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Diagnostics (Basel, Switzerland) Dec 2022Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features...
Palmoplantar psoriasis (PP) is a relatively uncommon variant of psoriasis that affects palms and soles, and that frequently shares both clinical and histologic features with chronic eczema, hyperkeratotic hand dermatitis and allergic contact dermatitis. The present study aims to characterize the histologic features of PP on a series of 21 cases. The following morphological features and their distribution were included: parakeratosis, dilated vessels in papillary dermis, psoriasiform acanthosis with elongation of rete ridges, perivascular lymphocytic infiltrate, decrease/loss of granular layer, Munro's microabscesses, spongiform pustules of Kogoj, spongiosis and lymphocytic exocytosis. The main diagnostic clues and histologic differential diagnoses are also discussed.
PubMed: 36553078
DOI: 10.3390/diagnostics12123071 -
Frontiers in Immunology 2022Psoriasis is a chronic skin disease associated with deregulated interplays between immune cells and keratinocytes. Neutrophil accumulation in the skin is a histological...
BACKGROUND
Psoriasis is a chronic skin disease associated with deregulated interplays between immune cells and keratinocytes. Neutrophil accumulation in the skin is a histological feature that characterizes psoriasis. However, the role of neutrophils in psoriasis onset and development remains poorly understood.
METHODS
In this study, we utilized the model of psoriasiform dermatitis, caused by the repeated topical application of an imiquimod containing cream, in neutrophil-depleted mice or in mice carrying impairment in neutrophil functions, including p47phox -/- mice (lacking a cytosolic subunit of the phagocyte nicotinamide adenine dinucleotide phosphate - NADPH - oxidase) and Sykfl/fl MRP8-cre+ mice (carrying the specific deletion of the Syk kinase in neutrophils only), to elucidate the specific contribution of neutrophils to psoriasis development.
RESULTS
By analyzing disease development/progression in neutrophil-depleted mice, we now report that neutrophils act as negative modulators of disease propagation and exacerbation by inhibiting gammadelta T cell effector functions via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species (ROS) production. We also report that Syk functions as a crucial molecule in determining the outcome of neutrophil and γδ T cell interactions. Accordingly, we uncover that a selective impairment of Syk-dependent signaling in neutrophils is sufficient to reproduce the enhancement of skin inflammation and γδ T cell infiltration observed in neutrophil-depleted mice.
CONCLUSIONS
Overall, our findings add new insights into the specific contribution of neutrophils to disease progression in the IMQ-induced mouse model of psoriasis, namely as negative regulatory cells.
Topics: Mice; Animals; Imiquimod; Neutrophils; NADP; Psoriasis; Disease Models, Animal; Eczema; NADPH Oxidases; Disease Progression
PubMed: 36466913
DOI: 10.3389/fimmu.2022.1049079 -
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 -
Frontiers in Immunology 2022Transient receptor potential melastatin 4 (TRPM4) is a Ca-activated, monovalent cation channel that is expressed in a wide range of cells. We previously reported two...
Transient receptor potential melastatin 4 (TRPM4) is a Ca-activated, monovalent cation channel that is expressed in a wide range of cells. We previously reported two gain-of-function (GoF) mutations of TRPM4 as the cause of progressive symmetric erythrokeratodermia (PSEK), which shares similar clinical and histopathological features with psoriasis. Using CRISPR/Cas9 technology, we generated TRPM4 mice that have the equivalent mutation to one of the two genetic mutations found in human PSEK (equivalent to human TRPM4). Using this mutant mice, we examined the effects of TRPM4 GoF at the cellular and phenotypic levels to elucidate the pathological mechanisms underlying PSEK. In the absence of experimental stimulation, TRPM4 mice did not show a phenotype. When treated with imiquimod (IMQ), however, TRPM4 mice were predisposed to more severe psoriasiform dermatitis (PsD) than wild-type (WT), which was characterized by greater accumulation of CCR6-expressing γδ T cells and higher mRNA levels of . In TRPM4 mice, dendritic cells showed enhanced migration and keratinocytes exhibited increased proliferation. Moreover, a TRPM4 inhibitor, glibenclamide, ameliorated PsD in WT and TRPM4 mice. Our results indicate elevated TRPM4 activities boosted susceptibility to cutaneous stimuli, likely through elevation of membrane potential and alteration of downstream cellular signaling, resulting in enhanced inflammation. Our results further suggest a possible therapeutic application of TRPM4 inhibitors in psoriasis.
Topics: Mice; Humans; Animals; Gain of Function Mutation; Imiquimod; Psoriasis; Skin; Eczema; TRPM Cation Channels
PubMed: 36341417
DOI: 10.3389/fimmu.2022.1025499 -
Annals of Dermatology Oct 2022
PubMed: 36198636
DOI: 10.5021/ad.20.094 -
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 -
Cureus Aug 2022Immune checkpoint inhibitors (ICIs), a class of anticancer agents that upregulate T-cell response to tumor cells, are associated with immune-related adverse events...
Immune checkpoint inhibitors (ICIs), a class of anticancer agents that upregulate T-cell response to tumor cells, are associated with immune-related adverse events (irAEs), and the skin is one of the most commonly affected organs. We report the first two cases of a unique ICI-induced clinicopathological entity. A psoriasiform-appearing eruption with psoriasiform, spongiotic, and lichenoid dermatitis pattern on histopathology. A 73-year-old male with stage IV melanoma treated with nivolumab and a 63-year-old female with stage IV colorectal cancer treated with pembrolizumab and TAK-981 separately presented to our clinic with a psoriasiform rash. In both patients, punch biopsy revealed an unusual combination of psoriasiform, spongiotic, and lichenoid dermatitis. Treatment with apremilast in the first patient yielded some improvement, while treatment with ixekizumab in the second patient yielded a complete resolution of the eruption. Our cases add to the growing body of reported immune toxicities related to ICI use and illustrate the utility of targeted immune suppression of pathways in disease phenotype to allow for ICI continuation and optimization of cancer treatment.
PubMed: 36134105
DOI: 10.7759/cureus.28010 -
British Journal of Clinical Pharmacology Feb 2023Secukinumab, the first interleukin 17A inhibitor, is widely used to treat immune diseases, including plaque psoriasis, psoriatic arthritis and ankylosing spondylitis....
AIMS
Secukinumab, the first interleukin 17A inhibitor, is widely used to treat immune diseases, including plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. Recently, many studies have reported adverse events associated with secukinumab, including gastrointestinal disorders, infections and infestations, and hypersensitive and nervous system disorders.
OBJECTIVE
Here, we aimed to explore the clinical characteristics, outcomes and time to onset of the four main toxicities of secukinumab using post-marketing data.
METHODS
Our study utilized data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2015 to 2021, using disproportionality analysis. Toxicities were defined based on the standardized Medical Dictionary for Regulatory Activities queries. Two disproportionality methods were used to detect potential signals: information component (IC) and reporting odds ratio (ROR). The signals were defined as ROR > 1 and IC > 0.
RESULTS
A total of 73 945 398 records were included in this study, of which 300 665 records were related to secukinumab. Diarrhoea (N = 3538), nasopharyngitis (N = 3458), pruritus (N = 4277) and rash (N = 3270) were the most common adverse events. Inflammatory bowel disease (IC /ROR = 3.25/9.69), genital candidiasis (IC /ROR = 3.46/11.54), dermatitis psoriasiform (IC /RO = 1.94/4.04) and anosmia (IC /ROR = 1.62/3.17) had the highest IC values of all toxicities. The time to onset of the four toxicities was mainly concentrated in the first month. Some patients simultaneously presented with two or more toxicities.
CONCLUSION
This pharmacovigilance study systematically explored the four main toxicities of secukinumab and provided new safety signals based on past safety information. Some high-risk signals need to be given attention.
Topics: United States; Humans; Pharmacovigilance; United States Food and Drug Administration; Antibodies, Monoclonal, Humanized; Psoriasis; Adverse Drug Reaction Reporting Systems
PubMed: 36106653
DOI: 10.1111/bcp.15535 -
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 -
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