Image-based remote evaluation of PASI scores with psoriasis by the YOLO-v4 algorithm.

As a chronic relapsing disease, psoriasis is characterized by widespread skin lesions. The Psoriasis Area and Severity Index (PASI) is the most frequently utilized tool for evaluating the severity of psoriasis in clinical practice. Nevertheless, long-term monitoring and precise evaluation pose difficulties for dermatologists and patients, which is time-consuming, subjective and prone to evaluation bias. To develop a deep learning system with high accuracy and speed to assist PASI evaluation, we collected 2657 high-quality images from 1486 psoriasis patients, and images were segmented and annotated. Then, we utilized the YOLO-v4 algorithm to establish the model via four modules, we also conducted a human-computer comparison through quadratic weighted Kappa (QWK) coefficients and intra-class correlation coefficients (ICC). The YOLO-v4 algorithm was selected for model training and optimization compared with the YOLOv3, RetinaNet, EfficientDet and Faster_rcnn. The model evaluation results of mean average precision (mAP) for various lesion features were as follows: erythema, mAP = 0.903; scale, mAP = 0.908; and induration, mAP = 0.882. In addition, the results of human-computer comparison also showed a median consistency for the skin lesion severity and an excellent consistency for the area and PASI score. Finally, an intelligent PASI app was established for remote disease assessment and course management, with a pleasurable agreement with dermatologists. Taken together, we proposed an intelligent PASI app based on the image YOLO-v4 algorithm that can assist dermatologists in long-term and objective PASI scoring, shedding light on similar clinical assessments that can be assisted by computers in a time-saving and objective manner.

Successful guselkumab treatment of a refractory psoriasis patient with Graves' disease: a case report.

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn's disease and thyroid diseases. Graves' disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.

Evaluation of linear dermatoses by reflectance confocal microscopy in children.

Lichen striatus (LS), linear psoriasis (LPs), linear cutaneous lupus erythematosus (LCLE) and linear lichen planus (LLP) often have similar clinical manifestations, which makes clinical diagnosis with the naked eye difficult; therefore, they are easily misdiagnosed. The purpose of this study was to determine whether reflectance confocal microscopy (RCM) is helpful in differentiating between these four linear dermatoses in children. This retrospective study included 14 patients with LS, nine with LPs, eight with LCLE and 12 with LLP. All patients were analysed using RCM, and biopsies were collected from lesions previously imaged by RCM. For LS, the dermal papillary rings were partially absent, but when present, manifested with small, homogeneously round, bright cells and occasionally highly refractive plump cellular structures, aggregated in clusters. LPs exhibited dark cyst-like structures with small, bright, round cells aggregated at the epidermal level; at the dermal-epidermal junction, homogeneously distributed, enlarged, faint dermal papillary rings and numerous enlarged low-refractive canalicular structures were observed in the superficial dermis. LCLE and LLP exhibited similar manifestations, including epidermal disarray, almost total absence of dermal papillary rings, and various sized refractive structures densely distributed in the dermis. The key distinguishing features of LCLE were the different sized structures mainly clustered around hair follicles, while LLP demonstrated dense structures with a scattered distribution. RCM may be used to distinguish between the key features of LS, LPs, LCLE and LLP in children.

Efficacy and safety of topical rosuvastatin & melatonin vs. placebo in patients with mild to moderate plaque psoriasis: A preliminary randomized double-blinded clinical trial.

BACKGROUND: Considering the pathogenesis of psoriasis and also the anti-oxidant, immunomodulatory, and anti-inflammatory properties of rosuvastatin and melatonin, the current clinical trial aimed to evaluate the efficacy of topical rosuvastatin and melatonin in patients with mild to moderate psoriasis. METHODS: The current randomized placebo-controlled clinical trial was conducted using a 3-arm parallel group included 77 adult patients (≥18 years old) with mild to moderate plaque psoriasis. Patients were randomized into a 1:1:1 ratio to one of three groups to receive one of the three interventions: melatonin cream, 5.0% (w/w), rosuvastatin cream, 5.0% (w/w), or placebo cream with a similar transparent appearance twice a day for 12 weeks. The primary outcome was severity of the disease using Psoriasis Area Severity Index (PASI). The secondary outcomes included the Dermatological Sum Score (DSS) to assess the erythema, scaling, and plaque elevation and the Dermatology Life Quality Index (DLQI). Photographs of the lesions were also taken at the baseline and at different periodic intervals thereafter. RESULTS: Among 77 randomized patients, 52 (mean (SD) age, 40.67 (10.85) years; 22 (42.30%) men) completed the study. A significant reduction of 45% (mean (SD) of 2.67 (0.98) to 1.74 (1.12)) and 70% (mean (SD) of 2.67 (0.98) to 1.31 (1.13)) in PASI score, and 46% (mean (SD) of 2.91(1.85) to 1.57 (1.11)) and 77% (mean (SD) of 2.91 (1.85) to 0.87 (0.67)) in DSS score on days 30 and 60 with rosuvastatin cream, 5% w/w (P < 0.001) compared with baseline was observed, respectively. Also a significant decrease of 35% (mean (SD) of 2.67 (0.98) to 1.74 (1.12)) and 51% (mean (SD) of 2.67 (0.98) to 1.31 (1.13)) in PASI score, and 40% (mean (SD) of 5.00 (1.58) to 3.00 (1.76))and 61% (mean (SD) of 5.00 (1.58) to 1.92 (1.71)) in DSS score on days 30 and 60 with melatonin cream, 5% w/w (P < 0.001) compared with baseline were observed, respectively. In each of the melatonin or rosuvastatin groups, DLQI improved significantly on days 30 (P < 0.0001) and 60 (P < 0.001) while the changes in the control group were not significant. CONCLUSION: The results of this clinical trial demonstrated that topical melatonin and rosuvastatin diminished the severity of mild to moderate plaque psoriasis with a satisfactory safety profile. Future clinical trials should assess both the long-term efficacy and safety of melatonin and rosuvastatin creams in larger study populations.

Combination of secukinumab and acitretin for generalized pustular psoriasis: A case report and review of literature.

Generalized pustular psoriasis (GPP) is characterized by painful and occasionally disfiguring cutaneous manifestations with sepsis-like systemic symptoms, and is a rare severe variant of psoriasis. Currently, there is no standard treatment for GPP. Here, we report a case of a female patient with ankylosing spondylitis (AS) and mild scalp psoriasis, who developed GPP and alopecia following three courses of adalimumab therapy. The patient's condition gradually improved following cessation of adalimumab and treatment with secukinumab and acitretin. After eight weeks of treatment, the patient achieved almost complete clearance of her psoriasis, her alopecia improved, and her AS was relieved. Therefore, we believe that a combination of secukinumab with acitretin may be a rational approach for the treatment of severe GPP.

Dermoscopy to differentiate clinically similar inflammatory and neoplastic skin lesions.

INTRODUCTION: Over the few last decades, dermoscopy has become an invaluable and popular imaging technique that complements the diagnostic armamentarium of dermatologists, being employed for both tumors and inflammatory diseases. Whereas distinction between neoplastic and inflammatory lesions is often straightforward based on clinical data, there are some scenarios that may be troublesome, e.g., solitary inflammatory lesions or tumors superimposed to a widespread inflammatory condition that may share macroscopic morphological findings. EVIDENCE ACQUISITION: We reviewed the literature to identify dermoscopic clues to support the differential diagnosis of clinically similar inflammatory and neoplastic skin lesions, also providing the histological background of such dermoscopic points of differentiation. EVIDENCE SYNTHESIS: Dermoscopic differentiating features were identified for 12 relatively common challenging scenarios, including Bowen's disease and basal cell carcinoma vs. psoriasis and dermatitis, erythroplasia of Queyrat vs. inflammatory balanitis, mammary and extramammary Paget's disease vs. inflammatory mimickers, actinic keratoses vs. discoid lupus erythematosus, squamous cell carcinoma vs. hypertrophic lichen planus and lichen simplex chronicus, actinic cheilitis vs. inflammatory cheilitis, keratoacanthomas vs. prurigo nodularis, nodular lymphomas vs. pseudolymphomas and inflammatory mimickers, mycosis fungoides vs. parapsoriasis and inflammatory mimickers, angiosarcoma vs granuloma faciale, and Kaposi sarcoma vs pseudo-Kaposi. CONCLUSIONS: Dermoscopy may be of aid in differentiating clinically similar inflammatory and neoplastic skin lesions.

Detection of significant liver fibrosis in Chinese psoriasis patients receiving methotrexate: a comparison between transient elastography and liver histology.

INTRODUCTION: Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. METHODS: This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. RESULTS: A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). CONCLUSION: Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.

Curcumin-Based Ionic Liquid Hydrogel for Topical Transdermal Delivery of Curcumin To Improve Its Therapeutic Effect on the Psoriasis Mouse Model.

Psoriasis is a systemic, recurrent, chronic autoimmune skin disease. However, psoriasis drugs have poor skin permeability and high toxicity, resulting in low bioavailability and affecting their clinical application. In this study, we propose a curcumin-based ionic liquid hydrogel loaded with ilomastat (Cur-Car-IL@Ilo hydrogel), which can effectively maintain the sustained release of drugs and improve the skin permeability of drugs. We used a model of imiquimod-induced psoriasis and demonstrated that local application of Cur-Car-IL@Ilo hydrogel can improve skin lesions in mice with significantly reduced expression levels of inflammatory factors, matrix metalloproteinase 8, and collagen-I. The expressions of iron death-related proteins SLC7A11 and ASL4 were significantly decreased after treatment with Cur-Car-IL@Ilo hydrogel. Flora analysis showed that the content of anaerotruncus, proteus, and UCG-009 bacteria in the gut of psoriatic mice increased. The levels of paludicola, parabacteroides, prevotellaceae_UCG-001, escherichia-shigella, and aerococcus decreased, and the levels of some of the above bacteria tended to be normal after treatment. Therefore, the curcumin-based ionic liquid hydrogel can be used as a multifunctional, nonirritating, noninvasive, and highly effective percutaneous treatment of psoriasis.

Generalized pustular psoriasis in a toddler with IL36RN mutation: a case report.

Generalized Pustular Psoriasis (GPP) is a dermatological autoinflammatory disease that rarely occurs in children and is associated with complex genetic factors. GPP pathogenesis has been associated with mutations in IL36RN gene, which encodes an interleukin-36 receptor antagonist. GPP usually occurs without a history of psoriasis in the patients or their family members. This case report describes the clinical course of a 3-year-old toddler with GPP. The diagnosis of GPP was confirmed through a comprehensive series of examinations, and genetic testing revealed an IL36RN mutation, providing further insight into the genetic basis of the condition. This case highlights the importance of a genetic perspective for diagnosing GPP, particularly in children.

Gasdermin E promotes translocation of p65 and c-jun into nucleus in keratinocytes for progression of psoriatic skin inflammation.

Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme-/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1ß, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.

Single-cell RNA-seq reveals keratinocyte and fibroblast heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis.

The pathogenesis of psoriasis, a chronic inflammatory autoimmune skin disease with a high global prevalence, remains unclear. We performed a high-resolution single-cell RNA sequencing analysis of 94,759 cells from 13 samples, including those from psoriasis model mice and wild-type mice. We presented a single-cell atlas of the skin of imiquimod-induced mice with psoriasis and WT mice, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial-mesenchymal transition and validated the results with drug verification. Moreover, we conducted a tentative exploration of the potential pathways involved and revealed that the IL-17 signalling pathway may be the most relevant pathway. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.

Successful treatment of acrodermatitis continua of Hallopeau coexisting with generalized pustular psoriasis with spesolimab: a case report.

Generalized pustular psoriasis (GPP) is a rare chronic inflammatory pustular dermatosis that presents as painful erythema with sterile pustules on nonacral skin. No unified standard and guideline for the treatment of GPP has been established. Several biologics have been tried for GPP, with varying success. Acrodermatitis continua of Hallopeau (ACH) is a very rare disabling variant of pustular psoriasis characterized by sterile pustules on the fingers and toes, including the nail bed. Comparatively, treating ACH is highly challenging due to its commonly therapy-resistant disease course. The pathogenic role of IL-36 signaling axis has been currently identified in GPP development. Spesolimab, the first anti-interleukin-36 receptor biologic, has been approved for treating GPP flares and shown promising results. In view of a shared pathogenesis between GPP and ACH, specolimab may be an effective treatment for ACH. Currently, there is no case and clinical trial data exist on this condition. Therefore, this case was aim to describe real-world experience of spesolimab use in ACH coexisting with GPP. We report an Asian patient with a 16-year-history of GPP and ACH with marked pustulosis on the nail bed and onychodystrophy. He received conventional systemic regimen acitretin, cyclosporine and biologics adalimumab and secukinumab, but experienced relapse for skin lesions and refractory for nail lesions. He was then treated with a single dose of spesolimab in combination with secukinumab, which resulted in skin clearance and nearly complete resolution of nail lesions over a 32-week period. Our observation suggests that spesolimab should be considered for the treatment of ACH, especially in the patients with intractable nail lesions and concomitant GPP.

Qinzhuliangxue mixture ameliorates psoriasis by restraining apoptosis in psoriasis via downregulating the MDA-5 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is characterized by hyperkeratosis that produces the classic silvery scales, and the pathogenesis of psoriasis involves abnormal proliferation of keratinocytes. Emerging evidence supports that apoptosis regulates keratinocyte proliferation and formation of stratum corneum, which maintains the homeostasis of the skin. Qinzhuliangxue mixture (QZLX) is a representative formula for the treatment of psoriasis, which was earliest recorded in the classic Chinese medicine book Xia's Surgery. In our previous clinical studies, QZLX demonstrated 83.33% efficacy with few side effects in the treatment of psoriasis. Furthermore, our published basic research has also proved that the QZLX mixture effectively inhibits the hyperproliferation of keratinocytes, thus exerting therapeutic effects on psoriasis. However, whether QZLX mixture can regulate keratinocytes apoptosis requires further clarification. OBJECTIVE OF THE STUDY: To investigate the mechanism of QZLX in the treatment of psoriasis from the perspective of keratinocyte apoptosis. MATERIALS AND METHODS: First, psoriasis-like mice with imiquimod (IMQ)-induced were given QZLX intragastric administration and Psoriasis Area Severity Index (PASI) scores were recored for 11 consecutive days to appraise the efficacy. Then, tissue samples were collected for transcriptome analysis. The DEseq2 method detected significantly differentially expressed genes (DEGs), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway databases were used to analyze the functions and pathway enrichment of DEGs. After that, the therapeutic mechanisms of QZLX in intervening with psoriasis were explored using TUNEL, immunohistochemical staining, and western blotting. RESULTS: QZLX ameliorated the symptoms and pathological characteristics of IMQ-induced psoriasis in mice. The epidermal cell hyperplasia in the skin was inhibited, in accordance with the suppressed expression of PCNA and Ki67 after treatment. Transcriptome sequencing showed that melanoma differentiation associated gene-5 (MDA-5) was downregulated. GO and KEGG enrichment analysis of the signaling pathways indicated that the differentially expressed genes were significantly enriched in apoptosis pathways. Besides, QZLX treatment decreased the apoptosis of keratinocyte as shown by reduced TUNEL-positive cells. As MDA-5 protein levels decreased, so did the expression of the downstream protein Caspase-8, which indicates that the apoptotic pathway was triggered. Furthermore, QZLX therapy might also help to balance the apoptotic Bcl-2 family expression. CONCLUSION: QZLX restrains the apoptosis of keratinocyte in psoriasis-like mice by downregulating the MDA-5 pathway. The restoration of the balance between cell apoptosis and proliferation in the skin may lead to considerable psoriasis relief. Our study reveals the possible molecular processes behind the effects of QZLX therapy on the skin lesions of psoriasis, and lends support to its clinical efficacy.

Deep analysis of skin molecular heterogeneities and their significance on the precise treatment of patients with psoriasis.

Background: Psoriasis is a highly heterogeneous autoinflammatory disease. At present, heterogeneity in disease has not been adequately translated into concrete treatment options. Our aim was to develop and verify a new stratification scheme that identifies the heterogeneity of psoriasis by the integration of large-scale transcriptomic profiles, thereby identifying patient subtypes and providing personalized treatment options whenever possible. Methods: We performed functional enrichment and network analysis of upregulated differentially expressed genes using microarray datasets of lesional and non-lesional skin samples from 250 psoriatic patients. Unsupervised clustering methods were used to identify the skin subtypes. Finally, an Xgboost classifier was utilized to predict the effects of methotrexate and commonly prescribed biologics on skin subtypes. Results: Based on the 163 upregulated differentially expressed genes, psoriasis patients were categorized into three subtypes (subtypes A-C). Immune cells and proinflammatory-related pathways were markedly activated in subtype A, named immune activation. Contrastingly, subtype C, named stroma proliferation, was enriched in integrated stroma cells and tissue proliferation-related signaling pathways. Subtype B was modestly activated in all the signaling pathways. Notably, subtypes A and B presented good responses to methotrexate and interleukin-12/23 inhibitors (ustekinumab) but inadequate responses to tumor necrosis factor-α inhibitors and interleukin-17A receptor inhibitors. Contrastly, subtype C exhibited excellent responses to tumor necrosis factor-α inhibitors (etanercept) and interleukin-17A receptor inhibitors (brodalumab) but not methotrexate and interleukin-12/23 inhibitors. Conclusions: Psoriasis patients can be assorted into three subtypes with different molecular and cellular characteristics based on the heterogeneity of the skin's immune cells and the stroma, determining the clinical responses of conventional therapies.

Dual blockade of interleukin-17A and interleukin-17F as a therapeutic strategy for liver fibrosis: Investigating the potential effect and mechanism of brodalumab.

Liver fibrosis is a terminal manifestation of various chronic liver diseases. There are no drugs that can reverse the condition. Recently, the importance of interleukin-17 (IL17) in the pathophysiology has been revealed and has attracted attention as a therapeutic target. We aimed to reveal the roles of IL17A and IL17F in liver fibrosis, and to validate the potential of their dual blockade as therapeutic strategy. First, we retrospectively reviewed the longitudinal change of FIB-4 index, a clinical indicator of liver fibrosis, among psoriasis patients treated by brodalumab, which blocks IL17 receptor A (IL17RA). Next, we examined anti-fibrotic efficacy of anti-IL17RA antibody (Ab) in two murine liver fibrosis models by histopathological investigation and real-time reverse transcription polymerase chain reaction (RT-PCR). Finally, we analyzed the effect of IL17A and IL17F upon human hepatic stellate cells with RNA sequencing, real-time RT-PCR, western blotting, chromatin immunoprecipitation, and flow cytometry. Clinical data showed that FIB-4 index significantly decreased among psoriasis patients treated by brodalumab. In vivo studies additionally demonstrated that anti-IL17RA Ab ameliorates liver fibrosis induced by tetrachloride and methionine-choline deficient diet. Furthermore, in vitro experiments revealed that both IL17A and IL17F enhance cell-surface expression of transforming growth factor-ß receptor II and promote pro-fibrotic gene expression via the JUN pathway in human hepatic stellate cells. Our insights suggest that IL17A and IL17F share their pro-fibrotic function in the context of liver fibrosis, and moreover, dual blockade of IL17A and IL17F by anti-IL17RA Ab would be a promising strategy for the management of liver fibrosis.

Real world insights for psoriasis: the association of severity of skin lesions with work productivity, medical consumption costs and quality of life.

BACKGROUND: Psoriasis is a prevalent, chronic skin disease with a potential impact on work productivity, medical consumption costs, and quality of life. The influence of the extent of skin lesions on these outcomes is not well known. OBJECTIVE: We determined associations of self-reported skin lesions with self-reported work productivity, medical consumption costs, and health-related quality of life in respondents with psoriasis. METHODS: In this cross-sectional study, we included respondents with self-reported psoriasis in the Netherlands in an online questionnaire. We assessed the self-reported percentage body surface area (BSA) of psoriasis lesions. We used validated instruments to assess work productivity (WPAI-PsO), medical consumption costs (iMCQ), and health-related quality of life (EQ-5D-5L and the DLQI). We used ordinal logistic regression to associate BSA categories >1% versus 0-1% with outcomes adjusted for multiple confounders. RESULTS: We included 501 respondents with a mean age of 43 ± 12 years; 64% were men. Median BSA was 2% (interquartile range 1-5%). A higher BSA was associated with higher overall work impairment due to psoriasis (common odds ratio [cOR] 2.44, 95% confidence interval [CI] 1.40-4.29; n = 205), higher medical consumption costs (cOR 2.06, 95% CI 1.45-2.94) and lower health-related quality of life. Associations were strongest with a BSA cutoff of 0% or 1% compared to 2% or higher categories. DISCUSSION: In our study, having few to no lesions in psoriasis was associated with lower overall work impairment due to psoriasis, lower medical consumption costs, and higher health-related quality of life.

Acute methotrexate toxicity in a patient with psoriasis: a case report.

Aside from rheumatoid arthritis, methotrexate is also used to treat cancer, psoriasis, and other diseases. Side effects with methotrexate are possible, as they are with any medication. This drug is extremely potent and has the potential to produce serious adverse effects. Those who use this medication need to be tracked often. We provide a case of a patient with psoriasis vulgaris who died due to methotrexate administration without proper dosage verification. A female patient in her forties had a history of psoriasis vulgaris of the lower limbs. Under treatment, she developed acute methotrexate toxicity. This drug was taken as an intramuscular injection per day in an infirmary without checking that the dose regimen prescribed was per week. She developed extensive bullous and pustular lesions associated with digestive signs related to generalized toxiderma. But at that point, she had septic shock, which led to her death a few weeks after the methotrexate injection. The medical responsibilities of the doctor, pharmacist, and nurse were discussed. To conclude, methotrexate is not a killer drug in most cases, but it can be extremely harmful if it's overused. Acute toxicity is a potentially fatal condition, and a deeper understanding of its potential toxicity is still necessary.

Pentraxin 3 exacerbates psoriasiform dermatitis through regulation of macrophage polarization.

OBJECTIVE: To elucidate the mechanism of Pentraxin 3 (PTX3) in the pathogenesis of psoriasiform dermatitis using Ptx3-knockout (Ptx3-KO) background mice. METHODS: An Imiquimod (IMQ)-induced murine psoriatic model was created using Ptx3-KO (Ptx3-/-) and wild-type (Ptx3+/+) mice. Skin lesion severity and expression of inflammatory mediators (IL-6 and TNFα) were assessed using PASI score and ELISA, respectively. Cutaneous tissues from the two mice groups were subjected to histological analyses, including HE staining, Masson staining, and Immunohistochemistry (IHC). The PTX3, iNOS, COX2, and Arg1 expressions were quantified and compared between the two groups. We used RNA-seq to clarify the underlying mechanisms of the disease. Flow cytometry was used to analyze systemic Th17 cell differentiation and macrophage polarization. RESULT: The psoriatic region exhibited a higher PTX3 expression than the normal cutaneous area. Moreover, PTX3 was upregulated in HaCaT cells post-TNFα stimulation. Upon IMQ stimulation, Ptx3-/- mice displayed a lower degree of the psoriasiform dermatitis phenotype compared to Ptx3+/+ mice. Consistent with the RNA-seq results, further experiments confirmed that compared to the wild-type group, the PTX3-KO group exhibited a generally lower IL-6, TNFα, iNOS, and COX2 expression and a contrasting trend in macrophage polarization. However, no significant difference in Th17 cell activation was observed between the two groups. CONCLUSIONS: This study revealed that PTX3 was upregulated in psoriatic skin tissues and TNFα-stimulated HaCaT cells. We also discovered that PTX3 deficiency in mice ameliorated the psoriasiform dermatitis phenotype upon IMQ stimulation. Mechanistically, PTX3 exacerbates psoriasiform dermatitis by regulating macrophage polarization rather than Th17 cell differentiation.