Dermoscopy is an important non-invasive form of examination that plays a critical role in the diagnosis of rheumatic diseases accompanied by skin lesions. This technique is performed in real-time and can thus assist in determining the skin biopsy site. Skin lesions are common and important manifestations of most rheumatic diseases, including lupus erythematosus. In some rheumatic diseases, such as rheumatoid arthritis, the incidence of skin rashes may not be as high; however, those lesions that do develop can be diverse and deceptive, thereby complicating diagnosis. Dermoscopy and the observation of microscopic characteristics can assist in diagnosing primary diseases in their early stages. Herein, we present a protocol that provides a detailed overview of the standardized operation process of dermoscopy. Further, using discoid lupus erythematosus as an example, we demonstrate the important role of dermoscopy in the diagnosis of many different rheumatic diseases. Finally, we discuss the diverse dermoscopic manifestations of different rheumatic diseases and their associated skin lesions.

Pemphigus vegetans (P Veg), the rarest subtype of pemphigus, is characterized by vegetative plaques, primarily affecting intertriginous areas. The most common autoantibodies target desmoglein 3 (Dsg3). A 60-year-old female patient presented with well-demarcated red vegetative plaques on her feet, vulva, and thigh, accompanied by surrounding pustules. Histopathological examination revealed epidermal hyperplasia with significant infiltration of neutrophils and eosinophils in the dermis. Enzyme-linked immunosorbent assay showed elevated anti-Dsg3 antibodies (203.2 U/ml), and immunohistochemical staining confirmed positive expression of anti-Dsg3 IgG antibodies in keratinocytes. The patient was diagnosed with P Veg and achieved remission after treatment with either 900 mg of intravenous spesolimab or oral methylprednisolone.

Discoid lupus erythematosus (DLE) is the most common variant of cutaneous lupus erythematosus (CLE). It typically affects the scalp, face, auricle, and lips. When lesions extend beyond these areas to involve the trunk and limbs, the condition is termed disseminated DLE (DDLE). The pathognomonic skin lesions present as well-demarcated discoid erythematous plaques with firmly adherent scales or crusts, central atrophy, characteristic scarring, and pigmentary changes, potentially leading to irreversible scarring alopecia. Histopathological and immunopathological examination of the skin lesions is instrumental in diagnosing DLE. Histologically, DLE is characterized by hyperkeratosis, follicular plugging, focal epidermal thinning, vacuolar alteration of the dermo-epidermal interface, thickening of the epidermal basement membrane, and a superficial and deep perivascular and periadnexal lymphocytic infiltrate, often in conjunction with interstitial mucin. Direct immunofluorescence (DIF) may reveal deposits of immunoglobulins and complement at the dermo-epidermal junction (DEJ). The following article outlines the protocols for DLE lesion assessment, skin biopsy procedures, histopathological and immunopathological analysis, and management options, with the aim of providing a comprehensive, standardized, and replicable diagnostic and therapeutic process to assist clinical physicians in practice.

Background:To investigate the clinical efficacy of narrow-margin modified Mohs microsurgery (mMMS) in the treatment of extramammary Paget's disease (EMPD). Methods:A retrospective cohort review was conducted on 52 patients with EMPD who were treated at the Skin Disease Hospital of Tongji University in Shanghai between 2017 and 2023. The primary objectives of this study were to assess the long-term local recurrence rates of tumors treated with narrow-margin mMMS and to explore the final margin width as well as the factors that may influence postoperative recurrence. Results:A total of 52 patients were included in this retrospective study. Most patients were male (n = 48, 92.3%) with a mean age of 69.5 years (SD:9.08, range:44-91). The follow-up rate was 78.7% (41/52), and the mean follow-up time was 36.17 months (SD:18.25, range 5.8-62.5). The recurrence rate was 9.7% (4/41) and the 5-year tumor-free rate was 85.9%. Approximate 95% of tumors with 1 cm of non-scrotal skin extension or 1.5 cm of scrotal skin extension could be completely cleared. Univariable analysis revealed that hypopigmented patches (HR=14.0, 95% CI=1.269,154.395, p = 0.031) correlated with tumors recurrence. Conclusion:Narrow-margin mMMS is the ideal therapy combine a disease control rate with more satisfying functional results. Determination of tumor boundaries requires attention to skin lesions with hypopigmented macules. The initial resection margins width of the extension cut can be reduced in non-scrotal skin lesions at the time of surgery to minimize pointless margin expansion.

To the Editor: Porokeratosis (PK) is a primary disorder of the epidermis that is characterized by annular plaques with an atrophic center and hyperkeratotic edges.1 According to the clinical manifestations, 6 clinical types of PK are currently known: PK of Mibelli, actinic PK, disseminated superficial actinic PK, linear PK, punctate PK, and genitogluteal PK. Here, we describe a case of PK in an elderly woman who presented with hypokeratosis, which was indicative of circumscribed palmar or plantar hypokeratosis (CPH). CPH was first described and named by Pérez et al2 in 2002, and several cases were later reported. However, to the best of our knowledge, only one other case of PK concomitant with CPH has been reported before.3 Therefore, the findings of this case would be valuable for the differential diagnosis of similar cases in the future. A 74-year-old woman presented with lesions on the thenar area of the right palm that had first appeared 9 years ago and had gradually increased in size due to repeated scratching and irritation, and it was occasionally accompanied by itching. However, she had not sought treatment at the time. She did not have a history of chronic diseases, such as diabetes and hypertension. A cutaneous examination revealed a well-defined, reddish, annular plaque about 2 × 3 cm in size, with hyperkeratotic edges (Fig. 1). Initial histopathological examination of a paraffin-embedded section showed an abrupt decrease in the thickness of the stratum corneum that resembled a vertical knife cut and had a reduced granular layer below. Dyskeratotic cells were observed at the junction of the 2 layers. The spinous layer was thickened and extended into the dermis. The superficial dermis contained a sparse, perivascular, predominantly lymphocytic infiltrate (Fig. 2). Further examination of a deeper section revealed the presence of an incomplete cornoid lamella above the aforementioned dyskeratotic cells that was located in the area where the stratum corneum was reduced. On the basis of the histopathological findings, a definite diagnosis of PK was made.FIGURE 1.: Clinical presentation. A pale red elliptical plaque on thenar eminence of the right hand, characterized by a well-defined border, mildly elevated margins, and central depression.FIGURE 2.: Pathological features. An abrupt decrease in the thickness of the stratum corneum, resembling a vertical knife cut, with reduced granular layer below. Dyskeratotic cells were observed at the junction. The spinous layer was thickened, extending downward into the dermis. A few inflammatory cells infiltrated around superficial dermal blood vessels (A, H&E, ×20). An abrupt decrease in the thickness of the stratum corneum, with absence of the granular layer. Dyskeratotic cells were observed at the junction (B, H&E, ×40). The deeper pathological examination demonstrated an abrupt thinning of the stratum corneum and a reduction in the underlying granular layer at the site of the skin lesion. At the junction and within the area of decreased cornification, 2 incomplete cornoid lamellae were observed inserting into the epidermis, accompanied by a cluster of dyskeratotic cells below (C, H&E, ×40). The deeper pathological examination revealed the insertion of cornoid lamellae into the epidermis, with underlying dyskeratotic cells, absence of the granular layer, and vacuolar degeneration (D, H&E, ×100).While the patient presented with the characteristic histopathological findings of PK: cone-shaped lamellar parakeratosis columns extends throughout the stratum corneum, the underlying granular layer is either absent or markedly reduced, and vacuolar degeneration. Furthermore, a distinct feature of this case was reduced keratinization. It should be noted that in the initial pathological examination, typical cornoid lamellae were not observed, and only abrupt thinning of the stratum corneum and a reduction in the underlying granular layer were observed. This presentation closely resembled that of CPH. However, the clustering of dyskeratotic cells, the presence of epidermal hyperplasia beneath the reduced keratinization layer, the thickening of the spinous layer, and more pronounced infiltration of inflammatory cells in the superficial dermis were less consistent with the features of CPH. In addition, the lesion clinically presented as a central depression on a patch, rather than a simple concave shape. Based on these findings, we performed a deeper sectioning of the original paraffin block and ultimately confirming the diagnosis. Based on Groysman et al's4 classification of CPH, it may be appropriate to diagnose pseudo-CPH concurrently, which refers to secondary keratinization abnormalities resulting from trauma and certain skin diseases, such as traumatic poroma, dermatofibroma, common warts, and squamous cell carcinoma. In the one other case of PK occurring with hypokeratosis reported previously by Kim et al,3 the clinical and histopathological manifestations were consistent with the patient's manifestations. However, in their case, the lesions were smaller, and the hyperplasia was not as pronounced. Given the rarity of these cases, the connection between PK and hypokeratosis is unclear. Some viewpoints suggest that CPH is associated with localized developmental abnormalities of the epidermis and clonal proliferation of genetically abnormal keratinocytes.5 This mechanism shares similarities with the pathogenesis of PK, indicating a potential common pathway or link between the 2 conditions. Accordingly, Blanco-Barrios et al6 also proposed a possible association between PK and CPH. This type of isolated palmoplantar PK does not correspond to any of the existing 6 clinical types, and the coexistence of localized hypokeratosis in the histopathological findings may represent a distinct variant. Further observation and research are needed to explore the current classification of PK, as well as the pathogenic mechanisms of and the relationship between PK and hypokeratosis in patients with this presentation. This case provides valuable insights into the histopathological features of CPH and demonstrates that its features can be similar to those of palmoplantar PK. Therefore, when clustered dyskeratotic cells, parakeratosis, and inflammatory cell infiltration are observed, it is advisable to section multiple areas and search for evidence of PK.

Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily (TNFSF). It acts through its receptor fibroblast growth factor-inducible 14 (Fn14). Studies have indicated that TWEAK/Fn14 pathway activation controls multiple cellular responses, including proliferation, angiogenesis and induction of inflammatory cytokines. TWEAK/Fn14 is manifested in many tissues of our body and most importantly in the skin causing inflammation and many autoimmune and neoplastic cutaneous disorders. Evidence suggests that the TWEAK/Fn14 axis, the downstream signalling pathway and its inflammatory molecular expressions are involved in the pathogenesis of many cutaneous disorders such as psoriasis, atopic dermatitis (AD) vitiligo and melanoma. So, this literature review describes a brief introduction of TWEAK and TWEAK/Fn14 pathway and summarises the case-series and open-label studies performed in the field of dermatology and its potential therapeutic benefit.

Context . In the process of combating the coronavirus disease 2019 (COVID-19) epidemic, medical personnel were at the forefront of the fight. As the future medical workforce, medical students often experienced firsthand how their seniors and teachers had to commit to working hard in combating the epidemic. Many were directly involved in the front line of the fight and that experience could easily have affected their intention to seek employment in a medically related career. Objective . The study intended to evaluate the impact of the COVID-19 pandemic on Chinese medical students' employment intentions and the factors associated with them to put forward relevant suggestions to provide a basis for medical education in the future. Design . The research team conducted a cross-sectional study, using an anonymous online questionnaire. Setting . The study took place in many provinces and cities in China and was conducted in an online questionnaire. Participants . Participants were 1114 college students studying clinical medicine, college students studying nursing, and students interning during standardized resident training, medical interns. Outcome Measures . The participants completed a self-administered questionnaire, which investigated their psychological statuses related to anxiety and depression as well as COVID-19's impact on their intentions related to job searches, regarding their willingness to engage in clinical or basic research in epidemic-related specialties and epidemic-related work. Results . Compared to college students studying clinical medicine, the employment intentions of nursing students and medical interns were more vulnerable to the epidemic. Females and nursing students were more reluctant to choose clinical work, and the choice was associated with depression. Nursing college students and medical interns were significantly less willing to engage in infection medicine, respiratory medicine, and intensive care medicine (all P <.001). Medical students with a bachelor's degree and postgraduate degrees were significantly less willing to engage in infection medicine and respiratory medicine (all P <.001), but medical students from regions with stable epidemics were more willing to engage in intensive care medicine. Medical students with a bachelor's degree were significantly less likely to be involved in epidemiology-related work than undergraduate students, and students from severe epidemic regions were significantly less willing to work in isolation wards or to go to Wuhan as volunteers. Conclusions . Participants' psychological statuses related to anxiety and depression, genders, degrees, current educational statuses, and regions affected employment intentions during the epidemic.

There have been several case reports regarding newly developed vitiligo following the coronavirus disease 19 (COVID-19) vaccination. However, the relationship between COVID-19 vaccine and vitiligo progression remains unclear. To explore the relationship between COVID-19 vaccine and vitiligo progression and its potential influencing factors, A cross-sectional study was conducted on 90 patients with vitiligo who received inactivated COVID-19 vaccination. Detailed information covering demographic characteristics (age and sex), vitiligo clinical features (disease subtypes, duration, stage and comorbidities) and disease activity was collected through an electronic questionnaire. Ninety patients with vitiligo included 44.4% males, with an average age of 38.1 years (standard deviation, SD = 15.0). Patients were divided into progress group (29, 32.2%) and normal group (61, 67.8%) based on whether they experienced vitiligo progression after inactivated COVID-19 vaccination. 41.3% of patients in the progress group experienced vitiligo progression within 1 week after vaccination, and disease progression mainly occurred after the first dose inoculation (20, 69.0%). Logistic regression revealed that patients aged <45 years (odds ratio (OR) was 0.87, 95% confidence interval (CI): 0.34-2.22) and male patients (OR = 0.84, 95% CI: 0.34-2.05) had lower risk for vitiligo progression, while patients with segmental vitiligo (SV) subtype (OR = 1.68, 95% CI: 0.53-5.33), with <5 years disease duration (OR = 1.32, 95% CI: 0.51-3.47) had higher risk for vitiligo progression after COVID-19 vaccination, but without statistical significance. Over 30% patients experienced vitiligo progression after inactivated COVID-19 vaccination, and female patients, elder age, shorter disease duration and SV subtype are potential risk factors for vitiligo progression.

报道2例Iso-Kikuchi综合征,均为先天性发病.例1女,7个月,因左手食指甲板异常7个月就诊;例2男,3岁,因左手食指甲板异常3年余就诊.2例均表现为左手食指中央无正常甲板,甲床两侧各有1个微小、独立的甲板.结合临床特点,2例均诊断为Iso-Kikuchi综合征.本文例1母亲孕期有使用黄体酮保胎史,2例患儿母亲孕期均因甲状腺功能减退症持续服用甲状腺激素治疗,且例2的母亲有妊娠期糖尿病病史.尚不能明确这些疾病和药物是否与Iso-Kikuchi综合征有直接关系.

Vitiligo is a skin disease characterized by selective loss of melanocytes, which seriously affects the appearance and causes great psychological stress to patients. In this study, we performed a comprehensive analysis of two vitiligo microarray datasets from the GEO database using bioinformatics tools to identify 297 up-regulated mRNAs and 186 down-regulated mRNAs, revealing important roles for pathways related to melanin synthesis, tyrosine metabolism, and inflammatory factors, such as “PPAR signaling pathway”, “tyrosine metabolism”, “nonalcoholic fatty liver disease (NAFLD) pathway”, “melanogenesis”, and “IL-17 signaling pathway”. Combining the Search Tool for Interacting Chemicals (STITCH) database 5.0 and the drug-gene interaction database 3.0 (DGIdb), we identified that the PPAR-γ agonist rosiglitazone may promote melanin synthesis via EDNRB. Next, we investigated the mechanism of rosiglitazone and PPAR-γ pathway in promoting melanin production. Consistent with the results of bioinformatics analysis, the expression levels of PPAR-γ, EDNRB, and TYR were significantly reduced in human non-segmental vitiligo skin along with the reduction of MITF, a key gene for epidermal melanogenesis. Meanwhile, rosiglitazone increased melanin synthesis capacity in melanocytes and zebrafish by activating PPAR-γ and upregulating TYR, TYRP-1, and TYRP-2. Conversely, treatment of melanocytes with the PPAR-γ antagonist GW resulted in inhibition of melanin synthesis and expression of melanin-related factors. At the same time, simultaneous treatment of rosiglitazone with GW reversed the inhibitory effect of GW on melanin synthesis. In this study, we identified that rosiglitazone, an important insulin sensitizer, promotes melanin synthesis in melanocytes by increasing PPAR-γ activity and upregulating the expression levels of EDNRB and TYR. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of non-segmental vitiligo.

Primary cutaneous anaplastic large cell lymphoma is a kind of cluster of differentiation 30+ primary cutaneous lymphoproliferative disorders with a relatively good prognosis in the absence of high-stage disease. Primary cutaneous anaplastic large cell lymphoma shows a higher frequency in males and commonly affects the head and neck. Palpebral involvement is very rare. We present a 42-year-old lady patient with primary cutaneous anaplastic large cell lymphoma involving the eyelid which was initially misdiagnosed as stye. The patient underwent a total excision of the lesion and showed complete regression of the lesion after surgery without any other treatment. There was no evidence of local or systemic disease during follow-up after nine months.

Hand-foot skin reaction (HFSR) is the most debilitating and prevalent side effect caused by multikinase inhibitors (MKIs) that share vascular endothelial growth factor receptor (VEGFR) as the common inhibition target, such as sorafenib, regorafenib, axitinib, etc. Though not life-threatening, HFSR can significantly deteriorate patients' quality of life and jeopardize the continuity of cancer therapy. Despite years of efforts, there are no FDA-approved treatments for HFSR and the understanding of the precise pathogenic mechanism is still limited. In this study, we hypothesized that nitric oxide has the potential therapeutic effect to reverse the toxicity caused by MKI through upregulation of several VEGF/VEGFR downstream signaling pathways. We found that glyceryl trinitrate (GTN), a nitric oxide donor, could stimulate cell proliferation, migration, and protect cells from apoptosis induced by MKIs in vitro. Local application of GTN mitigated tissue damage in a rat model, while not impacting the anti-tumor effect of the MKI in HepG2 tumor-bearing mice. Finally, GTN ointment alleviated cutaneous damages and improved quality of life in 6 HFSR patients. Our study proposed and validated the mechanism to counteract VEGFR inhibition, providing GTN as the potential treatment to MKI-induced HFSR, which may further improve the therapeutic window of various MKI based cancer therapies.

Atopic dermatitis (AD) is a chronic and relapsing cutaneous disorder characterized by compromised immune system, excessive inflammation, and skin barrier disruption. Post-translational modifications (PTMs) are covalent and enzymatic modifications of proteins after their translation, which have been reported to play roles in inflammatory and allergic diseases. However, less attention has been paid to the effect of PTMs on AD. This review summarized the knowledge of six major classes (including phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, o-glycosylation, and glycation) of PTMs in AD pathogenesis and discussed the opportunities for disease management.

Backgrounds Psoriasis and atopic dermatitis are two common chronic inflammatory skin diseases that enormously deteriorate the psycho-physical and socio-economic condition of the patients. Although differential immune responses have been found to operate in the pathomechanisms of atopic dermatitis and psoriasis, the epidermal keratinocytes are the major targets in both diseases, and sometimes, they show similar clinical presentations. The skin barrier, itching, and inflammation are current and future treatment targets for both of them, but the relevant shared mechanisms of the two diseases are far from understood. Methods The differential analyses of GSE14905 (psoriasis) and GSE32924 (atopic dermatitis) deposited in GEO database were conducted and obtained their differential expressed genes. Moreover, PPI, functional modules, GO, and KEGG enrichment analyses were used for the further analysis. The mouse models of psoriasis and atopic dermatitis were established, and then, RT-qPCR and Western blotting assay were performed to check the abundant changes of hub genes. Results There are 732 differentially expressed genes in psoriasis versus nonlesional skin samples. Besides, 611 differentially expressed genes were identified in atopic dermatitis versus nonlesional skin data sets. Based on these differentially expressed genes, we predicted their joint and individual protein-protein interaction networks and functional modules in both psoriasis and atopic dermatitis. Through the PPI network of genes, we calculated the hub nodes and do the GO and KEGG enrichment analysis of overlapped genes of psoriasis and atopic dermatitis, which suggested there were some terms like “positive regulation of interleukin-12 production,” “centromeric region,” and “TNF signaling pathway.” Conclusion We constructed the predicted PPI networks and functional modules related to psoriasis and atopic dermatitis and distinguished the key candidate target genes CXCL8, STAT1, and MMP9 in the diagnosis and therapy of similar pathogenesis.

Introduction: To investigate the effects and influencing factors of the COVID-19 epidemic on the employment intention of resident physicians in China. Methodology: 409 questionnaires were statistically analyzed after removing the missing values. We used the Chi-Square test for single-factor analysis and logistic regression analysis for multivariate analysis. The questions include the residents' employment intention and their willingness to engage in epidemic-related subspecialties and participate in epidemic-related work. Results: Residents of severe and high-risk epidemic regions had much lower employment intentions than those of stable epidemic regions (OR = 1.917, 95% CI: 1.024, 3.591, p = 0.042). The higher the Center for Epidemiologic Studies Depression Scale (CES-D) score, the more susceptible was the resident's employement intention (OR = 1.085, 95% CI: 1.044, 1.128, p < 0.001). Residents from severe and high-risk epidemic regions were more willing to participate in clinical work (OR = 4.263, 95% CI: 1.892, 9.604, p < 0.001), and the higher the CES-D score, the lower was the proportion of residents willing to choose clinical work (OR = 0.941, 95% CI: 0.893, 0.992, p = 0.023). Residents from severe epidemics and high-risk provinces were less willing to participate in respiratory medicine ( χ 2 = 5.070, p = 0.027) and critical care medicine ( χ 2 = 7.046, p = 0.011). Compared to residents with bachelor’s degrees, residents with master’s and doctoral degrees were less willing to participate in isolation wards (OR = 1.831, 95% CI: 1.122, 2.990, p = 0.016). Residents in epidemic-related current rotation departments were less willing to go to Wuhan as volunteers (OR = 2.197, 95% CI: 1.110, 4.347, p = 0.024). Conclusions: The COVID-19 outbreak had a negative impact on the job intentions of Chinese residents in general.

报道一例传染性软疣样表现的先天性自愈性朗格汉斯组织细胞增生症.患儿,女,5个月.出生4个月后周身出现多发肤色扁平小丘疹,表面光滑,边界清楚,部分中央脐凹样改变.组织病理示真皮乳头内单一核细胞浸润,免疫组化:CD1a(+),S100(+),Langerin(+).病理取材1周后所有皮疹均消退,结合患儿临床症状及随访结果诊断为先天性自愈性朗格汉斯组织细胞增生症.

Background Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway. Methods In this study, whole exome sequencing was used to screen for both somatic and germline deleterious mutations in three sisters with a lethal GS. The mutations we found were confirmed by subcloning and Sanger sequencing of the genomic DNA. RNA-seq was performed to profile gene expression in paired BCCs samples and the expression levels for selected genes were validated by quantitative PCR. Results The clinical and histopathologic features were analyzed for the proband in the three-generation GS family. We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT. Conclusions The distinct non-clock-like signatures of BCCs indicated that GS was not a life-threatening illness. The main reasons for untimely death of GS patients were PTCH1 mutation, exposure to intense ultraviolet radiationand the poor economic conditions.