International multicentre observational study to assess the efficacy and safety of a 0·5 mg kg-1 per day starting dose of oral corticosteroids to treat bullous pemphigoid.

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.

Intraoperative dermoscopy features of subungual squamous cell carcinoma: a study of 53 cases.

BACKGROUND: Subungual squamous cell carcinoma (SU-SCC) is the most common malignant tumour of the nail unit. Intraoperative nail dermoscopy has been described only for pigmented tumours, onychomatricoma and glomus tumours. AIM: To establish a description of intraoperative dermoscopic features of SU-SCC. METHODS: A single-centre retrospective cohort of 53 SU-SCC cases over a 5-year period was reviewed by six examiners who individually scored 31 intraoperative dermoscopic features as present or absent. For each feature, the frequency and interobserver agreement was evaluated, then the data were compared and a consensus was reached. RESULTS: No feature had perfect or substantial interobserver agreement. Regarding anatomy and architecture, most tumours involved both the nail bed and nail matrix (n = 34, 64.2%) and had nonparallel lateral side edges (n = 36, 67.9%). Regarding vascular features, several different patterns were found: dotted vessels (n = 49, 92.5%), irregular vessels (n = 47, 88.7%), curved vessels (n = 46, 86.8%), sagittal vessels (n = 45, 84.9%), milky-red areas (n = 42, 79.2%), linear and regular vessels (n = 30, 56.6%), coiled and hairpin vessels (n = 23, 43.4%), and arborizing vessels (n = 16, 30.2%). Pigmented dermoscopy structures included dotted purpura, grey granulation and splinter haemorrhages, which were found in 49 (20.8%), 9 (17%) and 9 (17%) cases, respectively. Other dermoscopic signs were pink background, translucent structureless area, whitish scaly areas, distal plug, yellowish scales and dots, and 'digitiform' proximal edge, which were found in 49 (84.9%), 49 (84.9%), 43 (81.1%), 37 (69.8%), 28 (52.8%) and 22 (41.5%) cases, respectively. CONCLUSION: Analysis of this first large series of SU-SCC studied by intraoperative dermoscopy suggests that it gives useful information to better approach the diagnosis and to target biopsies.

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.

Pigeon tick bite: A neglected cause of idiopathic nocturnal anaphylaxis.

Anaphylaxis is a serious systemic allergic reaction with rapid onset and potentially life-threatening. We report in detail a case of severe nocturnal anaphylaxis due to pigeon tick bite showing the diagnostic value of the extract and the recombinant allergen in the diagnostic procedures (basophil activation test, IgE immunoblot, and experimental ImmunoCAP). Apart from the presented case, we describe that during the last 10 years, we have collected 28 cases of allergy to Argas reflexus from several European countries. We suspect that this allergy is underdiagnosed because of the lack of diagnostic reagents. Because of the growing number of pigeons in Middle and Southern Europe cities, some cases of idiopathic anaphylaxis could potentially be caused by A. reflexus in those countries. The identification of pigeon ticks as a trigger of anaphylaxis would greatly improve medical care and advice for these patients as the parasite can be exterminated by eradication measures to avoid further incidents.

Treatment of prurigo with methotrexate: a multicentre retrospective study of 39 cases.

BACKGROUND: Prurigo is a common primary pruritic condition. Treatment is challenging. Methotrexate (MTX) is effective for the treatment of pruriginous dermatoses, but its use in prurigo has been little studied. OBJECTIVES: To investigate the efficacy and safety of MTX in the treatment of difficult-to-treat prurigo. METHODS: Patients from six university dermatology departments treated with MTX between 2006 and 2016 for difficult-to-treat prurigo (i.e. with failure to conventional therapies) were included in this retrospective multicentre study. Patients with other pruritic dermatoses were excluded. Clinical efficacy was recorded after 3, 6 and 12 months of treatment: (i) subjective efficacy, that is, evaluation of the pruritus by the patient and (ii) objective efficacy, that is, assessment of cutaneous lesions by the physician: complete or almost complete remission (CR) (healing of lesions), partial remission (PR) (incomplete improvement of lesions) or failure (no improvement or worsening). The overall response rate (ORR) included CR and PR. RESULTS: Thirty-nine patients with previous failure of topical steroids, H1-antihistamine drugs or phototherapy were included. The median weekly dose of MTX was 15 mg (range 5-25 mg). The median follow-up was 16 months (2-108). The mean time between onset of MTX and objective efficacy was 2.4 ± 1.2 months and the mean duration of response was 19 ± 15 months. The ORR was 91% at 3 months [n = 36, CI 95% (81.2-100.8%), CR 44%], 94% at 6 months [n = 32, CI 95% (85.7-102.2%), CR 56%] and 89% at 12 months [n = 28, CI 95% (77.4-100.6%), CR 57%]. Seven patients stopped MTX because of failure, and five because of the discovery of hepatocarcinoma (n = 1), elevated transaminases (n = 1), infectious pneumonitis (n = 1) or gastrointestinal symptoms (n = 2). CONCLUSION: Methotrexate is a therapeutic option in difficult-to-treat prurigo.

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.

Intraoperative dermoscopic features of onychomatricoma: a review of 10 cases.

BACKGROUND: Amelanotic nail tumours are difficult to diagnose. Dermoscopy is an accessible tool successfully used in diagnosis of amelanotic or melanotic skin tumours. We have previously shown the usefulness of dermoscopy in the preoperative diagnosis of onychomatricoma (OM). In this study, we completed this work by identifying additional intraoperative criteria to better establish the initial diagnosis of this tumour. AIMS: Evaluation of intraoperative dermoscopy in a small series of OM cases in order to define relevant diagnostic criteria. METHODS: In total, 10 patients with OM diagnosed in our centre were enrolled in the study. Six trained dermoscopists individually evaluated each criterion, then the data were compared and a consensus reached after discussion between the observers. For each criterion, we analysed its frequency and its interobserver accordance. We defined three architectural criteria (the 'Sagrada Familia' sign, digitations and the 'mirror sign'), and three vascular criteria (sagittal vessels, dotted vessels and irregular vessels). RESULTS: The Sagrada Familia sign, digitations and mirror sign were found in 100%, 90% and 70% of the cases, respectively, with high interobserver agreement. The vascular criteria were less regularly observed: sagittal, dotted and irregular vessels were respectively found in 80%, 70% and 50% of the OM cases, and were more difficult to assess, as shown by the lower interobserver agreement rates. CONCLUSION: Intraoperative dermoscopy of the nail matrix and bed offers useful information for the diagnosis and management of OM. Larger comparative studies should be performed to evaluate the true benefit of this approach.

Clinical and immunological features and outcome of anti-p200 pemphigoid.

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.

Reflectance confocal microscopy features of acral lentiginous melanoma: a comparative study with acral nevi.

BACKGROUND: Acral lentiginous melanoma (ALM) can be difficult to differentiate from acral nevus. Reflectance confocal microscopy (RCM) is widely used for the diagnosis of melanocytic tumours, but the RCM features of ALM and acral nevus have not been described yet. OBJECTIVE: To determine the RCM features of ALM and acral nevus, and their correlation with clinical and histological characteristics. METHODS: Retrospective study of 17 cases of ALM and 26 acral nevi. RESULTS: Pagetoid cells were present in all ALMs with a visible epidermis and in three nevi. A proliferation of atypical melanocytes at the dermal-epidermal junction (DEJ) and/or in the dermis was visible in nine ALMs but not in nevi. The histopathological examination of initial skin biopsies was unable to diagnose ALM in four cases, differing from RCM that could identify malignant tumour cells by exploring the whole lesions. CONCLUSION: Reflectance confocal microscopy can help in the differentiation of ALM and acral nevus, and to guide the biopsy.

Intraoperative diagnosis of nonpigmented nail tumours with ex vivo fluorescence confocal microscopy: 10 cases.

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.

Reflectance confocal microscopy of mucosal pigmented macules: a review of 56 cases including 10 macular melanomas.

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.

Gonococcemia mimicking a lupus flare in a young woman.

Gonorrhea is a common sexually transmitted infection, which can present as the 'arthritis-dermatitis syndrome'. Patients with systemic lupus erythematosus often develop disseminated neisserial infections, because of inherited and acquired complement deficiencies. Neisserial infection, and particularly gonococcemia, can mimic a lupus flare. We report one case of gonococcemia presenting as acral papulo-vesiculous lesions of the digits in a young woman with lupus.

[Recurrent pyoderma gangrenosum-like ulcers induced by oral anticoagulants]. / Ulcérations récidivantes à type de pyoderma grangrenosum induites par les antivitamines K.

BACKGROUND: Other than the classic skin necrosis induced by oral anticoagulants (OAC) in patients with protein C and S deficiencies, other types of OAC induced-skin ulcers are little known. Herein, we describe an original case of recurrent pyoderma gangrenosum (PG)-like ulcers induced by OAC. PATIENTS AND METHODS: A 70-year-old female heart-transplant recipient presented deep, hyperalgesic and quickly-spreading necrotic ulceration of the right leg 6 weeks after starting oral anticoagulant therapy with fluindione. Histological analysis revealed dermal infiltrate containing polynuclear neutrophils, which accords with the histopathological diagnosis of leukocytoclastic vasculitis or PG. Infectious, autoimmune and thrombophilic causes were ruled out. Fluindione was withdrawn and the ulcer healed completely within a month. Six months later, right leg ulceration recurred two weeks after the patient resumed fluindione but healed within 1 month of discontinuation of the drug. An OAC from another chemical family (warfarin) was then introduced, with further recurrence of ulceration after 2 weeks of treatment. DISCUSSION: The chronology of events and the negativity of aetiological explorations allowed a diagnosis to be made of OAC-induced skin ulcer, a rare complication of which the pathophysiology is unclear. This is the first case of PG-like ulcers induced by OAC.

Dermoscopy of dermatofibrosarcoma protuberans: a study of 15 cases.

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.