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Pediatric Cronkhite-Canada Syndrome

  • Author: Simon S Rabinowitz, MD, PhD, FAAP; Chief Editor: Carmen Cuffari, MD  more...
 
Updated: Nov 17, 2015
 

Background

Cronkhite-Canada syndrome (CCS) is a rare nonfamilial syndrome characterized by marked epithelial disturbances in the GI tract and epidermis that was first described in 1955. The GI changes are generalized hamartomatous polyposis with abnormal intervening mucosa. The mucosal proliferation leads to fluid and electrolyte abnormalities, malabsorption, malnutrition, GI bleeding, and surgical complications. The prevalence of GI malignancy in patients with CCS is about 10%. Epidermal manifestations include alopecia, onychodystrophy, and hyperpigmentation. Approximately two thirds of all cases occur in individuals of Japanese descent. A few case reports have described an infantile form of this syndrome associated with a poor prognosis.[1]

Many case reports and several accumulated series bring the total cases reported in the medical literature to more than 400. Until recently, the understanding of the disease was based on small series and anecdotal reports. However, a Japanese survey that included 200 patients provided the most comprehensive characterization of this unique syndrome.[2] Although this survey includes the most detailed description of the clinical features, the impact of the various therapeutic options and the prognosis, the etiology, and the factors leading to disease progression or spontaneous remission have still not been established. In particular, the coordination of profound disturbances in two discrete epithelia, either concurrently or sequentially, is a provocative but unexplained phenomenon. Presently, the most common postulated pathogenesis factors include an autoimmune and/or an infectious trigger for the symptoms. 

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Pathophysiology

The characteristic features are GI polyposis and ectodermal changes. The polyps are part of a generalized GI mucosal disturbance that presents with malabsorption and protein-losing enteropathy. These changes lead to the clinical symptoms, including diarrhea, abdominal pain, and profound malnutrition. Ultimately, the polyps can become malignant, necessitating the need for ongoing surveillance.[3]  

Dermatologic signs accompany the GI symptoms. The vast majority of affected individuals have alopecia and alterations in the nail beds and skin pigmentation. Although data from most cases support the belief that ectodermal features are the result of profound malnutrition, many symptoms and signs appear or remit in a manner inconsistent with this theory. 

Diarrhea is secondary to chronic inflammation in the GI tract and is multifactorial. Dilated glands in the GI mucosa release protein-enriched secretions into the lumen of the gut. The disrupted mucosa cannot digest disaccharides or absorb carbohydrates and lipids. The beneficial effects of antibiotics are attributed to small-bowel overgrowth. Steroids are most likely effective as anti-inflammatory agents. Polyps are believed to contribute to diarrhea. However, some therapeutic modalities and spontaneous remissions have improved diarrhea without affecting the number of polyps.

The disease usually evolves rapidly over several months. Mild GI and nutritional symptoms progress to substantial weight loss and edema. Ectodermal changes are usually observed several weeks or months after GI symptoms begin. Aside from the consequences of malnutrition, which can become life-threatening, most of the complications encountered are manifestations of the polyposis. Untreated, the disease progresses, with occasional spontaneous remissions and frequent relapses and rare progression to malignancy.[2] The most common agent employed to successfully treat CCS patients is corticosteroids which has suggested an autoimmune basis. The concurrence of gastrointestinal infections such as Helicobacter pylori and Candida have suggested an infectious etiology. One case report describes a woman who showed complete regression of CCS lesions following abdominal colectomy and eradication of Helicobacter pylori infection.[4]  The observation of CCS in a patient with eosinophilic gastroenteritis suggests the possibility of an allergic etiology.[5]  

Juvenile GI polyposis is a syndrome described in infants who present with hamartomatous polyposis, macrocephaly, alopecia, nail dystrophy, clubbing of fingers and toes, hypotonia, hepatosplenomegaly, anemia, and hypoproteinemia due to protein-losing enteropathy. Although some authors consider this syndrome a form of CCS others think it is a different entity. The prognosis is usually very poor.

With the increasing observation of gastric and colorectal cancer in patients with CCS, various authors have attempted to hypothesize about this association. A group from Japan found a 40% prevalence of serrated adenomatous polyps in patients with CCS compared with a 1% incidence of this histology in all GI polyps.[6] Furthermore, this same group described a patient with microsatellite instability and overexpression of the p53 protein in the cancer and serrated adenoma. They proposed the possibility of a serrated adenoma-carcinoma sequence underlying some CCS GI malignancy.

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Epidemiology

Frequency

United States

As of 1995, only 15 authenticated cases were reported in American literature. As the number of cases reported has increased over the last decade, this has increased.

International

Two thirds of the 450 or so reported cases come from Japan.[7] An old estimate is a prevalence of 1 case in 1 million population. In Japan, which has a population of approximately 125 million and over 250 cases, the prevalence is thus approximately 1 case per 500,000. 

Mortality/Morbidity

Earlier, the mortality had been reported to be up to 50% but that cohort was untreated, inadequately treated, or had treatment delay. The recent Japanese survey reported that 15.7% of those diagnosed had died, but only about one third (10/33) were related to CCS. Of these 10, 3 died of gastric cancer, 3 died of colon cancer, and 4 died of sepsis secondary to colitis and pancreatitis. The other deaths were secondary to unrelated causes because of their advanced age.[2]

  • Malnutrition: Acute fluid and electrolyte disturbances can follow long-term nutrient depletion and can be exacerbated by enteral losses of serum proteins. These disturbances result in anasarca, congestive heart failure, and immunologic deficiencies.
  • Anemia: Acute and chronic GI blood losses secondary to gastroduodenal ulceration and erosions of colorectal polyp epithelium compound nutritional deficiencies of iron, folate, and, possibly, vitamin B-12 and reticulocytopenia found in chronic disease. Packed RBC transfusions may be required. Patients may die from severe GI hemorrhage.
  • Surgery: In the early literature, bowel resection was performed to make a diagnosis. It is now mainly reserved for emergency complications. A compromised preoperative state contributes to the high surgical mortality rate. The recent Japanese survey also reported 30% prevalence of carcinomas (19 gastric, 41 colon, and none in the stomach or small bowel). Carcinomas were found throughout the colon. [2]  

Race

The cause of the frequent case reports from Japan is unclear. The author of the largest series postulates that mental and physical stresses are contributory factors.[7] Evidence does not suggest a genetic or specific infectious basis. A single case report describes the disease in a 50-year-old Indian man and his 22-year-old son.[8] After Japanese patients, most patients are whites from North America and Western Europe.

Sex

In Japan, the male-to-female ratio is 2:1. Outside Japan, the small number of cases has no sexual predilection.

Age

The age distribution of published cases ranges from 31-85 years, with onset of disease occurring most commonly in patients aged 50-60 years. Similar to the experience of one author presented in abstract form, an Italian group has described a case of a 17-year-old with clinical features consistent with Cronkhite-Canada syndrome.[9]

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Prognosis

Although early publications predicted a guarded prognosis, the recent Japanese epidemiologic survey confirms that with aggressive glucocorticoid and possibly added nutritional therapy there can be good short term improvement in the nutritional parameters. This will yield a resolution of the protein-losing enteropathy/hypoalbuminemia, the ectodermal changes seen in the nails, alopecia, and dysgeusia. Persistence of polyps then becomes the focus with endoscopic decrease a therapeutic end point. This will often require a much more prolonged course of therapy. Subsequently, steroids should be weaned slowly. Decreasing the long term mortality is then centered around detecting and removing malignant polyps. Thus, ongoing surveillance for gastric and colonic cancer is recommended[2] .  

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Patient Education

Patients should be familiarized with the spectrum of ectodermal changes that are seen in the syndrome. Any aberrant gastrointestinal syndromes and weight loss should be brought to the attention of their gastroenterologists. Even if a patient achieves a resolution of symptoms, he or she remains at risk for GI malignancy and should continue to have annual surveillance endoscopies and colonoscopies or at a schedule determined in conjunction with their gastroenterologist. 

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Contributor Information and Disclosures
Author

Simon S Rabinowitz, MD, PhD, FAAP Professor of Clinical Pediatrics, Vice Chairman, Clinical Practice Development, Pediatric Gastroenterology, Hepatology, and Nutrition, State University of New York Downstate College of Medicine, The Children's Hospital at Downstate

Simon S Rabinowitz, MD, PhD, FAAP is a member of the following medical societies: American Gastroenterological Association, American Academy of Pediatrics, Phi Beta Kappa, American Association for the Advancement of Science, American College of Gastroenterology, American Medical Association, New York Academy of Sciences, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Kanika Puri, MD Resident Physician, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David A Piccoli, MD Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine

David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching.

Additional Contributors

Chris A Liacouras, MD Director of Pediatric Endoscopy, Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Chris A Liacouras, MD is a member of the following medical societies: American Gastroenterological Association

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor Dr Minoj Sheth to the development and writing of this article.

References
  1. Ruymann FB. Juvenile polyps with cachexia. Report of an infant and comparison with Cronkhite-Canada syndrome in adults. Gastroenterology. 1969 Oct. 57(4):431-8. [Medline].

  2. Watanabe C, Komoto S, Tomita K, Hokari R, Tanaka M, Hirata I, et al. Endoscopic and clinical evaluation of treatment and prognosis of Cronkhite-Canada syndrome: a Japanese nationwide survey. J Gastroenterol. 2015 Jul 28. [Medline].

  3. Kopáčová M, Urban O, Cyrany J, et al. Cronkhite-Canada syndrome: review of the literature. Gastroenterol Res Pract. 2013. 2013:856873. [Medline].

  4. Kato K, Ishii Y, Mazaki T, Uehara T, Nakamura H, Kikuchi H, et al. Spontaneous Regression of Polyposis following Abdominal Colectomy and Helicobacter pylori Eradication for Cronkhite-Canada Syndrome. Case Rep Gastroenterol. 2013 Jan. 7(1):140-6. [Medline]. [Full Text].

  5. Yashiro M, Kobayashi H, Kubo N, et al. Cronkhite-Canada syndrome containing colon cancer and serrated adenoma lesions. Digestion. 2004. 69(1):57-62. [Medline].

  6. Goto A. Cronkhite-Canada syndrome: epidemiological study of 110 cases reported in Japan. Nippon Geka Hokan. 1995 Jan 1. 64(1):3-14. [Medline].

  7. Vernia P, Marcheggiano A, Marinaro V, et al. Is Cronkhite-Canada Syndrome necessarily a late-onset disease?. Eur J Gastroenterol Hepatol. 2005 Oct. 17(10):1139-41. [Medline].

  8. Patil V, Patil LS, Jakareddy R, Verma A, Gupta AB. Cronkhite-Canada syndrome: a report of two familial cases. Indian J Gastroenterol. 2013 Mar. 32(2):119-22. [Medline].

  9. Hizawa K, Nakamori M, Yao T, Matsumoto T, Iida, M. A Case of Cronkhite-Canada Syndrome with Colorectal Adenomas: Effect of the Nonsteroidal Anti-Inflammatory Drug Sulindac. Am J Gastroenterol. August 2007. 102 (8):1831-2. [Medline].

  10. Riegert-Johnson DL, Osborn N, Smyrk T, Boardman LA. Cronkhite-Canada Syndrome Hamartomatous Polyps are Infiltrated with IgG4 Plasma Cells. Digestion. 2007/05. 75 (2-3):96-97. [Medline].

  11. Dachman AH, Buck JL, Burke AP, Sobin LH. Cronkhite-Canada syndrome: radiologic features. Gastrointest Radiol. 1989. 14(4):285-90. [Medline].

  12. Kilcheski T, Kressel HY, Laufer I, Rogers D. The radiographic appearance of the stomach in Cronkhite-Canada syndrome. Radiology. 1981 Oct. 141(1):57-60. [Medline].

  13. Goto A, Mimoto H, Shibuya C, Matsunami E. Cronkhite-Canada syndrome: an analysis of clinical features and follow-up studies of 80 cases reported in Japan. Nippon Geka Hokan. 1988 Nov 1. 57(6):506-26. [Medline].

  14. Freeman K, Anthony PP, Miller DS, Warin AP. Cronkhite Canada syndrome: a new hypothesis. Gut. 1985 May. 26(5):531-6. [Medline].

  15. [Guideline] Dominic OG, McGarrity T, Dignan M, Lengerich EJ. American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008. Am J Gastroenterol. 2009 Oct. 104(10):2626-7; author reply 2628-9. [Medline].

  16. Cao XC, Wang BM, Han ZC. Wireless capsule endoscopic findings in Cronkhite-Canada syndrome. Gut. 2006. 55 (6):899-900. [Medline].

  17. Daniel ES, Ludwig SL, Lewin KJ, et al. The Cronkhite-Canada Syndrome. An analysis of clinical and pathologic features and therapy in 55 patients. Medicine (Baltimore). 1982 Sep. 61(5):293-309. [Medline].

  18. Nonomura A, Ohta G, Ibata T, et al. Cronkhite-Canada syndrome associated with sigmoid cancer case report and review of 54 cases with the syndrome. Acta Pathol Jpn. 1980 Sep. 30(5):825-45. [Medline].

  19. Russell DM, Bhathal PS, St John DJ. Complete remission in Cronkhite-Canada syndrome. Gastroenterology. 1983 Jul. 85(1):180-5. [Medline].

  20. Samoha S, Arber N. Cronkhite-Canada syndrome. Digestion. 2005. 71(4):199-200. [Medline].

  21. Ward EM, Wolfsen HC. Pharmacological management of Cronkhite-Canada syndrome. Expert Opin Pharmacother. 2003 Mar. 4(3):385-9. [Medline].

  22. Anderson RD, Patel R, Hamilton JK, Boland CR. Cronkhite-Canada syndrome presenting as eosinophilic gastroenteritis. Proc (Bayl Univ Med Cent). 2006 Jul. 19(3):209-12. [Medline].

  23. Nakayama M, Muta H, Somada S, Maeda T, Mutoh T, Shimizu K. Cronkhite-Canada syndrome associated with schizophrenia. Intern Med. 2007. 46(4):175-80. [Medline].

  24. Watanabe-Okada E, Inazumi T, Matsukawa H, Ohyama M. Histopathological insights into hair loss in Cronkhite-Canada syndrome: Diffuse anagen-telogen conversion precedes clinical hair loss progression. Australas J Dermatol. 2013 May 29. [Medline].

  25. Suzuki R, Irisawa A, Hikichi T, Takahashi Y, Kobayashi H, Kumakawa H. Cronkhite-Canada syndrome associated with myelodysplastic syndrome. World J Gastroenterol. 2009 Dec 14. 15(46):5871-4. [Medline].

  26. Sweetser S, Ahlquist DA, Osborn NK, Sanderson SO, Smyrk TC, Chari ST, et al. Clinicopathologic features and treatment outcomes in Cronkhite-Canada syndrome: support for autoimmunity. Dig Dis Sci. 2012 Feb. 57(2):496-502. [Medline].

  27. Qiao M, Lei Z, Nai-Zhong H, Jian-Ming X. Cronkhite-Canada syndrome with hypothyroidism. South Med J. 2005 May. 98(5):575-6. [Medline].

  28. Yuan B, Jin X, Zhu R, Zhang X, Liu J, Wan H. Cronkhite-Canada syndrome associated with rib fractures: a case report. BMC Gastroenterol. 2010. 10:121. [Medline].

  29. Hatogai K, Hosoe N, Imaeda H, Rey JF, Okada S, Ishibashi Y. Role of enhanced visibility in evaluating polyposis syndromes using a newly developed contrast image capsule endoscope. Gut Liver. 2012 Apr. 6(2):218-22. [Medline].

  30. Karasawa H, Miura K, Ishida K, Sase T, Kobayashi T, Kinouchi M. Cronkhite-Canada syndrome complicated with huge intramucosal gastric cancer. Gastric Cancer. 2009. 12(2):113-7. [Medline].

  31. Peitl A, Vucic Peitl M, Pavlovic E, Ljubicic D. Acute brain syndrome as a consequence of the Cronkhite-Canada syndrome. Psychiatr Danub. 2005 Jun. 17(1-2):90-3. [Medline].

  32. Samet JD, Horton KM, Fishman EK, Iacobuzio-Donahue CA. Cronkhite-Canada Syndrome: Gastric Involvement Diagnosed by MDCT. Case Report Med. 2009. 2009:148795. [Medline].

  33. Tseng KC, Sheu BS, Lee JC, Tsai HM, Chiu NT, Dai YC. Application of technetium-99m-labeled human serum albumin scan to assist surgical treatment of protein-losing enteropathy in Cronkhite-Canada syndrome: report of a case. Dis Colon Rectum. 2005 Apr. 48(4):870-3. [Medline].

  34. Watari J, Morita T, Sakurai J, Yamasaki T, Okugawa T, Toyoshima F, et al. Endoscopically treated Cronkhite-Canada syndrome associated with minute intramucosal gastric cancer: an analysis of molecular pathology. Dig Endosc. 2011 Oct. 23(4):319-23. [Medline].

 
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