Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review.

This manuscript explores the role of pyroptosis, an inflammatory programmed cell death, in the pathogenesis of two chronic dermatoses, psoriasis and hidradenitis suppurativa (HS). The diseases, though clinically diverse, share common pathogenetic pathways involving the unbalanced interaction between the adaptive and innate immune systems. This review focuses on the molecular changes in psoriatic and HS skin, emphasizing the activation of dendritic cells, secretion of interleukins (IL-17, IL-22, and TNF-α), and the involvement of inflammasomes, particularly NLRP3. This manuscript discusses the role of caspases, especially caspase-1, in driving pyroptosis and highlights the family of gasdermins (GSDMs) as key players in the formation of pores leading to cell rupture and the release of proinflammatory signals. This study delves into the potential therapeutic implications of targeting pyroptosis in psoriasis and HS, examining existing medications like biologics and Janus kinase inhibitors. It also reviews the current limitations and challenges in developing therapies that selectively target pyroptosis. Additionally, the manuscript explores the role of pyroptosis in various inflammatory disorders associated with psoriasis and HS, such as inflammatory bowel disease, diabetes mellitus, and cardiovascular disorders. The review concludes by emphasizing the need for further research to fully elucidate the pathomechanisms of these dermatoses and develop effective, targeted therapies.

Review of Fractional Nonablative Lasers for the Treatment of Dermatologic Conditions in Darker Skin Phototypes.

BACKGROUND: Fractional nonablative lasers (NAFLs) have demonstrated efficacy and safety for treating dermatologic conditions in patients with darker skin phototypes. Nonablative lasers are preferred in darker skin tones due to lower risk of postinflammatory hyperpigmentation. OBJECTIVE: This review aims to identify the ideal laser options and parameters for treating common dermatologic conditions in patients with skin types IV-VI. MATERIALS AND METHODS: A comprehensive literature search was conducted on PubMed in May 2023. Of 1,065 articles were identified, and 40 articles met the inclusion criteria. The studies were classified based on design, dermatologic condition, and skin phototype of patients, and assigned levels of evidence according to the Modified Criteria of the Oxford Center of Evidence Based Medicine. RESULTS: Strong level 1 evidence supports the treatment of melasma and atrophic scars using NAFL. Moderate level 2 evidence was found for using NAFL in acne vulgaris, striae, and skin rejuvenation; 45% of the studies examined skin types III-IV, 20% III-V, 7.5% II-IV, 5% II-V, 5% IV alone, and 2.5% I-IV. CONCLUSION: Further research is needed to determine the optimal treatment modalities and parameters for skin types V and VI. Appropriate device selection and conservative treatment settings are crucial for optimizing outcomes and minimizing adverse events.

Assessing the Impact of Visual and Audio Media on Sunscreen Use Among People of Color: Pre- and Post-Survey.

BACKGROUND: Poor melanoma outcomes in people of color (POC) are attributed to a variety of factors, including healthcare literacy, socioeconomic status, and healthcare access barriers.  Methods: We designed a survey to determine if visual and audio media (VAM) would increase POC's understanding of the need for sunscreen and their willingness to use it. Patients recruited at a dermatology clinic were asked to watch a 2.5-minute video on sun protection and complete a pre- and post-survey assessing their knowledge. RESULTS: Forty-one (41) patients were recruited, 43.9% of whom identified as POC and 31.7% as Hispanic or Latino. In the post-survey, 100% of participants agreed that daily sunscreen use helps prevent sun-related risks, compared to 68% before (P<.0001). 71% of the participants intended to use sunscreen daily after watching the video, compared to 24% who did so before (P<.0001). One-hundred percent (100%) of Black participants in the post-survey agreed that sunscreen wear helps prevent risks associated with sun exposure, compared to 46% in the pre-survey (P= 0.0052); no significant difference among White participants (80% vs 100%; P=0.1121). LIMITATIONS: Small sample size, no long-term follow-up. CONCLUSIONS: This study demonstrates the persistence of health disparities and the effectiveness of VAM in enhancing Black patients' healthcare literacy. J Drugs Dermatol. 2024;23(7):525-528.     doi:10.36849/JDD.7821.

Optical coherence tomography confirms non-malignant pigmented lesions in phacomatosis pigmentokeratotica using a support vector machine learning algorithm.

INTRODUCTION: Phacomatosis pigmentokeratotica (PPK), an epidermal nevus syndrome, is characterized by the coexistence of nevus spilus and nevus sebaceus. Within the nevus spilus, an extensive range of atypical nevi of different morphologies may manifest. Pigmented lesions may fulfill the ABCDE criteria for melanoma, which may prompt a physician to perform a full-thickness biopsy. MOTIVATION: Excisions result in pain, mental distress, and physical disfigurement. For patients with a significant number of nevi with morphologic atypia, it may not be physically feasible to biopsy a large number of lesions. Optical coherence tomography (OCT) is a non-invasive imaging modality that may be used to visualize non-melanoma and melanoma skin cancers. MATERIALS AND METHOD: In this study, we used OCT to image pigmented lesions with morphologic atypia in a patient with PPK and assessed their quantitative optical properties compared to OCT cases of melanoma. We implement a support vector machine learning algorithm with Gabor wavelet transformation algorithm during post-image processing to extract optical properties and calculate attenuation coefficients. RESULTS: The algorithm was trained and tested to extract and classify textural data. CONCLUSION: We conclude that implementing this post-imaging machine learning algorithm to OCT images of pigmented lesions in PPK has been able to successfully confirm benign optical properties. Additionally, we identified remarkable differences in attenuation coefficient values and tissue optical characteristics, further defining separating benign features of pigmented lesions in PPK from malignant features.

Noninvasive imaging exploration of phacomatosis pigmentokeratotica using high-frequency ultrasound and optical coherence tomography: Can biopsy of PPK patients be avoided?

BACKGROUND: Phacomatosis pigmentokeratotica (PPK) is a distinct and rare type of epidermal nevus syndrome characterized by coexisting nonepidermolytic organoid sebaceous nevus (SN) with one or more speckled lentiginous nevi (SLN). Atypical nevi including compound Spitz and compound dysplastic may manifest within regions of SLN. Patients with PPK, or similar atypical nevus syndromes, may be subject to a significant lifetime number of biopsies, leading to pain, scarring, anxiety, financial burden, and decreased quality of life. The current literature includes case reports, genetics, and associated extracutaneous symptoms of PPK, but use of noninvasive imaging techniques have not been explored. We aim to investigate the value of high-frequency ultrasound (HFUS) and optical coherence tomography (OCT) in discriminating morphological features of pigmented lesions and nevus sebaceous within one patient with PPK. MATERIALS AND METHODS: Two modalities, (1) HFUS imaging, based on acoustic properties and (2) OCT imaging, based on optical properties, were used to image a patient with PPK. Benign pigmented lesions, which may raise clinical suspicion for significant atypia, and nevus sebaceous, were selected on different areas of the body to be studied. RESULTS: Five pigmented lesions and one area of nevus sebaceous were imaged and analyzed for noninvasive features. Distinct patterns of hypoechoic features were seen on HFUS and OCT. CONCLUSION: HFUS provides a deep view of the tissue, with ability to differentiate gross structures beneath the skin. OCT provides a smaller penetration depth and a higher resolution. We have described noninvasive features of atypical nevi and nevus sebaceous on HFUS and OCT, which indicate benign etiology.

Mohs Micrographic Surgery for the Treatment of External Ear Melanoma: an Outcome Study.

BACKGROUND: The external ear is composed of thin skin overlying cartilage making melanoma on the external ear difficult to resect while preserving the intricate anatomy. Although surgeons have achieved robust clinical outcomes for nonmelanoma and most recently melanoma skin cancers with Mohs micrographic surgery (MMS), there is still not enough evidence on the MMS application for external ear melanoma treatment. OBJECTIVE: The authors examined survival outcomes in patients treated with MMS, narrow margin excision (NME), and wide margin excision (WME) for melanoma on the external ear. METHODS: Data from the NCI SEER program was retrospectively analyzed. Patients who received surgical treatment on the external ear and had microscopically confirmed diagnosis of cutaneous melanoma were included in the study. The effect of different surgery types: MMS, NME, and WME, on melanoma survival was evaluated. RESULTS: A total of 8,212 melanoma cases of the external ear performed during the years 2000 to 2015 were considered for analysis. There were no significant differences in survival comparing NME and WME with MMS. CONCLUSION: Mohs micrographic surgery is at least equivalent to WME for the treatment of melanoma of the external ear.

Mycoplasma pneumoniae-associated mucositis complicated by herpes simplex virus dissemination and Staphylococcus Epidermidis bacteremia.

Prominent mucositis with minimal or no cutaneous involvement in the setting of Mycoplasma pneumoniae infection describes a clinical entity recently termed Mycoplasma-induced rash and mucositis (MIRM). About 81% of patients with MIRM experience complete resolution; however, the disease course in approximately 11% of patients is complicated by mucosal sequelae. We describe a patient with MIRM complicated by HSV dissemination and Staphylococcus epidermidis bacteremia and outline the management of mucocutaneous eruptions without systemic immunosuppressant agents.

Melanoma Biomarkers and Their Potential Application for In Vivo Diagnostic Imaging Modalities.

Melanoma is the deadliest form of skin cancer and remains a diagnostic challenge in the dermatology clinic. Several non-invasive imaging techniques have been developed to identify melanoma. The signal source in each of these modalities is based on the alteration of physical characteristics of the tissue from healthy/benign to melanoma. However, as these characteristics are not always sufficiently specific, the current imaging techniques are not adequate for use in the clinical setting. A more robust way of melanoma diagnosis is to "stain" or selectively target the suspect tissue with a melanoma biomarker attached to a contrast enhancer of one imaging modality. Here, we categorize and review known melanoma diagnostic biomarkers with the goal of guiding skin imaging experts to design an appropriate diagnostic tool for differentiating between melanoma and benign lesions with a high specificity and sensitivity.

IL-4 dysregulates microRNAs involved in inflammation, angiogenesis and apoptosis in epidermal keratinocytes.

IL-4 plays an important role in the pathogenesis of atopic dermatitis (AD) by dysregulating many key factors at the transcriptional level. In this study, a microRNA array technique and IL-4 transgenic mice were used to demonstrate that IL-4 dysregulates microRNAs involved in inflammation, angiogenesis, lymphangiogenesis and apoptosis. Of the 372 common microRNAs examined, 26 and one microRNAs were found to be up- and down-regulated, respectively. MicroRNA-101-5p, -122-5p, -142-3p, -204-5p, -335-3p, -376a-3p, -378a-5p, -639 and -9-5p are among the most significantly up-regulated microRNAs. MicroRNA-147a, the only one that was down- regulated in the present study, attenuates TLR-induced inflammatory responses. These dysregulated microRNAs may provide post-transcriptional regulation of key genes in AD.

Treatment of Actinic Keratoses: A Randomized Split-Site Approach Comparison of Sequential 5-Fluorouracil and 5-Aminolevulinic Acid Photodynamic Therapy to 5-Aminolevulinic Acid Photodynamic Monotherapy.

BACKGROUND: Actinic keratoses (AKs) are skin lesions resulting from sun exposure and carry a risk of developing into squamous cell carcinoma. Current therapies for AK eradication include topical 5-fluorouracil (5-FU) and photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA). However, sequential therapy with 5-FU-ALA-PDT may offer improved outcome compared to ALA-PDT alone. OBJECTIVE: The purpose of this study is to compare the long-term efficacy of AK clearance by sequential therapy with 5-FU-ALA-PDT versus ALA-PDT alone. MATERIALS AND METHODS: This is a single center, randomized split-site approach study on equivalent anatomical and clinical sites. Seventeen patients were enrolled with one half of the site randomized to receive sequential 5-FU-ALA-PDT and the other side with ALA-PDT monotherapy. Total AKs were counted at baseline, 6 and 12 months. RESULTS: Median percentage reduction in AK number at 6 months for 5-FU-ALA-PDT versus ALA-PDT was 100% for 5-FU-ALA-PDT (N = 21) and 66.7% for ALA-PDT (N = 21), p = .001. Median percentage reduction in AK number at 12 months for 5-FU-ALA-PDT versus ALA-PDT was 100% for 5-FU-ALA-PDT (N = 22) and 82.6% for ALA-PDT (N = 22), p = .0002. CONCLUSION: Sequential therapy with 5-FU-ALA-PDT is more effective at AK clearance at 6 and 12 months compared to ALA-PDT monotherapy.