Don’t forget HLH

A recent clinical challenge (Gastroenterol 2013; 145: 289, 489) regarding a a 78-year-old with a 12-year history of ulcerative colitis serves as a good reminder to remember hemophagocytic lymphohistiocytosis (HLH) in inflammatory bowel disease patients with high fever, even in the presence of recognized viral infections like cytomegalovirus and Epstein-Barr virus which can trigger HLH.  Patients receiving immunosuppressive medications are at risk.

Other clinical points:

  • Consider HLH when cytopenias are present in addition to fever
  • Ferritin values >10,000 mcg/L serves as a good screen

Take-home point: HLH has a significant mortality rate.  Quick recognition can improve outcome.

Related blog post:

Diagnosing hemophagocytic lymphohistiocytosis … – gutsandgrowth

NASPGHAN: Enteral Nutrition for Crohn’s Remission

A new document from NASPGHAN highlights the potential for enteric formulas (oral and nasogastric) as an alternative 1st line therapy for Crohn’s disease remission.  The following is a link with specific case examples along with background information and practical advice:

http://goo.gl/p19o0z 

Related blog post:

Rest easy with enteral nutrition | gutsandgrowth

Extensive Workup Not Needed for IBS

Another study has shown that an extensive workup is not needed for IBS (Clin Gastro Hepatol 2013; 11 956-62).

In this study from Denmark, the authors enrolled 302 patients aged 18-50 from a primary care setting with suspected IBS.  250 patients completed the entire study including a 1-year followup.  These patients fulfilled Rome III criteria and had no alarm signals which were the following:

  • Unexplained weight loss >3 kg
  • Rectal bleeding
  • Unexplained fever or anemia
  • Family history of inflammatory bowel disease (IBD) or colorectal cancer (CRC)
  • Abnormal physical exam

Patients were randomly assigned to either an extensive diagnostic group which included blood tests (including celiac screen & lactase gene test), stool exams, and sigmoidoscopy or to a “positive strategy” which involved testing only with a blood count (CBC/diff) and C-reactive protein.

The group which underwent a more extensive workup had no cases of serious disease, like IBD or CRC identified.  11 patients were identified with lactose intolerance, 1 patient had a rectal adenoma, 1 patient had a benign polyp, and 1 patient had giardiasis.

Overall, the authors and the accompanying editorial (pgs 963-964) conclude that the positive strategy was noninferior to the more extensive evaluation.  One limitation of this study was that patients had carried symptoms compatible with IBS for an average of 7 years before enrollment.

Take-home message: this study “adds to the growing body of evidence in favor of a relatively minimal symptom-based approach to diagnosing IBS.”

Related blog posts:

Understanding IBD Therapy Risks -A Good Link

This link was posted on the GI Bulletin Board.  It is a 6 minute internet video overview of the treatments for IBD -it would be a useful resource for most families:

http://www.youandibd.com/en/understanding-ibd/understanding-the-risks-and-benefits-of-ibd-therapies.html

Some related blog posts:

Data Supporting Miralax

A summary of the effectiveness of polyethylene glycol for chronic constipation, fecal disimpaction, and as a bowel preparation are presented in a recent article (JPGN 2013; 57: 134-40).

The article provides information on the biochemistry and mechanism of action along with a good number of references –49.

From the summary:

“PEG is an osmotic laxative used in children in the last few years.  It is more effective than lactulose for the treatment of chronic constipation.  It is equally effective compared with milk of magnesia and mineral oil for the long-term treatment of constipation but has a much better acceptance rate…It is a safe medication without any significant adverse effects.  Because PEG can be mixed in a beverage of the patient’s choice, it has excellent long-term patient acceptance.”

Related blog posts:

High Rates of Anxiety Develop in Kids with RAP

From NY Times review of a recent Pediatrics study:

Children with chronic stomach pains are at high risk for anxiety disorders in adolescence and young adulthood, a new study has found (goo.gl/I2UvHP ), suggesting that parents may wish to have their children evaluated at some point for anxiety.

Researchers at Vanderbilt University tracked 332 children with recurring stomachaches that could not be traced to a physical cause — so-called functional abdominal pain — comparing them as they reached young adulthood with 147 children who had never had such stomachaches.

About half the teenagers and young adults who had had functional abdominal pain as children developed an anxiety disorder at some point, compared with 20 percent of the control group, the researchers found. The vulnerability to anxiety persisted into adulthood even if the pain had disappeared, although the risk was highest if the pain continued.

Forty percent of the children with functional abdominal pain went on to experience depression, compared with 16 percent of those who had never had these stomachaches.

The study was published on Monday in the journal Pediatrics.

“What this study shows is a strong connection between functional abdominal pain and anxiety persists into adulthood, and it drives home the point that this isn’t by chance,” said Dr. John V. Campo, chairman of the department of psychiatry at Ohio State University, who was not involved in the new study….

Chronic abdominal pain affects 8 percent to 25 percent of school-age children. The problem can lead to school absences and take a toll on families.

“Somebody might say, ‘Of course they have mental issues or they are emotionally distressed — it’s because of the pain,’ ” said Lynn S. Walker, senior author of the study and director of the division of adolescent health at Monroe Carell Jr. Children’s Hospital at Vanderbilt.

“But we found even if the pain went away, these adolescents and young adults still have anxiety,” Dr. Walker said. “So maybe we need to treat their anxiety.”

The state-of-the-art treatment for functional abdominal pain is rehabilitative, focused on getting patients to participate in daily activities despite their stomachaches. “There’s no question that there are triggers for the pain, but the problem is in the perception of the pain and adaptation to the pain,” said Dr. Samuel Nurko, director of a functional abdominal pain center at Children’s Hospital Boston.

Dr. Nurko compared the pain to a light on a dimmer switch, which psychological techniques can help children control. “You don’t take away the pain,” he said. “You ‘dim’ it to be able to cope better.”

The new study underscores the importance of screening children with the condition for anxiety or depression, the authors said. Anxious children tend to be good children who are concerned about doing their best, Dr. Walker said, and parents may be flummoxed by the suggestion that such a child could be grappling with a mental health issue.

Related blog link:

Anxiety and Functional Abdominal Pain | gutsandgrowth  This link has additional links on related material.

Thiopurines associated with reduced risk of colon cancer

A recent study provides some good news for those using thiopurines (6-mercaptopurine and azathioprine) (Gastroenterol 2013; 145: 166-75).

Using the observational cohort enrolled in the French CESAME study (Cancers et Surrisque Associe aux Maladies Inflammatoires Intestinales En France), the authors followed 19,486 patients with IBD.  60.3% had Crohn’s disease, and 30.1% were receiving thiopurine therapy.  The study period was 2004-2007.  At the start of the study, 2841 patients (14.6%) had long-standing extensive colitis.

Among patients with long-standing extensive colitis, the hazard ratio for colrectal high grade dysplasia and cancer was 0.28 for those who received thiopurine therapy compared with those who never received thiopurine therapy.

Thus, this prospective study showed that while colorectal cancer (CRC) was increased in IBD patients with long-standing colitis, this risk was less among the subset who were treated with thiopurines.  Some previous studies have not found a reduction in CRC risk, though they may have been underpowered and biased as these studies came from referral centers.

The authors also cautioned that more than 1/3rd of CRC cases occurred in those without extensive colitis which may necessitate a lower threshold for screening colonoscopy.

Related blog posts:

Magnets: Clear and Present Danger

As noted in previous blogs (see below for links), ingested magnets represent a significant problem.  Two more studies add data to this issue:

  • JPGN 2013; 57: 14-17.
  • JPGN 2013; 57: 18-22.

The first study relates a retrospective single-hospital experience from 1995-2012 (from Boston).  In total, 112 cases of magnet injuries were identified using an initial computer search followed by manual chart review.  The mean patient age was 6 years.  The incidence rate ratio of 3.44 during the period 2007-2012 indicates a significant uptick in these injuries compared with the prior period. In addition, “office toys” accounted for 18 of 45 injuries during this latter period. Nature of injuries: swallowed magnets accounted for 86% of these injuries with 13 (12%) requiring endoscopic removal and 4 (4%) needing surgical intervention.

The second study analyzed a nationally representative same from the US Consumer Product Safety Commision Database (NEISS) for emergency department (ED) visits involving magnet ingestion in children (< 18 years) from 2002-2011.  NEISS sample includes >100 hospitals and 7 children’s hospitals.  The authors note that searching NEISS is not always straight-forward as specific product codes need to be entered like toy, kitchen gadget, and others.  The findings:

  • 16,386 suspected magnet ingestion related ED visits from 2002-2011
  • 59.4% were boys , 54.7% were younger than 5 years
  • There was a >8-fold increase in visits for these ingestions from 2002 to 2011.
  • Study limitations: NEISS database –likely underestimates problem, and no specific NEISS code for magnets

The authors note that one institution has started screening for magnets prior to MRI after a 5 year-old with unrecognized magnet ingestion developed intestinal perforations after undergoing an MRI for torticollis.

Take-home message: Magnets are, in the words of Tom Clancy, a ‘Clear and Present Danger’ as ingestion of more than one magnet creates a high risk of perforation or fistula.

Related blog posts:

 

 

 

What is Gluten-Free?

An excerpt from the National Foundation for Celiac Awareness Press Release:

NFCA Press Release about FDA Gluten-Free Labeling Rule

AMBLER, Pa. (August 2, 2013) – The National Foundation for Celiac Awareness (NFCA), a national non-profit organization dedicated to increasing diagnoses and improving quality of life for those with gluten-related disorders, is responding promptly to the U.S. Food & Drug Administration’s (FDA) final rule on gluten-free labeling by announcing new resources for gluten-free consumers to understand the federal regulations.

“For years, gluten-free labels have gone unregulated, putting our gluten-free community in danger,” said Alice Bast, President of NFCA. “We applaud the FDA for finally publishing a standard definition of gluten-free.”NFCA logo

The new regulations state that a food must contain less than 20 parts per million (ppm) of gluten in order to bear a “gluten-free” label. Researchers support less than 20 ppm as a safe threshold for a product to be consumed by individuals with celiac disease and other gluten-related disorders.

“Evidence-based research conclusively supports the 20 ppm level as a safety threshold for gluten-free products,” said Dr. Alessio Fasano, Director of the Center for Celiac Research at MassGeneral Hospital for Children in Boston. “We welcome the new FDA regulations, which will bring us in line with gluten-free labeling regulations for millions of people around the world.”

Related Links:

Thanks to Kayla Lewis for forwarding the press release.

 

TNF Antagonists and Psoriasis

Using data from the adverse event reporting system (AERS) from the FDA, the authors of a recent report identified a large number of psoriasis rashes which developed among patients receiving tumor necrosis factor α (TNF) antagonists (Inflamm Bowel Dis 2013; 19: 1164-72).

From more than 13 million AERS reports (2004-2011), a total of 5432 reports of psoriasis were noted: 1789 for infliximab, 3475 for adalimumab, and 168 for certolizumab compared with 88 for a control group which consisted of the following medications: propranolol, melamine, and lithium. While the absolute number for certolizumab is lower, the relative risk is similar to infliximab when adjusted for frequency of usage.

The AERS database relies on voluntary reporting and there are numerous reporting biases.  Given that AERS captures only a fraction of all true adverse events, the authors extrapolate that more 15,000 psoriasisiform adverse events occur each.  They note that these reactions typically occur in individuals without a personal or family history of psoriasis.  The onset is variable, but typically occurs 9-11 months after initiating therapy.

Additional references:

  • -IBD 2011; 17: 2512.  n=50.  Skin reactions with adalimumab.  62% of pts develop skin reactions: eczema, acne-like dermatitis, psoriasis-like (6 of 50).  Adalimumab d/c’d in 22%.
  • -JPGN 2010; 52: 230. 6 of 73 pts (8%) developed IFX-induced psoriasis -managed with topical Rx.
  • -Clin Gastro & Hep 2010; 8: xxiv. Image of psoriaform rash assoc with infliximab
  • -Aliment pharmacol Ther 2009; 29: 921-27. Review of psoriaform rash assoc with infliximab. Majority improved when TNF stopped.  Options: Rx w steroids for 3 days around Rx or add MTX.
  • -NEJM 2009; 361: 496. Review of psoriasis.

Unrelated link:

For those of you who do not have teenage sons, perhaps you are not familiar with Jimmy Kimmel’s:  This Week in Unnecessary Censorship – YouTube