Tag Archives: fatigue

A Treatment for Severe Fatigue Associated with Inflammatory Bowel Disease?

Posted on by

The proverb “Necessity is the mother of invention” is often attributed to Plato. In the dialogue of The Republic, Plato wrote, “our need will be the real creator”. This quote came to mind as I was reading about the use of f for fatigue in inflammatory bowel disease (IBD).

CD Moulton et al. Clin Gastroenterol Hepatol 2024; 22: 1737-1740. Open Access! Modafinil for Severe Fatigue in Inflammatory Bowel Disease: A Prospective Case Series

Background: “Fatigue is highly prevalent in patients with IBD, affecting 72% of patients with active inflammatory bowel disease (IBD) and 47% in remission, and is associated with poor quality of life, absenteeism and presenteeism.1 However, understanding the mechanisms of IBD fatigue remains limited, as reflected in a lack of effective treatments.1“

Methods: “Ten patients with IBD and severe fatigue were referred to a consultant psychiatrist. In all cases, mucosal inflammation and organic causes of fatigue (anemia, B12 deficiency, hypothyroidism) had been investigated and treated as much as possible. We measured fatigue severity using the IBD Fatigue Assessment Scale (IBD-FAS), designed specifically for IBD.5 Scores of 11 or higher out of 20 indicate severe fatigue and we only included patients scoring in this range.5

Dosing (for adults) of modafnil is described in the article.

Key findings:

  • “At baseline, the mean IBD-FAS score was 16.0 (SD, 1.7) of 20. After modafinil treatment [at 6 months], the mean IBD-FAS score was 6.7 (SD, 3.0), representing a mean improvement of 58.1% from baseline.”
  • “Although all 10 patients were severely fatigued at baseline, only 2 patients were still in the severe fatigue range after treatment.”
  • “Tolerability was good: 1 patient reported transient headache and 1 patient reported transient dizziness; another patient reported mild palpitations; but none of the patients reported gastrointestinal side effects.”

My take: Perhaps, modafinil will be helpful –pharmacologic therapy for severe fatigue is an unmet need. More studies are needed as this is a small study without a control group.

Related blog posts:

IBD Updates: Extending Mirkizumab Induction, Best Biologic, Fatigue in Pediatric IBD, Adalimumab Success in Patients with Abdominal Abscess

Posted on by
  1. G D’Haens et al. Inflamm Bowel Dis 2024; https://doi.org/10.1093/ibd/izae004. Extended Induction and Prognostic Indicators of Response in Patients Treated with Mirikizumab with Moderately to Severely Active Ulcerative Colitis in the LUCENT Trials

Key findings:

  • Of patients not achieving clinical response during 12-week induction, 53.7% achieved response following extended induction (additional 3 doses of IV infusion every 4 weeks)
  • With “extended induction,” total of 80.3% mirikizumab-treated patients achieved clinical response by W24

2. S Schreiber et al. Inflamm Bowel Dis 2024; 30: S7. NETWORK META-ANALYSIS TO EVALUATE THE COMPARATIVE EFFICACY OF BIOLOGICS FOR MAINTENANCE TREATMENT OF ADULT PATIENTS WITH CROHN’S DISEASE

Methods: A network meta-analysis (NMA) was conducted to evaluate comparative efficacy of licensed biologics. Phase 3 randomized controlled-trials (RCTs) evaluating biologics approved by the European Medicines Agency or United States Food and Drug Administration as of 31 March 2023 for maintenance treatment of adult patients with moderate-to-severe CD were included, i.e. infliximab (IFX) intravenous (IV) and SC, adalimumab (ADL) SC, vedolizumab (VDZ) IV and SC, ustekinumab (UST) SC, and risankizumab (RZB) SC.

Key findings:

  • Among 8 comparator arms, IFX SC 120 mg every 2 weeks (Q2W) showed the highest odds ratio (95% credible interval) vs. PBO for clinical remission during the maintenance phase (3.52 [2.18–5.65]).

My take: This meta-analysis shows a favorable response for IFX SC; however, head-to-head trials are needed to really determine which biologic has the highest efficacy.

3. N Bevers et al. JPGN 2024; 2023; 77: 628-633. Fatigue and Physical Activity Patterns in Children With Inflammatory Bowel Disease

In this cross-sectional study with 104 children (24 with fatigue), biological parameters (CRP, fecal calprotectin) did not discriminate fatigued from non-fatigued patient

4. Y Bouhnik et al. Clin Gastroenterol Hepatol 2023; 21: 3365-3378. Adalimumab in Biologic-naïve Patients With Crohn’s Disease After Resolution of an Intra-abdominal Abscess: A Prospective Study From the GETAID

In this multicenter prospective study with 117 patients, the authors examined the success rate of adalimumab (ADA) in patients with CD with an intra-abdominal abscess resolved without surgery.

Key findings:

  • At W24, the survival rate without abscess recurrence or surgery was 74% (n=87)
  • Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18)

My take (borrowed from authors): Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess

Adjacent to Honeymoon Beach, St John

IBD Updates: Fatigue Trajectory, Risk of IBD with Derm Findings

Posted on by

NZ Borren et al. Inflamm Bowel Dis 2021; 27: 1740-1746. Open Access: Longitudinal Trajectory of Fatigue in Patients With Inflammatory Bowel Disease: A Prospective Study

In this prospective study using the CCFA IBD Partners cohort, the authors examined fatigue symptoms with questionnaires (FACIT-F and MDI) at 3 timepoints over a 1 year period. There was likely a strong selection bias among participants (mean disease duration was 18 years) who chose to complete theses questionnaires. Key findings:

  • Persistent fatigue (at baseline and at 6 months) was the most common pattern, affecting two-thirds (65.8%) of patients
  • The strongest predictor of incident fatigue was sleep disturbance at baseline (odds ratio, 2.91.
  • Only 12.3% of those with fatigue at baseline had symptom resolution by 6 months. Resolution was more likely in patients with a diagnosis of ulcerative colitis, quiescent disease, and an absence of significant psychological comorbidity

My take: In those with fatigue, it is often persistent.

Related blog post: #MondayNightIBD and Fatigue

D King et al. Inflamm Bowel Dis 2021; 27: 1731-1739. The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients With Dermatological Disorders Associated With Inflammatory Bowel Disease

The authors retrospectively studied 7447 patients with dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet’s syndrome, and aphthous stomatitis which can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs).

Key findings:

  • 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs
  • Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs

My take: The absolute risk if IBD is low in patients with D-EIMs but still increased 6-fold. This would probably be a good population to screen for IBD with a biomarker (eg. calprotectin)

Related blog post: Review of Pyoderma Gangrenosum

J Shah et al. Inflamm Bowel Dis 2021; 27: 1832-1838. Ocular Manifestations of Inflammatory Bowel Disease Nice review: “ocular manifestations of IBD include keratopathy, episcleritis, scleritis, and uveitis and are among the most common extraintestinal manifestations.” Urgent referral to ophthalmology needed if deep eye pain that can awaken from sleep (?scleritis), if photosensitivity/blurry vision/headache (?anterior uveitis), or if floaters/decreased vision (?posterior uveitis)

#MondayNightIBD and Fatigue

Posted on by

#MondayNightIBD is an open access learning forum on twitter. It was recently highlighted in Gastroenterology and Endoscopy News: A #MondayNightIBD Conversation: Fatigue, a Frustrating, Multifactorial Manifestation of IBD (requires login)

For the issue of fatigue and IBD, besides active IBD and anemia, the authors recommend considering medication side effects (especially from immunomodulators/corticosteroids and cannabis), mental health, sleep disorders, and nutritional concerns (?role for thiamine supplementation). Even when all these issues are addressed, many times fatigue persists.

Here is the proposed algorithm from July 24, 2020.

#MondayNightIBD has a lot of topics that they have covered including functional medicine, COVID, sexual health, utilizing social medicine, grief and pharmacology.

Nutrition Imbalance for Ventilated Children

Posted on by

A recent study documents a high rate of nutritional problems among a prospective cohort of 20 children on home ventilators and documents a metabolic assessment aimed at improving these problems (Martinez EE, et al. J Pediatr 2015; 166: 350-7, ed 228-29).

In these children the authors did careful nutritional assessment with anthropometry, bioelectrical impedance analysis (BIA), actual energy intake (AEI), and indirect calorimetry in the subject’s home. Indirect calorimetry was used to calculate a measured energy expenditure (MEE).

Indirect calorimetry allows measurement of energy expenditure: (From NASPGHAN Foundation N2U Course 2012, Praveen Goday: “Energy and Protein Metabolism”)

  • “When carbohydrate, protein, and fat are oxidized, oxygen is consumed and carbon dioxide is produced.”
  • “If oxygen consumption and carbon dioxide production can be measured, the energy released in the course of the utilization of these gases (or the energy expenditure can be determined.”
  • “The techniques is referred to as indirect, because gas exchange does not actually measure heat production.”

Key findings:

  • 13 were either underfed (AEI:MEE <90%) or overfed (AEI:MEE >110%)
  • 11 of 19 had suboptimal protein intake
  • 15 subjects were hypo or hypermetabolic

The authors conclude that a “majority of children on home ventilation are characterized by malnutrition, altered metabolic status, and suboptimal macronutrient intake” (especially low protein intake).  The discussion lists many of the study limitations: small number, discrepancies between some of their measuring tools, lack of long-term followup, lack of widespread availability of mobile indirect calorimetry, diverse comorbidities, and reliance of 3-day food records. In addition, the indirect calorimetry must be properly calibrated, performed when patient at baseline state, and feedings held (if on bolus feeds).

Although I think this study makes some important points, I think the ‘high-tech’ approach is overemphasized.  It would be interesting to see how (if at all) these interventions would improve a child who is followed closely by a nutritionist and a GI physician.  While precise measurement of resting energy expenditure, when performed properly, is informative, I think this information is much less helpful than serial basic measurements.

At the same time, there are many limitations on optimal nutrition in these children.  The mobility problems of many kids on home ventilators can make gaining weight problematic for care providers.  It is not practical for all caregivers to manage a 60 kg adolescent.

Recent advice from N2U () regarding children who were tube-fed/wheelchair-bound:

  • In children older than 10 years, if they are receiving 6 cans/day of commercial formula product, they are likely receiving adequate nutrients.
  • In children younger than 10 years, if if they are receiving 4 cans/day of commercial formula product, they are likely receiving adequate nutrients.
  • The newer reduced calorie formulas make it easier to provide adequate nutrients without excessive calories
  • Avoid obesity in these children.  Losing weight can be very difficult in this population.

Bottomline: Children on ventilators often are too heavy or too thin and need to be followed closely.  Whether indirect calorimetry is useful in this regard is not clear to me.

Briefly noted: A high nutrient diet appears to help treat fatigue (Nutrients 2015, 7(3), 1965-1977).  From abstract (thanks to Kipp Ellsworth): A group of 98 children (2–18 years old) with unexplained symptoms of fatigue was examined. Children in the intervention group were asked to follow the diet for three months, whereas the control-group followed their normal diet.  The dietary modifications consisted of green vegetables, beef, whole milk and full-fat butter.

From NPR: Empathy Cards “Please Let Me Be the First to Punch the Next Person Who Says Everything Happens for a Reason”

Sarcopenia, fatigue, and nutrition in chronic liver disease

Posted on by

Several articles from a recent Clinical Gastroenterology and Hepatology have addressed nutritional aspects of chronic liver disease.

1. Sarcopenia?  This term refers to generalized loss of skeletal muscle.  It does not equate to malnutrition though there is significant overlap.  (Clinical Gastroenterology and Hepatology 2012; 10: 166-73 & editorial 100).  In this study, 112 adults with cirrhosis had CT scans which examined skeletal muscle at the L3 level; 40% had sarcopenia. Sarcopenia was independently associated with mortality and was not reflected in MELD score.  Patients had increased risk of death from sepsis and liver failure (HR 2.18).  Thus, sarcopenia joins hyponatremia, refractory ascites, hepatic encephalopathy as additional factors which add prognostic information to MELD score.

2. Fatigue in cirrhosis. (Clinical Gastroenterology and Hepatology 2012; 10: 174-81 & editorial 103).  Fatigue is common in cirrhosis and is multifactorial.  In this prospective study, 108 patients were evaluated with a fatigue impact scale. Fatigue improved after liver transplantation. Fatigue can be peripheral due to muscle weakness and dysfunction. And, fatigue can be central due to difficulty performing physical and mental activities.  Central fatigue is associated with an increased perceived effort for tasks and often related to depression; this type of fatigue is much more common with cirrhosis.  Although improved, fatigue often does not completely resolve with liver transplantation.

3. Nutrition recommendations. (Clinical Gastroenterology and Hepatology 2012; 10: 117-25).  A summary of nutrition recommendations in adults  with chronic liver disease is given in this article.  One common misconception is protein restriction.  This is not beneficial.  Protein recommendations are for adult patients with cirrhosis to receive 1-1.5 g/kg/day.  This amount is higher than for healthy individuals.  Protein restriction leads to protein catabolism, muscle breakdown and increases the likelihood of hepatic encephalopathy.

Additional references:

  • -Age Ageing 2010; 39: 412-23.  Sarcopenia consensus definitions in older people.
  • -Gastroenterology 2008; 134: 1741. Evaluation and management of end-stage liver disease in children. Recs vaccines due to functional asplenia/portal hypertension at age 2 for Neisseria (MCV4) or polysaccharide (MPSV4); at 6 weeks of age for pneumococcal conjugate vaccines. Reviews nutrition, varices, ascites, encephalopathy….
  • -Liver Transplant 2008; 14: 585-591. Poor growth often due to growth hormone resistance. Chronic malnutrition is a factor, but children with advanced liver dz may not grow despite adequate calories. Recs: for chronic liver dz: 130-150% of RDA based on ideal body wt; in infants 120-150 cal/kg/day. Increase MCT either thru formula or supplemental MCT.
  • -Liver Transplant 2006; 12: 1310. Review article on nutrition for OLTx patient.
  • -JPGN 2000; 30: 361. nutrition review and chronic liver disease.