Over a 13-year period, the course of 109 pregnancies in 68 women with Crohn's disease was studied. A total of 76 children were delivered. There were no gemellary deliveries, and none of the children had congenital malformations. Pregnancy entailed no increased risk of an exacerbation of the bowel disease. As compared with the reference population and with women with ulcerative colitis, the total material showed an increased risk of premature delivery and spontaneous abortion, but a further analysis showed that this was due only to an increased risk in women with active disease at the time of conception and in women who had undergone bowel resection during pregnancy. Birth weight and birth length corresponded to those in the reference population. The frequency of neonatal hyperbilirubinaemia was not higher in children of mothers with Crohn's disease than in children of healthy mothers. Treatment with sulphasalazine, salazosulphadimidine, and corticosteroids did not influence the course of pregnancy or the frequency of neonatal jaundice or malformations. Consequently, in Crohn's disease a pregnant woman should be given the same medical treatment as when not pregnant. Generally, the women should be advised preferably to conceive at a time when their bowel disease is inactive. The risk groups should be followed up with frequent obstetrical examinations throughout pregnancy.
Blau syndrome is a hereditary granulomatous disease caused by mutations in the CARD15 gene that is diagnosed in children of young age with exanthema/erythema, arthritis/periarthritis and/or uveitis. We report two cases of Blau syndrome in Danish Caucasian monozygotic male twins, exhibiting a heterozygous de novo R334W mutation in codon 334 of CARD15. The patients were initially diagnosed as having sarcoidosis. In both twins, symptoms (exanthema, arthritis/periarthritis) started at 1 year of age, and were followed by uveitis at 7-10 years of age. There was no involvement of the lungs or other organs. An initial course of standard antituberculous treatment had no effect on the symptoms. Hydroxychloroquine and cyclosporine A were also ineffective, and the latter caused impaired renal function. Partial symptomatic relief was obtained with prednisolone and increased benefit was observed in combination with methotrexate. Subsequent introduction of the TNF-alpha inhibitor eternacept did not discernibly benefit the clinical condition, but was associated with recurrent infections. In contrast, a trial of infliximab therapy demonstrated clinical efficacy and eliminated all symptoms, restoring a high quality of life. At follow up at 20 years of age (after 2-5 years of infliximab treatment) the twins had an almost normal physical appearance and a normal psychomotoric development, indicating a favourable short-term prognosis of the disease. Blau syndrome has pathologic, clinical and therapeutic features in common with sarcoidosis, but rarely involves the lungs or other parenchymatous organs. In children, discrimination between early onset sarcoidosis and Blau syndrome should include a CARD15 mutation analysis.
Cytokines, particularly the proinfiammatory cytokines, whose role and natural regulation in inflammatory bowel disease are reviewed here, are produced by many cell types, including immune cells. Cytokines function as important hormones of the immune system, and many act both regionally and systemically via specific receptors. The demonstration of increased circulating and mucosal levels of proinfiammatory (and other) cytokines (and receptors) in active inflammatory bowel disease does not by itself constitute any proof as to the primary involvement of these mediators. However, they may contribute significantly to disease manifestations, and specific therapeutic intervention at the cytokine or cytokine receptor level may show up to be clinically most relevant. This is underscored by the increasing evidence that proven therapies of inflammatory bowel disease to a great extent seem to function through cytokine modulation.
Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.
As compared with controls, non-inflamed colonic mucosal cells contain two up-regulated genes related to the innate immune system. Up-regulation of these genes, known to be induced by microorganisms, suggests either increased microflora antigenicity or an altered function in mucosal barrier defence.
The NGAL content in rectal dialysate and particularly in feces seems to be a reliable marker for severe disease activity in UC, whereas serum NGAL concentrations do not reflect disease activity.
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