Pediatrics International (2002) 44, 537–539

Patient Report

Crohn’s disease in a child with Down syndrome

MASAKI YAMAMOTO, WATARU ABO, TSUKASA HORI, TOSHIMASA NAKADA, NAOKI TACHIBANA, YASUMASA HATADA AND MITSUOMI KAIMORI

Departments of Pediatrics, Endoscopy and Pathology, Aomori Central Hospital, Aomori, Japan

Key words childhood, Crohn’s disease, Down syndrome, failure to thrive.

Crohn’s disease (CD) is a rare phenomenon in earlychildhood, with the peak incidence occurring during thesecond decade of life.1–3 However, it has been reported thatthe incidence of CD in childhood is rising.4 Associationsbetween CD and Down syndrome (DS) have rarely beenreported.5–7

Here we report a patient with DS associated with CD whopresented with apparent failure to thrive, low-grade fever,anemia and elevations of C-reactive protein (CRP) anderythrocyte sedimentation rate (ESR). We suggest that CDmay be added to the list of complications associated with DS,for patients who present with failure to thrive.

Case report

A Japanese girl was born weighing 3062 g to unrelatedhealthy parents, at 37 weeks’ gestation with no deliverycomplications. Diagnosis of DS by chromosome analysis wasmade during the first month of life. A heart murmur wasnoticed, which was diagnosed as a ventricular septal defect(VSD), pulmonary hypertension and patent foramen ovale,for which she received cardiac medication. She was under-developed, with mental and motor retardation and failure tothrive.

At 4 years of age she had acute enteritis with frequentdiarrhea and tested positive for occult blood in her stools.Apart from cardiac medication, she had no further treatmenthistory. At 6 years of age she was referred to our hospital forextensive investigation of failure to thrive and anemia. Dueto her taste preference, the patient had only been formula-feduntil the diagnosis of CD was made at 6 years and 5 monthsof age.

She was 96.5 cm in height (under the 25th percentile onthe growth chart for children with DS) and 14 kg in weight(under the 25th percentile).8 Clinical examination revealed asystolic heart murmur due to the VSD and mild hepatomeg-aly and skin tags perianally.

Laboratory findings (Table 1) showed her hemoglobinlevel was 10.2 g/dL, erythrocyte count 389 × 104/µL, reticu-locyte count 11‰, leukocyte count 2400/µL (54.6%polymorphs, 31.9% lymphocytes, 11.2% monocytes, 0.8%eosinophils) and platelet count 296 000/µL. Erythrocyte sedi-mentation rate was 83 mm/h and CRP was positive (4.61 mg/dL). Serum aspartate transferase and alanine transferase was19 and 10 IU/L, respectively. Serum total protein andalbumin was 7.8 and 3.5 mg/dL, respectively. Totalcholesterol level (229 mg/dL) was not decreased. A highlevel of γ-serum protein (3.1 g/dL) was due to a rise in IgG(2480 mg/dL) and IgA (618 mg/dL). The IgM level wasnormal (118 mg/dL). Bone marrow examination showed a bi-linage myelodysplasia and ringed cells, with no excess blastcells. Monosomy 7 and trisomy 8 were negative. Thetuberculin reaction was 13 × 12 mm. Stools sampled forbacterial cultures and acid-fast bacilli were negative. Smears,polymerase chain reaction and cultures of gastric washingsand a biopsy specimen were negative for acid-fast bacilli.

Colonoscopy showed fissuring and irregular ulcers at theileocecal region (Fig. 1). Barium enema showed linear ulcersand stenosis at the terminal ileum and transverse colon(Fig. 2). Histological examination of the biopsy specimenshowed chronic inflammation with ulceration includinggranulation (Fig. 3).

After being diagnosed with CD, the patient was initiallytreated with oral prednisolone (1 mg/kg per day) in additionto high caloric i.v. nutrition. However, she needed totalparenteral nutrition and a cycle of steroid-pulse therapy(30 mg/kg per day for 3 days), due to the condition ofdiarrhea not improving and the enlargement of colon with anassociation of elevated CRP. She is now well and controlledon maintenance therapy with an elemental diet in addition toi.v. lipid supplementation.

Correspondence: Wataru Abo MD, Department of Pediatrics,Aomori Central Hospital, 1-1-2, Higashi-Tsukurimichi, Aomori,030-8553, Japan. Email: abow@hosp.pref.aomori.jp

Received 24 January 2001; revised 30 November 2001; accepted30 November 2002.

538 M Yamamoto et al.

Discussion

Over the years, a number of reports have been publishedregarding the coexistence of various autoimmune diseases inpatients with DS.6,9 However, little is known about the

Table 1 Laboratory findings on admission for a 6-year-old Japanese girl with Crohn’s disease and Down syndrome

WBC (µL) 2400 AST (IU/L) 19 TP (g/dL) 7.8neu (%) 54.6 ALT (IU/L) 10 A/G 0.93lym (%) 31.9 ALP (IU/L) 350 Alb (%) 48.1mon (%) 11.2 γ-GTP (IU/L) 11 α1 (%) 4.2bas (%) 0.5 LDH (IU/L) 342 α2 (%) 11.4eos (%) 1.8 CK (IU/L) 19 β (%) 9.9RBC 389 × 104/µL CHE (IU/L) 184 γ (%) 26.4Hb (g/dL) 10.2 BUN (mg/dL) 10.9 Ht (%) 32.7Cr (mg/dL) 0.34 Plt 296 × 104/µL UA (mg/dL) 3.6Fe (µg/dL) 5 reti 11‰ Na (mg/dL) 138UIBC (µg/dL) 242 IgA (mg/dL) 618 K (mg/dL) 4.0TIBC (µg/dL) 247 IgG (mg/dL) 2480 Cl (mg/dL) 106Ferritin (ng/dL) 78.8 IgM (mg/dL) 118 Ca (mg/dL) 9.6TPHA negative CRP (mg/dL) 4.61 P (mg/dL) 5.4HBsAg negative ESR (mm/h) 83 T-chol (mg/dL) 229HCV Ab negative

A/G, albumin/globulin; Alb, albumin; ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate aminotransferase; bas,basophil; BUN, blood urea nitrogen; Ca, calcium; CHE, choline esterase; CK, creatine kinase; Cl, chlorine; Cr, creatinine; eos, eosinophil;ESR, erythroycte sedimentation rate; Fe, iron; γ-GTP, γ-guanosine triphosphate; Hb, hemogloblin; HBsAg, hepatitis B surface antigen; HCVAb, hepatitis C virus antibody; Ht, hemocrit; K, potassium; LDH, lactate dehydrogenase; lym, lymphocyte; mon, monocyte; Na, sodium;neu, neutrophil; P, phosphorus; Plt, platelet; RBC, red blood cell; reti, reticulocyte; T-chol, total cholesterol; TIBC, total iron-bindingcapacity; TP, total protein; TPHA, Treponema pallidum hemagglutination; UA, uric acid; UIBC, unsaturated iron-binding capacity; WBC,white blood cell.

Fig. 1 Colonoscopy shows fissuring (arrow) and irregularulcers at the ileocecal region.

Fig. 2 Barium enema shows stricture at the terminal ileum(arrow) and transverse colon.

Crohn’s disease and Down syndrome 539

relationship between these pathologies and CD. Crohn’sdisease in childhood is a rare phenomenon that can beconfused with allergic colitis, Behcet’s disease and idiopathicinflammation of the intestine.9 The pathological featuresinclude transmural involvement, slit-like mucosal ulcerations(fissures) and non-specific inflammatory changes, which arecharacteristic of the adult form of CD. In the case describedhere, the absence of chronic or bloody diarrhea was nottypical of CD. However, the diagnosis was made by bariumenema, endoscopies and histological findings and was alsosupported by the serum findings of elevated ESR and CRP.The barium enema showed ulcers and strictures at theterminal ileum and transverse colon, but not the entireintestine. These findings may be consistent with her normalserum proteins and lipids. We feel that follow-up programsfor DS patients should include an evaluation of the gastro-intestinal system for CD, for patients who have non-specificinflammation.

Crohn’s disease is commonly associated with leukocyto-sis, thrombocytosis and anemia.10 In the present case, therewas anemia but only a slight decrease in leukocyte count andthe platelet count was within normal limits. Her bone marrowexamination showed a bi-lineage myelodysplasia and ringedcells, but there were no excess of blast cells. The associationbetween CD and myelodysplastic syndrome (MDS) has beendiscussed in adult populations,10,11 but pediatric cases havenot been reported. This patient needs further clinical andhematological follow-up investigations, including a bonemarrow examination for MDS.

There were a number of factors that made diagnosisdifficult in the present case. Although our patient did nothave a low cholesterol level or hypoproteinemia, thenutritional imbalances could have been associated withmental retardation caused by trisomy 21. Ventricular septal

defect and its associated heart failure also complicated ourcase. We considered that these factors contributed to thepatient’s failure to thrive. Early diagnosis of CD was furtherhampered by the fact that the patient had been fully formula-fed. Koletzko et al. reported that an absence of breast-feedingand early diarrhea are independent risk factors associatedwith the development of CD later in childhood.12 We feel thatthere may be further cryptic patients with CD associated withDS who have presented with failure to thrive.

To our knowledge, there have been only a few reportedcases of an association between CD and DS. Vajro et al.discussed that the occurrence of inflammatory bowel diseasein DS could be more common than would be expected bychance alone.5 Kaushik et al. reported an adult patient withDS associated with CD and hepatobiliary disease.6 The casewe have described confirms the possibility of an associationbetween CD and DS.

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Fig. 3 Histological examination shows chronic inflammationwith ulceration (original magnification; ×50).