Structural skin changes in elderly people investigated by reflectance confocal microscopy.

BACKGROUND: Reflectance confocal microscopy (RCM) is particularly suitable for the study of skin ageing because it provides nearly histological information in vivo and non-invasively. However, there are no studies that evaluated RCM skin features of a large population older than 70 years. OBJECTIVES: The aim of our investigation was to study age-related skin changes in an elderly population by RCM and to evaluate their topographical and gender differences. METHODS: We obtained RCM images of photoprotected (volar arm) and chronic (face) and intermittently photoexposed (dorsal forearm) body sites of 209 volunteers (105 women and 104 men, mean age: 77.5, range 74-81 years). 15 previously reported and new RCM parameters related to skin ageing were assessed. RESULTS: Photoexposed sites had thicker suprapapillary epidermis, more linear, distant and thin furrows, higher presence of mottled pigmentation, polycyclic papillae and coarse and huddled collagen and lower presence of dermal papillae than the photoprotected site. Irregular honeycomb pattern was not higher in photoexposed sites, indicating that it is probably more dependent on intrinsic ageing. Two ageing scores defined for facial skin ageing (epidermal disarray score and epidermal hyperplasia score) were found useful for the identification of photoageing. Gender differences only concerned some RCM parameters (i.e. thickness of different layers of the epidermis, furrows and collagen score) and some body sites, in line with the fact that women and men of our cohort had no major differences in clinically visible skin ageing. CONCLUSIONS: Our study confirmed that RCM is a powerful non-invasive technique to microscopically quantify ageing signs and our observations contribute to highlight the differences between intrinsic and extrinsic ageing.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

Evaluation of large clinically atypical vulvar pigmentation with RCM: atypical melanosis or early melanoma?

BACKGROUND: Vulvar melanosis can occasionally be clinically challenging by mimicking an early melanoma. OBJECTIVE: To report our experience of initial evaluation and follow-up in this peculiar subset of vulvar melanosis using reflectance confocal microscopy (RCM). METHODS: We retrospectively evaluated 18 consecutive cases referred for atypical vulvar pigmentation or for which melanoma was considered and that underwent both RCM examination and histopathological assessment. In 13 cases with available dermoscopic pictures, RCM classification was compared to dermoscopic diagnosis, and in all cases, the density of melanocytes was evaluated on biopsies using MelanA immunostaining. RESULTS: Among the 18 atypical pigmented lesions, 17 vulvar melanosis and one melanoma were histologically determined. RCM concluded a benign vulvar melanosis in 10 of 17 cases, whereas dermoscopy did so in three of 12 cases. RCM identified the only early malignant lentiginous melanoma. In several cases of vulvar melanosis, RCM could identify foci of melanocytic hyperplasia in an otherwise benign pattern. CONCLUSIONS: In this clinically and dermoscopically challenging subset of vulvar pigmentations, RCM appears relevant for initial extensive evaluation, especially to target initial biopsy sampling, and to perform non-invasive monitoring of foci of melanocytic hyperplasia.

Imaging technique for the diagnosis of onychomatricoma.

Onychomatricoma is a rare tumour that derives from the nail matrix and grows within the nail plate. The clinical presentation can mimic many other tumours and conditions, and surgical biopsy and histopathological examination are necessary to confirm the diagnosis. As nail surgery is a painful experience for the patient and sometimes can leave permanent onychodistrophy, more precise preoperative diagnosis is needed to distinguish onychomatricoma from other nail diseases more accurately and to limit surgical interventions. The objective of this study was to evaluate current literature on imaging techniques for the diagnosis of onychomatricoma in order to understand how this technology can help the presurgical diagnosis of this tumour. We searched in the Cochrane Skin Group Specialised library, Medline, Embase and LILACS databases all studies evaluating imaging technique for the diagnosis of onychomatricoma up to February 2018. We found that not only nail dermoscopy, but also reflectance confocal microscopy, optical coherence tomography, ultrasonography and magnetic resonance can be useful in this field.

Dermoscopy vs. reflectance confocal microscopy for the diagnosis of lentigo maligna.

BACKGROUND: Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques. OBJECTIVE: We evaluated the diagnostic accuracy of dermoscopy and RCM for LM/LMM using a holistic assessment of the images. METHODS: A total of 223 facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical, dermoscopic and RCM examination was compared. Interinvestigator variability and confidence level in the diagnosis were also evaluated. RESULTS: Overall diagnostic accuracy of the two imaging techniques was good (area under the curve of the sROC function: 0.89). RCM was more sensitive (80%, vs. 61%) and less specific (81% vs. 92%) than dermoscopy for LM/LMM. In particular, RCM showed a higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher interinvestigator agreement and a higher confidence level in the diagnosis than dermoscopy. CONCLUSION: Reflectance confocal microscopy and dermoscopy are both useful techniques for the diagnosis of facial lesions and in particular LM/LMM. RCM is particularly suitable for the identification of hypomelanotic and recurrent LM/LMM.

Reflectance confocal microscopy and optical coherence tomography for the diagnosis of bullous pemphigoid and pemphigus and surrounding subclinical lesions.

BACKGROUND: Diagnosis of bullous pemphigoid (BP) and pemphigus is based on clinical features, histology, immunofluorescence and laboratory data. OBJECTIVES: To evaluate features of BP and pemphigus at reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in order to provide a rapid non-invasive bed-side diagnosis. Secondary objective was to evaluate the detectability of clinically non-visible lesions. METHODS: This was an observational, retrospective, multicentre study in which patients with suspicious lesions for BP or pemphigus underwent clinical assessment, RCM, OCT, blood tests and skin biopsy for histological and direct immunofluorescence examinations from January 2014 to December 2015. A total of 72 lesions in 24 selected patients were evaluated. Additionally, apparently unaffected skin at two different distances [near (1-2 cm) and far (2-3 cm)] from each lesion was examined to test subclinical lesion detectability. RESULTS: RCM was able to detect subepidermal and intra-epidermal blisters, respectively, in 75% and 50% of the patients affected by BP and pemphigus. At OCT, the exact blister level was identified in all patients. Acantholytic cells were observed only at RCM in pemphigus (62.5%). Fibrin deposition inside the blisters was only found in BP, evidenced both at RCM and OCT. Among patients with BP, subclinical blisters were detected in nine (9.4%) clinically healthy skin, while among patients with pemphigus were observed in 10 (20.8%) apparently unaffected skin. CONCLUSION: RCM and/or OCT provide useful information for a rapid diagnosis of BP and pemphigus and for the identification of biopsy site. Combined use of RCM and OCT is optimal because associates the higher resolution of RCM with the greater penetration depth of OCT. OCT could be an optimal tool for treatment monitoring, especially in the cases of subclinical lesions. However, histopathologic and immunologic examinations remain the gold standard for establishing the final diagnosis.

Evaluation of the Active Targeting of Melanin Granules after Intravenous Injection of Dendronized Nanoparticles.

The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [177Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell, which reduces the diffusion across the cells' membrane. Planar scintigraphy images demonstrated a moderate specific tumor uptake of melanoma-targeted [177Lu]Lu-NPs10@D1_ICF_DOTAGA at 2 h post-intravenous injection (pi), and the highest tumor uptake of the control probe [177Lu]Lu-NPs10@D1_DOTAGA at 30 min pi, probably due to the enhanced permeability and retention effect. In addition, ex vivo confocal microscopy studies showed a high specific targeting of human melanoma samples impregnated with NPs10@D1_ICF_Alexa647_ DOTAGA.

Reflectance confocal microscopy identification of subclinical basal cell carcinomas during and after vismodegib treatment.

BACKGROUND: Recently, it has been shown that reflectance confocal microscopy (RCM) could identify subclinical basal cell carcinoma (BCC) during vismodegib treatment of locally advanced BCC. OBJECTIVES: To evaluate specificity and sensitivity of clinical, dermoscopic and RCM examination for BCC in patients with multiple BCCs treated by vismodegib. METHODS: Ninety four BCCs had 710 clinical, dermoscopic and RCM examinations during 72 weeks of vismodegib treatment. Thirty-eight were biopsied at the end of the treatment. Sensitivity and specificity for these 38 lesions were calculated. BCC diagnoses of clinical, dermoscopic and RCM examination on all the 710 investigations were compared using chi-square test. RESULTS: Reflectance confocal microscopy was extremely more sensitive than dermoscopy and clinical examination and slightly less specific (sensitivity of 95%, 35% and 33% and specificity of 81%, 88% and 86% for RCM, dermoscopy and clinical examination, respectively) for the identification of residual BCC in the 38 biopsied cases. Considering all the 710 observations, RCM correctly diagnosed more BCCs than dermoscopy and clinical examination. CONCLUSION: Reflectance confocal microscopy is a non-invasive technique that can detect subclinical residual BCC during and after vismodegib treatment helping the clinician to identify incomplete tumour regression.

Mucosal melanoma: clinical, histological and c-kit gene mutational profile of 86 French cases.

BACKGROUND: Mucosal melanomas are rare and highly aggressive tumours. Few studies evaluated mucosal melanomas of locations other than the head and neck region, and other than those of the Asian population. OBJECTIVES: The objective of this study was to analyse the clinical and histological features, as well as the mutational status of c-kit and b-raf gene of mucosal melanoma in any localization in a French series. METHODS: We investigated clinical (sex, age, performance status, survival, treatment of the patients and lack of pigmentation of the tumours) and histopathological features (ulceration, Breslow's index, mitotic rate), as well as the mutational status of c-kit and b-raf of 86 mucosal melanomas diagnosed in 15 years in four French University Hospitals. RESULTS: Most melanomas affected women (72%) and the genital region (46.5%). A fifth of melanomas were amelanotic. 81% of melanomas had a Breslow's index ≥1, whereas all glans melanomas, and most vulvar melanomas had a Breslow index ≤1 mm. Overall survival was 54% at 3 years; 11.6% of the 43 tested mucosal melanomas were c-kit-mutated while the 15 tested genital melanomas were not. The c-kit gene mutation did not influence the overall survival. Age ≥ 50, amelanotic type and performance status ≥1 were not poor prognostic factors in our series. CONCLUSION: This study confirmed that mucosal melanomas are rare and could be difficult to diagnose being often amelanotic and in hidden sites. Most melanomas were thick at the diagnosis, but glans and vulvar melanomas were thinner probably because of their greater visibility. The frequency of the c-kit mutation varied depending on the initial tumour site. In our series, the prognosis was poor, independently from c-kit mutations and the patient's general health and age. The presence of metastasis at diagnosis was associated with a worse prognosis indicating the importance of an early diagnosis.