seventy-THIRD issue
November 13, 2024
Psychometric properties and meaningful change thresholds of the vitiligo area scoring index
JAMA Dermatology
JAMA Dermatology
Ready, set, vitiliGO! New scoring tools lead the race in vitiligo assessment.
Nonsegmental vitiligo is a chronic skin condition characterized by loss cutaneous of pigmentation. Vitiligo affects quality of life and requires effective treatment assessment. The Total Vitiligo Area Scoring Index (T-VASI) and Facial VASI (F-VASI) are potential tools for evaluating treatment responses in vitiligo. Still, clear thresholds for clinically meaningful improvements have yet to be established. This study aimed to assess the validity and reliability of the T-VASI and F-VASI using a secondary analysis of a phase 2 randomized clinical trial and qualitative interviews.
What did they find?
Main Takeaway: T-VASI and F-VASI are reliable and valid measures for assessing treatment efficacy in nonsegmental vitiligo. These tools may effectively differentiate clinically relevant improvements in vitiligo, making them valuable for future clinical trials.
Nonsegmental vitiligo is a chronic skin condition characterized by loss cutaneous of pigmentation. Vitiligo affects quality of life and requires effective treatment assessment. The Total Vitiligo Area Scoring Index (T-VASI) and Facial VASI (F-VASI) are potential tools for evaluating treatment responses in vitiligo. Still, clear thresholds for clinically meaningful improvements have yet to be established. This study aimed to assess the validity and reliability of the T-VASI and F-VASI using a secondary analysis of a phase 2 randomized clinical trial and qualitative interviews.
What did they find?
- The intraclass correlation coefficients were high for both T-VASI (0.98) and F-VASI (0.99), supporting test-retest reliability.
- Moderate to strong correlations were observed between T-VASI and physician-assessed vitiligo improvement (PhGVA-T) (r = 0.63-0.65) and between F-VASI and PhGVA-F (r = 0.65-0.71).
- A 30% improvement in T-VASI and 50% in F-VASI scores were identified as meaningful changes in repigmentation, suggesting that T-VASI 50 and F-VASI 75 may be conservative benchmarks.
- Qualitative interviews supported these thresholds as reflective of noticeable, meaningful repigmentation.
Main Takeaway: T-VASI and F-VASI are reliable and valid measures for assessing treatment efficacy in nonsegmental vitiligo. These tools may effectively differentiate clinically relevant improvements in vitiligo, making them valuable for future clinical trials.
Assessment of diagnostic delay, morbidity, and mortality outcomes in 302 calciphylaxis patients over a 17-year period
Journal of the American Academy of Dermatology
Journal of the American Academy of Dermatology
Cracking calciphylaxis: Breaking through diagnostic delays and improving outcomes
Calciphylaxis is a rare condition characterized by vascular calcification with associated thrombosis and skin necrosis, primarily affecting individuals with end-stage renal disease (nephrogenic calciphylaxis). Heterogeneity in the clinical presentation of calciphylaxis makes its diagnosis difficult, often prolonging time to diagnosis. Pain, wound healing difficulties, and the sequelae of calciphylaxis lead to high patient morbidity. In this retrospective cohort study of 302 patients with calciphylaxis (245 with nephrogenic calciphylaxis), the factors associated with diagnostic delay, morbidity outcomes, and mortality were evaluated.
What did they find?
Main Takeaway: Diagnostic delays have decreased, particularly for non-nephrogenic calciphylaxis, with morbidity and mortality also improving over time.
Calciphylaxis is a rare condition characterized by vascular calcification with associated thrombosis and skin necrosis, primarily affecting individuals with end-stage renal disease (nephrogenic calciphylaxis). Heterogeneity in the clinical presentation of calciphylaxis makes its diagnosis difficult, often prolonging time to diagnosis. Pain, wound healing difficulties, and the sequelae of calciphylaxis lead to high patient morbidity. In this retrospective cohort study of 302 patients with calciphylaxis (245 with nephrogenic calciphylaxis), the factors associated with diagnostic delay, morbidity outcomes, and mortality were evaluated.
What did they find?
- There was no difference in time to diagnosis in patients who had a biopsy versus those who did not (P=0.72).
- The time to diagnosis for both nephrogenic and non-nephrogenic patients improved over the 17 years investigated.
- Increased diagnostic delays were observed in patients with non-nephrogenic calciphylaxis (P=0.0004) and involvement of the fingers (P=0.0001), while decreased diagnostic delays were observed in patients with involvement of the arms (P=0.01) and genitalia (P=0.022).
- The rate of complications in the cohort decreased from 75% in 2011 to 32% in 2021. Decreases in wound infections (P=0.028), increase in lesion number (P=0.012), and recurrent hospitalizations (P=0.020) were observed.
- The 1-year mortality rates were 36.70% for nephrogenic calciphylaxis and 30.77% for non-nephrogenic calciphylaxis.
Main Takeaway: Diagnostic delays have decreased, particularly for non-nephrogenic calciphylaxis, with morbidity and mortality also improving over time.
Looking into the mechanism behind skin cancer induction by voriconazole
Journal of Investigative Dermatology
Journal of Investigative Dermatology
Anti-fungus among us: Voriconazole’s link to increased skin cancer risk
Voriconazole (VOR), a triazole antifungal, is widely used for fungal prophylaxis in immunosuppressed patients. Its adverse effects include phototoxicity and skin cancer, likely due to disruption of DNA nucleotide excision repair (NER), similar to mechanisms seen in xeroderma pigmentosum. This study investigated VOR-induced NER defects using a cell-based unscheduled DNA synthesis assay in control and VOR-treated fibroblasts.
What did they find?
Main Takeaway: VOR inhibits histone acetyltransferase, potentially explaining the increased skin cancer risk with long-term use. Researchers found that adding histone deacetylase inhibitors could counter this effect, indicating a possible preventive approach for at-risk patients.
Voriconazole (VOR), a triazole antifungal, is widely used for fungal prophylaxis in immunosuppressed patients. Its adverse effects include phototoxicity and skin cancer, likely due to disruption of DNA nucleotide excision repair (NER), similar to mechanisms seen in xeroderma pigmentosum. This study investigated VOR-induced NER defects using a cell-based unscheduled DNA synthesis assay in control and VOR-treated fibroblasts.
What did they find?
- Although VOR impairs NER, no effects were found on gene expression of DNA damage signaling factors.
- VOR treatment inhibited NER in skin fibroblasts of normal individuals and VOR-treated patients (P<0.05).
- Histone acetyltransferase (HAT) activity, a critical component of effective DNA repair, was reduced in VOR-treated cells by acetylation of H3K14 (P<0.05).
- When incubated together, histone deacetylase inhibitors reversed the acetylation of H2K14 in VOR-treated cells (P<0.05).
Main Takeaway: VOR inhibits histone acetyltransferase, potentially explaining the increased skin cancer risk with long-term use. Researchers found that adding histone deacetylase inhibitors could counter this effect, indicating a possible preventive approach for at-risk patients.
Histopathologic overlap between Bullous Lupus Erythematosus and Linear IgA Bullous Dermatosis: A comparative study
American Journal of Dermatopathology
American Journal of Dermatopathology
A blister twister...
Bullous lupus erythematosus (BLE) and linear IgA bullous dermatosis (LABD) are rare autoimmune blistering diseases driven by autoantibodies against distinct basement membrane (BM) antigens. Diagnosis relies on direct immunofluorescence (DIF) and serology. Though BLE and LABD differ in pathogenesis, they share overlapping clinical and histopathologic features. In this retrospective study, researchers identified patients with BLE (n=11) and LABD (n=11) based on DIF positivity for antibodies and/or complement in the BM zone and compared histopathologic features from tissue samples.
What did they find?
Main Takeaway: There was no statistically significant difference in the histopathologic features of bullous lupus erythematosus and linear IgA bullous dermatosis.
Bullous lupus erythematosus (BLE) and linear IgA bullous dermatosis (LABD) are rare autoimmune blistering diseases driven by autoantibodies against distinct basement membrane (BM) antigens. Diagnosis relies on direct immunofluorescence (DIF) and serology. Though BLE and LABD differ in pathogenesis, they share overlapping clinical and histopathologic features. In this retrospective study, researchers identified patients with BLE (n=11) and LABD (n=11) based on DIF positivity for antibodies and/or complement in the BM zone and compared histopathologic features from tissue samples.
What did they find?
- Blisters were neutrophil-predominant in 90% of BLE and 100% of LABD samples (P=0.997).
- Superficial perivascular inflammation (PVI) was seen in all cases while deep PVI was observed in 54% of BLE and 36.4% of LABD samples (P=0.669).
- Epidermal changes adjacent to the vesicle included spongiosis (37.5%; 40%), papillary microabscesses (22%; 20%), and basal tagging by neutrophils (77%; 70%) in BLE and LABD samples, respectively.
- Increased dermal mucin was seen in 60% of BLE and 45.5% of LABD cases.
Main Takeaway: There was no statistically significant difference in the histopathologic features of bullous lupus erythematosus and linear IgA bullous dermatosis.
Is the future of dermatologic procedures in the hands of nonphysician clinicians?
Dermatologic Surgery
Dermatologic Surgery
Shifting the skin-scape of procedural dermatology.
Dermatologists play a crucial role in diagnosing and treating cutaneous conditions, yet recent trends reveal significant changes in who performs dermatologic procedures. A longitudinal analysis of Medicare Public Use Files from 2016 to 2021 examined the distribution of procedural volumes among general dermatologists, Mohs surgeons, primary care providers (PCPs), and nonphysician clinicians (NPCs). The study focused on common procedures, including skin biopsies, excisions, and injections, with data stratified by provider type, geography, and economic factors.
What did they find?
Main Takeaway: NPCs are performing an increasing share of dermatologic procedures, a trend that could address care gaps but raises questions about training and quality assurance.
Dermatologists play a crucial role in diagnosing and treating cutaneous conditions, yet recent trends reveal significant changes in who performs dermatologic procedures. A longitudinal analysis of Medicare Public Use Files from 2016 to 2021 examined the distribution of procedural volumes among general dermatologists, Mohs surgeons, primary care providers (PCPs), and nonphysician clinicians (NPCs). The study focused on common procedures, including skin biopsies, excisions, and injections, with data stratified by provider type, geography, and economic factors.
What did they find?
- 3.0% overall decline in aggregate procedural volume from 2016 to 2021.
- General dermatologists saw a substantial 17.7% decrease in procedural volume.
- NPCs increased their procedural proportion by 57.5%.
- Declines were more pronounced in non-metro (27.1%) and low-income counties (26.1%).
Main Takeaway: NPCs are performing an increasing share of dermatologic procedures, a trend that could address care gaps but raises questions about training and quality assurance.
Is needle-assisted electrocoagulation with glucocorticoids and 5-fluorouracil effective at inhibiting keloid angiogenesis in vivo?
Journal of Cosmetic Dermatology
Journal of Cosmetic Dermatology
There may be a new KEY(loid) treatment in town!
Keloids are raised, thick scars resulting from an overactive healing response, making them difficult to treat. Researchers assessed the effectiveness and safety of combining needle electrocoagulation with pharmacotherapy for keloid treatment.
Human keloid specimens were implanted into 20 mouse models randomly assigned to control, electrocoagulation, glucocorticoid (GC) + 5-fluorouracil (5-FU), or electrocoagulation + GC + 5-FU groups. Keloid size was measured every 3 days, and samples were removed, weighed, and photographed 7 days post-treatment. Immunohistochemistry assessed fibroblast and collagen changes. Additionally, six human subjects with keloids received electrocoagulation and local injections of a 5:1 mixture of 1 mg/mL betamethasone and 25 mg/mL fluorouracil for three treatments over three weeks. Standardized photos were taken before and one month after treatment and evaluated using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS).
What did they find?
Keloids are raised, thick scars resulting from an overactive healing response, making them difficult to treat. Researchers assessed the effectiveness and safety of combining needle electrocoagulation with pharmacotherapy for keloid treatment.
Human keloid specimens were implanted into 20 mouse models randomly assigned to control, electrocoagulation, glucocorticoid (GC) + 5-fluorouracil (5-FU), or electrocoagulation + GC + 5-FU groups. Keloid size was measured every 3 days, and samples were removed, weighed, and photographed 7 days post-treatment. Immunohistochemistry assessed fibroblast and collagen changes. Additionally, six human subjects with keloids received electrocoagulation and local injections of a 5:1 mixture of 1 mg/mL betamethasone and 25 mg/mL fluorouracil for three treatments over three weeks. Standardized photos were taken before and one month after treatment and evaluated using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS).
What did they find?
- Electrocoagulation at 30, 40, 50, and 60 W for 0.5 seconds successfully ablated tissue at widths of 1.16, 1.45, 1.81, and 2.23 mm, respectively.
- Tissue volume was significantly reduced in groups treated with electrocoagulation, drug injection, or both compared to the control.
- The COAG + GC + 5-FU group showed the largest keloid reduction, with a 39.67% volume decrease (P<0.001) compared to the control.
- COAG + GC + 5-FU group showed the greatest reduction of fibroblasts (P<0.001) and irregular collagen arrangement (P<0.01) with upregulating metalloproteinases and downregulating collagen
- VSS score (pigmentation, vascularity, height, pliability) were significantly lower (P<0.05) post-treatment and OSAS scores (thickness, roughness, softness) were significantly reduced (P<0.05).
Underrepresentation of postinflammatory hyperpigmentation outcomes in Acne Vulgaris clinical trials
Skin of Color
Skin of Color
Are acne treatments missing the mark for skin of color?
Acne vulgaris is a common skin condition that can cause postinflammatory hyperpigmentation (PIH), particularly in individuals with skin of color (SOC). In many cases, PIH is as distressing as acne lesions themselves. This study, however, highlights that PIH is rarely considered an outcome in acne vulgaris clinical trials, limiting treatment options tailored specifically for patients with SOC.
What did they find?
Acne vulgaris is a common skin condition that can cause postinflammatory hyperpigmentation (PIH), particularly in individuals with skin of color (SOC). In many cases, PIH is as distressing as acne lesions themselves. This study, however, highlights that PIH is rarely considered an outcome in acne vulgaris clinical trials, limiting treatment options tailored specifically for patients with SOC.
What did they find?
- Only 5 of 165 U.S.-based acne trials since 2000 targeted SOC or Fitzpatrick skin types IV–VI.
- Fewer than 3% of trials included PIH as an outcome, with only 4 trials measuring it directly.
- Only one of the few studies that assessed PIH used the validated Postacne Hyperpigmentation Index, a tool designed for consistent and reliable evaluation of PIH.
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