Human papillomavirus Detection Rates in Bowen's Disease: Correlation with Pelvic and Digital Region Involvement and Specific p53 Immunostaining Patterns.

BACKGROUND: The relationship between human papillomavirus (HPV) and Bowen's disease (BD) is not fully understood. OBJECTIVES: To investigate the differences in HPV detection rates in BD samples across various body regions and analyze the expression patterns of p53, p16, and Ki-67 in relation to HPV presence. METHODS: Tissue samples from patients diagnosed with BD, confirmed through histopathology, were retrospectively collected. Next-generation sequencing was used for HPV DNA detection. Immunohistochemistry (IHC) for p16, p53, and Ki-67 was performed. RESULTS: Out of 109 patients with BD, 21 (19.3%) were HPV-positive. All identified types were α-HPVs, with HPV-16 being the most common. The HPV detection rate was significantly higher in the pelvic (69.2%, P<0.001) and digital (50.0%, P=0.022) areas compared to those in the other regions. HPV presence was significantly correlated with p53 negativity (P=0.002), the p53 "non-overexpression" IHC pattern (P<0.001), and p53-p16 immunostain pattern discordance (P<0.001). Conversely, there was no notable association between HPV presence and p16 positivity, the p16 IHC pattern, or Ki-67 expression. CONCLUSIONS: Our findings suggest the oncogenic role of sexually transmitted and genito-digitally transmitted α-HPVs in pathogenesis of BD in the pelvic and digital regions.

Successful Long-Term Multimodality Management of Facial Lesions in Tuberous Sclerosis Complex in an Adult Patient.

Angiofibroma and shagreen patches are common cutaneous manifestations of tuberous sclerosis complex (TSC) and have significant physical and psychological repercussions for patients. Several treatments have been proposed to improve lesions; however, clear treatment guidelines have not yet been presented. Thus, we introduce a case of angiofibroma and shagreen patch improved by application of pulsed dye laser, ablative fractional CO2 laser, and topical rapamycin, and present clinical implications for the treatment of angiofibroma and shagreen patch in TSC.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Ultrasonographic analysis of facial skin thickness in relation to age, site, sex, and body mass index.

BACKGROUND: Numerous nonsurgical but invasive cosmetic procedures are performed blindly in the dermis or subcutaneous fat layer of the facial skin. OBJECTIVES: To measure the numerical skin thickness of the facial areas where dermatological procedures are performed by applying ultrasound techniques, and to make it possible to estimate the skin thickness by investigating the influence of several individual constitutional factors such as age, sex, and body mass index (BMI), so that these variables can be applied to estimate skin thickness. MATERIALS AND METHODS: Skin thickness was measured at eight different facial points using an ultrasound machine (Affiniti 50; Philips Inc.). Demographic data were gathered using questionnaires. Manual BMI was calculated from the weight and height of each participant, and individual BMI measurements were performed using a body composition analyzer. RESULTS: In terms of whole skin thickness, the thickest point was the mouth corner, and the thinnest point was the lateral forehead. The thickest point in the epidermis was the chin, and the thinnest point was the nasolabial fold. The thickest point in the dermis was the corner of the mouth, and the thinnest was the lateral forehead. Full skin thickness and dermal thickness were mostly lower in females. Skin thickness was not significantly correlated with BMI. CONCLUSION: The skin thickness at different points on the face was variable, and realistic data about skin thickness can be obtained by in vivo ultrasonographic analysis of the skin.

Increased dental comorbidities in patients with psoriasis: a nationwide population-based cohort study in Korea.

BACKGROUND: Limited data are available regarding the association between psoriasis and common dental conditions. OBJECTIVES: To investigate the risk of potential dental comorbidities in patients with psoriasis. METHODS: We conducted a nationwide population-based cohort study to analyse the claims data of patients with psoriasis (n = 15 165) and age- and sex-matched controls (n = 75 825). The incidence risk of the following potential dental conditions was analysed: dental caries, pulp and periapical disease, periodontal disease, gingival changes and tooth loss. RESULTS: After adjusting for potential cofactors, the adjusted hazard ratios (aHRs) of dental caries [1.105; 95% confidence interval (CI) 1.078-1.132], pulp and periapical disease (1.07; 95% CI 1.044-1.096) and periodontal disease (1.108; 95% CI 1.088-1.129) were significantly higher than those in the control cohort (P < 0.001). However, among the subset of patients with psoriasis who received systemic antipsoriatic treatment (n = 4275), the aHR risk of all potential dental comorbidities was not significantly higher from that of the control cohort. CONCLUSIONS: Patients with psoriasis have an increased risk of dental comorbidities, and systemic antipsoriatic treatment may help mitigate this increased risk.

Guidelines for the Management of Patients with Alopecia Areata in Korea: Part I Topical and Device-based Treatment.

BACKGROUND: Alopecia areata (AA) is a chronic disease with an unpredictable disease course and severe psychological impact. OBJECTIVE: To provide evidence- and consensus-based insights regarding the treatment of patients with AA in Korea. METHODS: We searched for relevant studies on the topical and device-based treatment of AA in the literature from inception until May 2021. Evidence-based recommendations were also prepared. The evidence for each statement was graded and classified according to the strength of the recommendations. Hair experts from the Korean Hair Research Society (KHRS) voted on the statements, and an agreement of 75% or greater was considered as consensus. RESULTS: Currently, there remains a scarcity of topical treatments, which is supported by robust evidence from a number of high-quality randomized controlled trials. Current evidence supports the efficacy of topical corticosteroids, corticosteroid intralesional injection, and contact immunotherapy in AA patients. Topical corticosteroids and contact immunotherapy are recommended for pediatric AA. A consensus was achieved in 6 out of 14 (42.8%), and 1 out of 5 (20.0%) statements pertaining to topical and device-based treatments in AA, respectively. The expert consensus was from a single country, and the study may not cover all the treatments used. CONCLUSION: The present study provides up-to-date, evidence-based treatment guidelines for AA based on the consensus reached among experts after considering regional healthcare circumstances, adding diversity to the previous guidelines.

Guidelines for the Management of Patients with Alopecia Areata in Korea: Part II Systemic Treatment.

BACKGROUND: Alopecia areata (AA) is a chronic disease with an unpredictable course and can have a severe psychological impact on an individual. OBJECTIVE: To provide evidence and consensus-based statements regarding the treatment of patients with AA in Korea. METHODS: We searched for relevant studies from inception to May 2021 regarding the systemic treatment of AA. Evidence-based recommendations were also prepared. The evidence for each statement was graded and classified according to the strength of the recommendations. Hair experts from the Korean Hair Research Society (KHRS) voted on the statement, and an agreement of 75% or greater was considered as having reached consensus. RESULTS: Current evidence supports the efficacy of systemic corticosteroids, oral cyclosporine monotherapy or combination with systemic corticosteroids, and oral Janus kinase inhibitors in severe AA patients. Systemic steroids may be considered for pediatric patients with severe AA. A consensus was achieved in three out of nine (33.3%), and one out of three (33.3%) statements pertaining to systemic treatment in adult and pediatric AA, respectively. CONCLUSION: The present study produced up-to-date, evidence-based treatment guidelines for AA associated with the consensus obtained by experts based on the Korean healthcare system.

Periodontal disease does not increase the risk of subsequent psoriasis.

Previous studies suggested that chronic periodontitis may be a risk factor for psoriasis. However, no study has confirmed this relationship for all stages of periodontal disease (gingivitis and periodontitis). This nationwide population-based retrospective cohort study aimed to investigate whether periodontal disease is an independent risk factor for the development of subsequent psoriasis. Patients aged ≥ 20 years who underwent both medical and oral checkups from the National Health Screening Program between 2002 and 2007 were selected from a customized database provided by the National Health Insurance Service (NHIS). Then, patients with periodontal disease (n = 3,682,468) and without periodontal disease (control, n = 3,637,128) according to oral examination results were identified. We tracked each patient for subsequent psoriasis diagnosis until the end of 2018 using NHIS database. The incidence rates of psoriasis per 1000 person-years were 0.36 and 0.34 in the periodontal disease group and control groups, respectively. After adjusting for potential cofactors, no significant increase in risk (adjusted hazard ratio, 0.994; 95% confidence interval, 0.974-1.015) was observed. Similar results were observed when analyzing the risk of psoriasis in patients who required scaling or periodontal surgery. In conclusion, periodontal disease is not an independent risk factor of psoriasis.

Low detection rate of human papillomavirus in patients with cutaneous squamous cell carcinoma and keratoacanthoma

Background: The role of human papillomavirus (HPV) in keratoacanthoma (KA) remains unclear. Objectives: To identify possible differences in HPV DNA, detected by next-generation sequencing (NGS), between KAs and cutaneous squamous cell carcinomas (cSCCs), which may suggest different pathogenesis. Materials & Methods: We extracted DNA from formalin-fixed and paraffin-embedded (FFPE) tissue blocks from samples of 151 patients (105 with cSCCs and 46 with KAs). HPV DNA was detected using the NGS-based Ezplex® kit. HPV detection rates and other clinical characteristics were compared. Results: HPV was detected in 6.7% (7/105) of cSCC and 10.9% (5/46) of KA samples. Eight alpha-HPV genotypes (16, 57, 81, 31, 33, 45, 53, and 58) were detected, with HPV 16 being the most common. Only one type (57) is commonly classified as cutaneous type, and the rest are all mucosal types. HPV detection rate did not significantly differ between the KA and cSCC groups. Conclusion: HPV detection was relatively low in KA and cSCC samples. HPV might be related to the pathogenesis of only selected KA and cSCC cases.

Impact of Pediatric Alopecia Areata on Quality of Life of Patients and Their Family Members: A Nationwide Multicenter Questionnaire Study.

BACKGROUND: Pediatric alopecia areata (AA) can affect the quality of life (QoL) of patients and their family members. Research on the QoL and burden on family members in pediatric AA is limited. OBJECTIVE: This nationwide multicenter questionnaire study described the QoL and burden of the family members of patients with pediatric AA. METHODS: This nationwide multicenter questionnaire study enrolled AA patients between the ages of 5 and 18 years from March 1, 2017 to February 28, 2018. Enrolled patients and their parents completed the modified Children's Dermatology Life Quality Index (CDLQI) and the modified Dermatitis Family Impact (mDFI). The disease severity was measured using the Severity of Alopecia Tool (SALT) survey scores. RESULTS: A total of 268 patients with AA from 22 hospitals participated in this study. Our study found that the efficacy and satisfaction of previous treatments of AA decreased as the severity of the disease increased. The use of home-based therapies and traditional medicines increased with the increasing severity of the disease, but the efficacy felt by patients was limited. CDLQI and mDFI scores were higher in patients with extensive AA than those with mild to moderate AA. The economic and time burden of the family members also increased as the severity of the disease increased. CONCLUSION: The severity of the AA is indirectly proportional to the QoL of patients and their family members and directly proportional to the burden. Physicians need to understand these characteristics of pediatric AA and provide appropriate intervention to patients and their family members.

Treatment of patients with chronic pruritus of unknown origin with dupilumab.

BACKGROUND: Chronic pruritus of unknown origin (CPUO) is a highly debilitating disease that lacks effective treatments. This study explores a new therapeutic strategy with dupilumab. OBJECTIVES: To examine whether patients with CPUO demonstrate clinical response to dupilumab. PATIENTS AND METHODS: This is a retrospective case series examining all patients with CPUO who were treated with dupilumab from March 2017 to December 2019 at a tertiary referral clinic at Washington University School of Medicine in St. Louis, MO. Numerical rating scale (NRS) itch score changes over time were recorded and analyzed. RESULTS: Fifteen patients (67% women; mean [SD] age, 68.7 [12.6] years [range, 42-88 years]) were included in the analysis. All patients had a diagnosis of CPUO for a mean [SD] 2.6 [2.8] years. The median [IQR] pruritus NRS itch score before dupilumab injection was 8 [8-10] and the final median [IQR] NRS itch score was 1 [0-2.5]. The mean [SD] reduction in the NRS itch score was 7.0 [1.9]. Dupilumab was well tolerated with one report of mild injection site reaction that was self-resolving. CONCLUSION: This study suggests that dupilumab may be an effective treatment for patients with CPUO and supports the design of future randomized placebo-controlled trials to prove its efficacy.

Dynamic thermal imaging for pigmented basal cell carcinoma and seborrheic keratosis.

BACKGROUND: Clinical differentiation between pigmented basal cell carcinoma (BCC) and seborrheic keratosis (SK) can sometimes be difficult. Noninvasive diagnostic technologies, such as thermal imaging, can be helpful in these situations. This study explored the use of dynamic thermal imaging (DTI), which records thermal images after the application of external thermal stimuli (heat or cold) for the differential diagnosis of pigmented BCC and SK. MATERIALS AND METHODS: Twenty-two patients with pigmented BCC and 15 patients with SK participated in this study. Dynamic thermal images of lesions (pigmented BCC or SK) and control sites (contralateral normal skin) were recorded after the heat and cold stimuli. Temperature changes in the region of interest (ROI) are plotted as a thermal response graph. After fitting an exponential equation to each thermal response graph, the rate constants were compared between groups (pigmented BCC versus control, SK versus control). RESULTS: The thermal response graphs revealed that the average temperature of pigmented BCC showed faster thermal recovery to baseline than the control site. There was a significant difference in the rate constants of the fitted exponential equations between the pigmented BCCs and the control sites (p<.001). However, we did not find a significantly different thermal recovery pattern between SK lesions and control sites. CONCLUSIONS: DTI can be used as a diagnostic tool for distinguishing pigmented BCC from SK by comparing thermal recovery patterns between target lesions (pigmented BCC or SK) and the control site.

Tumor Necrosis Factor-Alpha Inhibitor-Associated Psoriatic Alopecia in a Patient with Ulcerative Colitis: A Case Report and Review of the Literature.

Paradoxical reactions in patients treated with tumor necrosis factor-alpha inhibitors (TNFis) have an estimated prevalence of 1.5% to 5%. Such reactions usually present as psoriasiform eruptions on the trunk and extremities along with palmar and flexural involvement. When affecting the scalp, new-onset psoriasis induced by TNFi can result in non-scarring or scarring alopecia. Although the paradoxical reaction was first reported in 2003, this TNFi-associated psoriatic alopecia (TiAPA) has been recently reported with increasing frequency. This condition is characteristically reversible and requires clinical and histopathological identification from other diseases for proper treatment. The cessation of TNFi therapy may not be mandatory, and decision to continue TNFi therapy depends on the severity of TiAPA and the risk-benefit ratio of treatment modification on the underlying disease. Herein, we report a case of TiAPA in a patient with inflammatory bowel disease whose alopecia improved following suspension of TNFi. We also describe the clinical and histopathological diagnostic criteria based on review of the literature.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 2. Management of H1-Antihistamine-Refractory Chronic Urticaria.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H1-antihistamines, even though the dose of H1-antihistamines is increased up to 4-fold. CSU that is not controlled with H1-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H1-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.

Human papillomavirus is more frequently detected in the pelvic than non-pelvic area in patients with squamous cell carcinoma in situ (Bowen's disease).

BACKGROUND: The detection rate of human papillomavirus (HPV) in Bowen's disease (BD) varies greatly. OBJECTIVES: To detect HPV DNA in BD samples using next-generation sequencing (NGS) and compare HPV detection rates between pelvic and non-pelvic BD. MATERIALS AND METHODS: We evaluated 99 patients with BD in our institution. DNA was extracted from formalin-fixed and paraffin embedded (FFPE) tissue blocks. The presence of HPV DNA material was detected using special kit-based NGS technology. Clinical characteristics and HPV detection rates were then compared between pelvic and non-pelvic BD samples. RESULTS: HPV was detected in 26 (26.3%) BD samples. A total of 10 types of α-HPV was detected: HPV 16, 53, 31, 58, 66, 26, 27, 57, 45, and 72. The most common HPV type was 16 (12.1%). Only two types (27 and 57) were frequently classified as cutaneous type, and the rest were mucosal types. The HPV detection rate was significantly higher in pelvic BD (45.2%) compared to non-pelvic BD (17.6%). CONCLUSION: The present study suggests that sexually transmitted mucosal α-HPV plays a significant role in the pathogenesis of BD, especially in the pelvic region.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.