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.

Background: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe systemic hypersensitivity drug reaction with diverse skin morphologies, including erythema multiforme (EM)-like lesions. Limited literature exists on the prognostic significance of EM-like lesions in patients with DRESS.

Methods: This was a prospective case-control study, comparing organ involvement and prognosis of DRESS with EM-like lesions with that of a matched control population of DRESS without EM-like lesions at a tertiary care centre in Northern India. Clinical records of patients enrolled in a prospective cohort of DRESS from January 2018 to August 2024 were reviewed. The diagnosis of DRESS was confirmed using European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria. Based on the RegiSCAR score, 72 patients with probable and definite DRESS were recruited and divided into two groups: those with EM-like lesions (cases, n = 25) and those without (controls, n = 47), matched by age, gender, and race.

Results: Patients with EM-like lesions had a significantly longer latency between drug intake and symptom onset (p=0.007), a higher incidence of purpuric lesions (p<0.001), a less common erythrodermic presentation (p=0.034), greater palm and sole involvement (p=0.003), facial edema (p<0.001), and mucosal involvement (p=0.016). Those with EM-like lesions had a significantly elevated total leukocyte count (p=0.028), higher CRP levels (p=0.023), abnormal liver enzymes (ALT, AST) and lower eosinophil counts (p=0.005) with a greater likelihood of hepatic involvement (OR=6.9).

Conclusions: DRESS patients with EM-like lesions experience a more severe disease course with greater hepatic involvement. These could be clinical markers for more aggressive disease necessitating multidisciplinary care.

Tebentafusp is a novel T-cell receptor-based bispecific protein that targets glycoprotein 100 and CD3. It is the only approved systemic therapy for patients with unresectable or metastatic human leucocyte antigen (HLA)-A*02:01-positive uveal melanoma. Cutaneous toxicities are common, yet there are limited studies in the literature. We conducted a retrospective observational cohort study of patients with HLA-A*02:01-positive unresectable or metastatic uveal melanoma who received tebentafusp therapy from August 2021 to January 2024 at the Royal Marsden NHS Foundation Trust (London, UK), a tertiary referral centre. Cutaneous toxicity occurred in 16/18 (89%) patients, but reactions were manageable, with no patients permanently discontinuing treatment. To our knowledge, we also report the first case of bullous pemphigoid associated with tebentafusp.