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.

[Long term persistence of yellow fever neutralising antibodies in elderly persons]. / Persistance à long terme des anticorps neutralisants de la fièvre jaune chez les personnes âgées de 60 ans et plus.

The activity of the yellow fever virus is reemerging in areas without recent transmission history, such as northern Argentina and Paraguay, and persists in an epidemic mode in other countries in Africa and Latin America. Thus more and more travelers are at risk of being exposed to this disease. The population is becoming older, sometimes suffering from multiple pathologies. Moreover, the risk of serious adverse events associated with live-attenuated YF17D vaccine, such as multiple organ failure (YEL-AVD), reaches 1/50,000 vaccines in people over 65 versus 1/200,000 in the general population. We analyzed, in a retrospective study, the results of neutralizing antibody titers against yellow fever in people aged 60 and older, who had been previously vaccinated against yellow fever and had visited the International Vaccination Centre of the Institut Pasteur between January 2005 and February 2009. In this population of 84 persons (median age 69 years), the date of the last vaccination was always more than 10 years: it was precisely known in 68 subjects and alleged in 16 subjects. The median time since the previous vaccination was 14 years, with a maximum of 60 years. The indications of serology were: immunosuppressive therapy (19% of cases), cancer (32%), hemopathy (10.7%), HIV infection (3.6%), chronic hepatitis/chronic renal failure/dialysis (2.4%), autoimmune diseases (2.4%), and in 29.8% of cases, age alone was the indication of serology. The antibody titer was at a protective level in 95.2% of cases. The four individuals with negative serology had no formal documented proof of a previous vaccination against yellow fever. This serological study was able to show a persistent protective antibody titer, after a previous vaccination, even going back 60 years, allowing patients to travel in a yellow-fever endemic area despite a contraindication, and without requiring any vaccine booster.

[The relevance of diagnostic criteria for latent tuberculosis before initiation of TNF-alpha inhibitors in psoriasis patients]. / Pertinence des critères diagnostiques de tuberculose latente avant traitement du psoriasis par anti-TNF-alpha.

BACKGROUND: Initiation of anti-TNF-alpha therapy requires prior screening for and treatment of tuberculosis. Diagnosis of relating to tuberculosis is based primarily on measurement of the papule induced by intradermal reaction to tuberculin (IDR). In this article, we discuss the validity of this criterion and the potential consequences of its use in relation to 15 patients. PATIENTS AND METHODS: This was a retrospective case study of patients presenting psoriasis and eligible for antibiotic therapy in whom latent tuberculosis was diagnosed and who received combined prophylactic antitubercular treatment for three months. All patients underwent thorough questioning and clinical examination, chest x-ray and QuantiFERON (QTF) testing, and all except one were tested for IDR. RESULTS: Thirteen patients were considered carriers of latent tuberculosis based on IDR greater than 5 mm, and on positive QTF for two others, one of whom had a documented history of primary tubercular infection. Six of these 15 patients (40%) developed hepatic cytolysis ascribable to their antitubercular treatment. DISCUSSION: Analysis of the respective characteristics of the IDR and QTF tests showed that only five of the 15 patients in our study were in fact presenting authentic latent tuberculosis, thereby suggesting that the diagnostic criteria for latent tuberculosis recommended by the French Medicines Agency (AFSSAPS), which are based solely on the size of the papule arising from IDR, are unsuitable for patients with psoriasis pending anti-TNF therapy. In our view, screening for latent tuberculosis in this patient population should involve both IDR for its sensitivity and QTF for its specificity, thereby avoiding overdiagnosis of tuberculosis leading to pointless exposure of patients to the risk of hepatic toxicity associated with antitubercular medication. CONCLUSION: We strongly recommend a change in the recommendations for prevention of tuberculosis by antibiotic therapy in patients with psoriasis, and that the review panels should include at least one dermatologist.

[Long-term seroprotection against Japanese encephalitis using an inactivated vaccine (Jevax)]. / Séroprotection à long terme avec le vaccin inactivé contre l'encéphalite japonaise (Jevax).

Japanese encephalitis vaccine (Jevax) is an inactivated vaccine using the Nakayama viral strain. Until 2007, Jevax was the only Japanese encephalitis vaccine available in France but the duration of seroprotection after vaccination and exact timing of booster injections was unclear for travelers from non-endemic areas. The purpose of this report is to describe the results of a retrospective study in which neutralizing antibody levels were measured in 71 subjects previously vaccinated with Jevax. All subjects underwent testing at the Pasteur Institute Medical Center as part of preparation for humanitarian missions to endemic Japanese encephalitis areas in 2005-2006. A neutralizing antibody level greater than or equal to 20 was considered as protective. Findings showed that 49 of the 71 subjects (69%) still had protective antibody levels at a median of 4 years after the last Jevax immunization. In multivariate analysis, the only factor correlated with long-term seroprotection was the total number of vaccinations received. Based on these findings, it was concluded that long-term seroprotection after Jevax vaccination requires repeated booster injections even in subjects frequently exposed to the virus. No correlation was found between seroprotection and the interval between the booster injections.

SIVMAC Vpx improves the transduction of dendritic cells with nonintegrative HIV-1-derived vectors.

Lentiviral vector (LV)-mediated gene therapy bears an intrinsic risk of insertional mutagenesis following integration into the host genome. Nonintegrative LVs may offer an alternative avenue at least in nondividing cells where episomal viral DNA persists stably. Owing to their central role in immune system functions, differentiated dendritic cells (DCs) offer an interesting cell target for these vectors. We have previously described that the transduction of DCs with wild-type HIV-1-derived vectors can be considerably improved by providing DCs with noninfectious virion-like particles (VLPs) carrying Vpx (Vpx-VLPs), a nonstructural protein coded by members of the SIV(SM)/HIV-2 lineage that removes a specific restriction to lentiviral infection in these cells. Here, we describe that the transduction efficiency of DCs with nonintegrative HIV-1 vectors can also be improved via Vpx-VLPs that promote the accumulation of complete and episomal viral DNA. In this setting, Vpx increases both the number of transduced cells and the levels of transgene expression. Thus, these results describe a simple procedure by which transduction of differentiated DCs can be achieved at low viral inputs with safer LVs to improve both the number of transduced cells and the levels of transgene expression.

High-concentration topical capsaicin in the management of refractory neuropathic pain in patients with neurofibromatosis type 1: a case series.

AIM: The aim of this case series was to report the use of 8% topical capsaicin patch (marketed under the trade name Qutenza®) a in the management of refractory neuropathic pain (NP) in adult patients with type 1 neurofibromatosis (NF1). METHODS: Capsaicin has been suggested for NF1 patients suffering from refractory peripheral NP despite several years of analgesic treatments. The patch was applied for 60 minutes on the painful area, with tolerability control (blood pressure, intensity of pain and dermal reaction). The evaluation was done at the beginning of treatment and during the 2 months following the first treatment (phone calls at weeks 1, 2, 4 and 8). The primary efficacy criterion was the response rate: a patient was considered to be responding if he or she reported an average relief ≥30% at the time of the follow-up calls. The secondary criteria were: interference scores (QCD), Patient Global Impression of Change (PGIC) and overall treatment satisfaction, self-reported by the patient. RESULTS: Eight patients (5 females/3 males, 41.8 ± 8.2 years of age) received a first treatment with capsaicin. Patients had pre-existing pain for 6.6 years (±6.0) and were currently receiving an average of 6.1 (±3.9) different analgesics. The response rate was 37.5%. The three responders felt globally improved and satisfied, with the improvement in overall condition as interference scores decreased. Apart from the expected local reactions, the treatment was not accompanied by systemic side effects. CONCLUSIONS: As suggested in this case series, capsaicin provided pain relief in certain NF1 patients with resistant NP. The response rate is that expected in multi-line refractory NP. A significant benefit on the overall condition of some patients was observed. In addition, this topical treatment is administered every 3 months without systemic effects. This study is limited by the small number of patients, but was intended to describe a new and well tolerated alternative treatment.

Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) can relieve neuropathic pain when applied at high frequency (HF: 5-20 Hz) over the primary motor cortex (M1), contralateral to pain side. In most studies, rTMS is delivered over the hand motor hot spot (hMHS), whatever pain location. Navigation systems have been developed to guide rTMS targeting, but their value to improve rTMS efficacy remains to be demonstrated. OBJECTIVE: To compare the analgesic efficacy of HF-rTMS targeting the hMHS (non-navigated procedure) or the M1 representation of the pain region (navigated procedure). METHODS: The analgesic effect of a single session of 10 Hz-rTMS of M1 was assessed in 66 patients with neuropathic pain of various causes and locations, according to three conditions: sham or active non-navigated rTMS of the hMHS and active navigated rTMS of the pain region. RESULTS: Pain was relieved by both active rTMS conditions, and not by sham. Pain location influenced the results: upper or lower limb pain was significantly relieved, but not facial or hemibody pain. Pain relief lasted 1 week only after navigated rTMS, compared to sham. CONCLUSION: Navigation may improve HF-rTMS efficacy in patients with limb pain, whereas targeting remains to be optimized for more diffuse or facial pain. WHAT DOES THIS STUDY ADD?: To produce analgesic effects, HF-rTMS should be applied over the precentral cortex contralaterally to the painful side. Although the hMHS is the target normally chosen for stimulation, the optimal target has not been defined yet. Neuronavigational methods have been recently developed; they allow the integration of MRI data and are thought to improve rTMS efficacy.

Infarction in the anterior rostral cerebellum (the territory of the lateral branch of the superior cerebellar artery).

We report 9 patients with an isolated infarct of the anterior part of the rostral cerebellum, ie, the territory of the lateral branch of the superior cerebellar artery. Clinicoanatomic correlations are based on CT, MRI, or both in 8 patients and on pathologic data in the ninth. The main clinical features were ipsilateral dysmetria and axial lateropulsion, dysarthria, and unsteadiness. In 1 patient, the clinical presentation mimicked a lacunar stroke (dysarthria and clumsy hand syndrome). There were no edematous cerebellar infarcts with signs of brainstem compression, and all patients spontaneously improved without significant sequellae. Angiography in 2 patients and pathologic examination of arteries in 1 patient disclosed no occlusion in the vertebrobasilar system. Six patients had a cardiac source of emboli. In conclusion, infarcts of the anterior part of the rostral cerebellum can be regarded as a benign condition in which there is, frequently, a cardiac source of emboli.

A human immunodeficiency virus Env inducible transcription system to examine consequences of gp120 expression.

According to several studies, the HIV-1 envelope gp120 protein and the co-receptor CXCR4 play an essential role in HIV-1 induced cell toxicity. Characterisation of the CD4-independent m7NDK isolate provided the opportunity of studying the effects of direct interactions between m7NDK gp120 and CXCR4. Therefore, an inducible expression system was designed enabling synthesis of HIV-1 Env proteins upon doxycycline induction. Analysis of the expression of the env gene of the m7NDK HIV-1 isolate revealed, unexpectedly, that even long-term expression of m7NDK gp120 did not result in cytotoxycity in CXCR4-positive or -negative cell lines. This is the first report of a CD4-independent HIV-1-protein inducible expression regulated through the Tet-On system and by an alternative splicing. Env inducible expression cell lines could constitute a useful cellular tool to undertake analysis of HIV Env protein expression.

Experimental production of antibodies against stratum corneum keratin polypeptides.

Anti-keratin polypeptide sera (K.P.S) were obtained by immunizing guinea pigs with fibrous proteins from stratum corneum, which were acquired from normal human epidermis by m eans of S.D.S. polyacrylamide gel electrophoresis. After absorption with red blood cells and liver powder the sera were tested by indirect immunofluorescence technique on different substrates. Antibodies against polypeptides P1 and P2 of M.W. 67,000 and 62,000 dalton, respectively, were directed toward cytoplasmic Ag of keratinocytes of spinous and graunular layer of normal human and rabbit epidermis. No labeling could be detected in the basal cell layer. This finding is in favor of various differentiation stages of the keratinizing cells. P3 of M.W. 53,000 dalton induced low titre anibodies which labelled the whole epidermis, including the basal cell layer. The fourth polypeptide of M.W. 49,000 dalton seemed not to be immunogenic in such experiences. In tumors, such as basal cell carcinom,a squamous cell carcinoma, and warts, the expression of keratin antigens is markedly diminished. No analogy could be drawn between experimental keratin polypeptide antibodies and the human epidermal cytoplasmic antibodies which were detected in some patient sera.

Magnetic resonance imaging in the exploration of dissection of the internal carotid artery.

Five patients with recent spontaneous or post-traumatic dissection of the internal carotid artery (ICA) were explored by magnetic resonance imaging (MRI), using T1-weighted axial sections in all cases. In four patients examined during the subacute phase (after 7 days) the diagnosis of ICA dissection was strongly suspected on the association of a very high intensity signal produced by the parietal haematoma with a contiguous signal void area corresponding to the lumen of the ICA. A control MRI examination performed in two patients 2 months after the onset of dissection showed that it had regressed and that the carotid arteries were patent, which was confirmed by angiography. In the fifth patient MRI provided evidence for the evolution of a post-traumatic dissection towards thrombosis. The MRI image of carotid dissection at the subacute phase seems to be characteristic. MRI is also useful to follow up dissections under treatment and to postpone angiography. The latter, however, remains necessary to investigate for associated arterial dysplasia and to evaluate the sequelae of dissection.

[Real information needs of the traveller before his departure. Results of a survey by questionnaire]. / Les besoins réels en information du voyageur avant son départ. Résultats d'une enquête par questionnaire. Société française de la Médecine des Voyages.

This study is based upon 727 questionnaires completed by French travellers 10 days after intercontinental travel. The response rate was 40%. Two out of 5 travellers had generally mild health problems: fever (12%), diarrhoea (36%). Forty-six of them took drugs, which they had brought with them during their travel. Ten per cent had a satisfactory visit to a local physician. Medical informations given before departure appears to be sufficient, useful and relevant in more than 90% of cases. The traveller would like to receive them from his own physician or from vaccination centers. Other informations as insurance, assistance, administration, finances, appeared to have been incorrectly perceived by 20% of the travellers. The travel agent is the one who should provide adequate information. The traveller, in general, plans to do more travelling for his own well being if not for his work. Would not the bigger risk for him be "not to travel at all".

[2 rare neuro-ophthalmologic complications of long-term treatment with lithium salts]. / Deux complications neuro-ophtalmologiques rares d'un traitement au long cours par les sels de lithium.

We describe two patients with unusual neuro-ophthalmologic complications during long-term therapy with lithium carbonate given for bipolar affective disorder, "benign" intracranial hypertension in one, and downbeat nystagmus, with oscillopsia in the other. A review of the literature is proposed. Though rare, such neuro-ophthalmologic manifestations are worth being recognised since they usually disappear with cessation--when possible--of lithium therapy.