Clinicopathological features and prognosis of pyoderma gangrenosum in Korea: A single centre, retrospective, observational study over 20 years.

BACKGROUND: Pyoderma gangrenosum is a rare autoinflammatory neutrophilic dermatosis that rapidly evolves. However, little is known about the clinicopathological features and prognosis of pyoderma gangrenosum. AIMS: We aimed to document clinicopathologic and prognostic data of the patients with pyoderma gangrenosum. METHODS: In this retrospective observational study, we reviewed case records of patients diagnosed with pyoderma gangrenosum between 1999-2019. RESULTS: Fifty-three patients were identified by reviewing medical records for skin biopsy; of these, 37 were men and 16 were women. Mean age at onset was 43.3 ± 18.5 years. The most frequently affected area was the lower extremities (60.4%), followed by the head and neck (17.0%). The most common subtype was ulcerative (47.2%), followed by bullous (22.6%). 30 cases had underlying diseases and the most common were malignancy (24.5%), followed by inflammatory bowel diseases (18.9%). The proportion of cases with history of trauma were significantly higher in post-operative type (100%) as compared to the bullous type (8.3%). Histologic features of granulation tissue were frequently found in post-operative type (66.7%) and bullous type (58.3%). Granulomas were predominantly found in bullous type (58.3%). Age <60 years appeared to be significantly associated with multiple lesions. Partial-to-complete remission was observed in 40 cases (75.5%). Nine (17.0%) cases experienced recurrence with a median progression-free period of six months (interquartile range of 3.0-9.0 months). Cases with underlying hematologic disorders and the bullous subtype were significantly associated with early recurrence. LIMITATIONS: This study was a single-centre study with a retrospective design. CONCLUSION: Pyoderma gangrenosum appears to have ethnic differences. Underlying haematologic disorders and bullous subtype have a worse prognosis. However, the type of histopathology did not correlate with the clinical outcome of pyoderma gangrenosum.

Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: a randomized, double-blind, split-face trial.

BACKGROUND: Filler injection has become an extremely popular method for facial skin rejuvenation, including the periorbital area. In the recent years, new polynucleotide (PN)-containing filler products have been used for esthetic purposes. AIM: We aimed to investigate the efficacy and safety of PN filler injection in the periorbital area. PATIENTS/METHODS: A total of 27 subjects were enrolled in this randomized, pair-matched, and active-controlled study. Each subject received filler injections thrice with two-week intervals, with a PN filler injection on one side and a non-crosslinked hyaluronic acid (HA) filler injection on the contralateral side of the periorbital area. RESULTS: Improvements in the visual analog scale and global esthetic improvement scale scores were not significantly different between the PN and HA groups. The improvement rates of skin elasticity and hydration decreased over time in both groups, with the PN group showing a higher improvement rate. The improvement rates of roughness and pore volume were higher in the PN group than in the HA group. The improvement rate of dermal density was not significantly different between the groups. No serious adverse events were reported. CONCLUSION: The PN filler injection is effective and safe for periorbital rejuvenation.

Efficacy and safety of guselkumab compared with placebo and adalimumab in Korean patients with moderate-to-severe psoriasis: post-hoc analysis from the phase III, double-blind, placebo- and active-comparator-controlled VOYAGE 1/2 trials.

BACKGROUND: The phase 3 studies, VOYAGE 1 and 2, were conducted to assess guselkumab in the treatment of patients with moderate-to-severe psoriasis. OBJECTIVES: To investigate the efficacy and safety of guselkumab in Korean patients. METHODS: The Korean sub-population of VOYAGE 1 and 2 study patients were included in this analysis. Efficacy and safety were evaluated through Weeks 24 and 28, respectively. RESULTS: Of 126 randomized Korean patients, 30, 63, and 33 received placebo, guselkumab, and adalimumab, respectively. At Week 16, guselkumab was superior to placebo in achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (cleared or minimal; 90.5 vs. 20.0%, p<.001) and a Psoriasis Area and Severity Index (PASI) 90 response (71.4 vs. 3.3%, p<.001). At week 24, a significantly higher proportion of guselkumab-treated patients achieved PASI 75 and IGA 0 (clear skin) responses compared to adalimumab-treated patients (PASI 75: 93.7 vs. 66.7%, p<.001; IGA 0: 52.4 vs. 21.2%, p=.004). Through Week 28, guselkumab and adalimumab showed comparable safety profiles. CONCLUSION: The efficacy and safety of guselkumab in Korean psoriasis patients through 28 weeks were consistent with findings for the overall VOYAGE 1 and 2 study population.

Clinical characteristics and long-term outcomes of 97 Korean patients with mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) shows racial and regional differences in terms of clinical features. The availability of therapeutic options as well as drugs differs from one country to another. There are only limited data on the clinical characteristics and treatment experience of MF from South Korea. METHODS: Medical records of 97 patients with MF were retrospectively analyzed to investigate clinical features, survivals, and prognostic factors. Assessment of prognostic variables was done using univariate Cox proportional hazard models. RESULTS: Median age at time of diagnosis was 45 years. The median time from onset of skin lesion to diagnosis of MF was 36 months with a median follow-up period of 96 months. A number of clinical variants of MF were observed. Treatment mainly consisted of narrow-band UVB, systemic retinoids, methotrexate, chemotherapy, and regional radiotherapy. Complete remission was observed in 78% of patients with records on their clinical course. About 12% experienced disease progression. No clinical prognostic factor apart from TNM staging was identified. CONCLUSION: Despite delay in diagnosis, most cases of MF in Korea were diagnosed in early stages. Prognosis of our patients was more favorable than those of other geographic regions as reported in previous studies. Good response to treatment, consisting mainly of phototherapy and radiation therapy, and relatively indolent clinical behavior of disease were observed in this homogeneous cohort of Korean patients with MF.

Partial unilateral lentiginosis: a clinicopathological analysis of 32 cases on the head and neck area in Korea.

BACKGROUND: Partial unilateral lentiginosis (PUL) is a rare acquired circumscribed hyperpigmentation characterized by multiple simple lentigines involving half of the body. Since the previous studies of PUL were mostly based on case reports and the current literature lacks well-designed retrospective studies that involve a large number of cases, PUL is not a well-defined entity, and differential diagnosis with nevus spilus is still difficult. This study aims to evaluate clinical and histopathological characteristics and treatment outcomes of PUL on head and neck area of Koreans. METHODS: Thirty-two patients with PUL on head and neck area were diagnosed clinicohistopathologically at the Asan Medical Center from 2004 to 2017. Their medical records, photographs, and biopsy specimens were reviewed, and immunohistochemical staining for protein kinase C (PKC)-ßΙΙ was evaluated for melanogenic activity. RESULTS: Four patients (12.5%) of PUL had congenital lesions, and 24 (75.0%) had age of onset younger than 10 years. Confluency of lentiginous lesions (100%) and mild to moderate background interlesional hyperpigmentation (90.6%) were observed. The lentiginous lesions showed increased melanocytes, melanophages, basal melanins, lentiginous hyperplasia, and perivascular inflammatory cells compared with background interlesional hyperpigmentation, and PKC-ßΙΙ was focally positive in 7 of 12 stained PUL lesions. Among the 16 patients who received laser treatments, 10 (62.5%) showed more than 50% of improvement. CONCLUSIONS: The findings of this study will allow for improved diagnosis of PUL and understanding of its features, which may facilitate proper management in the future.

Different progression pattern between acral and nonacral melanoma: A retrospective, comparative, clinicoprognostic study of 492 cases of primary cutaneous melanoma according to tumor site.

BACKGROUND: There are limited data regarding the difference in progression pattern between acral melanoma and nonacral melanoma. AIMS: The objectives of this study were to compare the progression pattern between acral and nonacral melanoma and evaluate its impact on clinical outcomes. METHODS: Clinical and histopathological features, survival outcomes and prognostic factors of 492 patients with acral melanoma or nonacral melanoma were retrospectively evaluated using the Asan Medical Center database. RESULTS: The male-to-female ratio and the mean age was 1:0.92 and 60.2 years for acral melanoma (n = 249), and 1:0.85 and 58.4 years for nonacral melanoma (n = 243), respectively. The demographic difference was not significant. Although prediagnosis duration was longer and the advanced stage was more common in acral melanoma than that in nonacral melanoma, the vertical growth phase was more common in nonacral melanoma than that in acral melanoma, whereas, the horizontal diameter is longer in acral melanoma than that in nonacral melanoma. Dissemination to lymph nodes was more common in acral melanoma than that in nonacral melanoma. Lymph node involvement was associated with deeper Breslow thickness in nonacral melanoma but not in acral melanoma. The degree of correlation of prediagnosis duration with horizontal diameter was remarkable in acral melanoma, but with Breslow thickness in nonacral melanoma. Overall survival was worse in acral melanoma than that in nonacral melanoma. The prognostic value of Breslow thickness was more remarkable in nonacral melanoma than that in acral melanoma. LIMITATIONS: This study is a retrospective, single-center design. CONCLUSION: Acral melanoma has a longer radial growth phase compared with nonacral melanoma. However, acral melanoma is commonly associated with lymph node dissemination which contributed to worse survival in acral melanoma than nonacral melanoma.

The Efficacy and Safety of Dual-Frequency Ultrasound for Improving Skin Hydration and Erythema in Patients with Rosacea and Acne.

Inflammatory skin diseases, such as rosacea and acne, are major causes of facial erythema and accompanying skin barrier dysfunction. Several methods to restore the impaired skin barrier and improve facial erythema, such as medication, radiofrequency, laser, and ultrasound therapy were attempted. This study evaluated the efficacy and safety of dual-frequency ultrasound with impulse mode, for improving skin hydration and erythema in Asian subjects with rosacea and acne. Twenty-six subjects with facial erythema received an ultrasound treatment once per week, for 4 weeks, over both cheeks. The erythema index and transepidermal water loss (TEWL) were measured at each visit. Clinicians assessed the erythema improvement and patients evaluated their satisfaction level. The average decrease in TEWL and erythema index at 6 weeks was 5.37 ± 13.22 g·h-1·m-2 (p = 0.020) and 39.73 ± 44.21 (p = 0.010), respectively. The clinician's erythema assessment and the subject satisfaction questionnaire score significantly improved at final follow-up (p < 0.001; p = 0.003, respectively). No serious adverse effects were observed during the treatment and follow-up periods. The dual-frequency ultrasound with impulse mode appears to be effective and safe for improving skin hydration and erythema in patients with rosacea and acne.

Clinical outcomes in adult patients with plaque psoriasis treated with ustekinumab under real-world practice in Korea: A prospective, observational, multi-center, postmarketing surveillance study.

Postmarketing surveillance is conducted to establish drug safety and effectiveness under real-world practice. We aimed to validate the effectiveness and safety of ustekinumab in the treatment of adult Korean patients with plaque psoriasis under real-world practice. This was a prospective, observational, and multi-center study. Subjects aged 18 years or older who were treated with ustekinumab for plaque psoriasis were enrolled. We enrolled 977 patients; 654 (66.9%) were men, with mean body surface area (BSA, ± standard deviation) of 27.0 ± 18.3% and mean psoriasis area severity index (PASI) score of 18.1 ± 9.7. The effectiveness analysis was performed in 581 patients who had at least one follow-up assessment and met treatment criteria per local label and reimbursement guidelines. Of these patients, 287 had effectiveness data for visit 6 at 53.7 ± 2.1 weeks. At visit 6, 91.6% (263/287), 51.2% (147/287), and 9.4% (27/287) patients achieved PASI 75, 90, and 100 responses, respectively. Adverse events (AEs) occurred in 112 of the 977 (11.5%) patients with an incidence rate of 21.5 per 100 patient-years (PYs). Serious AEs occurred in eight (0.8%) patients with an incidence rate of 1.2 per 100 PYs. The estimated 1-year drug survival rate was 87.7%. The multiple logistic regression analysis showed that higher baseline PASI score and no prior biologic exposure were significant predictors for PASI 90 response at visit 6. Ustekinumab was effective and safe, and displayed a high survival rate in the treatment of adult Korean patients with plaque psoriasis in real-world practice.

PD-1 and PD-L1 expression in Kaposi sarcoma: A comparative study according to the pathological stage and clinical characteristics.

BACKGROUND: Kaposi sarcoma (KS) is a mesenchymal tumor with distinct histopathological features according to stage of progression. Programmed death-1 (PD-1) and its ligand PD-L1 play major roles in the immune escape strategy of tumors. OBJECTIVES: This study evaluated expression of PD-1 and PD-L1 in various stages of KS and investigated associations between their expression and clinical characteristics. METHODS: Fifty cases with histopathologically diagnosed KS were classified as early or late stage. These specimens were stained with anti-PD-1 and anti-PD-L1 antibodies. The extent of expression in the intratumoral and peritumoral areas was judged by two dermatopathologists. RESULTS: PD-1 and PD-L1 were expressed in 72.2% (13/18) and 11.1% (2/18) of early-stage cases, respectively, compared with 43.8% (14/32) and 28.1% (9/32) of late-stage cases, respectively. At the late stage, PD-1 expression was significantly higher in the peritumoral area than in the intratumoral area (P = 0.001). PD-1 expression in the intratumoral area was significantly higher at the early stage than at the late stage (P = 0.013). PD-L1 expression in the peritumoral area was significantly higher at the late stage than at the early stage (P = 0.038). CONCLUSIONS: The pattern of PD-1 and PD-L1 expression differs according to the stage of KS, but is unaffected by clinical variables.

The efficacy and safety of BM-PHA for the correction of nasolabial folds: a multicenter, randomized, double-blind, split-face clinical trial.

Background: Multiple types of fillers have been developed for soft tissue augmentation.Objective: We investigated the efficacy and safety of the novel filler BM-PHA.Methods: In this multicenter, randomized, split-face study, 91 participants received injections of BM-PHA and Restylane Perlane (PER) into the nasolabial folds. Efficacy was determined by the improvements in the Wrinkle Severity Rating Score (WSRS) and Global Esthetic Improvement Scale (GAIS), and safety by adverse events, laboratory tests, and a check of vital signs.Results: WSRS scores assessed by independent evaluators at Week 24, the primary efficacy measure, showed no significant difference between the two treatments. The treatments also showed no significant differences in WSRS scores assessed by the evaluators at Week 8 and WSRS and GAIS scores assessed by the treating investigators and participants at Weeks 8 and 24. The proportion of nasolabial folds whose WSRS scores improved by at least one grade at Week 24 was similar between the treatments. Only minor local side effects were reported without sequelae.Conclusion: BM-PHA was not inferior to PER in the treatment of moderate to severe nasolabial folds and may be an appropriate alternative product for their improvement. Further studies are needed to confirm the long-term safety of BM-PHA.

The prognostic significance of VISTA and CD33-positive myeloid cells in cutaneous melanoma and their relationship with PD-1 expression.

V-domain Ig suppressor of T-cell activation (VISTA), which mediates immune evasion in cancer, is mainly expressed on hematopoietic cells and myeloid cells in the tumor. We evaluated correlations among the expression of VISTA, the myeloid-derived suppressor cell marker CD33, and programmed death-1 (PD-1), and determined their relationships with clinicopathological characteristics and disease outcomes in melanoma. Diagnostic tissue from 136 cases of melanoma was evaluated by immunohistochemistry for CD33, VISTA, and PD-1 expression. Dual immunofluorescence using CD33 and VISTA antibodies was performed. VISTA expression positively correlated with CD33 expression in melanoma tissue. Dual immunofluorescence staining revealed that VISTA was expressed by CD33-positive myeloid cells. PD-1 expression correlated with CD33 and VISTA expression. CD33 and VISTA expression were significantly associated with negative prognostic factors, including a deeper Breslow thickness and an advanced stage of disease. High expression of either CD33 or VISTA was associated with worse survival. Positivity for both VISTA and PD-1 predicted worse survival. Multivariate analysis showed that both CD33 and VISTA expression were independent prognostic factors in cutaneous melanoma. VISTA and CD33 expression are independent unfavourable prognostic factors in melanoma, which suggests their potential as therapeutic targets.

Lymphatic invasion in acral and non-acral melanoma: a comparative, clinicoprognostic study of primary cutaneous melanoma according to tumour site.

There have been limited studies comparing the clinical significance of lymphatic invasion in melanoma according to tumour site. The objective of this study was to evaluate the impact of lymphatic invasion on the clinicoprognostic features of acral and non-acral melanoma. Clinical and histopathological features and survival outcomes of 532 patients with acral melanoma or non-acral melanoma in the database of the Asan Medical Center, Korea, were retrospectively evaluated according to the presence of lymphatic invasion. Lymphatic invasion was significantly more common in acral melanoma than non-acral melanoma. In acral melanoma, lymphatic invasion was significantly associated with a higher frequency of lymph node involvement and advanced stages, but not associated with Breslow thickness or visceral dissemination. By contrast, lymphatic invasion in non-acral melanoma was significantly associated with a higher rate of visceral involvement, deeper Breslow thickness, as well as a higher rate of lymph node involvement and advanced stages. When acral melanoma and non-acral melanoma both with lymphatic invasion were compared, Breslow thickness was significantly shallower and vertical growth phase was significantly less common in acral melanoma. Meanwhile, visceral involvement was significantly more frequent in non-acral melanoma than acral melanoma. In conclusion, lymphatic invasion was more common in acral melanoma than non-acral melanoma and occurred in acral melanoma cases with relatively thin Breslow thickness, suggesting acral melanoma is lymphotropic.

Correlation Between Tumor-Associated Macrophage and Immune Checkpoint Molecule Expression and Its Prognostic Significance in Cutaneous Melanoma.

The association between tumor-associated macrophages (TAMs) and the expression of immune checkpoint molecules has not been well described in cutaneous melanoma. We evaluated the correlations between the expression of markers of TAMs, cluster of differentiation 163 (CD163), and immune checkpoint molecules, programmed cell death protein-1 (PD-1), and lymphocyte activating gene-3 (LAG-3). We also determined their relationships with the clinicopathological features and disease outcomes in melanoma. Diagnostic tissues collected from melanoma patients were evaluated using immunohistochemistry for CD163, PD-1, and LAG-3 expression. CD163 expression positively correlated with PD-1 and LAG-3 expression. High expression of both CD163 and PD-1 expressions was significantly associated with negative prognostic factors and worse prognosis than high expression of the single markers. High co-expression of CD163 and LAG-3 was associated with poor clinicopathological indexes of melanoma and worse survival compared to the high expression of the single markers. The expression of immune checkpoint molecules PD-1 and LAG-3 positively correlated with the M2-TAM density in melanoma tissue. Simultaneous high M2-TAM density and immune checkpoint molecules expression acted as independent poor prognostic factors in cutaneous melanoma.

Clinicoprognostic characteristics of cutaneous metastatic melanoma: a retrospective comparative study between acral and nonacral melanoma.

BACKGROUND: Although cutaneous melanoma has been widely evaluated, data elucidating the clinical features and prognostic factors of cutaneous metastatic melanoma are limited. OBJECTIVE: To determine and compare the clinicoprognostic features of cutaneous metastasis in acral and nonacral melanoma. METHODS: The Asan Medical Center database was reviewed for cases of cutaneous metastatic melanoma that had been confirmed by skin biopsy between January 1996 and December 2017. RESULTS: Cutaneous metastasis occurred in 12.4% (61 of 492 cases) of our cohort. The frequency of cutaneous metastasis was higher in nonacral melanoma than that in acral melanoma. The mean duration between the initial diagnosis of a primary tumor and cutaneous dissemination was 19.8 months. Cutaneous metastasis developed earlier during the disease course in acral melanoma than that in nonacral melanoma. Cutaneous metastasis was more disseminated, involving multiple anatomy sites in nonacral melanoma than that in acral melanoma. In-transit metastasis was significantly more common in acral melanoma than that in nonacral melanoma. The disease stage at the time of cutaneous metastasis was not significantly different between acral and nonaral melanoma. In-transit metastasis was commonly associated with visceral involvement in acral melanoma but not in nonacral melanoma. The extent and multiplicity of cutaneous metastasis were dependent on the status of other viscera during the cutaneous metastasis. No significant difference in survival during the cutaneous metastasis was observed between acral and nonacral melanoma. CONCLUSION: Clinicoprognostic features of cutaneous metastasis were different between acral and nonacral melanoma.

Twenty-eight-year incidence and characteristics of post-transplant skin cancers: Comparative analysis of past and recent 10-year experience.

Because primary skin cancers in organ transplant recipients are rare, little is known about the characteristics and risk factors for skin cancers in organ transplant recipients. We searched the Asan Medical Center database of 13 469 organ transplant recipients for cases of all skin cancers from January 1990 to December 2018. Characteristics of and risk factors for skin cancers were analyzed and compared according to the period of transplantation. Of the identified 113 patients with skin cancers, squamous cell carcinoma was the most common cancer followed by basal cell carcinoma and Kaposi sarcoma. The cumulative incidence of skin cancers at 28 years was 5.3%. Over the 10-year period from January 2009 to December 2018, the standardized incidence ratio for premalignant in situ skin lesions increased, whereas the standardized incidence ratio for skin cancers decreased. Age at transplantation and treatment with more than two immunosuppressive agents were risk factors for the development of new skin cancers in organ transplant recipients. Over the most recent 10-year period, post-transplant skin cancers have been found earlier and diversified compared with in the previous period.

A case of cutaneous extranodal natural killer/T-cell lymphoma clinically and histopathologically mimicking interface dermatitis.

Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare but aggressive cancer characterised by angiocentric and angiodestructive infiltration by NK-cells, or cytotoxic T-cell types. Histopathologically, ENKTL shows a multinodular or diffuse infiltration localised to vascular structures, resulting in angiodestruction and necrosis. We present a patient with an initially suspected diagnosis of benign interface dermatitis with a differential diagnosis of mycosis fungoides that was later found to be an aggressive extranodal natural killer/T-cell lymphoma of a nasal type and with a dismal prognosis.