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Background: Interest in the use of omalizumab to treat bullous pemphigoid (BP) in the event of resistance or contraindication to conventional therapies is currently based on limited evidence., Objectives: To assess the effectiveness and safety of omalizumab in BP and to identify predictive factors in response to treatment., Methods: We conducted a French national multicentre retrospective study including patients with a confirmed diagnosis of BP treated with omalizumab after failure of one or several treatment lines. We excluded patients with clinically atypical BP, as per Vaillant's criteria. The criteria for clinical response to omalizumab were defined according to the 2012 international consensus conference. Anti-BP180-NC16A IgE enzyme-linked immunosorbent assay was performed on sera collected before initiating omalizumab, when available., Results: Between 2014 and 2021, 100 patients treated in 18 expert departments were included. Median age at diagnosis was 77 years (range 20-98). Complete remission (CR) was achieved in 77% of patients, and partial remission in an additional 9%. CR was maintained 'off therapy' in 11.7%, 'on minimal therapy' in 57.1%, and 'on non-minimal therapy' in 31.2%. Median time to CR was 3 months (range 2.2-24.5). Relapse rate was 14%, with a median follow-up time of 12 months (range 6-73). Adverse events occurred in four patients. CR was more frequently observed in patients with an increased serum baseline level of anti-BP180-NC16A IgE (75% vs. 41%; P = 0.011). Conversely, urticarial lesions, blood total IgE concentration or eosinophil count were not predictive of CR. Patients with an omalizumab dosage > 300 mg every 4 weeks showed a similar final outcome to those with a dosage ≤ 300 mg every 4 weeks, but control of disease activity [median 10 days (range 5-30) vs. 15 days (range 10-60); P < 0.001] and CR [median 2.4 months (range 2.2-8.2) vs. 3.9 months (range 2.3-24.5); P < 0.001] were achieved significantly faster., Conclusions: We report the largest series to date of BP treated by omalizumab and confirm its effectiveness and safety in this indication. Serum baseline level of anti-BP180-NC16A IgE may predict response to treatment., Competing Interests: Conflicts of interest The authors declare no conflicts of interest related to this study., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: European guidelines propose a 0·5 mg kg -1 per day dose of oral prednisone as initial treatment for bullous pemphigoid (BP). We assessed the safety and efficacy of this regimen depending on BP extent and general condition of the patients., Methods: In a prospective international study, we consecutively included all patients diagnosed with BP. Patients received a 0·5 mg kg -1 per day dose of prednisone, which was then gradually tapered 15 days after disease control, with the aim of stopping prednisone or maintaining minimal treatment (0·1 mg kg -1 per day) within 6 months after the start of treatment. The two coprimary endpoints were control of disease activity at day 21 and 1-year overall survival. Disease severity was assessed according to the Bullous Pemphigoid Disease Area Index (BPDAI) score., Results: In total, 198 patients were included between 2015 and 2017. The final analysis comprised 190 patients with a mean age of 80·9 (SD 9·1) years. Control of disease activity was achieved at day 21 in 119 patients [62·6%, 95% confidence interval (CI) 55·3-69.5]; 18 of 24 patients (75%, 95% CI 53·3-90·2), 75 of 110 patients (68·8%, 95% CI 59·2-77·3) and 26 of 56 patients (46.4%, 95% CI 33·0-60·3) had mild, moderate and severe BP, respectively (P = 0·0218). A total of 30 patients died during the study. The overall Kaplan-Meier 1-year survival was 82·6% (95% CI 76·3-87·4) corresponding to 90·9%, 83·0% and 80·0% rates in patients with mild, moderate and severe BP, respectively (P = 0·5). Thresholds of 49 points for BPDAI score and 70 points for Karnofsky score yielded maximal Youden index values with respect to disease control at day 21 and 1-year survival, respectively., Conclusions: A 0·5 mg kg -1 per day dose of prednisone is a valuable therapeutic option in patients with mild or moderate BP whose general condition allows them to be autonomous., (© 2021 British Association of Dermatologists.)

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., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Anti-p200 pemphigoid is a rare autoimmune blistering disease (AIBD) of the dermoepidermal junction, characterized by autoantibodies to laminin γ1. The clinical course of anti-p200 pemphigoid in patients remains poorly investigated., Objectives: We aimed to describe the clinical and immunological features and the course of a series of patients with anti-p200 pemphigoid., Methods: We conducted a retrospective study by immunoblotting detection of sera on 200-kDa dermal protein extracts from the register of the French reference centre for AIBD. We recorded the clinical and immunological features and the course of patients., Results: A total of 14 patients with a mean age 81·6 ± 6·5 years were included. Only one patient had an associated neurological condition and one had psoriasis. Twelve patients had atypical clinical presentation, including eczematous, urticarial, prurigo-like, dyshydrosis-like and rosette-like skin lesions. Eight patients (57%) had mucosal involvement. Immunoblot analysis of sera on dermal and epidermal extracts showed a 200-kDa band in 14 and 10 cases, respectively. All eight of the sera tested by enzyme-linked immunosorbent assay detected recombinant human laminin γ1. Disease control was obtained in six of nine patients treated with topical corticosteroids, and four of five patients who received systemic treatment. Seven patients relapsed (50%) and five patients (36%) died during the median follow-up time of 12·6 months. At the end of the study, only one of the nine living patients was in complete remission off therapy., Conclusions: Many patients with anti-p200 pemphigoid had heterogeneous clinical presentation and a more severe prognosis than previously suspected., (© 2016 British Association of Dermatologists.)

Background: Ex vivo fluorescence confocal microscopy (FCM) permits real-time imaging of freshly excised skin tissues. Its usefulness as a time-sparing alternative to frozen sections in Mohs surgery of basal cell carcinoma is well documented., Objectives: The purpose of this study was to describe the ex vivo FCM features of a series of benign and malignant nonpigmented tumours of the nail unit, and to correlate them with conventional histopathology., Patients and Methods: Nail apparatus tumours from 10 patients were imaged during surgical exploration using ex vivo FCM after immersion in acridine orange. Confocal mosaics of the freshly performed biopsies were evaluated in real time and retrospectively compared with haematoxylin and eosin sections., Results: Our series included two invasive epithelial tumours (Group 1), four in situ or minimally invasive squamous cell carcinomas (SCC) (Group 2), three benign epithelial tumours (Group 3) and one nodular melanoma (Group 4). The correlation was excellent for malignant epithelial tumours exhibiting marked cytological and architectural atypias (Bowen disease, invasive SCC and onycholemmal carcinoma). Onychomatricomas exhibited a very peculiar aspect with densely cellular papillae. The correlation was less favourable for minimally invasive well-differentiated SCCs with slight cytological atypias. The correlation was poor for our case of amelanotic invasive subungual melanoma., Conclusions: Ex vivo FCM could be a useful tool to shorten management of nonpigmented nail tumours: in the case of a malignant tumour, it could indeed lead to performing wide excision during the same surgical procedure and possibly assessing the surgical margins., (© 2014 British Association of Dermatologists.)

Background: Although most mucosal pigmented macules are benign, it can be clinically challenging to rule out an early melanoma. Reflectance confocal microscopy (RCM) is a noninvasive imaging technique useful in discriminating between benign and malignant skin lesions., Objectives: To describe the confocal aspects of benign and malignant mucosal pigmented macules with histopathological correlations., Methods: We retrospectively reviewed the confocal images of 56 labial or genital pigmented macules including 10 macular melanomas. According to the retrospective nature of the study, we evaluated the recorded images chosen by the physicians that performed the RCM examination for each case., Results: In benign macules, the most frequently observed pattern was a ringed pattern characterized by round or polycyclic papillae, with a hyper-reflective basal layer; another pattern was characterized by sparse bright dendritic cells in the basal layer, the basal epithelial cells being otherwise less reflective. Roundish cells, a high density of dendritic cells with atypias and intraepithelial bright cells were clues to the presence of malignancy., Conclusions: Reflectance confocal microscopy seems to be a valuable tool to noninvasively differentiate benign from malignant mucosal pigmented macules and target biopsies in cases of equivocal features., (© 2013 British Association of Dermatologists.)

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant cutaneous tumour of which diagnosis is often delayed because of the lack of early clinical clues., Objectives: To describe the main dermoscopic features of DFSP., Methods: We performed dermoscopic examination in 15 unselected, consecutive cases of biopsy-proven DFSP. Firstly, six dermoscopic features were identified collegially, then all cases were reviewed separately by six experienced dermoscopists. In a given lesion, features recognized only by all dermoscopists were taken into account., Results: The median number of dermoscopic features was four per lesion. The following dermoscopic features were found: delicate pigmented network (87%), vessels (80%), structureless light brown areas (73%), shiny white streaks (67%), pink background coloration (67%) and structureless hypo- or depigmented areas (60%). When detected, vessels were of arborizing type in 11 of 12 cases, and presented as either unfocused only, or both unfocused and focused., Conclusions: This first study of the dermoscopic spectrum of DFSP identifies six dermoscopic features (often associated in a multicomponent pattern) and a peculiar vascular pattern. Whether dermoscopy can help to identify suspected DFSP remains to be established by further studies., (© 2013 The Authors BJD © 2013 British Association of Dermatologists.)

Background: New primary melanomas arising in patients with stage IV melanoma and receiving BRAF inhibitors have recently been reported. This raises the question of the nature of the earliest cellular events identifiable within pre-existing moles., Objectives: To use reflectance confocal microscopy (RCM) to investigate changing moles in patients using vemurafenib., Methods: In the first part of the study 23 lesions were examined by RCM before excision (performed because of digital dermoscopy changes) and histopathological examination. In the second part, 10 randomly chosen lesions in two patients were examined before and after 3 months of vemurafenib treatment., Results: The first step permitted the highlighting of an unusual RCM pattern identified in five lesions characterized by areas of marked atypia in otherwise nondysplastic lesions. In the second step, four initially nondysplastic lesions developed focal or multifocal areas of marked atypia under treatment, which were not always correlated with digital dermoscopy changes, but did correlate with histopathology. All four lesions were finally diagnosed as melanomas., Conclusions: Although the clinical relevance of such findings remains questionable, RCM allowed us to observe, at the cellular level, the earliest events occurring within vemurafenib-induced changing moles. Moreover, repeated RCM examinations permitted to confirm that microscopic marked atypia that led to the histopathological diagnosis of melanoma appeared under treatment and were not pre-existing., (© 2013 The Authors. BJD © 2013 British Association of Dermatologists.)

Background: Dermoscopy is now recognized as an essential tool for discriminating melanoma from other pigmented lesions, as corroborated by several robust meta-analyses. Although it is considered to be widely used in European countries, no published data on this topic are available to date, unlike in Australia and the U.S.A., Objectives:  To describe and quantify the use and learning of dermoscopy among French private practice dermatologists., Methods: A questionnaire of 19 items regarding demographic characteristics, dermoscopy use and training, and physician's judgment on dermoscopy was mailed to all French private practice dermatologists. Only questionnaires with an answer to the key item, 'Do you use dermoscopy?' were taken into account., Results:   Of 3179 mailed questionnaires, 1611 were returned and 1576 were analysable (49·6%). Most respondents declared using dermoscopy (94·6%), using their dermoscope several times a day (82·7%) and/or for the diagnosis of nonpigmented lesions (87·7%). Physicians learned dermoscopy mainly through books (75·8%) and/or conferences (88·6%); 12·8% reported a dedicated university degree. Dermoscopy helps to detect melanoma earlier and to perform fewer biopsies according to 86·6% and 74·6%, respectively. On multivariate analysis, female sex and age under 45 years were significantly associated with higher utilization rate of dermoscopy [odds ratio 1·89, 95% confidence interval (CI) 1·15-3·10; and 2·85, 95% CI 1·14-7·11, respectively]., Conclusions:   This is the first published nationwide survey of dermoscopy practice in Europe. Despite potential classification and/or selection bias, the particularly high penetration rate found in our study suggests that dermoscopy is now widely accepted by French private practice dermatologists for the routine management of both pigmented and nonpigmented lesions., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: Although dermoscopy of the nail plate is helpful to discriminate between benign and malignant causes of nail pigmentations, there remain ambiguous cases in which a matricial biopsy is required. When a subungual melanoma is diagnosed histopathologically, a complementary surgical treatment is performed secondarily, the duration of postoperative disability being accordingly prolongated., Objectives: The purpose of our study was to evaluate the feasibility of an intraoperative diagnosis by reflectance confocal microscopy (RCM)., Patients and Methods: Our series included nine consecutive patients who underwent a matricial biopsy for an acquired melanonychia (one benign lentigo and eight melanomas). RCM examination was performed in vivo on the nail matrix after reclination of the nail plate, and/or ex vivo on the fresh tissue biopsy. RCM data were compared with histopathology., Results: There was a good correlation between confocal and histopathological features. Seven melanoma cases were unequivocally diagnosed intraoperatively according to the confocal features, whereas the lentigo was correctly classified as a benign lesion according to RCM. The remaining lesion could not be unequivocally classified by RCM and corresponded histopathologically to an early melanoma that required immunostaining to be diagnosed., Conclusions: Intraoperative RCM examination of the nail matrix is an efficient diagnostic approach of melanonychia striata that permits an extemporaneous diagnosis of malignancy and therefore a one-step surgical treatment of in situ or minimally invasive melanoma, reducing dramatically the duration of postoperative disability., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: Lentigo maligna melanoma (LMM) is the most common subtype of melanoma on the face. Its presentation may be quite subtle, particularly in early stages, and delayed diagnosis is common. Few dermoscopic studies have been performed and the main dermoscopic features of LMM were defined by Stolz and coworkers in 2000., Objectives: To investigate classical as well as new dermoscopic features in a large series of LMM in a white-skinned population, in order to evaluate their diagnostic value., Methods: One hundred and twenty-five consecutive histopathology-proven LMMs were analysed retrospectively based on medical records, clinical and dermoscopic photographs by three independent observers for the presence of 19 predefined criteria., Results: At least one of the classical Stolz criteria was present in 87% of cases (hyperpigmented follicular opening, annular-granular pattern, pigmented rhomboidal structures, obliterated hair follicles). Three original criteria were also present at a relatively high frequency: increased density of the vascular network (58%), red rhomboidal structures (40%), target-like patterns (41%). Darkening at dermoscopic examination (when compared with naked-eye examination) was observed in 25% of lesions. Classical dermoscopic features of extrafacial melanoma (atypical pigment network, irregularly distributed globules, dots, streaks and pseudopods) and vertical growth phase-associated dermoscopic criteria (ulceration, blue papular areas and black structureless areas) were rarely seen. A large number of colours, pigmented rhomboidal structures, obliterated hair follicles and red rhomboidal structures were significantly more frequent in invasive LMMs. In contrast, in situ melanomas were more often associated with one or two colours and few distinctive dermoscopic features., Conclusions: We present herein, in a large series of LMM, confirmation of the diagnostic value of the classical Stolz dermoscopic criteria and describe four additional original criteria, mainly vascular. A correlation between the presence of some dermoscopic features and thicker tumoral invasion has also been demonstrated., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: Desmoplastic melanoma (DM) is a rare variant of cutaneous melanoma. Its diagnosis is often delayed by an unusual clinical presentation. The dermoscopic features of DM have not yet been described., Objective: To define the dermoscopic features of DM. Patients and methods A single-institution register-based retrospective study of six cases of histology-proven desmoplastic melanoma for which dermoscopy data were available. The criteria we studied included: network, dots and globules, streaks, regression features, ulceration, number of colours, blue/white veil, and vascular pattern., Results: Only three cases exhibited one classical feature for a melanocytic lesion; other cases were recognized on the basis of the presence of figures of regression (all six), i.e. white scar-like areas and 'peppering' (three of six), multiple (> 4) colours (five of six), and of melanoma-related vascular patterns (five) such as linear-irregular vessels (four) and milky-red areas (two)., Discussion: We believe that dermoscopy could help in the accurate diagnosis of this rare neoplasm. In the absence of a pigmented network, attention should be given to the identification of features of regression and to melanoma-associated vascular patterns.

Background: Metastatic melanoma of unknown origin is a difficult challenge diagnostically and therapeutically. Diagnosis of the putative primary lesion is difficult. This difficulty increases when the primary lesion has undergone complete regression., Objective: To define the dermoscopic features of fully regressed melanoma., Patients and Methods: A single-institution, register-based study of an unselected consecutive series of seven cases of metastatic melanoma in the lymph nodes with no known or visible primary lesion was carried out. Skin examination included dermoscopy; when a suspicious area was found, observed dermoscopic features were recorded and a biopsy was performed. Diagnosis of completely regressive cutaneous melanoma was based on clinical-pathological correlation according to widely accepted criteria., Results: Seven dermoscopic features were associated with completely regressive melanoma: scar-like depigmentation (100%); pink coloration of the background (100%); linear-irregular vessels (86%); globular pattern of the vessels (43%); remnants of pigmentation (86%), either macular (43%) or with a peppering aspect (43%); and white lighter transverse bands (43%). The last feature was only observed with polarized light dermoscopy devices., Conclusion: Dermoscopy more accurately distinguishes the vascular, pigmentary and scarring changes of fully regressive melanoma. We believe that dermoscopy should be included in the search for a regressive primary lesion in case of metastatic melanoma of unknown origin.

Background: Sentinel lymph node (SLN) positivity has been found to be strongly associated with a poor prognosis in melanoma., Objectives: This large referral centre study was conducted: (i) to confirm the powerful prognostic value of SLN biopsy (SLNB); (ii) to correlate patient prognosis to the micromorphometric features of SLN metastasis in SLN-positive patients; and (iii) to correlate these micromorphometric features to the likelihood of positive completion lymph node dissection (CLND)., Patients and Methods: SLNB was performed in 455 cases of primary melanoma between January 1999 and December 2004; for patients with positive SLN, the following micromorphometric features were registered: size of the largest metastasis (two diameters), depth of metastasis, number of millimetric slices involved, maximum number of metastases on a single section, presence of intracapsular lymphatic invasion and extracapsular spread. Kaplan-Meier survival curves were compared with the log-rank test; multivariate analysis was performed using a Cox regression model. Dependence of CLND status on micromorphometric features of SLN was assessed by the chi(2) test and predictive values of the different features were evaluated by multivariate analysis using a logistic regression model., Results: A positive SLN was identified in 98 of our 455 cases. Survival was significantly shorter in SLN-positive patients than in SLN-negative patients. Extracapsular invasion was found to be an independent prognostic factor of disease-free survival; ulceration of the primary and the maximum diameter of the largest metastasis were identified as independent predictive factors of disease-specific survival. Age and the lowest diameter of the largest metastasis were identified as independent predictive criteria of positive CLND, whereas depth of metastasis was not. Positivity of CLND was not significantly associated with a worse prognosis., Conclusions: Our study confirms the previously demonstrated strong prognostic value of SLNB. It also confirms the relationship between tumour burden in the SLN (evaluated by the maximum diameter of the largest metastasis) and clinical outcome. We point out a new micromorphometric feature of SLN, which seems to be predictive of CLND status: the lowest diameter of the largest metastasis.