Study of Purine Derivatives and Their Relation To Renal Disorders In Patients With Psoriasis

The 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.

source: Int J Dermatol

Summary

[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).

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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.



DMT310, A Novel Once-Weekly Topical Treatment For Patients With Moderate-To-Severe Acne Vulgaris

DMT310 once-weekly topical treatment significantly reduced both inflammatory and noninflammatory lesions and yielded a greater proportion of Investigator's Global Assessment treatment success at all time points in participants with moderate-to-severe acne.

source: JAAD

Summary

Results Of A Phase 2B Randomized, Double-Blind, Placebo-Controlled Trial

[Posted 23/Oct/2023]

AUDIENCE: Dermatology, Pediatric, Family Medicine

KEY FINDINGS: DMT310 once-weekly topical treatment significantly reduced both inflammatory and noninflammatory lesions and yielded a greater proportion of Investigator's Global Assessment treatment success at all time points in participants with moderate-to-severe acne.

BACKGROUND: Poor patient adherence with antiacne medications is a common clinical challenge. DMT310, a natural, topical product with a once-weekly application schedule, may alleviate this obstacle. Purpose of this study is to evaluate the safety, tolerability, and efficacy of DMT310 in treating moderate-to-severe acne. This 12-week, randomized, double-blind, placebo-controlled, multicenter clinical trial enrolled participants 12 years and older with moderate-to-severe acne.

DETAILS: The intent-to-treat population included a total of 181 participants (DMT310, N = 91; placebo, N = 90). Participants who received DMT310 vs participants treated with placebo demonstrated a statistically significant greater reduction in the number of inflammatory and noninflammatory lesions at all time points: inflammatory lesion counts at week 12 (-15.64 vs -10.84, P < .001); noninflammatory lesion counts at week 12 (-18.26 vs -12.41, P < .001). DMT310-treated participants also had higher rates of Investigator's Global Assessment treatment success than participants in the placebo group at all time points: Investigator's Global Assessment at week 12 (44.40% vs 17.78%; P < .001). No serious treatment related adverse events occurred.

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Source: Eichenfield, L. F., DuBois, J. C., Gold, M. H., et al. (2023). DMT310, A Novel Once-Weekly Topical Treatment For Patients With Moderate-To-Severe Acne Vulgaris: Results Of A Phase 2B Randomized, Double-Blind, Placebo-Controlled Trial. JAAD. 2023; 89(5): 945-951. Published: November, 2023. DOI: 10.1016/j.jaad.2023.05.070.



Bath Psoralen Plus Ultraviolet-A Photochemotherapy for Chronic Graft-Versus-Host Disease

Bath PUVA is well-tolerated and effective for extensive cutaneous chronic graft-versus-host disease. It allows rapid tapering of adjuvant immunosuppressants; however, most patients require prolonged maintenance phototherapy.

source: Int J Dermatol

Summary

A Retrospective Cohort Study

[Posted 4/Oct/2023]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: Bath PUVA is well-tolerated and effective for extensive cutaneous chronic graft-versus-host disease. It allows rapid tapering of adjuvant immunosuppressants; however, most patients require prolonged maintenance phototherapy.

BACKGROUND: Chronic graft-versus-host disease is a severe complication of allogeneic stem cell and bone marrow transplantation. First-line immunosuppressive agents, such as steroids, are used to prevent this disease; however, they have multiple side effects. Therefore, bath psoralen plus ultraviolet-A (PUVA) is an alternative second-line treatment. This study aimed to evaluate the clinical efficacy of bath PUVA for managing chronic graft-versus-host disease.

DETAILS: This retrospective, case-control study included 14 patients with extensive cutaneous chronic graft-versus-host disease, resistant to systemic corticosteroid, treated with bath PUVA. Major and partial responses were defined as clinical improvements of >70% and 50-70%, respectively. We analyzed the graft-versus-host disease clinical presentation and timing after allogeneic stem cell and bone marrow transplantation, bath PUVA doses, background diseases, additional treatments, and adverse effects. Researchers observed eight major (three lichenoid and five sclerodermatoid) and six partial (three lichenoid and three sclerodermatoid) responses after a mean of 28 treatment sessions. After 6 to 25 months, four of the eight patients with sclerodermatoid lesions and all those with lichenoid lesions experienced relapse but responded to additional treatment cycles.

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Source: Kassem, R., Barzilai, A., Pras, E., et al. (2023). Bath Psoralen Plus Ultraviolet-A Photochemotherapy for Chronic Graft-Versus-Host Disease: A Retrospective Cohort Study. Int J Dermatol. 2023; 62(10): 1261-1265. Published: October, 2023. DOI: 10.1111/ijd.16806.



A Comprehensive Investigation of Novel and Traditional Inflammatory and Metabolic Markers as Predictive Indicators in Psoriasis

The absence of specificity of these markers for psoriasis limits their practical application. However, the development of new objective measures by using them in combination with specific data such as PASI will provide significant benefits in terms of disease diagnosis, follow-up, and treatment.

source: Int J Dermatol

Summary

[Posted 29/Sep/2023]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: The absence of specificity of these markers for psoriasis limits their practical application. However, the development of new objective measures by using them in combination with specific data such as PASI will provide significant benefits in terms of disease diagnosis, follow-up, and treatment.

BACKGROUND: Psoriasis is a chronic inflammatory and papulosquamous dermatological disorder. While previous studies have discussed certain inflammatory markers for diagnosing and monitoring psoriasis, there is an absence of comprehensive research encompassing both novel and traditional inflammatory markers, as well as metabolic markers, in relation to psoriasis.

DETAILS: A total of 209 individuals participated, including 54 psoriasis patients and 155 controls. Psoriasis Area Severity Index (PASI) was calculated for the patient group. Potential predictive markers for psoriasis were identified: Uric acid/HDL ratio (UHR), D-dimer/albumin ratio (DAR), fibrinogen/albumin ratio (FAR), erythrocyte sedimentation rate, CRP, WBC, HOMA-IR, and vitamin D levels. Differences between groups and correlations with PASI and each other were analyzed using the Mann–Whitney U test and Spearman correlation coefficient. The results indicate that the patient group exhibited statistically significantly higher levels of UHR, FAR, CRP, WBC, and HOMA-IR. Upon analyzing the correlations between PASI and the identified markers, statistically significant positive correlation with WBC and negative correlation with vitamin D were observed. The correlations of PASI with other markers did not reach statistical significance. It should be underlined that our study was conducted in a predominantly mild-to-moderate patient population.

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Source: Metin, Z., Tur, K., Durmaz, K., et al. (2023). A Comprehensive Investigation of Novel and Traditional Inflammatory and Metabolic Markers as Predictive Indicators in Psoriasis. International Journal of Dermatology. 2023; 62(10): 1272-1280. Published: October, 2023. DOI: 10.1111/ijd.16813.



Adalimumab In Conjunction With Surgery Compared With Adalimumab Monotherapy For Hidradenitis Suppurativa

Combining adalimumab with surgery resulted in greater clinical effectiveness and improved quality of life after 12 months in patients with moderate to severe hidradenitis suppurativa.

source: JAAD

Summary

A Randomized Controlled Trial In A Real-World Setting

[Posted 21/Sep/2023]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: Combining adalimumab with surgery resulted in greater clinical effectiveness and improved quality of life after 12 months in patients with moderate to severe hidradenitis suppurativa.

BACKGROUND: Adalimumab, the only biologic registered for hidradenitis suppurativa, shows clinical response in up to 60% of patients, leaving many patients in need for other treatment options such as surgery. Aim of the study is to compare the clinical effectiveness of adalimumab combined with surgery vs adalimumab monotherapy in patients with moderate to severe hidradenitis suppurativa.

DETAILS: A pragmatic Randomized Controlled Trial was performed from August 2018 to July 2022. Primary outcome was the difference in mean International Hidradenitis Suppurativa Severity Score System reduction after 12 months of treatment with the difference in mean Dermatology Life Quality Index reduction as a key secondary outcome. Thirty-one patients were included per arm. The mean International Hidradenitis Suppurativa Severity Score System at baseline was 23.9 ± 10.7 in the surgery group and 20.9 ± 16.4, in the monotherapy group. After 12 months of treatment the surgery group had a significantly greater reduction in International Hidradenitis Suppurativa Severity Score System compared with the monotherapy group (-19.1 ± 11.3 vs -7.8 ± 11.8, P < .001). Moreover, the surgery group showed a greater reduction in Dermatology Life Quality Index after treatment compared with the monotherapy group (-8.2 ± 6.2 vs -4 ± 7.7, P = .02). Limitations: The study follow-up was too short to assess surgical recurrence rates.

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Copyright © Elsevier Ltd. All rights reserved.

Source: Aarts, P., van Huijstee, J. C., van der Zee, H. H., et al. (2023). Adalimumab In Conjunction With Surgery Compared With Adalimumab Monotherapy For Hidradenitis Suppurativa: A Randomized Controlled Trial In A Real-World Setting. Journal of the American Academy of Dermatology. 2023; 89(4): 677-684. Published: October, 2023. DOI: 10.1016/j.jaad.2023.04.034.



Lysosomal Function and Intracellular Position Determine the Malignant Phenotype in Malignant Melanoma

Rab7a overexpression is accompanied by reduced migration capacity. Taken together, the study emphasizes that alterations in lysosomal properties facilitate the malignant phenotype and declares the targeting of lysosomal function as a future therapeutic approach.

source: JID

Summary

[Posted 14/Sep/2023]

AUDIENCE: Dermatology, Oncology, Family Medicine

KEY FINDINGS: In addition, Rab7a overexpression is accompanied by reduced migration capacity. Taken together, the study emphasizes that alterations in lysosomal properties facilitate the malignant phenotype and declares the targeting of lysosomal function as a future therapeutic approach.

BACKGROUND: Lysosomes are central in cell homeostasis and participate in macromolecular degradation, plasma membrane repair, exosome release, cell adhesion/migration, and apoptosis. In cancer, alterations in lysosomal function and spatial distribution may facilitate disease progression.

DETAILS: In this study, authors show enhanced lysosomal activity in malignant melanoma cells compared with that in normal human melanocytes. Most lysosomes show perinuclear location in melanocytes, while they are more dispersed in melanoma, with retained proteolytic activity and low pH also in the peripheral population. Rab7a expression is lower in melanoma cells than in melanocytes, and by increasing Rab7a, lysosomes are relocated to the perinuclear region in melanoma. Exposure to the lysosome-destabilizing drug L-leucyl-L-leucine methyl ester causes higher damage in the perinuclear subset of lysosomes in melanomas, whereas differences in subpopulation susceptibility cannot be found in melanocytes. Interestingly, melanoma cells recruit the endosomal sorting complex required for transport-III core protein CHMP4B, involved in lysosomal membrane repair, rather than initiate lysophagy. However, when the perinuclear lysosomal position is promoted by Rab7a overexpression or kinesore treatment, lysophagy is increased.

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Copyright © The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. All rights reserved.

Source: Eriksson, I., Vainikka, L., Waster, P., et al. (2023). Lysosomal Function and Intracellular Position Determine the Malignant Phenotype in Malignant Melanoma. Journal of Investigative Dermatology. 2023; 143 (9): 1769-1778. Published: September, 2023. DOI: 10.1016/j.jid.2023.01.036.



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