Skin-directed radiotherapy for primary cutaneous T-cell lymphomas.

PURPOSE: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). MATERIALS AND METHODS: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. RESULTS: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. CONCLUSION: Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.

Prevalence, clinical features, and survival outcome trends of 627 patients with primary cutaneous lymphoma over 29 years: a retrospective review from single tertiary center in Korea.

The relative frequency of primary cutaneous lymphoma (PCL) subtypes shows wide variation across different geographical regions. This retrospective study was conducted in a tertiary referral center located in Korea to describe the relative frequency, demographics, survival outcomes, and temporal trend in PCL. A total of 627 PCL cases diagnosed between January 1994 and December 2022 were included. The majority of PCL cases (87.2%) were of T-/NK-cell lineage (CTCL), while the remaining cases (12.8%) were B-cell lineage lymphomas (CBCL). The prevalence of mycosis fungoides (MF) in CTCL increased significantly over time, while other CTCL subtypes, including primary cutaneous extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), decreased in frequency. Notably, the prevalence of CD4-positive small/medium T-cell lymphoproliferative disorder showed a substantial increase over time. Primary cutaneous marginal zone lymphoma was consistently the commonest CBCL subtype. Survival analysis demonstrated that CTCL had a more favorable 5-year overall survival (OS) than CBCL. OS rate of MF, SPTCL, and primary cutaneous peripheral T-cell lymphoma, NOS improved significantly over time. This study provides comprehensive insights into the dynamic change in the relative frequency and overall survival of PCL subtypes over time.

Spatial transcriptomic analysis of amelanotic acral melanoma versus pigmented acral melanoma reveals distinct molecular determinants.

BACKGROUND: Amelanotic acral melanoma (AAM) is a rare type of acral melanoma that has a poor prognosis. OBJECTIVES: To investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM). METHODS: Differences in the spatially resolved transcriptomic profiles of 9 patients with AAM with 29 regions of interest (ROIs) and 11 patients with PAM with 46 ROIs were investigated using S100b and CD3 morphology markers. RESULTS: In S100b+ tumour cell areas, we detected 11 upregulated differentially expressed genes (DEGs; including chaperone/ubiquitin--associated DEGs) and 82 downregulated DEGs (including human leucocyte antigen) in AAMs vs. 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 signalling and melanin biosynthesis pathways in S100b+ ROIs of AAMs compared with PAMs. In tumour-associated immune cell areas, the numbers of CD8 T cells (P = 0.04) and M1 macrophages (P = 0.01) were significantly decreased, whereas those of monocytes (P = 0.04) and endothelial cells (P = 0.04) were increased in AAMs compared with PAMs. CONCLUSIONS: These findings could widen our understanding of the biological differences between AAMs and PAMs, which might result in a different clinical course.

Melanoma is one of the most serious types of skin cancer. As melanoma starts in cells that produce melanin (the substance that produces hair, eye and skin colouration), melanoma tumours are usually brown or black. 'Amelanotic melanoma' is a subtype of melanoma that has little or no melanin pigmentation. Less than 2% of melanomas are amelanotic melanomas. 'Acral melanoma' is a type of melanoma that occurs on the hands and feet. In acral melanoma, the lack of pigmentation has been associated with worse outcomes for patients. Why amelanotic acral melanoma (or 'AAM') has a worse prognosis than pigmented acral melanoma (or 'PAM') is unclear. Using a type of technology called 'spatial transcriptomic analysis', we analysed a type of nucleic acid called RNA in 9 people with AAM and 11 with PAM. Seventy-five 'regions of interest' were selected. These regions of interest are known to be associated with tumour cells or immune cells around tumours. We found that pathways involved in making proteins (translation) and in a process that removes faulty proteins called 'messenger RNA' were more active in AAM. However, pathways involved in processing and presenting antigens (substances that can trigger an immune response), the signalling of other proteins called 'interferons' and melanin production were less active in AAM. The number of specific types of white blood cells that recognize and attack tumours were decreased, whereas other cell types such as cells that line blood vessels were increased in AAM. Our findings could increase our understanding of the differences between AAMs and PAMs. This may lead to an improvement in prognosis.

Facial Dermatoses Associated With Mask-Wearing in the COVID-19 Era: A Nationwide, Cross-Sectional, Multicenter, Questionnaire-based Study.

BACKGROUND: Daily usage of facial masks during coronavirus disease 2019 pandemic influenced on facial dermatoses. OBJECTIVE: This study investigated the impact of mask-wearing habits on facial dermatoses. METHODS: A nationwide, observational, questionnaire-based survey was conducted from July through August 2021, involving 20 hospitals in Korea. RESULTS: Among 1,958 facial dermatoses, 75.9% of patients experienced aggravation or development of new-onset facial dermatoses after wearing masks. In aggravated or newly developed acne patients (543 out of 743), associated factors were healthcare provider, female gender, and a long duration of mask-wearing. Irritating symptoms, xerosis, and hyperpigmentation were more frequently observed in this group. Aggravated or newly developed rosacea patients (515 out of 660) were likely to be female, young, and have a long duration of mask-wearing per day. Seborrheic dermatitis patients who experienced aggravation or de novo development (132 out of 184) were younger, and they more frequently involved the chin and jaw in addition to the nasolabial folds and both cheeks. Contact dermatitis patients (132 out of 147) with aggravation or de novo development tended to be female, involve both cheeks, and complain of pruritus. Aggravated or newly developed atopic dermatitis patients (165 out of 224) were more likely to be female, and had a higher baseline investigator global assessment score before mask-wearing. CONCLUSION: Clinical features and factors related to aggravation were different according to the types of facial dermatoses.

Risk of major adverse cardiovascular events and all-cause mortality among patients with psoriatic disease treated with tumor necrosis factor-α and interleukin-12/23 inhibitors: a nationwide population-based cohort study in Korea.

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.

Comparison of metabolic and neurological comorbidities in Asian patients with psoriasis and atopic dermatitis.

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.

Consensus Report on Truncal Acne: The Korean Acne and Rosacea Society Experts Panel.

BACKGROUND: More than half of acne patients have truncal acne on their chest, back, and shoulders. However, since most studies on acne have focused on the face, data on clinical characteristics and proper management for truncal acne are insufficient. OBJECTIVE: To establish a Korean Acne Rosacea Society (KARS) consensus for experts' perception and treatment patterns of truncal acne. METHODS: We conducted two rounds of the Dephi technique to gather expert opinion and reach a consensus on truncal acne. The first round comprised 48 questionnaires focusing on various aspects such as epidemiology, clinical features, diagnosis, treatment, prognosis and more, while second rounds consisted of 26 questionnaires. RESULTS: A total of 36 dermatologists (36/38 KARS members, 94.7%) completed this survey. In the first-round survey, consensus was reached on 20 out of the 48 questions (41.7%). In the second-round questionnaire, consensus was achieved on 9 of the 26 questions (34.6%). The most unresponsive lesion to truncal acne treatment was scars (atrophic/hypertrophic). The most commonly used treatments for each non-inflammatory and inflammatory truncal acne lesions were selected to use topical retinoids (78.1% of the responders) and oral antibiotics (93.8% of the responders). CONCLUSION: Our study has yielded valuable insights into the epidemiology, clinical manifestations, diagnosis, treatment, and quality of life of patients with truncal acne. We anticipate that this study will inspire further comprehensive research for individuals with truncal acne.

Baseline Serum neutrophil-to-lymphocyte ratio in acral melanoma compared with nonacral melanoma and its prognostic significance.

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.

A randomized, double-blinded, vehicle-controlled clinical trial of topical cryosim-1, a synthetic TRPM8 agonist, in prurigo nodularis.

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.

A rare case of secondary cutaneous lymphoplasmacytic lymphoma clinically presenting as acquired cutis laxa.

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.

Spatially Resolved Transcriptomes of CD30+-Transformed Mycosis Fungoides and Cutaneous Anaplastic Large-Cell Lymphoma.

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.

Morphological characteristics of facial scars: A retrospective analysis according to scar location, onset, age, and cause.

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.

Two Cases of Linear Lichen Planus Pigmentosus of the Chin in Korean Women Treated by Fractional Lasers and Polydeoxyribonucleotide Injection.

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.

Risk of incident autoimmune diseases in patients with newly diagnosed psoriatic disease: a nationwide population-based study.

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.

Cancer risks in patients with psoriasis administered biologics therapy: a nationwide population-based study.

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.