Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 17-3

Seventeen-Year-Old Boy



The patient is a 17-year-old boy who presents with 7 months of loose nonbloody stool and 1 week of fever to 39.5°C, severe abdominal pain, and bloody diarrhea. The patient was well until 7 months ago when he began having 3-4 loose stools per day whenever he ingested food. During those 7 months, he had no fevers, abdominal pain, nausea, emesis, bloody stool, rash, or arthritis. One week prior to admission, he developed intermittent fevers to a maximum of 39.5°C, periumbilical abdominal pain with ingestion of food, and multiple episodes per day of grossly bloody stool. On admission, the patient had just completed a 10-day course of oral clarithromycin for sinusitis. He denied recent travel outside the country, ingestion of undercooked food, or sick contacts. He did admit to a 7-lb weight loss during the past 7 months that had been unintentional.


Medical history is significant for seasonal allergic rhinitis for which the patient takes loratadine (Claritin) as needed. There is no known family history of any gastrointestinal or bleeding disorders.


T 37°C; RR 18/min; HR 60 bpm; BP 120/65 mmHg

Weight 55 kg, 10th percentile; Height 170 cm, 25th percentile

Physical examination revealed a lean but non-emaciated boy in no acute distress. He was anicteric with moist mucous membranes. Cardiac and respiratory examinations were normal. His abdomen was soft, nontender, and nondistended without hepatosplenomegaly or palpable masses. He had normoactive bowel sounds. On external anal examination he had no visible fissures, tags, or masses. Rectal examination revealed grossly heme-positive soft stool in the rectal vault. There were no palpable rectal masses. His skin examination revealed no rashes, petechiae, or purpura. Neurologic examination was normal.


Serum electrolytes, glucose, blood urea nitrogen, and creatinine were all normal. A complete blood count (CBC) revealed a WBC count of 23 700 cells/mm3, hemoglobin of 11.7 g/dL, and a platelet count of 302 000/mm3. Coagulation factors including PT, PTT, and INR were all normal. The erythrocyte sedimentation rate (ESR) was 5 mm/h and the C-reactive protein (CRP) was 1.5 mg/dL. A hepatic function panel was normal except for a serum albumin that was low at 2.4 g/dL and a serum alkaline phosphatase that was low at 58 U/L. Stool samples were negative for Clostridium difficile, bacterial pathogens, viral pathogens, and ova and parasites.


The patient was initially admitted to an outside hospital where he underwent flexible sigmoidoscopy, which reportedly showed inflammation that the physicians believed to be consistent with inflammatory bowel disease. The patient was placed on mesalamine enemas as well as oral mesalamine, omeprazole, and prednisone. He had some improvement in stool frequency, consistency, and amount of fecal blood and was discharged home.

Five days after discharge, the patient presented to our hospital with recurrence of bloody diarrhea and abdominal pain. After rehydration he underwent a complete endoscopy and colonoscopy that revealed multiple polyps in the small bowel and throughout the colon (Figure 17-3). Several polyps were removed and were sent to pathology for review. Due to findings seen on pathology, a retinal examination was performed which suggested a diagnosis.


FIGURE 17-3. Colonic polyps. (Reproduced, with permission, from McQuaid KR. Gastrointestinal disorders. In: Papadakis MA, McPhee SJ, Rabow MW, eds. CURRENT Medical Diagnosis & Treatment 2013. New York: McGraw-Hill; 2013 Accessed April 25, 2013.)



Chronic or persistent diarrhea (lasting more than 2 weeks) can occur in several conditions. In neonates and young infants, the most common etiologies of chronic diarrhea are infection, cow’s milk protein or soy protein intolerance, cystic fibrosis, disaccharidase deficiency, or immunodeficiency. In older children and adolescents, the most likely etiologies of chronic diarrhea are infection, celiac disease, lactose deficiency (primary or secondary), or inflammatory bowel disease. Other less common causes of chronic diarrhea to consider in children are disorders of the pancreas (cystic fibrosis, Shwachman-Diamond syndrome, Johanson-Blizzard syndrome, Pearson syndrome, pancreatic enzyme deficiency, or pancreatitis), bile acid disorders (secondary to cholestasis, terminal ileum resection, or bacterial overgrowth), altered gastrointestinal anatomy (Hirschsprung disease, small bowel obstruction, malrotation), hyperthyroidism, or malignancy (VIPoma).


To investigate chronic diarrhea, one should begin with an examination of the stool for red blood cells, white blood cells, fat, and reducing substances. The stool should be examined for bacterial, viral, and parasitic pathogens. The stool should also be tested for C. difficile, particularly if the patient has a history of recent antibiotic use. Hematologic and biochemical studies can also be useful in determining etiology. A CBC may show anemia suggesting chronic blood loss through the GI tract. An elevated white blood cell count and elevated CRP may suggest acute infection. An elevated platelet count and elevated erythrocyte sedimentation rate (ESR) may suggest a chronic inflammatory condition such as inflammatory bowel disease. Endoscopy and colonoscopy should be performed to obtain histologic clues as to etiology. An upper GI with small bowel follow through can be useful in identifying anatomic abnormalities seen in small bowel Crohn disease.


This patient had negative stool infectious studies suggesting against an infectious etiology for his diarrhea. Examination of the colonic polyps that were removed during colonoscopy revealed that he had adenomatous polyposis with carcinoma in situ. An upper GI with small bowel follow through showed multiple polyps throughout the small bowel. Due to the carcinoma in situ, the patient received a CT scan of the chest, abdomen, and pelvis which showed no signs of metastasis. Formal ophthalmologic examination revealed congenital hypertrophy of the retinal pigment epithelium. The patient was diagnosed with Gardner syndrome. The patient underwent total proctocolectomy, given the high risk of malignancy.


Gardner syndrome is a phenotypic variant of familial adenomatous polyposis, an autosomal dominant disease characterized by numerous adenomatous polyps in the GI tract which have a high potential for malignant transformation. The prevalence has been estimated to be 1:5000 to 1:17 000. Patients may have anywhere from only a few adenomatous polyps to thousands of polyps throughout the colon. The average age of onset of adenomatous polyposis is 16 years, and progression to carcinoma is likely to occur by the fifth decade of life. The presence of upper gastrointestinal polyps is associated with an increased risk of malignancy (Table 17-3).

TABLE 17-3. Polyposis syndromes in children.


In addition to adenomatous colonic polyps, patients with Gardner syndrome can have a number of extraintestinal manifestations. Commonly, patients may have osteomas of the mandible, skull, and long bones. They may have cutaneous manifestations including epidermal inclusion cysts, sebaceous cysts, or skin tumors. Dental abnormalities including impacted teeth, super-numerary teeth, or mandibular cysts can be seen. One characteristic finding on ophthalmologic examination is multiple, bilateral, pigmented ocular fundus lesions, also known as congenital hypertrophy of the retinal pigment epithelium. This finding can be seen in up to 90% of Gardner patients. Desmoid tumors of the abdomen, chest, and extremities are found in approximately 8%-18% of patients with Gardner syndrome. These tumors can result in bowel obstruction, bowel perforation, and intra-abdominal abscesses. Patients with Gardner syndrome are at risk for several malignancies including colorectal adenocarcinomas, duodenal carcinomas, adrenal adenomas, hepatoblastoma, pancreatic cancer, and thyroid cancer. The association of malignant brain tumors in patients with Gardner syndrome or familial adenomatous polyposis is known as Turcot syndrome.

Gardner syndrome is inherited in an autosomal dominant fashion, although spontaneous mutations can be seen in about one-third of cases. The molecular defect causing the occurrence of the multiple adenomatous colonic polyps is a mutation in the adenomatous polyposis coli (APC) tumor suppressor gene located on chromosome 5q21.


The clinical presentation of Gardner syndrome can vary greatly, from painless rectal bleeding to chronic abdominal pain with diarrhea. Asymptomatic iron-deficiency anemia from occult gastrointestinal blood loss may be seen. Colocolic intussusception is possible, with an adenomatous polyp serving as the lead point. Alternatively, patients may present primarily with extraintestinal manifestations. Exostoses of the mandible or long bones, or dental abnormalities such as supernumerary teeth, should raise the index of suspicion for Gardner syndrome.


Endoscopy and colonoscopy. Endoscopy and colonoscopy should be performed on every patient to visualize and remove polyps.

Upper gastrointestinal series with small bowel follow through. This radiologic study may help identify upper gastrointestinal polyps not detected by endoscopy or colonoscopy.

Roentgenograms of long bones and mandible. These radiographs can help identify the exostoses often associated with Gardner syndrome.

Computed tomography (CT). CT of the abdomen, chest, and pelvis may be helpful in identifying desmoid tumors or metastases.

Complete ophthalmologic examination. A thorough retinal examination is important in detecting the presence of congenital hypertrophy of the pigment epithelium which can help confirm a diagnosis of Gardner syndrome.

Genetic testing. Genetic testing can be performed using peripheral blood lymphocytes in an in vitro protein truncation assay; 80%-90% of affected patients are detected by this assay.


For patients with Gardner syndrome, prophylactic total proctocolectomy is the treatment of choice due to the unavoidable progression to neoplasia. Colectomy is recommended shortly after the diagnosis is confirmed. Oral calcium may help to inhibit future proliferation of the rectal epithelium. Sulindac and tamoxifen can be used if rectal polyps develop after colectomy.

Patients with Gardner syndrome need to be screened on a frequent basis for extracolonic malignancies. Patients should undergo screening for thyroid cancer (serum thyroid tests and thyroid ultrasound), brain cancer (brain MRI), liver cancer (LFTs, abdominal ultrasound, and alpha fetoprotein levels), skin cancer (frequent skin examinations by a dermatologist), and adrenal and small bowel cancer (abdominal CT).

Once an individual has been diagnosed with Gardner syndrome, screening of other family members should take place. Genetic testing is the method of choice under these circumstances. The general consensus is that children should undergo genetic testing around 8-10 years of life.


1. Corredor J, Wambach J, Barnard J. Gastrointestinal polyps in children: advances in molecular genetics, diagnosis, and management. J Pediatr. 2001;138(5):621-628.

2. Giardiello FM, Yang VW, Hylind LM, et al. Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med. 2002;346(14):1054-1059.

3. Juhn E, Khachemoune A. Gardner syndrome: skin manifestations, differential diagnosis, and management. Am J Clin Dermatol. 2010;11(2):117-122.

4. Rustgi A. Hereditary gastrointestinal polyposis and nonpolyposis syndromes. New Engl J Med. 1994;331 (25):1694-1702.

5. Traboulsi E, Krush AJ, Gardner EJ, et al. Prevalence and importance of pigmented ocular fundus lesions in Gardner’s syndrome. N Engl J Med. 1987;316: 661-667.