Effect of smoking cessation on psoriasis vulgaris, palmoplantar pustulosis and generalized pustular psoriasis.

BACKGROUND: Smoking is a known risk factor for psoriasis; however, the impact of smoking cessation on psoriasis has seldom been evaluated. OBJECTIVES: We aimed to examine the effects of smoking cessation on the development of psoriasis vulgaris (PsV), palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP). METHODS: Using the Korean National Health Insurance Service database, we retrospectively compiled a cohort of 5 784 973 participants without psoriasis, analysed their changes in smoking status from 2004 to 2007 and followed up new cases of psoriasis until 2021. The psoriasis risks were compared with those of sustained smokers, smoking quitters, sustained ex-smokers and never smokers using multivariate Cox proportional hazard models. RESULTS: The mean age of the participants was 47.1 years (SD 13.5) and 3 092 426 (53.5%) were male. During 77 990 688 person-years, 67 364 psoriasis cases were identified. Compared with sustained smokers, smoking quitters showed a reduced risk of developing psoriasis [adjusted hazard ratio (aHR) 0.91; 95% confidence interval (CI) 0.87-0.95], specifically PsV (aHR 0.92; 95% CI 0.88-0.97) and PPP (aHR 0.71; 95% CI 0.63-0.79). The reduction in risk due to smoking cessation was more prominent in sustained ex-smokers (psoriasis: aHR 0.77, 95% CI 0.74-0.79; PsV: aHR 0.76, 95% CI 0.73-0.79; PPP: aHR 0.56, 95% CI 0.51-0.61; GPP: aHR 0.64; 95% CI 0.52-0.78). When conducting sensitivity analyses to address the potential for changes in smoking habits after 2007, the results and trends were consistent with the main findings, and a more pronounced significance was observed. CONCLUSIONS: Compared with continuous smoking, smoking cessation was associated with a decreased risk of developing psoriasis. The risk-reducing effect of smoking cessation was more pronounced in those maintaining a smoke-free status. Smoking cessation and the maintenance of a smoke-free status should be encouraged to prevent the development of psoriasis and all other smoking-related diseases.

Psoriasis vulgaris (PsV) is a chronic inflammatory skin condition that causes scaly plaques on the body. Pustular psoriasis [including palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP)] is a variant characterized by sterile pustules. Limited evidence exists on how quitting smoking affects psoriasis and its subtypes. In this study conducted in South Korea, we aimed to investigate how changes in smoking habits, especially quitting smoking, could impact the development of psoriasis. We used medical claims records from the Korean National Health Insurance Service database, which included data from over 5.7 million people participating in health checkups between 2004 and 2007. We divided people into four groups based on their smoking habits: sustained smokers, smoking quitters, sustained ex-smokers and never smokers. We found that smoking quitters had a lower risk of developing psoriasis, especially PsV and PPP. Even people who had quit smoking and remained smoke-free for an extended period (sustained ex-smokers) showed a more pronounced reduction in the risk of psoriasis, including PsV, PPP and GPP. Our findings remained consistent across various groups of people, considering factors such as age, sex, weight and overall health. The results suggest that encouraging people to quit smoking and maintain a smoke-free lifestyle may help to prevent the onset of psoriasis. In conclusion, this large-scale study from South Korea provides real-world evidence to suggest that quitting smoking could reduce the risk of developing psoriasis. These findings are valuable for public health initiatives, emphasizing the benefits of quitting smoking for skin health.

The efficacy and safety of low- versus high-fluence fractional picosecond Nd:YAG 1064-nm laser in the treatment of acne scars: A randomized split-face comparison study.

BACKGROUND: Differences in clinical efficacy based on the fluence of fractional picosecond laser treatment for acne scars are unknown. OBJECTIVE: To compare the efficacy and safety of low-fluence versus high-fluence fractional picosecond Nd:YAG 1064-nm laser treatment in acne scar patients. METHODS: In this 12-week, investigator-blinded, randomized, split-face study, 25 patients with moderate-to-severe acne scars received three sessions of high-fluence laser treatment (1.0 J/cm2 ) on one side of their face and low-fluence (0.3 J/cm2 ) on the other side every 4 weeks. Patients were assessed using acne scar counts, the scar global assessment (SGA), and the ECCA scar grading scale every 4 weeks. The histological analysis compared the acne scars obtained before and 4 weeks after treatment. RESULTS: At their last visit, 88.00% and 92.00% of the subjects achieved >30% reduction in scar counts on the low- and high-fluence sides, respectively, without a significant difference between the two sides. On both sides, the scar counts, SGA, and ECCA score significantly improved 4 weeks after the last treatment. Although the high-fluence side showed a greater reduction in scar counts (-66.73%) than the low-fluence side (-62.13%), the two sides had no significant difference in the grading scores. The high-fluence side showed significantly more severe pain and higher side-effect scores immediately and 4 weeks after treatment. Histological analysis revealed a significantly increased collagen, elastin, and vimentin expression after treatment on the low-fluence side. CONCLUSIONS: The low-fluence setting demonstrated comparable efficacy and superior safety in treating acne scars compared with the high-fluence setting.

Knowledge and the behavioral patterns of photoprotection among Koreans with skin disease.

BACKGROUND: Photoprotection is crucial in preventing the development and progression of various skin diseases. However, patients with skin disease have limited awareness of photoprotection. We evaluated the knowledge and behavioral patterns of photoprotection among Koreans with skin diseases. METHODS: A cross-sectional study was conducted in 11 general hospitals across South Korea. The study population consisted of patients aged 19 years or older who visited dermatologic clinics for their skin diseases. A self-administered questionnaire was used to collect patient demographics, knowledge of photoprotection, and photoprotective habits. RESULTS: In this study, 1173 patients with skin cancer, hyperpigmentary disorders, hypopigmentary disorders, or other skin diseases participated. Females scored significantly higher in knowledge of photoprotection compared to males (mean score 8.4 vs. 7.8; p < .001), and younger patients (<50 years) scored higher than older patients (mean score 8.7 vs. 7.5; p < .001). Males also reported longer sun exposure times and lower usage of photoprotective measures (both p < .001). Patients with skin cancer had the lowest mean knowledge score (7.1 ± 2.6) and were less likely to use photoprotective measures compared to other groups (p < .001). In contrast, patients with hyperpigmentation actively avoided sun exposure compared with other groups (p < 0.001). CONCLUSIONS: Knowledge of photoprotection among Korean patients with skin diseases varied depending on the gender, age, and type of skin disease. Their photoprotective behaviors were inadequate, especially among males and those with skin cancer. These findings emphasize the importance of educating and tailoring photoprotection strategies for patients with skin diseases.

Effects of the epidermal growth factor receptor inhibitor, gefitinib, on lipid and hyaluronic acid synthesis in cultured HaCaT keratinocytes.

Epidermal growth factor receptor inhibitors (EGFRIs) are widely used for treating various cancers, including lung, colon, head and neck cancers. However, EGFRIs have unique dermatological side effects, including acneiform eruption, dry skin, paronychia and pruritus. In this study, we investigated the molecular changes induced by an EGFRI, gefitinib, in the expression of lipogenic enzymes and hyaluronic acid (HA) regulatory proteins in HaCaT keratinocytes, and whether EGF restored these changes. HaCaT cells were treated with gefitinib, with or without EGF, and treated with tumor necrosis factor α (TNFα) for inducing an inflammatory response. The mRNA and protein expression was analyzed by real-time RT-PCR, enzyme-linked immunosorbent assay (ELISA) and western blotting. Gefitinib enhanced the TNFα-induced expression of C-C motif chemokine ligand 2 (CCL2), CCL5 and C-X-C motif chemokine ligand 10 (CXCL10), and the expression of TNFα in HaCaT cells, while EGF restored these changes. At a similar concentration range, gefitinib reduced the mRNA and/or protein expression of various lipogenic enzymes for fatty acid, cholesterol and ceramide synthesis, except acidic sphingomyelinase. Gefitinib suppressed the mRNA and protein expression of HA synthase 2 (HAS2), HAS3, cluster of differentiation 44 (CD44), hyaluronidase 1 (HYAL1) and HYAL2, except the mRNA expression of HYAL1. EGF restored the changes induced by gefitinib, except for the mRNA expression of fatty acid synthase (FASN) and elongation of very long-chain fatty acid protein (ELOVL) 6. In conclusion, EGFRIs suppress lipogenesis and HA metabolism, which may contribute to adverse dermatological effects, including barrier function impairment in cancer patients treated with EGFRIs.

Tumor invasion in the hyponychium is associated with distant metastasis and poor prognosis in subungual melanoma: A histologic landscape of 44 cases.

BACKGROUND: Subungual melanoma (SUM) has a poor prognosis because of delayed diagnosis. Its progression, consensus on surgical treatment, and correlation with clinical outcomes remain unclear. OBJECTIVE: We aimed to identify the pattern of dermal invasion in different locations of the nail apparatus and its relationship with prognosis. METHODS: In this retrospective review of surgically treated SUM patients between January 2011 and April 2019, the nail apparatus was divided into 5 anatomic subunits: the dorsal roof of proximal nail fold, ventral floor of proximal nail fold, germinal matrix, nail bed, and hyponychium. Invasions in the subunits were categorized using 3 criteria: no tumor, in situ tumor, or invasion. RESULTS: Among 44 cases of SUM, dermal invasion occurred mostly in the distal areas, with 11, 30, 18, 7, and 4 in the hyponychium, nail bed, germinal matrix, ventral floor of proximal nail fold, and dorsal roof of proximal nail fold, respectively. The patients with hyponychial invasion showed a significantly greater Breslow depth (P = .009), a higher rate of lymph node metastasis (P = .019), distant metastasis (P = .036), and shorter disease-free survival (P = .001). CONCLUSION: Hyponychial invasion is an important prognostic predictor of SUM, given its strong association with invasion depth, metastatic progression, and disease-free survival. Patients with invasion in the hyponychium should undergo more strict workup, treatment, and surveillance.

Sleep during Mohs micrographic surgery: A prospective study.

Mohs micrographic surgery (MMS) is a highly specialized technique for treating skin cancer. Drawbacks of MMS are the multi-step procedure and long surgery time. Some patients sleep during surgery and involuntary movements during sleeping can interfere with surgery, which increases the risk of a fall injury. However, to our knowledge, there have been no studies regarding the characteristics of patients' sleep during MMS. This study aimed to investigate the prevalence and characteristics of sleeping patients during MMS. We performed a prospective study and included patients with skin cancers impending MMS. All patients rated their anxiety levels and sleep status using the State-Trait Anxiety Inventory, an anxiety visual analog scale, the Pittsburgh Sleep Quality Index, and the Leeds Sleep Evaluation Questionnaire. Our data showed that 21.9% of patients were asleep during MMS. Multivariable analysis showed that older age (odds ratio [OR], 1.142; p=0.003), lesion size >150 mm2 (OR, 7.904; p=0.031), and multi-stage MMS (OR, 12.201; p=0.011) were significantly associated factors of sleep. This study is the first to report the prevalence and associated factors of sleep during MMS. Physicians should monitor patients with risk factors during MMS to prevent possible medical accidents.

A First-in-Human Phase I Study of GC1118, a Novel Anti-Epidermal Growth Factor Receptor Antibody, in Patients with Advanced Solid Tumors.

LESSONS LEARNED: GC1118 is a novel fully human anti-epidermal growth factor receptor (EGFR) antibody with unique binding epitopes and different ligand-binding inhibitory activity compared with cetuximab or panitumumab.GC1118 showed promising antitumor activity, especially in patients with colorectal cancer resistant to prior EGFR antibody. Skin toxicities were more common and diarrhea was less frequent compared with other anti-EGFR antibodies. BACKGROUND: GC1118 is a novel monoclonal antibody targeting epidermal growth factor receptor (EGFR) with more potent ligand inhibition than cetuximab or panitumumab. We conducted a first-in-human, phase I study of GC118 in patients with refractory solid tumors. METHODS: In the dose escalation part, GC1118 was administered on days 1, 8, 15, and 22, followed by a 2-week rest, during which dose-limiting toxicities (DLTs) were evaluated. In the expansion part, patients were enrolled into three cohorts (Cohort 1 [C1], patients with colorectal cancer [CRC] without prior anti-EGFR treatment; Cohort 2 [C2], patients with CRC with tumors resistant to anti-EGFR therapy; Cohort 3 [C3], EGFR-overexpressing gastric cancer). RESULTS: In the dose escalation part, 24 patients were treated at five dose levels: 0.3, 1.0, 3.0, 4.0, and 5.0 mg/kg. In the 5.0 mg/kg cohort, two patients experienced DLTs (skin toxicities). The maximum-tolerated dose (MTD) was 4.0 mg/kg. Common adverse events were skin toxicities. In the expansion part, 39 patients were enrolled. In Cohort 1, stable disease (SD) was observed in 58%; in Cohort 2, partial response (PR) 17% and SD 8%; in Cohort 3, PR 8% and SD 17%. CONCLUSION: GC1118 showed promising antitumor activity and was well tolerated. Infrequent diarrhea compared with other anti-EGFR antibodies might be advantageous for further development.

Skin equivalent assay: An optimized method for testing for hair growth reconstitution capacity of epidermal and dermal cells.

Hair follicle reconstitution requires highly organized epithelial-mesenchymal interactions. Skin equivalents containing the epidermal and dermal cells with hair reconstitution capacity can reproduce these processes, but have not been established. This study was conducted to develop a hair follicle-producing three-dimensional (3D) skin equivalent assay using neonate mouse epidermal and dermal cells. A skin equivalent comprised of mouse dermal cells (MDCs) embedded in type I collagen and overlaid with mouse epidermal cells (MECs) was used. MDCs were mixed with type I collagen and cultured for 7 days. One day after adding MECs on top, the composites were grafted onto nude mice. MDCs cultured on a two-dimensional (2D) plate for 7 days and mixed with MECs as a negative control, and freshly isolated MDCs and MECs mixture (chamber assay) as a positive control were also grafted. Six weeks after grafting, regenerated hair follicles were analysed. Our 3D skin equivalent culture assay reproducibly regenerated hair follicles, while MDCs precultured in the 2D model with MECs did not. Compared to the chamber assay, which produced randomly oriented hair follicles, nearly all regenerated hair follicles in our assay extruded through the skin and numerous regenerated hair follicles were higher than those in the chamber assay. Several representative genes associated with hair induction showed higher expression in our assay than in the 2D model. When Wnt3a was added, the number of regenerated hairs increased. Organized hair follicle regeneration was accomplished using our assay. This approach can be applied to assess a test agent with hair growth-promoting effects.

Pruritus in Patients Under Targeted Anticancer Therapy: A Multidimensional Analysis Using the 5-D Itch Scale.

Pruritus is a very common symptom in patients, undergoing targeted anticancer therapy. However, the characteristics of pruritus, according to the targeted anticancer agents, are still unclear. The objective of this study was to determine the characteristics of pruritus, induced by targeted anticancer agents, using a questionnaire-based survey. The survey was administered to cancer patients currently receiving anticancer agents. Medical records were also reviewed. A total of 374 cancer patients completed the survey, of which 108 were treated with the targeted therapy. A total of 205 patients had pruritus, of which 66 were under the targeted therapy. Epidermal growth factor receptor inhibitor (EGFRI) users showed the highest prevalence rate of itching and numeric rating scale score for itching. The 5-D itch score was also highest among users of EGFRIs. In conclusion, patients receiving EGFRIs suffer from severe pruritus frequently. They not only experienced long lasting and intense itching, causing sleep discomfort, but also developed itching at specific body sites.

Association Between Premature Hair Greying and Metabolic Risk Factors: A Cross-sectional Study.

The association of hair greying with metabolic syndrome is not well known, while association with obesity and coronary artery disease has been suggested. A cross-sectional study was conducted to identify an association between premature hair greying and metabolic risk factors. Of the 1,929 young healthy subjects (1,067 men and 862 women), 704 (36.4%) were categorized in the premature hair greying group. Waist circumference (means of non-premature hair greying vs. premature hair greying, 74.3 vs. 76.3 cm; p < 0.001), systolic (109.2 vs. 111.7 mmHg; p<0.001) and diastolic (65.0 vs. 66.2 mmHg; p = 0.003) blood pressures, and fasting blood sugar (90.8 vs. 91.6 mg/dl; p = 0.013) were higher and serum high-density lipoprotein cholesterol (68.1 vs 65.4 mg/dl; p < 0.001) was lower in premature hair greying group. Multivariate logistic regression analysis showed that metabolic risk factors ≥ 2 was independently associated with premature hair greying after controlling for confounding factors (odds ratio 1.725; p = 0.036). The present study revealed an association between premature hair greying and metabolic risk factors.

Efficacy of interventions for prevention of chemotherapy-induced alopecia: a systematic review and meta-analysis.

Chemotherapy-induced alopecia (CIA) is a highly distressing event for cancer patients, and hence, we here aimed to assess the efficacy of various interventions in the prevention of CIA. We searched PubMed, EMBASE and the Cochrane Library, from June 20, 2013 through August 31, 2013. Two of the authors independently reviewed and selected clinical trials that reported the efficacy of any intervention for prevention of CIA compared with that of controls. Two authors extracted data independently on dichotomized outcome in terms of CIA occurrence. Relative risks (RRs) and 95% confidential intervals (CIs) were calculated for efficacy of CIA prevention by using random-effect or fixed-effect models. Out of 691 articles retrieved, a total of eight randomized controlled trials and nine controlled clinical trials involving 1,098 participants (616 interventions and 482 controls), were included in the final analyses. Scalp cooling, scalp compression, a combination of cooling and compression, topical minoxidil and Panicum miliaceum were used as interventions. The participants were mainly breast cancer patients receiving doxorubicin- or epirubicin-containing chemotherapy. Scalp cooling, which is the most popular preventive method, significantly reduced the risk of CIA (RR = 0.38, 95% CI = 0.32-0.45), whereas topical 2% minoxidil and other interventions did not significantly reduce the risk of CIA. No serious adverse effects associated with scalp cooling were reported. Our results suggest that scalp cooling can prevent CIA in patients receiving chemotherapy. However, the long-term safety of scalp cooling should be confirmed in further studies.

Association of premature hair graying with family history, smoking, and obesity: a cross-sectional study.

BACKGROUND: Many researchers have been concerned about the association of hair graying with systemic diseases. However, the common factors associated with hair graying and systemic diseases have not been elucidated. OBJECTIVE: This study aimed to identify risk factors for premature hair graying (PHG) in young men. METHODS: We conducted a cross-sectional study using questionnaires in young men. After a pilot study that included 1069 men, we surveyed 6390 men younger than 30 years about their gray hair status and various socioclinical characteristics. RESULTS: The age of participants in the main survey was 20.2 ± 1.3 years (mean ± SD). Of the 6390 participants, 1618 (25.3%) presented with PHG. Family history of PHG (odds ratio [OR], 12.82), obesity (OR, 2.61), and >5 pack-years history of smoking (OR, 1.61) were significantly associated with PHG. In the multivariate analysis, family history of PHG (OR, 2.63) and obesity (OR, 2.22) correlated with the severity of PHG. LIMITATIONS: Owing to the use of questionnaires, the possibility of recall bias exists. Women were not evaluated in this study. CONCLUSION: Smoking, family history of PHG, and obesity are important factors associated with PHG.

Clinical characteristics of chemotherapy-induced alopecia in childhood.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a frequent complication in patients with cancer. There are an increasing number of reports of permanent CIA. OBJECTIVE: We investigated the clinical characteristics of CIA, including permanent CIA in childhood. METHODS: We collected data on 159 pediatric patients who had undergone high-dose conditioning chemotherapy followed by hematopoietic stem cell transplantation and 167 control subjects, using a questionnaire, medical record reviews, and phototrichograms. RESULTS: Alopecia began at 1.5 ± 1.4 months and was sustained until 2.2 ± 1.6 months after chemotherapy initiation. Hair regrowth started 2.6 ± 1.6 months after chemotherapy ceased and lasted for 7.3 ± 4.9 months. The mean hair density and thickness were 198.3 ± 47.4/cm(2) and 76.3 ± 18.4 µm in the patient group and 229.6 ± 34.5/cm(2) and 79.5 ± 12.4 µm in the control group, respectively (both, P < .001). In all, 19 (12%) patients experienced permanent CIA. Thiotepa use was identified as a significant risk factor for permanent CIA (odds ratio 7.57, P = .002). LIMITATIONS: Cross-sectional study in a single-center is a limitation. CONCLUSION: CIA is common in pediatric patients. Use of thiotepa is strongly associated with permanent CIA.

Acral lentiginous melanoma: indolent subtype with long radial growth phase.

Acral lentiginous melanoma (ALM) is the most common type of cutaneous melanoma in Asian populations. Traditionally, ALM was believed to have a poorer prognosis than other subtypes of cutaneous melanoma because of its aggressive behavior. However, in Asians, there have been several unusual case reports that have shown only subtle melanocytic proliferation despite clinically malignant manifestations. We performed a retrospective study of 13 patients with ALM. We reviewed the clinical histories, histopathologies, and immunohistochemical staining from these patients. Clinically, the lesions were characterized by a brown to black pigmented patch with irregular borders and variegated pigmentation on the sole, heel, or finger. Histopathologically, most specimens revealed only bland scattered proliferation of atypical melanocytes without marked cellular atypia or dermal invasion. However, some of the lesions were suspected to progress to the invasive stage, into the papillary dermis after a long period of time. Although cytological atypia of the melanocytes is not sufficient to ALM in situ, the melanocytic proliferation pattern, dermal inflammation, and correlation with clinical presentation would suffice in making the correct diagnosis of ALM in situ. In these cases, more biopsies of other areas should be recommended for the precise diagnosis and early complete excision in accordance with ALM in situ.

Reduced economic disparity in biologics use for psoriasis after introducing the reducing copayment program.

Biologics for psoriasis are efficient and safe, but very expensive. We investigated the association of the reducing copayment program (RCP) with changes in biologics use patterns depending on the income levels of patients with moderate-to-severe psoriasis. This nationwide cohort study included patients identified as having moderate-to-severe psoriasis between 2014 and 2020. Logistic regression models were used to estimate the odds ratio for the use of biologics according to income levels. Among 57,139 patients with moderate-to-severe psoriasis, 3464 (6.1%) used biologics for psoriasis from 2014 to 2020. After the introduction of RCP in 2017, the proportion of patients with moderate-to-severe psoriasis using biologics rapidly increased from 5.0% in 2016 to 19.2% in 2020; the increase was more remarkable in patients with the lowest or mid-low income compared to those with Medical Aid. Drug survival of biologics was higher in patients with the highest income before the RCP, but became comparable between those with high and low incomes after RCP introduction. The introduction of RCP was associated with an increased use of biologics in patients with moderate-to-severe psoriasis of all income levels; however, the effect was more pronounced in low-income patients. The RCP may contribute to alleviating the disparity in access to biologics.