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Cronkhite-Canada Syndrome

  • Author: Kruti Parikh; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jan 14, 2016
 

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 Cronkhite-Canada syndrome (CCS) is unknown. No evidence exists to suggest a familial predisposition. The possibilities of asymptomatic offspring or afflicted patients have not been excluded. Reports suggest immune dysregulation as the basis of Cronkhite-Canada syndrome.[2, 3, 4, 5] Many patients with Cronkhite-Canada syndrome have positive antinuclear antibodies as well as a variety of autoimmune diseases such as systemic lupus erythematous, rheumatoid arthritis, scleroderma, and hypothyroidism.[6] Cronkhite-Canada syndrome patients have also been found to have elevated serum IgG4 levels. Elevated IgG4 plasma cells are also seen in colonic polyps from patients with CCS. This autoimmune etiology is further supported by excellent clinical response to systemic steroids and azathioprine.[2]

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.[7] Senesse et al described Cronkhite-Canada syndrome in association with arsenic poisoning.[8]

Gastrointestinal lesions in Cronkhite-Canada syndrome are hamartomatous polyps generally involving the entire gastrointestinal tract except for the esophagus.[4, 5, 9] Histologically they reveal 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, parental consanguinity was not present in either described case. This raises the question of whether infantile Cronkhite-Canada syndrome may be a sporadic condition.[10, 11]

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Epidemiology

Frequency

Cronkhite-Canada syndrome has a worldwide distribution; over 500 cases have been reported.[12] The majority of these cases have been documented in Japan, including a large series of 180 patients.[13] Cronkhite-Canada syndrome is a rare disorder.[13, 14, 15, 16] Based on the large Japanese series, the estimated incidence of Cronkhite-Canada syndrome is about 1 case per million population.[13]

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 does show a slight male predominance, with a male-to-female ratio of 3:2.[9]

Age

The typical onset of Cronkhite-Canada syndrome is during middle or old age. The average age is 59 years; the range is 31-86 years. Some reports suggest that the disease may remain asymptomatic, thus not being diagnosed for a long time.[17, 18]

Most patients are older than 50 years at the time of presentation.

The reported cases of infantile Cronkhite-Canada syndrome are scant (<10).[10]

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Contributor Information and Disclosures
Author

Kruti Parikh Rutgers Robert Wood Johnson Medical School

Disclosure: Nothing to disclose.

Coauthor(s)

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

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

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

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

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

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

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

Franklin Flowers, MD Department of Dermatology, Professor Emeritus Affiliate Associate Professor of Pathology, University of Florida College of Medicine

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

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

Acknowledgements

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

Disclosure: Nothing to disclose.

References
  1. Cronkhite LW Jr, Canada WJ. Generalized gastrointestinal polyposis; an unusual syndrome of polyposis, pigmentation, alopecia and onychotrophia. N Engl J Med. 1955 Jun 16. 252(24):1011-5. [Medline].

  2. 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. 2011 Sep 1. [Medline].

  3. Kao KT, Patel JK, Pampati V. Cronkhite-Canada syndrome: a case report and review of literature. Gastroenterol Res Pract. 2009. 2009:619378. [Medline].

  4. Chen HM, Fang JY. Genetics of the hamartomatous polyposis syndromes: a molecular review. Int J Colorectal Dis. 2009 Aug. 24 (8):865-74. [Medline].

  5. Riegert-Johnson DL, Osborn N, Smyrk T, Boardman LA. Cronkhite-Canada syndrome hamartomatous polyps are infiltrated with IgG4 plasma cells. Digestion. 2007. 75 (2-3):96-7. [Medline].

  6. Murata I, Yoshikawa I, Endo M, et al. Cronkhite-Canada syndrome: report of two cases. J Gastroenterol. 2000. 35(9):706-11. [Medline].

  7. 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. 2000 Oct. 43(10 Suppl):S29-33. [Medline].

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

  9. Ward EM, Wolfsen HC. Review article: the non-inherited gastrointestinal polyposis syndromes. Aliment Pharmacol Ther. 2002 Mar. 16 (3):333-42. [Medline].

  10. de Silva DG, Fernando AD, Law FM, Premarathne M, Liyanarachchi DS. Infantile Cronkhite-Canada syndrome. Indian J Pediatr. 1997 Mar-Apr. 64(2):261-6. [Medline].

  11. Scharf GM, Becker JH, Laage NJ. Juvenile gastrointestinal polyposis or the infantile Cronkhite-Canada syndrome. J Pediatr Surg. 1986 Nov. 21 (11):953-4. [Medline].

  12. Devulder F, Bouche O, Diebold MD, et al. [Cronkhite-Canada syndrome: a new French case]. Gastroenterol Clin Biol. 1999 Mar. 23(3):407-8. [Medline].

  13. Goto A. [Cronkhite-Canada syndrome; observation of 180 cases reported in Japan]. Nihon Rinsho. 1991 Dec. 49 (12):221-6. [Medline].

  14. Blonski WC, Furth EE, Kinosian BP, Compher C, Metz DC. A case of Cronkhite-Canada syndrome with taste disturbance as a leading complaint. Digestion. 2005. 71 (4):201-5. [Medline].

  15. She Q, Jiang JX, Si XM, Tian XY, Shi RH, Zhang GX. A severe course of Cronkhite-Canada syndrome and the review of clinical features and therapy in 49 Chinese patients. Turk J Gastroenterol. 2013. 24 (3):277-85. [Medline].

  16. Yun SH, Cho JW, Kim JW, Kim JK, Park MS, Lee NE, et al. Cronkhite-Canada syndrome associated with serrated adenoma and malignant polyp: a case report and a literature review of 13 cronkhite-Canada syndrome cases in Korea. Clin Endosc. 2013 May. 46 (3):301-5. [Medline].

  17. 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). 1982 Sep. 61(5):293-309. [Medline].

  18. 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. 2005 Oct. 17(10):1139-41. [Medline].

  19. Kindblom LG, Angervall L, Santesson B, Selander S. Cronkhite-Canada syndrome. Case report. Cancer. 1977 Jun. 39 (6):2651-7. [Medline].

  20. 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. 2008 Mar. 67(3):570-2. [Medline].

  21. Naoshima-Ishibashi Y, Murofushi T. A case of Cronkhite-Canada syndrome with vestibular disturbances. Eur Arch Otorhinolaryngol. 2004 Nov. 261(10):558-9. [Medline].

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

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

  24. 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].

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

  26. 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].

  27. Nakayama M, Muta H, Somada S, et al. Cronkhite-Canada syndrome associated with schizophrenia. Intern Med. 2007. 46(4):175-80. [Medline].

  28. Kim MS, Jung HK, Jung HS, et al. [A Case of Cronkhite-Canada syndrome showing resolution with Helicobacter pylori eradication and omeprazole]. Korean J Gastroenterol. 2006 Jan. 47(1):59-64. [Medline].

  29. Hanzawa M, Yoshikawa N, Tezuka T, et al. Surgical treatment of Cronkhite-Canada syndrome associated with protein-losing enteropathy: report of a case. Dis Colon Rectum. 1998 Jul. 41(7):932-4. [Medline].

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

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

  32. Misra SP, Misra V, Dwivedi M, Singh PA, Gupta SC. Cronkhite--Canada syndrome without colonic polyps. Endoscopy. 1997 May. 29 (4):333. [Medline].

  33. De Petris G, Chen L, Pasha SF, Ruff KC. Cronkhite-Canada syndrome diagnosis in the absence of gastrointestinal polyps: a case report. Int J Surg Pathol. 2013 Dec. 21 (6):627-31. [Medline].

  34. Ikeda K, Sannohe Y, Murayama H. A case of Cronkhite-Canada syndrome developing after hemi-colectomy. Endoscopy. 1981 Nov. 13(6):251-3. [Medline].

  35. Nagata K, Sato Y, Endo S, Kudo SE, Kushihashi T, Umesato K. CT endoscopy for the follow-up of Cronkhite-Canada syndrome. Int J Colorectal Dis. 2007 Sep. 22(9):1131-2. [Medline].

  36. Okamoto K, Isomoto H, Shikuwa S, Nishiyama H, Ito M, Kohno S. A case of Cronkhite-Canada syndrome: remission after treatment with anti-Helicobacter pylori regimen. Digestion. 2008. 78(2-3):82-7. [Medline].

  37. Herzberg AJ, Kaplan DL. Cronkhite-Canada syndrome. Light and electron microscopy of the cutaneous pigmentary abnormalities. Int J Dermatol. 1990 Mar. 29 (2):121-5. [Medline].

  38. Ortonne JP, Bazex J, Berbis P. [Cronkhite-Canada disease. Discussion apropos of a case and study of the pigmentation]. Ann Dermatol Venereol. 1985. 112 (12):951-8. [Medline].

  39. 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. 2014 May. 55 (2):145-8. [Medline].

  40. Burke AP, Sobin LH. The pathology of Cronkhite-Canada polyps. A comparison to juvenile polyposis. Am J Surg Pathol. 1989 Nov. 13(11):940-6. [Medline].

  41. 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].

  42. 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. 1998 Apr. 61(4):229-32. [Medline].

  43. Takahura M, Adachi H, Tsuchihashi N. A case of Cronkhite-Canada Syndrome markedly improved with mesalazine therapy. Digest Endos. 2004. 16:74-8.

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

  45. Oberhuber G, Stolte M. Gastric polyps: an update of their pathology and biological significance. Virchows Arch. 2000 Dec. 437(6):581-90. [Medline].

 
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