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Lack of Mucosal Healing From Modified Specific Carbohydrate Diet in Pediatric Patients With Crohn Disease

Wahbeh, Ghassan T.*; Ward, Brian T.*; Lee, Dale Y.*; Giefer, Matthew J.; Suskind, David L.*

Journal of Pediatric Gastroenterology and Nutrition: September 2017 - Volume 65 - Issue 3 - p 289–292
doi: 10.1097/MPG.0000000000001619
Short Communication: Gastroenterology: Inflammatory Bowel Disease

ABSTRACT Exclusive enteral nutrition is effective in pediatric Crohn disease but challenging as maintenance therapy. There is interest in food-based therapies such as the specific carbohydrate diet (SCD) but paucity of data on efficacy and effect on mucosal healing, an evolving target of IBD therapy. We conducted a retrospective review of the mucosal healing effect of the SCD in pediatric Crohn disease (CD). The endoscopic findings for children younger than 18 years with CD treated exclusively with the SCD or modified SCD (mSCD; SCD + addition of “illegal foods”) were reviewed before and after the diet. Ileocolonoscopic examinations were scored according to the Simple Endoscopic Score for CD and findings on upper endoscopy were described. Seven subjects were identified, all on mSCD. The average age at starting the SCD was 11 ± 3.4 years and median duration of SCD/mSCD therapy was 26 months. All subjects reported no active symptoms before repeat endoscopic evaluation on mSCD, the majority had consistently normal C-reactive protein, albumin and hematocrit assessments, and mildly elevated fecal calprotectin (>50 μg/g, median 201, range 65–312) at any point within 3 months before the repeat endoscopy. One patient showed complete ileocolonic healing but persistent upper gastrointestinal tract ulceration. Complete macroscopic mucosal healing of both the ileocolon and upper gastrointestinal tract was not seen in any patient.

*Inflammatory Bowel Disease Center

Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA.

Address correspondence and reprint requests to Ghassan T. Wahbeh, MD, Director IBD Center, Seattle Children's Hospital, University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA 98105 (e-mail: Ghassan.wahbeh@seattlechildrens.org).

Received 11 October, 2016

Accepted 4 April, 2017

The authors report no conflicts of interest.

What Is Known

  • Several diets, including the specific carbohydrate diet, have received interest in inflammatory bowel disease management and are perceived to improve symptoms.
  • Symptomatic improvement in inflammatory bowel disease may not correlate with biochemical remission or mucosal healing.
  • The degree of mucosal healing on the specific carbohydrate diet or modified specific carbohydrate diet is not known.

What Is New

  • Complete mucosal healing is not seen in patients on a modified specific carbohydrate diet as their only therapy for Crohn disease with mildly elevated stool calprotectin.
  • Improvement in symptoms, albumin, and C-reactive protein did not reflect complete mucosal healing, with stool calprotectin levels >50 μg/g.
  • Assessing for mucosal healing should be undertaken in patients on the modified specific carbohydrate diet.

See “Alas, Who and What Can We Trust? Patients, Parents, Surrogate Markers, or the Specific Carbohydrate Diet” by Cohen on page 266.

Managing Crohn disease (CD) traditionally involves immunosuppressive medications, but exclusive enteral nutrition (EEN) can be an effective, safe therapy in pediatric CD (1). Immunosuppressive medications have been associated with growth delay, increase risk of infection, and malignancy. Despite its safety and efficacy, particularly with the evolving therapeutic target of mucosal healing (MH) (2,3), EEN can be challenging for children secondary to the desire to eat “normal food,” and avoiding gavage feeding, which is sometimes required to deliver adequate nutrition. Disease flares are common once EEN monotherapy is stopped and immunomodulators and/or antitumor necrosis factor (anti-TNF) therapy are often started with or after EEN (4). These issues have stimulated strong interest in dietary modification to treat CD from patients, families, and physicians.

The specific carbohydrate diet (SCD) was developed to treat celiac disease in the mid-20th century (5,6). The diet replaces grains (including wheat, barley, corn, and rice) with nuts and nut flours (eg, almond, coconut), excludes processed foods and restricts most dairy products and sugars except fermented yogurt and honey. Several publications describe clinical improvement on the SCD (7–10). For many, after a period of strict SCD, once the symptoms and laboratory markers are improved, restrictions are eased off with the gradual addition of SCD “illegal” foods, that is, modified SCD (mSCD). Such foods include rice, oats, potatoes, and quinoa. Symptoms, growth, and inflammatory markers are generally followed to decide on further introduction or withdrawal of foods. There are, however, no published guidelines or studies describing a standard to follow in IBD, rather different Web and book sources (5,11,12). To date, there are no publications describing MH assessed by conventional endoscopy while on either the SCD or mSCD.

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AIM

To describe the extent of MH in children with CD on an mSCD as their only active treatment.

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METHODS

We conducted a retrospective review of children with CD treated with the SCD/mSCD followed in the Seattle Children's Hospital IBD Center between January 2013 and August 2016. Inclusion criteria were diagnosis of CD, age <18 years, use of the SCD/mSCD as the exclusive treatment for >3 months, and endoscopic assessment before and after starting the SCD/mSCD. Exclusion criteria were ulcerative colitis or unclassified IBD diagnosis, concomitant therapy with mesalamines, corticosteroids, azathioprine, mercaptopurine, methotrexate, and anti-TNF. Data included age, sex, diagnosis, disease phenotype and behavior (Paris classification (13)), treatment history, growth parameters, laboratory parameters, and history of SCD/mSCD use. Albumin, C-reactive protein (CRP), hemoglobin, and erythrocyte sedimentation rate were checked at different times during follow-up at the provider's discretion. All results between the beginning of the SCD treatment and the follow-up endoscopic examination were analyzed.

Endoscopic and histologic assessments (procedure description and images) pre- and post-SCD/mSCD were reviewed. Procedures were done by 2 providers (G.W. and D.S.). The examinations were assigned a score (by D.W., G.W., and D.S.) based on the Simple Endoscopic Score CD (SES-CD) (14), a validated scoring system based on the presence and extent of visible ulcers and stenosis on ileocolonoscopy (but not upper gastrointestinal tract). Complete MH was defined as the absence of any ulceration. Endoscopic disease severity was based on published proposed definitions (Table 2) (15). For upper endoscopies, we described ulcers present or absent. For individuals without gross inflammation, we describe the reported histologic changes (all patients with gross inflammation had microscopic changes). At our center, patients are offered the services of an IBD experienced dietician for education and resources. The study protocol was approved by the Seattle Children's Hospital Institutional Review Board (IRB STUDY00000174).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

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Statistical Analysis

All demographic and clinical variables were summarized using mean, median, and range, for continuous variables, and frequencies and percentages for categorical variables as appropriate.

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RESULTS

Patient Demographics and Clinical Background

Eight patients were identified, with 7 fitting the inclusion criteria. One patient was excluded due to a fecal microbiota transplant <4 weeks before the follow-up colonoscopy. All patients were on the mSCD. We did not identify any patient on strict SCD who underwent follow-up endoscopic examination. Patient demographics and clinical background at baseline are presented in Table 1. The average age at IBD diagnosis was 10 ± 2.6 years and the average age when the diet was started was 11 ± 3.4 years. The mean disease duration was 1.2 ± 1.7 years before initiating the SCD and 4 of 7 children had not received any anti-inflammatory medical therapy before the SCD (2 were on EEN), 3 of 7 had received anti-inflammatory medications (Table 1). Patients received no other medical therapy for their IBD beyond the mSCD at the time of repeat endoscopic examination. One child had a prior diagnosis of growth hormone deficiency and received hormone replacement before and after the diet initiation. Only 1 patient received alternative therapy at follow-up, namely fish oil, zinc, and “amino acid” supplement. The median duration of the mSCD therapy at the time of repeat endoscopic examination was 26 months (range 13–62). None of the patients complained of any persistent abdominal pain, diarrhea, rectal bleeding, sustained weight loss, or fevers. The indication for endoscopy in all instances was to check for MH.

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Labs

We examined the laboratory parameters at or immediately before the follow-up endoscopy (up to 3 months): albumin, hematocrit, and CRP were consistently normal for 5 of 7 children. For the remaining 2 patients, 1 had an albumin of 3.7 (normal >3.8 g/dL) and 1 had a CRP of 1.0 mg/dL (normal <0.8 mg/dL). Erythrocyte sedimentation rate (available for 2 patients) was normal (<20 mm/h). Fecal calprotectin (FCP) was checked in 5 of 7 patients while on the mSCD; a total of 15 FCP tests were performed. All 5 patients tested had elevated FCP levels >50 μg/g, with range of 65 to312, median 201 ± 74.

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Pre- and Postspecific Carbohydrate Diet Changes

No patient had complete MH (absence of any ulceration) from both the upper gastrointestinal (UGI) tract and ileocolon (Fig. 1). Table 1 summarizes the data before and after mSCD.

FIGURE 1

FIGURE 1

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Ileocolonic Endoscopic Examination

One patient was in complete ileocolonic MH on the mSCD, defined by absence of any lesion. For this patient, UGI tract ulcerations persisted.

We compared endoscopic severity based on SES-CD for the same patient from baseline to follow-up on the mSCD: 3 of 7 patients had no change in endoscopic severity (2 mild, 1 moderate). Two of 7 showed improvement (severe to moderate, moderate to mild), 1 of 7 showed resolution (severe to none), and 1 of 7 worsened (moderate to severe).

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Upper Gastrointestinal Tract and Ileal Disease Phenotype Changes

EGD was done for 6 of 7 patients before and on mSCD. Five of 6 had UGI ulcers at baseline; 4 had persistence of their baseline ulcers while 2 resolved (although microscopic changes persisted without activity—denoting less neutrophil presence).

At baseline 4 of 7 patients had ileal ulceration; with follow-up showing persistence in 2 and resolution in 2 (1 had persistent histologic changes although with less activity, the second cleared the ileal and colonic disease macroscopically, but continued to have microscopic colonic chronic inflammation with less activity). For the 3 patients with no ileal disease at baseline, all 3 developed macroscopic ileal ulceration on mSCD.

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Behavior

Four of 7 patients showed no behavior change. Two of 7 patients developed a nonobstructive stricture (B1 to B2). In the remaining patient, the perianal disease (fissure) resolved (B1P to B1).

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Growth

There were no observed changes in the weight and height z scores between baseline and follow-up. At baseline 3 of 7 had a body mass index (BMI) consistent with mild malnutrition (z score >−1.0) which persisted. In addition, 2 patients developed lower BMI z score (>−1.0 standard deviation) at the time of reevaluation on mSCD. Two patients maintained normal BMI. The study was not powered to detect significance in BMI changes.

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Therapy After Follow-up Examination

After restaging disease for MH, 5 of 7 patients were started on anti-TNF therapy. Three of 5 patients who started anti-TNF therapy showed improved BMI, 1 patient showed no clinical change (BMI normal), 1 patient moved and has not been seen in follow-up. Three of 5 patients remained on mSCD along with their medical therapy. For the remaining 2 patients who did not receive a biologic agent, 1 started EEN recently, whereas 1 remained on mSCD and added ranitidine, with follow-up FCP dropping <50 μg/g. None of our patients have undergone follow-up endoscopy at this time.

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DISCUSSION

The role of nutrition in the etiology and management of CD is an area of rising interest (16). EEN for 6 to 12 weeks, although challenging, is effective inducing remission and being superior to corticosteroids in achieving MH (17). Disease flares are common after EEN is completed raising interest in alternative diets, including the SCD.

The present study demonstrates that asymptomatic patients with CD on the mSCD, with mostly normal or mildly abnormal laboratories, elevations in FCP >50 μg/g (5/7) persistently low or decreasing BMI, had persistent mucosal disease.

Cohen et al (7) described mucosal improvements on the SCD assessed with capsule endoscopy in 10 pediatric patients with CD: at 12-week, clinical remission was seen in 6 of 10 (60%) and capsule endoscopic MH was observed in 40% (4/10). In addition, 80% of patients showed significant mucosal improvement at week 12 compared to baseline.

MH is an evolving therapeutic target with mounting evidence of its role in changing natural history and improving outcome in children and adults (3,18). The definition of MH has not been fully established (19). The ability of current medical and nutritional therapies to achieve the various levels of MH during both induction and maintenance has not been fully elucidated. Two published pediatric studies assessed complete MH (absence of any visible ulcer on ileocolonoscopy) on nutritional and medical therapy (18,20). Grover et al (18) showed complete MH in 33% of children after 6 weeks of EEN. Kang et al (20) demonstrated that early therapy with infliximab, azathioprine, and mesalazine was associated with 51% complete MH at week 14 and 74% complete MH at week 54. In the “step up” group (corticosteroids, mesalazine, and azathioprine followed by infliximab if active disease off corticosteroids): 32% had complete MH at week 14, with 42% MH at week 54. In Grover et al's study, only complete MH on EEN predicted long-term sustained remission on immunomodulators without steroids, surgery, or anti-TNF therapy. In our study, 1 patient out of 7 cleared the ileocolonic ulcers (SES-CD = 0) on the mSCD.

There are several limitations to the present study including its retrospective nature and small sample size. Patients may have been missed, because we depended on provider report and recall for inclusion. We did not identify any patient on the strict SCD who underwent follow-up endoscopic examination. We relied on patients’ and parents’ reported absence of symptoms. Certainly, there could be subjective positive reporting bias for patients describing improvement on mSCD. In addition, we assigned the endoscopic activity score based on procedure reports and images, which may be less accurate than scoring during endoscopy. Finally, the present study was limited by the inability to evaluate the patients’ definition of mSCD and the level of adherence to dietary therapy; therefore, our observations may not be applicable to the strict SCD. The SCD can be a difficult diet to follow and assessment of compliance can be equally challenging.

Despite the study limitations, we provide a real life scenario in which pediatric patients with CD on an mSCD were in clinical and biochemical remission, but had mildly elevated FCP levels and showed lack of complete endoscopic healing. Larger prospective studies are warranted to assess for MH given the popularity of the SCD and other alternative diets. This is particularly important if MH is a therapeutic target given the data in support of EEN, azathioprine, and anti-TNF therapy inducing MH. The present study highlights the need for close follow-up of children with CD on dietary therapy with or without abnormal inflammatory markers.

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CONCLUSIONS

In 7 asymptomatic patients with CD on an mSCD as sole therapy with normal or mildly abnormal albumin, CRP, and hematocrit but elevated stool calprotectin >50 μg/g, complete endoscopic MH of the UGI tract and ileocolon was not demonstrated. With deep MH evolving as a potential therapeutic endpoint, further scrutiny is required to assess the degree of MH on the SCD and other popularized diets.

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REFERENCES

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Keywords:

Crohn's; inflammatory bowel disease; mucosal healing; nutrition; pediatric; specific carbohydrate diet

© 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,