ABSTRACT
BACKGROUND: A set of criteria for severity classification is essential in alopecia areata (AA). Currently, no guidelines are universally accepted for defining AA severity. OBJECTIVE: This study aimed to establish a set of consensus criteria for classifying the severity of and identifying treatment refractoriness in AA. METHODS: A preliminary draft of the definition for moderate-to-severe AA was crafted based on available evidence, and members of the Korean Hair Research Society (KHRS) subsequently endorsed the recommendation through an online survey. RESULTS: In the first Delphi round, consensus was attained on 15 questions. After refining certain items in the second round, consensus was achieved on 23 out of 26 questions. The KHRS first defined AA severity using the severity of alopecia tool (SALT). SALT ≥50 was defined as severe, 20≤ SALT <50 as moderate, and SALT <20 as mild. Moderate AA was considered severe if it meets one or more of the following criteria: dermatology life quality index >10, presence of accompanying eyebrow or eyelash loss, positive hair loss activity, or treatment-refractory AA. CONCLUSION: These consensus criteria can help clinicians accurately diagnose AA, provide appropriate treatment, and monitor its progression.
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Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1-deficient mice are resistant to metastasis and further protected by combined immune-checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF-ß1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK-target cell responses, which is dysregulated and hijacked by tumors during metastatic progression.
Subject(s)
Disease Progression , Killer Cells, Natural , Melanoma , Killer Cells, Natural/immunology , Animals , Mice , Melanoma/genetics , Melanoma/pathology , Melanoma/immunology , Humans , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Disease Models, Animal , Neoplasm Metastasis , Cell Line, TumorABSTRACT
BACKGROUND: Amelanotic acral melanoma (AAM) is a rare type of acral melanoma associated with poor prognosis. OBJECTIVES: We aimed to investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM). METHODS: The differences in spatially resolved transcriptome profiles of 9 AAM patients with 29 regions of interest (ROIs) and 11 PAM patients with 46 ROIs were investigated using S100b and CD3 morphology markers. RESULTS: In S100b-positive tumor cell areas, we detected 11 upregulated differentially expressed genes (DEGs), including chaperone/ubiquitin-associated DEGs, and 82 downregulated DEGs, including human leukocyte antigen, in AAMs compared with PAMs. Protein-protein interaction network and pathway analyses revealed significant enrichment of dysregulated translational and nonsense-mediated decay pathways but significant decreases in antigen processing and presentation, interferon signaling, and melanin biosynthesis pathways in S100b-positive ROIs of AAMs compared with those of PAMs. In tumor-associated immune cell areas, the numbers of CD8â T cells (p = 0.044) and M1 macrophages (p = 0.014) were significantly decreased, whereas those of monocytes (p = 0.045) and endothelial cells (p = 0.04) were increased in AAMs compared with those in PAMs. CONCLUSIONS: In conclusion, these findings could widen our understanding of the biological differences between AAMs and PAMs that might result in a different clinical course.
Subject(s)
Eosinophilia , Eosinophils , Mycosis Fungoides , Skin Neoplasms , Humans , Mycosis Fungoides/pathology , Mycosis Fungoides/diagnosis , Mycosis Fungoides/immunology , Retrospective Studies , Eosinophilia/immunology , Eosinophilia/pathology , Eosinophilia/diagnosis , Eosinophils/immunology , Eosinophils/pathology , Male , Female , Middle Aged , Prognosis , Skin Neoplasms/pathology , Skin Neoplasms/immunology , Skin Neoplasms/diagnosis , Aged , Adult , Skin/pathology , Skin/immunology , Aged, 80 and overABSTRACT
PURPOSE: Few studies have investigated the impact of biologics on the risk of major adverse cardiovascular events (MACEs) among Korean patients with psoriatic diseases. We compared the risk of MACEs and all-cause mortality among patients with psoriatic disease treated with tumor necrosis factor (TNF)-α and interleukin (IL)-12/23 inhibitors in Korea. METHODS: Patients with psoriatic disease prescribed with TNF-α and IL-12/23 inhibitors since 2016 were selected from the Korean National Health Insurance Service (NHIS) Database. Follow-up data for MACEs and all-cause mortality between 2016 and 2020 were collected. A total of 2886 individuals were included, including 1987 IL-12/23 inhibitor users and 899 TNF-α inhibitor users. RESULTS: Compared with IL-12/23 inhibitor users, TNF-α inhibitor users had a higher prevalence of dyslipidemia and a significantly higher risk of all-cause mortality but not MACE. After controlling for age, female TNF-α inhibitor users had a significantly increased risk of all-cause mortality. Meanwhile, after controlling for sex, TNF-α inhibitor users aged 60 years or older demonstrated a significantly elevated risk of all-cause mortality. In conclusion, No statistically significant difference in MACE risk was observed between patients who used TNF-α and IL-12/23 inhibitors. Nevertheless, the use of IL-12/23 inhibitors, especially among older and female patients, resulted in a lower overall mortality.
Subject(s)
Cardiovascular Diseases , Interleukin Inhibitors , Psoriasis , Tumor Necrosis Factor Inhibitors , Female , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cohort Studies , Interleukin Inhibitors/adverse effects , Interleukin Inhibitors/therapeutic use , Psoriasis/complications , Psoriasis/drug therapy , Republic of Korea/epidemiology , Tumor Necrosis Factor Inhibitors/adverse effects , Tumor Necrosis Factor Inhibitors/therapeutic use , MortalityABSTRACT
Although various comorbidities have been noted to be associated with atopic dermatitis (AD) and psoriasis, few studies have compared comorbidities between the two diseases, and little is known about whether these comorbidities vary by the subtypes of psoriasis. In this study of 1:1 age- and sex-matched pair analysis between patients diagnosed with either psoriasis or AD at Asan Medical Center between 1991 and 2020, comorbidities, as determined by the International Classification of Diseases-10 codes, and likelihood ratios of metabolic and neurologic comorbidities in psoriasis compared with AD were studied using a logistic regression model. Among a total of 14,128 patients, the psoriasis group had higher odds of obesity (odds ratio [95% confidence interval]: 1.49 [1.34-1.66]), hypertension (1.14 [1.03-1.26]), diabetes mellitus (1.46 [1.29-1.66]), chronic kidney disease (1.59 [1.22-2.08]), and Parkinson's disease (2.1 [1.15-3.83]) than the AD group. Subgroup analysis revealed that patients with plaque psoriasis had higher odds of obesity (1.18 [1.05-1.33]), hypertension (1.18 [1.06-1.32]), diabetes mellitus (1.53 [1.34-1.75]), chronic kidney disease (1.66 [1.26-2.17]), and Parkinson's disease (2.12 [1.16-3.88]) compared with AD. Meanwhile, guttate psoriasis was associated with higher odds of dementia (3.63 [1.06-12.40]) and patients with generalized pustular psoriasis showed higher odds of diabetes mellitus (5.42 [1.56-18.83]) compared with AD. In conclusion, Asian patients with all types of psoriasis should be closely monitored for the development of metabolic and neurologic diseases, especially men and those aged ≥ 40 years.
Subject(s)
Dermatitis, Atopic , Diabetes Mellitus , Hypertension , Parkinson Disease , Psoriasis , Renal Insufficiency, Chronic , Male , Humans , Dermatitis, Atopic/epidemiology , Psoriasis/complications , Psoriasis/epidemiology , Comorbidity , Hypertension/complications , Hypertension/epidemiology , Diabetes Mellitus/epidemiology , Obesity/epidemiologyABSTRACT
BACKGROUND: Studies on the interaction between tumour-infiltrating immune cells (TIICs) and tumour cells in melanoma arising from congenital melanocytic nevus (CMN) are lacking. OBJECTIVE: The aim of this study was to determine the intratumoral immune landscape of TIICs and tumour cells during invasion and metastasis. METHODS: Tissue specimens were obtained from patients with melanoma originating from CMN. Differential gene expression in melanoma cells and TIICs during invasion and metastasis was determined using spatial transcriptomics. RESULTS: As invasion depth increased, the expression of LGALS3, known to induce tumour-driven immunosuppression, increased in melanoma cells. In T cells, the expression of genes that inhibit T-cell activation increased with increasing invasion depth. In macrophages, the expression of genes related to the anti-inflammatory M2 phenotype was upregulated with increasing invasion depth. Compared to primary tumour cells, melanoma cells in metastatic lesions showed upregulated expression of genes associated with cancer immune evasion, including AXL and EPHA2, which impede T-cell recruitment, and BST2, associated with M2 polarization. Furthermore, T cells showed increased expression of genes related to immunosuppression, and macrophages exhibited increased expression of genes associated with the M2 phenotype. CONCLUSIONS: The interaction between melanomas arising from CMN and TIICs may be important for tumour progression and metastasis.
Subject(s)
Melanoma , Nevus, Pigmented , Skin Neoplasms , Humans , Melanoma/genetics , Melanoma/immunology , Melanoma/pathology , Nevus, Pigmented/genetics , Nevus, Pigmented/immunology , Nevus, Pigmented/pathology , Nevus, Pigmented/metabolism , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Skin Neoplasms/immunology , Gene Expression Profiling , Lymphocytes, Tumor-Infiltrating/immunology , Neoplasm Invasiveness , Male , Macrophages/metabolism , Macrophages/immunology , Female , Galectin 3/genetics , Galectin 3/metabolism , T-Lymphocytes/immunology , Transcriptome , Axl Receptor Tyrosine Kinase , Cell Communication , Middle Aged , Galectins/genetics , Galectins/metabolism , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/metabolism , Blood ProteinsABSTRACT
BACKGROUND: Prurigo nodularis (PN) is an intensively pruritic skin disease that negatively influences quality of life. Cryosim-1 (Intrinsic IB Spot) is a synthetic, selective transient receptor potential melastatin 8 agonist. AIMS: To investigate the efficacy and safety of cryosim-1 in PN patients. PATIENTS/METHODS: A randomized, double-blinded, placebo-controlled clinical trial including 30 patients was conducted. The numerical rating scale (NRS) of pruritus was evaluated before and 2 h after cryosim-1 application at every visit. RESULTS: At week 8, the mean pruritus NRS before serum application (4.7 ± 0.4 treatment, 6.1 ± 0.5 placebo; p = 0.045) and 2 h after serum application (2.8 ± 0.4 treatment, 4.3 ± 0.5 placebo; p = 0.031) were significantly lower in the treatment group, and the mean NRS for sleep disorder was significantly lower in the treatment group (2.2 ± 0.5 treatment, 4.2 ± 0.8 placebo; p = 0.031). The mean satisfaction scales for pruritus improvement were significantly higher in the treatment group (7.2 ± 0.6) than in the placebo group (4.0 ± 0.9; p = 0.005). There was no difference in TEWL between the two groups, and no adverse reactions were reported. CONCLUSIONS: Cryosim-1 is a safe and effective topical treatment for PN patients.
Subject(s)
Prurigo , TRPM Cation Channels , Humans , Prurigo/drug therapy , Quality of Life , Pruritus/drug therapy , Pruritus/etiology , Administration, Topical , Research Design , TRPM Cation Channels/agonists , Membrane ProteinsABSTRACT
BACKGROUND: Acral lentiginous melanoma (ALM), a cutaneous melanoma subtype, exhibits a poorer prognosis than nonacral cutaneous melanoma (NACM). The neutrophil-to-lymphocyte ratio (NLR) is emerging as a prognostic indicator across diverse cancers. OBJECTIVE: We explored the baseline NLR disparities between ALM and NACM, and the NLR's prognostic significance in patients with ALM. METHODS: We reviewed records of patients with ALM and NACM diagnosed between 1997 and 2022, analyzing medical data. RESULTS: Among 327 and 159 patients with ALM and NACM, respectively, baseline NLR varied based on distinct clinicopathologic factors between ALM and NACM. In stage 3 to 4 melanomas, the median NLR for ALM (2.18; IQR, 1.70-3.08) significantly surpassed NACM (1.74; IQR, 1.33-2.53) (P = .029). In patients with ALM, high NLR (hazard ratio, 1.64; 95% CI, 1.02-2.66; P = .043) was independently correlated with poor progression-free survival when adjusting for ulceration, Breslow thickness of ≥2 mm, and nodal invasion. LIMITATIONS: Single-center, retrospective design. CONCLUSION: Advanced-stage ALM exhibited a significantly higher baseline NLR compared with that of NACM. Evaluating baseline NLR could provide valuable prognostic insights for patients with ALM.
Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/pathology , Skin Neoplasms/pathology , Prognosis , Retrospective Studies , Neutrophils/pathology , Lymphocytes/pathologyABSTRACT
Lymphoplasmacytic lymphoma (LPL) is a rare variant of non-Hodgkin lymphoma, accounting for <1% of cases. Skin involvement in LPL is quite rare-accounting for approximately 5% of extramedullary disease-and includes a variety of clinical morphologies, such as erythematous-to-violaceous plaques, violaceous nodules or tumors, and ulceration at various anatomical sites. Herein, we report the case of a 45-year-old Korean woman who presented with generalized erythematous indurated plaques and pendulous skin growths, which were asymptomatic, with marked diffuse infiltration of lymphocytes and plasma cells in the dermis. Immunohistochemical studies revealed that the lymphoid cells expressed CD3, CD79a, and cytoplasmic IgG, but lacked CD10 and IgM. Moreover, kappa light chain restriction and monoclonal immunoglobulin heavy chain gene rearrangement were observed. Upon further workup, lymphoma involvement was reported in multiple lymph nodes, including those in the cervical and axillary regions. This case shows a unique form of cutaneous LPL clinically presenting as acquired cutis laxa, emphasizing the dermatologists' need to be vigilant for variant forms of this disease.
Subject(s)
Cutis Laxa , Lymphoma, B-Cell , Lymphoma, T-Cell, Cutaneous , Skin Neoplasms , Waldenstrom Macroglobulinemia , Female , Humans , Middle Aged , Cutis Laxa/pathology , Skin Neoplasms/pathology , Lymphoma, T-Cell, Cutaneous/pathology , Plasma Cells/pathology , Waldenstrom Macroglobulinemia/diagnosisABSTRACT
Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic large-cell lymphoma (pcALCL). We investigated the differences in spatially resolved transcriptome profiles of MF-LCT and pcALCL using CD30 morphology markers and 28 and 24 regions of interest (ROIs) in MF-LCT and pcALCL, respectively. Differentially expressed genes, pathway analysis, and immune-cell deconvolution by selective analysis of CD30-positive tumor cells and CD30-negative extratumoral areas were undertaken. In CD30-positive ROIs of MF-LCT, 190 differentially expressed genes were upregulated (29 were directly or indirectly associated with extracellular matrix remodeling), whereas 255 differentially expressed genes were downregulated, compared with those of pcALCL. Except for cornified envelope formation and keratinization, all six pathways enriched in CD30-positive ROIs of MF-LCT were associated with extracellular matrix remodeling. In CD30-positive ROIs in MF-LCT compared with those in pcALCL, immune-cell deconvolution revealed significantly increased fibroblasts and M2 macrophages (P = 0.012 and P = 0.023, respectively) but decreased M1 macrophages (P = 0.031). In CD30-negative ROIs in MF-LCT compared with those in pcALCL, memory B (P = 0.021), plasma (P = 0.023), and CD8 memory T (P = 0.001) cells significantly decreased, whereas regulatory T cells (P = 0.024) increased. Predomination of extracellular matrix remodeling pathways and immunosuppressive microenvironment in MF-LCT indicates pathophysiological differences between MF-LCT and pcALCL.
Subject(s)
Lymphoma, Large-Cell, Anaplastic , Mycosis Fungoides , Skin Neoplasms , Humans , Lymphoma, Large-Cell, Anaplastic/genetics , Transcriptome , Ki-1 Antigen/analysis , Mycosis Fungoides/genetics , Mycosis Fungoides/pathology , Skin Neoplasms/pathology , Tumor Microenvironment/geneticsABSTRACT
The morphology of facial scars shows a wide variation in terms of texture and colour. To date, there are no reliable predictors of aberrant scarring. We conducted a retrospective analysis to identify factors associated with specific scar features and types. Photographs and medical records of 428 patients with facial scars were retrospectively reviewed. Patients with keloids were excluded. The mean age of the patients was 45.43 ± 23.13 years with a male-to-female ratio of 1:1.36. Atrophic scars were the most common (42.8%), followed by flat scars (38.7%) and hypertrophic scars (18.5%). Scars on the forehead were more likely to be atrophic, whereas scars on the chin/jaw and around the mouth were more likely to be hypertrophic. Hypopigmentation was significantly more common in scars located on the forehead. Redness (erythema) was significantly more common in scars located on the chin/jaw. Old scars were less likely to be erythematous, and hypertrophic. Atrophic scars were more common in younger patients. Scars caused by dermatologic conditions, such as acne, were more likely to be atrophic, whereas surgical scars had the lowest risk of being atrophic or hypertrophic. In conclusion, the location, onset, and cause of facial scars were associated with specific features of scars.
Subject(s)
Acne Vulgaris , Cicatrix, Hypertrophic , Keloid , Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Cicatrix/complications , Retrospective Studies , Cicatrix, Hypertrophic/etiology , Cicatrix, Hypertrophic/pathology , Keloid/etiology , Acne Vulgaris/complications , Erythema , Atrophy/complications , Treatment OutcomeABSTRACT
Linear lichen planus pigmentosus is a rare subtype of lichen planus pigmentosus that follows Blaschko's lines, leaving long-standing residual atrophy and pigmentation, especially in dark-skinned populations. Conventional treatments have several limitations regarding the alleviation of pigmentation and atrophy. We report two cases of Korean women with linear lichen planus pigmentosus on their faces who were successfully treated with fractional lasers and intralesional injection of polydeoxyribonucleotide.
ABSTRACT
There are limited large population-based cohort studies on the risk of incident autoimmune diseases among patients with newly diagnosed psoriatic disease. The objective of this study was to assess the risk of autoimmune diseases in patients with newly diagnosed psoriatic disease. Using the Korean National Health Insurance Service database, patients with newly diagnosed psoriatic disease between 2007 and 2019 were included. Comparators were randomly selected and matched according to age and sex. A total of 321,354 patients with psoriatic disease and 321,354 matched comparators were included in this study. Patients with psoriatic disease had a significantly higher risk of Crohn's disease [adjusted hazard ratio (aHR), 1.95; 95% confidence interval (CI) 1.42-2.67], ulcerative colitis (aHR, 1.65; 95% CI 1.39-1.96), systemic lupus erythematosus (aHR, 1.86; 95% CI 1.34-2.57), rheumatoid arthritis (aHR, 1.63; 95% CI 1.52-1.76), ankylosing spondylitis (aHR, 2.32; 95% CI 1.95-2.77), alopecia areata (aHR, 1.41; 95% CI 1.35-1.46), and type 1 diabetes (aHR, 1.23; 95% CI 1.11-1.37). However, the risk of Graves' disease, Hashimoto's disease, Sjögren's syndrome, and systemic sclerosis was not significantly different between the groups. In conclusion, patients with newly diagnosed psoriatic disease may have a significantly increased risk of incident autoimmune diseases.
Subject(s)
Arthritis, Rheumatoid , Autoimmune Diseases , Graves Disease , Hashimoto Disease , Spondylitis, Ankylosing , Humans , Autoimmune Diseases/complications , Autoimmune Diseases/epidemiology , Risk Factors , IncidenceABSTRACT
PURPOSE: To assess cancer risks in patients with psoriasis and the effect of TNF-α inhibitor and interleukin (IL)-12/23 inhibitor therapy on those cancer risks. METHODS: Using the Korean Health Insurance Review and Assessment Service database, patients with newly diagnosed psoriasis between 2008 to 2019 were included. Standardized incidence ratios (SIRs) of overall and specific cancers were calculated in patients with psoriasis. The effect of TNF-α inhibitor and IL-12/23 inhibitor exposure on the risk of cancers was assessed by multivariable Cox regression models. RESULTS: In total, 191,678 patients with psoriasis were included in this study. The overall risk of cancer was significantly higher in patients with psoriasis than in the general population (SIR, 1.12; 95% confidence interval (CI), 1.09-1.14). TNF-α inhibitor users had a significantly higher risk for overall cancer (adjusted hazard ratio (aHR), 1.41; 95% CI 1.01-1.97). In contrast, IL-12/23 inhibitor exposure had a significantly lower risk for overall cancer (aHR, 0.57; 95% CI 0.37-0.87). Among specific cancers, the risks of non-Hodgkin lymphoma (aHR, 2.98; 95% CI 1.02-8.69) were increased by TNF-α inhibitor therapy, while the risk of other cancers, including nonmelanoma skin cancer (aHR, 2.31; 95% CI 0.51-10.46), was not significantly altered by TNF-α inhibitor therapy. CONCLUSION: TNF-α inhibitor therapy in psoriasis is associated with a significantly increased risk of overall cancer and lymphoma, while the risk of solid organ cancer was not affected by this therapy. The IL-12/23 inhibitor is not associated with an increased risk of any cancer.