Active Colitis More Likely in Children in Clinical Remission Who Have PSC and IBD

A recent study (A Ricciuto et al. Clin Gastroenterol Hepatol 2018; 16: 1098-1105) provides more data regarding the lack of symptom correlation and inflammatory bowel disease (IBD) activity in children with primary sclerosing cholangitis (PSC).

In a prospective study of children with colonic IBD with and without PSC, the authors followed clinical features (eg. PUCAI), fecal calprotectin and endoscopy severity.

Key findings:

  • Patients with PSC-IBD (n=37) in clinical remission had higher endoscopic scores and greater odd of active endoscopic disease than IBD-only controls (n=50) (odds ratio 5.9, with CI 1.6-21.5)
  • Fecal calprotectin level <93 mcg/g were identified mucosal healing with 100% sensitivity and 92% specificity when compared with UC Endoscopic Index of Severity (UCEIS)

Overall, this study is in agreement with a prior adult study showing higher levels of active disease in those with PSC-IBD compared to those with IBD alone, despite clinical remission (Why does PSC increase the risk of colorectal cancer in UC?).

My take: Particularly in individuals with the combination of IBD-PSC, objective biomarkers (eg. Calprotectin) are needed to identify the accuracy of clinical remission; though, even in patients with IBD without PSC, objective biomarkers are needed as well due to the limitations of clinical symptom indices.

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Moraine Lake, Banff

How to Change Your Microbiome Quickly?

Change your diet.

From NPR, http://n.pr/JeWCh4, an excerpt:

Switching to a diet packed with meat and cheese — and very few carbohydrates — alters the trillions of microbes living in the gut, scientists report Wednesday [12/111/13] in the journal Nature.

The change happens quickly. Within two days, the types of microbes thriving in the gut shuffle around. And there are signs that some of these shifts might not be so good for your gut: One type of bacterium that flourishes under the meat-rich diet has been linked to inflammation and intestinal diseases in mice.

“I mean, I love meat,” says microbiologist Lawrence David, who contributed to the study and is now at Duke University.

[The researchers] wanted to know whether fiber — or lack of it — could alter gut bacteria more rapidly.

To figure that out, the researchers got nine volunteers to go on two extreme diets for five days each.

The first diet was all about meat and cheese. “Breakfast was eggs and bacon,” David says. “Lunch was ribs and briskets, and then for dinner, it was salami and prosciutto with an assortment of cheeses. The volunteers had pork rinds for snacks.”

Then, after a break, the nine volunteers began a second, fiber-rich diet at the other end of the spectrum: It all came from plants. “Breakfast was granola cereal,” David says. “For lunch, it was jasmine rice, cooked onions, tomatoes, squash, garlic, peas and lentils.” Dinner looked similar, and the volunteers could snack on bananas and mangoes.

“The animal-based diet is admittedly a little extreme,” he says. “But the plant-based diet is one you might find in a developing country.”

David and the team analyzed the volunteers’ microbiomes before, during and after each diet. And the effects of all that meat and cheese were immediately apparent.

“The relative abundance of various bacteria species looked like it shifted within a day after the food hit the gut,” David says. After the volunteers had spent about three days on each diet, the bacteria in the gut even started to change their behavior. “The kind of genes turned on in the microbes changed in both diets,” he says.

In particular, microbes that “love bile” — the Bilophila — started to dominate the volunteers’ guts during the animal-based diet. Bile helps the stomach digest fats. So people make more bile when their diet is rich in meat and dairy fats.

A study last year found that blooms of Bilophila cause inflammation and colitis in mice. “But we didn’t measure levels of inflammation in our subjects,” David says. “That’s the next step.”

Hemophagocytic Lymphohistioctosis: Advances

A recent medical progress report provides a concise update on hemophagocytic lymphohistiocytosis (HLH) (J Pediatr 2013; 163: 1253-59).

  • Table 1 summarizes the subtypes of HLH.
  • Atypical presentations include colitis and hypogammaglobulinemia.
  • Table 2 provides the diagnostic criteria.
  • The treatment approach is outlined as well.  In the short-term, with primary HLH, the goal is controlling the hyperinflammatory state (often with dexamethasone and etoposide).  The long-term goal aims to definitively correct the underlying genetic defect by allogeneic hematopoietic stem cell transplantation (HCT)

Other points:

  • A genetic diagnosis of familial HLH can be made in 40-80% of HLH cases with the identification of PRF1, UNC13D, STX11, and STXBP2 genes.
  • UNC13D are the predominant defects identified in Caucasians in U.S.
  • PRF1 is most common in African-American patients.
  • Ferritin remains an excellent screening tool.  A level >500 mcg/L is suggestive (but not specific) for HLH; a level >10,000 has much greater specificity (96%) along with fairly high sensitivity (90%).
  • HLH is commonly referred to as macrophage activation syndrome (MAS) in the setting of a rheumatologic illness.
  • There is no broad consensus on management of secondary HLH.  In MAS, therapy often includes pulsed steroids and/or cyclosporine.

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