Incidence of Chronic Radiodermatitis after Fluoroscopically Guided Interventions: A Retrospective Study

International audiencePurpose: To assess the incidence and risk factors for chronic radiodermatitis after fluoroscopically guided interventions (FGIs) in high-risk patients.Materials and methods: Between 2010 and 2016, of 55,782 patients who underwent FGIs, 359 had a risk procedure for skin injury (maximal skin dose > 3 Gy, air kerma > 5 Gy, dose area product [DAP] > 500 Gy.cm2, or fluoroscopy time > 60 minutes). Ninety-one of these patients were examined by a dermatologist for radiodermatitis (median time after procedure, 31.2 months [95% confidence interval, 14.2-50.7]). In each case, the clinical features and topography of the skin lesions were recorded and their incidence calculated. The characteristics of the patients and of the FGIs were tested as risk factors.Results: Eight patients (8.8%) had chronic radiodermatitis; 19 (20.9%) had acute radiodermatitis. Body mass index, DAP value, and air kerma were the only risk factors identified.Conclusions: This study shows that chronic radiodermatitis may be considered a frequent side effect in an at-risk population. The lesions are commonly benign, but extensive sclerosis can occur. Patients should be better informed about the side effects and offered a skin exam periodically

Prevalence and Odds of Depressive and Anxiety Disorders and Symptoms in Children and Adults With Alopecia Areata

Importance Two recent meta-analyses reported a high prevalence of both anxiety and depression in patients with alopecia areata (AA), as well as a positive association of AA with anxiety and depression, without distinguishing between disorders and symptoms. Yet, depression and anxiety can manifest either as symptoms identified in questionnaires or as specific diagnoses defined by Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision criteria. Objective To perform a large meta-analysis separating the prevalence of depressive and anxiety disorders from that of depressive and anxiety symptoms in patients with AA. Data Sources PubMed, ScienceDirect, the Cochrane Library, Embase, and PsycINFO databases were searched from inception through August 1, 2020. Study Selection Studies that contained data on the prevalence of depressive or anxiety disorders or symptoms were included. Data Extraction and Synthesis The Meta-analysis of Observational Studies in Epidemiology ( MOOSE ) reporting guidelines were used. Pooled prevalence was calculated with a random effects model meta-analysis that took into account between- and within-study variability. Meta-regressions were used to study the association between variations in prevalence and study characteristics. Main Outcomes and Measures The prevalence of depressive and anxiety disorders and symptoms in patients with AA. Results Thirty-seven articles (29 on depression and 26 on anxiety) that met the inclusion criteria were identified. By distinguishing between disorders and symptoms, the prevalence of both depressive disorders (9%) and unspecified anxiety disorders (13%) in patients with AA was shown to be greater than that in the general population. The prevalence and odds ratio (OR) of depressive disorders (prevalence, 9%; OR, 1.38) and anxiety disorders of which each category had been specifically studied (prevalence, 7%-17%; OR, 1.51-1.69) were markedly lower than that of depressive symptoms (prevalence, 37%; OR, 2.70) and anxiety symptoms (prevalence, 34%; OR, 3.07). Meta-regressions showed that variations in prevalence were mainly associated with methodological differences between studies. Conclusions and Relevance In this systematic review and meta-analysis, the separate analyses showed that 7% to 17% of patients with AA had depressive or anxiety disorders that require psychiatric care, including specific medication. Additionally, more than one-third of patients had symptoms that are warning signs and that need monitoring because they can develop into disorders

Lower Emotion Awareness in Skin-Restricted Lupus Patients: A Case-Controlled Study

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Psychiatric symptomatology in skin-restricted lupus patients without axis I psychiatric disorders: A post-hoc analysis

Background Skin-restricted lupus is a chronic inflammatory disease associated with high rates of depression and anxiety disorders. Patients without psychiatric disorders can experience anxiety and depressive symptoms at a subclinical level, which could be risk factors for progression towards psychiatric disorders. It was decided, therefore, to investigate the presence of specific symptoms in skin-restricted lupus patients without axis I psychiatric disorders and their impact on the occurrence of axis I psychiatric disorders during the study follow-up. Methods Longitudinal data of 38 patients and 76 matched controls without active axis I psychiatric disorders from the LuPsy cohort were used. Depressive, neurovegetative, psychic and somatic anxiety symptom scores were established from the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating scale (HAMA). Results None of the participants had any current active axis I psychiatric disorders but the patients had personality disorders more frequently and had received more past psychotropic treatments than the controls. They also had higher MADRS and HAMA scores than the controls, in particular neurovegetative, psychic anxiety and somatic symptoms scores. No dermatological factor tested was associated with these scores, whereas being a lupus patient was associated with higher neurovegetative and somatic symptoms scores, having a current personality disorder with higher depressive and neurovegetative scores and receiving more past psychotropic treatments with psychic anxiety and somatic symptoms scores. The occurrence of psychiatric disorders during the study follow-up was associated with an elevated psychic anxiety score at baseline and past psychotropic treatment but not with history of psychiatric disorder. Limitations The LuPsy cohort included a large number of patients with axis I psychiatric disorders, the sample without axis I psychiatric disorders is therefore limited. Conclusions We observed numerous psychiatric symptoms among the skin-restricted lupus patients. They should therefore receive special attention in the management of their subclinical symptoms before they progress towards full psychiatric disorders

Treatment of Psychiatric Disorders and Skin-Restricted Lupus Remission

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Immune checkpoint inhibitors reverse tolerogenic mechanisms induced by melanoma targeted radionuclide therapy

International audienceIn line with the ongoing phase I trial (NCT03784625) dedicated to melanoma targeted radionuclide therapy (TRT), we explore the interplay between immune system and the melanin ligand [131I]ICF01012 alone or combined with immunotherapy (immune checkpoint inhibitors, ICI) in preclinical models. Here we demonstrate that [131I]ICF01012 induces immunogenic cell death, characterized by a significant increase in cell surface-exposed annexin A1 and calreticulin. Additionally, [131I]ICF01012 increases survival in immunocompetent mice, compared to immunocompromised (29 vs. 24 days, p = 0.0374). Flow cytometry and RT-qPCR analyses highlight that [131I]ICF01012 induces adaptive and innate immune cell recruitment in the tumor microenvironment. [131I]ICF01012 combination with ICIs (anti-CTLA-4, anti-PD-1, anti-PD-L1) has shown that tolerance is a main immune escape mechanism, whereas exhaustion is not present after TRT. Furthermore, [131I]ICF01012 and ICI combination has systematically resulted in a prolonged survival (p < 0.0001) compared to TRT alone. Specifically, [131I]ICF01012 + anti-CTLA-4 combination significantly increases survival compared to anti-CTLA-4 alone (41 vs. 26 days; p = 0.0011), without toxicity. This work represents the first global characterization of TRT-induced modifications of the antitumor immune response, demonstrating that tolerance is a main immune escape mechanism and that combining TRT and ICI is promising

Efficacy of Targeted Radionuclide Therapy Using [131I]ICF01012 in 3D Pigmented BRAF- and NRAS-Mutant Melanoma Models and In Vivo NRAS-Mutant Melanoma

International audiencePurpose: To assess the efficiency of targeted radionuclide therapy (TRT), alone or in combination with MEK inhibitors (MEKi), in melanomas harboring constitutive MAPK/ERK activation responsible for tumor radioresistance.Methods: For TRT, we used a melanin radiotracer ([131I]ICF01012) currently in phase 1 clinical trial (NCT03784625). TRT alone or combined with MEKi was evaluated in three-dimensional melanoma spheroid models of human BRAFV600E SK-MEL-3, murine NRASQ61K 1007, and WT B16F10 melanomas. TRT in vivo biodistribution, dosimetry, efficiency, and molecular mechanisms were studied using the C57BL/6J-NRASQ61K 1007 syngeneic model.Results: TRT cooperated with MEKi to increase apoptosis in both BRAF- and NRAS-mutant spheroids. NRASQ61K spheroids were highly radiosensitive towards [131I]ICF01012-TRT. In mice bearing NRASQ61K 1007 melanoma, [131I]ICF01012 induced a significant extended survival (92 vs. 44 days, p < 0.0001), associated with a 93-Gy tumor deposit, and reduced lymph-node metastases. Comparative transcriptomic analyses confirmed a decrease in mitosis, proliferation, and metastasis signatures in TRT-treated vs. control tumors and suggest that TRT acts through an increase in oxidation and inflammation and P53 activation.Conclusion: Our data suggest that [131I]ICF01012-TRT and MEKi combination could be of benefit for advanced pigmented BRAF-mutant melanoma care and that [131I]ICF01012 alone could constitute a new potential NRAS-mutant melanoma treatment