-
The American Journal of Gastroenterology May 2013This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten...
This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical trials, but are not yet approved for use in practice. Given the incomplete response of many patients to a GFD-free diet as well as the difficulty of adherence to the GFD over the long term, development of new effective therapies for symptom control and reversal of inflammation and organ damage are needed. The prevalence of celiac disease is increasing worldwide and many patients with celiac disease remain undiagnosed, highlighting the need for improved strategies in the future for the optimal detection of patients.
Topics: Abdominal Pain; Antibodies; Atrophy; Celiac Disease; Clinical Trials as Topic; Diagnosis, Differential; Diarrhea; Diet, Gluten-Free; Edible Grain; Endoscopy, Gastrointestinal; Evidence-Based Medicine; Flatulence; GTP-Binding Proteins; Genetic Predisposition to Disease; Gliadin; Glutens; HLA-DQ Antigens; Humans; Immunoglobulin A; Intestinal Mucosa; Intestine, Small; Patient Education as Topic; Protein Glutamine gamma Glutamyltransferase 2; Sensitivity and Specificity; Steatorrhea; Transglutaminases; Weight Loss
PubMed: 23609613
DOI: 10.1038/ajg.2013.79 -
Clinical and Translational... Nov 2018Rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their...
OBJECTIVES
Rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort.
METHODS
We performed targeted next-generation sequencing of the four CP-associated genes in 1061 Han Chinese CP patients and 1196 controls. To evaluate gene-environment interactions, the patients were divided into three subgroups, idiopathic CP (ICP; n = 715), alcoholic CP (ACP; n = 206), and smoking-associated CP (SCP; n = 140). The potential impact of rare pathogenic variants on the age of onset of CP and clinical outcomes was evaluated using the Kaplan-Meier model.
RESULTS
We identified rare pathogenic genotypes involving the SPINK1, PRSS1, CTRC, and/or CFTR genes in 535 (50.42%) CP patients but in only 71 (5.94%) controls (odds ratio = 16.12; P < 0.001). Mutation-positive patients had significantly earlier median ages at disease onset and at diagnosis of pancreatic stones, diabetes mellitus and steatorrhea than mutation-negative ICP patients. Pathogenic genotypes were present in 57.1, 39.8, and 32.1% of the ICP, ACP, and SCP patients, respectively, and influenced age at disease onset and clinical outcomes in all subgroups.
CONCLUSIONS
We provide evidence that rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes significantly influence the age of onset and clinical outcomes of CP. Extensive gene-environment interactions were also identified.
Topics: Adolescent; Adult; Age of Onset; Asian People; Calculi; Chymotrypsin; Cystic Fibrosis Transmembrane Conductance Regulator; Diabetes Mellitus; Gene-Environment Interaction; Genetic Predisposition to Disease; Genotype; Humans; Kaplan-Meier Estimate; Middle Aged; Mutation; Pancreatic Diseases; Pancreatitis, Alcoholic; Pancreatitis, Chronic; Smoking; Steatorrhea; Trypsin; Trypsin Inhibitor, Kazal Pancreatic; Young Adult
PubMed: 30420730
DOI: 10.1038/s41424-018-0069-5 -
California Medicine Apr 1965Cystic fibrosis, a disease thought to be transmitted as a recessive genetic trait, is found as a disease in about one in 1,000 to one in 10,000 births. It involves all... (Review)
Review
Cystic fibrosis, a disease thought to be transmitted as a recessive genetic trait, is found as a disease in about one in 1,000 to one in 10,000 births. It involves all of the exocrine glands with presenting symptoms dependent upon the extent of involvement of any group of glands. Many aspects of the disease can be corrected by substitution therapy. This applies particularly to the use of animal pancreas for the steatorrhea and salt for prevention of heat prostration. Unfortunately, the obstructive pulmonary disease with secondary bronchial infections can only be treated symptomatically by the use of mucus thinning agents, postural drainage, and antibiotics. Nevertheless, longevity can be increased and a great deal of hope offered to the families of these unfortunate children by careful supervision of their medical care.
Topics: Anti-Bacterial Agents; Child; Cystic Fibrosis; Drainage, Postural; Exocrine Glands; Humans; Infant; Infant, Newborn; Mucus; Pancreas; Steatorrhea
PubMed: 14288148
DOI: No ID Found -
Clinical Microbiology Reviews Jan 1992Giardiasis is one of the most common pathogenic intestinal protozoal infections worldwide. Giardia lamblia is the most frequently identified etiologic agent in outbreaks... (Review)
Review
Giardiasis is one of the most common pathogenic intestinal protozoal infections worldwide. Giardia lamblia is the most frequently identified etiologic agent in outbreaks associated with the ingestion of surface water, often due to ineffective filtration or pretreatment. In addition to humans, other sources of infection include beavers, perhaps muskrats, and possibly domestic animals. A low infecting dose (10 to 25 cysts) is reported to be sufficient to produce human infection. Clinical manifestations range from asymptomatic to a transient or persistent acute stage, with steatorrhea, intermittent diarrhea, and weight loss, or to a subacute or chronic stage that can mimic gallbladder or peptic ulcer disease. Diagnosis is usually based on repeated stool examinations but examination of duodenal fluid or biopsy material may also be necessary. Enzyme immunoassay or indirect immunofluorescence methods for direct detection of antigen or whole organisms in clinical specimens have also been developed. These tests are reported to be more sensitive than routine stool examination. Demonstration of serum immunoglobulin M and G antibodies may help differentiate recent from past infection or help detect recurrence in individuals who have been treated previously. Serum immunoglobulin A levels may be a useful indicator of exposure in waterborne outbreaks of diarrhea. Drugs available for treatment within the United States include metronidazole, quinacrine hydrochloride, and furazolidone.
Topics: Animals; Giardiasis; Humans
PubMed: 1735095
DOI: 10.1128/CMR.5.1.93 -
Deutsches Arzteblatt International Aug 2010Treatment with pancreatic enzymes must be based on an understanding of the normal physiology and pathophysiology of exocrine pancreatic function, as well as of the... (Review)
Review
BACKGROUND
Treatment with pancreatic enzymes must be based on an understanding of the normal physiology and pathophysiology of exocrine pancreatic function, as well as of the diseases that cause exocrine pancreatic insufficiency of either a structural or a functional type. These include chronic pancreatitis, pancreatic cancer, cystic fibrosis, pancreaticocibal asynchrony after gastric or pancreatic surgery, and celiac disease.
METHODS
Selective review of the literature.
RESULTS
Exocrine pancreatic insufficiency can cause meteorism, diarrhea, steatorrhea, and weight loss. All of these manifestations are non-specific except steatorrhea. Enzyme supplementation is indicated only for the treatment of demonstrated pancreatic dysfunction; unfortunately, however, no sensitive and specific pancreatic function tests are currently available. As a result, pancreatic enzyme supplementation is considered to be indicated on pragmatic grounds when, for example, the patient is suffering from diarrhea and weight loss and has been demonstrated to have a disease leading to exocrine pancreatic insufficiency. To be acceptable for clinical use, a pancreatin preparation must satisfy the following criteria: it must be enterically coated, so that it will not be destroyed by gastric acid; mix well with gastric chyme; exit the stomach simultaneously with chyme; and be rapidly released from its enteric coating upon entering the duodenum. Although there have been no large-scale, randomized comparative studies of different types of pancreatin preparation, the current clinical preference is for enterically coated micropellets or minitablets with a diameter of 2 mm or less. The initial dosage is 20 000 to 40 000 units of lipase taken once or twice per meal, with dose adjustment afterward as needed. The dose can be raised, and a proton-pump inhibitor can be added on.
CONCLUSION
There is still no simple test that can be used to diagnose pancreatic exocrine insufficiency with certainty. The treatment is symptomatic; its goals are to lessen steatorrhea and reverse weight loss.
Topics: Dosage Forms; Dose-Response Relationship, Drug; Exocrine Pancreatic Insufficiency; Humans; Pancreatic Function Tests; Pancreatin; Predictive Value of Tests
PubMed: 21904592
DOI: 10.3238/arztebl.2011.0578