All demographic and clinical variables were summarized using mean, median, and range, for continuous variables, and frequencies and percentages for categorical variables as appropriate.
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.
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.
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.
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).
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.
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).
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.
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.
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.
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.
1. Ruemmele FM, Veres G, Kolho KL, et al. ECCO/ESPGHAN: consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's
disease. J Crohns Colitis
2. Peyrin-Biroulet L, Reinisch W, Colombel JF, et al. Clinical disease activity, C-reactive protein normalisation and mucosal healing
disease in the SONIC trial. Gut
3. Baert F, Moortgat L, Van Assche G, et al. Mucosal healing
predicts sustained clinical remission in patients with early-stage Crohn's
2010; 138:463–468. quiz e10-1.
4. Penagini F, Dilillo D, Borsani B, et al. Nutrition
in pediatric inflammatory bowel disease
: from etiology to treatment. A systematic review. Nutrients
2016; 8:pii: E334.
5. Gottschall E. Breaking the Viscious Cycle. 2nd edBaltimore, ON: Kirkton Press Limited; 1994.
6. Haas SV, Haas MP. The treatment of celiac disease with the specific carbohydrate diet
; report on 191 additional cases. Am J Gastroenterol
7. Cohen SA, Gold BD, Oliva S, et al. Clinical and mucosal improvement with specific carbohydrate diet
Crohn disease. J Pediatr Gastroenterol Nutr
8. Kakodkar S, Farooqui AJ, Mikolaitis SL, et al. The specific carbohydrate diet
for inflammatory bowel disease
: a case series. J Acad Nutr Diet
9. Obih C, Wahbeh G, Lee D, et al. Specific carbohydrate diet
for pediatric inflammatory bowel disease
in clinical practice within an academic IBD center. Nutrition
10. Suskind DL, Wahbeh G, Gregory N, et al. Nutritional therapy in pediatric
Crohn disease: the specific carbohydrate diet
. J Pediatr Gastroenterol Nutr
13. Levine A, Griffiths A, Markowitz J, et al. Pediatric
modification of the Montreal classification for inflammatory bowel disease
: the Paris classification. Inflamm Bowel Dis
14. Daperno M, D’Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's
disease: the SES-CD. Gastrointest Endosc
15. Vuitton L, Marteau P, Sandborn WJ, et al. IOIBD technical review on endoscopic indices for Crohn's
disease clinical trials. Gut
16. Wedrychowicz A, Zajac A, Tomasik P. Advances in nutritional therapy in inflammatory bowel diseases: review. World J Gastroenterol
17. Borrelli O, Cordischi L, Cirulli M, et al. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's
disease: a randomized controlled open-label trial. Clin Gastroenterol Hepatol
18. Grover Z, Burgess C, Muir R, et al. Early mucosal healing
with exclusive enteral nutrition
is associated with improved outcomes in newly diagnosed children with luminal Crohn's
disease. J Crohns Colitis
19. Pineton de Chambrun G, Blanc P, Peyrin-Biroulet L. Current evidence supporting mucosal healing
and deep remission as important treatment goals for inflammatory bowel disease
. Expert Rev Gastroenterol Hepatol
20. Kang B, Choi SY, Kim HS, et al. Mucosal healing
in paediatric patients with moderate-to-severe luminal Crohn's
disease under combined immunosuppression: escalation versus early treatment. J Crohns Colitis
Keywords:© 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
Crohn's; inflammatory bowel disease; mucosal healing; nutrition; pediatric; specific carbohydrate diet