Dermatologic immune-related adverse events : the toxicity spectrum and recommendations for management

Immune checkpoint inhibitors are a new class of oncologic drugs that act via the inhibition of check- points, thereby unlocking the immune system to attack cancer cells. Their emergence has radically changed the concept of therapy in oncologic patients. However, despite their overall favorable profile, their use has been associated with specific toxicities that may potentially affect treatment. The so-called immune-related adverse events (irAEs) mostly correspond to dysimmune reactions that can affect nearly every organ system, in theory, notably with the development of colitis, hepatitis, pneumonitis, or thy- roiditis. Dermatologic irAEs are also among the most common, reaching a rate of approximately 40%. They are characterized by a wide phenotypic range, including mainly eczematous or lichenoid rashes, psoria- sis, or autoimmune bullous disorders. Pruritus may accompany the aforementioned rashes or develop as an isolated symptom without the presence of skin changes. Depigmentation and hair/nail changes can be also observed in association with immune checkpoint inhibitor treatment. In the current article, we present an overview of the clinical spectrum of irAEs and provide tips for early recognition and manage- ment of dermatologic irAEs. We highlight the role that dermatologists can play in relieving patients and allowing for oncologic treatment to be maintained and administered more safely.The Cancer Association of South Africa and the National Research Foundation of South Africa.https://www.sciencedirect.com/journal/international-journal-of-womens-dermatologyam2022Immunolog

Race-Specific and Skin of Color Dermatoscopic Characteristics of Skin Cancer: A Literature Review

Introduction: Individuals with melanin-rich skin account for the majority of the world's population. However, literature data regarding dermoscopic characteristics of skin cancer in skin of color (SoC) are scarce. The dermoscopic characteristics of cutaneous tumors might differ among skin types due to heterogeneity in composition and pigmentation. Objectives: To summarize literature data on the dermoscopic findings of skin neoplasms according to the skin color and race. Methods:  The literature search was performed using the PubMed database up to December 30, 2022, and was conducted with the use of terms referring to dermoscopy, race (Caucasians, Hispanics, Asians, and Black/African), and skin cancer types (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], keratoacanthoma, Bowen disease, and melanoma). Results: In total, 30 race-specific records were included. Nine SoC records for BCCs (2 BCC studies in Hispanics, 1 BCC study in Black individuals, and 6 BCC studies in Asians), 9 SoC records for SCCs ( 1 SCC study in Hispanics ,1 SCC study in Black individuals and 7 SCCs in Asian population), and 8 SoC records for melanoma (2 melanoma studies in Hispanics, 1  in Blacks, and 5  in Asians) were compared with 4 records that involved only a Caucasian population, according to their participant section as well as with studies on dermoscopy characteristics without focusing on race origins and phototype of the patient. Conclusion: Based on a review of studies including Caucasians, Hispanics, Asians and Blacks /Africans, SoC patients present with more frequent and unique dermatoscopy features of skin cancers.

Effect of estrogen in malignant melanoma

Background Melanoma is associated with poor prognosis in its advanced stages. Potential influence of estrogen and its metabolites on melanoma growth has been suggested. Aims The objective of this review was to provide an overview on the evidence related to estrogen in malignant melanoma. Materials and Methods Literature search using PubMed, Google Scholar and relevant cross-references of the retrieved articles was performed to review relevant published articles related to estrogen and its effects in malignant melanoma. Results Effect of estrogen signaling on a tissue largely depends on the relative expression of estrogen receptors (ER) α and β. Gender differences in melanoma may be explained by the difference in expression of these receptors. ERβ is the principal ER in melanoma. Discussion Although there is uncertainty about role of estrogen in pathogenensis and progression of melanoma, evidence suggests that its growth and metastasis are influenced by estrogen stimulation. Role ER on the proliferation of melanoma cells is well described. Conclusion There is a need of safe and effective therapy for melanoma, especially for advanced cases. After the establishment of specific role of estrogen and its receptor, analysis of specific genetic mutation can be performed for proper utilization of targeted therapies

Seven Plus One Steps to Assess Pigmented Nail Bands (Melanonychia Striata Longitudinalis)

Melanonychia striata longitudinalis might involve one or more fingers and/or toes and might result from several different causes, including benign and malignant tumors, trauma, infections, and acti-vation of melanocytes that might be reactive or related to the pigmentary trait,drugs and some rare syndromes.This broad differential diagnosis renders the clinical assessment of melanonychia striata particularly challenging. Nail matrix melanoma is relatively rare, occurs almost always in adults in-volves more frequently the first toe or thumb.The most common nail unit cancer,squamous cell carcinoma / Bowen disease (SCC) of the nail matrix is seldom pigmented. Histopathologic examina-tion remains the gold standard for melanoma and SCC diagnosis,but excisional or partial biopsies from the nail matrix require training and is not routinely performed by the majority of clinicians.Furthermore, the histopathologic evaluation of melanocytic lesions of the nail matrix is particularly challenging, since early melanoma has only bland histopathologic alterations. Dermatoscopy of the nail plate and its free edge significantly improves the clinical diagnosis, since specific patterns have been associated to each one of the causes of melanonychia. Based on knowledge generated and pub-lished in the last decades, we propose herein a stepwise diagnostic approach for melanonychia striata longitudinalis: 1) Hemorrhage first 2) Age matters 3) Number of nails matters 4) Free edge matters 5) Brown or gray? 6) Size matters 7) Regular or irregular and, finally,“follow back”

Dermoscopic Features of Actinic Cheilitis and Other Common Inflammatory Cheilitis: A Multicentric Retrospective Observational Study by the International Dermoscopy Society

Background: Clinical differentiation between different cheilitis variants may be difficult. Application of mucoscopy, in addition to clinical background, could provide additional diagnostic clues facilitating initial patient management. Objectives: To determine mucoscopic clues differentiating actinic cheilitis from the main forms of inflammatory cheilitis, including eczematous cheilitis, discoid lupus erythematosus, and lichen planus of the lips. Methods: This was a retrospective, multicenter study being a part of an ongoing project "Mucoscopy - an upcoming tool for oral mucosal disorders" under the aegis of the International Dermoscopy Society. Cases included in the current study were collected via an online call published on the IDS website (www.dermoscopy-ids.org) between January 2019 and December 2020. Results: Whitish-red background was found in actinic cheilitis as well as in cheilitis due to discoid lupus erythematous and lichen planus. Polymorphous vessels were more likely to be seen in actinic cheilitis compared to other causes of cheilitis. White scales, ulceration, and blood spots predominated in actinic cheilitis and lichen planus, whereas yellowish scales typified eczematous and discoid lupus erythematous cheilitis. Radiating white lines although most common in lichen planus patients were also seen in actinic cheilitis. Conclusion: Despite differences in the frequency of mucoscopic structures, we have not found pathognomonic features allowing for differentiation between analyzed variants of cheilitis

A reinforcement learning model for AI-based decision support in skin cancer

: We investigated whether human preferences hold the potential to improve diagnostic artificial intelligence (AI)-based decision support using skin cancer diagnosis as a use case. We utilized nonuniform rewards and penalties based on expert-generated tables, balancing the benefits and harms of various diagnostic errors, which were applied using reinforcement learning. Compared with supervised learning, the reinforcement learning model improved the sensitivity for melanoma from 61.4% to 79.5% (95% confidence interval (CI): 73.5-85.6%) and for basal cell carcinoma from 79.4% to 87.1% (95% CI: 80.3-93.9%). AI overconfidence was also reduced while simultaneously maintaining accuracy. Reinforcement learning increased the rate of correct diagnoses made by dermatologists by 12.0% (95% CI: 8.8-15.1%) and improved the rate of optimal management decisions from 57.4% to 65.3% (95% CI: 61.7-68.9%). We further demonstrated that the reward-adjusted reinforcement learning model and a threshold-based model outperformed naïve supervised learning in various clinical scenarios. Our findings suggest the potential for incorporating human preferences into image-based diagnostic algorithms

The Impact of Immune Checkpoint Inhibitors-Induced Skin Toxicity on Patients’ Quality of Life and the Role of Dermatologic Intervention

Introduction: Data regarding quality of life (QoL) of oncologic patients experiencing dermatologic immune-related adverse events (dirAEs)and their course after dermatologic intervention are scarce. Objectives To assess the impact of dirAEs on patients' QoL and to investigate the correlation between dermatologic and oncologic indexes used for estimating QoL. Methods We enrolled oncologic patients with dirAEs managed in two supportive oncodermatology outpatient clinics in Greece. Patient-reported outcomes included DLQI, EORTC-QLQ-C30 and Numerical Rating Scale for pruritus (pNRS). Results Overall, 110 patients were enrolled in the study. Mean(SD) DLQI and pNRS scores were 15.54 (5.44) and7.25 (2.95), correspondingly, while functional, symptom and summary scores of EORTC-C30 were 79.17 (2.11), 17.66 (3.60) and 80.67 (3.08), respectively. After therapeutic interventions, there was a statistically significant decrease in DLQI scores after1st intervention compared to baseline, and 2nd intervention compared to 1st [mean (SD) decrease 4.38 (2.91), p<0.001 and 5.16 (3.99), p<0.001, respectively]. DLQI showed no correlation with global health status/QoLs (rho 0.01, p=0.90) of EORTC-C30. Conclusions dirAEs negatively affect QoL. Dermatologic intervention improves patients’ QoL, facilitating an unimpaired oncologic treatment. Poor correlation between DLQI and EORTC-QLQ-30 highlights the need for adapted QoL measurement tools in the context of ICIs treatment. 

Dermoscopic hemorrhagic dots: an early predictor of response of psoriasis to biologic agents

17siBACKGROUND: Biologic agents are routinely used in the treatment of severe psoriasis. The evaluation of treatment response is mainly based on the physician's global clinical assessment. OBJECTIVE: To investigate whether dermoscopy might enhance the assessment of response of psoriasis to treatment with biologic agents. METHODS: Patients with severe psoriasis scheduled to receive a biologic agent were enrolled in the study. A target lesion from each patient was clinically and dermoscopically documented at baseline and after one, two and six months. The clinical response was evaluated by the recruiting clinicians at all visits, while dermoscopic images were evaluated by two independent investigators, blinded to the clinical information. Chi Square test was used for cross-tabulation comparisons, while odds ratios, 95% confidence intervals and p values were calculated using univariate logistic regression. RESULTS: Overall, there was a significant correlation between clinical response and vessel distribution at all time points: a regular vessel distribution correlated with no response, a clustered distribution with partial response, and the dermoscopic absence of vessels with complete response. The presence of dermoscopic hemorrhagic dots was a potent predictor of favorable clinical response at the subsequent visit at all time points. Among lesions initially clinically responding and later recurring, 87.5% displayed dermoscopic dotted vessels despite the macroscopic remission. CONCLUSION: Dermoscopy might be a useful additional tool for evaluating the response of psoriatic patients to biologic agents. Hemorrhagic dots represent an early predictor of clinical response, while the persistence or reappearance of dotted vessels might predict clinical persistence or recurrence, respectively.openopenLallas, Aimilios; Argenziano, Giuseppe; Zalaudek, Iris; Apalla, Zoe; Ardigo, Marco; Chellini, Patricia; Cordeiro, Natalia; Guimaraes, Mariana; Kyrgidis, Athanassios; Lazaridou, Elizabeth; Longo, Caterina; Moscarella, Elvira; Papadimitriou, Ilias; Pellacani, Giovanni; Sotiriou, Elena; Vakirlis, Efstratios; Ioannides, DimitriosLallas, Aimilios; Argenziano, Giuseppe; Zalaudek, Iris; Apalla, Zoe; Ardigo, Marco; Chellini, Patricia; Cordeiro, Natalia; Guimaraes, Mariana; Kyrgidis, Athanassios; Lazaridou, Elizabeth; Longo, Caterina; Moscarella, Elvira; Papadimitriou, Ilias; Pellacani, Giovanni; Sotiriou, Elena; Vakirlis, Efstratios; Ioannides, Dimitrio

Delphi Consensus Among International Experts on the Diagnosis, Management, and Surveillance for Lentigo Maligna

Introduction: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. Objectives: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. Methods: A modified Delphi method was used. The invited participants were either members of the International Dermoscopy Society, academic experts, or authors of published articles relating to skin cancer and melanoma. Participants were required to respond across three rounds using a 4-point Likert scale). Consensus was defined as >75% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing. Results: Of the 31 experts invited to participate in this Delphi study, 29 participants completed Round 1 (89.9% response rate), 25/31 completed Round 2 (77.5% response rate), and 25/31 completed Round 3 (77.5% response rate). Experts agreed that LM diagnosis should be based on a clinical and dermatoscopic approach (92%) followed by a biopsy. The most appropriate primary treatment of LM was deemed to be margin-controlled surgery (83.3%), although non-surgical modalities, especially imiquimod, were commonly used either as alternative off-label primary treatment in selected patients or as adjuvant therapy following surgery; 62% participants responded life-long clinical follow-up was needed for LM. Conclusions: Clinical and histological diagnosis of LM is challenging and should be based on macroscopic, dermatoscopic, and RCM examination followed by a biopsy. Different treatment modalities and follow-up should be carefully discussed with the patient

New Trends in Dermoscopy to Minimize the Risk of Missing Melanoma

During the last decades, induction of dermoscopy in the clinical setting resulted in significant modifications in the management of melanocytic lesions. Indeed, the dermatoscope reveals a fascinating world of morphologic structures invisible to the naked eye, adding valuable information to a clinician evaluating a mole. However, since the technique counts only a couple of decades, new research data are continuously gathering and modify the “optimal” management of melanocytic lesions. In the present paper, we summarize the latest trends in dermoscopy concerning early melanoma diagnosis, management of nodular lesions, diagnosis of mucosal melanoma, and digital followup