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The Journal of Investigative Dermatology Dec 2018Psoriasis is a chronic inflammatory skin disease dependent on the IL-23/IL-17 axis, a potent inflammatory pathway involved in pathogen clearance and autoimmunity....
Psoriasis is a chronic inflammatory skin disease dependent on the IL-23/IL-17 axis, a potent inflammatory pathway involved in pathogen clearance and autoimmunity. Several triggers have been proposed as initiators for psoriasis, including alarmins such as adenosine triphosphate. However, the role of alarmins in psoriasis pathogenesis and cutaneous inflammation has not been well addressed. Studies show that signaling through the P2X7 receptor (P2X7R) pathway underlies the development of psoriasiform inflammation. In this regard, psoriasiform dermatitis induced by IL-23 is dependent on P2X7R signaling. Furthermore, direct activation of the P2X7R is sufficient to induce a well-characterized psoriasiform dermatitis. Mechanistic studies determined that P2X7R-induced inflammation is largely dependent on the IL-1β/NLRP3 inflammasome pathway and neutrophils. In conclusion, this work provides basic mechanistic insight into local inflammatory circuits induced after purinergic P2X7R signaling that are likely involved in the pathogenesis of many inflammatory diseases, such as psoriasis.
Topics: Adenosine Triphosphate; Animals; Dermatitis; Disease Models, Animal; Extracellular Space; Female; Humans; Imiquimod; Inflammation Mediators; Interleukin-17; Interleukin-1beta; Interleukin-23; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Neutrophils; Psoriasis; Receptors, Purinergic P2X7; Signal Transduction; Skin
PubMed: 29870687
DOI: 10.1016/j.jid.2018.05.018 -
Australian Journal of General Practice Oct 2023It is important to be able to manage patients regardless of ethnicities. The understanding of skin diseases, including atopic dermatitis, in patients with skin of colour...
BACKGROUND
It is important to be able to manage patients regardless of ethnicities. The understanding of skin diseases, including atopic dermatitis, in patients with skin of colour (SOC) is lagging compared with that in patients with lighter skin and has been identified as an educational gap among medical practitioners.
OBJECTIVE
This paper synthesises the latest literature on the diagnosis, assessment, treatment outcomes and cultural considerations for managing atopic dermatitis in children with SOC in the general practice setting.
DISCUSSION
Atopic dermatitis in children with SOC can vary from traditional descriptions and appear psoriasiform, lichenoid, scaly, papular, hypopigmented or violaceous. It can be misdiagnosed and its severity underestimated. Complications from atopic dermatitis, as well as the treatments provided, might result in inadequate treatment unless the treating doctor is aware of specific nuances in children with SOC.
Topics: Humans; Child; Dermatitis, Atopic; Skin Pigmentation; Skin; Treatment Outcome; Psoriasis
PubMed: 37788687
DOI: 10.31128/AJGP-01-23-6684 -
Dermatology Online Journal Nov 2020A 26-year-old woman with Crohn disease and palmoplantar psoriasis on ustekinumab presented with a diffuse and intensely pruritic rash with a few pin-point pustules...
A 26-year-old woman with Crohn disease and palmoplantar psoriasis on ustekinumab presented with a diffuse and intensely pruritic rash with a few pin-point pustules within days after initiation of an over-the-counter Align brand probiotic. Biopsy revealed psoriasiform and spongiotic dermatitis with spongiform subcorneal pustules and scattered eosinophils, consistent with acute generalized exanthematous pustulosis. Our case highlights a unique presentation of acute generalized exanthematous pustulosis following probiotic exposure with fewer than usual pustular lesions. IL23 suppression by ustekinumab may have contributed to the patient's reduced pustular presentation.
Topics: Acute Generalized Exanthematous Pustulosis; Adult; Crohn Disease; Diagnosis, Differential; Female; Humans; Probiotics; Psoriasis; Ustekinumab
PubMed: 33342179
DOI: No ID Found -
Clinical, Cosmetic and Investigational... 2021Psoriasis is a common cutaneous disease with multiple characteristics including inflammation and aberrant keratinocyte proliferation. However, the pathogenesis of...
PURPOSE
Psoriasis is a common cutaneous disease with multiple characteristics including inflammation and aberrant keratinocyte proliferation. However, the pathogenesis of psoriasis is not completely clear yet. The objective of this study is to perform an in-depth analysis of the association between SPRR and LCE in the pathogenesis of psoriasis.
METHODS
In this study, we explore the differentially expressed genes (DEGs) in psoriasis by analyzing different gene expression profiles obtained from the Gene Expression Omnibus (GEO) database. The DEGs were examined using gene ontology (GO) functional enrichment analysis and protein-protein interactions (PPI) network. Correlation analysis in R studio software was used to analyze the association between SPRR and LCE genes. Further, potential direct protein-protein interactions between SPRR proteins and LCE3D were verified by co-localization observations and co-immunoprecipitation (CO-IP) assays in 293T cells. Also, the expression levels of SPRR and LCE genes were detected in lesional skin of the IMQ-induced psoriasiform dermatitis mice using RT-PCR.
RESULTS
Interestingly, the small proline-rich (SPRR) and late cornified envelope (LCE) genes were identified as a module in the constructed PPI network. And the analysis of the gene expression profile GSE63684 showed that both SPRR family and LCE family genes were significantly upregulated in imiquimod (IMQ) induced psoriasiform dermatitis mice. Also, the correlation analysis in R studio software recognized the association of SPRR and LCE genes, which were further verified by co-localization and co-immunoprecipitation (CO-IP) assays in 293T cells, and the results show that the direct interactions between SPRR2 and LCE3D. Notably, we also found that the expression levels of SPRR and LCE genes were significantly increased in the IMQ-induced psoriasiform dermatitis mice, while specifically decreased under the tazarotene cream treatment, indicating that the SPRR and LCEs were regulated simultaneously in psoriasis.
CONCLUSION
In summary, our study found that interactions between SPRR proteins and LCE proteins may provide new insights into the pathogenesis of psoriasis.
PubMed: 34594126
DOI: 10.2147/CCID.S336072 -
Clinical, Cosmetic and Investigational... 2023As a mediator of inflammation resolution, lipoxin A4 (LXA4) mainly plays an anti-inflammatory role and promotes inflammation resolution. LXA4 plays an inhibiting...
INTRODUCTION
As a mediator of inflammation resolution, lipoxin A4 (LXA4) mainly plays an anti-inflammatory role and promotes inflammation resolution. LXA4 plays an inhibiting inflammatory role in a variety of diseases, tissues and cells, including keratinocytes. Psoriasis is a chronic inflammatory skin disease mediated by dysregulation of inflammation of immune cells and keratinocytes. However, the expression and role of LXA4 in psoriasis-like mouse models are still unclear.
METHODS
Imiquimod (IMQ) topical treatment of dorsal skin induces psoriasis-like dermatitis in BALB/c mice, pretreated intraperitoneally with or without LXA4 prior to IMQ application. Severity of dorsal lesions is assessed by using a modified human scoring system and histopathology. The concentration of LXA4 and the expression of ALOX15 (a key gene in LXA4 metabolic synthesis) in lesional skins were detected by ELISA and Western blot. Quantitative PCR and ELISA were conducted to detect the mRNA and secretion levels of inflammatory cytokines. The proportion of IL-17A-producing γδT cells in skin and skin draining cervical lymph nodes and helper (Th) 17 cells in spleens was evaluated by flow cytometry. Western blotting was used to analyze the expressions of p-STAT3 and TRAF6.
RESULTS
The concentration of LXA4 and the expression of ALOX15 were decreased in IMQ-induced lesional skin. LXA4 significantly relieved psoriasis-like lesions in IMQ-induced mouse models. Furthermore, LXA4 decreased IMQ-induced systemic inflammation, including reduced the proportion of IL-17A-producing gdT cells in skin and skin draining cervical lymph nodes and Th17 cells in spleens, the secretion and expression of CCL20, IL-17A, IL-1β, and TNF-α in skin and serum. LXA4 markedly inhibited IMQ-induced expression of TRAF6 and p-STAT3.
CONCLUSION
LXA4 significantly ameliorates IMQ-induced psoriasis-like inflammation, and LXA4 can be used as a target for psoriasis treatment.
PubMed: 37575152
DOI: 10.2147/CCID.S418467 -
World Journal of Clinical Cases Sep 2023Atopic dermatitis and asthma are two diseases whose pathogenesis is largely attributable to the activation, at least in the initial stages, of T helper (Th)-2...
BACKGROUND
Atopic dermatitis and asthma are two diseases whose pathogenesis is largely attributable to the activation, at least in the initial stages, of T helper (Th)-2 Lymphocytes, the related cytokine axis, and B lymphocytes with antibody production. Psoriasis is conversely a pathology resulting from a recruitment of Th-17 and Th-1 lymphocytes, after an initial role of innate immunity. Mepolizumab is a humanized monoclonal antibody directed against interleukin (IL)-5, a central cytokine in the Th-2 axis, therefore involved in the pathogenesis of asthma. Several authors have described the appearance of psoriatic lesions in patients with asthma or atopic dermatitis following the therapy with dupilumab, a monoclonal antibody that blocks the interleukin (IL)-4, another Th-2 cytokine.
CASE SUMMARY
We present the case of a 59-year-old patient who developed psoriasiform lesions on the palms after mepolizumab therapy for asthma, for the activation of the parallel cytokine cascade after the blockade of IL-5. We successfully treated the patient with a topical calcipotriol and betamethasone ointment.
CONCLUSION
We should investigate with further attention the possible impact on the human immunological ecosystem put in place by the inhibition of the activity of individual inflammatory mediators, so as to be able to recognize the initial adverse effects early.
PubMed: 37731552
DOI: 10.12998/wjcc.v11.i26.6154 -
Journal of Dermatological Science May 2018Classifying inflammatory skin diseases is challenging, especially for the expanding group of disorders triggered by genetic factors resulting in hyperactivated innate... (Review)
Review
Classifying inflammatory skin diseases is challenging, especially for the expanding group of disorders triggered by genetic factors resulting in hyperactivated innate immunity that result in overlapping patterns of dermal and epidermal inflammation with hyperkeratosis. For such conditions, the umbrella term "autoinflammatory keratinization diseases" (AIKD) has been proposed. AIKD encompasses diseases with mixed pathomechanisms of autoinflammation and autoimmunity, and includes IL-36 receptor antagonist (IL-36Ra)-related pustulosis, CARD14-mediated pustular psoriasis, pityriasis rubra pilaris (PRP) type V, and familial keratosis lichenoides chronica (KLC). Mechanistically, the entities include generalized pustular psoriasis (GPP) without psoriasis vulgaris, impetigo herpetiformis and acrodermatitis continua, which are IL-36Ra-related pustuloses caused by loss-of-function mutations in IL36RN; GPP with psoriasis vulgaris and palmoplantar pustular psoriasis which are CARD14-mediated pustular psoriasiform dermatoses with gain-of-function variants of CARD14; PRP type V which is caused by gain-of-function mutations in CARD14; and, familial KLC in which mutations in NLRP1, an inflammasome sensor protein predominantly expressed in skin, have been identified. It is likely that further inflammatory keratinization disorders will also fall within the concept of AIKD, as elucidation of novel pathogenic mechanisms of inflammatory keratinization diseases emerges. A better understanding of the pathophysiology of AIKD is likely to lead to innovative, targeted therapies that benefit patients.
Topics: Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Autoimmune Diseases; CARD Signaling Adaptor Proteins; Dermatitis; Guanylate Cyclase; Humans; Immunity, Innate; Interleukins; Membrane Proteins; Mutation; NLR Proteins; Skin; Skin Diseases, Papulosquamous
PubMed: 29422292
DOI: 10.1016/j.jdermsci.2018.01.012 -
The Journal of Investigative Dermatology Apr 1999Research into the pathogenesis of psoriasis has been hampered by the lack of an animal disease resembling this common human skin disorder. Over the past few years,... (Review)
Review
Research into the pathogenesis of psoriasis has been hampered by the lack of an animal disease resembling this common human skin disorder. Over the past few years, however, various rodent models that mirror aspects of the psoriatic phenotype and pathogenesis have become available. Here, the most prominent models are compared with human psoriasis and potential uses for psoriasis research are reviewed. Asebia (ab), flaky skin (fsn), and chronic proliferative dermatitis (cpd) are spontaneous mouse mutations with psoriasiform skin alterations of unclear pathogenesis. Transgenic mice with cutaneous overexpression of cytokines, such as interferon-gamma, interleukin-1alpha, keratinocyte growth factor, transforming growth factor-alpha, interferon-6, vascular endothelial growth factor, or bone morphogenic protein-6, are valuable tools for studying in vivo effects of individual cytokines in the pathogenesis of psoriasiform features. Psoriasiform lesions also were seen in beta2-integrin hypomorphic mice backcrossed to the PL/J strain and in beta1-integrin transgenic mice. A T cell-based immunopathogenesis of psoriasiform features was shown in a form of graft-versus-host disease in scid/scid mice reconstituted with CD4+/CD45RB(hi) T lymphocytes as well as in HLA-B27/hbeta2m transgenic rats, demonstrating that dysregulated T cells can induce psoriasiform skin alterations without a primary epithelial abnormality. Finally, xenotransplantation models using human skin grafted on to immunodeficient mice are attractive, as different cell types and some environmental factors leading to psoriasiform features may be studied in human tissue. Overall, although there is no animal model imitating psoriasis completely, many aspects of this common human skin disorder are mirrored in the currently available models and psoriatic plaques can be created in xenotransplantation models.
Topics: Animals; Cell Adhesion Molecules; Cytokines; Disease Models, Animal; Humans; Mice; Psoriasis; Rats; T-Lymphocytes; Transplantation, Heterologous
PubMed: 10201521
DOI: 10.1046/j.1523-1747.1999.00538.x -
Scientific Reports Mar 2019Imiquimod (IMQ)-induced skin inflammation is currently the most widely accepted psoriasis animal model, however, it features several limitations. We have modified the...
Imiquimod (IMQ)-induced skin inflammation is currently the most widely accepted psoriasis animal model, however, it features several limitations. We have modified the IMQ-model to minimize its systemic effects towards effectively maintaining the characteristic skin reactions. The original protocol (OP) uses 62.5 mg Aldara cream (or vaseline) on the shaved back skin of mice for 4 days. In contrast, in our modified protocol (MP) 25 mg Aldara and vaseline are applied simultaneously in separate Finn chambers over the dorsal skin of mice. In both the OP and MP groups, histology showed unequivocal hallmarks of psoriasiform dermatitis. Additionally, skin scaling and blood perfusion values were similar. While Aldara elicited significantly increased skin thickness in the MP group, significant weight loss, spleen enlargement, increased inflammatory cytokine levels in plasma, and treatment related death were only observed in the OP group. Our new method reproduces psoriatic skin alterations highlighting considerably reduced systemic inflammatory reactions. Possessing psoriasiform and control skin areas on the same mouse also reduces inter-individual differences. Additionally, the new method permits prolonged IMQ treatment studies to mimic the chronic nature of psoriasis. Finally, our experimental approach may also be used in other mouse models, to prevent the undesired systemic effects of topically applied drugs.
Topics: Animals; CD11b Antigen; Cytokines; Dermatitis; Disease Models, Animal; Female; Imiquimod; Mice, Inbred C57BL; Petrolatum; Psoriasis
PubMed: 30842501
DOI: 10.1038/s41598-019-39903-x -
The Journal of Dermatology Jan 2023Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a typical type-2 inflammation involving T-helper type-2 cells and impairing quality of life due to nasal...
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a typical type-2 inflammation involving T-helper type-2 cells and impairing quality of life due to nasal obstruction, discharge and reduced sense of smell. Recently, the anti-IL4Rα antibody dupilumab was approved for CRSwNP. While dermatologic side effects in patients treated with dupilumab for atopic dermatitis are frequently observed, there is limited knowledge about these effects in patients with CRSwNP. We aimed to investigate frequency and characteristics of dermatologic side effects following initiation of dupilumab treatment in a cohort of Austrian CRSwNP patients. Therefore, CRSwNP patients presenting at the Department of Otorhinolaryngology, Head and Neck Surgery at the Vienna General Hospital were retrospectively evaluated for newly developed skin eruptions while under dupilumab treatment. Incidence was calculated and details on clinical symptoms were collected. One hundred and ninety-two CRSwNP patients receiving dupilumab treatment were included, comprising a cumulative follow-up of 89.65 years (median: 5.5, IQR: 5.9). We observed dermatologic side effects in four patients starting at a median time of 15.5 (range 4-23) weeks after dupilumab initiation corresponding to an incidence-rate of 4.46 (95%-confidence interval 1.39-11.23) events per 100 patient-years follow-up. The majority (75%, 3/4) of affected patients developed psoriasis-like dermatitis, whereas one individual experienced rosacea-like folliculitis and alopecia areata. While dupilumab dosing was reduced in 3/4 CRSwNP patients, one patient completely stopped dupilumab therapy. Our study provides the first comprehensive evaluation of both frequency and characteristics of dermatologic side effects caused by dupilumab in CRSwNP patients. All affected patients developed Th1-inflammatory associated skin disorders - previously observed only in individuals with prior affections of the skin (i.e. atopic dermatitis). Thus, individuals receiving dupilumab for CRSwNP may develop novel symptoms that require interdisciplinary management. Future studies on dupilumab in a real-world setting will be required to further explore its spectrum of side effects.
Topics: Humans; Dermatitis, Atopic; Quality of Life; Retrospective Studies; Antibodies, Monoclonal, Humanized; Sinusitis; Drug-Related Side Effects and Adverse Reactions; Nasal Polyps; Chronic Disease
PubMed: 36177732
DOI: 10.1111/1346-8138.16595