Cronkhite-Canada Syndrome 

  • Author: Agnieszka B Serwin, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jan 24, 2012
 

Background

Cronkhite-Canada syndrome (CCS) is a rare, sporadically occurring, noninherited disorder reported for the first time in 1955 by Leonard W. Cronkhite, Jr, and Wilma J. Canada as a new distinct clinical entity in 2 female patients with generalized gastrointestinal polyps, cutaneous pigmentation, alopecia, and onychodystrophy.[1]

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Pathophysiology

The etiology of the disease is unknown. No evidence exists to suggest a familial predisposition. The possibilities of asymptomatic offspring or afflicted patients have not been excluded. Mental and physical stress have been postulated as the most important risk factors for Cronkhite-Canada syndrome. The stress acts on the gastrointestinal mucosa, inducing a local inflammatory reaction. One patient with Cronkhite-Canada syndrome developed typical ectodermal lesions 2 weeks after starting oral thyroxine, and the cutaneous signs improved following cessation of the treatment.[2, 3]

Negoro et al demonstrated that germlike mutations of the tumor suppressor gene PTEN (phosphatase and tensin homologue), located at 10q23.3, which is responsible for another gastrointestinal polyposis syndrome (Cowden disease), is not detected in persons with Cronkhite-Canada syndrome.[4] Senesse et al described Cronkhite-Canada syndrome in association with arsenic poisoning.[5] Murata et al suggested the possible role of an autoimmune response in the pathogenesis of Cronkhite-Canada syndrome because of the presence of antinuclear antibodies in a serum of a patient with Cronkhite-Canada syndrome who had a history of chronic pityriasis lichenoides.[6, 7] The effectiveness of corticosteroid therapy in many cases of Cronkhite-Canada syndrome seems to support the involvement of the immune system in the pathogenesis of Cronkhite-Canada syndrome.

Gastrointestinal lesions in Cronkhite-Canada syndrome are hamartomatous polyps (or polyps of polyposis syndromes according to a newly proposed classification; World Health Organization tumorlike lesions), histologically revealing pseudopolypoid-inflammatory changes. Cutaneous symptoms are believed to be due to malabsorption; however, ectodermal changes did not appear to parallel the disease activity and improved despite gut dysfunction in some reported cases. Multiple brownish macules and patches also preceded the onset of gastrointestinal symptoms in one of the first reported cases of Cronkhite-Canada syndrome.

Infantile Cronkhite-Canada syndrome (similar to typical Cronkhite-Canada syndrome) includes juvenile gastrointestinal polyps, alopecia, nail changes, and macrocephaly. Infantile Cronkhite-Canada syndrome is believed to be a special variant of juvenile gastrointestinal polyposis. Its mode of inheritance is assumed to be autosomal recessive; however, paternal consanguinity was not present in either described case. This raises the question of whether infantile Cronkhite-Canada syndrome may be a sporadic condition.[8]

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Epidemiology

Frequency

International

Cronkhite-Canada syndrome has a worldwide distribution,[9] and 75% of reports come from Japan. Cronkhite-Canada syndrome is a rare disorder. At the end of 2002, only 467 cases have been reported in the world literature, 354 of which were reported by Japanese groups.

Mortality/Morbidity

Cronkhite-Canada syndrome is considered a relentlessly progressive disease with a variable course and poor prognosis depending mainly on control of protein and electrolyte balance. Mortality rate exceeds 50% regardless of therapy. As reported in cases of Cronkhite-Canada syndrome, coexistent malignant changes in the polyps, gastrointestinal bleeding, and the possibility of intussusception or prolapse of gastric polyp-bearing mucosa increase the mortality.[10]

  • The first 2 described patients with Cronkhite-Canada syndrome died of starvation 7 and 8 months after the onset of symptoms.
  • Cases of spontaneous remission after nutritional support have been reported.
  • The prognosis in children is believed to be generally less optimistic than in adults.

Race

No data are available on racial predisposition. Cronkhite-Canada syndrome has a worldwide distribution; however, most reported cases come from Japan.

Sex

Cronkhite-Canada syndrome seems to affect both sexes almost equally. The male-to-female ratio is approximately 1.5-1.3:1.

Age

The typical onset of Cronkhite-Canada syndrome is during middle or old age. The average age is 55 years; the range is 31-86 years. Vernia et al have suggested that the disease may remain asymptomatic, thus not being diagnosed for a long time.[11]

  • Most patients are older than 50 years at the time of presentation.
  • The reported cases of infantile Cronkhite-Canada syndrome are scant (< 10).
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Contributor Information and Disclosures
Author

Agnieszka B Serwin, MD  Consulting Staff, Department of Dermatology and Venereology, Medical Academy of Bialystok, Poland

Disclosure: Nothing to disclose.

Coauthor(s)

Hanna Mysliwiec, MD  Staff Physician, Department of Dermatology and Venereology, Medical Academy of Bialystok, Poland

Disclosure: Nothing to disclose.

Specialty Editor Board

Franklin Flowers, MD  Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

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  2. Ho V, Banney L, Falhammar H. Hyperpigmentation, nail dystrophy and alopecia with generalised intestinal polyposis: Cronkhite-Canada syndrome. Australas J Dermatol. Nov 2008;49(4):223-5. [Medline].

  3. Daniel ES, Ludwig SL, Lewin KJ, Ruprecht RM, Rajacich GM, Schwabe AD. The Cronkhite-Canada Syndrome. An analysis of clinical and pathologic features and therapy in 55 patients. Medicine (Baltimore). Sep 1982;61(5):293-309. [Medline].

  4. Negoro K, Takahashi S, Kinouchi Y, et al. Analysis of the PTEN gene mutation in polyposis syndromes and sporadic gastrointestinal tumors in Japanese patients. Dis Colon Rectum. Oct 2000;43(10 Suppl):S29-33. [Medline].

  5. Senesse P, Justrabo E, Boschi F, et al. [Cronkhite-Canada syndrome and arsenic poisoning: fortuitous association or new etiological hypothesis?]. Gastroenterol Clin Biol. Mar 1999;23(3):399-402. [Medline].

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  11. Vernia P, Marcheggiano A, Marinaro V, Morabito S, Guzzo I, Pierucci A. Is Cronkhite-Canada Syndrome necessarily a late-onset disease?. Eur J Gastroenterol Hepatol. Oct 2005;17(10):1139-41. [Medline].

  12. Yasuda T, Ueda T, Matsumoto I, Shirasaka D, Nakajima T, Sawa H, et al. Cronkhite-Canada syndrome presenting as recurrent severe acute pancreatitis. Gastrointest Endosc. Mar 2008;67(3):570-2. [Medline].

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  14. Sweetser S, Alexander GL, Boardman LA. A case of Cronkhite-Canada syndrome presenting with adenomatous and inflammatory colon polyps. Nat Rev Gastroenterol Hepatol. Aug 2010;7(8):460-4. [Medline].

  15. Bruce A, Ng CS, Wolfsen HC, Smallridge RC, Lookingbill DP. Cutaneous clues to Cronkhite-Canada syndrome: a case report. Arch Dermatol. Feb 1999;135(2):212. [Medline].

  16. Yashiro M, Kobayashi H, Kubo N, Nishiguchi Y, Wakasa K, Hirakawa K. Cronkhite-Canada syndrome containing colon cancer and serrated adenoma lesions. Digestion. 2004;69(1):57-62. [Medline].

  17. Hutnik CM, Nichols BD. Cataracts in systemic diseases and syndromes. Curr Opin Ophthalmol. Feb 1999;10(1):22-8. [Medline].

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  22. Bacher T, Schonekas H, Steurer KT, Wunsch PH. [The Cronkhite-Canada Syndrome. A rare differential diagnosis of generalized gastrointestinal polyposis]. Dtsch Med Wochenschr. May 23 1997;122(21):676-81. [Medline].

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  28. Allbritton J, Simmons-O'Brien E, Hutcheons D, Whitmore SE. Cronkhite-Canada syndrome: report of two cases, biopsy findings in the associated alopecia, and a new treatment option. Cutis. Apr 1998;61(4):229-32. [Medline].

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  30. Sampson JE, Harmon ML, Cushman M, Krawitt EL. Corticosteroid-responsive Cronkhite-Canada syndrome complicated by thrombosis. Dig Dis Sci. Apr 2007;52(4):1137-40. [Medline].

 
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