United States

Delayed but Long-term Resolution of Nevus of Ota 
After Cessation of Picosecond 755-nm Alexandrite Laser Treatment 
Moore, Angela, MD1,2,3,4; Nguyen, An, B.S4; Nguyen, Ly4, Michael Thornton, D.O.5
1Arlington Center for Dermatology, Arlington, TX; 2Arlington Research Center, Arlington, TX; 3Baylor University Medical Center, Dallas, TX;4Texas Christian University Anne Burnett Marion School of Medicine, Fort Worth, TX; 5Mansfield Cosmetic Surgery Center, Mansfield, TX

Key words: Nevus of Ota, hyperpigmentation, picosecond, alexandrite
Corresponding author:
Angela Yen Moore, MD
Arlington Center for Dermatology
711 East Lamar Blvd., Suite 200, Arlington, Texas 76011
817-795-7546 phone
817-385-7568 fax
acderm@acderm.com
Word Count: 399
References: 9
Figure/Tables: 2
Funding: None
Conflicts of interest: None

Consent: Consent for the publication of all patient photographs and medical information was provided by the authors at the time of article submission to the journal stating that all patients gave consent for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available. 

Introduction
Nevus of Ota presents as unilateral benign melanosis in the distribution of the trigeminal nerve, with increased risk of uveal melanoma and glaucoma¹.
Since the advent of selective photothermolysis, Q-switched nanosecond lasers have been reported for treatment of dermal pigmented lesions⁷. Two prospective, randomized, split-lesion, controlled studies have concluded that picosecond lasers were more effective³. In these cases, treatment until clinical clearance was performed. We would like to report a case of nevus of Ota that was treated with a picosecond 755 nm Alexandrite laser displaying continued marked resolution after cessation of treatment, without recurrence for 5 years.
Case Report
A thirty-five-year-old Asian woman with a bluish-gray confluent pigmentation along the right V1 distribution presented for diagnosis and treatment. Six treatments with a 750-picosecond pulse duration 755-nm alexandrite laser were performed, with one session every 2 weeks over 10 weeks. Patient was instructed to use topical sunscreen with zinc oxide &gt;11% and topical healing creams. The patient experienced 8/10 pain with the first treatment session that decreased to 2/10 with pre-application of topical anesthetic cream (benzocaine 20%/ lidocaine 4%/ tetracaine 1%) 30 minutes prior to each session. Local skin reactions included temporary erythema and mild transient hyperpigmentation but no hypopigmentation. 
The hyperpigmentation decreased progressively but with persistent central blue-black pigmentation.Treatment was terminated when the patient moved away. When the patient was seen 1 year later, the nevus of Ota had resolved completely and the patient reported continued improvement for the 6 months after the last laser session until full clearance. The only continued maintenance treatment was usage of topical sunscreen with 11% zinc oxide. 
Bibliography
Picosecond lasers rely on photomechanical effects rather than photothermal. In contrast to nanosecond-domain Q-switched lasers, picosecond-domain lasers have a pulse width shorter than the stress relaxation time of dermal dendritic melanocytes and melanophages⁵. 
Mechanical stress generated within a very short period of time results in stress lock-in causing rise in pressure and fracture of the target particle and photoacoustic destruction of the particle, with a minimal photothermal component. The bursts of energy have been speculated to break down the melanin granules and melanophages, with clinical resolution occurring as macrophages carry away the fractured particles even after cessation of laser sessions⁴. 
This case report of delayed but persistent clinical resolution of a nevus of Ota validates theories on how picosecond lasers achieve clinical response through photomechanical effects followed by immunologic response.














References
Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls 
[Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560574/
Chesnut, Cameron MD; Diehl, Joseph MD; Lask, Gary MD. Treatment of Nevus of Ota 
With a Picosecond 755-nm Alexandrite Laser. Dermatologic Surgery 41(4):p 508-510, April 2015. | DOI: 10.1097/DSS.0000000000000326
Ge Y, Yang Y, Guo L, Zhang M, Wu Q, Zeng R, Rong H, Jia G, Shi H, Fang J, Lin T. 
Comparison of a picosecond alexandrite laser versus a Q-switched alexandrite laser for the treatment of nevus of Ota: A randomized, split-lesion, controlled trial. J Am Acad Dermatol. 2020 Aug;83(2):397-403. doi: 10.1016/j.jaad.2019.03.016. Epub 2019 Mar 16. PMID: 30885760.
Imagawa, K., Kono, T., Hanai, U. et al. Prospective comparison study of a 550 
picosecond 755 nm laser vs a 50 ns 755 nm laser in the treatment of nevus of Ota. Lasers Med Sci 38, 55 (2023). https://doi.org/10.1007/s10103-023-03721-5
Kasai K. Picosecond Laser Treatment for Tattoos and Benign Cutaneous Pigmented 
Lesions (Secondary publication). Laser Ther. 2017 Dec 31;26(4):274-281. doi: 10.5978/islsm.17-RE-02. PMID: 29434427; PMCID: PMC5801452.
Luo B, Kang L, Lu J. Successful and quick treatment of nevus of Ota with 755nm 
picosecond laser in Chinese. J Cosmet Laser Ther. 2020 Feb 17;22(2):93-95. doi: 10.1080/14764172.2020.1740274. Epub 2020 Mar 11. PMID: 32160794.
Wong THS. Picosecond Laser Treatment for Acquired Bilateral Nevus of Ota–like 
Macules. JAMA Dermatol. 2018;154(10):1226–1228. doi:10.1001/jamadermatol.2018.2671
Yang H, Guo L, Jia G, Gong X, Wu Q, Zeng R, Zhang M, Ding H, Fang F, Zheng H, Liu 
X, Ge Y, Yang Y, Lin T. Treatment of nevus of Ota with 1064 nm picosecond Nd:YAG laser: A retrospective study. Dermatol Ther. 2021; 34(6):e15152. doi: 10.1111/dth.15152. Epub 2021 Oct 14. PMID: 34609042.
Yu W, Zhu J, Yu W, Lyu D, Lin X, Zhang Z. A split-face, single-blinded, randomized 
controlled comparison of alexandrite 755-nm picosecond laser versus alexandrite 755-nm nanosecond laser in the treatment of acquired bilateral nevus of Ota-like macules. JAAD. 2018; 79(3): 479-486. doi: 10.1016



AMA Research Challenge 2024 

Delayed Cessation but Long-term Resolution of Nevus of Ota After Picosecond 755-nm Alexandrite Laser Treatments

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Delayed but Long-term Resolution of Nevus of Ota 
After Cessation of Picosecond 755-nm Alexandrite Laser Treatment 
Moore, Angela, MD1,2,3,4; Nguyen, An, B.S4; Nguyen, Ly4, Michael Thornton, D.O.5
1Arlington Center for Dermatology, Arlington, TX; 2Arlington Research Center, Arlington, TX; 3Baylor University Medical Center, Dallas, TX;4Texas Christian University Anne Burnett Marion School of Medicine, Fort Worth, TX; 5Mansfield Cosmetic Surgery Center, Mansfield, TX

Key words: Nevus of Ota, hyperpigmentation, picosecond, alexandrite
Corresponding author:
Angela Yen Moore, MD
Arlington Center for Dermatology
711 East Lamar Blvd., Suite 200, Arlington, Texas 76011
817-795-7546 phone
817-385-7568 fax
acderm@acderm.com
Word Count: 399
References: 9
Figure/Tables: 2
Funding: None
Conflicts of interest: None

Consent: Consent for the publication of all patient photographs and medical information was provided by the authors at the time of article submission to the journal stating that all patients gave consent for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available. 

Introduction
Nevus of Ota presents as unilateral benign melanosis in the distribution of the trigeminal nerve, with increased risk of uveal melanoma and glaucoma¹.
Since the advent of selective photothermolysis, Q-switched nanosecond lasers have been reported for treatment of dermal pigmented lesions⁷. Two prospective, randomized, split-lesion, controlled studies have concluded that picosecond lasers were more effective³. In these cases, treatment until clinical clearance was performed. We would like to report a case of nevus of Ota that was treated with a picosecond 755 nm Alexandrite laser displaying continued marked resolution after cessation of treatment, without recurrence for 5 years.
Case Report
A thirty-five-year-old Asian woman with a bluish-gray confluent pigmentation along the right V1 distribution presented for diagnosis and treatment. Six treatments with a 750-picosecond pulse duration 755-nm alexandrite laser were performed, with one session every 2 weeks over 10 weeks. Patient was instructed to use topical sunscreen with zinc oxide >11% and topical healing creams. The patient experienced 8/10 pain with the first treatment session that decreased to 2/10 with pre-application of topical anesthetic cream (benzocaine 20%/ lidocaine 4%/ tetracaine 1%) 30 minutes prior to each session. Local skin reactions included temporary erythema and mild transient hyperpigmentation but no hypopigmentation. 
The hyperpigmentation decreased progressively but with persistent central blue-black pigmentation.Treatment was terminated when the patient moved away. When the patient was seen 1 year later, the nevus of Ota had resolved completely and the patient reported continued improvement for the 6 months after the last laser session until full clearance. The only continued maintenance treatment was usage of topical sunscreen with 11% zinc oxide. 
Bibliography
Picosecond lasers rely on photomechanical effects rather than photothermal. In contrast to nanosecond-domain Q-switched lasers, picosecond-domain lasers have a pulse width shorter than the stress relaxation time of dermal dendritic melanocytes and melanophages⁵. 
Mechanical stress generated within a very short period of time results in stress lock-in causing rise in pressure and fracture of the target particle and photoacoustic destruction of the particle, with a minimal photothermal component. The bursts of energy have been speculated to break down the melanin granules and melanophages, with clinical resolution occurring as macrophages carry away the fractured particles even after cessation of laser sessions⁴. 
This case report of delayed but persistent clinical resolution of a nevus of Ota validates theories on how picosecond lasers achieve clinical response through photomechanical effects followed by immunologic response.














References
Agarwal P, Patel BC. Nevus of Ota and Ito. [Updated 2023 Jul 10]. In: StatPearls 
[Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560574/
Chesnut, Cameron MD; Diehl, Joseph MD; Lask, Gary MD. Treatment of Nevus of Ota 
With a Picosecond 755-nm Alexandrite Laser. Dermatologic Surgery 41(4):p 508-510, April 2015. | DOI: 10.1097/DSS.0000000000000326
Ge Y, Yang Y, Guo L, Zhang M, Wu Q, Zeng R, Rong H, Jia G, Shi H, Fang J, Lin T. 
Comparison of a picosecond alexandrite laser versus a Q-switched alexandrite laser for the treatment of nevus of Ota: A randomized, split-lesion, controlled trial. J Am Acad Dermatol. 2020 Aug;83(2):397-403. doi: 10.1016/j.jaad.2019.03.016. Epub 2019 Mar 16. PMID: 30885760.
Imagawa, K., Kono, T., Hanai, U. et al. Prospective comparison study of a 550 
picosecond 755 nm laser vs a 50 ns 755 nm laser in the treatment of nevus of Ota. Lasers Med Sci 38, 55 (2023). https://doi.org/10.1007/s10103-023-03721-5
Kasai K. Picosecond Laser Treatment for Tattoos and Benign Cutaneous Pigmented 
Lesions (Secondary publication). Laser Ther. 2017 Dec 31;26(4):274-281. doi: 10.5978/islsm.17-RE-02. PMID: 29434427; PMCID: PMC5801452.
Luo B, Kang L, Lu J. Successful and quick treatment of nevus of Ota with 755nm 
picosecond laser in Chinese. J Cosmet Laser Ther. 2020 Feb 17;22(2):93-95. doi: 10.1080/14764172.2020.1740274. Epub 2020 Mar 11. PMID: 32160794.
Wong THS. Picosecond Laser Treatment for Acquired Bilateral Nevus of Ota–like 
Macules. JAMA Dermatol. 2018;154(10):1226–1228. doi:10.1001/jamadermatol.2018.2671
Yang H, Guo L, Jia G, Gong X, Wu Q, Zeng R, Zhang M, Ding H, Fang F, Zheng H, Liu 
X, Ge Y, Yang Y, Lin T. Treatment of nevus of Ota with 1064 nm picosecond Nd:YAG laser: A retrospective study. Dermatol Ther. 2021; 34(6):e15152. doi: 10.1111/dth.15152. Epub 2021 Oct 14. PMID: 34609042.
Yu W, Zhu J, Yu W, Lyu D, Lin X, Zhang Z. A split-face, single-blinded, randomized 
controlled comparison of alexandrite 755-nm picosecond laser versus alexandrite 755-nm nanosecond laser in the treatment of acquired bilateral nevus of Ota-like macules. JAAD. 2018; 79(3): 479-486. doi: 10.1016



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Artificial Intelligence (AI) systems like ChatGPT are increasingly explored for diagnostic purposes, particularly as more people may turn to these tools for self-diagnosis of skin conditions. This study evaluates ChatGPT-4 Turbo and ChatGPT-4 Omni (ChatGPT-4O) using the HAM10K dermatoscopic image dataset to classify 500 melanoma and 500 non-melanoma cases, with an additional 1,000 non-melanoma images to test false-positive rates. ChatGPT-4O achieved 57.7% accuracy (95% CI: 54.7%-60.8%) in identifying melanoma, while ChatGPT-4 Turbo had 54.6% accuracy (95% CI: 51.5%-57.7%). Both models showed high sensitivity but low specificity for melanoma diagnosis. For non-melanoma lesions, ChatGPT-4O’s accuracy was 6.56% (95% CI: 4.94%-8.18%), improving to 25.25% (95% CI: 22.55%-27.95%) when binary prompts were used. ChatGPT exhibited a tendency to conservatively classify lesions as melanoma, with explicit prompts improving performance. Despite these gains, the models’ diagnostic accuracy remains inadequate compared to specialized neural networks, suggesting that ChatGPT is not yet reliable for autonomous skin cancer diagnosis, even as more people may seek to use it for self-assessment.

Evaluating the Capability & Accuracy of CHATGPT’s Newest Models in Diagnosing between Melanoma and Non-Melanoma Lesions

Background
Melanoma, an invasive and potentially fatal form of skin cancer, is estimated to account for 5.0% of new cancer cases and 1.4% of cancer-related deaths in 2024 alone.2 Survival rates are closely linked to the stage at detection, with thicker tumors at initial diagnosis associated with reduced overall survival rate.3,4 Increased distance to healthcare providers creates barriers to early detection. Moreover, disparities in sun exposure and healthcare access between rural and urban populations underscore the need for targeted interventions to address these inequities. This review aims to bridge the knowledge gap regarding the relationship between rurality or distance to health providers with melanoma staging at detection, informing policies and interventions to improve outcomes in at-risk populations.
Methods
A search was conducted of the PubMed and Embase databases, following the Preferred
Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.23 The studies included were those that compared melanoma staging or Breslow thickness in rural areas to urban areas as well as studies doing the same comparison with distance to healthcare providers. 
Results
In this review, six cross-sectional and seven retrospective cohort studies were included, with international and U.S.-based studies represented. The scopes of these studies were hospital-wide, regional, and countrywide, with samples mainly consisting of all patients of the specified region with a diagnosis of primary melanoma. Most studies utilized population-based cancer registry data, while hospital-wide studies relied on electronic health records.
Studies examining the influence of rurality on melanoma staging and Breslow thickness yielded inconclusive findings, largely due to statistically insignificant results in related papers. However, consistent results were reported in studies evaluating the impact of distance from the provider on staging and tumor thickness at initial diagnosis. Increased distance to the provider is shown to have a significantly positive correlation with advanced staging and thickness. However, the limited sample representation poses the risk of biases affecting the reliability of such conclusions.
Conclusion
This review highlights the critical impact of healthcare accessibility on melanoma outcomes, particularly emphasizing the influence of distance to healthcare providers over rurality in determining Breslow thickness and tumor stage at initial diagnosis. The findings across studies evaluating provider distance underscore the necessity of reducing geographic barriers to dermatological services to improve early detection and management of melanoma. This reinforces the importance of ensuring equitable access to dermatological services regardless of region.

Geospatial Impacts on Melanoma Stage at Initial Diagnosis - A Systematic Review

Background: Psoriasis is one of the most prevalent chronic inflammatory skin conditions; however, its effects span much farther than its cutaneous manifestations. This study aims to assess the impact of biologic treatments on the development of depressive comorbidities in patients with psoriasis.

Methods: A retrospective chart analysis with data from TriNetX was performed for patients after propensity matching on TNF-α inhibitors (Cohort A), IL-17 inhibitors (Cohort B), and IL-23 + IL-12/23 inhibitors (Cohort C).

Results: All comparator groups showed a statistically significant decrease in new onset MDD, new onset DE, and new prescription of antidepressants. The risk ratios for both new onset MDD and DE, as well as odds ratio for new antidepressant prescription, respectively, were as follows: for Cohort A, 1.857 (CI: 1.233-2.797), 1.416 (CI: 1.176-1.705), 1.169 (CI: 1.031, 1.326); Cohort B, 2.636 (CI: 1.32-5.265), 2.35 (CI: 1.63-3.387), 1.169 (CI: 1.031, 1.326); Cohort C, 2.586 (CI: 1.687-3.964), 2.489 (CI: 1.965-3.154), 1.975 (CI: 1.71, 2.281.

Limitations: The TriNetX database has inherent limitations based on diagnosis codes and lack of sufficient data on cutaneous response.

Conclusion: Our study provides compelling evidence that biologic therapies for psoriasis, including IL-17, IL-12/23, IL-23, and TNF-𝛼 inhibitors, significantly reduce the risk of new diagnoses of MDD, new depressive episodes in patients, as well as lower the odds of starting a new prescription of antidepressant.

Impact of biologic treatments on the development of depressive comorbidities in patients with psoriasis

Abstract Title
Investigating the Association Between Ozempic Use and Psoriasis: An Analysis of FDA Adverse Event Reporting System Data from 2019-2024.


Background
GLP-1 agonists, including Ozempic, are prescribed to treat type 2 diabetes. While it is used for blood glucose control, the added advantage of Ozempic is weight reduction in patients with and without diabetes; because of this, its usage has increased over the years and has run into a shortage issue. Even though Ozempic is very effective for weight reduction and diabetes management, there have been cases described with adverse events, including psoriasis. This study aims to investigate a potential association between using Ozempic and psoriasis as an adverse event by analyzing cases of reported adverse events from the FDA Adverse Event Reporting System from 2019-2024.

Methods
In the FAERS database, the search terms "Ozempic" and "psoriasis" were used to identify reported cases of psoriasis in patients treated with Ozempic from 2019 to 2024. Non-plaque psoriasis variants, including pustular, guttate, and erythrodermic psoriasis, were excluded during data retrieval. Descriptive statistics, including Chi-Square tests, correlation analysis, and trend visualizations, were used to analyze case counts, age, gender, and severity. 

Results
In the FAERS database, from 2019 to June 2024, a total of 20 cases of psoriasis associated with Ozempic use were identified. Most cases lacked specified age data. The gender distribution was nearly equal, with 10 cases in males, 9 in females, and 1 with unspecified gender. Hospitalization was reported in one case. Statistical analysis using a Chi-Square test revealed no significant association between age, gender, and the development of psoriasis (χ² = 4.52, p = 0.34, dof = 4). A statistically significant association between Ozempic use and the development of psoriasis was observed (χ² = 5.75, p = 0.026, dof = 1). A trend analysis signified a slight increase in psoriasis cases over time, with the highest reported cases occurring in 2023. However, the correlation was weak (r = 0.147).


Conclusion
The study's findings imply that Ozempic use may be related to the development of psoriasis. However, the study is significantly limited by its small sample size, lack of detailed patient demographics, and potential reporting biases. Furthermore, confounding factors, such as the use of other medications or comorbid conditions, were not analyzed, further limiting the study’s initial findings. Additionally, to validate our study's preliminary findings and understand the potential biological mechanism involved in Ozempic leading to psoriasis, more extensive, controlled studies are required. The studies can help improve patient management strategies and risk assessment for Ozempic treatment. 




Investigating the Association Between Ozempic Use and Psoriasis: An Analysis of FDA Adverse Event Reporting System Data from 2019-2024.

Biologics have revolutionized psoriasis treatment, yet there remains limited data regarding ocular adverse events (AEs) associated with these therapies. Using the FDA Adverse Event Reporting System (FAERS), we investigated the most commonly reported ocular AEs linked to biologics approved for psoriasis from 1998 to 2024. A total of 70,884 reports related to 13 biologics were analyzed. The most frequently reported AEs were visual impairment (10,569), cataracts (9,457), blurred vision (7,506), and uveitis (5,654). Adalimumab, etanercept, and infliximab accounted for the majority of severe ocular AEs, including 52% of blindness cases. Females represented 64.7% of cases, and AEs were uncommon in children and those over 85 years of age. These findings underscore the importance of monitoring for ocular complications in patients on biologics and suggest further research to assess long-term safety and preventive strategies.

Ocular adverse events associated with biologics approved for psoriasis: an FDA Adverse Event Reporting database study

Introduction: Despite comprising the minority of patients diagnosed with skin cancers, racial and ethnic minority groups experience worse prognoses and are at increased risk for adverse outcomes compared to non-Hispanic, White patients. We aim to quantify disparities in treatment-associated outcomes across race and ethnicity for patients with cutaneous malignancies of the head and neck. 
Methods: We analyzed patients diagnosed with melanoma and nonmelanoma skin cancers between 2010 to 2021 using data from the National Cancer Database (NCDB). The primary outcome variable, treatment refusal, was examined via logistic regression. Secondary variables included days from diagnosis to treatment, tumor depth, and mortality. These were analyzed using multi-way ANOVA and binary logistic regression.
Results: Of 151,733 patients analyzed, most were non-Hispanic White (99%) and male (71%). Black patients had the greatest odds of treatment refusal (4.166, 95% CI: 2.054-8.452, p<0.001) across all cutaneous malignancies of the head and neck. Black and Hispanic patients also had increased times from diagnosis to treatment (p<0.001). Black patients had a higher odd of 90-day mortality compared to non-Hispanic White patients (p<0.001). This coincided with greater tumor depth in Black and Hispanic patients compared to non-Hispanic White patients (p<0.001).
Conclusions: Black patients are more likely to refuse treatment for cutaneous head and neck malignancies overall and both Black and Hispanic patients experience more treatment delays. These findings may relate to the increased 90-day mortality among Black patients and increased tumor depth for both Black and Hispanic patients. Further investigation into quality of life and functional impairment are warranted alongside culturally sensitive interventions to reduce these disparities.

Racial & Ethnic Disparities in Treatment Refusal for Head & Neck Cutaneous Malignancies

Background: In the treatment of keratinocyte carcinoma, curettage alone has been described as a simpler, less expensive, and quicker method than electrodessication and curettage; however, there are limited studies examining recurrence rates for such lesions.
Objective: To investigate the 5-year recurrence rates of keratinocyte carcinoma treated with curettage alone and compare these results to previously reported recurrence rates for electrodessication and curettage.
Methods: A retrospective cohort and interview study determined 5-year recurrence rates for 1853 total lesions treated with curettage alone using chart review data and patient phone calls. 
Results: Our study yielded a per-protocol 5-year recurrence rate of 2.41% for BCCs, 4.52% for SCCs, and an average of 3.71% across both types of keratinocyte carcinoma. Lesions on the head and neck displayed a significantly greater recurrence rate of 7.18% when treated with curettage alone.
Limitations: We were limited to the use of previously published data to determine recurrence rates for lesions treated with full electrodessication and curettage.
Conclusion: Curettage alone provides comparable efficacy in curing keratinocyte carcinoma when compared to electrodessication and curettage.


Recurrence Rates of Keratinocyte Carcinoma Treated with Curettage Alone, a Retrospective Cohort and Interview Study

Background
Dissecting cellulitis (DC), also known as perifolliculitis capitis abscedens et suffodiens or Hoffman disease, is characterized by a perifollicular inflammatory infiltrate, comprising lymphocytes, predominantly CD8+ T cells, and neutrophils. Its etiology is attributed to aberrant follicular keratinization, resulting in follicular blockage and subsequent bacterial infection. DC may manifest concomitantly with conditions such as acne conglobata and inverse acne, forming part of the follicular occlusion triad. Symptoms of DC encompass tender nodules, alopecia, and lesions that, despite incision and drainage, demonstrate recurrence. Interconnected sinus tracts form in DC which can either be deep sinus tracts or tortuous ridges linking the nodules and abscesses. Treatment modalities for DC encompass isotretinoin, dapsone, intralesional steroid injections, and doxycycline. Tobacco smoking is recognized as a significant risk factor for the development and subsequent exacerbation of DC. In recent times, Electronic Nicotine Dispensing Systems (ENDS) or vaping has gained popularity; however, the potential risk of DC linked with vaping remains unclear. We hypothesized that the risk of developing DC might be elevated in individuals with a vaping history due to increased exposure to toxic metabolites. Subsequently, we compared the risk of DC development between individuals using vaping devices and tobacco products.

Methods
We conducted a retrospective cohort study utilizing de-identified patient data from the TriNetX platform, a comprehensive electronic health records (EHR) system. Cohorts included patients with vaping history (Cohort A) compared to tobacco smokers (Cohort B). Propensity score matching was utilized to balance baseline characteristics between the cohorts, including age, sex, ethnicity, and comorbidities.

Results
Risk of DC development for Cohort A was 2.53 %, compared to Cohort B 3.94% (p<0.0001 (95% CI (1.269, 1.912); Risk ratio: 1.557).

Conclusion
Benzo(a)pyrene, found in cigarette smoke, has been linked to vitamin A deficiency which can increase the risk of intraductal keratinization of the epithelial cells, potentially obstructing ductal structures. Chemical profiles of ENDSs vary due to manufacturing differences and addition of various flavors and stabilizing agents. While toxic chemicals related to tobacco smoking have been extensively studied, the ENDSs chemicals and their effect on the human body remains a poorly understood area. DC may be misdiagnosed as cystic acne therefore, a punch biopsy is required for accurate diagnosis. Treatment of DC should target both infection and inflation; thus, azithromycin and doxycycline are commonly used for their anti-inflammatory effect. Adalimumab and TNF-α have been reported to be efficacious in treatment of DC.

Risk Associated with Electronic Nicotine Dispensing Systems versus Tobacco Use and Development of Dissecting Cellulitis

Background: Palmoplantar pustulosis (PPP) is a chronic, debilitating inflammatory skin disorder characterized by erythematous pustules and desquamation on the palms and soles with severe impact on quality of life. While IL-17 pathways have been implicated in PPP pathogenesis, clinical trials with IL-17 inhibitors have yielded conflicting results, underscoring the need for a deeper understanding of its underlying mechanisms.
Methods: We employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to analyze skin biopsies from PPP patients (n=3) and healthy controls (n=5). We identified distinct cellular populations, their gene expression profiles, and interactions contributing to PPP pathology.
Results: We analyzed 32,364 cells using scRNAseq, identifying nine major cell types and revealing significant differences in cellular compositions between lesional PPP, nonlesional skin, and healthy controls. Within the lymphocyte population, regulatory T cells (Treg) and T helper 17 cells (Th17) were exclusively presented in PPP samples. Further characterization uncovered two distinct Th17 subpopulations with differential cytokine expression and regulation. A subpopulation termed “regulatory Th17” expressed immune regulatory molecules FOXP3 and CTLA4 and demonstrated elevated levels of IL17F and IL26 in lesional cells. These cells directly interact with IL36G+ supraspinous keratinocytes, amplifying the inflammatory response. Immunohistochemistry analysis further confirmed elevated levels of IL-26 and IL-17 in lesional skin, implicating these cytokines in the inflammatory cascade associated with PPP.
Conclusions: Our findings underscore the complexity of PPP pathogenesis, involving unique immunological environments and T cell plasticity. The identification of regulatory Th17 cells as major IL-26 producers and their interaction with inflammatory keratinocytes suggests potential therapeutic targets. 


Single-Cell Analysis Reveals Distinct Subpopulations of T Cells and Elevated
IL-26 and IL-17 Levels in Palmoplantar Pustulosis Lesions

Background: Basal cell carcinoma (BCC) is the most prevalent skin malignancy, with a growing global incidence attributed to increased UV exposure and an aging population. While early-stage BCC can be treated with Mohs surgery and photodynamic therapy, options for advanced cases are limited. Existing systemic therapies, including SMOOTHENED inhibitors that target the Hedgehog (HH)-signaling pathway in BCC, are associated with significant adverse effects, such as muscle spasms, hair loss, and teratogenicity. Additionally, the emergence of resistance to these inhibitors underscores the need for diversifying systemic treatment options. This study aims to deepen our understanding of HH-signaling pathway, with the goal of identifying FDA-approved drugs with favorable genetics profile to disrupt this pathway.

Methods: Expression levels of mRNA transcripts for six key genes involved in BCC pathogenesis—Gli1, Gli2, Gli3, Shh, Ptch1, Ptch2, and Smo—were acquired from 269 human neck skin tissues in the Gene Network 2.0 database. Pearson Correlation Matrix analysis revealed statistically significant correlations among these genes (p < 0.05). Signaling network analysis with NetworkAnalyst 3.0 identified key molecular pathways shared among these genes. Subsequently, a protein-protein interaction (PPI) network was constructed based on the six key genes using the IMEx Interactome database, and functional annotation analysis was conducted using KEGG, REACTOME, and Gene Ontology databases to identify associated biological processes, molecular functions, and cellular components. Lastly, a Protein-Drug Network analysis was performed using DrugBank 5.0 database to identify FDA-approved drugs capable of inhibiting protein components of the PPI network.

Results: Pearson correlation matrix analyses revealed significant positive correlations among Gli1, Gli2, Ptch1, and Ptch2 expressions. Notably, positive correlations were observed for Gli1-Gli2 (r = 0.651, p < 0.05), Ptch1-Ptch2 (r = 0.734, p < 0.01), and Gli1-Ptch1 (r = 0.528, p < 0.05). Signaling network analysis identified notable pathways, such as 'Chemokine signaling,' ‘RAS signaling,’ ‘Proteoglycans in cancer,’ and ‘Apelin signaling,’ latter of which has not been previously explored in the context of BCC pathogenesis. Subsequent PPI networks identified 198 proteins regulating various cancer-related pathways, specifically Histone Deacetylase 1 (HDAC1), AKT Serine/Threonine Kinase 2 (AKT2), Phosphatase and Tensin Homolog (PTEN) that are frequently dysregulated in cancerous cells. Subsequent functional annotation analysis identified ‘Positive regulation of transcription,’ ‘Chromatin binding,’ and ‘Nucleus’ as the primary associated biological process, molecular function, and cellular compartment. Finally, Protein-Drug analysis of the PPI network identified six FDA-approved drugs—Amitriptyline, Nintedanib, Pazopanib, Ponatinib, Regorafenib, and Sorafenib—that may disrupt the PPI network by targeting proteins involved in 'PI3K-AKT signaling pathway,’ 'RAS signaling pathway,' and 'Chemokine signaling pathway.'

Conclusion: This study provides deeper insights into the molecular components and signaling pathways in BCC pathogenesis. The significant correlations and identified pathways highlight interdependent regulation of Gli1, Gli2, Ptch1, and Ptch2 expressions. Identifying FDA-approved drugs that may disrupt HH-signaling pathways suggests potential therapeutic strategies to diversify treatment for advanced BCC. These findings support repurposing existing drugs to improve treatment options, warranting further research and clinical trials.

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