One Hundred and Twelfth issue
June 10th, 2026
Prevalence of familial melanoma genes and cancer risk among genomically ascertained individuals
JAMA Dermatology
JAMA Dermatology
Not all family heirlooms are worth keeping
Pathogenic variants (PVs) in familial melanoma genes have historically been studied in individuals with a known personal or family history of cancer. However, this study design risks ascertainment bias and may overestimate prevalence and distort risk associations. In this genome-first cohort study, investigators analyzed genetic data from 696,665 individuals enrolled in two large biobanks regardless of cancer history (US Geisinger MyCode and UK Biobank) to estimate the prevalence and cancer risks of PVs across eight established familial melanoma genes (ACD, BAP1, CDKN2A, CDK4, MITF E318K, POT1, TERF2IP, and TERT promoter).
What did they find?
Limitations: Both cohorts are predominantly of European genetic ancestry, limiting generalizability to Non-European populations.
Main Takeaway: In this genome-first analysis of nearly 700,000 individuals, PVs in familial melanoma genes were identified in approximately 1 in 110 to 1 in 200 people in the general population. PV prevalence in individuals with multiple melanomas or early-onset disease exceeded the established clinical testing threshold, supporting genetic testing in these groups regardless of family history.
Pathogenic variants (PVs) in familial melanoma genes have historically been studied in individuals with a known personal or family history of cancer. However, this study design risks ascertainment bias and may overestimate prevalence and distort risk associations. In this genome-first cohort study, investigators analyzed genetic data from 696,665 individuals enrolled in two large biobanks regardless of cancer history (US Geisinger MyCode and UK Biobank) to estimate the prevalence and cancer risks of PVs across eight established familial melanoma genes (ACD, BAP1, CDKN2A, CDK4, MITF E318K, POT1, TERF2IP, and TERT promoter).
What did they find?
- Approximately 1 in 110 to 1 in 200 people in the general population carried a PV in one of the eight familial melanoma genes, with the majority attributed to the MITF E318K variant.
- Genetic testing is generally recommended when the likelihood of finding a pathogenic variant exceeds 2.5%. Among individuals with multiple melanomas, PV prevalence far exceeded this threshold in both cohorts (7.0%, 95% CI = 3.6%–10.5% in GMC; 5.3%, 95% CI = 4.0%–7.1% in UKBB). Those diagnosed with their first melanoma before age 40 also exceeded this threshold (3.7% GMC; 3.2% UKBB), supporting genetic testing in these groups regardless of family history.
- The study confirmed known cancer associations, including elevated risks of brain, head and neck, and pancreatic cancers in CDKN2A carriers; increased kidney cancer risk in MITF E318K carriers; and increased risk of thyroid and blood cancers in POT1 carriers.
- New or previously inconsistent associations were also identified, including BAP1 with prostate cancer, CDKN2A with biliary tract and nonmelanoma skin cancers, and POT1 with myeloma (OR = 10.1, 95% CI = 2.49–40.8, p = 1.21 × 10⁻³ in UKBB).
Limitations: Both cohorts are predominantly of European genetic ancestry, limiting generalizability to Non-European populations.
Main Takeaway: In this genome-first analysis of nearly 700,000 individuals, PVs in familial melanoma genes were identified in approximately 1 in 110 to 1 in 200 people in the general population. PV prevalence in individuals with multiple melanomas or early-onset disease exceeded the established clinical testing threshold, supporting genetic testing in these groups regardless of family history.
When intuition says one thing and the data say another
Spironolactone and low-dose oral minoxidil (LDOM) are commonly prescribed together for female hair loss, but data on the safety and tolerability of combination therapy remain limited. In this retrospective cohort study, investigators reviewed 432 adult female patients receiving concurrent spironolactone and LDOM to characterize adverse effects, identify risk factors for intolerance, and evaluate prescribing patterns.
What did they find?
Main Takeaway: Combination spironolactone and low-dose oral minoxidil appears to be safe and well-tolerated for most women with hair loss. Simultaneous initiation may reduce hypertrichosis without increasing hypotension-related adverse effects, while patients taking additional blood pressure-lowering medications may warrant closer monitoring.
Spironolactone and low-dose oral minoxidil (LDOM) are commonly prescribed together for female hair loss, but data on the safety and tolerability of combination therapy remain limited. In this retrospective cohort study, investigators reviewed 432 adult female patients receiving concurrent spironolactone and LDOM to characterize adverse effects, identify risk factors for intolerance, and evaluate prescribing patterns.
What did they find?
- Adverse effects were reported in 37.7% of patients, with hypertrichosis (12.3%) and dizziness/lightheadedness/orthostasis (12.0%) being the most common events.
- Simultaneous initiation of spironolactone and LDOM reduced the risk of hypertrichosis by 64.8%, compared with sequential initiation (OR = 0.35, 95% CI = 0.13 - 0.94, p = 0.037).
- Use of 1 or more additional blood pressure-altering medications increased the risk of hypotension-related symptoms by more than threefold (OR = 3.29, 95% CI = 1.65 - 6.58, p = 0.001).
- Most adverse effects were mild and manageable, with no ICU admissions reported and 94.3% of treatment modifications occurring in the outpatient setting.
Main Takeaway: Combination spironolactone and low-dose oral minoxidil appears to be safe and well-tolerated for most women with hair loss. Simultaneous initiation may reduce hypertrichosis without increasing hypotension-related adverse effects, while patients taking additional blood pressure-lowering medications may warrant closer monitoring.
Two phase III trials of bimekizumab for the treatment of moderate-to-severe hidradentitis suppurativa: a critically appraised research paper
British Journal of Dermatology
British Journal of Dermatology
A dual IL-17 blocker for HS? Groundbreaking.
Hidradenitis suppurativa (HS) is a painful, debilitating condition in which IL-17 family cytokines are a key pathogenic driver. Bimekizumab is the first approved biologic to block both IL-17A and IL-17F. BE-HEARD I and II phase III trials enrolled 1,014 adults with moderate-to-severe HS and inadequate response to systemic antibiotics with the HiSCR (Hidradenitis Suppurativa Clinical Response) 50 at week 16 was the primary endpoint (indicative of a 50% reduction in abscess and inflammatory nodule count).
What did they find?
Limitations: The predominantly White (80%) and female (57%) cohort, exclusion of patients with >20 draining tunnels, and UCB Pharma funding, limit generalizability to the most severe phenotypes and introduces potential bias.
Main Takeaway: In two phase III trials, the dual IL-17A/F inhibitor bimekizumab appears effective in reducing clinical severity and safe for moderate-to-severe HS.
Hidradenitis suppurativa (HS) is a painful, debilitating condition in which IL-17 family cytokines are a key pathogenic driver. Bimekizumab is the first approved biologic to block both IL-17A and IL-17F. BE-HEARD I and II phase III trials enrolled 1,014 adults with moderate-to-severe HS and inadequate response to systemic antibiotics with the HiSCR (Hidradenitis Suppurativa Clinical Response) 50 at week 16 was the primary endpoint (indicative of a 50% reduction in abscess and inflammatory nodule count).
What did they find?
- Dosing of bimekizumab once every 2 weeks (q2w) met the primary endpoint more frequently than placebo in both trials [BE-HEARD I: 48% vs 29% placebo (OR = 2.23, 97.5% CI = 1.16 - 4.31, p = 0.006); BE-HEARD II: 52% vs 32% (OR = 2.29, 97.5% CI = 1.22 - 4.29, p = 0.003)]. Dosing once every 4 weeks only differed from placebo in BE-HEARD II (OR = 2.42, 97.5% CI = 1.22 - 4.80, p = 0.004).
- HiSCR 75 favored the q2w arm (33% vs 18% and 36% vs 16%), and bimekizumab produced significant Dermatology Life Quality Index improvements over placebo in both trials (p < 0.001).
- A notably high placebo response was observed, with 31% (45/146) of placebo patients meeting the primary endpoint, possibly reflecting limitations of HiSCR or the pathogenic complexity of HS.
- Bimekizumab was generally well tolerated (64/995 serious Treatment-Emergent Adverse Events). The most common TEAEs were candida infections (23 - 25%) and hypersensitivity reactions (21 - 27%).
Limitations: The predominantly White (80%) and female (57%) cohort, exclusion of patients with >20 draining tunnels, and UCB Pharma funding, limit generalizability to the most severe phenotypes and introduces potential bias.
Main Takeaway: In two phase III trials, the dual IL-17A/F inhibitor bimekizumab appears effective in reducing clinical severity and safe for moderate-to-severe HS.
This psoriasis study might be the wake-up call you need!
Psoriasis is a chronic immune-mediated inflammatory skin condition with well-established genetic susceptibility and associations with poor sleep. However, population-level analyses of sleep patterns and incident psoriasis remain limited, particularly with respect to genetic susceptibility. This prospective cohort study analyzed 372,048 psoriasis-free UK Biobank participants followed for a median of 16 years to assess incident psoriasis across sleep patterns and genetic risk groups.
What did they find?
Main Takeaway: Poor sleep patterns were associated with a higher incidence of psoriasis, and this effect was greater among females and those with genetic susceptibility, suggesting that sleep may represent an important modifiable risk factor for psoriasis, particularly in susceptible individuals.
Psoriasis is a chronic immune-mediated inflammatory skin condition with well-established genetic susceptibility and associations with poor sleep. However, population-level analyses of sleep patterns and incident psoriasis remain limited, particularly with respect to genetic susceptibility. This prospective cohort study analyzed 372,048 psoriasis-free UK Biobank participants followed for a median of 16 years to assess incident psoriasis across sleep patterns and genetic risk groups.
What did they find?
- Participants with poor sleep patterns had a 65.6% higher risk of developing incident psoriasis compared to participants with healthy sleep patterns (hazard ratio [HR] = 1.656, 95% CI = 1.403 - 1.954, p < 0.001)
- The risk of incident psoriasis increased as sleep scores worsened, even after adjustment for demographic, socioeconomic, and lifestyle factors (p < 0.001).
- Poor sleep patterns were associated with a significantly greater increase in incident psoriasis risk among females (HR = 2.050, 95% CI = 1.646–2.554, p < 0.001) than among males (HR = 1.543, 95% CI = 1.205–1.975, p = 0.001).
- Participants with poor sleep patterns and high genetic risk had the highest risk of incident psoriasis compared to participants with healthy sleep patterns and low genetic risk (HR = 3.620, 95% CI = 2.671 - 4.907, p < 0.001).
Main Takeaway: Poor sleep patterns were associated with a higher incidence of psoriasis, and this effect was greater among females and those with genetic susceptibility, suggesting that sleep may represent an important modifiable risk factor for psoriasis, particularly in susceptible individuals.
Call that a beta-QUACK-tam.
Staphylococcal scalded skin syndrome (SSSS) is an acute, exfoliative dermatological condition caused by exotoxins produced during severe Staphylococcus aureus infection, primarily affecting children. Although SSSS continues to be treated with antimicrobial therapy, research on antimicrobial susceptibility patterns of causative S. aureus strains has been limited. This retrospective study analyzed microbiological and susceptibility data in 120 pediatric patients with SSSS at a tertiary referral center.
What did they find?
Main Takeaway: First-line β-lactam agents, such as cloxacillin, remain favorable in the treatment of SSSS in pediatric patients, with possible alternatives being co-trimoxazole and ciprofloxacin.
Staphylococcal scalded skin syndrome (SSSS) is an acute, exfoliative dermatological condition caused by exotoxins produced during severe Staphylococcus aureus infection, primarily affecting children. Although SSSS continues to be treated with antimicrobial therapy, research on antimicrobial susceptibility patterns of causative S. aureus strains has been limited. This retrospective study analyzed microbiological and susceptibility data in 120 pediatric patients with SSSS at a tertiary referral center.
What did they find?
- Isolates were most susceptible to co-trimoxazole (90.9%), followed by cloxacillin (88.4%), ciprofloxacin (85.2%), clindamycin (83.3%), and vancomycin (83.3%).
- Specific to blood cultures, 100% (6/6) of S. aureus isolates were sensitive to gentamicin and showed moderate sensitivity to cloxacillin and clindamycin (83.3%, 5/6).
- Clinical outcomes were favorable, with no in-hospital mortality, a mean hospital stay of only 4.38 days total, and a complete recovery in 69.2% of patients.
Main Takeaway: First-line β-lactam agents, such as cloxacillin, remain favorable in the treatment of SSSS in pediatric patients, with possible alternatives being co-trimoxazole and ciprofloxacin.
Prospective evidence on artificial intelligence-assisted melanoma diagnostics: A systematic review and meta-analysis
Innovations/Scoop
Innovations/Scoop
The robots are officially on their way to applying to dermatology residency.
Artificial Intelligence (AI) has shown impressive results for melanoma detection in retrospective studies, but prospective, real-world evidence is needed before clinical application. This systematic review and meta-analysis evaluated how AI performs compared with dermatologists in prospective dermoscopy-based melanoma diagnosis. Authors systematically reviewed 11 prospective studies and pooled diagnostic performance metrics, including sensitivity, specificity, accuracy, and balanced accuracy for AI, dermatologists, and AI-assisted dermatologists.
What did they find?
Main Takeaway: Current evidence suggests that AI can diagnose melanoma at a level comparable to dermatologists and may further improve performance when used as an assistive tool. However, larger multicenter studies using unselected real-world patient populations are still needed before AI can be considered fully validated for routine clinical practice.
Artificial Intelligence (AI) has shown impressive results for melanoma detection in retrospective studies, but prospective, real-world evidence is needed before clinical application. This systematic review and meta-analysis evaluated how AI performs compared with dermatologists in prospective dermoscopy-based melanoma diagnosis. Authors systematically reviewed 11 prospective studies and pooled diagnostic performance metrics, including sensitivity, specificity, accuracy, and balanced accuracy for AI, dermatologists, and AI-assisted dermatologists.
What did they find?
- Dermatologists achieved a pooled sensitivity of 78.6% (95% CI = 67.5% - 88.1%) and specificity of 75.2% (95% CI = 63.3% - 84.3%) for melanoma diagnosis.
- AI systems demonstrated a pooled sensitivity of 80.9% (95% CI = 63.6% - 94.5%) and specificity of 75.6% (95% CI = 64.5% - 85.6%), showing comparable overall performance to dermatologists.
- In the only study evaluating AI-assisted dermatologists, diagnostic performance improved to 91.9% sensitivity and 83.7% specificity, suggesting that AI may function best as a decision-support tool rather than a replacement for clinicians.
- Across direct head-to-head comparisons, AI generally demonstrated higher specificity with similar sensitivity compared with dermatologists, potentially reducing unnecessary biopsies while maintaining melanoma detection rates. However, pooled analyses found no statistically significant differences between AI and dermatologist performance.
Main Takeaway: Current evidence suggests that AI can diagnose melanoma at a level comparable to dermatologists and may further improve performance when used as an assistive tool. However, larger multicenter studies using unselected real-world patient populations are still needed before AI can be considered fully validated for routine clinical practice.
A multicenter trial of an enhanced serum comprised of 13 plant-based adaptogens targeting skin quality in females impacted by hormonal decline
Integrative Dermatology
Integrative Dermatology
When estrogen clocks out for retirement, adaptogens are ready to pick up the extra shift.
Declining estrogen levels during menopause contribute to reduced collagen production, impaired barrier function, skin dryness, wrinkles, and loss of elasticity. In this 16-week open-label multicenter trial, 55 perimenopausal and postmenopausal women applied MYS-REV, a serum containing 13 plant-derived adaptogens—including ginseng, cocoa leaf, hops, Echinacea purpurea, chamomile, turmeric, magnolia bark, copaiba resin, Japanese pagoda tree, black currant seed oil, evening primrose oil, grape flower cell extract, and sea buckthorn—twice daily and underwent investigator assessments, bioinstrumentation testing, and self-reported evaluations.
What did they find?
Main Takeaway: A serum formulated with plant-derived adaptogens and antioxidant technologies demonstrated significant improvements in multiple clinical signs of menopause-associated skin aging while maintaining excellent tolerability. Controlled studies will be needed to determine how these results compare with established anti-aging and hormone-related skincare interventions.
Declining estrogen levels during menopause contribute to reduced collagen production, impaired barrier function, skin dryness, wrinkles, and loss of elasticity. In this 16-week open-label multicenter trial, 55 perimenopausal and postmenopausal women applied MYS-REV, a serum containing 13 plant-derived adaptogens—including ginseng, cocoa leaf, hops, Echinacea purpurea, chamomile, turmeric, magnolia bark, copaiba resin, Japanese pagoda tree, black currant seed oil, evening primrose oil, grape flower cell extract, and sea buckthorn—twice daily and underwent investigator assessments, bioinstrumentation testing, and self-reported evaluations.
What did they find?
- Elastosis/crepey skin improved by 32% and lines/wrinkles improved by 22% at week 16 compared with baseline (p < 0.0001).
- Significant improvements were observed in erythema (65%), texture/ roughness (53%), dullness (49%), uneven pigmentation (28%), and pore size (23%) at week 16 (all p < 0.0001).
- Skin hydration increased immediately after application (35%) and reached a 60% improvement at week 16, while trans-epidermal water loss decreased by 27% (p < 0.0001).
- Subject satisfaction was high: 96% reported improved overall skin quality, 94% reported more hydrated skin, and 92% reported more rejuvenated and revitalized skin after 16 weeks.
Main Takeaway: A serum formulated with plant-derived adaptogens and antioxidant technologies demonstrated significant improvements in multiple clinical signs of menopause-associated skin aging while maintaining excellent tolerability. Controlled studies will be needed to determine how these results compare with established anti-aging and hormone-related skincare interventions.
The Asian burden of urticaria in adolescents and young adults: estimates from 1990-2921 and projections to 2036
Global Derm
Global Derm
Urticaria is overstaying its visa in Central Asia
Urticaria has been closely linked to epidemiological factors, including population density and socioeconomic status. Research indicates that the global prevalence is increasing year by year, with a significant impact on patients’ quality of life, sleep, and school/ work performance, especially in children, women, and populations in low-income countries. In this study, data from the Global Burden of Disease (GBD) 2021 were utilized to evaluate the burden of urticaria among adolescents and young adults across Asia.
What did they find?
Main Takeaway: The burden of urticaria among adolescents and young adults in Asia has increased over the past three decades and is projected to continue rising through 2036, with females and certain regions, particularly Central Asia, experiencing the greatest impact. These findings highlight the need for earlier recognition, targeted public health strategies, and equitable medical resource distribution to address this growing dermatologic burden.
Urticaria has been closely linked to epidemiological factors, including population density and socioeconomic status. Research indicates that the global prevalence is increasing year by year, with a significant impact on patients’ quality of life, sleep, and school/ work performance, especially in children, women, and populations in low-income countries. In this study, data from the Global Burden of Disease (GBD) 2021 were utilized to evaluate the burden of urticaria among adolescents and young adults across Asia.
What did they find?
- From 1990 to 2021, the burden of urticaria among Asian adolescents and young adults increased, with prevalence rising from 863.13 [95% uncertainty interval (UI): 761.99 to 983.08] to 877.84 (95% UI: 775.68 to 1000.20) and incidence rising from 1525.51 (95% UI: 1341.63 to 1728.55) to 1552.60 (95% UI: 1369.05 to 1758.22) per 100,000 population.
- Urticaria prevalence was higher in females, and the most substantial rise was observed in the 10-14 age group
- Central Asia has the highest age-standardized prevalence, incidence, and disability-adjusted life years, aligning with the region’s environmental pollution, inadequate healthcare resources, and thermal instability that may trigger cutaneous vascular responses.
- Between 2021 and 2036, the prevalence of urticaria among individuals aged 10-24 years in Asia is projected to increase across all evaluated metrics.
Main Takeaway: The burden of urticaria among adolescents and young adults in Asia has increased over the past three decades and is projected to continue rising through 2036, with females and certain regions, particularly Central Asia, experiencing the greatest impact. These findings highlight the need for earlier recognition, targeted public health strategies, and equitable medical resource distribution to address this growing dermatologic burden.
DERMLITE Dermoscopy QUESTION OF THE WEEK
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