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.

Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.

Tattoo complications in treated and non-treated psoriatic patients.

BACKGROUND: Tattooing is a widespread phenomenon, with an estimated prevalence of 10-30% in Western populations. For psoriasis patients, current recommendations are to avoid having a tattoo if the disease is active and they are receiving immunosuppressive treatments. Although scientific data supporting these recommendations are lacking, dermatologists are often reluctant to advocate tattooing in psoriasis patients. OBJECTIVE: We aimed to evaluate the frequency of tattoo complications in patients with psoriasis and determine whether the occurrence of complications was associated with psoriasis status and treatments received at the time of tattooing. METHODS: We performed a multicentre cross-sectional study. Adults with psoriasis were consecutively included and classified as tattooed or non-tattooed. Prevalence of complications associated with tattoos was then evaluated according to psoriasis onset and treatments. The study was divided into three parts, in which data were collected through a series of questionnaires filled in by the dermatologist. Complications included pruritus, oedema, allergic reaction/eczema, infection/superinfection, granuloma, lichenification, photosensitivity, Koebner phenomenon and psoriasis flare after tattooing. Diagnosis of complications was made retrospectively. RESULTS: We included 2053 psoriatic patients, 20.2% had 894 tattoos. Amongst non-tattooed patients, 15.4% had wished to be tattooed, with psoriasis being stated as a reason for not having a tattoo by 44.0% and 5.7% indicating that they planned to have a tattoo in the future. Local complications, such as oedema, pruritus, allergy and Koebner phenomenon, were reported in tattoos in 6.6%, most frequently in patients with psoriasis requiring treatment at the time of tattooing (P < 0.0001). No severe complications were reported. CONCLUSIONS: The rate of tattoo complications in psoriasis patients was low. Although the risk of complications was highest amongst patients with psoriasis requiring treatment at the time of tattooing, all the complications observed were benign. These results can be helpful for practitioners to give objective information to patients.

Reliability outcomes and inter-limb differences in ankle joint stiffness in children with unilateral cerebral palsy depend on the method of analysis.

Children with cerebral palsy (CP) present increased passive ankle joint stiffness, measured as the slope of the torque-angle curve relationship. However, large discrepancies in results exist among studies, likely because of various methodologies used. The purpose of this study was to determine the influence of different calculation methods on the outcomes and their inter-session reliability in children with unilateral CP (UCP). Thirteen children (mean age: 9.8 years) with spastic UCP underwent passive ankle mobilization at 2°/s on both legs using a dynamometer, on two occasions separated by one week. Passive ankle joint stiffness was calculated as the slope of the torque-angle curve using linear regression on three different relative ranges of torque (i.e. 30%-100%, 20-80% and 50-90% of maximal torque for method 1, 2 and 3, respectively) for both the paretic and non-paretic legs. Inter-session reliability was significantly lower on paretic leg (mean CV = 13.8%, ICC = 0.62) when compared to non-paretic leg (mean CV = 6%, ICC = 0.85), and method 3 presented lower reliability outcomes (mean CV = 11.7%, ICC = 0.75) than methods 1 (mean CV = 7.5%, ICC = 0.78) and 2 (mean CV = 6.6%, ICC = 0.79). Paretic values (0.24 Nm/°) were not different from the non-paretic leg (0.25 Nm/°), although significantly higher when considering the same angular sector (0.18 Nm/°). Passive ankle joint stiffness measurement can be reliably performed in children with UCP using method 1 and 2 while method 3 should be avoided. The non-paretic leg may be used for comparison with the paretic leg when taking into account differences in maximal dorsiflexion angle between legs. ClinicalTrials.gov Identifier: NCT02960932.

Risk factors for treatment failure in scabies: a cohort study.

BACKGROUND: Treatment failure, which occurs in about one-third of cases, is considered as a major factor in the increasing incidence of scabies in developed countries. OBJECTIVES: To identify predictors of treatment failure of scabies in ambulatory populations. METHODS: This multicentre study compared the clinical characteristics and treatment modalities between a group of patients with scabies treated successfully and another group who were not cured 3 months after antiscabies treatment. RESULTS: In total 210 patients with a diagnosis of scabies were included, comprising 98 patients in the treatment success group and 112 in the treatment failure group. The main risk factors for treatment failure were (i) the use of only one type of treatment, topical benzyl benzoate (BB) or oral ivermectin, vs. the combination of both treatments [odds ratio (OR) 2·15, 95% confidence interval (CI) 1·22-3·77]; (ii) the use of a single intake (vs. two) of oral ivermectin (OR 10·2. 95% CI 4·49-23·2); (iii) intake of ivermectin during a meal vs. on an empty stomach (OR 4·31, 95% CI 1·89-9·84); (iv) absence of decontamination of furnishings (OR 8·72, 95% CI 3·50-21·8), in particular sofa and cushions (OR 5·90, 95% CI 2·34-14·9), mattresses (OR 4·16, 95% CI 1·35-12·8) or car seats (OR 6·57, 95% CI 3·27-13·2) and (v) absence of written documents explaining treatment modalities (OR 5·18, 95% CI 2·57-10·4). In multivariate analysis, treatment failure was mainly associated with (i) use of a single intake (vs. two) of ivermectin (OR 6·62, 95% CI 2·71-16·2); (ii) use of BB alone vs. two intakes of ivermectin (OR 3·51, 95% CI 1·55-7·95) and (iii) absence of decontamination of furniture with acaricides (OR 5·81, 95% CI 1·96-16·7). CONCLUSIONS: Use of topical BB alone and a single intake (vs. two) of ivermectin are predictors of treatment failure.

Molecular and epigenetic regulations and functions of the LAFL transcriptional regulators that control seed development.

The LAFL (i.e. LEC1, ABI3, FUS3, and LEC2) master transcriptional regulators interact to form different complexes that induce embryo development and maturation, and inhibit seed germination and vegetative growth in Arabidopsis. Orthologous genes involved in similar regulatory processes have been described in various angiosperms including important crop species. Consistent with a prominent role of the LAFL regulators in triggering and maintaining embryonic cell fate, their expression appears finely tuned in different tissues during seed development and tightly repressed in vegetative tissues by a surprisingly high number of genetic and epigenetic factors. Partial functional redundancies and intricate feedback regulations of the LAFL have hampered the elucidation of the underpinning molecular mechanisms. Nevertheless, genetic, genomic, cellular, molecular, and biochemical analyses implemented during the last years have greatly improved our knowledge of the LALF network. Here we summarize and discuss recent progress, together with current issues required to gain a comprehensive insight into the network, including the emerging function of LEC1 and possibly LEC2 as pioneer transcription factors.

LEC1 (NF-YB9) directly interacts with LEC2 to control gene expression in seed.

The LAFL transcription factors LEC2, ABI3, FUS3 and LEC1 are master regulators of seed development. LEC2, ABI3 and FUS3 are closely related proteins that contain a B3-type DNA binding domain. We have previously shown that LEC1 (a NF-YB type protein) can increase LEC2 and ABI3 but not FUS3 activity. Interestingly, FUS3, LEC2 and ABI3 contain a B2 domain, the function of which remains elusive. We showed that LEC1 and LEC2 partially co-localised in the nucleus of developing embryos. By comparing protein sequences from various species, we identified within the B2 domains a set of highly conserved residues (i.e. TKxxARxxRxxAxxR). This domain directly interacts with LEC1 in yeast. Mutations of the conserved amino acids of the motif in the B2 domain abolished this interaction both in yeast and in moss protoplasts and did not alter the nuclear localisation of LEC2 in planta. Conversely, the mutations of key amino acids for the function of LEC1 in planta (D86K) prevented the interaction with LEC2. These results provide molecular evidences for the binding of LEC1 to B2-domain containing transcription factors, to form heteromers, involved in the control of gene expression.

Regulation and evolution of the interaction of the seed B3 transcription factors with NF-Y subunits.

The LAFL genes (LEC2, ABI3, FUS3, LEC1) encode transcription factors that regulate different aspects of seed development, from early to late embryogenesis and accumulation of storage compounds. These transcription factors form a complex network, with members able to interact with various other players to control the switch between embryo development and seed maturation and, at a later stage in the plant life cycle, between the mature seed and germination. In this review, we first summarize our current understanding of the role of each member in the network in the light of recent advances regarding their regulation and structure/function relationships. In a second part, we discuss new insights concerning the evolution of the LAFL genes to address the more specific question of the conservation of LEAFY COTYLEDONS 2 in both dicots and monocots and the putative origin of the network. Last we examine the current major limitations to current knowledge and future prospects to improve our understanding of this regulatory network.

Calculation of cut-off values based on the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI) pemphigus scoring systems for defining moderate, significant and extensive types of pemphigus.

BACKGROUND: Two pemphigus severity scores, Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI), have been proposed to provide an objective measure of disease activity. However, the use of these scores in clinical practice is limited by the absence of cut-off values that allow differentiation between moderate, significant and extensive types of pemphigus. OBJECTIVES: To calculate cut-off values defining moderate, significant and extensive pemphigus based on the ABSIS and PDAI scores. METHODS: In 31 dermatology departments in six countries, consecutive patients with newly diagnosed pemphigus were assessed for pemphigus severity, using ABSIS, PDAI, Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI) scores. Cut-off values defining moderate, significant and extensive subgroups were calculated based on the 25th and 75th percentiles of the ABSIS and PDAI scores. The median ABSIS, PDAI, PGA and DLQI scores of the three severity subgroups were compared in order to validate these subgroups. RESULTS: Ninety-six patients with pemphigus vulgaris (n = 77) or pemphigus foliaceus (n = 19) were included. The median PDAI activity and ABSIS total scores were 27·5 (range 3-84) and 34·8 points (range 0·5-90·5), respectively. The respective cut-off values corresponding to the first and third quartiles of the scores were 15 and 45 for the PDAI, and 17 and 53 for ABSIS. The moderate, significant and extensive subgroups were thus defined, and had distinguishing median ABSIS (P < 0·001), PDAI (P < 0·001), PGA (P < 0·001) and DLQI (P = 0·03) scores. CONCLUSIONS: This study suggests cut-off values of 15 and 45 for PDAI and 17 and 53 for ABSIS, to distinguish moderate, significant and extensive pemphigus forms. Identifying these pemphigus activity subgroups should help physicians to classify and manage patients with pemphigus.

[Cryosurgery and photodynamic therapy for the treatment of Paget's disease of the vulva: two cases]. / Traitement de la maladie de Paget vulvaire par cryochirurgie et photothérapie dynamique topique.

BACKGROUND: Surgery is the standard treatment for vulvar Paget's disease, despite its mutilating consequences and the high associated recurrence rate. Alternative treatments such as CO2 laser, application of imiquimod and topical photodynamic therapy (PDT) have recently been proposed. We report on two patients with vulvar Paget's disease treated with combined cryosurgery and PDT. PATIENTS AND METHODS: Case 1: a 40-year-old pregnant woman presented large vulvar lesions suggestive of Paget's disease. After imiquimod treatment failed, three sessions of cryosurgery were performed on all lesions at 5-month intervals, followed by PDT sessions for the residual erythema. Because of recurrent focal lesions, further sessions of localized cryosurgery were performed for 18 months. Case 2: a 61-year-old patient with extensive vulvar Paget's disease relapsed after imiquimod treatment and was treated by cryosurgery and multiple PDT sessions. She was in complete remission 12 months after this treatment. DISCUSSION: Combined cryosurgery and PDT may offer a therapeutic alternative to conventional surgery for the treatment of large or recurrent multifocal vulvar Paget's disease, or in elderly people. Indeed, although palliative, these two non-invasive techniques can be used to treat many lesions in a single session. Recurrences can be treated again using either technique, or both, without any aesthetic or functional consequences.

Protein components of low-density lipoproteins purified from hen egg yolk.

To identify apoproteins present in purified low-density lipoproteins from hen egg yolk in relation with their emulsifying properties, they have been separated by SDS-PAGE. We identified two different proteins by liquid chromatography-tandem mass spectrometry analysis of the peptides obtained by the trypsin digestion of protein gel bands. Apovitellenin I was identified as a monomer and a dimer. Its amino acid sequence was totally confirmed, and molecular mass determination by liquid chromatography-mass spectrometry showed that it did not present post-translational modifications but only a slight heterogeneity by the loss of one or two amino acids at the C-terminal part of the protein. Apolipoprotein B was identified into seven bands corresponding to fragments resulting of a processing of the hen blood apo-B protein. The identity of the fragments was determined by the observation of the sequence coverage by trypsin peptides and the sequence alignment with homologous human blood apolipoprotein B-100.

A third species of Hypoderma (Diptera: Oestridae) affecting cattle and yaks in China: molecular and morphological evidence.

Cattle and yak hypodermosis in China is caused by Hypoderma bovis and H. lineatum, with a prevalence reaching up to 98-100% of the animals and maximum intensities exceeding 400 warbles for each animal. A third species, H. sinense, is also considered by Chinese researchers to affect livestock. The molecular characterization of the most variable region of the mitochondrial cytochrome oxidase I gene and of the ribosomal 28S gene has been performed for the third-stage larvae collected from cattle and yaks in China and identified (on the basis of the spinulation on the ventral side of the 10th segment) as H. bovis, H. lineatum, and H. sinense. Amplicons were digested with the HinfI and BfaI restriction enzymes, which provided diagnostic profiles to simultaneously differentiate the 3 Hypoderma species. Third-stage larvae of H. sinense were also examined by scanning electron microscopy, which revealed proper morphological characteristics different from those of H. bovis and H. lineatum. The molecular and morphological evidence herein reported support the existence of a third species of Hypoderma affecting cattle and yaks in China, and the results provide new tools for unequivocal identification of this species and present key components for the evaluation of its endogenous cycle and pathogenicity in animals and humans.