No Evidence of Gut Microbiota Alteration in Psoriasis Patients Switching to Brodalumab after Loss of TNFα Inhibition Effect.

Biological agents used to treat severe psoriasis may alter the gut microbiota, though current knowledge is limited. This study examines whether switching from TNFα inhibitors, from which patients had reduced or lost effect, to brodalumab, an IL-17 inhibitor, affects the gut microbiota in patients with psoriasis and how these changes correlate with the clinical variables of psoriasis severity and depressive symptoms. Fecal samples from patients were collected before the treatment switch and 12 weeks after the switch and were analyzed for the microbiota composition using next-generation sequencing targeting the V3-V5 region of the 16S rRNA gene, followed by bioinformatics analysis. No significant changes in overall gut microbiota composition were observed after the treatment switch, although individual variations in the Firmicutes/Bacteroidetes ratio were noted, and no significant correlations with clinical variables were found. These findings suggest that short-term changes in gut microbiota in patients with psoriasis are limited and that dysbiosis may be influenced by the interplay of various microbial populations rather than specific taxa. This study provides a foundation for further research into the effects of biological treatments on the gut microbiota in patients with psoriasis.

Air-oxidized linalool elicits eczema in allergic patients - a repeated open application test study.

BACKGROUND: Linalool is a commonly used fragrance terpene that forms potent sensitizers upon oxidation. In a recent multicentre study, we found that 7% of 2900 patients showed positive patch test reactions to oxidized linalool at 6.0%. No elicitation studies have been performed. OBJECTIVE: To identify threshold concentrations for elicitation of allergic contact dermatitis caused by oxidized linalool in allergic individuals with repeated exposures. METHODS: Repeated open application tests were performed in 6 participants previously diagnosed with contact allergy to oxidized linalool. Creams containing 3.0%, 1.0% and 0.30% oxidized linalool (corresponding to 0.56%, 0.19% and 0.056% linalool hydroperoxides, respectively) and 'fine fragrance' containing 1.0%, 0.30% and 0.10% oxidized linalool (corresponding to 0.19%, 0.056% and 0.019% linalool hydroperoxides, respectively) were used twice daily for up to 3 weeks. Patch testing with a dilution series of oxidized linalool was performed. RESULTS: Five of 6 participants reacted to the cream containing 3% oxidized linalool. With 1% oxidized linalool, a reaction was seen in 3 (cream) and 4 (fine fragrance) participants, respectively. With 0.3% oxidized linalool, 2 (cream) and 1 (fine fragrance) participants reacted. CONCLUSION: Repeated exposure to low concentrations of oxidized linalool can elicit allergic contact dermatitis in previously sensitized individuals.

Effects of brodalumab on psoriasis and depressive symptoms in patients with insufficient response to TNF-α inhibitors.

The objective of this study was to evaluate emotions of depression and anxiety in psoriatic patients that due to insufficient response to tumor necrosis factor-alpha inhibition (TNF-α), underwent a treatment switch from TNF-α to interleukin 17 inhibition using brodalumab. The Self-rated Montgomery-Asberg Depression Rating Scale and the Hospital Anxiety and Depression Scale were used to assess depression and anxiety. A total of 20 patients with psoriasis were enrolled in the study. They were monitored for a period of 3 months following the transition to brodalumab treatment. The results showed a significant improvement in both the Psoriasis Area and Severity Index as well as symptoms of depression; anxiety symptoms showed a reduction, though not statistically significant. Perhaps of more interest, the positive effects on depression and anxiety seem to be independent of the reduction in skin related psoriatic lesions. These findings highlight the importance of addressing depressive and anxiety symptoms, together with psoriasis severity and quality of life, when managing patients with psoriasis.

Large scale identification of proteins, mucins, and their O-glycosylation in the endocervical mucus during the menstrual cycle.

The mucus filling the human cervical opening blocks the entry to the uterus, but this has to be relative and allow for the sperm to penetrate at ovulation. We studied this mucus, its content of proteins and mucins, and the mucin O-glycosylation in cervical secretions before, during, and after ovulation. Cervical mucosal secretions from 12 subjects were collected, reduced-alkylated, separated with polyacrylamide or agarose/polyacrylamide gel electrophoresis, and stained with silver, Alcian blue, or Coomassie Blue stain. Protein and mucin bands from before and during ovulation were digested and subsequently analyzed by nano-LC-FT-ICR MS and MS/MS. We identified 194 proteins after searches against the NCBI non-redundant protein database and an in-house mucin database. Three gel-forming (MUC5B, MUC5AC, and MUC6) and two transmembrane mucins (MUC16 and MUC1) were identified. For the analysis of mucin O-glycosylation, separated mucins from six individuals were blotted to PVDF membranes, and the O-glycans were released by reductive beta-elimination and analyzed with capillary HPLC-MS and -MS/MS. At least 50 neutral, sialic acid-, and sulfate-containing oligosaccharides were found. An increase of GlcNAc-6GalNAcol Core 2 structures and a relative decrease of NeuAc residues are typical for ovulation, and NeuAc-6GalNAcol and NeuAc-3Gal- epitopes are typical for the non-ovulatory phases. The cervical mucus at ovulation is thus characterized by a relative increase in neutral fucosylated oligosaccharides. This comprehensive characterization of the mucus during the menstrual cycle suggests mucin glycosylation as the major alteration at ovulation, but the relation to the altered physicochemical properties and sperm penetrability is still not understood.