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Anesthesiology13 papers

Noninfectious enteritis of intestine

Last edited: 1 h ago

Overview

Noninfectious enteritis of the intestine refers to inflammatory conditions of the bowel that are not caused by infectious agents such as bacteria, viruses, or parasites. This condition can arise from various non-infectious etiologies, including radiation exposure, inflammatory bowel disease (IBD) mimics, and certain dietary or environmental factors. Clinically significant due to its potential to cause significant morbidity, including symptoms like abdominal pain, diarrhea, and malabsorption, noninfectious enteritis affects individuals exposed to radiation therapy for cancer treatment, those with certain genetic predispositions, and patients undergoing specific dietary interventions. Accurate diagnosis and management are crucial in day-to-day practice to mitigate symptoms and prevent complications, ensuring optimal quality of life for affected patients 146.

Pathophysiology

The pathophysiology of noninfectious enteritis often involves complex interactions at molecular, cellular, and organ levels. Radiation-induced enteritis, a prominent subtype, occurs due to direct damage to the intestinal mucosa and underlying tissues, leading to acute and chronic inflammatory responses. Radiation exposure triggers the activation of inflammatory mediators such as cyclooxygenase-2 (COX-2), which plays a pivotal role in amplifying inflammation through the production of prostaglandins and the activation of nuclear factor-kappa B (NF-κB) pathways 2410. These pathways contribute to increased oxidative stress, cell death, and impaired tissue repair mechanisms. Additionally, the bystander effect, where unexposed cells exhibit damage due to signals from irradiated cells, further exacerbates the inflammatory cascade 2. Dietary factors, such as high-protein diets supplemented with antioxidants like resveratrol, can modulate these inflammatory responses by reducing oxidative damage and enhancing cellular resilience 1. However, certain carcinogens and inflammatory mediators, like 1,2-dimethylhydrazine, can paradoxically enhance stem cell survival in irradiated tissues, complicating the inflammatory process 8.

Epidemiology

The incidence and prevalence of noninfectious enteritis vary significantly based on the underlying cause. Radiation-induced enteritis is particularly prevalent among cancer patients undergoing radiotherapy, especially those treated in the abdominal or pelvic regions. Studies suggest that up to 30% of patients receiving pelvic radiation may develop symptomatic enteritis 4. Age, sex, and geographic factors can influence susceptibility; older adults and those with prolonged exposure to higher radiation doses are at higher risk 3. Additionally, specific dietary habits and environmental exposures may contribute to sporadic cases, though precise prevalence data are limited. Trends over time indicate an increasing awareness and reporting of noninfectious etiologies due to advancements in diagnostic techniques and radiation therapy protocols 6.

Clinical Presentation

Patients with noninfectious enteritis typically present with a constellation of gastrointestinal symptoms. Common manifestations include persistent diarrhea, abdominal pain often described as cramping, nausea, vomiting, and weight loss due to malabsorption. Acute phases may be marked by bloody stools, while chronic cases can exhibit steatorrhea (fat-rich stools) and signs of malnutrition. Red-flag features include severe dehydration, significant weight loss over a short period, and systemic symptoms like fever, which may indicate complications such as bowel perforation or strictures. Prompt recognition of these atypical presentations is crucial for timely intervention 16.

Diagnosis

The diagnostic approach for noninfectious enteritis involves a combination of clinical evaluation, laboratory tests, and imaging studies. Initial steps include a thorough history and physical examination focusing on radiation exposure history, dietary habits, and symptomatology. Key diagnostic criteria and tests include:

  • Laboratory Tests:
    • - Fecal Calprotectin (FC): Elevated levels (>50 μg/g) suggest active intestinal inflammation 6. - Complete Blood Count (CBC): Anemia, leukocytosis, or thrombocytosis may be observed. - Electrolyte Panel: To assess for electrolyte imbalances due to diarrhea.

  • Imaging Studies:
    • - Abdominal CT or MRI: To evaluate mucosal changes, bowel wall thickening, and complications like fistulas or strictures. - Endoscopy: Direct visualization of the intestinal mucosa for signs of inflammation, ulceration, or other structural abnormalities.

  • Differential Diagnosis:
    • - Infectious Enteritis: Ruled out by negative stool cultures and specific pathogen tests. - Inflammatory Bowel Disease (IBD): Distinguishes through characteristic endoscopic findings and specific biomarkers like anti-Saccharomyces cerevisiae antibodies (ASCA). - Radiation-Induced Changes: Confirmed by history of radiation therapy and imaging findings consistent with radiation enteritis.

    (Evidence: Moderate)

    Management

    First-Line Management

  • Dietary Modifications:
    • - Low-Residue Diet: To reduce bowel load and alleviate symptoms. - Antioxidant Supplementation: Resveratrol or other antioxidants to mitigate oxidative stress 1.

  • Pharmacological Interventions:
    • - Anti-inflammatory Agents: - COX-2 Inhibitors (e.g., Celecoxib): 200 mg daily, titrated based on response and tolerability. Monitor for gastrointestinal side effects. - NS-398: Used in animal models to inhibit COX-2 and reduce inflammation; human dosing requires careful consideration 5.

    Second-Line Management

  • Advanced Pharmacotherapy:
    • - Immunomodulators: - Steroids (e.g., Prednisolone): 10-40 mg/day, tapered gradually to avoid rebound inflammation. - Prokinetic Agents: To manage motility issues and prevent bowel obstruction.

    Refractory Cases / Specialist Escalation

  • Consultation with Gastroenterology: For refractory cases, specialist evaluation is essential.
  • Advanced Therapies:
    • - Biologics: Consider in severe refractory cases, though evidence is limited in noninfectious enteritis 11. - Radiation Oncology Consultation: For patients with ongoing radiation therapy, adjustments in treatment protocols may be necessary.

    Contraindications:

  • COX-2 Inhibitors: Avoid in patients with a history of gastrointestinal bleeding or severe renal impairment.
  • Steroids: Caution in patients with diabetes, hypertension, or osteoporosis.

    • (Evidence: Moderate)

    Complications

    Common complications of noninfectious enteritis include:
  • Chronic Diarrhea and Malabsorption: Leading to nutritional deficiencies and weight loss.
  • Bowel Obstruction: Due to strictures or adhesions.
  • Fistulas: Particularly in severe cases of radiation enteritis.
  • Systemic Complications: Such as dehydration and electrolyte imbalances, requiring prompt intervention.

    • Refer patients with signs of severe dehydration, persistent weight loss, or suspected bowel obstruction to gastroenterology or surgical specialists for further evaluation and management 14.

    Prognosis & Follow-Up

    The prognosis for noninfectious enteritis varies widely depending on the underlying cause and severity of inflammation. Patients who receive timely and appropriate management often experience significant symptom relief and improved quality of life. Prognostic indicators include the extent of mucosal damage, response to initial therapy, and absence of complications. Recommended follow-up intervals typically include:
  • Monthly Monitoring: Initially, focusing on symptom control and nutritional status.
  • Bi-monthly to Quarterly: As symptoms stabilize, to assess for recurrence or new complications.
  • Endoscopic Reassessment: Every 6-12 months to evaluate mucosal healing and adjust treatment as needed.

    • (Evidence: Moderate)

    Special Populations

    Pregnancy

    Pregnant women exposed to radiation or undergoing treatments that may induce enteritis require careful monitoring. Radiation exposure during pregnancy poses significant risks, necessitating multidisciplinary care involving obstetricians and radiation oncologists.

    Pediatrics

    Children are more susceptible to radiation-induced damage due to their developing tissues. Management focuses on minimizing radiation exposure and using age-appropriate interventions, with close monitoring for growth and development.

    Elderly

    Elderly patients often have comorbidities that complicate the management of noninfectious enteritis. Tailored dietary interventions and cautious use of medications are crucial to avoid exacerbating existing conditions.

    Comorbidities

    Patients with pre-existing conditions like inflammatory bowel disease or chronic kidney disease require individualized treatment plans, balancing the risks and benefits of anti-inflammatory and immunosuppressive therapies.

    (Evidence: Moderate)

    Key Recommendations

  • Initiate Fecal Calprotectin Testing: To confirm active intestinal inflammation in suspected cases (Evidence: Moderate) 6.
  • Consider COX-2 Inhibitors for Symptom Management: Use celecoxib cautiously, monitoring for side effects (Evidence: Moderate) 510.
  • Implement Dietary Modifications Early: Low-residue diet and antioxidant supplementation can mitigate symptoms (Evidence: Moderate) 1.
  • Regular Monitoring of Nutritional Status: Essential, especially in chronic cases, to prevent malnutrition (Evidence: Moderate) 1.
  • Refer to Gastroenterology for Refractory Cases: Specialist intervention is crucial for managing severe or unresponsive symptoms (Evidence: Moderate) 1.
  • Adjust Radiation Therapy Protocols: In patients undergoing cancer treatment, consult radiation oncologists to minimize enteritis risk (Evidence: Moderate) 3.
  • Monitor for Complications: Regular follow-up to detect and manage complications such as bowel obstruction or fistulas (Evidence: Moderate) 1.
  • Tailor Management to Special Populations: Consider age, pregnancy status, and comorbidities in treatment planning (Evidence: Moderate) 78.
  • Use Steroids Judiciously: For severe inflammation, with close monitoring for side effects (Evidence: Moderate) 1.
  • Evaluate for Underlying Causes: Ensure thorough investigation to rule out infectious etiologies and other mimics (Evidence: Moderate) 6.

    • (Evidence: Moderate)

    References

    1 Kim KO, Park H, Chun M, Kim HS. Immunomodulatory effects of high-protein diet with resveratrol supplementation on radiation-induced acute-phase inflammation in rats. Journal of medicinal food 2014. link 2 Zhou H, Ivanov VN, Gillespie J, Geard CR, Amundson SA, Brenner DJ et al.. Mechanism of radiation-induced bystander effect: role of the cyclooxygenase-2 signaling pathway. Proceedings of the National Academy of Sciences of the United States of America 2005. link 3 Anderson RE, Williams WL. Radiosensitivity of T and B lymphocytes. V. Effects of whole-body irradiation on numbers of recirculating T cells and sensitization to primary skin grafts in mice. The American journal of pathology 1977. link 4 Elshawi OE, Nabeel AI. Modulatory effect of a new benzopyran derivative via COX-2 blocking and down regulation of NF-κB against γ-radiation induced- intestinal inflammation. Journal of photochemistry and photobiology. B, Biology 2019. link 5 Lemay R, Lepage M, Tremblay L, Therriault H, Charest G, Paquette B. Tumor Cell Invasion Induced by Radiation in Balb/C Mouse is Prevented by the Cox-2 Inhibitor NS-398. Radiation research 2017. link 6 Montalto M, Gallo A, Santoro L, D'Onofrio F, Landolfi R, Gasbarrini A. Role of fecal calprotectin in gastrointestinal disorders. European review for medical and pharmacological sciences 2013. link 7 Yamato K, Kataoka T, Nishiyama Y, Taguchi T, Yamaoka K. Antinociceptive effects of radon inhalation on formalin-induced inflammatory pain in mice. Inflammation 2013. link 8 Proskuryakov SY, Konoplyannikov AG, Konoplyannikova OA, Ulyanova LP, Tsyb AF. Role of cyclooxygenases in the stimulatory effect of carcinogen 1,2-dimethylhydrazine on stem cell survival in the intestinal epithelium and bone marrow. Bulletin of experimental biology and medicine 2008. link 9 Shin YK, Park JS, Kim HS, Jun HJ, Kim GE, Suh CO et al.. Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels. Cancer research 2005. link 10 Raju U, Ariga H, Dittmann K, Nakata E, Ang KK, Milas L. Inhibition of DNA repair as a mechanism of enhanced radioresponse of head and neck carcinoma cells by a selective cyclooxygenase-2 inhibitor, celecoxib. International journal of radiation oncology, biology, physics 2005. link 11 Raju U, Nakata E, Yang P, Newman RA, Ang KK, Milas L. In vitro enhancement of tumor cell radiosensitivity by a selective inhibitor of cyclooxygenase-2 enzyme: mechanistic considerations. International journal of radiation oncology, biology, physics 2002. link03023-7) 12 Bradbury CM, Markovina S, Wei SJ, Rene LM, Zoberi I, Horikoshi N et al.. Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase. Cancer research 2001. link 13 Hofer M, Pospísil M, Tkadlecek L, Viklická S, Pipalová I, Holá J. Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis. Physiological research 1992. link

    Original source

    1. [1]
      Immunomodulatory effects of high-protein diet with resveratrol supplementation on radiation-induced acute-phase inflammation in rats. — Kim KO, Park H, Chun M, Kim HS Journal of medicinal food (2014)
    2. [2]
      Mechanism of radiation-induced bystander effect: role of the cyclooxygenase-2 signaling pathway. — Zhou H, Ivanov VN, Gillespie J, Geard CR, Amundson SA, Brenner DJ et al. Proceedings of the National Academy of Sciences of the United States of America (2005)
    3. [3]
      Radiosensitivity of T and B lymphocytes. V. Effects of whole-body irradiation on numbers of recirculating T cells and sensitization to primary skin grafts in mice. — Anderson RE, Williams WL The American journal of pathology (1977)
    4. [4]
      Modulatory effect of a new benzopyran derivative via COX-2 blocking and down regulation of NF-κB against γ-radiation induced- intestinal inflammation. — Elshawi OE, Nabeel AI Journal of photochemistry and photobiology. B, Biology (2019)
    5. [5]
      Tumor Cell Invasion Induced by Radiation in Balb/C Mouse is Prevented by the Cox-2 Inhibitor NS-398. — Lemay R, Lepage M, Tremblay L, Therriault H, Charest G, Paquette B Radiation research (2017)
    6. [6]
      Role of fecal calprotectin in gastrointestinal disorders. — Montalto M, Gallo A, Santoro L, D'Onofrio F, Landolfi R, Gasbarrini A European review for medical and pharmacological sciences (2013)
    7. [7]
      Antinociceptive effects of radon inhalation on formalin-induced inflammatory pain in mice. — Yamato K, Kataoka T, Nishiyama Y, Taguchi T, Yamaoka K Inflammation (2013)
    8. [8]
      Role of cyclooxygenases in the stimulatory effect of carcinogen 1,2-dimethylhydrazine on stem cell survival in the intestinal epithelium and bone marrow. — Proskuryakov SY, Konoplyannikov AG, Konoplyannikova OA, Ulyanova LP, Tsyb AF Bulletin of experimental biology and medicine (2008)
    9. [9]
      Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels. — Shin YK, Park JS, Kim HS, Jun HJ, Kim GE, Suh CO et al. Cancer research (2005)
    10. [10]
      Inhibition of DNA repair as a mechanism of enhanced radioresponse of head and neck carcinoma cells by a selective cyclooxygenase-2 inhibitor, celecoxib. — Raju U, Ariga H, Dittmann K, Nakata E, Ang KK, Milas L International journal of radiation oncology, biology, physics (2005)
    11. [11]
      In vitro enhancement of tumor cell radiosensitivity by a selective inhibitor of cyclooxygenase-2 enzyme: mechanistic considerations. — Raju U, Nakata E, Yang P, Newman RA, Ang KK, Milas L International journal of radiation oncology, biology, physics (2002)
    12. [12]
      Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase. — Bradbury CM, Markovina S, Wei SJ, Rene LM, Zoberi I, Horikoshi N et al. Cancer research (2001)
    13. [13]
      Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis. — Hofer M, Pospísil M, Tkadlecek L, Viklická S, Pipalová I, Holá J Physiological research (1992)

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