The microbiome and psoriatic arthritis.

Psoriatic arthritis is a chronic inflammatory joint disease, seen in combination with the chronic inflammatory skin disease psoriasis and belonging to the family of spondylarthritides (SpA). A link is recognized between psoriatic arthritis and inflammatory bowel disease (IBD). Environmental factors seem to induce inflammatory disease in individuals with underlying genetic susceptibility. The microbiome is a subject of increasing interest in the etiology of these inflammatory immune-mediated diseases. The intestinal microbiome is able to affect extra-intestinal distant sites, including the joints, through immunomodulation. At this point, evidence regarding a relationship between the microbiome and psoriatic arthritis is scarce. However, we hypothesize that common immune-mediated inflammatory pathways seen in the "skin-joint-gut axis" in psoriatic arthritis are induced or at least mediated by the microbiome. Th17 has a crucial function in this mechanism. Further establishment of this connection may lead to novel therapeutic approaches for psoriatic arthritis.

[Acute neuropsychiatry: a confused patient and a puzzled doctor]. / Acute neuropsychiatrie: verwarring bij patiënt en specialist.

BACKGROUND: Anti-NMDA-receptor-encephalitis is a progressive autoimmune disease with significant mortality if left untreated. CASE DESCRIPTION: A 58-year-old man without previous psychiatric or neurologic history presented at the emergency department after brief loss of consciousness at work. Within a few hours, the patient developed acute neuropsychiatric symptoms, including altered levels of consciousness, aggression, incoherence, change in behaviour, and psychomotor agitation. Initially, additional blood, cerebrospinal fluid and EEG tests showed no abnormalities. Over the course of the following days, catatonia, orofacial dyskinesia and autonomic-function disorder developed, eventually with respiratory insufficiency, necessitating transfer to the intensive-care unit. At this stage, the EEG did show abnormalities, and cerebrospinal fluid analysis showed marginal pleocytosis. The patient was treated with intravenous methylprednisolone and immunoglobins. Anti-NMDA-receptor antibodies were present in the blood and cerebrospinal fluid. Screening for malignancy identified small-cell lung carcinoma, for which the patient was treated with cytostatic agents. CONCLUSION: Acute neuropsychiatric symptoms in a middle-aged patient with no psychiatric medical history are suggestive of an underlying somatic cause. Timely recognition and treatment of anti-NMDA-receptor encephalitis is essential to improve the prognosis.

Fumarates and Cancer.

Accumulation of intermediate metabolites of the tricarboxylic acid (TCA) cycle in tumor cells can cause epithelial-to-mesenchymal transition (EMT), although the exact mechanisms remain elusive. Recent studies show that the oncometabolite fumarate, which accumulates in fumarate hydratase-deficient renal cancers, confers tumor aggressiveness by causing epigenetic changes in the antimetastatic miRNA cluster mir-200ba429. This may have important implications for the use of fumarates in the clinic.

Depletion of Saccharomyces cerevisiae in psoriasis patients, restored by Dimethylfumarate therapy (DMF).

BACKGROUND: Psoriasis and inflammatory bowel disease (IBD) are chronic inflammatory diseases sharing similar pathogenic pathways. Intestinal microbial changes such as a decrease of bakers' yeast Saccharomyces cerevisiae have been reported in IBD, suggesting the presence of a gut-skin axis. OBJECTIVE: To investigate whether the S. cerevisiae abundance was altered in psoriasis patients versus healthy controls, and whether dimethylfumarate (DMF) interacted with this yeast. METHODS: Using qPCR, faecal samples were compared between psoriasis patients without DMF (n = 30), psoriasis patients with DMF (n = 28), and healthy controls (n = 32). RESULTS: Faecal S. cerevisiae abundance was decreased in psoriasis compared to healthy controls (p<0.001). Interestingly, DMF use raised S. cerevisiae levels (p<0.001). Gastrointestinal adverse-effects of DMF were correlated with a higher S. cerevisiae abundance (p = 0.010). In vitro, a direct effect of DMF on S. cerevisiae growth was observed. In addition, anti-Saccharomyces cerevisiae antibodies were not elevated in psoriasis. CONCLUSION: The abundance of baker's yeast S. cerevisiae is decreased in psoriasis patients, but appears to be restored upon DMF use. S. cerevisiae is generally classified as a yeast with beneficial immunomodulatory properties, but may also be involved in the occurrence of DMF's gastrointestinal adverse-effects. Potentially, DMF might be a new therapy for IBD.

Prevalence and Phenotype of Concurrent Psoriasis and Inflammatory Bowel Disease.

BACKGROUND: Psoriasis, psoriatic arthritis (PsA), and inflammatory bowel disease (IBD) are related inflammatory immune-mediated diseases, with considerable overlap. However, it is as yet unclear whether co-occurrence of these diseases affects disease course and characteristics of the individual complaints. The objective of this study was to identify the prevalence of IBD and PsA in a psoriasis cohort and to examine whether patients with concurrent psoriasis and IBD carry a distinct phenotype. METHODS: Data of all patients with psoriasis visiting a general hospital in the Netherlands between 2009 and 2014 were retrospectively retrieved from electronic patient files. In addition, clinical characteristics of patients with concurrent psoriasis and IBD (n = 40) were compared with psoriasis-only (n = 1643) and IBD-only (n = 385) cohorts. RESULTS: Among 1669 hospital-based patients with psoriasis, prevalence of PsA was 12.2% (n = 203, 95% confidence interval, 10.5-13.7) and of IBD 1.6% (n = 26, 95% confidence interval, 1.0-2.2), including 12 Crohn's disease (CD) and 14 ulcerative colitis. Psoriasis-PsA patients were more likely to have IBD than psoriasis-only patients (3.0 versus 1.4%).Psoriasis-CD patients were younger at CD diagnosis (20.0 versus 32.0 yr, P = 0.001), and psoriasis diagnosis (28.0 versus 43.5 yr, P = 0.004) than psoriasis-only patients. Psoriasis-IBD patients had a mild psoriasis phenotype similar to psoriasis-only patients, but the CD-phenotype was significantly more severe than in CD-only patients. CONCLUSIONS: The prevalence of IBD in psoriasis was approximately 4 times higher than that in the general population, with the highest risk for psoriasis-PsA patients. Psoriasis-CD patients have a mild (early-onset) psoriasis but an earlier-onset and severe CD-phenotype.

Similar Depletion of Protective Faecalibacterium prausnitzii in Psoriasis and Inflammatory Bowel Disease, but not in Hidradenitis Suppurativa.

BACKGROUND AND AIMS: Psoriasis and hidradenitis suppurativa [HS] co-occur more often with inflammatory bowel disease [IBD] than expected, due to shared pathogenic and genetic features. It is known that IBD patients harbour an altered intestinal microbiome characterised by a depletion of Faecalibacterium prausnitzii and increase of Escherichia coli. At present, it is unclear whether a similar intestinal microbiome trend can be identified in IBD-associated skin disorders. We therefore investigated the F. prausnitzii and E. coli abundance in psoriasis and HS, with and without concomitant IBD. METHODS: Using quantitative polymerase chain reaction , we compared the F. prausnitzii and E. coli abundances in faecal samples from healthy controls [n = 33] with samples from patients with psoriasis [n = 29], IBD [n = 31], and concomitant IBD and psoriasis [n = 13]. Likewise, we analysed samples from patients with HS [n = 17], and concomitant IBD and HS [n = 17]. RESULTS: Psoriasis patients harboured a significantly lower abundance of F. prausnitzii in their stool than healthy controls [p < 0.001], which was similar to IBD patients. Together with the reduced F. prausnitzii levels, the psoriasis patients had a significantly higher abundance of E. coli [p < 0.001]. No significant difference in F. prausnitzii or E. coli abundance was found in HS. It was apparent that patients with concomitant IBD and associated skin disorder had the greatest decrease of F. prausnitzii and increase of E. coli. CONCLUSIONS: The study demonstrates, for the first time, an IBD-like decrease of F. prausnitzii together with an increase of E.coli in psoriasis, supporting the presence of a gut-microbiome-skin axis in psoriasis and IBD.