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.

[Children with psoriasis in secondary care: Clinical aspects and comorbidities diverge from the generally published data]. / Psoriasis de l'enfant vu en milieu libéral : les aspects cliniques et épidémiologiques diffèrent des données habituellement publiées.

BACKGROUND: Psoriasis affects 0.2-0.7 % of children and is associated with obesity. Published studies have been conducted in hospital settings (tertiary care). The PsoLib study evaluated childhood psoriasis in private practice (secondary care) in terms of epidemiology, clinical aspects and comorbidities. PATIENTS AND METHODS: This was a non-interventional, cross-sectional, multicenter study of children with psoriasis performed by 41 dermatologists working in private practice. The clinical and therapeutic aspects and comorbidities were systemically evaluated. We compared data to the χ-Psocar study performed in hospitals using the same methodology. RESULTS: In all, 207 children (girls: 60.4 %; mean age: 10.5±4.2 years) were included. Scalp psoriasis (40.6 %) was the most frequent clinical type, while plaque psoriasis represented 26 % of cases. Nail, tongue, and arthritic involvement were rare. Less than 1 % of children suffered from hypertension, diabetes or dyslipidemia, but 16.4 % were overweight and 7.0 % were obese. Severity (PG≥4 at peak) was associated with excess weight (P=0.01). CONCLUSION: Scalp psoriasis is the most frequent clinical type of psoriasis in childhood. Comorbidities and extracutaneous localization are rare. Even in private practice, the severity of the disease is associated with excess weight.

[Congenital erythropoeietic porphyria treated by haematopoietic stem cell allograft]. / Porphyrie érythropoïétique congénitale traitée par allogreffe de cellules souches hématopoïétiques.

BACKGROUND: Congenital erythropoietic porphyria (CEP) is a genodermatosis associated uroporphyrinogen III synthase deficit that results in porphyrin accumulation in various organs, particularly the skin. It is the most severe form of porphyria associated with haemolytic anaemia and cutaneous phototoxicity. We report a severe case of CEP treated by allogeneic bone marrow transplantation. CASE REPORT: A one-year-old child presented erythrodontia and scarring on exposed areas. The diagnosis of CEP was confirmed by the decline of uroporphyrinogen III synthase activity. Demonstration of p.Cys73Arg mutation confirmed the severity of the disease. Allogeneic bone marrow transplantation resulted in persistent resolution of clinical signs 25 months after grafting. DISCUSSION: Symptomatic treatment is ineffective in this serious disease associated with early mortality. 11 of the 13 patients treated by allogeneic hematopoietic stem cell graft, including our patient, continued to be asymptomatic an average of seven years after transplantation. CONCLUSION: This new case confirms the role of allogeneic hematopoietic stem cell grafting in the treatment of congenital erythropoietic porphyria.

Multifocal aggressive squamous cell carcinomas induced by prolonged voriconazole therapy: a case report.

Voriconazole is a treatment for severe fungal infections. Prolonged voriconazole therapy may induce skin reactions, with 1% of severe photosensitivity accidents. Recently the imputability of voriconazole in skin carcinogenesis has been suggested. This report concerns a 55-year-old man suffering from pulmonary aspergillosis who presented a phototoxic reaction a few months after introduction of voriconazole, followed by multiple squamous cell carcinomas of sun-exposed skin areas. After voriconazole discontinuation, no new carcinoma was observed. The detection of EBV and HPV in skin lesions was negative. Exploration of gene mutations involved in skin carcinogenesis showed two variants of the MICR gene. The occurrence of multiple, recurrent, aggressive squamous cell carcinomas is rare with voriconazole, but its imputability is strongly suggested. A plausible hypothesis is that several factors including voriconazole uptake, immunosuppression, and genetic background could explain the phenotype of fast-developing skin carcinomas. Voriconazole therapy should be accompanied by stringent photoprotection and skin monitoring.

Alkaloids of Datura ferox from Argentina.

Chromatographic procedures (HPLC, GC-MS) are outlined in this paper for the analysis of alkaloids in poisonous Datura ferox seeds of Argentina, from which previously only quantitative analysis for scopolamine was known. Five additional tropane alkaloids are now identified as 3 alpha-tigloyloxytropane (tigloyltropeine), 3-phenylacetoxy-6 beta,7 beta-epoxytropane (3-phenylacetoxyscopine), aposcopolamine (apohyoscine), 7 beta-hydroxy-6 beta-propenyloxy-3 alpha-tropoyloxytropane, traces of 7 beta-hydroxy-6 beta-isovaleroyloxy-3 alpha-tigloyloxytropane and a pyrrolidine alkaloid, hygrine. Two new structures, 3-phenylacetoxy-6 beta,7 beta-epoxytropane (3-phenylacetoxyscopine) and 7 beta-hydroxy-6 beta-propenyloxy-3 alpha-tropolyoxytropane, are proposed on the basis of their spectra. Hyoscyamine, nicotine and tropane N-oxides were not detected in all samples studied.

Stimulation of neurite outgrowth in vitro by a glycero-ganglioside.

A glycerol-containing analog of ganglioside, with sialic acid attached to a diglyceride-like structure possessing two ether-linked alkyl chains, was prepared synthetically and applied exogenously to three culture systems; neuro-2A neuroblastoma cells, PC12 cells and dorsal root ganglia. This resulted in pronounced stimulation of neurite outgrowth in all three, demonstrating that sialo-lipids(s) lacking ceramide and possessing sialic acid as the sole carbohydrate are able to promote neuritogenesis in approximately the same manner as naturally occurring gangliosides.

Total synthesis of ceramide trihexoside accumulating with Fabry's disease.

We report the synthesis of natural ceramide trihexoside, viz. gal (alpha-1 leads to 4) gal (beta-1 leads to 4) gluc (beta-1 leads to 1) ceramide (XIII). It involves the Koenigs-Knorr reaction of the bromide II with the aglucon XIX, and of the chloride VII with the D-enantiomer of the ceramide ester XII. A positional isomer of XIII was obtained as a by-product. A novel technique in the Koenings-Knorr reaction is described.

Destruction of coliforms in water and sewage water by dye-sensitized photooxidation.

A new approach to disinfection of water and sewage water, by oxidative destruction of microorganisms by photosensitization, is described. Samples of water and sewage water, to which an inoculum of fecal Escherichia coli had been added, were exposed to solar radiation in the presence of a dye sensitizer, under continuous aeration. The effects of the sensitizer methylene blue at concentrations of 0 to 10 mg/liter, different radiation times from 0 to 2 h, and sunlight intensities of 0, 68, and 2,030 muE/m2 per s were investigated. In laboratory-scale experiments, 1.3 X 10(9) coliforms in 100 ml of oxidation pond municipal sewage water containing 0.5 mg of methylene blue were destroyed in about 30 min. Similar results were obtained with nonchlorinated potable water. These results demonstrate the possibilities available for the disinfection of water and sewage water by this method.

A method for fractionation of cerebrosides into classes with different fatty acid compositions.

A method is described for the separation of beef brain cerebrosides into three fractions containing different classes of fatty acids: nonhydroxy (I), unsaturated nonhydroxy (II), and hydroxy fatty acid cerebrosides (III). The procedure consists of benzoylation of either crude or purified cerebrosides, followed by column chromatographic separation of benzoylated derivatives containing nonhydroxy acids from those containing hydroxy fatty acids. The benzoyl groups are removed by sodium methoxide-catalyzed transesterification; from the reaction mixtures, fractions I and III precipitate. The fraction II present in mother liquor of I was shown to contain mainly short-chain and unsaturated nonhydroxy fatty acid cerebrosides. The fatty acid composition of each fraction was obtained by gas-liquid chromatography.