[Use of rituximab in maintenance treatment of pemphigus: A retrospective series]. / Utilisation en pratique du rituximab en 2nde ligne et au-delà dans le traitement du pemphigus: série rétrospective.

INTRODUCTION: Rituximab (RTX), currently recommended as first-line treatment in moderate to severe pemphigus vulgaris (PV) and superficial pemphigus (PS) along with initial systemic steroids, may also be used as second-line or subsequent treatment, and this therapeutic strategy was investigated in a real-life monocentre retrospective survey. MATERIAL AND METHODS: All patients treated between January 2010 and March 2018 with RTX as second-line or subsequent treatment for moderate to severe PV or PS and followed for at least one year were included. The main objective was to evaluate rates and times of complete clinical remission (CCR) after a first course of RTX. The secondary objectives consisted mainly of treatment safety, and frequency and time to relapse after the initial CCR. RESULTS: The 24 patients selected received on average 2 cycles of RTX (i.e. 24 initial cycles and 24 additional cycles in all) over a mean follow-up period of 45 months. 18/24 (75%) patients achieved initial CCR within a mean 7.7 months. Despite at least one relapse in 13/18 initially responding patients regardless of relapse time, 59% (14/24) and 33% (8/24) were either in CCR and off treatment, or in partial remission, whether treated or untreated, according to the latest patient news, with an overall response rate of 92%. Safety was fair in these fragile patients. DISCUSSION AND CONCLUSION: This survey of the practical use of RTX confirms its interest in moderate to severe pemphigus as a second-line or subsequent treatment, a situation that probably remains relevant even if this molecule is increasingly used as first-line therapy.

Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation.

BACKGROUND: Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise. OBJECTIVES: To describe the dermatological manifestations of NS, compare them with the literature findings, and test for dermatological phenotype-genotype correlations with or without the presence of PTPN11 mutations. METHODS: We performed a large 4-year, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and café-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations. CONCLUSIONS: The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.

Biological treatments for paediatric psoriasis : a retrospective observational study on biological drug survival in daily practice in childhood psoriasis.

BACKGROUND: Three biotherapies - etanercept, adalimumab and ustekinumab - are licensed in childhood psoriasis. The few data available on their efficacy and tolerance are mainly derived from industry trials. However, biological drug survival impacts long-term performance in real-life settings. OBJECTIVE: The objective of this study was to evaluate the survival rates of biological therapies in children with psoriasis in real-life conditions. Secondary objectives were to evaluate the factors associated with the choice of the biological therapy and to report severe adverse events. MATERIALS AND METHODS: This study was an observational retrospective study. Data were extracted from the clinical records of 134 children. Kaplan-Meier estimates were used to analyse drug survival overall and in subgroups of plaque psoriasis, bio-naïve and non-naïve patients. RESULTS: We analysed 184 treatment courses: 70 with etanercept, 68 with adalimumab and 46 with ustekinumab. Factors associated with the choice of first-line biological agent were age at initiation (younger for adalimumab, P < 0.0001), age at onset of psoriasis (younger for adalimumab and etanercept, P = 0.03) and baseline Psoriasis Assessment Severity Index and Physician global assessment (both higher for adalimumab, P < 0.001). Drug survival rates were higher for ustekinumab than for adalimumab and etanercept (P < 0.0001) for all treatment and all psoriasis types, plaque-type psoriasis (P = 0.0003), patients naïve for biological agents (P = 0.0007) and non-naïve patients (P = 0.007). We reported eight serious adverse events (SAEs): severe infections (n = 3), significant weight gain (n = 2), psoriasis flare (n = 1) and malaise (n = 1). Biological therapy was discontinued in three children (one with psoriasis flare and two with weight gain). Only the two cases of weight gain resulted in an unfavourable outcome. CONCLUSIONS: Our real-life comparative study found that ustekinumab had the best drug survival outcome. The profile of SAEs in children was comparable to that in adults. These results will assist dermatologists in the decision-making process when choosing treatment options for children with psoriasis in daily practice.

Methotrexate efficacy and tolerance in plaque psoriasis. A prospective real-life multicentre study in France.

BACKGROUND: Methotrexate (MTX) is a major systemic treatment for moderate to severe plaque psoriasis. A randomized trial has recently been published evaluating a single weekly dosage (17.5mg), but few prospective real-life data are available. The main objective of this study was to prospectively evaluate the efficacy of MTX in real-life. The secondary objectives were to evaluate predictive parameters for treatment efficacy and the frequency of adverse events. PATIENTS AND METHODS: A prospective cohort involving consecutive at in 25 centres belonging to GEM RESOPSO included all adults with plaque psoriasis in whom MTX treatment was initiated. The efficacy criterion was achievement of PASI 75 at week (W) 12/16. The impact of demographic data, psoriasis characteristics (duration, topography, rheumatism), dosage (W12/16 dosage, cumulative dose after 4 weeks), and mode of administration (subcutaneous vs. oral, concomitant use of folic acid) on efficacy was evaluated. Intention-to-treat (ITT),per protocol (PP), and multivariate analyses were performed. RESULTS: Two hundred and fifty-six patients (F/M: 105/151; mean age: 45.0 years; rheumatism: 12.6%) with plaque psoriasis were included. 99 patients were not analysed at W12/16 (16 because of inefficacy, 16 because of intolerance, 56 were lost to follow-up or had data missing). PASI 75 was achieved in 98 patients, with efficacy of 38.3% in the ITT analysis and 58.3% in the PP analysis. In the ITT analysis, absence of previous use of cyclosporine (P=0.01) and a cumulative dose of MTX>60mg after 4 weeks (P<0.0001) were associated with higher PASI 75 rates. In the PP analysis, only absence of previous use of cyclosporine (P=0.0009) was associated with a better PASI 75 results. There was no association between PASI 75 and patient characteristics (including body mass index), clinical aspects of psoriasis, route of administration, combination with folic acid, or W12/16 dose. Adverse events were reported by 34.8% of patients. These consisted mainly of digestive disorders (nausea, abdominal pain), asthenia and moderate hepatic cytolysis. The frequency of adverse events was correlated with methotrexate dosage. DISCUSSION: The efficacy of MTX in plaque psoriasis in this real-life study of 256 patients is consistent with the data in the literature, including the recently published randomized trial (41% PASI 75). This rate was unaffected by patient weight, route of administration and combined use of folic acid. Absence of previous use of cyclosporine appears to be associated with better efficacy although there is no clear explanation for this. The initial dosage (high dose in the first month) appears to be associated with superior efficacy for W12/W16.

Distinctive cutaneous and systemic features associated with specific antimyositis antibodies in adults with dermatomyositis: a prospective multicentric study of 117 patients.

BACKGROUND: Identification of myositis-specific autoantibodies (MSAs) for dermatomyositis (DM) could allow the characterization of an antibody-associated clinical phenotype. OBJECTIVE: We sought to define the clinical phenotype of DM and the risk of cancer, interstitial lung disease (ILD) and calcinosis based on MSA. METHODS: A 3.5-year multicentre prospective study of adult DM patients was conducted to determine the clinical phenotype associated with MSAs and the presence of cancer, ILD and calcinosis. RESULTS: MSAs were detected in 47.1% of 117 included patients. Patients with antimelanoma differentiation-associated protein-5 antibodies (13.7%) had significantly more palmar violaceous macules/papules [odds ratio (OR) 9.9], mechanic's hands (OR 8), cutaneous necrosis (OR 3.2), articular involvement (OR 15.2) and a higher risk of ILD (OR 25.3). Patients with antitranscriptional intermediary factor-1 antibodies (11.1%), antinuclear matrix protein-2 antibodies (6.8%) and antiaminoacyl-transfer RNA synthetase (5.1%) had, respectively, significantly more poikiloderma (OR 5.9), calcinosis (OR 9.8) and articular involvement (OR 15.2). Cutaneous necrosis was the only clinical manifestation significantly associated with cancer (OR 3.1). CONCLUSION: Recognition of the adult DM phenotype associated with MSAs would allow more accurate appraisal of the risk of cancer, ILD and calcinosis.

[Misdiagnosis of hidradenitis suppurativa continues to be a major issue. The R-ENS Verneuil study]. / Errance médicale des patients atteints d'hidradénite suppurée : un problème majeur et persistant. Étude « R-ENS Verneuil ¼.

OBJECTIVE: To provide physicians with an understanding of the factors behind significant delays in the diagnosis of hidradenitis suppurativa (HS) in France. PATIENTS AND METHODS: This prospective multicentre national study conducted from October 2015 to March 2016 included all patients consulting for HS. Patient data were collected by means of a standardized questionnaire. Univariate and multivariate analyses were conducted to collect factors associated with a significant time to diagnosis of at least 5.5years, defined as the period between the onset of initial clinical signs and the time of formal diagnosis. RESULTS: The 16 participating centres enrolled 312 patients (62% women), of average age 35years. The average age at onset of HS was 22years. Before formal diagnosis by a dermatologist (64% of cases), 170 (54%), 114 (37%) and 45 (15%) patients had previously consulted at least 3, 5 and 10 general physicians, respectively. The average time between the initial clinical signs of HS, the first dermatology visit and the definitive diagnosis was 6.2 and 8.4 years, respectively. Active smoking (OR adjusted 1.85; P=0.027) and disease onset at a younger age (adjusted OR 0.92; P<0.001) were both associated with significant delays in diagnosis. CONCLUSION: These results emphasized misdiagnosis among HS patients but did not evidence any association between either sociodemographic or economic characteristics and the existence of significant times to diagnosis.

[Psoriatic patients: Analysis of patients dissatisfied with their management]. / Patients atteints de psoriasis : analyse de la population insatisfaite de sa prise en charge.

BACKGROUND: The French are frequently regarded as grouchy. In a recent study, we observed a high proportion of patients initially consulting for psoriasis because they were dissatisfied with their previous therapy. We analyzed the characteristics of these patients. PATIENTS AND METHODS: This was a cross-sectional multicenter study in 40 centers belonging to the ResoPso (psoriasis treatment network) multicenter study group, with consecutive inclusions over a period of 11months in 2014. All adults (age>18 years) consulting for the first time for psoriasis at a center were included in the study. RESULTS: Among patients, 1205 were included, of whom 249 (20.3%) were consulting because of their dissatisfaction with treatment. In the univariate analysis, these patients were younger (P=0.02) and presented psoriasis that had begun earlier in life (P<0.0001). It consisted mostly of generalized plaque psoriasis (P=0.047) and more severe forms of psoriasis (PASI and/or DLQI score>10, P<0.02). There were fewer cases of psoriatic arthritis (P=0.01). The "dissatisfied" patients reported significantly more frequent use of topical treatments (P<0.0001) and alternative medicines (P=0.02), and more infrequent use of biologics (P=0.006) as well as longer treatment periods (P=0.0005). They consulted at hospitals (P=0.01) and had previously seen more GPs and dermatologists (P≤0.0008). There was no impact of gender on the dissatisfaction profile by either comorbidities (metabolic, blood pressure, alcohol and tobacco consumption, and depression), or socio-economic data. In the multivariate analysis, DLQI>10 (P=0.01; 95% CI: 1.01-1.07) and longer duration of care (P=0.004; 95% CI: 1.23-2.99) were associated with dissatisfaction. CONCLUSION: Twenty percent of our psoriatic patients seem dissatisfied with their treatment. It is difficult to draw a specific demographic and socioeconomic profile of dissatisfied patients. Only disease severity and possibly inadequate treatment at the initial consultation are associated with patient dissatisfaction. Explanations related to the individual patients and doctors may be proposed. Finally, while the French may be considered grouchy, the frequency of patient dissatisfaction seen in our study does not appear to be any greater than that observed in other countries.

Psoriasis in the elderly: epidemiological and clinical aspects, and evaluation of patients with very late onset psoriasis.

BACKGROUND: Age of the patients and age of onset of psoriasis may have an impact on the disease. There is little information about psoriasis in elderly patients. OBJECTIVE: We evaluated epidemiological, clinical aspects, comorbidities and treatments of psoriasis in the elderly (>70 years) patients, and in patients with very late onset psoriasis (onset ≥ 70 years). METHODS: This observational multicentre non-interventional study of adults with psoriasis was conducted in 29 departments of dermatology in France. A total of 2210 adults with psoriasis were included. RESULTS: A total of 212 (9.5%) patients were elderly. This group had a higher frequency of females (P = 0.005), a later onset of the disease (P < 0.0001), a lower frequency of familial (P < 0.0001) and plaque psoriasis (P < 0.0001), but higher frequency of guttate and inverse psoriasis (P ≤ 0.005). Hypertension, diabetes, dyslipidaemia, and major cardiovascular events (MACE) were more frequent in this group (P < 0.0001), but not tobacco (P < 0.0001). Systemic and biological therapies were used less frequently in the elderly group (P < 0.0001). Fifty-eight (2.7%) patients had late onset psoriasis. Patients with very late onset psoriasis were more frequently women (P = 0.02) and older (P < 0.0001), among elderly group. They had significantly less frequently familial (P < 0.0001) and plaque psoriasis (P < 0.0001), and were less often on systemic treatment including biological. Frequencies of comorbidities were not statically different but patients with 'early' onset psoriasis have a tendency (P < 0.5) to have higher frequencies of obesity, diabetes, dyslipidaemia, hypertension and MACE. CONCLUSION: This study highlights phenotypic features of psoriasis in elderly and in very late onset psoriasis. The management of these fragile patients remains poorly codified and needs further investigation.

[Terra firma-forme dermatosis]. / Dermatose « en terre sèche ¼ (« terra firma-forme ¼).

BACKGROUND: Terra firma-forme (i.e. resembling dry earth) is a condition chiefly affecting children wrongly considered as dermatosis arising out of negligence and inadequate corporal hygiene. It is in fact an acquired and asymptomatic grey-brown hyperpigmentation of the skin that persists despite normal washing with soap and water, but which subsides on rubbing with isopropyl alcohol 70%. Herein we report 10 new cases of this disorder. OBSERVATIONS: Ten patients aged between 7 months in 17 years were seen for acquired macular skin pigmentation, either brown or grey, fragmented and confluent. In six patients, this abnormality was the main reason for the consultation, generally on aesthetic grounds, and more rarely for diagnosis or suspicion of acanthosis nigricans. In all cases, questioning revealed normal hygiene measures. The condition comprised macular or acquired papular pigmentation, either brown or grey, of bilateral and symmetrical disposition and electively affecting the neck, trunk and retro-malleolar area of the ankles. Clinical examination together with a test involving rubbing with isopropyl alcohol 70° confirmed the diagnosis, revealing healthy underlying skin. DISCUSSION: Terra firma-forme dermatosis is frequently seen in clinical practice but is largely ignored in the French literature, possibly because of relevant indifference towards the condition. It affects both sexes equally, with no predilection for age or ethnicity, although it is classically seen to a greater extent during adolescence. Diagnosis of the condition, which is easily made thanks to the hyperpigmentation of dirty brown appearance on the neck and the ankles in particular, should not mislead the practitioner into blaming patients for supposedly deficient body hygiene. Knowledge of this form of dermatosis is useful because of its potentially harmful aesthetic and social effects, despite the ease of treatment by insistent rubbing of the affected areas with medical alcohol or ether. Early recognition also avoids pointless additional investigations associated with differential diagnosis in relation to various other acquired or hereditary dermatoses involving brown or grey pigmentation.

[Multiple familial "eruptive" dermatofibromas]. / Dermatofibromes multiples « éruptifs ¼ familiaux.

BACKGROUND: Multiple eruptive dermatofibromas (DF) are rare and frequently associated with immune and neoplastic diseases. There have also been reports of rare familial cases. Herein we report a new such case. PATIENTS AND METHODS: A 79-year-old woman and her 37-year-old daughter were seen for disseminated DF over a period of several decades, from adolescence onwards. Neither had any history of diseases or treatments normally associated with multiple DF. History-taking revealed similar lesions in other family members. DISCUSSION: DF are common benign cutaneous tumours, generally seen on the lower limbs of young or middle-aged women. These lesions occur either in isolation or are relatively few. Multiple or so-called eruptive DF, defined by the presence of more than 15 lesions in a single patient, is rare and is associated in 60% of cases with autoimmune diseases, HIV infection, neoplastic disease or immunosuppressant therapy. Familial forms such as those described herein are extremely rare.

[Intravascular B-cell lymphoma with febrile inflammatory lymphoedema of the lower limbs and lower back]. / Lymphome B intravasculaire à type de lymphoedème inflammatoire fébrile des membres inférieurs et des lombes.

BACKGROUND: Intravascular lymphomas are diffuse large-cell lymphomas belonging to a group of high-grade non-Hodgkin's lymphomas and are generally of phenotype B. They are rare and carry a severe prognosis. Clinical polymorphism is dominated by neurological and cutaneous involvement. PATIENTS AND METHODS: We report the case of an 80-year-old woman with cutaneous intravascular B-cell lymphoma as revealed by an isolated episode of febrile bilateral inflammatory lymphoedema. Following combined chemotherapy with rituximab and mini-CHOP (cyclophosphamide, adriamycin, oncovin and prednisone), complete remission was obtained rapidly, with no relapse at two years. DISCUSSION: Diagnosis of these tumours is rendered difficult by the clinical polymorphism and multifocal nature of lymphocytic proliferations. In the present case, diagnosis was based on histology results since presentation of the disease in the form of bilateral inflammatory oedema of the lower limbs is not sufficient to establish lymphoma. Combined rituximab and polychemotherapy comprising a CHOP regimen appears to yield the best results.