Epidermal growth factor receptor inhibitors in advanced cutaneous squamous cell carcinoma: A systematic review and meta-analysis.

Patients with advanced cutaneous squamous cell carcinoma (cSCC) who are not eligible for or who fail to respond to anti-PD1 immunotherapy have few treatment options. Epidermal growth factor receptor (EGFR) inhibitors have been investigated as a therapeutic option for advanced cSCC; however, data are limited to small single-arm trials or retrospective studies. A systematic review and meta-analysis was conducted to PRISMA guidelines (CRD42023394300). Studies reporting on outcomes of EGFR inhibition in advanced cSCC were identified. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse event (AE) rate were pooled using a random effects model and the inverse variance method. Twelve studies (six prospective, six retrospective) were identified, representing 324 patients. Pooled ORR was 26% (95% confidence interval [CI] 18-36), median PFS was 4.8 months (95% CI 3.9-6.6) and median OS was 11.7 months (95% CI 9.2-14.1). Any grade AEs occurred in 93% of patients (95% CI 85-97) while grade 3 and higher AEs occurred in 30% (95% CI 14-54). These results were similar between anti-EGFR monoclonal antibodies (MAbs) and tyrosine kinase inhibitors (TKIs). EGFR inhibitors can be considered in patients with advanced cSCC who are contraindicated for or progress on first-line anti-PD1 immunotherapy. Future studies should evaluate their activity and safety following anti-PD1, identify predictive biomarkers for their efficacy and explore combination approaches.

Resident cutaneous memory T cells: a clinical review of their role in chronic inflammatory dermatoses and potential as therapeutic targets.

Resident memory T cells (T-RMs) remain in epithelial barrier tissues after antigen exposure and the initial effector phase. These T-RMs provide effective antimicrobial and anticancer immunity; however, pathogenic T-RMs have been shown to mediate various chronic inflammatory disorders in a variety of tissue types. In the skin, T-RMs are referred to as resident cutaneous memory T cells (cT-RMs). Understanding the mechanisms leading to the development and establishment of these cT-RMs populations may allow for targeted treatments that provide durable responses in chronic immune-mediated skin diseases, even after cessation. In this review, we summarize the evidence on cT-RMs as drivers of chronic inflammatory dermatoses, including psoriasis, vitiligo, atopic dermatitis, cutaneous lupus erythematosus and alopecia areata, among others. Data from in vitro, animal model and ex vivo human studies are presented, with a focus on the potential for cT-RMs to trigger acute disease flares, as well as recurrent disease, by establishing an immune 'memory' in the skin. Furthermore, the available data on the potential for existing and novel treatments to affect the development or survival of cT-RMs in the skin are synthesized. The data suggest a dynamic and rapidly growing area in the field of dermatology; however, we also discuss areas in need of greater research to allow for optimal treatment selection for long-term disease control.

Chemotherapy in Cutaneous Melanoma: Is There Still a Role?

PURPOSE OF REVIEW: In the preceding decade, the management of metastatic cutaneous melanoma has been revolutionised with the development of highly effective therapies including immune checkpoint inhibitors (specifically CTLA-4 and PD-1 inhibitors) and targeted therapies (BRAF and MEK inhibitors). The role of chemotherapy in the contemporary management of melanoma is undefined. RECENT FINDINGS: Extended analyses highlight substantially improved 5-year survival rates of approximately 50% in patients with metastatic melanoma treated with first-line therapies. However, most patients will progress on these first-line treatments. Sequencing of chemotherapy following failure of targeted and immunotherapies is associated with low objective response rates and short progression-free survival, and thus, meaningful benefits to patients are minimal. Chemotherapy has limited utility in the contemporary management of cutaneous melanoma (with a few exceptions, discussed herein) and should not be the standard treatment sequence following failure of first-line therapies. Instead, enrolment onto clinical trials should be standard-of-care in these patients.

Academic dermatology in Australia and New Zealand between 2017 and 2022: A cross-sectional bibliometric analysis.

INTRODUCTION: Academic dermatologists in Australia and New Zealand provide high-quality and meaningful contributions to the understanding of disease and therapeutic translational research. Concerns have been raised by the Australian Medical Association regarding the decline of clinical academics in Australia as a whole, however, such trends in scholarly output have not previously been analysed for Australasian dermatologists. METHODS: A bibliometric analysis of dermatologists in Australia and New Zealand was conducted in January and February 2023. Available Scopus profiles for all dermatologists were used to measure lifetime H index, scholarly output, citation counts and field-weighted citation impact (FWCI) in the last 5 years (2017-2022). Trends in output over time were measured using non-parametric tests. Differences in output between subgroups stratified by gender and academic leadership positions (associate professor or professor) were measured using Wilcoxon rank-sum and one-way ANOVA tests. The scholarly output of recent College graduates was also analysed as a subgroup, comparing the same bibliographic variables in the 5 years preceding and 5 years following awarding of their fellowships. RESULTS: From the 463 practising dermatologists in Australia and New Zealand, 372 (80%) were successfully matched to Scopus researcher profiles. Of these dermatologists, 167 were male (45%) and 205 (55%) were female, and 31 (8%) held academic leadership positions. Most dermatologists (67%) published at least one paper in the last 5 years. The median lifetime H index was 4, and between 2017 and 2022 median scholarly output was 3, the median citations were 14 and the median FWCI was 0.64. There was a non-significant trend towards fewer publications per year, however, citation count and FWCI decreased significantly. By subgroups, female dermatologists published significantly more papers between 2017 and 2022, and other bibliographic variables were comparable to male dermatologists. However, women were underrepresented in positions of academic leadership-comprising only 32% of this cohort despite representing 55% of dermatologists. Professors were also significantly more likely to have higher bibliographic outcomes than associate professors. Finally, analysis of recent College graduates highlighted a significant decline in bibliometric outcomes pre- and post-fellowship. CONCLUSION: Overall, our analysis identifies a trend towards decreased research output by dermatologists in Australia and New Zealand in the last 5 years. Strategies to support dermatologists in research endeavours, particularly women and recent graduates, will be essential in maintaining strong scholarly output among Australasian dermatologists and thereby sustaining optimal evidence-based patient care.

BRAF inhibition and the spectrum of granulomatous reactions.

V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors have emerged as a promising targeted therapy for malignancies with BRAF mutations, particularly metastatic melanoma. However, granulomatous reactions (GRs), including sarcoidosis and sarcoid-like reactions, have been reported as a consequence of BRAF inhibition. It is important to adequately characterize these GRs, including cutaneous manifestations and systemic involvement, in order to guide investigations and management. A literature review was conducted to characterize the spectrum of GRs associated with BRAF inhibitors, identifying 55 reactions affecting 51 patients, with 37 reactions limited to cutaneous involvement. Further, a possible correlation with cancer response, mechanisms of granuloma formation, and a proposed workup and management approach for these GRs are presented.

Full-body skin examination in screening for cutaneous malignancy: a focus on concealed sites and the practices of Australian dermatologists.

BACKGROUND: Full-body skin examination (FSE) is a vital practice in the diagnosis of cutaneous malignancy. Precisely how FSE should be conducted with respect to concealed site inclusion remains poorly elucidated. OBJECTIVE: To establish the approach of Australian dermatologists to concealed site examination (CSE). METHODS: A cross-sectional study was performed consisting of an online self-administered 11-question survey delivered to fellows of the Australasian College of Dermatologists. RESULTS: There were 237 respondents. Anogenitalia was the least often examined concealed site (4.6%), and 59.9, 32.9, and 14.3% reported always examining the scalp, breasts, and oral mucosa, respectively. Patient concern was the most frequently cited factor prompting examination, while many cited low incidence of pathology and limited chaperone availability as the main barriers to routine examination of these sites. CONCLUSION: Most Australian dermatologists do not routinely examine breasts, oral mucosal, or anogenital sites as part of an FSE. Emphasis should be made on identifying individual patient risk factors and education regarding self-examination of sensitive sites. A consensus approach to the conduct of the FSE, including concealed sites, is needed to better delineate clinician responsibilities and address medicolegal implications.

Disseminated Mycobacterium chelonae infection complicating rheumatoid arthritis: A case report and review of the literature.

INTRODUCTION: Rheumatoid arthritis (RA) may predispose patients to opportunistic infections-either from innate immune dysregulation, or as a result of immunosuppressant use to treat the RA. Particularly concerning opportunistic infections are those caused by non-tuberculous mycobacterial (NTM) organisms, the incidence of which has been increasing in epidemiological studies. Despite this, guidelines on the management of patients with RA who develop NTM infections are scarce, particularly with respect to immunosuppressant regimen modulation and duration of antibiotic therapy. CASE REPORT: Herein, we present a case of disseminated Mycobacterium chelonae infection, manifesting as arthralgia and cutaneous nodules. DISCUSSION: In addition, a review of the literature was conducted to Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines to identify similar cases in the literature-revealing that all RA-associated M. Chelonae infections occurred in immunosuppressed patients (the majority with corticosteroids or tumor necrosis factor inhibitors), and considerable heterogeneity in management approaches. Further research regarding risk factors, preventative approaches and best management of such NTM infections in vulnerable patients with RA is required in order to establish consensus guidelines and consistency.

Pigmentation of lower limbs: Contribution of haemosiderin and melanin in chronic venous insufficiency and related disorders.

BACKGROUND: To determine the composition of skin pigmentation in chronic venous insufficiency (CVI) and other less common vascular conditions of lower limbs. METHODS: Forty-five skin biopsies were obtained from 17 patients. Samples were taken from pigmented regions and compared with control non-lesional samples from the same patient. Perl's Prussian Blue was used to identify haemosiderin and Schmorl's for melanin. RESULTS: Seven patients presented with CVI, one with concurrent livedo vasculopathy (LV). One patient had LV only. Two patients had acroangiodermatitis (AAD). Six patients had post-sclerotherapy pigmentation (PSP), one with concurrent post-inflammatory hyperpigmentation (PIH). One patient had PIH only. The predominant pigment in CVI samples was haemosiderin. C5-C6 patients showed increased epidermal melanin. LV, AAD, and PSP samples showed dermal haemosiderin but no increase in epidermal melanin. PIH samples showed prominent epidermal melanin whilst no haemosiderin was detected. CONCLUSION: The predominant pigment in CVI and other vascular conditions was haemosiderin. Melanin was present in later stages of CVI (C5-C6) and in PIH.