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American Family Physician May 2013Ulcerative colitis is a chronic inflammatory disease of the colon. The etiology is unknown. Risk factors include a history of recent infection with Salmonella or... (Review)
Review
Ulcerative colitis is a chronic inflammatory disease of the colon. The etiology is unknown. Risk factors include a history of recent infection with Salmonella or Campylobacter, living in Western industrialized nations and at higher latitudes, and a family history of the disease. The incidence peaks in early adulthood, but patients can develop the disorder from early childhood through adulthood. Ulcerative colitis often presents with abdominal pain, diarrhea, and hematochezia. It is important to exclude infectious etiologies. Anemia and an elevated erythrocyte sedimentation rate or C-reactive protein level may suggest inflammatory bowel disease, but the absence of laboratory abnormalities does not rule out ulcerative colitis. The diagnosis is suspected clinically and confirmed through endoscopic biopsy. First-line treatment is therapy with 5-aminosalicylic acid. Corticosteroids may be added if 5-aminosalicylic acid therapy is ineffective. Infliximab can be added to induce and sustain remission. Patients with severe or nonresponsive ulcerative colitis should be hospitalized, and intravenous corticosteroids should be given. If medical management has been ineffective, surgical intervention is indicated for severe disease. Patients with ulcerative colitis have an increased risk of colon cancer and should have periodic colonoscopy beginning eight to 10 years after diagnosis.
Topics: Colitis, Ulcerative; Diagnosis, Differential; Humans; Risk Factors
PubMed: 23939448
DOI: No ID Found -
Digestion 2023Two major types of 5-aminosalicylic acid (5-ASA)-containing preparations, namely, mesalazine/5-ASA and sulfasalazine (SASP), are currently used as first-line therapy for... (Review)
Review
BACKGROUND
Two major types of 5-aminosalicylic acid (5-ASA)-containing preparations, namely, mesalazine/5-ASA and sulfasalazine (SASP), are currently used as first-line therapy for ulcerative colitis. Recent reports show that optimization of 5-ASA therapy is beneficial for both patient outcomes and healthcare costs. Although 5-ASA and SASP have good efficacy and safety profiles, clinicians occasionally encounter patients who develop 5-ASA intolerance.
SUMMARY
The most common symptoms of acute 5-ASA intolerance syndrome are exacerbation of diarrhea, fever, and abdominal pain. Patients who discontinue 5-ASA therapy because of intolerance have a higher risk of adverse clinical outcomes, such as hospital admission, colectomy, need for advanced therapies, and loss of response to anti-tumor necrosis factor (TNF) biologics. When patients develop symptoms of 5-ASA intolerance, the clinician should consider changing the type of 5-ASA preparation. Recent genome-wide association studies and meta-analyses have shown that 5-ASA allergy is associated with certain single-nucleotide polymorphisms. Although there are no modalities or biomarkers for diagnosing 5-ASA intolerance, the drug-induced lymphocyte stimulation test can be used to assist in the diagnosis of acute 5-ASA intolerance syndrome with high specificity and low sensitivity. This review presents a general overview of 5-ASA and SASP in the treatment of inflammatory bowel disease and discusses the latest insights into 5-ASA intolerance.
KEY MESSAGES
5-ASA is used as first-line therapy for ulcerative colitis. Optimization of 5-ASA may be beneficial for patient outcomes and healthcare systems. Acute 5-ASA intolerance syndrome is characterized by diarrhea, fever, and abdominal pain. Periodic renal function monitoring is recommended for patients receiving 5-ASA.
Topics: Humans; Mesalamine; Colitis, Ulcerative; Anti-Inflammatory Agents, Non-Steroidal; Genome-Wide Association Study; Remission Induction; Administration, Oral; Sulfasalazine; Fever; Abdominal Pain
PubMed: 36366816
DOI: 10.1159/000527452 -
Cellular and Molecular Life Sciences :... Aug 2022Colitis develops via the convergence of environmental, microbial, immunological, and genetic factors. The medicine 5-aminosalicylic acid (5-ASA) is widely used in...
Colitis develops via the convergence of environmental, microbial, immunological, and genetic factors. The medicine 5-aminosalicylic acid (5-ASA) is widely used in clinical practice for colitis (especially ulcerative colitis) treatment. However, the significance of gut microbiota in the protective effect of 5-ASA on colitis has not been explored. Using a dextran sulfate sodium (DSS)-induced colitis mouse model, we found that 5-ASA ameliorated colitis symptoms in DSS-treated mice, accompanied by increased body weight gain and colon length, and a decrease in disease activity index (DAI) score and spleen index. Also, 5-ASA alleviated DSS-induced damage to colonic tissues, as indicated by suppressed inflammation and decreased tight junction, mucin, and water-sodium transport protein levels. Moreover, the 16S rDNA gene sequencing results illustrated that 5-ASA reshaped the disordered gut microbiota community structure in DSS-treated mice by promoting the abundance of Bifidobacterium, Lachnoclostridium, and Anaerotruncus, and reducing the content of Alloprevotella and Desulfovibrio. Furthermore, 5-ASA improved the abnormal metabolism of bile acids (BAs) by regulating the Farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5) signaling pathways in DSS-treated mice. In contrast, 5-ASA did not prevent the occurrence of colitis in mice with gut microbiota depletion, confirming the essential role of gut microbiota in colitis treatment by 5-ASA. In conclusion, 5-ASA can ameliorate DSS-induced colitis in mice by modulating gut microbiota and bile acid metabolism. These findings documented the new therapeutic mechanisms of 5-ASA in clinical colitis treatment.
Topics: Animals; Bile Acids and Salts; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Mesalamine; Mice; Mice, Inbred C57BL
PubMed: 35913641
DOI: 10.1007/s00018-022-04471-3 -
The Lancet. Respiratory Medicine Apr 2020Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens.
METHODS
We did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug.
FINDINGS
58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed.
INTERPRETATION
Fluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis.
FUNDING
Canadian Institutes of Health Research, Centers for Disease Control and Prevention (USA), American Thoracic Society, European Respiratory Society, and Infectious Diseases Society of America.
Topics: Adult; Aminosalicylic Acid; Antitubercular Agents; Canada; Clofazimine; Diarylquinolines; Drug-Related Side Effects and Adverse Reactions; Female; Fluoroquinolones; Humans; Incidence; Linezolid; Male; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 32192585
DOI: 10.1016/S2213-2600(20)30047-3 -
Antibiotics (Basel, Switzerland) Jan 2023Small intestinal bacterial overgrowth (SIBO) is characterized as the increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract... (Review)
Review
Small intestinal bacterial overgrowth (SIBO) is characterized as the increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract and accompanies various bowel symptoms such as abdominal pain, bloating, gases, diarrhea, and so on. Clinically, SIBO is diagnosed by microbial culture in duodenum/jejunum fluid aspirates and/or the breath tests (BT) of hydrogen/methane gases after ingestion of carbohydrates such as glucose. The cultural analysis of aspirates is regarded as the golden standard for the diagnosis of SIBO; however, this is invasive and is not without risk to the patients. BT is an inexpensive and safe diagnostic test but lacks diagnostic sensitivity and specificity depending on the disease states of patients. Additionally, the urinary excretion tests are used for the SIBO diagnosis using chemically synthesized bile acid conjugates such as cholic acid (CA) conjugated with para-aminobenzoic acid (PABA-CA), ursodeoxycholic acid (UDCA) conjugated with PABA (PABA-UDCA) or conjugated with 5-aminosalicylic acid (5-ASA-UDCA). These conjugates are split by bacterial bile acid (cholylglycine) hydrolase. In the tests, the time courses of the urinary excretion rates of PABA or 5-ASA, including their metabolites, are determined as the measure of hydrolytic activity of intestinal bacteria. Although the number of clinical trials with this urinary excretion tests is small, results demonstrated the usefulness of bile acid conjugates as SIBO diagnostic substrates. PABA-UDCA disulfate, a single-pass type unabsorbable compound without the hydrolysis of conjugates, was likely to offer a simple and rapid method for the evaluation of SIBO without the use of radioisotopes or expensive special apparatus. Treatments of SIBO with antibiotics, probiotics, therapeutic diets, herbal medicines, and/or fecal microbiota transplantation are also reviewed.
PubMed: 36830173
DOI: 10.3390/antibiotics12020263 -
British Journal of Clinical Pharmacology Nov 2020Following its introduction as an antituberculosis agent close to 75 years ago, the use of para-aminosalicylic acid (PAS) has been limited by gastrointestinal intolerance... (Review)
Review
Following its introduction as an antituberculosis agent close to 75 years ago, the use of para-aminosalicylic acid (PAS) has been limited by gastrointestinal intolerance and multiple formulations were produced in attempts to reduce its occurrence. More recently, an enteric-coated, granular, slow-release PAS formulation (PASER) was introduced and is now in wide-spread use for the treatment of drug-resistant tuberculosis. The current PASER dosing regimen is based on recommendations derived from older studies using a variety of different PAS formulations and relegate PAS to a role as an exclusively bacteriostatic agent. However, there is ample evidence that if sufficiently high serum concentrations are reached, PAS can be bactericidal and that intolerance following once daily dosing, that aids the achievement of such concentrations, is no worse than that following intermittent daily dosing. In particular, prevention of resistance to companion drugs appears to be dependent on the size of the single dose, and hence the peak concentrations, and not on maintaining serum levels consistently above minimum inhibitory concentration. We present a narrative review of the development of PAS formulations, dosing practices, and published data regarding pharmacokinetics and pharmacodynamics and the relationship of PAS dosage to intolerance and efficacy. Our conclusions suggests that we are at present not using PAS to its maximum ability to contribute to regimen efficacy and protect companion drugs.
Topics: Aminosalicylic Acid; Antitubercular Agents; Delayed-Action Preparations; Humans; Microbial Sensitivity Tests; Tuberculosis, Multidrug-Resistant
PubMed: 32470182
DOI: 10.1111/bcp.14395 -
Inflammatory Intestinal Diseases Jan 2022Due to the increased incidence of colorectal cancer in inflammatory bowel diseases (IBDs), the value of chemoprevention for this patient group has been repeatedly... (Review)
Review
BACKGROUND
Due to the increased incidence of colorectal cancer in inflammatory bowel diseases (IBDs), the value of chemoprevention for this patient group has been repeatedly debated in the past decade. This review describes available evidence and the current recommendations for chemoprevention in national and international guidelines IBD guidelines.
SUMMARY
5-Aminosalicylic acid (5-ASA) compounds are the preferred therapeutic option for mild to moderate ulcerative colitis (UC). Aside from the known anti-inflammatory effects, their chemopreventive abilities have been described in vitro and in vivo. Pooling the increasing number of retrospective and population-based clinical studies over the last 15 years, 7 consecutive meta-analyses revealed partially conflicting results for the chemopreventive efficacy of 5-ASA, and thus, not all IBD guidelines currently recommend chemoprevention with mesalamine compounds. Accumulating evidence for decreasing the colorectal cancer (CRC) risk in support of thiopurines more recently shows a protective effect. This effect seems solely mediated by control of intestinal inflammation since, for this drug class, another mechanistic interference in IBD-associated CRC pathogenesis is not known. The results regarding chemopreventive efficacy for ursodeoxycholic acid or folic acid are equivocal, and the use of these medications to prevent CRC is not firmly established. Like UC, the risk of CRC is also significantly increased in patients with Crohn's disease (CD), especially Crohn's colitis. However, no published studies exclusively assess the effects of surveillance on the early detection of cancer or CRC chemoprevention in CD patients. In meta-analyses, which predominantly included UC patients, 5-ASA or thiopurines were not beneficial in small CD subgroups. The level of evidence for anti-TNFα agents, anti-integrin (e.g., vedolizumab), or anti-IL-12/IL-23 agents (e.g., ustekinumab) and Janus kinase inhibitors is currently too low or nonexistent to use them solely for chemoprevention in UC or CD patients.
KEY MESSAGE
Intestinal inflammation is one of the main risk factors for developing CRC in IBD, and all drugs that induce and maintain mucosal healing most likely also decrease the IBD-associated CRC risk. Thus, a therapeutic strategy of adding a 5-ASA therapy to a successfully mucosal healing-inducing therapy, for example, with a biologic or a small molecule merely to prevent CRC appears to be obsolete.
PubMed: 35224015
DOI: 10.1159/000518865 -
The Canadian Journal of Hospital... 2016Use of medications containing the 5-aminosalicylic acid (5-ASA) moiety may cause a rare but potentially lethal side effect involving inflammation of the heart... (Review)
Review
BACKGROUND
Use of medications containing the 5-aminosalicylic acid (5-ASA) moiety may cause a rare but potentially lethal side effect involving inflammation of the heart (myocarditis) or pericardium (pericarditis) or both (myopericarditis). Early recognition of 5-ASA as the cause is important to prevent progression of the inflammation.
OBJECTIVE
To provide clinicians with information to assist in recognizing the signs and symptoms of 5-ASA-induced cardiac inflammation and the characteristics of the suspected therapy, and in determining the appropriate approach to treatment.
DATA SOURCES STUDY SELECTION AND DATA EXTRACTION
The Embase database was searched, for the period 1974 to July 17, 2015, for published descriptions of cases of cardiac inflammation caused by 5-ASA-containing medications. The search terms included the names of specific agents, as well as terms for different types of cardiac inflammation. Articles in any language were retained for inclusion in this narrative review.
FINDINGS
There is no symptom, sign, laboratory test, or constellation of symptoms and signs that is pathognomonic for 5-ASA-induced myocardial-pericardial toxicity. Similarly, there is no single laboratory, electrocardiographic, or echocardiographic finding or combination of findings that implicates 5-ASA as the cause of nonspecific symptoms. However, most patients present with chest pain, shortness of breath, and fever within the first 28 days after initiating 5-ASA. Physical examination, electrocardiography, and diagnostic imaging will yield findings consistent with myocarditis, with or without accompanying pericarditis. Prompt discontinuation of the 5-ASA will result in resolution of symptoms within days, without the need for any adjunctive therapies. Rechallenge with any 5-ASA-containing compound carries a high risk for recurrence of the inflammation.
CONCLUSIONS
Any patient presenting with chest pain, shortness of breath, or fever within 28 days after initiating a 5-ASA-containing drug should be considered as exhibiting drug-induced inflammation. The 5-ASA-containing drug should be stopped immediately until other causes can be proven (or excluded); if no other cause is discovered, the 5-ASA should not be restarted.
PubMed: 28123193
DOI: No ID Found