All this new knowledge in the pathogenesis of Crohns disease allows us to put this multifactorial disease in the group of autoinflammatory syndromes.Some examples of how the innate immune system affects bowel inflammation have been described. A meta-analysis of CD genome-wide association studies revealed 71 distinct CD-susceptibility loci. Interestingly, three very important CD-susceptibility genes (the intracellular pathogen-recognition receptor, NOD2; the autophagy-related 16-like 1, ATG16L1 and the immunity-related GTPase M, IRGM) are involved in innate immune responses against gut microbiota, while one (the X-box binding protein 1) is involved in regulation of the [adaptive] immune pathway via MHC class II, resulting in autoinflammatory inflammation. Studies have also found that increased ILC3 can overexpress major histocompatibility complex (MHC) II. MHC class II can induce CD4+ T cell apoptosis, thus avoiding the T cell response to normal bowel micro bacteria. Further studies of IBD patients compared with non-IBD patients found that the expression of MHC II by ILC3 was significantly reduced in IBD patients, thus causing an immune reaction against intestinal cells or normal bowel bacteria and damaging the intestines. This can also make the intestines more susceptible to environmental factors, such as food or bacteria.The thinking is, that because Crohns disease has strong innate immune system involvement and has NOD2 mutations as a predisposition, Crohns disease is more likely an autoinflammatory disease than an autoimmune disease. Immunodeficiency theory
A substantial body of data has emerged in recent years to suggest that the primary defect in Crohns disease is actually one of relative immunodeficiency.
Contraindications
Phentermine/topiramate ER is contraindicated in pregnancy, glaucoma, hyperthyroidism, during or within 14 days of taking monoamine oxidase inhibitors, and in patients with hypersensitivity or idiosyncrasy to sympathomimetic amines. Phentermine/topiramate ER can cause an increase in resting heart rate. History
Phentermine and topiramate was developed by Vivus, a California pharmaceutical company. In December 2009 VIVUS, Inc. submitted a new drug application (NDA) to the FDA and on March 1, 2010, VIVUS, Inc. announced that the FDA accepted the NDA for review. In October 2010, the FDA announced its decision to not approve phentermine/topiramate ER in its current form and issued a Complete Response Letter to VIVUS due to lack of long-term data and concerns about side effects including elevated heart rate, major adverse cardiovascular events, and birth defects.The FDA expressed concerns about the potential for phentermine/topiramate ER to cause birth defects and requested that Vivus assess the feasibility of analyzing existing healthcare databases to determine the historical incidence of oral cleft in offspring of women treated with topiramate for migraine prophylaxis (100 mg).In October 2011, VIVUS resubmitted the NDA to the FDA with responses to the issues addressed in the CRL. The FDA accepted the NDA in November 2011.On September 18, 2012, Qsymia became available on the US market. References
External links
"Phentermine mixture with topiramate". Drug Information Portal. U.S. National Library of Medicine.