Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 23-year-old man presenting with acute pancreatitis and autoimmune hemolytic anemia was diagnosed with primary sclerosing cholangitis (PSC) without evidence of ulcerative colitis. This constellation of rare associations constitutes a unique mode of presentation of PSC. Within two years he also developed ankylosing spondylitis with sacroiliitis. Disordered immune regulation as a major factor in the mechanism of injury in PSC is supported by its increased association with other immunologically mediated disorders, most notably ulcerative colitis. Autoimmune hemolytic anemia, however, has been reported to be associated with PSC on only two occasions, and ankylosing spondylitis in the absence of ulcerative colitis is also unusual. In addition, the presentation of PSC with acute pancreatitis has rarely been described. This patient presented with several unusual features of PSC.
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PMID:Unusual presentation of primary sclerosing cholangitis. 911 99

There is a paucity of randomized, controlled therapy studies of the extraintestinal manifestations of inflammatory bowel disease (IBD). Most current therapeutic approaches are empiric or based on approaches to therapy in other settings. In the past year anecdotal evidence has emerged for the use of therapies that neutralize tumor necrosis factor-a in both ankylosing spondylitis and the dermatologic extraintestinal manifestations. Topical tacrolimus has also emerged as a potentially useful therapy for dermatologic manifestations. Finally, patients with IBD occasionally become transplant recipients. One study reported worsening IBD after orthotopic liver transplantation for primary sclerosing cholangitis, and another reported the benefit of renal transplantation in amyloidosis-induced renal failure.
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PMID:Treatment of the extraintestinal manifestations of inflammatory bowel disease. 1244 Oct 42

Osteoporosis has received increasing attention as a potential complication of inflammatory bowel disease (IBD). The first population-based data on incidence of fractures in an IBD population were published this past year. The incidence of fractures was one per 100 patient years. Compared with the general population, the fracture rate was increased; however, the relative risk was 1.4 and, therefore, not as high as might be expected from the myriad of studies reporting high rates of osteopenia measured by dual energy x-ray absorptiometry (DXA). Another area receiving increasing attention is that of the enhanced risk of venous thrombosis in patients with IBD. The first population-based incidence rates of venous thrombosis in IBD were also published this past year and showed that IBD patients are affected by venous thrombosis at a rate of approximately one per 200 patient years. The relative risk for venous thrombosis compared with the general population was 3.5. Several studies have reported on associated risk markers or genetic clotting abnormalities, but no clear paradigm has emerged to account for those patients who will suffer a clot. Finally, the first North American population-based study was published, quantifying the prevalence rates of extraintestinal manifestations in patients with IBD for at least 10 years. Some gender- and disease-specific findings emerged. This study found that iritis and uveitis were more common in female patients with ulcerative colitis (3.2%), primary sclerosing cholangitis (PSC) was most common in male patients with ulcerative colitis (3%), ankylosing spondylitis was most common in male patients with Crohn disease (2.7%), and erythema nodosum was most likely to occur in female patients with Crohn disease (1.9%).
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PMID:Osteoporosis and other complications of inflammatory bowel disease. 1703 17

Crohn's disease (CD) and ulcerative colitis (UC), both should be considered as systemic diseases as they are associated with clinical manifestations involving the organs outside the alimentary tract. In a genetically susceptible host with inflammatory bowel disease (IBD), complex interaction of bacterial or other local factors in the colon with antigen presenting cells may trigger an immune reaction to a shared antigen in the involved organs. These extraintestinal manifestations (EIM) are observed in up to 20-40% of the patients with IBD. Patients with CD are more susceptible to EIMs than patients with UC. Joints, eyes, skin and biliary tract are the most commonly involved organ systems. Some manifestations such as uveitis, episcleritis may precede the onset bowel disease and some may occur in conjunction with or subsequent to the diagnosis of active bowel disease. Although many EIMs tend to follow the clinical course of IBD and respond to the treatment of underlying bowel disease, some EIMs such as primary sclerosing cholangitis and ankylosing spondylitis tend to follow a course independent of the bowel disease activity. Biological agents, particularly anti-TNFa based therapies now assume an important role in the treatment of EIMs. Early recognition and treatment of EIMs are crucial in preventing major morbidity.
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PMID:Pathogenesis and clinical approach to extraintestinal manifestations of inflammatory bowel disease. 1791 86

Inflammatory bowel disease (IBD) is a disorder driven by immune dysregulation, characterized by a relapsing-remitting pattern which is punctuated by flares associated with abdominal pain and bloody diarrhea. Management in general is guided by potent immunosuppressive regimens, often with equally potent associated toxicities. Treatment of refractory disease has been revolutionized by biologic therapies. Surgery remains an important part of the overall treatment plan, especially in patients presenting with acute mechanical complications and for prophylactic total colectomy in certain patients at high risk for colorectal cancer (CRC). IBD is associated with a host of intestinal disease-related complications such as intestinal stricture and fistula formation, small bowel obstruction, toxic megacolon, CRC and malnutrition. In addition to these complications there exist a myriad of extraintestinal manifestations that affect almost every organ system, such as primary sclerosing cholangitis, ankylosing spondylitis, pyoderma gangrenosum and uveitis.
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PMID:Inflammatory bowel disease: complications and extraintestinal manifestations. 1943 44

Inflammatory bowel diseases (IBD) are often associated with extraintestinal manifestations (EIMs), which occur in approximately one third of patients. There is only few published data on the occurrence of these manifestations in children and adolescents, so most of the data are taken by studies in adult patients. The organs most commonly affected are joints, skin, eyes and biliary tract, although nearly every organ may be involved. Some of the EIMs are clearly related to intestinal disease activity (i.e., erythema nodosum, peripheral arthritis, orofacial lesions), whereas others occur independently (i.e., pyoderma gangrenosum, anterior uveitis/iritis, ankylosing spondylitis, primary sclerosing cholangitis). Many extraintestinal disorders may be direct inflammatory and metabolic complications of the intestinal inflammation (i.e., osteoporosis, growth retardation, nephrolithiasis, ureteral obstruction, thromboembolic disease). In this review we provide an overview on the prevalence and clinical aspects of the more commonly reported EIMs of Crohn's disease and ulcerative colitis in pediatric patients, focusing on specific issues of children affected by IBD (growth failure and metabolic osteopathy).
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PMID:Extradigestive manifestations of IBD in pediatrics. 1953 May 8

Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders that comprise Crohn's disease (CD) and ulcerative colitis (UC). Genome-wide association studies have identified approximately 100 loci that are significantly associated with IBD. These loci implicate a diverse array of genes and pathophysiologic mechanisms, including microbe recognition, lymphocyte activation, cytokine signaling, and intestinal epithelial defense. Consistent with epidemiologic predictions, many IBD-associated loci demonstrate genome-wide significant associations to both CD and UC, notably, genes whose products function in the interleukin-23 pathway, and transcription factors, including NK2 transcription factor related, locus 3 (NKX2-3), SMAD3, STAT3, ZMIZ1, and c-REL. Although CD and UC are both associated with genomic regions that implicate products of genes involved in leukocyte trafficking, there is evidence for association patterns that are distinct between CD and UC. CD-predominant associations include NOD2 and genes that regulate autophagy. In UC, the predominant association signal is on chromosome 6p21, in the major histocompatibility complex region, near HLA class II genes. UC-predominant loci have also implicated genes mediating epithelial defense function. There is a striking overlap of loci between diseases, which could provide comparative insight into mechanisms of disease pathogenesis. Genes that encode factors that function in the interleukin-23 pathway have been associated with a number of chronic inflammatory diseases, notably psoriasis and ankylosing spondylitis. Distinct genetic associations indicate that the colitis associated with primary sclerosing cholangitis is pathophysiologically distinct from UC that is not associated with primary sclerosing cholangitis. As many as 14 susceptibility loci are shared between IBD and celiac disease, indicating significant overlap in pathophysiology. Future genetic studies will be directed toward identifying uncommon variations with potentially greater statistical effects, defining population differences, and more completely accounting for familial transmission of disease.
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PMID:Recent insights into the genetics of inflammatory bowel disease. 2153 Jul 36

Inflammatory bowel disease (IBD) is a systemic disease associated with a large number of extraintestinal manifestations (EIM). EIM are present in 15-20% of patients with ulcerative colitis and in 20-40% of patients with Crohn's disease. The management of EIM is best provided by a multidisciplinary team, which includes specialists in the affected organ systems with training in the treatment of IBD. Therapeutic strategy is often empirical. This is explained by the paucity of randomized-controlled studies for the specific treatment of EIM in IBD and by the fact that treatment models are based on extrapolation from patients with similar conditions but without IBD. For most EIM, the mainstay of therapy is the treatment of the underlying active IBD. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis and primary sclerosing cholangitis run a clinical course independent of IBD activity and need specific therapy (e.g. TNF antagonists in ankylosing spondylitis and skin manifestations). This review summarizes the conventional and novel (e.g. anti-TNF) treatment modalities, and the therapeutic implications for the management of extraintestinal symptoms in IBD, in order to assist clinicians in optimizing treatment strategies for IBD patients with EIM.
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PMID:Treatment of extraintestinal manifestations in inflammatory bowel disease. 2305 24

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern; PTPN22 C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves' disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison's disease. By contrast, PTPN22 C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn's disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with PTPN22 C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of PTPN22 polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations.
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PMID:Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue. 2307 37

Extra-intestinal manifestations (EIMs) are reported frequently in patients with inflammatory bowel disease (IBD) and may be diagnosed before, concurrently or after the diagnosis of IBD. EIMs in IBD may be classified based on their association with IBD disease activity. The first group has a direct relationship with the activity of the bowel disease and includes pauciarticular arthritis, oral aphthous ulcers, erythema nodosum and episcleritis. The second group of EIMs appears to follow an independent course from the underlying bowel disease activity and include ankylosing spondylitis and uveitis. The third group includes EIMs that may or may not be related to intestinal inflammation, such as pyoderma gangrenosum and probably primary sclerosing cholangitis (PSC). Genetic susceptibility, aberrant self-recognition and immunopathogenic autoantibodies against organ-specific cellular antigens shared by the colon and extra-colonic organs may contribute to the pathogenesis and development of these EIMs. The use of biological agents in the IBD armamentarium has expanded the treatment options for some of the disabling EIMs and these agents form the cornerstone in managing most of the disabling EIMs. PSC is one of the most common hepatobiliary manifestations associated with IBD in which no clear treatment options exist other than endoscopic therapy and liver transplantation. Future research targeting the pathogenesis, early diagnosis and treatment of these EIMs is required.
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PMID:Diagnosis and therapeutic management of extra-intestinal manifestations of inflammatory bowel disease. 2318 71


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