Basal cell carcinoma is the most common malignancy among caucasians worldwide. Accurate epidemiological data can be difficult to obtain, but does suggest that the overall incidence is increasing. Risk factors include skin type, prior skin cancers and immunosuppression. Research in free radical-mediated cellular injury and innate defence mechanisms, and ultraviolet radiation-induced genetic mutations have improved our understanding of the development of this disorder.
This retrospective study was conducted to assess and compare the diagnostic accuracy between referring general practitioners and dermatologists with regard to skin conditions. Six hundred and fifty-six consecutive general practitioner referrals to a private dermatology practice and a dermatology outpatient department were assessed. The concordance rate in diagnoses from a wide spectrum of dermatological diseases was compared between general practitioners and dermatologists. Referring general practitioners agreed with dermatologists' clinical diagnosis and histology (when available) in 42% of cases. The concordance between general practitioners and dermatologists in the setting of non-biopsied cases is 45%. One hundred and fifty-one of 656 (23%) conditions had histological confirmation. Overall, general practitioners agreed with the histological diagnosis in 24% of cases and dermatologists agreed with the histological diagnosis in 77% of cases.
A prospective study was conducted to assess general practitioners' diagnostic skills in a referral setting. The primary objective was to identify general practitioners' strengths and weaknesses in diagnosing a broad spectrum of skin conditions. The diagnoses of 315 skin conditions made by 165 general practitioners were compared with a reference standard. The reference standard was made up of 73 histopathological diagnoses, 119 dermatologists' clinical diagnoses and 123 dermatologists' diagnoses plus follow up. The diagnoses assigned by referring general practitioners were consistent with dermatologists' clinical diagnoses and histology (where available) in 57% of cases. General practitioners made the correct diagnosis in 44% of cases when compared with histopathology. General practitioners were generally good at diagnosing conditions such as acne, warts, rosacea, molluscum contagiosum, vitiligo and skin tags. The proportion of correct diagnoses for premalignant and malignant skin tumours was 47%, and that of skin rashes requiring a diagnosis was 44%. Further education of general practitioners would help to improve their diagnostic skills in certain skin conditions.
Imiquimod is being investigated as a therapeutic option for the management of actinic keratosis. Three recent clinical trials have demonstrated a reasonable efficacy rate and high safety profile. 'Cycle' therapy may improve the safety profile while maintaining efficacy. 'Field' treatment with imiquimod may uncover and treat 'subclinical' actinic keratoses, which in turn may potentially result in fewer recurrences. Longer follow-up studies are required to investigate this possibility.
Imiquimod is the first of a new class of drugs (immune response modifiers) to become commercially available. It is approved in many countries for the treatment of genital warts caused by the human papilloma virus infection. However, there are reports of its use in a variety of dermatological conditions, such as basal cell carcinomas, actinic keratoses, lentigo maligna, common warts and molluscum contagiosum. Its mechanism of action is through stimulation of the T helper cell Type 1 (Th1) immune response via activation of cell surface pathogen recognition receptors (mainly toll-like receptor 7). This activation stimulates the immune system's own defence mechanism against both virally infected and tumour cells. Imiquimod and other analogues show promise in the prophylactic treatment of skin tumours in some patients, especially those who are immunocompromised.
Clinically amyopathic dermatomyositis (CADM) is a rare form of dermatomyositis. Patients with this condition present with the typical skin findings of dermatomyositis but lack the characteristic muscle weakness associated with dermatomyositis. This case presentation highlights the unusual clinical manifestation of CADM in a 49-year-old Vietnamese female. The patient initially presented with persistent hyperpigmented plaques on her hands, which did not respond to the standard treatment for atopic dermatitis. The patient later developed respiratory failure and lung fibrosis in Vietnam. This case underscores the challenges in diagnosing and managing CADM, particularly in patients with atypical presentations, and emphasizes the difficulties in managing such cases of CADM in the community setting.
Adaptive Immune Response in Leprosy
Introduction: It has been proposed that the presence of inflamed tumor phenotypes, characterized by the presence of infiltrating lymphocytes and the expression of specific chemokines and cytokines, can predict response to immunotherapy and result in better patient outcomes [1, 2]. We hypothesized that pelareorep, an immuno-oncolytic virus (IOV), may elicit predictive proinflammatory gene signatures in select cancer cell lines permissive to viral infection. Methods: Cell lines derived from non-small cell lung cancer (NSCLC, H522), colorectal cancer (CRC, SW-620), and hepatocellular carcinoma (HCC, SNU 387) were infected at an multiplicity of infection equal to 50. We examined changes in gene expression and conducted cell viability assays at 6, 12, and 18 hours post pelareorep infection (including a non-infected control). To monitor changes in gene expression we employed a custom 780-gene Pan Cancer Immune panel developed by nanoString Technologies and specifically monitored for changes in the expression of key interferon and NF-κB signalling genes, immune checkpoint ligands, and a 12-gene chemokine signature predictive of a positive response to immunotherapy identified by Messina et al. [2]. Results: All cell lines examined were susceptible to pelareorep induced cytopathic effect. Strikingly, principal component analysis revealed that the changes in gene expression were unique and different for each cell line. Of the cell lines examined, only HCC cells infected with pelareorep promoted an inflammatory signature, similar to the one used to predict response to immunotherapy in melanoma [2]. Conclusions: This study demonstrates that pelareorep can prime or promote a predictive inflamed tumor phenotype in HCC, which correlates with the innate response recently described in HCC- animal models treated with pelareorep [3]. The role of pelareorep in the treatment of hepatocellular carcinoma deserves further investigation, particularly in combination with other immunotherapies. References: [1] Gajewski, T.F., The Next Hurdle in Cancer Immunotherapy: Overcoming the Non-T-Cell-Inflamed Tumor Microenvironment. Semin Oncol, 2015. 42(4): p. 663-71. [2] Messina, J.L., et al., 12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy? Sci Rep, 2012. 2: p. 765. [3] Samson, A., et al., Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer. Gut, 2016. Citation Format: Grey A. Wilkinson, Aine Piar, Zoe Cesarz, Hue Tran, Romit Chakrabarty, Andres Gutierrez, Matt Coffey. Pelareorep promotes the expression of a chemokine signature that predicts response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4707.
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