Pediatric Cronkhite-Canada Syndrome Workup

Because the diagnosis of Cronkhite-Canada syndrome (CCS) is clinical, relatively little effort is made to comprehensively categorize laboratory data in affected patients. Testing is necessary to identify and monitor complications of the disease.

• Baseline blood testing: Important baseline blood results include serum electrolyte (eg, calcium, magnesium, potassium, zinc), BUN, creatinine, albumin, and total protein levels, as well as the prothrombin time (PT) and/or the activated partial thromboplastin time (aPTT) and CBC count.
• Erythrocyte sedimentation rate (ESR) testing: In the early stages of the syndrome, blood obtained for ESR testing and stools obtained for cultures and evaluation for ova, parasites, and leukocytes are helpful in ruling out other causes of diarrhea.
• Serial evaluations

  • Results of serial evaluations may guide therapy and minimize morbidity.
  • Evaluations help in identifying treatable causes of anemia (eg, iron, folate, and vitamin B-12 deficiency); the Schilling test is occasionally used.
  • Evaluations are performed to characterize malabsorption by using the serum xylose, carotene, hydrogen breath, fecal alpha-1-antitrypsin, and fat excretion tests.
  • Evaluations elucidate secondary immunologic deficiencies by measuring serum globulins.
  • Nuclear medicine studies based on technetium-labeled human serum albumin can be used to localize the site of protein-losing enteropathy and to direct surgical resection.
• Other tests

  • Previous investigators determined that Cronkhite-Canada syndrome is not primarily associated with pituitary, adrenal, pancreatic, renal, or liver abnormalities.
  • A small number of patients have hypothyroidism. The nature of this association is unknown.

• Upper GI series: This, along with small-bowel follow-through, is used to evaluate polyps in the stomach and small bowel, especially those beyond the ligament of Treitz.
• Colonoscopy: When colonoscopy is unavailable, barium enema with reflux into the terminal ileum is used to investigate colonic and distal small-bowel polyps.
• Plain radiography and contrast-enhanced studies: Complications that require surgical intervention, such as ulcer perforation and intussusception, are diagnosed with plain radiography of the abdomen and contrast studies.
• Imaging and endoscopic studies

  • Although the esophagus is rarely involved, the stomach and colon almost always contain polyps. Polyps are noted in the small bowel in approximately one half of all patients, most often in the duodenum and terminal ileum.^[7] Although most polyps are sessile, pedunculated lesions are frequently encountered.
  • Gastric folds can enlarge^[8] and create the appearance of Menetrier syndrome.
• Wireless capsule endoscopy: This has recently been used to visualize the abnormal mucosal appearance that was found throughout most of the small bowel.^[9] This noninvasive technique may enhance our understanding of the temporal relationships between mucosal changes and the development of malabsorption and clinical symptoms. It may also have a role in evaluating the early response of patients with Cronkhite-Canada syndrome to various treatment modalities.

• Diagnostic endoscopy: This test, which is superior to radiographic imaging, allows direct visualization and biopsy of the GI mucosa. Abnormal intervening mucosa distinguishes Cronkhite-Canada syndrome from the generalized polyposis syndromes prior to the ectodermal changes.
• Therapeutic endoscopy: This is used to identify and treat sources of GI bleeding and to remove polyps with suspected dysplasia and carcinoma.

• The universal finding is hamartomatous polyps of the juvenile (retention) type throughout the GI tract without typically involving the esophagus. Mucosal changes are characterized by intact surface epithelium, edematous chronically inflamed lamina propria, and proliferated tortuous glands, some of which are cystically dilated and filled with proteinaceous fluid or inspissated mucus. The mucosa often contains engorged vascular channels, surface erosions, and prominent eosinophilic infiltration. Compared with the hamartomas seen in patients with juvenile colonic polyposis, colonic Cronkhite-Canada syndrome polyps generally have a broader sessile base.
• In Cronkhite-Canada syndrome, but not in generalized juvenile polyposis coli, the mucosa between polyps is also abnormal, with edema, congestion, and inflammation of the lamina propria and focal glandular ectasia. Adenomatous changes and carcinoma occur in, or in close proximity to, hamartomatous polyps in almost 15% of affected patients. As indicated above, future work may corroborate the importance of serrated adenoma as a premalignant lesion.

No staging system is available for this rare entity. However, Goto et al have divided the clinical presentation into 5 categories; this may assist clinicians considering this diagnosis.^[10] The categories, based on presenting symptoms and subsequent clinical course, are as follows:

• Diarrhea (35%)

  • Skin hyperpigmentation and nail dystrophy (56%)
  • Hypogeusia, alopecia, skin hyperpigmentation, and nail dystrophy (28.2%)
  • Nail dystrophy, alopecia, skin hyperpigmentation, and hypogeusia (15.4%)
• Hypogeusia (40.9%)

  • Diarrhea, alopecia, hyperpigmentation of skin, and nail dystrophy (71.1%)
  • Nail dystrophy, alopecia, skin hyperpigmentation, and diarrhea (22.2%)
  • Nail dystrophy and alopecia (13.3%)
• Xerostomia (6.4%) - Diarrhea, alopecia, skin hyperpigmentation, and nail dystrophy
• Abdominal discomfort (9.1%) - Alopecia, hyperpigmentation of skin, nail dystrophy, and diarrhea
• Alopecia (8.2%)

  • Diarrhea, nail dystrophy, skin hyperpigmentation, and hypogeusia (55.6%)
  • Skin hyperpigmentation, diarrhea, and hypogeusia (44.4%)