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.
It has been also suggested that antibiotics change the enteric flora, and their continuous use may pose the risk of overgrowth with pathogens such as Clostridium difficile.Medications used to treat the symptoms of Crohns disease include 5-aminosalicylic acid (5-ASA) formulations, prednisone, immunomodulators such as azathioprine (given as the prodrug for 6-mercaptopurine), methotrexate, and anti-TNF therapies and monoclonal antibodies, such as infliximab, adalimumab, certolizumab, vedolizumab, ustekinumab, and natalizumab. Hydrocortisone should be used in severe attacks of Crohns disease. Biological therapies are medications used to avoid long-term steroid use, decrease inflammation, and treat people who have fistulas with abscesses. The monoclonal antibody ustekinumab appears to be a safe treatment option, and may help people with moderate to severe active Crohns disease. The long term safety and effectiveness of monoclonal antibody treatment is not known. The monoclonal antibody briakinumab is not effective for people with active Crohns disease and it is no longer being manufactured.The gradual loss of blood from the gastrointestinal tract, as well as chronic inflammation, often leads to anemia, and professional guidelines suggest routinely monitoring for this. Adequate disease control usually improves anemia of chronic disease, but iron deficiency may require treatment with iron supplements. Guidelines vary as to how iron should be administered. Besides, other problems include a limitation in possible daily resorption and an increased growth of intestinal bacteria. Some advise parenteral iron as first line as it works faster, has fewer gastrointestinal side effects, and is unaffected by inflammation reducing enteral absorption.