Coeliac disease in patients with Kawasaki disease. Is there a link?

OBJECTIVE: Kawasaki disease (KD) is an acute febrile systemic vasculitis, mainly affecting infants and young children. Immunological abnormalities during the acute phase of KD have been described extensively. However, the occurrence of a second immunological disorder in a patient with a history of KD is rarely reported. We evaluated the presence of autoimmune thyroiditis and coeliac disease (CD) in patients with KD diagnosis. METHODS: Ninety consecutive children (57 males and 33 females, median age 5.2 yr, age range 1.6-14.1 yr) with KD were evaluated. All patients were evaluated for thyroid function (thyroid-stimulating hormone, thyroxine and triiodothyronine), anti-thyroglobulin (TgA) and anti-peroxidase (TPOA) antibodies, and antigliadin, anti-endomysium and antitransglutaminase antibodies. CD was confirmed by jejunal biopsy if the specific antibody profile was positive. One hundred and fifty Italian children, matched for age and sex and from the same geographic area, acted as controls. RESULTS: A total of five patients (three boys, two girls; 5.5%; P<0.05) were found positive for coeliac antibodies. In all of these patients the diagnosis of CD was confirmed histologically. Regarding thyroid function and autoantibodies, no patient showed subclinical hypothyroidism or autoimmune thyroiditis. No differences in the familial occurrence of autoimmune diseases between KD patients and controls were found (9.1 and 7.9%, respectively). CONCLUSIONS: Our data showed a higher prevalence of CD in children with KD, and this suggests that children with KD should be monitored carefully for CD. However, there was no increase in the prevalence of autoimmune thyroid diseases in patients with KD or the familial occurrence of autoimmune diseases.     

Cytomegalovirus and inflammatory bowel disease: Is there a link?

The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection in inflammatory bowel disease (IBD). A review of published reports on this topic was carried out, with particular attention paid to the selection of patients included in studies and the diagnostic methods employed. CMV is frequently associated with IBD. In some cases, CMV infection is as sociated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The use of anti-viral therapy in IBD is controversial and an empirical study with controls is needed. The natural history of CMV infection related to the development and treatment of IBD has not been clarified but it is important to take it in consideration because of the possibility of viral persistence in the immunocompromised host and viral interaction with the immune system.     

Apolipoprotein CIII and diabetes. Is there a link?

Apolipoprotein CIII (ApoCIII), a small protein that resides on the surface of lipoprotein particles, is a key regulator of triglyceride metabolism. The inhibition of lipoprotein lipase (LPL), the increased assembly and secretion of very low‐density lipoproteins (VLDL) and the decreased reuptake of triglyceride‐rich lipoproteins (TRLs) by the liver are mechanisms associating elevated serum ApoCIII levels and hypertriglyceridemia. ApoCIII concentration is high in individuals with diabetes mellitus, indicating a possible positive correlation with impairment of glucose metabolism. The aim of this review (based on a Pubmed search until August 2018) is to present the possible mechanisms linking ApoCIII and deterioration of carbohydrate homeostasis. ApoCIII enhances pancreatic β‐cells apoptosis via an increase of the cytoplasmic Ca²⁺ levels in the insulin‐producing cells. In addition, overexpression of ApoCIII enhances non‐alcoholic fatty liver disease and exacerbates inflammatory pathways in skeletal muscles, affecting insulin signalling and thereby inducing insulin resistance. Moreover, recent studies reveal a possible mechanism of body weight increase and glucose production through a potential ApoCIII‐induced LPL inhibition in the hypothalamus. Also, the presence of ApoCIII on the surface of high‐density lipoprotein particles is associated with impairment of their antiglycemic and atheroprotective properties. Modulating ApoCIII may be a potent therapeutic approach to manage hypertriglyceridemia and improve carbohydrate metabolism.     

Autoimmune hepatitis and anti-Ro antibodies. Is there a link?

Antinuclear antibodies (ANA) are considered to be markers of autoimmune disease. Several specific reactivities of ANA are known, among them the Ro (SS-a) complex. Although the presence of anti-Ro antibodies is widely known in systemic connective tissue diseases such as lupus erythematous or Sj?gren's syndrome, few studies have attempted to link this finding with autoimmune hepatitis (AIH). We present a case of acute AIH in a 55-year-old woman who tested positive for anti-Ro 60 kD antibodies. The Ro (SS-A) antigen is a complex ribonucleoprotein whose structure is still the subject of debate. Two fractions, of 50 and 60 kD, have been identified. A review of the literature revealed frequencies of 21-34% for anti-Ro 52 kD and of 9-13-6% for anti-Ro 60 kD in AIH. Although no relationship has been demonstrated between this complex and the etiopathogenic mechanisms or clinical patterns of AIH, we propose that multicenter investigations with large series should be performed before the possible involvement of anti-Ro antibodies in these diseases is definitively ruled out.     

Helicobacter pylori infection and inflammatory bowel disease: Is there a link?

Helicobacter pylori(H.pylori)infection is one of the most widely spread infectious diseases in humans.It can cause chronic gastritis,peptic ulcer disease and gastric malignancies and has been associated with extra-gastric disorders.H.pylori elicit a chronic systemic inflammatory response which,under certain conditions,may trigger autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases.Although the pathogenesis of inflammatory bowel disease(IBD)is unknown,it is thought to result from complex interactions between environmental factors and microbiota in the gut of individuals who are genetically susceptible.Several bacterial and viral agents have been implicated in the aetiology of IBD.In theory,H.pylori infection could be involved in the pathogenesis of IBD by inducing alterations in gastric and/or intestinal permeability or by causing immunological derangements resulting in absorption of antigenic material and autoimmunity via various immunological pathways.Similar mechanisms may also be responsible for the co-existence of IBD with other autoimmune diseases and/or extra-intestinal manifestations.However,the epidemiological data fail to support this association.Infact,various studies indicate that the prevalence of H.pylori infection is low in patients with IBD,suggesting a protective role for this infection in the development of IBD.In this report,we aim to shed light on proposed mechanisms and confounding factors underlying the potential link between H.pylori infection and IBD.     

Cytomegalovirus and inflammatory bowel disease： Is there a link？

The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection in inflammatory bowel disease (IBD). A review of published reports on this topic was carried out, with particular attention paid to the selection of patients included in studies and the diagnostic methods employed. CMV is frequently associated with IBD. In some cases, CMV infection is associated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The use of anti-viral therapy in IBD is controversial and an empirical study with controls is needed. The natural history of CMV infection related to the development and treatment of IBD has not been clarified but it is important to take it in consideration because of the possibility of viral persistence in the immunocompromised host and viral interaction with the immune system.     

Is there a pathogenic link between gamma heavy chain disease and chronic arthritis?

In 1991, gamma heavy chain disease was diagnosed in a 43-year-old female, who 3 years earlier had contracted an erosive seronegative chronic arthropathy. In 1996, her lymphoproliferative disorder required treatment with melphalan and prednisolone. Laboratory studies revealed a gamma3 heavy chain monoclonal component in serum and urine. Massive localization of plasma cells and blasts with cytoplasmic or cell membrane staining for gamma3 chains, but no staining for light chains, was observed by immunohistochemical studies of bone marrow as well as affected synovial tissue. Large amounts of extracellular gamma3-chains were also deposited in the synovial membrane. This is the first documentation of gamma heavy chain deposition disease directly affecting articular structures. Whether it represents the primary pathogenic event followed by reactive inflammatory changes in the joints, or another example of gamma heavy chain disease preceded by chronic arthritis, remains elusive. Regardless, several common cellular and molecular mechanisms discussed here suggest a pathogenic link between the two disease processes.     

Diabetes,pancreatic cancer and vitamin D. Is there a link?

The role of vitamin D is not merely limited to maintaining skeletal health but also extends to maintaining glucose homeostasis by preserving insulin secretion and sensitivity and thus deficiency of vitamin D plays an important role in aetiopathogenesis of T2 diabetes. In addition to its many other roles, vitamin D has recently been found to have growth inhibiting affects on pancreatic cancer cells. Ecological studies have shown that there exists an inverse correlation between sun exposure and death rates for pancreatic cancer. Since vitamin D has promising role in both type 2 diabetes mellitus and pancreatic cancer, its deficiency may be associated to any or both of these chronic diseases. The present review thus aims to find correlation between diabetes and pancreatic cancer and if vitamin D is a common link between the two.     

Coronary artery disease and periodontal disease: is there a link?

BACKGROUND: Cardiovascular disease is the number one killer worldwide. The so-called classic risk factors of coronary heart disease do not account for all of its clinical and epidemiological features. Recent evidence suggests that certain infections, among them dental infections and in particular periodontal disease, are involved in the pathogenesis of coronary artery disease. AIM: To evaluate the association between periodontal disease and coronary artery disease. PATIENTS AND METHODS: Fifty patients referred for diagnostic coronary angiography were assessed for periodontal disease. All patients underwent a thorough physical examination, routine laboratory testing, cardiac evaluation and dental examination which included pantomography x-ray evaluation. RESULTS: Pantomography x-rays and coronary angiograms of the participants were scored blindly by a dentist and cardiologists respectively. The association between periodontal disease and coronary atheromatosis remained significant after adjustment for age, smoking, blood lipids, body mass index, hypertension and the presence of diabetes. IMPLICATIONS: Periodontal disease was still significantly associated after all the known risk factors were accounted for. The implication here is that periodontal disease could be a potential risk factor for heart disease by predisposing the individual to chronic low-grade infections. If so, then dental health becomes an important parameter for medical health.     

Genes and irritable bowel syndrome: Is there a link?

Advances in genetics and genomics during the past decade, including sequencing of the human genome and DNA sequencing technologies, have made it possible to discover the genetic basis for many diseases. With the discovery of multiple genetic loci for gastrointestinal diseases such as Crohn’s disease, some have begun to wonder—Could there be a genetic basis for irritable bowel syndrome (IBS)? This article summarizes the evidence for and against a link between genes and IBS. In addition, a gene-environment paradigm is presented to combine the two opposing hypotheses, as IBS may represent a complex genetic disorder that results from the interaction of several genes and environmental risk factors.     

Celiac disease and chronic liver disease: Is there a relationship?

Celiac disease is a multisystem disease, and the liver is affected in a subset of patients. We herein present a case series of 25 patients with celiac disease who had evidence of cirrhosis of the liver. We retrospectively reviewed the case records of patients with celiac disease having concomitant cirrhosis. The diagnosis of celiac disease was made on the basis of the modified European Society of Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Of 25 patients (nine males; mean age 28.8?±?16.6 years) with celiac disease and cirrhosis, 17 patients presented predominantly with cirrhosis, while 8 presented primarily with celiac disease. Five patients had known cause of cirrhosis (autoimmune hepatitis, three; PBC, one; hepatic venous outflow tract obstruction, one); the remaining 20 were cryptogenic. Gluten-free diet led to improvement in diarrhea and anemia and to a better control of ascites and other features of liver failure. Some patients with cryptogenic cirrhosis have coexistent celiac disease, and they show response to gluten-free diet. Patients with cryptogenic cirrhosis should be screened for celiac disease.     

Vitamin D and type 2 diabetes: Is there a link?

Prevention, or at least delay in onset of type 2 diabetes is possible by intensive lifestyle intervention. This is costly and labour intensive, and alternative methods of preventing diabetes have been sought. Vitamin D has important physiological effects aside from its effects on bone metabolism, including an important role in glucose homeostasis, insulin release and response. Observational data strongly support the role of vitamin D deficiency in the pathogenesis of type 2 diabetes. The time is ripe for a well conducted randomised controlled trial of vitamin D in high risk individuals to test the hypothesis that vitamin D delays the onset of type 2 diabetes.     

GERD and H. pylori: is there a link?

The incidence of gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma have increased in recent years as the incidence of peptic ulcer disease and distal gastric cancer have declined. Given the simultaneous decline in Helicobacter pylori infection, it is tempting to propose a relationship between H. pylori infection and these opposing time trends. Although H. pylori infection clearly does not cause GERD, it may protect certain susceptible individuals from developing GERD and its complications. The most likely mechanism in which H. pylori infection protects against GERD is by decreasing the potency of the gastric refluxate in patients with corpus predominant gastritis. A variety of implications of H. pylori infection on GERD treatment have also arisen in recent years. These focus on the risk of gastric atrophy while on proton pump inhibitor therapy and the efficacy of proton pump inhibitors before and after eradication of H. pylori. This article puts into perspective our current understanding of the complex, incompletely understood relationship between H. pylori infection and GERD.     

Is there a link between cervical inlet patch and Barrett's esophagus?

BACKGROUND: Heterotopic gastric-type mucosa occurs as a flat island or islands of red mucosa in the proximal third of the esophagus where it gives rise to the "cervical inlet patch" (CIP). The aim of the present study was to delineate the clinical epidemiology of the CIP, especially its possible relationship to Barrett's esophagus. METHODS: A case-control study compared 53 case subjects with CIP and 4882 control subjects without CIP. In a multivariate logistic regression, the presence of CIP was chosen as the outcome variable, whereas demographic characteristics, social habits, and presence of other endoscopic diagnoses served as predictor variables. RESULTS: The prevalence of CIP was 1.1%. Its presence was associated with hiatal hernia (odds ratio 2.26: 95% CI [1.12, 4.56]) gastric ulcer (2.93: 95% CI [1.34, 6.40]) and Barrett's esophagus (4.41: 95% CI [2.31, 8.41]). CONCLUSIONS: The coincidence of the cervical inlet patch and Barrett's esophagus could suggest a shared embryonic etiology.     

Helicobacter pylori and colorectal neoplasia: Is there a causal link?

Ever since Helicobacter pylori(H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from casecontrol and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori /H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation.