A Nonrandomized Controlled Trial

[Posted 17/Jan/2023]

AUDIENCE: Dermatology

KEY FINDINGS: These findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways.

BACKGROUND: Cutaneous disease in dermatomyositis has no standardized treatment approach and so presents a challenging task for patients and clinicians. Purpose of this trial was to study the efficacy and safety of apremilast as an add-on therapy in patients with recalcitrant cutaneous dermatomyositis.

DETAILS: This phase 2a, open-label, single-arm nonrandomized controlled trial was conducted at a single center from June 2018 to June 2021. Participants were 8 patients with recalcitrant cutaneous dermatomyositis, defined by a cutaneous disease activity severity index (CDASI) score greater than 5 despite treatment with steroids, steroid-sparing agents, or both. Data were analyzed from June 2018 to June 2021. The primary outcome was the overall response rate (ORR) at 3 months. Key secondary outcomes were the safety and toxicity of apremilast and the durability of response at 6 months. The CDASI, muscle score, dermatology life quality index (DLQI), and depression assessments were performed at baseline and regularly until month 7. Skin biopsies were performed at baseline and 3 months after apremilast (defined as 3 months into active apremilast therapy) and tested for gene expression profiling and immunohistochemical stains. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0. Among 8 patients with recalcitrant cutaneous dermatomyositis (all women; mean [SD] age, 54 [15.9] years), a response was found at 3 months after apremilast among 7 patients (ORR, 87.5%). The mean (SD) decrease in CDASI was 12.9 (6.3) points at 3 months (P .001). Apremilast was well tolerated, with no grade 3 or higher adverse events. Sequencing of RNA was performed on skin biopsies taken from 7 patients at baseline and at 3 months after therapy. Appropriate negative (ie, no primary antibody) and positive (ie, tonsil and spleen) controls were stained in parallel with each set of slides studied. Of 39,076 expressed genes, there were 195 whose expression changed 2-fold or more at P < .01 (123 downregulated and 72 upregulated genes). Gene set enrichment analysis identified 13 pathways in which apremilast was associated with downregulated expression, notably signal transducers and activators of transcription 1 (STAT1), STAT3, interleukin 4 (IL-4), IL-6, IL-12, IL-23, interferon γ (IFNy), and tumor necrosis factor α (TNFα) pathways. In immunohistochemical staining, there was a mean (SD) decrease in phosphorylation levels STAT1 (22.3% [28.3%] positive cells) and STAT3 (13.4% [11.6%] positive cells) at the protein level, a downstream signaling pathway for the downregulated cytokines.

Copyright © American Medical Association. All Rights Reserved.

Source: Bitar, C., Ninh, T., Brag, K., et al. (2022). Apremilast in Recalcitrant Cutaneous Dermatomyositis: A Nonrandomized Controlled Trial. JAMA Dermatol. 2022;158(12): 1357-1366. Published: December, 2022. DOI: 0.1001/jamadermatol.2022.3917.

[Posted 1/Feb/2023]

AUDIENCE: General Surgery, Family Medicine

KEY FINDINGS: OCT is an effective method for evaluating changes in aging skin. The results illustrate a decline in skin density with chronological age. Additionally, it was illustrated that structural change in the epidermis and dermis does occur, however on a microscopic scale, there are no significant differences based on laterality. OCT holds promise as a noninvasive technique for characterization of aging skin. Its utility and application in the clinical management and treatment of aged skin requires further research; however, the technology has potential to personalize therapies based on objective findings.

BACKGROUND: The skin aging exposome encompasses internal and external factors that contribute to clinical signs of facial aging. Aging skin can be characterized by distinctive features such as wrinkles, lentigines, elastosis, and roughness. Optical coherence tomography (OCT) is capable of noninvasively measuring skin characteristics. This study aimed to assess bilateral features using OCT to explore temporal skin changes among decades and potential changes in facial skin aging based on laterality.

DETAILS: A total of 97 subjects between 20 and 89 years old with Fitzpatrick skin types I to IV were enrolled. VivoSight, a Multi-Beam OCT system intended to gather topographical and histological images of skin, was used to scan the area inferolateral to the lateral canthus, bilaterally. Investigators compared characteristics of skin roughness, attenuation coefficient and blood flow across age groups and based on laterality to determine any differences. Only data from successful OCT scans were used. Seventy subjects, 10 from each specified decade, had successful bilateral scans and were thus included in the analysis. Chronological aging was characterized by significantly decreased dermal attenuation coefficient with increased age. Skin roughness measurements showed trends of increased roughness with age; however, no statistically significant changes were seen between groups. Qualitative differences amongst scans taken on right and left sides of the face showed no significance regarding roughness, density or blood flow at depths ranging from 0.05 to 0.5 mm.

Copyright © Wiley Periodicals LLC. All rights reserved.

Source: Vingan, N. R., Parsa, S., Barillas, J., et al. (2023). Evaluation and Characterization of Facial Skin Aging Using Optical Coherence Tomography. Lasers Surg. Med.. 2023; 55(1): 23-24. Published: January, 2023. DOI: 10.1002/lsm.23611.

A Multicenter Cohort Study

[Posted 31/Jan/2023]

AUDIENCE: Dermatology, Oncology

KEY FINDINGS: SLN⁺ is low in patients with T1a melanomas, but younger age, lymphovascular invasion, mitogenicity, and head/neck primary site appear to confer a higher risk of SLN⁺.

BACKGROUND: Sentinel lymph node biopsy is not routinely recommended for T1a cutaneous melanoma due to the overall low risk of positivity. Prognostic factors for positive sentinel lymph node (SLN⁺) in this population are poorly characterized. Aim of this study was to determine factors associated with SLN+ in patients with T1a melanoma

DETAILS: Patients with pathologic T1a (<0.80 mm, nonulcerated) cutaneous melanoma from 5 high-volume melanoma centers from 2001 to 2020 who underwent wide local excision with sentinel lymph node biopsy were included in the study. Patient and tumor characteristics associated with SLN⁺ were analyzed by univariate and multivariable logistic regression analyses. Age was dichotomized into <=42 (25% quartile cutoff) and >42 years. Of the 965 patients identified, the overall SLN⁺ was 4.4% (N = 43). Factors associated with SLN⁺ were age <=42 years (7.5% vs 3.7%; odds ratio [OR], 2.14; P = .03), head/neck primary tumor location (9.2% vs 4%; OR, 2.75; P = .04), lymphovascular invasion (21.4% vs 4.2%; OR, 5.64; P = .01), and >=2 mitoses/mm² (8.2% vs 3.4%; OR, 2.31; P = .03). Patients <42 years with >=2 mitoses/mm² (N = 38) had a SLN⁺ rate of 18.4%.

Copyright © Elsevier Ltd. All rights reserved.

Source: Shannon, A. B., Sharon, C. E., Straker III, R. J., et al. (2023). Sentinel Lymph Node Biopsy In Patients With T1A Cutaneous Malignant Melanoma: A Multicenter Cohort Study. JAAD. 2023; 88(1): 52-59. Published: January, 2023. DOI: 10.1016/j.jaad.2022.09.040.

[Posted 24/Jan/2023]

AUDIENCE: Dermatology

KEY FINDINGS: Pso, being a hyperproliferative disease, is associated with hyperuricemia, which has a harmful effect on kidney function. The related PDs may be unique serological biomarkers for patients with Pso who are at high risk of developing renal abnormalities, especially with higher severity scores.

BACKGROUND: Psoriasis (Pso) is a chronic proliferative skin condition associated with hyperuricemia that may impair renal function.

DETAILS: This case–control study comprises 30 psoriatic patients and 30 age- and sex-matched healthy controls. The enzyme-linked immunosorbent assay (ELISA) was used to assess serum xanthine oxidase (XO) and urine albumin levels. Serum uric acid (SUA) and urinary creatinine were measured using the colorimetric method. There was a rise in the related PDs levels in patients with Pso compared to controls, as evidenced by the enhanced SUA levels (p 0.001) and XO levels (p 0.001). The presence of the related PDs in the serum was linked to the severity of Pso, and there was also a connection between the related PDs levels in the blood and indicators of renal dysfunction. Moreover, SUA and urinary albumin creatinine ratio (UACR) were found to be significantly correlated (r = 0.371 and p = 0.044), as were XO and UACR (r = 0.422 and p = 0.020). In psoriatic patients with itching and palmoplantar affection, mean SUA levels were considerably more significant than those in other instances ( < p = 0.005 and p = 0.018, respectively).

Copyright © John Wiley & Sons, Inc. All rights reserved.

Source: Bazid, H. A. S., Shoeib, M. A., El-Saued, S., et al. (2022). Study of Purine Derivatives And Their Relation To Renal Disorders In Patients With Psoriasis. International Journal of Dermatology. 2023; 62(1): 73-78. Published: January, 2023. DOI: 10.1111/ijd.16343.