Clinical and Experimental Dermatology最新文献

Background: Penile squamous cell carcinoma (PeSCC) is thought to arise through two principal pathogenic pathways, via lichen sclerosus and high-risk human papillomavirus. Molecular alterations in morphologically normal peri tumoral environment are known as 'field effect' and are recognised in other epithelial cancers. Whether similar field effects exist around PeSCC is unknown. As Wnt signaling is a key driver of carcinogenesis, including in PeSCC, perturbations in this pathway may represent an early event in penile tumour evolution.

Objectives: To determine whether a peritumoral molecular field exists around PeSCC by assessing expression and spatial colocalisation of key Wnt-related proteins in cancer-adjacent versus normal penile skin.

Methods: A specialist genitourinary histopathologist reviewed haematoxylin and eosin-stained sections and identified tumour-involved regions, demarcating them from adjacent epithelium that appeared morphologically normal. In this study, immunofluorescence-stained formalin fixed paraffin embedded tissue arrays were probed for Wnt4, cyclin D1, MMP7 and c-MYC proteins. The expression intensity and spatial colocalisation metrics were quantified. Comparisons between normal and cancer-adjacent tissues from 41 patients were conducted for the epidermis and dermis.

Results: Cancer-adjacent tissue showed significant downregulation of Wnt4 in both epidermis and dermis (p < 0.001), and marked upregulation of c-MYC (epidermis: Cohen's d = 2.05; dermis: d = 1.37). MMP7 and Cyclin D1 expression was not significantly changed. Colocalisation analysis revealed significantly increased Global Intersection Coefficients for five combinations within the epidermis (Wnt4/cyclin D1, Wnt4/MMP7, Wnt4/c-MYC, cyclin D1/c-MYC, MMP7/c-MYC), and for two within the dermis (Wnt4/MMP7, Wnt4/c-MYC), indicating enhanced signalling convergence in cancer-adjacent tissues.

Conclusions: This study provides the first evidence of molecular changes in peritumour tissue to demonstrate field effect in PeSCC, characterised by downregulation of Wnt4, upregulation of c-MYC, and altered spatial colocalisation of Wnt-related proteins in cancer-adjacent skin. These findings suggest that peritumoral tissues exhibit early molecular alterations that extend beyond the morphologically defined tumour margin. Recognising these changes may have implications for understanding tumour microenvironment conditioning and for the future development of biomarkers relevant to margin assessment in penile carcinogenesis.

Background: The long-term impact of SARS-CoV-2 infection on inflammatory dermatoses remain incompletely defined.

Objective: To evaluate the association between COVID-19 infection and a broad range of inflammatory dermatoses.

Methods: In this cohort study, electronic health-record data were analyzed for 204,241 patients seen at a tertiary medical center between March 2020 and May 2023, including 22,368 with confirmed COVID-19 and 181,873 controls with negative testing. Diagnoses of 16 inflammatory dermatoses were extracted from standardized documentation fields and verified diagnostic codes.

Results: Elevated risks were observed for atopic dermatitis (IRR, 1.35; 95% CI, 1.25-1.46; P < .001), acne vulgaris (IRR, 1.53; 95% CI, 1.17-1.98; P = .002), rosacea (IRR, 2.41; 95% CI, 1.53-3.66; P < .001), alopecia areata (IRR, 2.39; 95% CI, 1.44-3.80; P < .001), and seborrheic dermatitis (IRR, 1.74; 95% CI, 1.29-2.30; P < .001). No significant associations were observed for psoriasis, hidradenitis suppurativa, lupus erythematosus, pemphigus, or bullous pemphigoid.

Conclusions: Covid-19 infection emerged as a novel risk factor for several inflammatory dermatoses.

Background: The Severity of Alopecia Tool (SALT) score is widely used. However, its inter- and intrarater reliability and smallest detectable difference (SDD) have not been rigorously evaluated.

Objectives: To determine the interrater and intrarater reliability of the SALT score and to quantify its SDD across different levels of disease severity. We assessed the diagnostic accuracy of the SALT score for identifying key clinical thresholds (e.g., SALT50).

Methods: Ten patients were scored live by three experienced raters, and 53 photographic cases were scored by 11 observers. After a two-week interval, 9 raters performed test-retest scoring.

Results: Interrater and intrarater reliability were excellent, with ICCs of 0.949 and 0.939, respectively. SDD was lowest in minimal disease (6.42%) and highest in extensive disease (up to 29.84%). SALT50 was identified with 97% accuracy, although accuracy dropped to 72% when only patients between SALT40-60 were considered. Intrarater reliability was consistently higher than interrater reliability, particularly in patients with a high disease burden.

Conclusion: The SALT score demonstrates high inter- and intrarater reliability, particularly at the extremes of disease severity. However, moderate variability in mid-range scores affects classification near clinical trial thresholds. Rater training and integration of standardized scoring aids may improve its performance.