Switches between biologics in patients with moderate-to-severe psoriasis: results from the French cohort PSOBIOTEQ.

BACKGROUND: Biologics are the cornerstone of treatment of patients with moderate-to-severe plaque psoriasis and switches between biologics are frequently needed to maintain clinical improvement over time. OBJECTIVES: The main purpose of this study was to describe precisely switches between biologics and how their pattern changed over time with the recent availability of new biologic agents. METHODS: We included patients receiving a first biologic agent in the Psobioteq multicenter cohort of adults with moderate-to-severe psoriasis receiving systemic treatment. We described switches between biologics with chronograms, Sankey and Sunburst diagrams, assessed cumulative incidence of first switch by competing risks survival analysis and reasons for switching. We assessed the factors associated with the type of switch (intra-class - i.e. within the same therapeutic class - vs. inter-class) in patients switching from a TNF-alpha inhibitor using multivariate logistic regression. RESULTS: A total of 2153 patients was included. The cumulative incidence of switches from first biologic was 34% at 3 years. Adalimumab and ustekinumab were the most prescribed biologic agents as first and second lines of treatment. The main reason for switching was loss of efficacy (72%), followed by adverse events (11%). Patients receiving a TNF-alpha inhibitor before 2016 mostly switched to ustekinumab, whereas those switching in 2016 or after mostly switched to an IL-17 inhibitor. Patients switching from a first-line TNF-alpha inhibitor before 2016 were more likely to switch to another TNF-alpha inhibitor compared with patients switching since 2018. Patients switching from etanercept were more likely to receive another TNF-alpha inhibitor rather than another therapeutic class of bDMARD compared with patients switching from adalimumab. CONCLUSION: This study described the switching patterns of biologic treatments and showed how they changed over time, due to the availability of the new biologic agents primarily IL-17 inhibitors.

Palmoplantar pustulosis and acrodermatitis continua of Hallopeau: demographic and clinical comparative study in a large multicentre cohort.

BACKGROUND: Acral pustular disease within the pustular psoriasis/psoriasis-like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. OBJECTIVES: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. METHODS: In this multicentre national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. RESULTS: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity and higher median BMI (P = 0.01, P = 0.02 and P = 0.05 respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1% respectively). CONCLUSION: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis-like entities for precision medicine.

Identification of three clinical neurofibromatosis 1 subtypes: Latent class analysis of a series of 1351 patients.

BACKGROUND: Neurofibromatosis 1 (NF1) is one of the most common inherited disorders characterized by mutations in the tumour suppressor gene NF1. Its clinical manifestations are highly variable and unpredictable. A specific NF1 mutation does not predict the severity or complications of the disease. OBJECTIVE: The objective of this study was to build an empirical classification scheme without any a priori hypotheses to identify the underlying NF1 subtypes that best explain the observed heterogeneity. METHODS: We performed latent class analysis (LCA) of 1351 consecutive NF1 patients aged >17 years seen between 2002 and 2014. Data and phenotypic features were collected prospectively on a standardized form. RESULTS: The median age was 36.8 (17-81) years. A three-class model showed the best fit: 706 (52%) belonged to the LC1 'Cutaneous neurofibromas' class having preferentially cutaneous neurofibromas (99%), plexiform neurofibromas (63%) and blue-red macules (29%); 593 (44%) belonged to the LC2 'Subcutaneous neurofibromas' class characterized by the presence of at least 10 subcutaneous neurofibromas (21%) and a familial form (77%) and 52 (4%) belonged to the LC3 'Dysmorphic phenotype' class characterized by dysmorphic features (78%) and learning difficulties (87%). Patients in LC1 had a higher likelihood of developing scoliosis (RR = 1.7, 95% confidence interval (CI) [1.2-2.4]). Patients in LC2 were more likely to be men (RR = 1.4, 95% CI [1.1-1.7]). Patients in LC3 were at higher risk of having an optic pathway glioma (RR = 4.8, 95% CI [1.9-11.8]) and epilepsy (RR = 4.5, 95% CI [1.8-11.6]). CONCLUSION: Our findings invite the performance of a larger cohort study to test whether the various latent classes reflect different underlying genetic modifiers of these phenotypic traits.

Meta-analysis results do not reflect the real safety of biologics in psoriasis.

BACKGROUND: In reported systematic reviews and meta-analyses of randomized controlled trials (RCTs) assessing treatments for psoriasis, the proportion of serious adverse events (SAEs) did not differ between treatments and placebo. Including cases of psoriasis worsening as SAEs may explain the lack of difference. OBJECTIVES: This systematic review and meta-analysis aimed to explore this possibility. METHODS: Among the 140 RCTs included in the Living Network Cochrane Review (last search on 8 May 2019), we selected those comparing a biologic treatment against placebo. The primary outcome was the numbers of SAEs in the treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were the number of adverse events (AEs) of special interest. The trial was registered on PROSPERO (CRD42019124495). RESULTS: We analysed 51 RCTs. Of these, 21 included at least one anti-tumour necrosis factor (TNF)-α arm, 15 one anti-interleukin (IL)-17 arm, 11 one anti-IL-23 arm and nine one anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biologic treatments and placebo did not differ: risk ratio (RR) 1·09, 95% confidence interval (CI) 0·88-1·36. After excluding cases of psoriasis worsening, the RR became significant (RR 1·30, 95% CI 1·02-1·65). By drug class, the RRs were for anti-TNF-α, 1·68 (95% CI 1·11-2·54; no missing data); anti-IL-17, 1·28 (95% CI 0·88-1·85; no missing data); anti-IL-23, 0·95 (95% CI 0·59-1·52; no missing data) and anti-IL-12/23, 1·18 (95% CI 0·72-1·94; no missing data). We were unable to examine potential differences in AEs of special interest between biologic treatments and placebo arms because of the small number of events. CONCLUSIONS: On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic than in the placebo arm. Given the rare events, we could not highlight whether this higher risk of SAEs was related to AEs of special interest. Reporting of SAEs in clinical trials has to be changed to provide more transparency through the separate reporting of disease flares leading to hospital admission and other SAEs.

Epidemiologic study in a real-world analysis of patients with treatment for psoriasis in the French national health insurance database.

BACKGROUND: Psoriasis is one of the most frequent chronic inflammatory dermatoses in the world. Data on the prevalence of psoriasis in adults differ depending on the study. OBJECTIVE: To estimate the prevalence of patients with treatment for psoriasis in France and to identify and characterize patients receiving systemic treatments. METHODS: This was a French, nationwide cohort study based on health administrative data from the French national health insurance scheme linked to the national hospital discharge database (SNDS-PMSI). All adults with psoriasis registered in the SNDS between 1 January 2008 and 31 December 2016 were eligible for inclusion. All patients with a new prescription for a systemic treatment for psoriasis were included. RESULTS: A total of 874 549 patients were identified as having psoriasis (mean ± SD age 53.8 ± 17 years; 52.4% males); 112 969 (13%) had filled at least one prescription for a systemic medication used to treat psoriasis. The prevalence of patients with treatment for psoriasis was estimated at 1.3%. Overall, 73 168 and 16 545 were new users of conventional systemic treatments and biologics, respectively. The most frequent comorbidities associated with psoriasis were hypertension, dyslipidaemia, diabetes and chronic obstructive pulmonary disease. CONCLUSION: The prevalence of psoriasis we found was lower than in other studies. It was probably underestimated because we identified only patients with treatment for psoriasis. Our results concerning comorbidities associated with psoriasis patients requiring systemic treatment were similar to those from other published studies using other data sources, highlighting our ability to catch moderate-to-severe psoriasis. This study highlights the usefulness and reliability of the use of insurance databases in studies, because they allow for a better application to the general population.

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.

Efficacy and safety of TNF blockers and of ustekinumab in palmoplantar pustulosis and in acrodermatitis continua of Hallopeau.

BACKGROUND: Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce. OBJECTIVES: To evaluate the real-life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH. METHODS: A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P = 0.18 and P = 0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR = 9.5 (95% CI 1.1-82.7), P = 0.04 and 0.1 (0.01-0.9), P = 0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3-28.6), P = 0.02 and 4.7 (1.0-22.7), P = 0.05]; with adalimumab, the ACH form [11.9 (2.7-52.3), P = 0.001]; and with infliximab, obesity [5.6 (1.1-29.4), P = 0.04]. CONCLUSIONS: We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis.

Persistence of apremilast in moderate-to-severe psoriasis: a real-world analysis of 14 147 apremilast- and methotrexate-naive patients in the French National Health Insurance database.

BACKGROUND: Real-world data on the persistence of apremilast vs. methotrexate are inconclusive. OBJECTIVES: To assess and compare the long-term persistence of apremilast and methotrexate in a large cohort of patients with psoriasis. METHODS: All adult patients with psoriasis registered in the French national health insurance database ('Système National des Données de Santé') between 2009 and 2017 were eligible for inclusion. The study population comprised apremilast- and methotrexate-naive patients, defined as those with a first prescription of apremilast or methotrexate. Levels of persistence were compared using a Cox model with propensity-score matching that included potential confounders (notably age, sex, psoriatic arthritis, comorbidities and previous exposure to topical and systemic treatments). RESULTS: In this nationwide population-based cohort, 14 147 adult patients with psoriasis (mean age 52·3 years, 55·2% male) were found to be naive to both apremilast and methotrexate. After propensity-score matching, two subgroups of 4805 patients with similar baseline characteristics were included, of whom 3207 apremilast-treated patients and 2736 methotrexate-treated patients discontinued their treatment. Kaplan-Meier survival propensity-score analyses revealed a discontinuation rate of 69% for apremilast and 59% for methotrexate in the first year of treatment. Apremilast-treated patients had a higher risk of discontinuation than methotrexate-treated patients when considering the study population as a whole (hazard ratio 1·28, 95% confidence interval 1·23-1·34) or in a propensity-score-matched analysis (hazard ratio 1·34, 95% confidence interval 1·27-1·41; P < 0·001). CONCLUSIONS: Our real-world data suggest that in the first year of treatment, the discontinuation rate was significantly higher for apremilast-treated patients than for methotrexate-treated patients, regardless of the previous therapeutic lines received. What's already known about this topic? Psoriasis is a common chronic, relapse-remitting, inflammatory skin disease associated with severe psychosocial impact. Apremilast, a phosphodiesterase 4 inhibitor, is one of the most recently commercialized psoriasis drugs. Little is known about the long-term clinical effectiveness of apremilast. What does this study add? The discontinuation rate at 1 year for apremilast was 69%, compared with 58% for methotrexate, in a nationwide population-based cohort including 14 147 nonselected adult patients with psoriasis. Patients in the apremilast cohort had a higher risk of discontinuation than patients in the methotrexate cohort using propensity-score matching, including potentially relevant individual risk factors such as age, sex, comorbidities and psoriatic arthritis, and regardless of the previous therapeutic lines received. In daily practice, physicians should take these results into account when choosing between methotrexate and apremilast as a first-line systemic therapy.

Pathogen identification by shotgun metagenomics of patients with necrotizing soft-tissue infections.

BACKGROUND: Necrotizing soft-tissue infections (NSTIs) are life threatening, requiring broad-spectrum antibiotics. Their aetiological diagnosis can be limited by poor performance of cultures and administration of antibiotics before surgery. OBJECTIVES: We aimed (i) to compare 16S-targeted metagenomics (TM) and unbiased semiquantitative panmicroorganism DNA- and RNA-based shotgun metagenomics (SM) with cultures, (ii) to identify patients who would best benefit from metagenomics approaches and (iii) to detect the microbial pathogens in surrounding non-necrotic 'healthy' tissues by SM-based methods. METHODS: A prospective observational study was performed to assess the analytical performance of standard cultures, TM and SM on tissues from 34 patients with NSTIs. Pathogen identification obtained with these three methods was compared. RESULTS: Thirty-four necrotic and 10 healthy tissues were collected from 34 patients. The performance of TM was inferior to that of the other methods (P < 0·05), whereas SM performed better than standard culture, although the result was not statistically significant (P = 0·08). SM was significantly more sensitive than TM for the detection of all bacteria (P = 0·02) and more sensitive than standard culture for the detection of anaerobic bacteria (P < 0·01). There was a strong correlation (r = 0·71, Spearman correlation coefficient) between the semiquantitative abundance of bacteria in the culture and the bacteria-to-human sequence ratio in SM. Low amounts of bacterial DNA were found in healthy tissues, suggesting a bacterial continuum between macroscopically 'healthy' and necrotic tissue. CONCLUSIONS: SM showed a significantly better ability to detect a broader range of pathogens than TM and identify strict anaerobes than standard culture. Patients with diabetes with NSTIs appeared to benefit most from SM. Finally, our results suggest a bacterial continuum between macroscopically 'healthy' non-necrotic areas and necrotic tissues. What's already known about this topic? Necrotizing soft-tissue infections (NSTIs) are characterized by rapidly progressive necrosis of subcutaneous tissues and high mortality, despite surgical debridement combined with broad-spectrum antibiotics. The spectrum of potentially involved pathogens is very large, and identification is often limited by the poor performance of standard cultures, which may be impaired by previous antibiotic intake. Metagenomics-based approaches show promise for better identification of the pathogens that cause these infections, but they have not been evaluated in this medical context. What does this study add? Shotgun metagenomics (SM) showed higher sensitivity than 16S rRNA gene sequencing and a better ability than culture to detect anaerobic bacteria. As a result, a significant proportion of infections with bacteria, such as Pasteurella multocida or Clostridium perfringens, were detected only by SM. SM bacterial quantification enabled better detection of low amounts of bacterial DNA from macroscopically 'healthy' tissue, suggesting a subclinical infectious extension. What is the translational message? The high analytical performance of SM shown in this study should allow its future implementation for the diagnosis of necrotizing fasciitis, complementing or replacing routine methods. The large amount of data, including additional information on antimicrobial resistance, virulence profiles and metabolic adaptation of the pathogens, will improve microbiological documentation. Our results will improve our understanding of infectious pathophysiology in the future, leading to potentially better medical care.

Efficacy and satisfaction of surgical treatment for hidradenitis suppurativa.

BACKGROUND: Surgery is a radical treatment for hidradenitis suppurativa (HS) and may be considered as the only one potentially curative. OBJECTIVES: To characterize HS recurrence in patients after surgery and assess the risk factors of recurrence. METHODS: We conducted a monocentric retrospective cohort study. All consecutive patients who had surgery (January 1, 2012 to March 31, 2017) were included. We estimated the rate of recurrence of HS lesions after surgery (<1 cm from the scar), and recurrence-associated factors were analysed by univariate then multivariate logistic regression, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 75 patients [median age 31.4 years (range 16-71); 36 females], corresponding to 115 interventions were included. The Hurley score at surgery was III for 70 (60%) patients. In total, 61/115 (53%) interventions involved wide excision and 50 (43%) limited local excision. The localizations were axillary folds (n = 46; 40%), buttocks (n = 15, 13%), genital area (n = 13; 11%), perineal area (n = 12; 10%) and inguinal folds (n = 18; 16%). We observed 11 (10%) complications and 40 (35%) recurrences. On multivariate analysis, probability of recurrence was associated with only one-stage surgical closure [OR 3.2 (95% CI 1.4-7.3), P = 0.005]. Overall, 44 (52%) patients were completely satisfied and 22 (26%) partially satisfied, and most (81%) considered the surgery the best treatment. CONCLUSIONS: Hidradenitis suppurativa recurrence in our study was 35% and associated with one-stage surgical closures, but two-thirds of patients were satisfied with surgical treatment and would recommend surgery.

Persistence of treatment with biologics for patients with psoriasis: a real-world analysis of 16 545 biologic-naïve patients from the French National Health Insurance database (SNIIRAM).

BACKGROUND: Long-term clinical effectiveness of biologics in psoriasis is needed. OBJECTIVES: We aimed to assess the long-term persistence of biologics used to treat psoriasis in a real-life setting. METHODS: All adults with psoriasis having been registered in the French National Health Insurance database (SNIIRAM) between 2008 and 2016 were eligible for inclusion. Psoriasis was defined as the fulfilment of at least two prescriptions for topical formulations of a vitamin D derivative within a 2-year period. The study population comprised biologic-naïve patients, i.e. those with a first prescription of etanercept, infliximab, adalimumab or ustekinumab. Persistence of treatment with a biologic was defined as the time interval between initiation and discontinuation. RESULTS: In this nationwide population-based cohort, 16 545 out of 874 549 patients with psoriasis were biologic-naïve (mean age 48·6 years; males 57·3%, mean follow-up 3·6 years). The mean ± SD length of follow-up for biologic-naïve patients was 3·6 ± 2·4 years. There were 9988 treatment discontinuations. Kaplan-Meier survival analyses revealed a persistence rate of 61·9% for the first, 33·3% for the third and 22·6% for the fifth year. Ustekinumab had a higher persistence rate than the other biologics. This finding should be interpreted with caution, in view of differences in administration between the biologics. About 85% of patients, having discontinued their first biologic, resumed systemic treatment of some type in the following year (biologics in 85% of cases). CONCLUSIONS: Our data suggest that biologics are less effective than physicians have been led to believe in a real-life, nonselected population. Further, long-term disease control requires several courses of different biologics.

Factors associated with the choice of the first biologic in psoriasis: real-life analysis from the Psobioteq cohort.

BACKGROUND: Decision-making is a complex process. The aim of our study was to assess factors associated with the choice of the first biological treatment in patients with moderate-to-severe psoriasis. METHODS: Data on all patients included in the French prospective, observational, cohort, Psobioteq and initiating a first biologic prescription between July 2012 and July 2016 were analysed. Demographic information and clinical features were collected during routine clinical assessments by the dermatology team at the recruiting centres using a standardized case report form. The primary outcome was the nature of the first biologic treatment. Four groups were identified as follows: adalimumab, etanercept, ustekinumab and infliximab groups. Factors associated with the choice of the first biological agent were determined by a multinomial logistic regression model adjusted on year of inclusion. RESULTS: The study population included the 830 biological-naïve patients who initiated a first biological agent. The mean age was 46.6 years (±SD 13.9), and 318 patients (38.3%) were female. The most commonly prescribed biologic was adalimumab: 355 (42.8%) patients, then etanercept (n = 247, 29.8%), ustekinumab (n = 194, 23.4%) and infliximab (n = 34, 4.0%). In the multinomial logistic regression analysis, patients were significantly more likely to receive adalimumab if they had a severe psoriasis as defined by baseline PASI or if they had psoriatic arthritis compared to etanercept (aOR, 0.42; 95% CI, 0.16-1.07) and ustekinumab (aOR, 0.15; 95% CI, 0.04-0.52). Patients were significantly more likely to receive ustekinumab (aOR, 2.39; 95% CI, 1.04-5.50) if they had a positive screening for latent tuberculosis compared to adalimumab. Younger patients were also more likely to receive ustekinumab. Patients with chronic obstructive pulmonary disease were more likely to be prescribed ustekinumab or etanercept compared to adalimumab. There was a trend in favour of etanercept prescription in patients with cardiovascular comorbidities, metabolic syndrome and in patients with a history of cancer. CONCLUSION: We identified patient- and disease-related factors that have important influence on the choice of the first biological agent in clinical practice. Clinicians appear to have a holistic approach to patient characteristics when choosing a biological agent in psoriasis.

Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a clinically and immunologically heterogeneous, subepidermal, autoimmune bullous disease (AIBD), for which the long-term evolution is poorly described. OBJECTIVES: To investigate the clinical and immunological characteristics, follow-up and prognostic factors of adult idiopathic LABD. METHODS: This retrospective study, conducted in our AIBD referral centre, included adults, diagnosed between 1995 and 2012, with idiopathic LABD, defined as pure or predominant IgA deposits by direct immunofluorescence. Clinical, histological and immunological findings were collected from charts. Standard histology was systematically reviewed, and indirect immunofluorescence (IIF) on salt-split skin (SSS) and immunoblots (IBs) on amniotic membrane extracts using anti-IgA secondary antibodies were performed, when biopsies and sera obtained at diagnosis were available. Prognostic factors for complete remission (CR) were identified using univariate and multivariate analyses. RESULTS: Of the 72 patients included (median age 54 years), 60% had mucous membrane (MM) involvement. IgA IIF on SSS was positive for 21 of 35 patients tested; 15 had epidermal and dermal labellings. Immunoelectron microscopy performed on the biopsies of 31 patients labelled lamina lucida (LL) (26%), lamina densa (23%), anchoring-fibril zone (AFz) (19%) and LL+AFz (23%). Of the 34 IgA IBs, 22 were positive, mostly for LAD-1/LABD97 (44%) and full-length BP180 (33%). The median follow-up was 39 months. Overall, 24 patients (36%) achieved sustained CR, 19 (29%) relapsed and 35% had chronic disease. CR was significantly associated with age > 70 years or no MM involvement. No prognostic immunological factor was identified. CONCLUSIONS: Patients with LABD who are < 70 years old and have MM involvement are at risk for chronic evolution.

Inherited epidermolysis bullosa and squamous cell carcinoma: a systematic review of 117 cases.

BACKGROUND: Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by exacerbated skin and/or mucosal fragility and blister formation after minor mechanical trauma. Level of cleavage in the skin, clinical features with immunofluorescence antigen mapping and/or electron microscopy examination of a skin biopsy and/or gene involved, type(s) of mutation present and sometimes specific mutation(s), allow to define the EB type and subtype. This family of genodermatoses exposes patients to several complications, cutaneous squamous cell carcinoma (cSCC) being the most severe of them. OBJECTIVE: The aim of this systematic review was to document patients with EB who developed cSCC. METHODS: A systematic literature search was performed, from inception to March 2014, using Medline, Embase, Cochrane and ClinicalTrials.gov databases. Only articles published in English and French were selected. The diagnosis of EB had to be confirmed by EM and/or IFM and/or mutation analysis, while cSCC had to be confirmed by histological analysis. RESULTS: Of 167 references in the original search, 69 relevant articles were identified, representing 117 cases. cSCCs were identified in all types of EB, though predominantly in recessive dystrophic EB (RDEB) forms (81 cases (69.2 %)). The median age at diagnosis was 36 years old (interquartile range (IQR), 27-48 years and range, 6-71 years) for all forms. Of those with measurements in the literature (88 cases (75.2 %)), tumor size was greater than 2 centimeters in 52 cases (59.1 %). The histopathological characteristics were specified in 88 cases (75.2 %) and well-differentiated forms predominated (73.9 %). No conclusion could be drawn on the choice of surgical treatment or the management in advanced forms. LIMITATIONS: This study was retrospective and statistical analysis was not included due to various biases. This study design did not allow to infer prevalence, nor EB subtype risk for cSCC occurrence. CONCLUSIONS: Our study correlated with historical data shows that most of the cSCCs occurred in subjects with the RDEB subtype, however reports also show that cSCCs can present in any patients with EB. The first signs of cSCC developed at a younger age in EB patients than in non-EB patients. Interestingly, the cSCC duration, before its diagnosis, was shorter in individuals with RDEB than with junctional EB (JEB) and dominant dystrophic EB (DDEB). This study further emphasizes the importance of regular monitoring of EB patients, particularly with the RDEB subtype as they developed cSCC at a younger age.

Dermatomyositis: factors predicting relapse.

BACKGROUND: The course of dermatomyositis (DM) can be chronic with relapses, which are associated with major morbidity. OBJECTIVE: The aim of this study was to identify presentation features that predict DM relapses. METHODS: We retrospectively reviewed data of patients with DM recorded from 1990 to 2011, including muscle biopsy results. Characteristics of patients with and without relapses were compared. Hazard ratios (HRs) were estimated using a Cox model. RESULTS: We identified 34 patients, with a mean age of 46 ± 17 years (range, 18-77) and 24 (71%) women. The muscle and skin abnormalities relapsed in 21 (61%) patients. By univariate analysis, two presentation features were significantly associated with a subsequently relapsing course, namely, dysphonia [HR = 3.2 (1.2-8.5)] and greater skin lesion severity defined as a Cutaneous Disease Area Severity Index [CDASI] > 20 [HR = 3.5 (1.2-7.9)]. CONCLUSION: Dysphonia and skin lesion severity at disease onset must be recorded, as they significantly predict a relapsing disease course.

[Necrotizing fasciitis: results of a survey on management practices in French-speaking intensive care units]. / Prise en charge des dermohypodermites bactériennes nécrosantes et fasciites nécrosantes en réanimation : résultats d'une enquête de pratique francophone.

OBJECTIVES: Necrotizing fasciitis (NF) are rare and severe soft tissue infections associated with a high mortality rate. In order to assess the management of NF in French-speaking intensive care units (ICUs), we conducted a survey endorsed by the French Society of Anesthesia and Intensive Care (SFAR). STUDY DESIGN: Online self-administered survey. METHODS: A link to an online survey was sent by email to 4620 anesthesiologists and/or intensivists and was available online from January to February 2014. RESULTS: One hundred and seventy-five physicians (3.8%) who worked in 135 ICUs filled out the online survey. Among respondents, 42% reported having managed up to two patients with NF during the previous year; 59% and 72% of respondents reported not having a surgical and a medical specialist consultant, respectively. A delayed access to the operating room (OR) of more than 6hours was reported in 31% of cases and access to the OR was reported not to be routinely considered as a priority in 13% of cases. Only 17% of respondents reported that time to transfer to the OR was never a cause for delayed surgery. The main causes for delayed surgery were: delayed diagnosis (45%), delayed validation of surgical intervention (37%), and difficulty of access to the OR (8%). Finally, 83% of respondents estimated that creating dedicated multidisciplinary teams for managing NFs could lead to improving outcomes. CONCLUSION: This survey illustrates the heterogeneous management of NF in French-speaking ICUs and points out several logistical aspects that should be improved to reduce the time to the first surgical debridement.