THIRTY-FIRST ISSUE
april 5, 2023
Get your lovastatin cream as DSAP as possible!
Disseminated superficial actinic porokeratosis (DSAP) is a variant of porokeratosis that predominantly affects sun-exposed areas starting in the 3rd to 4th decade. Although most commonly benign, DSAP holds the potential for malignant transformation. Currently, treatment for DSAP is very challenging. This double-blind clinical trial randomized 31 participants with DSAP to receive topical lovastatin 2% cream (n=14) or topical lovastatin 2% plus cholesterol 2% cream (n=17) for 12 weeks. Disease severity was analyzed at baseline and 12-weeks using the DSAP General Assessment Severity Index (DSAP-GASI).
What did they find?
Main takeaways: Lovastatin 2% cream may be effective for the treatment of DSAP, without concern for serious AEs. The addition of cholesterol 2% cream may be of limited benefit.
Disseminated superficial actinic porokeratosis (DSAP) is a variant of porokeratosis that predominantly affects sun-exposed areas starting in the 3rd to 4th decade. Although most commonly benign, DSAP holds the potential for malignant transformation. Currently, treatment for DSAP is very challenging. This double-blind clinical trial randomized 31 participants with DSAP to receive topical lovastatin 2% cream (n=14) or topical lovastatin 2% plus cholesterol 2% cream (n=17) for 12 weeks. Disease severity was analyzed at baseline and 12-weeks using the DSAP General Assessment Severity Index (DSAP-GASI).
What did they find?
- Disease severity decreased by 51.4% in the lovastatin group (2.92 to 1.50, p-value<0.001), and by 50% in the lovastatin-cholesterol group (3.08 to 1.54, p-value<0.001)
- There was no significant difference in application frequency
- The most commonly reported adverse events (AEs) included application discomfort (n=4), myalgia (n=2), elevated creatine kinase (n=1), and rash (n=1)
- No serious AEs occurred
Main takeaways: Lovastatin 2% cream may be effective for the treatment of DSAP, without concern for serious AEs. The addition of cholesterol 2% cream may be of limited benefit.
Tralokinumab may improve microbial dysbiosis, a factor that contributes to the pathophysiology of atopic dermatitis
Journal of the American Academy of Dermatology
Antibody interested in learning more about tralokinumab?
Atopic dermatitis (AD) is a common skin condition that can significantly decrease quality of life. Multifactorial causes include impaired skin barrier, microbial dysbiosis, and immune dysfunction. Tralokinumab is a monoclonal antibody with activity against IL-13 (a cytokine that plays a role in AD pathogenesis) that has demonstrated efficacy and safety for treatment of AD in phase 3 trials.
Researchers wanted to know whether tralokinumab also works by combating the microbial dysbiosis component of AD, since 90% of those with AD are colonized with high levels of S. aureus and lack microbial diversity seen in normal skin. In the double-blind, randomized, placebo-controlled ECZTRA 1 trial, 802 adults with moderate-to-severe AD were randomized 3:1 to 300 mg subcutaneous tralokinumab or placebo for 52 weeks.
What did they find?
Main Takeaway: Tralokinumab is associated with reduction of S. aureus and increased microbial diversity in skin, which may play a role in treating atopic dermatitis.
Atopic dermatitis (AD) is a common skin condition that can significantly decrease quality of life. Multifactorial causes include impaired skin barrier, microbial dysbiosis, and immune dysfunction. Tralokinumab is a monoclonal antibody with activity against IL-13 (a cytokine that plays a role in AD pathogenesis) that has demonstrated efficacy and safety for treatment of AD in phase 3 trials.
Researchers wanted to know whether tralokinumab also works by combating the microbial dysbiosis component of AD, since 90% of those with AD are colonized with high levels of S. aureus and lack microbial diversity seen in normal skin. In the double-blind, randomized, placebo-controlled ECZTRA 1 trial, 802 adults with moderate-to-severe AD were randomized 3:1 to 300 mg subcutaneous tralokinumab or placebo for 52 weeks.
What did they find?
- Patients treated with tralokinumab had a 10-fold reduction in baseline skin S. aureus levels compared to placebo at week 16 (ratio = 0.09, P < 0.0001)
- Among patients who achieved EASI-75 (75% reduction in Eczema Area and Severity Index), tralokinumab was associated with stronger reduction of S. aureus
- Patients treated with tralokinumab had significantly increased microbial diversity at week 8 and week 16
Main Takeaway: Tralokinumab is associated with reduction of S. aureus and increased microbial diversity in skin, which may play a role in treating atopic dermatitis.
Stage of Keratinocyte Differentiation is a Key Determinant of Viral Susceptibility in Human Skin
Journal of Investigative Dermatology
*skin* is like an onion…it has layers.
Human skin is made of four main layers: basal layer, spinous layer, granular layer, and stratum corneum. In this study, the authors asked whether specific layers of the skin and/or different stages of keratinocyte differentiation are more susceptible to viral infection. The authors performed a combination of in vitro work on cultured human keratinocytes, single cell RNA sequencing, and immunohistochemical staining to answer these questions.
What did they find?
Main takeaways: Viral infections can preferentially affect certain skin layers and stages of differentiation. However, there remains a lot to be learned about mechanisms of viral susceptibility and future studies are required.
Human skin is made of four main layers: basal layer, spinous layer, granular layer, and stratum corneum. In this study, the authors asked whether specific layers of the skin and/or different stages of keratinocyte differentiation are more susceptible to viral infection. The authors performed a combination of in vitro work on cultured human keratinocytes, single cell RNA sequencing, and immunohistochemical staining to answer these questions.
What did they find?
- Human keratinocytes were infected with HSV (herpes simplex virus) and VV (vaccinia virus) at different stages of cellular differentiation
- Cells infected at the initiation of differentiation had increased viral gene expression compared to at other stages. Infected cells at these stages also had increased cytopathic effect, meaning they formed more plaques, corresponding with increased cell lysis, replication, and spread
- Undifferentiated keratinocytes could be infected but did not have a cytopathic effect
- Analyzing a published RNA sequencing dataset, the authors found that viral susceptibility was not likely due to changes in the expression of viral entry receptors
- Examining histopathology from human biopsies of VZV (varicella zoster virus) infected skin, the authors found that the basal layers were relatively spared. Instead, most of the HSV biopsies had similar localizations of infections below the spinous layers and sparing the basal layers
Main takeaways: Viral infections can preferentially affect certain skin layers and stages of differentiation. However, there remains a lot to be learned about mechanisms of viral susceptibility and future studies are required.
derm innovations
“Swinning” the Fight Against Psoriasis
Plaque psoriasis presents as well-demarcated, scaly erythematous plaques and affects more than 7.5 million US adults. Currently, the gold standard of evaluating the disease is by the Psoriasis Area and Severity Index (PASI), which evaluates patients based on the current presentation of their disease. Because of the nature of the scoring, it is restricted due to the subjectivity and possible inconsistency of the individual conducting the exam. The use of artificial neural networks (ANN) in accordance with PASI and Swin Transformer may be able to evade variability in scoring and ultimately predict better treatment for patients.
In this study, 149 patients provided a database of 2232 images of psoriasis plaques. The affected areas were scored with a PASI score and were directly analyzed by three board certified dermatologists to obtain ground truth to be further compared with the automated psoriasis detector (ADP).
What did they find?
Main takeaway: Use of PASI in accordance with this specific ANN outperformed three board-certified dermatologists and other on the market ANN-aided PASI systems. Use of the PASI with ANN can better predict disease severity with consistency and ultimately provide better tailored treatment protocols for patients.
Plaque psoriasis presents as well-demarcated, scaly erythematous plaques and affects more than 7.5 million US adults. Currently, the gold standard of evaluating the disease is by the Psoriasis Area and Severity Index (PASI), which evaluates patients based on the current presentation of their disease. Because of the nature of the scoring, it is restricted due to the subjectivity and possible inconsistency of the individual conducting the exam. The use of artificial neural networks (ANN) in accordance with PASI and Swin Transformer may be able to evade variability in scoring and ultimately predict better treatment for patients.
In this study, 149 patients provided a database of 2232 images of psoriasis plaques. The affected areas were scored with a PASI score and were directly analyzed by three board certified dermatologists to obtain ground truth to be further compared with the automated psoriasis detector (ADP).
What did they find?
- The ADP was found to have a mean absolute error (MAE) of 95.96% and an intraclass correlation coefficient (ICC) of 0.973, showing excellent reliability
- The three dermatologists had a MAE of 76.43% and ICC of 0.781
- ADP outperformed the dermatologist in PASI area score in both MAE and ICC
Main takeaway: Use of PASI in accordance with this specific ANN outperformed three board-certified dermatologists and other on the market ANN-aided PASI systems. Use of the PASI with ANN can better predict disease severity with consistency and ultimately provide better tailored treatment protocols for patients.