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Objective To investigate the efficacy and safety of Sonidegib for basal cell carcinoma. Methods Clinical data and skin histology were analyzed in a patient with ulcerated brown plaque on the nasal dorsum. After the diagnosis of basal cell carcinoma, patient was orally given a Hedgehog pathway inhibitor, Sonidegib. Results The patient was diagnosed with basal cell carcinoma. After the treatment with Sonidegib, the skin lesions became flat and ulcers were healed, without the development of new ulcers. Prior to the treatment, patient's liver and muscle enzymes were normal. Following one-week treatment with Sonidegib, the patient experienced muscle weakness, loss of appetite, vomiting, fatigue, and drowsiness, with an EGOG level of 3. After 4 weeks of treatment, the liver enzymes and serum CK were 2.5 times over normal levels. Sonidegib was discontinued at week 6 due to his intolerance of side effects. Then the patient was given the Mohs surgery and skin grafting. Conclusions Sonidegib can induce liver damage and musculoskeletal reactions. Adverse reactions should be dynamically monitored in clinical use of this drug. If the tumor is large or direct surgical removal may cause severe trauma, neoadjuvant therapy can be beneficial. In clinic, drugs can be intermittently administered according to patients' tolerance to improve tolerance and adherence.

Objective To investigate the target of indirubin in psoriasis, and to elucidate the possible effect of indirubin on psoriasis through MAPK14. Methods The GSE30999 and GSE78097 psoriasis datasets downloaded from the Gene Expression Omnibus (GEO) database were used as training and validation sets, respectively. The differentially expressed genes were screened, and their biological functions and pathways were analyzed. Intersections with indirubin target genes were used to obtain differentially expressed indirubin target genes. Meanwhile gene correlation was analyzed and differential gene expression was verified. LASSO and Cox regression model were used to screen the best target genes for indirubin. Molecular docking of indirubin was performed to analyze the structural relationship. Results A total of 8 indirubin target genes were found in the GSE30999 dataset, which were differentially expressed compared with the control group. Seven genes had high diagnostic value (AUC>0.8), and one gene had low diagnostic value (AUC>0.6). GO and KEGG enrichment analyses showed that the eight indirubin target genes were mainly related to cell aging, chemical carcinogenic receptor activation, lipid and atherosclerosis, acute myeloid leukemia, and AGE-RAGE signaling pathways in diabetic complications. The best target gene of indirubin, MAPK14 gene, was screened by LASSO and Cox regression model. Molecular docking suggested that indirubin was tightly bound to MAPK14. Conclusion Indirubin may be involved in the regulation of the pathogenesis and treatment of psoriasis through MAPK14.

Objective To evaluate the efficacy and safety of Spesolimab in the treatment of generalized pustular psoriasis(GPP). Methods A 30 years old female with GPP was intravenously given 900 mg of Spesolimab once. The safety and the changes in modified generalized pustular psoriasis area severity index (GPPASI) and generalized pustular psoriasis physician global assessment (GPPGA) were evaluated. Results After 1 week of the treatment, the GPPGA reached 2. After 2 months of the treatment, pustules almost completely subsided and both GPPASI and GPPGA reached 1. During the treatment, the patient developed anaphylactic adverse reactions, which were improved following the injection of betamethasone, antihistamine and symptomatic therapy. Conclusion Spesolimab is an effective and safe agent for the treatment of generalized pustular psoriasis.

Objective To investigate the expression and regulatory mechanism of PTPN2 in psoriasis, and to analyze the effects of PTPN2 on psoriasis related immunity in order to determine whether PTPN2 can be used as a potential therapeutic target for psoriasis. Methods R language (3.6.3 version) was used to determine the difference in expression levels of PTPN2 between psoriatic patients and controls, and the receiver operating characteristic (ROC) curve of PTPN2. The Gene Enrichment Analysis software (GSEA) and the Protein Interaction Analysis Database (STRING) were used to determine enrichment pathway of PTPN2 in the psoriasis dataset, and the interaction network of PTPN2 co-expressed genes. The distribution and expression of immune cells in psoriasis datasets were analyzed with CIBERSORT software. The differential expression of immune response pathways and immune response gene sets in psoriasis and their correlation with PTPN2 were analyzed using R language (version 3.6.3). Results PTPN2 mRNA was highly expressed in psoriatic lesions. Immune infiltrating cells, immune response pathways, and immune response gene sets were abnormal in psoriatic lesions. PTPN2 was associated with some immune infiltrating cells, immune response pathways, and immune response gene sets in psoriasis. Conclusions PTPN2 mRNA is highly expressed in psoriatic lesions, and may participate in the occurrence and development of psoriasis by regulating the immune microenvironment.

Objective To report a case of hemophagocytic lymphohistiocytosis syndrome (HLH) secondary to systemic hydroa vacciniforme lymphoproliferative disorder (systemic HVLPD) and review relevant literature, in order to improve understanding of the disease. Methods Clinical data of the case, laboratory examination, histopathology, immunohistochemistry, TCR gene rearrangement, and whole exon gene sequencing were collected for analyses. Results A 19 years old man was admitted to the hospital due to generalized papules, blisters, necrotic scabs and fever for 7 months. The clinical manifestations included hydroa vacciniforme-like rashes, lymphadenopathy, splenomegaly, pancytopenia, hypertriglyceridemia, decreased NK cell activity, high levels of sIL-2r, positive for VCA-IgA and EA-IgA, and elevated EBV DNA load. The whole exon sequencing did not show pathogenic gene mutations. Histopathological changes in the skin lesions included liquefaction degeneration of epidermal and follicular basal cells, pigmentary incontinence, lymphocytic infiltrates of the epidermis and follicular epithelium, perivascular and perifollicular infiltrates of lymphocytes and eosinophils in the dermis, extravasation of erythrocytes, as well as focal infiltrates of atypical lymphoid cells around appendages and small blood vessels. Pathologic mitosis was visible. Immunohistochemistry showed CD3 (+), CD5 (+), CD20 (individual+), CD30 (small patch+), CD79a (individual+), CD4 (+), CD7 (+), CD8 (+), TIA-1 (+), CD56 (scattered lymphocyte+), ≈50% of Ki-67(+), and in situ hybridization EBER (+). TCRβ gene monoclonal rearrangements were detected. According to the results of clinical and auxiliary examination, patient was diagnosed with HLH secondary to systemic HVLPD. After 8 months of follow-up, the patient passed away while waiting for transplantation of allogeneic hematopoietic stem cells. Conclusions Systemic HVLPD is rare and requires vigilance for the development of secondary hemophagocytic syndrome. The awareness of hemophagocytic syndrome should be improved to avoid possible misdiagnosis and delayed treatment.

Objective To report a case of hereditary skin disease mainly characterized by burning pain of the lower legs and feet, accompanied by flush and elevated skin temperature, and to identify the pathogenic genes and mutation sites in order to explore effective treatment methods. Methods The clinical data of the case were collected and peripheral blood was taken from the patient and relatives to extract genomic DNA. Next-generation sequencing of hereditary skin disease genes was performed, and suspected pathogenic mutations were verified with Sanger sequencing. The patient was treated with aspirin for anti-inflammation, rizatriptan benzoate tablet, mexiletine hydrochloride, carbamazepine, local injection of botulinum toxin analgesia, topical compound polymyxin B ointment and cooling therapy. Results A heterozygous mutation of SCN9A:NM_002977.3:c.688+142G>A or SCN9A:ENST00000375387.4:c.626G>A was detected in the patient's peripheral blood genomic DNA. The same mutation was found in the patient's sister, an uncle and a cousin. Based on the pathogenic gene and clinical manifestations, the patient was diagnosed with primary erythromelalgia (PEM). After the treatment, the pain was significantly alleviated. Conclusions The intron mutation of NM_002977.3:c.688+142G>A or missense mutation c.626G>A(p.Gly209Asp) of the SCN9A gene is the cause of PEM in this case. Combination therapy of aspirin, rizatriptan benzoate, mexiletine hydrochloride, carbamazepine and local treatment can effectively control the symptoms of PEM, reduce the frequency of acute attacks and improve the prognosis.

Objective To investigate the mechanisms of nicotinamide phosphoribosyl transferase (NAMPT) in the pathogenesis of psoriasis and to elucidate the effect of NAMPT on the nicotinamide adenine dinucleotide (NAD+) metabolic pathway in psoriasis. Methods Mitophagy gene and psoriasis microarray datasets were downloaded from the human autophagy gene database and GEO database to screen differentially expressed genes (DEGs) of mitophagy. Validation and assessment were performed by differential expression and receiver operating characteristic (ROC) curve analysis. LASSO and COX regression models were used to screen signature genes. Gene correlation and functional analysis were performed using Pearson and gene enrichment analysis (GSEA). Results A total of 16 differentially expressed mitophagy genes were identified in psoriasis, which all were highly expressed in psoriasis with high diagnostic value. The DEGs of mitophagy were mainly associated with NOD-like receptor signaling pathway, autophagy-animal, influenza A, chemo carcinogenic-receptor activation and lipid/atherosclerotic pathways. NAMPT was identified as a signature gene of psoriasis, mainly associated with the proteasome, pyrimidine metabolism, ubiquitin-mediated proteolysis, DNA replication, antigen processing and presentation, aminoacyl tRNA biosynthesis, cytoplasmic DNA sensing pathway, oocyte meiosis, homologous recombination and TOLL-like receptor signaling pathway. In psoriasis, NAD metabolic pathways were activated and positively correlated with NAMPT. In the NAD+ metabolic pathway, expression levels of BST1 were low and negatively correlated with NAMPT. In contrast, expression levels of PARP9 and PNP were high and positively correlated with NAMPT. Conclusions In psoriasis, NAMPT is highly expressed and NAD+ metabolic pathway is activated. Expression levels of NAMPT are positively correlated with the activity of NAD+ metabolic pathway. NAMPT may be involved in the pathogenesis of psoriasis through BST1, PARP9 and PNP in the NAD+ metabolic pathway.

We report a case of eosinophilic fasciitis. A 58-year-old man complained of muscle weakness and stiffness, and joint pain of the limbs for 11 months. Dermatological examination revealed groove sign, which became more prominent when raising the arm. The skin of the forearms and calves was waxy appearance and tight. Muscle weakness and pain were apparent. The laboratory examination showed the absolute eosinophil count was 1.51×109/L in December, 2020, and 0.45 ×109/L in June, 2021. The erythrocyte sedimentation rate was 104 mm/h. Other test results were immunoglobulin G (IgG) 32.7 g/L, C3 0.881 g/L, gamma globulin 36.5%, and the anti-Scl-70 antibody (negative). The histopathology of the lesion on the right forearm was manifested by epidermal atrophy, collagen thickening in the fascia, hyaline degeneration, perivascular infiltration of plasma cells, lymphocytes, and eosinophils, remarkable reduction in elastic fibers in the fascia, and alcian blue stain(+). Patient was diagnosed with eosinophilic fasciitis. The patient refused the treatment with baricitinib and was without follow up.

Objective Using bioinformatic technique to identify key genes and pathways involved in the pathogenesis of pemphigus foliaceus (PF), in order to elucidate the pathogenesis of PF. Methods Gene microarray dataset GSE53873 of peripheral blood CD4+ T cells from PF patients was obtained from Gene Expression Omnibus database, and various bioinformatics methods such as Limma difference analysis, gene function and pathway enrichment analysis, and protein-protein interaction network analysis were integrated to determine the key genes and pathways associated with PF. Results A total of 121 significantly upregulated genes and 48 significantly downregulated genes were identified in PF patients compared with healthy controls. The differentially expressed genes in PF patients were involved in multiple functions such as T cell differentiation, T cell activation, leukocyte differentiation and metabolism. CXCL10 and OAS1 were identified as key genes in the pathogenesis of PF. Receiver operating characteristic (ROC) results suggested that CXCL10 (AUC=0.86) and OAS1 (AUC=0.86) had high diagnostic efficacy for PF. Gene function and pathway enrichment analysis indicated that CXCL10 was mainly associated with TOLL-like receptor signaling pathway, COVID-19 infection, and cytokine interaction, while OSA1 was mainly associated with viral infection and type I interferon signaling pathway. Conclusions CXCL10 and OAS1 are the key genes associated with PF. The pathogenesis of pemphigus is associated with pathways such as T cell differentiation and activation, leukocyte differentiation and metabolism.

Objective To investigate the roles of cytokines, IL-36γ and IL-38, in the inflammatory response in psoriasis vulgaris. Methods Both serum and peripheral blood mononuclear cells (PBMC) were collected from 29 patients with psoriasis vulgaris (PV) and 19 healthy controls. PV group was divided into mild to moderate group (n=14) and severe group (n=15) according to psoriasis area and severity index (PASI). In addition, serum and PBMC were collected from 12 PV patients before and after the treatment with IL-17A monoclonal antibody (IL-17A mAb). Serum levels of IL-36γ and IL-38 were measured using ELISA, and the relative expression levels of IL-36γ and IL-38 mRNA in PBMC were determined using RT-quantitative real-time PCR (RT-qPCR). Moreover, human immortalized keratinocytes (HaCaT) cocultured with IL-17A were sampled at different time points to measure expression levels of IL-36γ and IL-38 mRNA. Results Serum IL-36γ levels were significantly higher in patients with either mild to moderate or severe psoriasis than in healthy controls (t=12.27 and 16.45, respectively, P

Objective To detect the expression and localization of Sprouty 2, E-cadherin (E-cad) and Ki-67 in skin tissue of squamous cell carcinoma (CSCC), and to analyze the correlation of Sprouty 2 with E-cad and Ki-67. Methods From March 2018 to July 2018, cancerous tissues (squamous cell carcinoma group), paracancerous tissues (paracancer group), normal skin tissues (case control group) were collected from 15 patients with cephalic and facial CSCC and 10 cases of control normal skin specimens (healthy control group) at Dermatology Hospital of Southern Medical University. Expression and localization of Sprouty 2, E-cad and Ki-67 were detected by qRT-PCR, Western blot and immunohistochemical staining. Results Immunohistochemistry showed that Sprouty 2 was expressed in the keratinocytes and cytoplasm of the whole epidermal layer in all groups. E-cad was expressed in the cell membrane of keratinocytes of all epidermal layers in all groups. Ki-67 was localized in keratinocytes of the basal layer and lower spinous layer in all groups. qRT-PCR and Western blot showed that the mRNA and protein expression in squamous cell carcinoma group were lower than that in paracancer group, case control group and healthy control group (mRNA 0.03±0.03 vs. 0.28±0.36,0.92±0.60, 1.12±0.56; protein 0.68±0.47 vs 1.40±0.72, 1.59±0.86, 1.71±1.28, all P

We report a case of skin damage due to overdose methotrexate poisoning. A 74-year-old woman presented with erythema and desquamation of trunk and limbs accompanied with pain for 8 days. Before admission, MTX 5 mg/d was taken orally for 10 days, and the accumulative dose was 50 mg. On the third day of taking the medicine, erythema and desquamation appeared all over the body. Dermatology examination revealed that oral mucosal erosion and skin of trunk and limbs with erythema diffuse distributed, and erosion oozing on the surface of skin desquamated and some areas. Laboratory examinations revealed that the decreased number of leukocyte and platelets and elevated transaminase. The case was diagnosed with methotrexate poisoning. The patient was treated with Leucovorin, methylprednisolone, hydration, alkalized urine, recombinant human granulocyte stimulating factor, recombinant human thrombopoietin, topical medicine, and other symptomatic and supportive treatments. After 2-week treatments, the patient recovered.

The increasing evidence showed that psoriasis and inflammatory bowel disease are now considered as chronic systemic inflammatory diseases, and they are comorbidities for each other. Due to multiply overlapping pathophysiological mechanisms, drugs targeting to their common pathways have become hot spots in the current treatment of these two comorbidities. This review summarizes the common pathways involved in psoriasis and inflammatory bowel disease, including extracellular tumor necrosis factor, IL-23, IL-17 signaling pathways, as well as intracellular JAK-STAT pathway, cAMP signaling pathway, and ROR-γT/Th17 axis. Additional, this paper also briefly summarizes the drugs targeting to these common pathways. Altogether, the paper can provide some ideas for clinical treatment of these two comorbidities.

Objective To explore the function and mechanism of lncRNA on the cell cycles in psoriasis. Methods We first identified the differentially expressed genes through integrative analysis of RNA-seq datasets from a psoriasis cohort. Then KEGG analysis was performed to identify the key signaling pathways in psoriasis. WGCNA was used to construct the lncRNA-protein coding genes (PCGs) co-expression network. A specific siRNA was used to knockdown LINC01206 in HaCaT keratinocytes and the cell cycle progression was detected by flow cytometry. Results Integrative analysis of RNA-seq datasets from the psoriasis cohort demonstrated a dysregulation of the cell cycle pathway in psoriasis. Moreover, lncRNA-protein coding gene (PCGs) co-expression analysis showed that LINC01206, LINC01269, LINC01215and LINC02159 interacted with the key factors CCNA2, CCNB1 and CCNE1, in cell cycle pathway to regulate the progress of psoriasis. Flow cytometry analysis showed that knockdown of LINC01206 induced cell cycle arrest at the G2/M phase. Conclusions Our results demonstrate the functional mechanism of lncRNAs in the cell cycle. LncRNA may be a therapeutic target for psoriasis.

A case of epidermolytic palmoplantar keratosis caused by KRT9 mutation is reported. A 32-year-old Chinese man presented with a 30-year history of palmoplantar hyperkeratotic plaques. Dermatological examination showed the hyperkeratotic plaques on bilateral palms and soles, and rough thickened skin in gray-yellow color. The histopathology revealed markedly epidermolytic hyperkeratosis, acanthosis and vacuolar changes of the stratum granulosum. Whole-exome sequencing showed a exon mutation of KRT9 gene [c. 487C>T (p. Arg163Trp) ]. The patient was diagnosed as epidermolytic palmoplantar keratosis.

Objective: To investigate the effect of indirubin on the expression of proinflammatory cytokines in HaCaT cells, and to elucidate the mechanisms of Diqing ointment in the treatment of psoriasis. Methods: The human immortalized keratinocyte cell line, HaCaT cells, were used to observe the changes in the expression levels of IL-1β, IL-6, and TNF-α in HaCaT cells after treatment with different concentrations of indirubin. HaCaT cells were divided into 4 groups. The secretion levels of IL-1β, IL-6, and TNF-α in the culture supernatants were detected by enzyme-linked immunosorbent assay ELISA, and the expression levels of IL-1β, IL-6, and TNF-α mRNA were detected by real-time PCR (RT-qPCR). Results: Expression levels of both mRNA and protein of IL-1β, IL-6, and TNF-α were significantly and dose-dependently decreased after treatment with indirubin. Conclusion: Indirubin, the main component of Qingdai ointment, can lower expression levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in keratinocytes, leading to the improvements of psoriasis.

Objective: To explore the effect of YangxueJiedu decoction on IL-36 expression in a mouse model of imiquimod-induced psoriasis-like lesions. Methods: Eighteen mice were randomly divided into the control, model and experimental groups, with 6 mice per group. The psoriasis severity was assessed by PASI score. The expression levels of mRNA for IL-36α, IL-36β, IL-36γ, and IL-36Ra were measured by RT-qPCR. Expression levels of IL-36β protein were evaluated by both Western blot and immunohistochemistry. Results: PASI scores were significantly lower in experimental group than in the model group (1.17±0.37 vs 7.83±0.69, t=19.07, P