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Clinical, Cosmetic and Investigational... 2022Urea as an ingredient in topical skin applications can aid skin integrity and hydration and have keratolytic, anti-fungal, anti-bacterial, and anti-pruritic effects....
PURPOSE
Urea as an ingredient in topical skin applications can aid skin integrity and hydration and have keratolytic, anti-fungal, anti-bacterial, and anti-pruritic effects. Skin conditions that urea-containing formulations have been utilized to treat include hand eczema/dermatitis, seborrheic dermatitis and psoriasiform dermatoses of the scalp. Two monocentric, simple blind, observational studies were carried out in healthy participants to examine the efficacy and safety of two urea-containing products in these skin conditions.
PATIENTS AND METHODS
Study 1 tested the actions of a commercially available 30% urea topical cream on hand eczema. The product was applied ≥2/day for 28 ±2 days. Transepidermal water loss, skin redness, skin hydration, and participant ratings of efficacy and qualities were assessed prior to first product application and on days 14 and 29. Study 2 tested the actions of a commercially available foaming product containing 10% urea on seborrheic dermatitis and scalp psoriasiform dermatoses. The product was applied ≥2/day for 28 ±2 days. Desquamation index and surface occupied by squames, analysis of extracted squames, microscopic assessment of scalp photos and participant ratings of product efficacy and qualities was carried out prior to first product application and on days 14 and 29.
RESULTS
In Study 1 (n = 20 females), results showed a significant (p < 0.05) decrease in transepidermal water loss, with an increase in hydration level of the upper skin layers, and a decrease in skin redness. In Study 2 (n = 13 females, 7 males), product use led to significant (p < 0.05) decreases in desquamation measures and dryness. In both studies, the majority of participants "agreed" or "slightly agreed" that the product had good efficacy and was easy to apply. No adverse reactions were reported.
CONCLUSION
These findings point to the utility of urea in topically applied vehicles for hand eczema, seborrheic dermatitis, and psoriasiform dermatoses.
PubMed: 36387960
DOI: 10.2147/CCID.S377718 -
The Journal of Investigative Dermatology Mar 2023Psoriasis is driven by the interplay between hyperproliferative keratinocytes and infiltrating inflammatory cells. GDF15, a member of the TGF-β superfamily, has been...
Psoriasis is driven by the interplay between hyperproliferative keratinocytes and infiltrating inflammatory cells. GDF15, a member of the TGF-β superfamily, has been implicated in cachexia, metabolic control, and cancer invasion. However, the expression and immunomodulatory role of GDF15 in inflammatory diseases has not been clarified. In this study, we report that GDF15 is decreased in the epidermis of patients with psoriasis and in an imiquimod-induced psoriasis-like mouse model. TNF-α suppresses GDF15 expression in keratinocytes by inhibiting the protein level of the transcription factor GATA2. GDF15 deficiency aggravates the development of psoriatic lesions, as evidenced by more severe skin inflammation in imiquimod-treated Gdf15-knockout (Gdf15) mice compared with that in wild-type mice. Importantly, GDF15 limited the synthesis of a panel of keratinocyte cytokines and chemokines by inhibiting TAK1/NF-κB activation and directly inhibited neutrophil adhesion and migration by inhibiting the activation of the small GTPase Rap1. Epidermal hyperplasia, infiltration of neutrophils, and transcripts of psoriasis-related markers in imiquimod-induced psoriasiform dermatitis were significantly alleviated by a topical supplement of recombinant murine GDF15. In summary, our study revealed an unexpected role of GDF15 in keratinocyte and neutrophil function in the skin of psoriasis, implying its therapeutic potential in treating psoriasis.
Topics: Mice; Animals; Imiquimod; Neutrophil Infiltration; Psoriasis; Skin; Dermatitis; Keratinocytes; Disease Models, Animal; Mice, Inbred BALB C
PubMed: 36049542
DOI: 10.1016/j.jid.2022.07.026 -
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 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Mar 2022To investigate the effects and mechanisms of Astragalus polysaccharide on improving imiquimod-induced psoriasiform dermatitis in mice. Forty healthy female C57BL/6...
To investigate the effects and mechanisms of Astragalus polysaccharide on improving imiquimod-induced psoriasiform dermatitis in mice. Forty healthy female C57BL/6 mice were randomly divided into 5 groups, including blank control group, model group, astragalus polysaccharide high-dose group (200 mg/kg), medium-dose group (100 mg/kg) and low-dose group (50 mg/kg), with 8 mice in each group. The mice in model group and astragalus polysaccharide treatment group were treated with 5% imiquimod cream on the back to induce psoriasiform dermatitis. PASI score was monitored, and the secretion of inflammatory factors was determined by ELISA. The secretion of inflammatory factors was closely related to the infiltration of macrophages. The infiltration of macrophages in skin was detected by flow cytometry to further explore the effect of different concentrations of APS on psoriasis. Compared with control group, the PASI score and the serum levels of TNF-α, IL-1β and IL-6 were increased significantly (<0.05), and the infiltration of macrophages in skin tissue was increased significantly in model group (<0.05). Compared with model group, the PASI score was decreased significantly (<0.05), and the serum levels of TNF-α, IL-1β and IL-6 were down-regulated significantly in astragalus polysaccharide high-dose and medium-dose groups (<0.05). The infiltrating macrophages in skin tissue were decreased significantly in Astragalus polysaccharide high-dose group (<0.05). Astragalus polysaccharide improve psoriasiform dermatitis in mice by inhibiting the infiltration of macrophages in skin tissue and decreasing the secretion of TNF-α, IL-1β and IL-6 in serum.
Topics: Animals; Astragalus Plant; Dermatitis; Disease Models, Animal; Female; Imiquimod; Interleukin-6; Mice; Mice, Inbred C57BL; Polysaccharides; Skin; Tumor Necrosis Factor-alpha
PubMed: 36031574
DOI: 10.12047/j.cjap.6214.2022.022 -
Mediators of Inflammation 2022Itch is one of the major clinical manifestations of psoriasis, which is closely related with neurogenic inflammation and difficult to control. Colquhounia Root (CR) is a...
Itch is one of the major clinical manifestations of psoriasis, which is closely related with neurogenic inflammation and difficult to control. Colquhounia Root (CR) is a Chinese herb exhibiting broad bioactivities on anti-inflammation. This study was designed to explore the antipsoriatic and anti-itch potential of CR and its underlying mechanisms. Mice in a model of imiquimod-induced psoriasiform dermatitis were treated topically with CR for 7 days, and the severity of skin lesions and itch was significantly ameliorated. CR reduced the inflammatory cell infiltration, as well as mast cells in skins. Particularly, the expression of inflammatory cytokines and chemokine including , , and and itch-related molecules such as , , and in lesions were decreased in diseased mice upon application with CR. The normal human epidermal keratinocytes were stimulated with the M5 cytokine cocktail, the mixture of IL-17A, IL-22, Oncostatin M, IL-1, and TNF-, and cell viability and mRNA expression levels of inflammatory factors and itch-related molecules were measured after being treated with CR. We found that CR inhibited both cell hyperproliferation and overexpression of inflammatory cytokines and itch-related molecules . Altogether, we conclude that CR relieves psoriatic lesions and itch via controlling immunological and neurogenic inflammation.
Topics: Animals; Disease Models, Animal; Eczema; Imiquimod; Inflammation; Mice; Psoriasis; Skin
PubMed: 35069008
DOI: 10.1155/2022/5782922 -
Pharmaceuticals (Basel, Switzerland) Nov 2023: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is...
: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. : Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords "ustekinumab" or "Stelara" in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. : Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. : Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.
PubMed: 38004414
DOI: 10.3390/ph16111548 -
Archive of Clinical Cases 2019Psoriasiform dermatoses represent a wide spectrum of inflammatory conditions, with several major forms represented by psoriasis, as the prototype of this category,... (Review)
Review
Psoriasiform dermatoses represent a wide spectrum of inflammatory conditions, with several major forms represented by psoriasis, as the prototype of this category, followed by pustular psoriasis, Reiter's syndrome, pityriasis rubra pilaris, lichen simplex chronicus and large-plaques parapsoriasis. They create a diagnostic challenge, both clinical and histopathological, because of their complexity and frequent overlapping of the microscopical features. The characteristic histopathological features of psoriasiform reaction comprise extensive hyperkeratosis, with horizontally confluent but vertically intermittent parakeratosis, which alternate with orthokeratosis, thin granular layer, with relative frequent mitoses, uniform elongated and fused rete ridges, edematous superficial papillary dermis, with dilated capillaries, perivascular lymphocytic infiltrate, Munro's microabscesses, and spongiform pustules of Kogoj. Our paper aims to review the histopathology of major form of psoriasiform dermatoses and to emphasize the characteristic microscopical differences between them, for a better approach of the diagnosis as an important key for clinical and therapeutical management. Using the clinicopathological correlations, a thoroughly evaluation of the microscopical features and compartments distribution or special stainings and techniques, the range of differential diagnosis can be decreased and a more accurate diagnostic can be usually achieved. The insights into the pathogenic mechanisms can lead to new therapeutic opportunities targeted to the specific type of inflammatory lesion.
PubMed: 34754910
DOI: 10.22551/2019.24.0603.10155 -
Journal of Lower Genital Tract Disease Jul 2022The aim of the study was to evaluate clinicopathologic features of cases demonstrating an acanthotic tissue reaction not clearly consistent with psoriasis, lichen...
OBJECTIVE
The aim of the study was to evaluate clinicopathologic features of cases demonstrating an acanthotic tissue reaction not clearly consistent with psoriasis, lichen simplex chronicus, mycosis, or condyloma.
MATERIALS AND METHODS
This is a retrospective pathologic case series of biopsies reported as "benign acanthotic lesion" and "acanthotic tissue reaction" that lacked a clear diagnosis on expert review. Cases with nuclear atypia were excluded. Clinical and histopathologic data were collected, immunohistochemistry for p16 and p53 were obtained, and molecular testing for 28 common anogenital human papillomavirus (HPV) genotypes was undertaken.
RESULTS
There were 17 cases with a median age of 47 years. Unilaterality and medial location were clinical reasons for diagnostic difficulty. Histopathologic uncertainty often related to lack of papillary dermal fibrosis to support lichen simplex chronicus or psoriasiform lesions without parakeratosis, subcorneal pustules, and/or mycotic elements. Firm pathologic diagnoses were not possible, but 3 groups emerged: favoring chronic dermatitis, favoring psoriasis, and unusual morphologies. p16 results were negative or nonblock positive while p53 was normal or basal overexpressed. Human papillomavirus testing was negative in 12, low positive for HPV 16 in 1, unassessable in 3, and not requested in 1.
CONCLUSIONS
There is a group of acanthotic tissue reactions that cannot be classified with standard histopathologic assessment. Further clinicopathologic research into unilateral acanthotic lesions may provide insight into separation of psoriasis and mycosis when organisms are absent. Once nuclear atypia is excluded, immunohistochemistry for p16 and p53 and HPV molecular testing do not assist in diagnostic identification.
Topics: Alphapapillomavirus; Female; Humans; Middle Aged; Neurodermatitis; Papillomaviridae; Papillomavirus Infections; Psoriasis; Retrospective Studies; Tumor Suppressor Protein p53; Vulvar Neoplasms
PubMed: 35543596
DOI: 10.1097/LGT.0000000000000681 -
International Journal of Nanomedicine 2018Psoriasis is a chronic and currently incurable inflammatory skin disease characterized by hyperproliferation, aberrant differentiation, and inflammation, leading to...
Chitosan-based nanoformulated (-)-epigallocatechin-3-gallate (EGCG) modulates human keratinocyte-induced responses and alleviates imiquimod-induced murine psoriasiform dermatitis.
BACKGROUND
Psoriasis is a chronic and currently incurable inflammatory skin disease characterized by hyperproliferation, aberrant differentiation, and inflammation, leading to disrupted skin barrier function. The use of natural agents that can abrogate these effects could be useful for the treatment of psoriasis. Earlier studies have shown that treatment of keratinocytes and mouse skin with the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) mitigated inflammation and increased the expression of caspase-14 while promoting epidermal differentiation and cornification. However, bioavailability issues have restricted the development of EGCG for the treatment of psoriasis.
MATERIALS AND METHODS
To overcome these limitations, we employed a chitosan-based polymeric nanoparticle formulation of EGCG (CHI-EGCG-NPs, hereafter termed nanoEGCG) suitable for topical delivery for treating psoriasis. We investigated and compared the efficacy of nanoEGCG versus native or free EGCG in vitro and in an in vivo imiquimod (IMQ)-induced murine psoriasis-like dermatitis model. The in vivo relevance and efficacy of nanoEGCG formulation (48 µg/mouse) were assessed in an IMQ-induced mouse psoriasis-like skin lesion model compared to free EGCG (1 mg/mouse).
RESULTS
Like free EGCG, nanoEGCG treatment induced differentiation, and decreased proliferation and inflammatory responses in cultured keratinocytes, but with a 4-fold dose advantage. Topically applied nanoEGCG elicited a significant (<0.01) amelioration of psoriasiform pathological markers in IMQ-induced mouse skin lesions, including reductions in ear and skin thickness, erythema and scales, proliferation (Ki-67), infiltratory immune cells (mast cells, neutrophils, macrophages, and CD4 T cells), and angiogenesis (CD31). We also observed increases in the protein expression of caspase-14, early (keratin-10) and late (filaggrin and loricrin) markers of differentiation, and the activator protein-1 factor (JunB). Importantly, a significant modulation of several psoriasis-related inflammatory cytokines and chemokines was observed compared to the high dose of free EGCG (<0.05). Taken together, topically applied nanoEGCG displayed a >20-fold dose advantage over free EGCG.
CONCLUSION
Based on these observations, our nanoEGCG formulation represents a promising drug-delivery strategy for treating psoriasis and possibly other inflammatory skin diseases.
Topics: Administration, Topical; Aminoquinolines; Animals; Antineoplastic Agents; Antioxidants; Catechin; Cell Differentiation; Cells, Cultured; Chitosan; Dermatitis; Filaggrin Proteins; Humans; Imiquimod; Keratinocytes; Mice; Mice, Inbred BALB C; Nanoparticles; Psoriasis
PubMed: 30057446
DOI: 10.2147/IJN.S165966 -
International Journal of Molecular... May 2024Psoriasis is a systemic autoimmune/autoinflammatory disease that can be well studied in established mouse models. Skin-resident macrophages are classified into epidermal... (Review)
Review
Psoriasis is a systemic autoimmune/autoinflammatory disease that can be well studied in established mouse models. Skin-resident macrophages are classified into epidermal Langerhans cells and dermal macrophages and are involved in innate immunity, orchestration of adaptive immunity, and maintenance of tissue homeostasis due to their ability to constantly shift their phenotype and adapt to the current microenvironment. Consequently, both macrophage populations play dual roles in psoriasis. In some circumstances, pro-inflammatory activated macrophages and Langerhans cells trigger psoriatic inflammation, while in other cases their anti-inflammatory stimulation results in amelioration of the disease. These features make macrophages interesting candidates for modern therapeutic strategies. Owing to the significant progress in knowledge, our review article summarizes current achievements and indicates future research directions to better understand the function of macrophages in psoriasis.
Topics: Psoriasis; Animals; Macrophages; Disease Models, Animal; Mice; Humans; Langerhans Cells; Immunity, Innate; Skin
PubMed: 38791342
DOI: 10.3390/ijms25105306