Psoriasiform Dermatitis Research Articles

A Single-Center Experience with Dupilumab for Atopic or Psoriasiform Dermatitis in Patients with Inflammatory Bowel Disease.

Dupilumab blocks IL4/IL13 and is used in atopic disease. There are concerns that blockade may lead to inflammatory bowel disease (IBD) inception or activity. Limited data exist on the use of this therapy in patients with IBD; we aimed to describe our experience using dupilumab in IBD to treat concomitant atopic dermatitis (AD) or anti-TNF-induced dermatitis. We analyzed the electronic medical records (2018-2022) in a single, tertiary care center to identify patients with IBD on dupilumab. Clinical and demographic data were gathered, including disease location/behavior, personal/family history of atopy, indication for and response to dupilumab, IBD medication history, and adverse events. Seventeen patients (65% Crohn's) were identified with IBD on dupilumab for dermatitis; 9 for severe AD and 8 for a worsened dermatitis, either AD or psoriasiform dermatitis (PD), induced by anti-TNF. They were treated for a median 1.2 [IQR 0.6-2.3] years. All patients had a dermatologic response to dupilumab and remained on dupilumab at last follow-up. No adverse events were identified, including no increase in IBD activity. In those with dermatitis worsened or induced by anti-TNF, all started dupilumab in combination with another biologic: 3 with anti-TNF, 4 with ustekinumab, and 1 with vedolizumab. Seven of the eight had a response to the initial combination of biologics; however, one patient using dupilumab-anti-TNF ultimately changed to combination dupilumab-ustekinumab to achieve resolution of the dermatitis. Dupilumab is safe and effective for dermatitis in patients with IBD, both primary atopic dermatitis and dermatitis induced or worsened by anti-TNF.

34316 Successful treatment of hypopigmented mycosis fungoides in a pediatric patient with excimer laser

A 10-year-old girl with a history of facial pityriasis alba presented with an asymptomatic hypopigmented patch on the right leg. Treatment with triamcinolone cream did not alter the appearance and hair loss was noted within the lesion. After cessation of topical steroids, a biopsy revealed a spongiotic and psoriasiform dermatitis with lymphocyte exocytosis and perifollicular and perieccrine lymphocytic inflammation with a CD8 shift. T-cell gene rearrangement was positive. A diagnosis of hypopigmented mycosis fungoides (MF) was made.

Decreasing GDF15 Promotes Inflammatory Signals and Neutrophil Infiltration in Psoriasis Models

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.

Immune Checkpoint Inhibitor-Induced Psoriasiform, Spongiotic, and Lichenoid Dermatitis: A Novel Clinicopathological Pattern

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.

565 Metformin and akkermansia muciniphila attenuated psoriasiform dermatitis exacerbated by short-term exposure to glucose

We have previously shown that short-term feeding (<1 month) with a high-sugar, moderate-fat diet (i.e., Western diet) is enough to induce clinically and molecularly-detectable psoriasiform dermatitis (PsD), suggesting that certain diet patterns could contribute to the development of PsD. However, the role of specific dietary components like sugar remains to be elucidated. Herein, we showed that short-term exposure to glucose (4 weeks) enhances the susceptibility of mice to PsD induced by imiquimod (IMQ).

313 Evaluating the effectiveness of topical tofacitinib in reducing non-atopic dermatitis chronic itch

Introduction: Chronic and refractory pruritus is a highly common complaint amongst patients with dermatological conditions and remains difficult to treat with current drug therapies. There is an unmet need for potent topical antipruritics. Janus kinase (JAK) inhibitors have shown significant effect in treating atopic eczema itch. Objective: Topical tofacitinib compounding cream was investigated for treatment of non-AD related chronic pruritic diseases. Methods: A comprehensive chart review was completed where data was collected on numerous variables that help recognize the efficacy of tofacitinib. 19 patients with chronic itch of different types (excluding those with AD) treated with topical tofacitinib 2% compounding cream within the last four years were identified and evaluated regarding their demographic information, diagnosis, location and characteristics of itch, itch intensity scale ratings, adverse effects and reasons for discontinuation (if applicable). Paired-sample t-test was performed to evaluate average 24-hour itch intensity scale ratings prior to and after initiating topical tofacitinib. Results: 13 (68%) out of 19 patients demonstrated a quantifiable reduction in itch. Average 24-hour itch scale ratings decreased significantly (p<0.001) after initiation of tofacitinib from 7.82 (± 2.23) to 4.47 (± 3.55) across all patients, with score reduction of 3.34 (± 3.34). Tofacitinib was effective for many causes of non-AD itch, particularly in patients with prurigo nodularis and psoriasiform dermatitis. Overall, the drug was safe with no major adverse effects; the main reason for discontinuation of the drug was no relief or short duration of relief time after application. Conclusion: Topical tofacitinib cream significantly decreased the average itch intensity of patients and is generally well-tolerated, making it a promising therapeutic for non-AD related chronic itch.

486 Glibenclamide ameliorates skin inflammation in a TRPM4 gain-of-function murine model of imiquimod-mediated psoriasiform dermatitis

A heterozygous (het) gain-of-function (GoF) mutation (I1033M or I1040T) of TRPM4, a calcium-activated nonselective monovalent cation channel, has been reported as the cause of progressive symmetric erythrokeratodermia. This genetic disease is characterized by red, scaly plaques in periorificial and acral regions that are reminiscent of human psoriasis. To determine whether the TRPM4 mutation alone is sufficient to lead to skin disease, we created a mouse (TRPM4I1029M, genetically equivalent to the human I1033M mutation) using CRISPR-Cas9 methods. Unperturbed homo and het TRPM4I1029M mice showed no apparent skin changes compared to wild type (WT) littermates. We compared the response of TRPM4I1029M and WT littermates to topical imiquimod (IMQ) application, a model of psoriasiform dermatitis (PsD). Het TRPM4I1029M showed enhanced skin inflammation with greater clinical severity scores (200% vs WT), thicker epidermis, more infiltration of CCR6+ γδ low T cells, higher expression of p-STAT3 protein, and higher mRNA levels of Il17a (1.5-fold) compared to WT mice. In vivo dendritic cell (DC) migration assay showed enhanced DC migration in het TRPM4I1029M. Cell cycle analysis showed that keratinocytes (KCs) from het TRPM4I1029M were in proliferative cell cycle status compared to KCs from WT mice. However, TRPM4I1029M did not show exaggerated responses in other in vivo models such as croton oil-induced irritant dermatitis and DNFB-induced contact dermatitis models. Glibenclamide, a classic diabetes drug, is a known TRPM4 inhibitor and ameliorated IMQ-PsD both in TRPM4I1029M and WT mice with milder clinical scores (50% vs vehicle), thinner epidermis, less infiltration of CCR6+ γδ low T cells, and lower mRNA levels of Il17a (30% vs vehicle). Our results suggest a possible therapeutic application of TRPM4 inhibitors in psoriasis.

833 Reintroduction of caveolin-1 scaffolding domain improves pathogenesis of psoriasiform dermatitis

Psoriasis is a chronic, inflammatory skin disease characterized by well-defined, erythematous plaques with silvery scale secondary to aberrant keratinocyte proliferation. We have previously identified that a structural membrane protein caveolin-1 (Cav1) is involved in regulation of aberrant keratinocyte proliferation and differentiation, and thus the aim of this study was to elucidate the role of Cav1 in pathogenesis of psoriasis vulgaris. We utilized spatial genomic & proteomic analyses combined with immunohistochemistry (IHC) with patient samples and mouse models. Omics analyses identified caveolae and their structural components (Cav1, -2 and cavin-1) as downregulated in imiquimod (IMQ)-treated mouse model of psoriasis. These observations were validated in patient samples of multiple types of psoriasis stratified by PASI score (plaque, inverse, guttate and nail) by IHC staining and quantified by QuPath image analysis software. Although all biopsy samples exhibited an inverse relationship with levels of Cav1, plaque psoriasis samples were the most pronounced. To assess whether reintroduction of Cav1 can alleviate some of the features associated with IMQ-induced model of psoriasis (increased skin thickness/scaling and upregulation of psoriasis associated markers), C57BL6 and K14cre-Cav1 knockout mice were treated with soluble caveolin scaffolding domain (CSD) peptide, in presence or absence of IMQ. We observed that Cav1ko mice exhibited a trend in increased skin thickness and expression of CD11b, CD14, IL-6, IL-12, IL-17a and TNFa, although to a lesser than IMQ-treated C57BL6 mice (Cav1 wild type). Moreover, topical CSD treatment decreased both skin thickness and scaling, as well as dampened upregulation of aforementioned inflammatory markers. Together, these data support the hypothesis that Cav1 is major pathophysiological target in psoriasis and introduce different approach to localized topical treatment of psoriasis by targeting structural components of the specialized membrane microdomains, such as caveolae.

ANGPTL4 Regulates Psoriasis via Modulating Hyperproliferation and Inflammation of Keratinocytes.

Background: Psoriasis is characterized by keratinocyte proliferation and massive inflammatory leukocytes infiltration, affecting 0.14%–1.99% of the world’s population. Our aim was to identify novel potential therapeutic strategies for psoriasis. Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules that were closely related to psoriasis based on the GSE30999 dataset, which contained expression data from 85 patients with moderate-to-severe psoriasis. Then, angiopoietin-like 4 (ANGPTL4), one of the most related hub genes, was selected for in vitro and in vivo functional assays. In our experiments, imiquimod (IMQ)-induced psoriasiform dermatitis in mice and human keratinocytes (HaCaT) cells were used to study the potential roles and mechanisms of ANGPTL4 in psoriasis. Results: WGCNA analysis revealed the turquoise module was most correlated with psoriasis, and ANGPTL4 is one of the most related hub genes that significantly upregulated in psoriasis lesions compared with non-lesional skin. Consistent with the bioinformatic analysis, the expression of ANGPTL4 was significantly upregulated in IMQ-induced psoriasiform skin of mice. Exogenous recombinant ANGPLT4 protein treatment could promote the proliferation and induce the expression of inflammatory cytokines in HaCaTs, whereas silencing of ANGPTL4 effectively inhibited these effects. Then we demonstrated that recombinant ANGPTL4 protein exacerbated psoriasiform inflammation and epidermal hyperproliferation in vivo. Mechanismly, extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) pathways were involved in ANGPTL4-mediated regulation of proliferation and inflammation. Conclusion: We found ANGPTL4 was significantly increased in IMQ-induced psoriasiform skin of mice. ANGPTL4 could promote keratinocyte proliferation and inflammatory response via ERK1/2 and STAT3 dependent signaling pathways in psoriasis.

Laser-assisted nanocarrier delivery to achieve cutaneous siRNA targeting for attenuating psoriasiform dermatitis.

Psoriasis is an autoimmune skin disorder presenting the excessive expression of interleukin (IL)-6. The topical use of small interfering RNA (siRNA) has been increasingly discovered for treating skin diseases. A delivery system capable of protecting siRNA while facilitating both skin targeting and cellular entrance is critical for the successful medication of topically-applied siRNA. Herein, we developed a delivery system for siRNA based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles and combined this system with an ablative laser to promote skin absorption for topical psoriasis therapy. The siRNA absorption enhancement was compared by two laser modalities: a fractional CO2 laser and a fully-ablative Er:YAG laser. We characterized the effect of the delivery system by the cellular uptake, IL-6 silencing, in vitro skin absorption, cutaneous biodistribution, and in vivo psoriasiform dermatitis in mice. The nanocarriers showed minimal cytotoxicity and facile cellular uptake to knock down the IL-6 expression. The nanoformulation containing a cationic surfactant (Forestall) for ion pairing with siRNA achieved a 66% and 77% IL-6 knockdown efficiency toward keratinocytes and macrophages, respectively. In the Franz cell absorption, the lasers increased the naked siRNA penetration to the receptor compartment by 3.7-5.0-fold but remarkably reduced skin deposition using imiquimod (IMQ)-treated psoriasiform skin as the barrier. The fractional laser facilitated nanoparticle-associated siRNA skin deposition up to 3.3-fold, whereas the transport of the nanocarriers to the receptor was negligible. Qualitatively, the lasers increased nanoparticle delivery in the epidermis with limited effect to elevate the penetration depth. The fractional-mediated nanocarrier delivery dramatically attenuated the erythema and scaly lesions of psoriasiform dermatitis. The histological examination displayed a reduction of epidermal hyperplasia and macrophage infiltration by the combination of laser and nanosystem. The passive and laser-assisted naked siRNA delivery was less effective in mitigating dermatitis. The topical delivery of fractional laser-assisted nanoparticles on mice resulted in a 56% IL-6 knockdown. Our results manifested the benefit of cutaneous siRNA targeting using ablative lasers to deliver nanocarriers for treating psoriatic inflammation.

Cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes.

Recent studies have illustrated that psoriatic lesions are innervated by dense sensory nerve fibers. Psoriatic plaques appeared to improve after central or peripheral nerve injury. Therefore, the nervous system may play a vital role in psoriasis. We aimed to clarify the expression of nerve fibers in psoriasis and their relationship with immune cells and keratinocytes, and to explore the effect of skin nerve impairment. Our results illustrated that nerve fibers in psoriatic lesions increased and were closely innervated around immune cells and keratinocytes. RNA-seq analysis showed that peripheral sensory nerve-related genes were disrupted in psoriasis. In spinal cord hemi-section mice, sensory impairment improved psoriasiform dermatitis and inhibited the abnormal proliferation of keratinocytes. Botulinum toxin A alleviated psoriasiform dermatitis by inhibiting the secretion of calcitonin gene-related peptide. Collectively, cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes. Neurological intervention may be a new treatment strategy for psoriasis.

Case of durvalumab‐induced annular psoriasiform dermatitis in lung cancer

We present a case of annular psoriasiform drug eruption by durvalumab. Histopathologically, scaly annular erythema showed histopathological psoriasis-like epidermal thickening and sites where necrosis of epidermal keratinized cells was observed as the infiltration of many CD8-positive T cells and TIA-positive cells was seen. This suggests that durvalumab-induced psoriasiform dermatitis was associated with histopathological keratinocyte apoptosis by the activation of cytotoxic T cells. A 69-year-old Japanese man was diagnosed with liver metastases (Stage III) from non-small-cell lung cancer, and durvalumab administration was started. The patient had no history of medication that could have induced psoriasis. After two cycles of durvalumab, scaly erythema appeared on the palms. After 4 cycles of durvalumab, interstitial pneumonitis developed, so durvalumab administration was discontinued, and oral prednisolone was started, and the erythema became pigmented. After the resumption of durvalumab administration, scaly annular erythema appeared on the head and face. After 14 cycles of durvalumab, Trousseau syndrome developed, and durvalumab administration was discontinued, but the erythema expanded. The clinical findings at the first visit were scaly annular erythema (Figure 1A,B) on the head and face, scaly erythema on the abdomen (Figure 1C), and diffuse erythematous plaques (Figure 1D,E) on the fingers and soles of the feet. There were no nail or joint lesions, and no fungi were detected on the erythematous plaques. A skin biopsy of the scaly annular erythema on the head showed hyperkeratosis with parakeratosis and thickening of the epidermis, loss of the granular layer, and perivascular infiltration of lymphocytes on the upper dermis (Figure 1F). Lymphocytes had infiltrated the epidermis, keratinocyte apoptosis was observed, and there were psoriasis-like epidermal changes. A skin biopsy of the abdominal erythema showed similar results. Immunohistochemically, CD4-positive T cells had mainly infiltrated the region around the dermal blood vessels, and there was little infiltration into the epidermis (Figure 1G). In addition, many TIA-positive cells and CD8-positive T cells had infiltrated sites where necrosis of keratinized cells was observed in the epidermis (Figure 1H,I). Local calcipotriol hydrate betamethasone dipropionate and narrowband ultraviolet B phototherapy caused pigmentation of the annular erythema on the head after approximately one month. However, he died due to respiratory failure 15 months after the start of durvalumab administration. Immune checkpoint inhibitors (ICIs) have been shown to be effective in a variety of cancers.1 Durvalumab is an anti-PD-L1 monoclonal antibody that is indicated for the treatment of unresectable stage III non-small-cell lung cancer. There have been many reports of psoriasiform dermatitis with anti-PD-1 antibodies, but none of these cases developed annular erythema. 2 There have been four cases of psoriasiform dermatitis due to anti-PD-L1 antibodies, only one of which was scaly annular erythema.3 There was no history of psoriasis, and topical steroid and narrowband ultraviolet B phototherapy were used in the previous report. In this case, scaly annular erythema on the head showed histopathological psoriasis-like epidermal thickening and sites where necrosis of epidermal keratinized cells was observed as the infiltration of many CD8-positive T cells and TIA-positive cells was seen. It was reported that anti-PD-1 antibodies induced the activation of T cells including Th1 and Th17 cells triggering epidermal thickening and Th9 cells triggering cytotoxic effect.4, 5 Therefore, it was suggested that durvalumab also has induced psoriasiform dermatitis that was also associated with histopathological keratinocyte apoptosis by the activation of these T cells. Approval of the research protocol: No human participant was involved in this study. Informed Consent: N/A. Registry and the Registration No: N/A. Animal Studies: N/A. The authors declare no conflicts of interest.

Drug Delivery through the Psoriatic Epidermal Barrier-A "Skin-On-A-Chip" Permeability Study and Ex Vivo Optical Imaging.

Psoriasis is a chronic inflammatory disease with unmet medical needs. To clarify potential therapeutic targets, different animal models have been developed. In the current study, imiquimod-induced psoriasiform dermatitis was used for monitoring the changes in skin thickness, transepidermal water loss, body weight, blood perfusion and drug permeability for a topical cream formulation of caffeine, both in wild type and in knock out mice. Morphological characterization of control and diseased tissues was performed by scanning electron microscopy and two-photon microscopy. The chemically induced psoriatic group showed increased skin permeability for the model drug during disease progression. In wild type and TRPA1 KO mice, however, enhanced skin thickness and hyperkeratosis blocked further increase of drug penetration at the late phase (96 h). These results indicate that topical drug therapy can be more effective in early phases of plaque development, when skin thickness is lower. Although paracellular connections (tight junctions) are looser in the advanced phase, hyperkeratosis blocks drug delivery through the transappendageal routes. Novel drug formulations may have the potency for effective drug delivery across the epidermal barrier even in the advanced phase. For development of more effective topical drugs, further research is proposed to explore drug penetration both in healthy and diseased conditions.

Outcomes of Children with Inflammatory Bowel Disease who Develop Anti-tumour Necrosis Factor-induced Skin Reactions.

Anti-tumour necrosis factor [anti-TNF] induced skin reactions are common adverse events in paediatric inflammatory bowel disease [IBD]. We aimed to report on outcomes of children with anti-TNF induced skin reactions who switched to ustekinumab [UST] vs. continued anti-TNF therapy. Charts were reviewed for paediatric IBD patients with anti-TNF induced skin reactions. Skin reactions, including psoriasiform dermatitis [PD], were classified as mild or severe based on a severity score. Primary outcome was frequency of skin resolution at 6 months. Secondary outcomes were combined clinical remission and skin resolution at 6 months and skin resolution at latest follow-up. A total of 111/638 [17%] children ([85, 21%] infliximab [IFX]; [26, 11%] adalimumab [ADA]) developed skin reactions. Eighty [72%] had PD, 25 [23%] infections, and four [4%] alopecia areata; 71 [64%] continued anti-TNF; and 40 [36%] switched to UST. In all, 73 [66%] had severe reactions and were more likely to switch to UST than if mild (37 [51%] vs. 3 [8%]; p <0.0001). Switching to UST had a higher rate and odds of resolution (29 [73%] vs. 24 [34%]; p <0.0001; odds ratio [OR] = 19.7, 95% confidence interval [CI]: 5.6, 69.5; p <0.0001) and combined remission (21 [52%] vs. 22 [31%]; p = 0.03; OR = 8.5, 95% CI: 2.5, 28.4; p = 0.0005] vs. continuing anti-TNF at 6 months. Children who switched to UST after anti-TNF induced skin reactions were more likely to have improved outcomes than those who continued anti-TNF therapy. Future studies are needed to determine immune mechanisms of anti-TNF induced skin reactions and treatment response.

Dipeptidyl peptidase-4 inhibitor-associated cutaneous eruptions: a retrospective observational study.

Dipeptidyl peptidase (DPP)-4 plays a complex role in immune regulation and its inhibition can have effects on the pathogenesis of various skin diseases. Studies have shown that DPP-4 inhibitors are associated with an increased risk of bullous pemphigoid (BP). To analyse the clinical and histopathological features of cutaneous adverse events in patients on DPP-4 inhibitors. We performed a retrospective review of patients with suspected DPP-4 inhibitor-associated cutaneous adverse events, at a tertiary teaching hospital from 1 January 2017 to 31 December 2020. Exclusion criteria included previous history of chronic skin disease and lack of histopathological reports or follow-up records. The clinical characteristics, latency period, Naranjo Adverse Drug Reaction Probability Scale and clinical outcomes were evaluated. In total, 18 patients (10 men, 8 women; mean age 68.6 years, range 38-89 years) were included. The DPP-4 inhibitors used were teneligliptin (n = 6), vildagliptin (n = 6), sitagliptin (n = 4), linagliptin (n = 1) and saxagliptin (n = 1). The mean interval between therapy initiation and lesion onset was 8.8 months (range 1-24 months). The dermatoses noted were BP (n = 12; 66.6%), lichenoid dermatitis (n = 4; 22.2%), psoriasiform dermatitis (n = 1; 5.6%) and spongiotic dermatitis (n = 1; 5.6%). Eight patients (44.4%) had necrotic keratinocytes as one of the distinct histological features. Causality assessment using the Naranjo scale rated the causative role of DPP-4 inhibitors as 'possible' in all patients. Of the 18 patients, 11 (61.1%) noted improvement in their condition following discontinuation of DPP-4 inhibitors, with 5 having complete remission within 6 months of stopping the drug. DPP-4 inhibitor-associated dermatoses are not necessarily limited to BP. It is necessary to recognize the possibility of other dermatoses in patients on DPP-4 inhibitors as drug substitution/cessation may improve disease morbidity.

Effects of Astragalus polysaccharide on imiquimod-induced psoriasiform dermatitis in mice and its mechanisms

Objective: To investigate the effects and mechanisms of Astragalus polysaccharide on improving imiquimod-induced psoriasiform dermatitis in mice. Methods: 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. Results: Compared with control group, the PASI score and the serum levels of TNF-α, IL-1β and IL-6 were increased significantly (P＜0.05), and the infiltration of macrophages in skin tissue was increased significantly in model group (P＜0.05). Compared with model group, the PASI score was decreased significantly (P＜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 (P＜0.05). The infiltrating macrophages in skin tissue were decreased significantly in Astragalus polysaccharide high-dose group (P＜0.05). Conclusion: 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.

CB2R Deficiency Exacerbates Imiquimod-Induced Psoriasiform Dermatitis and Itch Through the Neuro-Immune Pathway.

Background: Cannabinoid receptor 2 (CB2R) is a potential target for anti-inflammatory and pain therapeutics given its significant immunomodulatory and analgesic effects. However, the role of CB2R in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) and itch is poorly understood. Objective: To investigate the function and mechanism of CB2R in PsD and itch in mice. Methods: Following daily treatment with topical IMQ cream for 5-7 consecutive days in C56BL/6 wild-type (WT) and CB2R gene knockout (KO) mice, we assessed the Psoriasis Area and Severity Index (PASI) scores and the scratch bouts every day, and hematoxylin and eosin (H&E) staining, toluidine blue staining were used to observe the histological changes. mRNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels were detected by western blotting (WB), immunohistochemistry (IHC), immunofluorescence (IF) and cytometric bead array (CBA). Flow cytometry (FCM) was used to examine the proportion of Th17/Treg cells. Results: We found that CB2R expression levels were increased in mice with psoriasis. Compared with WT mice, CB2R deficiency exacerbated IMQ-induced PsD and scratching bouts and upregulated the expression of proinflammatory cytokines by increasing the infiltration of CD4+ T cells and the Th17/Treg ratio. Obvious proliferation and prolongation of nerve fibers and high expression of nerve growth factor (NGF) were observed in PsD and CB2R KO mice. Pretreatment with the CB2R agonist, JWH-133 significantly reversed inflammation and scratching bouts. CB2R didn't participate in the induction of itch in psoriasis by regulating the expression of IL-31, thymic stromal lymphopoietin (TSLP) and mast cells in mouse skins. Conclusion: Our results demonstrate that CB2R plays a pivotal role in the pathophysiology of psoriasis, providing a new potential target for anti-inflammatory and antipruritic drugs.

Topical Treatment of Colquhounia Root Relieves Skin Inflammation and Itch in Imiquimod-Induced Psoriasiform Dermatitis in Mice.

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 Il17a, Il22, and Ccl20 and itch-related molecules such as SP, CGRP, and NGF 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-1α, and TNF-α, 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 in vitro. Altogether, we conclude that CR relieves psoriatic lesions and itch via controlling immunological and neurogenic inflammation.

Prenatal infection predisposes offspring to enhanced susceptibility to imiquimod-mediated psoriasiform dermatitis in mice

Background: Infection can upregulate T helper 17 (Th17) signaling and exacerbate psoriasis. Literature has indicated that prenatal infection induces embryonic development toward Th17 signaling and is a risk factor for developing certain Th17-skewing disorders such as autism in offspring. However, it remains unclear if a prenatal infection is a risk factor for developing psoriasis in offspring. Objectives: We investigated if a prenatal infection predisposes mice offspring to enhanced susceptibility to psoriatic inflammation. Methods: Pregnant C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid poly I:C to simulate prenatal bacterial and viral infection, respectively. Phosphate-buffered saline (PBS) injection was used as the control. When mice offspring were at the age of 9–10 weeks, imiquimod (IMQ) cream or control vehicle was applied topically on ears for 5 consecutive days to induce psoriasiform dermatitis. The extent of epidermal hyperplasia and the number of Munro microabscesses were examined by histologic analysis. Protein expressions of neutrophil marker Ly6 g and Th17-associated cytokines were measured by western blotting. Results: Prenatal infection with LPS or poly I:C induced a greater extent of epidermal hyperplasia and more Munro microabscesses after IMQ application as compared with prenatal PBS injection. Mice offspring with prenatal infection also had higher protein expressions of Ly6 g, IL-17a, and interleukin-23 after IMQ stimulation compared with their PBS controls. Conclusion: Prenatal infection predisposes mice offspring to enhanced susceptibility to IMQ-mediated psoriasiform dermatitis. The data obtained from the present animal study suggest that prenatal infection might be a risk factor for developing psoriasis in offspring.

DIAGNOSTIC UTILITY OF KI 67 IMMUNOSTAINING IN DIFFERENTIATION OF PSORIASIS VS OTHER PSORIASIFORM DERMATITIS

BACKGROUND: Psoriasis is a prototype of psoriasiform tissue pattern and needs to be differentiated from other psoriasiform dermatoses(PD)bothclinicallyandhistopathologically. AIM: To study the morphology of psoriasis and other psoriasiform conditions and to study the expression of Ki67 to distinguish psoriasis from the other psoriasiformdermatitislesions. METHODS:Astudywasperformedonparafnblocksof28psoriasis and22psoriasiformdermatitispatientsbetween2018and2020.The selectedformalin xed parafn embedded tissuesfrom each biopsy specimen were cut into 3-5 µm section and were stained with hematoxylin and eosin. Primary antihuman antibodiesagainstki67wereapplied. RESULTS: Out of 50 patients, 62% were men and in the age group of 21-40 years. Mean staining of Ki 67 was higherin psoriasisthan other psoriasiform dermatitis. CONCLUSION:ThepresentstudyshowedtheexpressionofKi67biomarkerhigherinpsoriasisascomparedtotheotherpsoriasiformdermatitislesions.