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Drugs for Treatment of Diarrhea-Predominant IBS01:17

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Diarrhea-predominant irritable bowel syndrome (IBS-D) is a subtype of IBS characterized primarily by frequent, loose, or watery stools, abdominal pain, and abdominal discomfort. Therapeutic approaches to managing IBS-D include dietary changes, stress management techniques, and pharmaceutical interventions.
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Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
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Acute diarrhea, a common gastrointestinal disturbance, is characterized by the rapid evacuation of fluid stools, leading to an excessive weight in fluid. This condition typically arises from disorders affecting intestinal water and electrolyte transport. It can be triggered by an increased osmotic load within the intestine, excessive secretion of electrolytes and water, mucosal exudation of protein and fluid, or altered intestinal motility. The primary risks of acute diarrhea are dehydration...
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Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
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Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
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Diarrhea is characterized by the occurrence of frequent, watery bowel movements. Various factors can trigger diarrhea, including viral or bacterial infections, foodborne illnesses, side effects from certain medications, and underlying digestive disorders. If not adequately managed, diarrhea can lead to complications such as dehydration, electrolyte imbalances, and nutrient deficiencies. Severe diarrhea can lead to significant weight loss, malnutrition, and weakened immune function.
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Immune checkpoint inhibitor associated diarrhoea.

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Area of Science:

  • Oncology
  • Gastroenterology
  • Immunology

Background:

  • Immunotherapy with immune checkpoint inhibitors like pembrolizumab is a standard treatment for various cancers.
  • Adverse events related to immunotherapy can affect multiple organ systems.
  • Gastrointestinal side effects are common, but pancreatic exocrine insufficiency is a less recognized complication.

Purpose of the Study:

  • To report a case of pancreatic exocrine insufficiency secondary to pembrolizumab treatment.
  • To highlight the diagnostic challenges and successful management of this rare adverse event.

Main Methods:

  • A case report of an elderly male patient with lung adenocarcinoma undergoing pembrolizumab therapy.
  • Clinical assessment, exclusion of common gastrointestinal pathologies, and endoscopic evaluation.
  • Biochemical testing including fecal elastase levels.

Main Results:

  • The patient developed symptoms consistent with colitis, which were refractory to standard treatment.
  • Endoscopic findings were unremarkable for colitis.
  • Low fecal elastase confirmed pancreatic exocrine insufficiency.
  • Symptoms resolved with pancreatic enzyme replacement therapy.

Conclusions:

  • Pembrolizumab can induce pancreatic exocrine insufficiency, mimicking other gastrointestinal conditions.
  • Fecal elastase testing is crucial for diagnosing this immunotherapy-induced complication.
  • Pancreatic enzyme replacement therapy is an effective treatment for pembrolizumab-induced pancreatic exocrine insufficiency.