their correlation with the serum level ofmethylglyoxal (MG). They concluded that MG levels in thepatients with PV were significantly increased as comparedto healthy control. A significant correlation was also foundbetween serum MG level and TPX, TAC, OSI, psoriasisarea and severity index. They suggested that MG serumlevel, reflecting simultaneously OxS could be used as amarker of disease activity in clinical trials.Oxidative stress arises as a result of overproduction ofoxygen radicals or inadequate antioxidant defense mecha-nisms [1]. It has received increased interest because of itspathogenesis of the disease and its complications, e.g.,cardiovascular disease and diabetes [3]. In recent years,OxS was proposed to be effective in etiopathogenesis ofpsoriasis [2, 4]. In addition, it can be impressed by otherinflammatory dermatological diseases (such as irritantcontact dermatitis, atopic dermatitis, acne, seborrheic der-matitis, physical urticaria, rosacea) [1, 7] and antioxidantsupplements. In this point of view, in the current study, theauthors did not mention whether the patients with psoriasishad other inflammatory skin diseases, usage of antioxidantsupplements, which possibly affect the redox status. Itwould be very useful, if the authors provided informationabout these factors.Furthermore, increased plasma levels of MG and MG-glycated proteins are the key pathogenic event in the vas-cular dysfunction in diabetes and hypertension [6]. Chronichyperglycemia leads to the production of advanced glyca-tion end products such as MG [5]. On the other hand, thefasting plasma glucose level is strongly affected by dailymeals, and the measurement of glycated hemoglobin(HbA1c) is recommended as an indicator of the patient’sblood glucose state in the previous 1–2 months [5].Therefore, in the present study, if the authors had assessedlevel of HbA1c instead of blood glucose level whileexcluding diabetes, the results would be different.After all, thanks to the authors for their valuableresearch which emphasizes serum MG level and diseaseseverity in patients with psoriasis.

Psoriasis as a disease associated with the immune system disorders

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Chomiczewska-Skóra D, Trznadel-Grodzka E, Rotsztejn H. Review paperPsoriasis as a disease associated with the immune system disorders. Central European Journal of Immunology. 2013;38(1):129-133. doi:10.5114/ceji.2013.34370. APA Chomiczewska-Skóra, D., Trznadel-Grodzka, E., & Rotsztejn, H. (2013). Review paperPsoriasis as a disease associated with the immune system disorders. Central European Journal of Immunology, 38(1), 129-133. https://doi.org/10.5114/ceji.2013.34370 Chicago Chomiczewska-Skóra, Dorota, Ewa Trznadel-Grodzka, and Helena Rotsztejn. 2013. "Review paperPsoriasis as a disease associated with the immune system disorders". Central European Journal of Immunology 38 (1): 129-133. doi:10.5114/ceji.2013.34370. Harvard Chomiczewska-Skóra, D., Trznadel-Grodzka, E., and Rotsztejn, H. (2013). Review paperPsoriasis as a disease associated with the immune system disorders. Central European Journal of Immunology, 38(1), pp.129-133. https://doi.org/10.5114/ceji.2013.34370 MLA Chomiczewska-Skóra, Dorota et al. "Review paperPsoriasis as a disease associated with the immune system disorders." Central European Journal of Immunology, vol. 38, no. 1, 2013, pp. 129-133. doi:10.5114/ceji.2013.34370. Vancouver Chomiczewska-Skóra D, Trznadel-Grodzka E, Rotsztejn H. Review paperPsoriasis as a disease associated with the immune system disorders. Central European Journal of Immunology. 2013;38(1):129-133. doi:10.5114/ceji.2013.34370.

A Rare Association Between Leukocyte Adhesion Deficiency Type I and Psoriasis in Humans

The β2 integrins are expressed exclusively on leukocytes and participate in many immune and inflammatory processes. This subfamily comprises four heterodimeric glycoproteins with a common β-subunit, designated β2 (CD18). Spontaneous mutations of the CD18 gene result in leukocyte adhesion deficiency type I (LAD-I). Low level of CD18 expression has also been implicated in the pathogenesis of psoriasis. We here describe a child with recurrent skin infections without pus formation, persistent gingivitis and periodontitis. His blood counts showed persistent leukocytosis (neutrophilia). CD11b expression was defective on neutrophils, while that of CD18 was normal. So, our patient represents a mild variant of LAD-I with possible dysfunctional CD18. Moreover, he developed psoriasis with reduced CD18 expression on CD4+ T-cells. Psoriasiform dermatitis has been described before in association with LAD-I, however, clinically and histologically confirmed psoriasis in association with LAD-I has been described only in CD18 hypomorphic mice. Therefore, our patient represents the first clinically and histopathologically documented association between LAD-I and psoriasis in humans. It lends support to the role of β2 integrins in the etiopathogenesis of psoriasis.

Flare-up of pustular psoriasis with fluoxetine: Possibility of a serotoninergic influence?

In this article, we report two cases of pustular psoriasis flaring up after fluoxetine administration. A 21-year-old male patient with localized pustular psoriasis became erythrodermic following commencement of fluoxetine. Even though the lesions were unresponsive to cyclosporine A (Cyc A) treatment, dramatic resolution was observed with discontinuation of fluoxetine. A 44-year-old female patient with pustular psoriasis who was on Cyc A and acitretin therapy was given fluoxetine for her psychiatric symptoms. In the following 5 days, her lesions flared. Owing to previous experience, fluoxetin was stopped. Her lesions improved dramatically in the following 3 days. Exacerbation of psoriasis with antidepressant therapy has been rarely described. An extensive review of the literature revealed four such cases, all of which were seen after the use of selective serotonin reuptake inhibitors (SSRI). A serotoninergic influence in the etiopathogenesis of psoriasis may be possible together with a pharmacogenetic difference in the drug metabolism of these patients. Considering the two patients we presented and the patients previously reported in the literature, aggravation of pustular psoriasis by SSRI should be borne in mind.

Is prolactin involved in etiopathogenesis of psoriasis?

Is prolactin involved in etiopathogenesis of psoriasis?

Biologic Agents in the Treatment of Psoriasis

Psoriasis is a cutaneous inflammatory disease, which affects 1-5% of general population and can have, particularly in its moderate-severe forms, a significant impact on the quality of life of patients. Although the etiopathogenesis of psoriasis is not yet fully understood, it has been demonstrated that the disease is the result of a complex interaction of genetic, endogenous and environmental factors, where the immune system has a pivotal role. For this reason, the immune system is the main target of many treatments for psoriasis. The most recent evolution in this field are the so-called biologic agents, custom-designed biomolecules obtained by bioengineering. This review summarizes the currently available data about efficacy, safety and undesired effects of five patented biologics officially approved for the treatment of moderate-to-severe psoriasis: adalimumab, alefacept, efalizumab, etanercept and infliximab. Some patent applications concerning possible future evolutions of the above biologics are also discussed.

Echinococcosis: A Possible Etiology in Psoriatic Disease

We aimed to investigate seroprevalence of Echinococcus granulosus in patients with psoriasis to determine a possible etiologic role, since both echinococcosis and psoriasis are defined as T cell-mediated diseases. Forty psoriatic patients and 50 age- and sex-matched control subjects were included in the study. IgG-specific ELISA was used to determine seropositivity. E. granulosus-specific IgG antibodies were found to be positive in 17/40 (42.5%) of the patients with psoriasis and in 11/50 (22%) of the control subjects (p = 0.008). Our results suggest thatechinococcosis might be one of the causative pathogens in the etiopathogenesis of psoriasis in highly endemic regions.

Nitric Oxide Levels in Patients with Psoriasis Treated with Methotrexate

Psoriasis is a chronic, recurrent, inflammatory, and hyperproliferative disease. Recently there have been studies regarding increases in the levels of NO in inflammatory dermatoses including psoriasis. In this study, 22 patients with psoriasis were scored with PASI (psoriasis area and severity index) and the levels of serum nitrite-nitrate were evaluated before and after therapy with methotrexate (Mtx). The results were compared with age- and sex-matched healthy volunteers. The relation of the results with the clinical severity and the cumulative Mtx dose were also evaluated. The serum levels of nitrite-nitrate of the psoriatic patients with active lesions were found to be significantly higher than the levels of the healthy volunteers and the patients after therapy. The elevated nitrite-nitrate serum levels in the inflammatory period may suggest the possible role of this mediator in the etiopathogenesis of psoriasis and the potential future use of No inhibitors in the treatment of psoriasis.

HIV-associated psoriasis.

Psoriasis occurs with at least undiminished frequency in HIV-infected individuals. The behavior of psoriasis in HIV disease is of interest, in terms of pathogenesis and therapy because of the background of profound immunodysregulation. It is paradoxical that, while drugs that target T lymphocytes are effective in psoriasis, the condition should be exacerbated by HIV infection. The etiopathogenesis of psoriasis is unknown, but genetic and environmental factors are thought to be involved. There are controversial issues regarding the immunological basis of psoriasis and the role of CD4+ versus CD8+ T lymphocytes. Current opinion favors an autoimmune basis for psoriasis although the precipitating activating signal(s) within psoriatic plaques remains unknown. Candidate skin autoantigens that have cross-reactive determinants with bacterial antigens include keratins. The immunodysregulation resulting from HIV infection may trigger psoriasis in those genetically predisposed by the Cw*0602 allele. Because CD8 T cells recognize antigen in the context of class I molecules, the identification of a human leucocyte antigen (HLA) class I association in HIV-associated psoriasis strengthens the argument for an important role for CD8+ T lymphocytes in the immunopathogenesis of psoriasis. HLA-Cw*0602 could act as a cross-reactive target for cytotoxic T lymphocytes (CTLs) responding to processed peptides from microorganisms.

Histological changes induced by application of lithium carbonate to mouse ear skin

The precipitation and exacerbation of psoriasis by the administration oral lithium carbonate has been reported recently [1, 5 7]. Investigations have shown that lithium may promote epidermal proliferation as well as leukocytic activities linked to its effects on cyclic AMPmediated processes and other mechanisms [2-5]. These findings provide clues to the etiopathogenesis of psoriasis. The aim of this study is to investigate whether a psoriasiform lesion can be induced in animals by topical application of lithium carbonate. Male BALB/c mice aged 12 weeks and weighing approximately 25 g were used. To the ventral surface of the left ear of each mouse t0% lithium carbonate in a cream vehicle was applied twice daily, while the vehicle alone was applied contralaterally. Ten mice were killed by cervical dislocation before application, 8 and 16 mice after 3 and 6 days application respectively, and 5 mice on the 3rd day after the final application. Specimens of the ears taken from these mice were fixed in 10% formalin and processed for routine microscopy. Parameters for statistical analysis included thickness of the epidermis measured from the basal layer to the underside of the stratum corneum with a calibrated eyepiece ruler and densities of both the mononuclear and polymorphonuclear cells measured with a calibrated eyepiece reticule. For every parameter of each specimen, 15 measurements (three sections, five measurements per section) were taken from the middle part of the ear and a mean value was calculated. All measurements were made in a single-blind way and rechecked 2 weeks later to confirm their reproducibility. Student's t-test was used to compare the data between ears on different sides in each group of mice. In addition, 20 mice were treated with 1% and 3% dinitrochloro-

Stress, symmetry, and psoriasis: Possible role of neuropeptides

The role of stress as a triggering factor in the exacerbation of psoriasis and the clinically symmetric distribution of psoriatic plaques suggested a possible role for neuropeptides in the etiopathogenesis of psoriasis. Several observations by other investigators involving substance P suggested to us a possible role for substance P as a modulator of the inflammatory response in psoriasis. A hypothesis for the role of substance P that would account for the temporal onset with stress, the clinical symmetry of lesions, and the histopathologic features of psoriasis is presented.