• Does Mucosal Healing Mean Transmural Healing in Children With Crohn’s Disease?

Does Mucosal Healing Mean Transmural Healing in Children With Crohn’s Disease?

 One-third of children with Crohn’s disease have healing in only the mucosa or the bowel wall (not both), researchers report in the July issue of Clinical Gastroenterology and Hepatology. Levels of fecal calprotectin below 300 μg/identify children with mucosal healing.

Calprotectin (A) and C-reactive protein (B) levels in children with mucosal healing (MH), transmural healing (TH), and deep healing (DH).

In patients with CD, mucosal healing is associated with reduced risk of relapse, hospitalization, and surgery. However, CD is transmural (in the bowel wall), so it is not clear whether endoscopy is sufficient to establish complete healing—cross-sectional imaging techniques, such as magnetic resonance enterography (MRE), might be required to determine whether healing is complete. Also, transmural healing has not been investigated in children with CD.

Inbar Weinstein-Nakar et al analyzed data from the ImageKids study to determine associations among mucosal healing (assessed by endoscopy), transmural healing (assessed by MRE), and levels of calprotectin and C-reactive protein in 151 children with CD (ages, 6–18 years).

Mucosal healing was defined as simple endoscopic severity index in CD score below 3, and transmural healing as an MRE visual analogue score below 20 mm.

Weinstein-Nakar et al found mucosal healing with transmural inflammation in 9 children (6%), transmural healing with mucosal inflammation in 38 children (25%), a combination of transmural and mucosal healing (deep healing) in 21 children (14%), and mucosal and transmural inflammation in 83 children (55%).

The median level of calprotectin was lowest in children with deep healing (mean level, 10 μg/g), followed by children with either transmural or mucosal inflammation. The highest median level of calprotectin was in children with mucosal and transmural inflammation (810 μg/g).

Fecal level of calprotectin identified children with deep healing with an area under the receiver operating characteristic curve (AUROC) value of 0.93. Level of C-reactive protein identified children with deep healing with an AUROC value of 0.81.

A calprotectin cutoff value of 100 μg/g identified children with deep healing with 71% sensitivity and 92% specificity; a cutoff value of 300 μg/g identified children with mucosal healing with 80% sensitivity and 81% specificity.

In the 21 children with deep healing, the median calprotectin level was 10 μg/g and the median C-reactive protein level was 1 mg/L . These values were significantly lower than in children with either mucosal or transmural inflammation (see Figure).

A C-reative protein cutoff value <3 mg/L best identified children with deep healing.

Weinstein-Nakar et al conclude that one-third of pediatric patients with CD have either mucosal healing with transmural inflammation or vice versa. This supports the concept that MRE is an important addition to colonoscopy in assessing CD.

They warn physicians that progression to bowel damage can still occur in patients with mucosal healing, because residual transmural inflammation often persists. Achieving transmural healing in addition to mucosal healing (deep healing) might be best, but further studies are needed to determine the number needed to treat to achieve this goal, and to identify the the best candiates for the extended treatment.

In an editorial that accompanies the article, Julián Panés and Jordi Rimola write that the study confirms the value of biomarkers, particularly calprotectin, in identifying healing. Values of calprotectin less than 100 μg/mL appear to accurately identify patients with healing, but higher levels should lead to imaging assessments (endoscopy or MRE) to certify the presence of inflammatory lesions.

Panés and Rimola add that MRE is a promising approach for clinical research—particularly in pediatric populations, in whom avoidance of endoscopy is important. MRE might be used to characterize populations for study, such as those with penetrating or stenosing complications, and increase recruitment to clinical trials by allowing the inclusion of subjects with incomplete ileocolonoscopies.

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