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.

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.

[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.

With a little help from a friend: increasing HIV transduction of monocyte-derived dendritic cells with virion-like particles of SIV(MAC).

Modification of dendritic cells (DCs) is a promising avenue for gene therapy purposes, given the versatility and the multiplicity of functions of these cells. In this study, we show that preincubation of monocyte-derived DCs with low amounts of non-infectious virion-like particles derived from the simian immunodeficiency virus (SIV(MAC) VLPs) increases up to 10-fold the efficiency of transduction by HIV-1 lentiviral vectors at low multiplicity of infections yielding up to 90% of transduced cells, in the absence of alterations of DCs behavior. This effect is restricted to DCs and specified by the viral accessory protein Vpx. Thus, preincubation with empty VLPs of SIV(MAC) can be used in transduction protocols to increase the efficacy of HIV-1-mediated modification of DCs.

High levels of drug-resistant human immunodeficiency virus variants in patients exhibiting increasing CD4+ T cell counts despite virologic failure of protease inhibitor-containing antiretroviral combination therapy.

The genotypic mutations associated with indinavir resistance were analyzed in 27 patients who exhibited sustained CD4+ T cell responses to highly active antiretroviral therapy (HAART), despite virologic failure of treatment. After 12 months of HAART, 1 or 2 primary resistance mutations had occurred in 18 (66%) of the patients, and secondary mutations had accumulated in 22 (88%) of the patients. The number and patterns of mutations in the patients who exhibited discrepant responses to HAART did not differ from those observed in patients who exhibited immunologic and virologic failure to therapy. Results indicate that many patients have prolonged immunologic benefits, despite the development of virologic failure and protease inhibitor mutations. The clinical course of this group of patients calls into question the relevance of genotypic resistance and plasma human immunodeficiency virus RNA level as surrogate markers in patients receiving HAART.

Phylogenetic analyses indicate an atypical nurse-to-patient transmission of human immunodeficiency virus type 1.

A human immunodeficiency virus (HIV)-negative patient with no risk factor experienced HIV type 1 (HIV-1) primary infection 4 weeks after being hospitalized for surgery. Among the medical staff, only two night shift nurses were identified as HIV-1 seropositive. No exposure to blood was evidenced. To test the hypothesis of a possible nurse-to-patient transmission, phylogenetic analyses were conducted using two HIV-1 genomic regions (pol reverse transcriptase [RT] and env C2C4), each compared with reference strains and large local control sets (57 RT and 41 C2C4 local controls). Extensive analyses using multiple methodologies allowed us to test the robustness of phylogeny inference and to assess transmission hypotheses. Results allow us to unambiguously exclude one HIV-positive nurse and strongly suggest the other HIV-positive nurse as the source of infection of the patient.

Effect of UVB 311 nm irradiation on normal human skin.

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1+ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a+ cells and a moderate increase of HLA-DR+ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1+ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.

Prognosis of ruptured intracranial mycotic aneurysms: a review of 12 cases.

Intracranial mycotic aneurysms (IMA) occur in 1-3% of all infective endocarditis. Although spontaneous resolution was evidenced on serial angiograms in many asymptomatic cases, the prognosis, if they rupture, is reported to be worse and partly contingent on the therapeutic approach. Among 12 patients (six acute and six subacute endocarditis) with ruptured IMA, six were treated surgically and four were treated medically. Two patients died during rupture before any treatment could be started. Six patients had a sudden rupture manifested by coma, less clear consciousness seizures, hemiparesis unilateral mydriasis. CT-Scan showed intracerebral, intraventricular and subarachnoid haemorrhage. Ten angiograms showed 11 IMA. For patients with ruptured IMA, the decision for surgical treatment was made in the presence of deepening coma and extensive mass-lesion on CT-scan (one of six died in the postoperative period). Others received medical treatment (four cases: all survived) and were followed-up with serial angiographies. Of the nine patients who survived, five remained free of any disability 1-4 years later. We suggest that the prognosis of ruptured IMA (25% mortality rate) is not as bad as previously reported if surgery following angiography is performed early in the presence of deepening coma and extensive lesion.

[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.

[The role of surgery and low molecular weight heparin in the treatment of cerebral venous thrombosis. Apropos of 2 cases]. / Place de la chirurgie et des héparines de bas poids moléculaire dans le traitement des thromboses veineuses cérébrales. A propos de 2 cas.

For one case of thrombosis of sinus sagittalis superior joint haemorrhagic cerebral softening necessitates surgical draining of haemorrhagic focus grown to a true intracranial haematoma; for the another case direct low molecular weight heparin treatment obtained a mere evolution. Authors are of the opinion that early low molecular weight heparin treatment is able to avoid massive haemorrhage.

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.

[Does linear psoriasis exist? (author's transl)]. / Le psoriasis linéaire existe-t-il?

A child had both a congenital nevus unius lateris and a linear psoriasis of recent onset which first appeared localized to the nevus, and later became generalized. Histology of the psoriatic lesion overlying the nevus revealed the typical features of psoriasis and epidermolytic hyperkeratosis. Psoriasis and nevus have both disappeared with Ro 10.9359 therapy. Five similar cases of psoriasis overlying an epidermal nevus have been found in the literature. The epidermal nevus is a fertile site for the development of psoriatic lesions in a predisposed person. It is an example of the Köbner phenomenon. A wider definition of this phenomenon is suggested. The features of linear psoriasis are studied and we now believe that true linear psoriasis is not a distinct clinical entity and that previously reported cases correspond in fact to an inflammatory linear verrucous epidermal nevus (ILVEN).

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.