Staphylococcus aureus causes aberrant epidermal lipid composition and skin barrier dysfunction.

BACKGROUND: Staphylococcus (S) aureus colonization is known to cause skin barrier disruption in atopic dermatitis (AD) patients. However, it has not been studied how S. aureus induces aberrant epidermal lipid composition and skin barrier dysfunction. METHODS: Skin tape strips (STS) and swabs were obtained from 24 children with AD (6.0 ± 4.4 years) and 16 healthy children (7.0 ± 4.5 years). Lipidomic analysis of STS samples was performed by mass spectrometry. Skin levels of methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) were evaluated. The effects of MSSA and MRSA were evaluated in primary human keratinocytes (HEKs) and organotypic skin cultures. RESULTS: AD and organotypic skin colonized with MRSA significantly increased the proportion of lipid species with nonhydroxy fatty acid sphingosine ceramide with palmitic acid ([N-16:0 NS-CER], sphingomyelins [16:0-18:0 SM]), and lysophosphatidylcholines [16:0-18:0 LPC], but significantly reduced the proportion of corresponding very long-chain fatty acids (VLCFAs) species (C22-28) compared to the skin without S. aureus colonization. Significantly increased transepidermal water loss (TEWL) was found in MRSA-colonized AD skin. S. aureus indirectly through interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, and IL-33 inhibited expression of fatty acid elongase enzymes (ELOVL3 and ELOVL4) in HEKs. ELOVL inhibition was more pronounced by MRSA and resulted in TEWL increase in organotypic skin. CONCLUSION: Aberrant skin lipid profiles and barrier dysfunction are associated with S. aureus colonization in AD patients. These effects are attributed to the inhibition of ELOVLs by S. aureus-induced IL-1ß, TNF-α, IL-6, and IL-33 seen in keratinocyte models and are more prominent in MRSA than MSSA.

Real-world effectiveness of a fractional CO2 laser with topical antifungal agents for the treatment of onychomycosis.

Current therapeutic agents for onychomycosis have limited efficacy or cause side effects. Recently, successful treatment using fractional CO2 lasers has been reported; however, the results are inconsistent. We analyzed the real-world effectiveness of a Fractional CO2 laser for the treatment of Onychomycosis A single-center retrospective chart review was conducted during January 2015-December 2018. Patients, diagnosed with onychomycosis through fungal culture and/or potassium hydroxide staining, underwent three or more fractional CO2 laser treatments and used topical antifungal agents. Treatment effects were assessed by using clinical images at 6, 12 months, and the last visit. Ninety-six patients were included; they underwent an average of 7.7 laser treatment sessions. Finally, 15 patients (15.6%) showed complete response (100% clearing of all nails), 24 patients (25%) showed partial response, and 57 patients (59.4%) showed no response (no 100% clearing of nails among all treated toenails per patient including mild improvement or temporary cosmetic improvement). Multivariable logistic regression analysis revealed longer disease duration (p = 0.006, OR = 1.16 [95% CI: 1.05-1.31]), patients with diabetes (p = 0.021, OR = 9.82 [95% CI: 1.75-94.01]) and fewer number of laser treatment sessions (p = 0.001, OR = 0.76 [95% CI: 0.64-0.89]) were significantly associated with non-response group. In conclusion, fractional CO2 laser with topical antifungal could be a safe alternative treatment in patients with onychomycosis, who are difficult to take oral antifungals.

Rare Case of Double-Positive CD4/CD8 Immunophenotype in Lennert Lymphoma With Cutaneous Involvement: A Case Report.

ABSTRACT: Lennert lymphoma is a lymphoepithelioid variant of peripheral T-cell lymphoma (not otherwise specified) with characteristics that do not fit into other peripheral T-cell lymphoma categories. Lennert lymphoma is primarily a nodal disease, and skin involvement may be exhibited. Cutaneous manifestations in Lennert lymphoma are nonspecific and include erythematous papules, nodules, and small plaques. Histological examination of cutaneous involvement characteristically presents epithelioid histiocytes and atypical small lymphocytes around vessels or appendages. A lymph node (LN) biopsy is essential for Lennert lymphoma diagnosis. In Lennert lymphoma, immunohistochemistry of both LNs and the involved skin reveals T-cell marker positivity. Although most Lennert lymphoma cases present with a single-positive CD4/CD8 immunophenotype, few cases present with a double-positive CD4/CD8 immunophenotype. We report a case of a 54-year-old woman presenting with fever, chills, general weakness, and a skin rash of erythematous patches on the trunk, extremities, and buttocks. A skin biopsy of the buttocks revealed atypical lymphocytes around the dermal vessels. In immunohistochemistry, these atypical lymphocytes stained positive for CD3, CD4, CD8, and CD68 but negative for CD20, CD30, and granzyme B. Similarly, a biopsy of the axillary LN revealed numerous epithelioid cells with atypical lymphocytes, exhibiting positivity for CD3, CD4, CD8, and CD68 but negativity for CD20, CD30, and S-100. Ki-67 was overexpressed in both the skin and LN. The final diagnosis of the patient was Lennert lymphoma with cutaneous involvement and a rare double-positive CD4/CD8 immunophenotype. The patient was transferred to another hospital for chemotherapy as per her request.

A Case of Eosinophilic Pustular Folliculitis Associated With Herpes Zoster.

ABSTRACT: Patients with eosinophilic pustular folliculitis (EPF), a sterile eosinophilic infiltration of hair follicles, often present with papulopustules that tend to form annular plaques. Histopathologic examination revealed eosinophilic infiltration around the pilosebaceous units and eosinophilic microabscess formation. Although the pathogenesis of EPF is unknown, T-helper type 2 immune responses were suggested to be important based on their stimulating effect on the sebaceous glands. Here, we report the first case of EPF associated with herpes zoster, indicating that herpes zoster and EPF are correlated with T-helper type 2 immune responses.

A case of multinucleate cell angiohistiocytoma in a 14-year-old boy showing two different clinical and histopathological findings.

Multinucleate cell angiohistiocytoma (MCAH) is a rare cutaneous disease entity characterized by multiple red-to-brown or violaceous papules usually located on the acral regions, such as the face and the distal arms and legs. It affects elderly women more than men and rarely occurs at a young age. The exact pathogenic mechanism of MCAH is not yet clearly understood. We report an exceptionally rare case of a 14-year-old boy who presented with multiple asymptomatic erythematous papules and a single flat brownish plaque on the left chest. The brownish plaque lesion histologically showed proliferation of dilated small vessels in the upper-mid dermis and numerous oddly shaped multinucleate cells intermingled with lymphocytes and macrophages. The erythematous papules also showed dilated small vessels in the upper-mid dermis and multiple interstitial histiocytic infiltrations, but no multinucleate cells were detected. In immunohistochemistry studies, CD68 and vimentin staining were positive for both specimens. Based on the clinicopathological findings and immunohistochemistry studies, MCAH was diagnosed. To the best of our knowledge, this is the first case report of MCAH occurring in young age and showing two different clinical and histological phases at the same time.

Unusual Complex Apocrine Tumor Consisting of Syringocystadenoma Papilliferum and Apocrine Hidrocystoma within a Single Lesion: A Case Report.

Syringocystadenoma papilliferum (SCAP) and apocrine hidrocystoma (AH) are benign apocrine neoplasms that usually occur separately. SCAP arises predominantly in head and neck, while AH typically develop in periorbital area. We report a case of a 68-year-old male with an asymptomatic erythematous papulonodule that occurred on his back 3 years ago. Histologic examination showed cystic invagination extending from the epidermis into the dermis with some papillary projections. The invaginated portion was lined by epithelial bilayer composed of cuboidal and columnar cells, and decapitation secretion was observed in the inner epithelial layer. In the deep dermis, multiple cystic spaces with variable sizes were observed, and these cysts also presented double layers of the epithelium and decapitation secretion. According to such histologic features, the coexistence of SCAP and AH within a single lesion was demonstrated. The patient was recommended to completely remove the remaining lesion after punch biopsy, but he refused further surgical management. Herein, we report an unusual case of complex apocrine tumor with a rare composition in an atypical site.

Real-World Outcomes of Adalimumab Treatment for Moderate and Severe Psoriasis in Korean Patients (RAPSODI Study).

BACKGROUND: Psoriasis imposes a significant treatment burden on patients, particularly impacting well-being and quality of life (QoL). The psychosocial impact of psoriasis treatments remains unexplored in most patient populations. OBJECTIVE: To assess the impact of adalimumab on health-related QoL (HRQoL) in Korean patients with psoriasis. METHODS: This 24-week, multicenter, observational study, assessed HRQoL in Korean patients treated with adalimumab in a real-world setting. Patient-reported outcomes (PROs) including European Quality of Life-5 Dimension scale (EQ-5D), EQ-5D VAS, SF-36, and DLQI were evaluated at week 16 and 24, versus baseline. Patient satisfaction was assessed using TSQM. RESULTS: Among 97 enrolled patients, 77 were assessed for treatment effectiveness. Most patients were male (52, 67.5%) and mean age was 45.4 years. Median baseline body surface area and Psoriasis Area and Severity Index (PASI) scores were 15.00 (range 4.00~80.00) and 12.40 (range 2.70~39.40), respectively. Statistically significant improvements in all PROs were observed between baseline and week 24. Mean EQ-5D score improved from 0.88 (standard deviation [SD], 0.14) at baseline to 0.91 (SD, 0.17) at week 24 (p=0.0067). The number of patients with changes in PASI 75, 90, or 100 from baseline to week 16 and 24 were 65 (84.4%), 17 (22.1%), and 1 (1.3%); and 64 (83.1%), 21 (27.3%), and 2 (2.6%), respectively. Overall treatment satisfaction was reported, including effectiveness and convenience. No unexpected safety findings were noted. CONCLUSION: Adalimumab improved QoL and was well-tolerated in Korean patients with moderate to severe psoriasis, as demonstrated in a real-world setting. Clinical trial registration number (clinicaltrials.gov: NCT03099083).

Alterations of Epidermal Lipid Profiles and Skin Microbiome in Children With Atopic Dermatitis.

PURPOSE: We aimed to investigate epidermal lipid profiles and their association with skin microbiome compositions in children with atopic dermatitis (AD). METHODS: Specimens were obtained by skin tape stripping from 27 children with AD and 18 healthy subjects matched for age and sex. Proteins and lipids of stratum corneum samples from nonlesional and lesional skin of AD patients and normal subjects were quantified by liquid chromatography tandem mass spectrometry. Skin microbiome profiles were analyzed using bacterial 16S rRNA sequencing. RESULTS: Ceramides with nonhydroxy fatty acids (FAs) and C18 sphingosine as their sphingoid base (C18-NS-CERs) N-acylated with C16, C18 and C22 FAs, sphingomyelin (SM) N-acylated with C18 FAs, and lysophosphatidylcholine (LPC) with C16 FAs were increased in AD lesional skin compared to those in AD nonlesional skin and that of control subjects (all P < 0.01). SMs N-acylated with C16 FAs were increased in AD lesional skin compared to control subjects (P < 0.05). The ratio of NS-CERs with long-chain fatty acids (LCFAs) to short-chain fatty acids (SCFAs) (C24-32:C14-22), the ratio of LPC with LCFAs to SCFAs (C24-30:C16-22) as well as the ratio of total esterified omega-hydroxy ceramides to total NS-CERs were negatively correlated with transepidermal water loss (rho coefficients = -0.738, -0.528, and -0.489, respectively; all P < 0.001). The proportions of Firmicutes and Staphylococcus were positively correlated to SCFAs including NS ceramides (C14-22), SMs (C17-18), and LPCs (C16), while the proportions of Actinobacteria, Proteobacteria, Bacteroidetes, Corynebacterium, Enhydrobacteria, and Micrococcus were negatively correlated to these SCFAs. CONCLUSIONS: Our results suggest that pediatric AD skin shows aberrant lipid profiles, and these alterations are associated with skin microbial dysbiosis and cutaneous barrier dysfunction.

Cutaneous Small-vessel Vasculitis after ChAdOx1 COVID-19 Vaccination: A Report of Five Cases.

Amidst the Coronavirus Disease 2019 (COVID-19) pandemic, vaccination against severe acute respiratory syndrome 2 (SARS-CoV-2) is recommended for everyone over 18 years in South Korea, with the exception of pregnant women. Unexpected adverse cutaneous reactions after the COVID-19 vaccination have been recently reported. Cutaneous small-vessel vasculitis (CSVV) predominantly affects small blood vessels, defined as small intraparenchymal arteries, arterioles, capillaries, and venules, without any detectable involvement of non-cutaneous organs. We report five cases of CSVV after the ChAdOx1 COVID-19 vaccination in 44- to 68-year-old women. The symptoms commonly appeared within 2 days after vaccination. The lesion was localized to the lower limbs in four patients and spread to the upper limbs in one patient. All patients demonstrated a favorable response to oral methylprednisolone, antihistamines, and topical steroids. Considering the importance of the COVID-19 vaccination, clinicians should be aware of CSVV as a potential adverse event. Further studies are required to elucidate the causative link and pathogenesis.

Postherpetic Trigeminal Trophic Syndrome: A Case Report.

Trigeminal trophic syndrome (TTS) is a rare condition characterized by anesthesia, paresthesia, and facial ulceration involving the trigeminal dermatome secondary to self-manipulation of the skin after a peripheral or central injury to the trigeminal nerve or its branches. Differential diagnosis of TTS includes conditions presenting with chronic facial ulceration, such as various infectious diseases, malignancy, vasculitis, pyoderma gangrenosum and dermatitis artefacta. We report a case of postherpetic TTS and highlight the importance of early diagnosis and prompt treatment of this condition, which may commonly be misdiagnosed.

Livedo reticularis following administration of ChAdOx1 nCoV-19 vaccine (AZD1222): a report of two cases.

The cutaneous appearance of transient or persistent livedo reticularis is characterized by violaceous, mottled, ring-shaped interconnecting lesions that form a reticular or net-like pattern. It can occur physiologically in response to cold exposure, such as in cutis marmorata, but can also be induced by pathological conditions such as vascular obliterans or venodilation. We report two cases of livedo reticularis that occurred on the lower limbs of two patients post ChAdOx1 nCoV-19 vaccination. As the patients had no other likely causes of livedo reticularis, the reticular skin lesions were suspected to occur in association with the ChAdOx1 nCoV-19 vaccination. Livedo reticularis is an uncommon adverse reaction, with few cases being reported post ChAdOx1 nCoV-19 vaccination.

Particulate matter causes skin barrier dysfunction.

The molecular mechanisms that underlie the detrimental effects of particulate matter (PM) on skin barrier function are poorly understood. In this study, the effects of PM2.5 on filaggrin (FLG) and skin barrier function were investigated in vitro and in vivo. The levels of FLG degradation products, including pyrrolidone carboxylic acid, urocanic acid (UCA), and cis/trans-UCA, were significantly decreased in skin tape stripping samples of study subjects when they moved from Denver, an area with low PM2.5, to Seoul, an area with high PM2.5 count. Experimentally, PM2.5 collected in Seoul inhibited FLG, loricrin, keratin-1, desmocollin-1, and corneodesmosin but did not modulate involucrin or claudin-1 in keratinocyte cultures. Moreover, FLG protein expression was inhibited in human skin equivalents and murine skin treated with PM2.5. We demonstrate that this process was mediated by PM2.5-induced TNF-α and was aryl hydrocarbon receptor dependent. PM2.5 exposure compromised skin barrier function, resulting in increased transepidermal water loss, and enhanced the penetration of FITC-dextran in organotypic and mouse skin. PM2.5-induced TNF-α caused FLG deficiency in the skin and subsequently induced skin barrier dysfunction. Compromised skin barrier due to PM2.5 exposure may contribute to the development and the exacerbation of allergic diseases such as atopic dermatitis.

Efficacy of bleomycin application on periungual warts after treatment with ablative carbon dioxide fractional laser: a pilot study.

Background: Treating periungual warts is a therapeutic challenge. Treatments are often ineffective and may cause complications including permanent nail changes, pain, and scaring. Translesional bleomycin delivery via the multipuncture technique is now reported.Objective: To investigate the efficacy and safety of bleomycin solution (1 U/mL) after ablative fractional carbon dioxide (CO2) laser for treating periungual warts.Methods: Warts were treated with ablative CO2 fractional laser, after which bleomycin was applied. Patients were treated every 2 weeks until the lesions disappeared. Treatment was discontinued if adverse events occurred or the patient wanted to stop.Results: Seventeen patients (11 women, mean age 16.23 years) with a total of 38 warts were enrolled from May 2017 to Aug 2018. Twenty-six lesions (68.4%) achieved complete clearance; three (7.8%) had excellent partial response (>75% improvement). The warts clearing completely did not recur over the follow-up period of 6 months. No significant long-term adverse effects occurred. One lesion showed postinflammatory hyperpigmentation, resolving within 1 month; five patients (29%) had short-term localized moderate pain after treatment.Conclusions: Bleomycin solution after ablative fractional CO2 laser is effective and safe to treat periungual warts. Further large controlled studies are necessary to validate effectiveness and find an optimal regimen.

Validity of Diagnostic Codes for Identification of Psoriasis Patients in Korea.

BACKGROUND: Recently, the number of nationwide medical researches on psoriasis using the National Health Insurance Service database has been on the rise. However, identification of psoriasis using diagnostic codes alone can lead to misclassification. Accuracy of the diagnostic codes and their concordance with medical records should be validated first to identify psoriasis patients correctly. OBJECTIVE: To validate the diagnostic codes of psoriasis (International Classification of Diseases, 10th Revision L40) and to find the algorithm for the identification of psoriasis. METHODS: We collected medical records of patients who received their first diagnostic codes of psoriasis during 5 years from five hospitals. Fifteen percent of psoriasis patients were randomly selected from each hospital. We performed a validation by reviewing medical records and compared 5 algorithms to identify the best algorithm. RESULTS: Total of 538 cases were reviewed and classified as psoriasis (n=368), not psoriasis (n=159), and questionable (n=11). The most accurate algorithm was including patients with ≥1 visits with psoriasis as primary diagnostic codes and prescription of vitamin D derivatives. Its positive predictive value was 96.5% (95% confidence interval [CI], 93.9%~98.1%), which was significantly higher than those of the algorithm, including patients with ≥1 visits with psoriasis as primary diagnostic codes or including ≥1 visits with diagnostic codes of psoriasis (primary or additional) (91.0% and 69.8%). Sensitivity was 90.8% (95% CI, 87.2%~93.4%) and specificity was 92.5% (95% CI, 86.9%~95.9%). CONCLUSION: Our study demonstrates a validated algorithm to identify psoriasis, which will be useful for the nationwide population-based study of psoriasis in Korea.

A case of latanoprost-induced diffuse facial skin hyperpigmentation.

INTRODUCTION: Latanoprost is a prostaglandin F2α analogue, which has been used as a first-line drug for open-angle glaucoma. Common side effects of latanoprost include hyperpigmentation. While it usually occurs on irides or periocular skin, diffuse facial hyperpigmentation is rarely reported. CASE PRESENTATION: A 71-year-old woman was presented with diffuse gray-brown colored maculopatches on her face. The symptom appeared 1 week after she started to use latanoprost eye drops for glaucoma. Biopsy specimen revealed vacuolar degeneration of dermo-epidermal junction and pigment incontinence in dermis. OBJECTIVE: The aim of this paper is to introduce a rare adverse effect of latanoprost and effective way of treatment. METHODS: We stopped her from using latanoprost. She was also treated with 532-nm potassium titanyl phosphate laser and low-fluence 1064-nm Q-switched Nd:YAG laser, while using topical agents. RESULT: After 10 weeks, we observed hyperpigmentation of her face was effectively and safely treated. The patient was satisfied with the result. CONCLUSION: Diffuse facial pigmentation could be one of the latanoprost-induced adverse effects and the laser treatments with topical agents we used can make it improve faster.

2019 Consensus Korean Diagnostic Guidelines to Define Severity Classification and Treatment Refractoriness for Atopic Dermatitis: Objective and Subjective Assessment of Severity.

BACKGROUND: Systemic immunomodulatory treatment is actively recommended in the treatment for moderate to severe atopic dermatitis (AD) patients. However, consensus criteria for the classification of AD severity or treatment refractoriness have not been established yet. OBJECTIVE: To establish consensus criteria on the definition of severity classification and treatment refractoriness of AD to provide a basis for proper treatment strategy. METHODS: The Korean Atopic Dermatitis Association (KADA) comprised a task force team to establish a definition of moderate to severe AD. A draft of definition of moderate to severe AD was made on the basis of evidence. The recommendation was confirmed by KADA members through a web-based survey. RESULTS: KADA approved that AD with 16≤eczema area and severity index (EASI)<23 should be basically defined as moderate AD whereas AD with EASI score ≥23 should be considered as severe AD. They agreed that it would be reasonable to raise the severity level if patient's daytime or nighttime pruritus numerical rating scale is equal to or higher than 7 (≥7) or dermatology life quality index score exceeds 10. AD patients who do not reach EASI 50 after appropriate treatment for three months should be considered as a non-responder. Patients with recurrence (EASI ≥16) within three months after cessation of treatment should be considered as a recurrent AD. CONCLUSION: KADA built a consensus of definition of moderate and severe AD and treatment-refractoriness. These guidelines are expected to help physicians determine proper treatment options in need.