Treatment of moderate-to-severe psoriasis in adults: An expert consensus statement using a Delphi method to produce a decision-making algorithm.

BACKGROUND: New highly effective drugs for moderate-to-severe cutaneous psoriasis are regularly marketed, and the hierarchy of treatments thus requires frequent review. OBJECTIVES: A Delphi method was used to enable a structured expert consensus on the use of systemic treatments and phototherapy among adults with moderate-to-severe psoriasis. METHODS: The Delphi method consists in achieving a convergence of opinions among a panel of experts using several rounds of questionnaires with controlled feedback between rounds. A two-part Delphi questionnaire was administered online to French psoriasis experts. In the first part, 180 items related to the prescription of systemic treatments and phototherapy for adult patients with moderate-to-severe psoriasis were grouped into 21 sections covering different lines of treatment and different forms of cutaneous psoriasis. The experts voted on each proposal using an ordinal 7-point Likert scale. The second part comprised 11 open-ended questions about special indications for each therapeutic class. These were converted into 101 questions for subsequent rounds. Consensus was deemed to have been reached if more than 80% of the experts agreed with a given proposal. RESULTS: Three rounds of questionnaires were sequentially sent to 35 participants between November 2021 and March 2022. Thirty-three (94%) completed all three rounds. For plaque psoriasis, only methotrexate was recommended by the experts as first-line systemic treatment (89% of votes). Cyclosporin was advocated in pustular and erythrodermic psoriasis, and acitretin was suggested for hyperkeratotic and palmoplantar psoriasis. In the event of failure of or intolerance to non-biological systemic treatments, guselkumab, risankizumab, ixekizumab or secukinumab were recommended by more than 80% of the experts. Tumor Necrosis Factor (TNF) inhibitors remain useful for patients with cardiovascular risk factors. Special indications were provided for each therapeutic class (methotrexate/narrowband ultraviolet B phototherapy, psoralen/ultraviolet A phototherapy, cyclosporin, acitretin, apremilast, TNF inhibitors, interleukin (IL)-12/23 inhibitors, IL-17(R)A inhibitors, and IL-23 inhibitors). CONCLUSIONS: This expert consensus statement indicate that newly available IL-17 and IL-23 inhibitors may be favored over TNF and IL-12/23 inhibitors as first-line biologics. The Centre of Evidence of the French Society of Dermatology has drawn up a decision-making algorithm to guide clinicians in the therapeutic management of moderate-to-severe psoriasis.

Impact of patient psoriasis on partner quality of life, sexuality and empathy feelings: a study in 183 couples.

BACKGROUND: The impact of psoriasis on quality of life (QoL), sexuality and empathy requires better understanding in patient-partner relationships. OBJECTIVES: To evaluate the influence of psoriasis on partner QoL, presence of sexual dysfunction (SDy) in couples and empathy in partners of psoriasis patients. METHODS: A total of 183 adult psoriasis patients and their partners participated in this observational, cross-sectional and non-comparative study. Severity of psoriasis was measured using the Psoriasis Area and Severity Index. Patient QoL was assessed using the Dermatology Life Quality Index and the Short Form-12 (SF12). The impact of psoriasis on partner QoL was measured with the Family Pso and the SF12. Presence of SDy and empathy in partners were assessed using the Family Pso. RESULTS: Overall, 49.7% of the patients had moderate-to-severe psoriasis. Patient psoriasis severity and patient QoL were correlated with partner psychological distress. The largest QoL impairment was observed in female patients with moderate-to-severe psoriasis. The stronger QoL alteration observed in female psoriasis patients, compared to their partners, was not observed in male psoriasis patients vs. their partners. There was no relationship between partner QoL and patient age and duration of psoriasis. Most patients, but less than half of the partners, reported SDy with age being a being a significantly more important impacting factor than disease severity. Both psoriasis clinical severity and/or a significant impact on QoL were associated factors for SDy in male partners of psoriasis women, but not in female partners of psoriatic men. Reporting empathy was higher among young male partners of psoriasis patients. In both male and female partners, patient psoriasis clinical severity was not associated with empathy. CONCLUSIONS: Psoriasis impact on patient-partner QoL, sexuality and empathy should be considered more thoroughly by dermatologists when formulating treatment plans and making treatment decisions.

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.

Crossed looks on the dermatologist's position and the patient's preoccupations as to psoriasis and pregnancy: preliminary results of the PREGNAN-PSO study.

BACKGROUND: While some information on psoriasis impact on pregnancy is available, very little is known on the preoccupations of women afflicted by the disease or on the dermatologists' (D) positioning as to psoriasis and pregnancy. The 'Objectifs Peau' project demonstrated a 4.7% prevalence of psoriasis in women aged 18-45 years in France. OBJECTIVE: This project sought to further address these issues in view of a targeted action plan. METHODS: A questionnaire was made available to 361 D of different types. RESULTS: Overall, 152 D answered the questionnaire, 50.7% working in private or mixed practice and 49.3% in hospitals, with 63% females (DF) and 37% males (DM). Over the last 3 months, the mean percentage of women of child-bearing age seen by these D was 28.6%. The main issue addressed by D upon psoriasis diagnosis was the patient's wish to become pregnant in the short-term (84%), while the compatibility of drug treatment with pregnancy was the issue prioritized by patients (64%). Among DM and DF, 46% and 29% reported having been confronted with an unplanned pregnancy, with their reaction mainly dependent on the treatment taken in 66%. Regarding follow-up, 26% D declared having shared their decision-making with gynaecologists, while 56% considered the first pregnancy trimester to be the highest-risk period. Only 28% D were familiar with existing recommendations, with only 21% of them considering them appropriate. CONCLUSION: Overall, 26.2% of French psoriasis women are of child-bearing potential, in line with our dataset (28.6%). Only 56% D considered the 1st pregnancy trimester to be the highest-risk period, with only one-third familiar with existing recommendations. The gap between recommendations and actual practices must be addressed through policies that take women's preoccupations better into account.

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.

[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.

Extensor carpi ulnaris injuries in tennis players: a study of 28 cases.

Pain on the ulnar side of the wrist is common among elite tennis players. Ten years of experience has allowed identification of a pathology involving the extensor carpi ulnaris (ECU) tendon. On the basis of 28 clinical cases seen over the last five years, three clinical patterns are described: (a) acute instability of the ECU; (b) tendinopathy; (c) ECU rupture. Each of these clinical entities requires a different therapeutic approach. A review of the relevant anatomy is provided.

[The accessory soleus muscle: a report of 21 cases and a review of the literature]. / Le muscle soléaire accessoire: à propos de 21 observations et revue de la littérature.

PURPOSE OF THE STUDY: Well known to anatomy specialists, the accessory soleus muscle was first demonstrated to be involved in painful syndromes in 1965 (Dunn). This supranumerary muscle situated in front of the calcaneum can be taken for a soft tissue tumor. The purpose of this work was to report a series of 21 patients with an accessory soleus muscle and to present the characteristic features, diagnostic methods, and treatment indications and modalities. MATERIAL AND METHODS: This series included 20 patients (one symptomatic bilateral case), fourteen men and six women, mean age 25 years. Seventeen patients practiced sports and ten had had a prior operation. All patients complained of exercise-related pain. The physical examination was normal with the exception of a tumefaction, which was soft at rest and hard at triceps contraction against resistance, lying laterally to the Achilles tendon. We studied plain x-rays, ultrasound studies, computed tomographies, and electromyograms and later MRI which became the reference method to demonstrate the details of normal muscle structure. Ten patients (one bilateral case) were not particularly bothered by the supernumerary muscle. Functional treatment was given and provided patient satisfaction. For the other ten patients, who wished to continue their physical activities, two underwent fasciotomy (including our first case where fasciotomy was undertaken because a tumor was suspected) and eight underwent resection of the supranumerary muscle. RESULTS: The patients were followed for 6 to 19 years. Outcome was very good in all patients who were free of pain and had complete joint movement with symmetrical muscle force. Normal sports activities were resumed. DISCUSSION: The accessory soleus muscle is found in 10% of individuals. It is often asymptomatic. The muscle inserts on the anterior aspect of the soleus muscle or on the posterior aspect of the tibia or the muscles of the deep posterior compartment. It lies anterior to the calcaneal tendon and terminates on the calcaneal tendon or the superior or medial aspect of the calcaneus via fleshy fibers or a distinct tendon. Frequent in primates, this anatomic variant is present during embryological development. Its persistence depends on phylogenetic evolution. Among other hypotheses (exercise-induced intermittent claudication, compression of the tibial nerve, excessive tension on the nerve innervating the accessory soleus muscle), this supranumerary muscle is generally considered to be the cause of a localized compartment syndrome. Pain experienced during exercise is the only symptom regularly reported by patients. A careful examination is required to rule out another local cause. Besides tumefaction lateral to the Achilles tendon, often found bilaterally, there is no other clinical sign. Plain x-rays, ultrasound and computed tomography simply demonstrate a "mass" in front of the Achilles tendon. MRI is the examination of choice enabling confirmation of the muscle nature of the mass and ruling out the possible diagnosis of tumor. Since there is no risk of aggravation, surgical treatment can be avoided if there is no complaint. If the patient is seriously impaired, surgery can be proposed. In our opinion, complete resection of the supernumerary muscle is the safest solution and should be preferred over simple fasciotomy.

Infectious diarrhoeas: weakening of mucosa protection induced in rabbit ileal loops by a pathogenic Escherichia coli.

The histological, enzymatic, and electrolyte changes induced by a toxigenic strain of E. coli (0128B12) were studied in the rabbit. After 4 hours of contact with the bacteria, one-third of the goblet cells of the intestinal epithelium were totally degranulated, indicating an increase in the destruction of mucus and hence a weakening of mucosal protection through action of bacterial enzymes. The good histological conservation of the ileal mucosa at the end of the study period was confirmed by the stability of the disaccharidase of the glycocalyx and of the luminal surface membrane enzymes, alkaline phosphatase and leucine amino-peptidase. The observed water, sodium and bicarbonate losses were principally due to the action of the bacterial toxins on the ionic pumps of the epithelial cells.

A histological, enzymatic and water-electrolyte study of the action of smectite, a mucoprotective clay, on experimental infectious diarrhoea in the rabbit.

The histological, enzymatic and water-electrolyte modifications induced by the administration of smectite, a type of clay reputed to be mucoprotective, have been studied in the rabbit ileal mucosa during infection by saprophytic bacteria and toxigenic E. coli 0128B12. Smectite diminished the bacterial mucolysis and the destruction of the luminal surface membranes of the intestinal epithelium by pathogenic bacteria, as evidenced by the elevation of the disaccharidase and alkaline phosphatase levels. As a result of these effects, the net ion fluxes and net fluid changes favour absorption. These results could account for the mechanism of action of smectite in infectious human diarrhoea.

Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers.

STUDY OBJECTIVE: To evaluate the effect of fluoxetine on the pharmacokinetics and cardiovascular safety of cisapride at steady state in healthy men. DESIGN: Open-label, three-phase, sequential study. SETTING: Clinical research center. SUBJECTS: Twelve healthy male volunteers. INTERVENTIONS: Each subject was treated according to the following sequence: baseline; phase 1 (days 1-6): cisapride 10 mg 4 times/day; washout (days 7-13); phase 2 (days 14-44): fluoxetine 20 mg/day; and phase 3 (days 45-52): cisapride 10 mg 4 times/day (days 45-51) plus fluoxetine 20 mg/day (days 45-52). MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn and 12-lead electrocardiograms performed at specified time points after the last morning dose of cisapride in phases 1 and 3. Blood samples also were taken before morning doses on the 3rd, 4th, and 5th days of phases 1 and 3. Electrocardiograms were done at baseline and on the last day of the washout period and phase 2. Coadministration of fluoxetine significantly decreased cisapride plasma concentrations. There were no clinically significant changes in corrected QT intervals during administration of cisapride alone or with fluoxetine. Cisapride was well tolerated when administered alone or with fluoxetine. CONCLUSION: Cisapride can be administered safely to patients receiving low therapeutic dosages of fluoxetine.

An attempt to use artificial membranes to investigate cellular membrane permeation--application to nitroglycerin and isosorbide dinitrate.

The pharmacodynamic efficiency of nitroglycerin (TNG) is 3 to 4 times higher than that of isosorbide dinitrate (ISDN). In a previous work the authors have shown that this difference is partially due to the transmembrane diffusion potential of the molecules. The aim of this present study is to confirm this hypothesis by using artificial solid lipid membranes and thus to validate the method which will be used to predict the transmembrane diffusion of drugs. Two types of artificial membranes, having nearly the same liposolvent properties as the biological membrane, are tested to investigate intracellular drug penetration. These artificial membranes are fitted on the Dibbern's three phases apparatus: the Resomat 2. The results are in accordance with the data obtained on erythrocyte membranes showing that both drugs have a good transmembrane diffusibility and also that TNG presents a quicker intracellular penetration than ISDN. These results contribute to validate this method, using artificial membranes, to predict the intracellular penetration of molecules.

[Cytological study of the mode of contraceptive action of nonoxynol-9]. / Etude cytologique du mode d'action contraceptive du nonoxynol-9.

PIP: Vaginal spermicides, which were made of many different compounds prior to the 1960s, are today based on a few active principles only. Nonoxynol 9 is the most widely used of these safe and effective surfactants. Methods of evaluation of spermicides are all based on measurement of the time and dose levels necessary to achieve immobilization of sperm under specific conditions. Studies of the mode of action of nonoxynol 9 suggest that the spermicide causes major alterations of the surface membranes and in the organites. To determine whether nonoxynol 9 merely immobilizes or also kills sperm, specimens were collected from 21 donors after 3-5 days of abstinence. The sperm sample characteristics were compared with those of men of proven fertility to ensure that the sperm had fertile characteristics. 8 of the 21 donors were of proven fertility. Criteria for judging the effect of nonoxynol 9 included sperm mobility before and after nonoxynol 9 administration and percentage of live sperm before and after nonoxynol 9 administration. The technique for demonstrating whether sperm are still alive after coming in contact with nonoxynol 9 requires about 30 seconds to 1 minute for completion, so it cannot be stated that immobilization and death of the sperm are instantaneous. The quantities of nonoxynol 9 used were about 1/10 of those used in spermicide contraceptives. The dosage corresponded to about 10 mg of nonoxynol 9 for an ejaculate, while those of local contraceptives are usually 100 mg. This work demonstrated that the action of nonoxynol 9 was not limited to simple immobilization of sperm, but also involved killing them. The advice to spermicide users to avoid vaginal cleansing for several hours after intercourse should be reevaluated in light of these findings.^ieng

[Transmembrane passage of trinitrine and isosorbide dinitrate. Study of natural membranes]. / Etude du passage transmembranaire de la trinitrine et du dinitrate d'isosorbide. Etude sur membrane naturelle.

Nitroglycerin pharmacodynamic efficiency is 3 to 4 times higher than isosorbide dinitrate efficiency. Authors put forward that this difference is at least partially pertained to the transmembrane diffusion potential of the molecules. Data of this first study on red cell membranes are in accordance with this hypothesis.

[The transmembrane diffusion of trinitrine and isosorbide dinitrate. Study of artificial membranes]. / Etude du passage transmembranaire de la trinitrine et du dinitrate d'isosorbide. Etude sur membrane artificielle.

Nitroglycerin pharmacodynamic efficiency is 3 to 4 times higher than isosorbide dinitrate efficiency. Data of this study on physiological and artificial membranes point the greater nitroglycerin transmembrane diffusion, which is discussed as a possible relevant explanation.