Sections

Treatment

Medical Care

Because of the unknown etiology, treatment for Cronkhite-Canada syndrome (CCS) remains predominantly symptomatic. Controlled therapeutic trials have not been possible because of the rarity of the disease. Remissions may occur spontaneously.

The primary goal of the treatment is to correct fluid, electrolyte, and protein loss, and to regulate stool frequency. These measures help improve the patient's general condition. Most patients need symptomatic treatment for abdominal pain.

The most effective treatment is combination therapy composed of systemic corticosteroids together with an antiplasmin, an elemental diet, and hyperalimentation (nutritional supplements). Antibiotics are used to correct intestinal bacterial overgrowth syndrome. The indication for corticosteroids is gastrointestinal inflammation; however, its origin is not clear. Yamakawa et al reported two cases of steroid-resistant Cronkhite-Canada syndrome that were effectively treated with cyclosporine. Dramatic improvement of clinical symptoms and endoscopic findings were observed in both cases.^[20]Another case in which multiple treatments, including steroids, azathioprine, adalimumab, and cyclosporine, failed was treated with sirolimus, with apparent clinical and endoscopic remission of the disease.^[66]One case has been reported to be treated with rituximab.^[34]

Reports describe clinical response in Cronkhite-Canada syndrome to tumor necrosis factor (TNF) inhibitors, with improvement of symptoms, weight gain, and polyp regression. These findings reinforce the theory of this syndrome’s inflammatory etiology.^{[11, 29, 67, 68, 69]}Immunosuppression in Cronkhite-Canada syndrome patients should be cautiously performed, owing to the potential accelerated malignancy risk.

Nutritional supplementation includes oral and/or intravenous fluids, electrolytes, vitamins, minerals, amino acids, albumins, and lipids.

Transfusions are sometimes required for severe anemia or acute blood loss.

In one reported case with elevated gastric acid secretion, the patient responded very well to ranitidine therapy.^[70]Other medications used are sulfasalazine and metronidazole.

After H pylori eradication, gastric polypectomy can be of value.^[17]

Emergent re-admission of patients with Cronkhite-Canada syndrome may occur because of significant diarrhea, gastrointestinal bleeding, intussusception, prolapse of gastric polyp-bearing mucosa, and thromboembolic episodes due to dehydration.

Surgical Care

At present, surgery is needed only for complications of Cronkhite-Canada syndrome (CCS), such us prolapse, bowel obstruction, and malignancy. Other authors suggest that surgical intervention should also be reserved for patients who are not responsive to conservative methods.

Surgical intervention carries a significant risk in weakened patients with Cronkhite-Canada syndrome. Careful consideration must be given to the clinical course of Cronkhite-Canada syndrome before administration of systemic corticosteroids.

Consultations

Gastroenterologist consultation always is required to establish number, localization, and size of polypoid lesions.

Consultation with a surgeon can help determine if surgical intervention is necessary.

Acute brain syndrome requires psychiatrist consultation.

Long-Term Monitoring

Some Cronkhite-Canada syndrome (CCS) patients remain asymptomatic after the hospital treatment and do not require further therapy. Prolonged corticosteroid therapy is necessary in other patients.

Controlling the macronutrient and micronutrient balance, periodically performing endoscopic examination of the gastrointestinal tract, and testing for occult blood presence in the stool are recommended.

It is essential to explain that patients must be reliable with follow-up care and regular examination of the gastrointestinal tract. Large polyps (>1 cm in diameter) require biopsy and pathologic examination.

Medication

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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Kao KT, Patel JK, Pampati V. Cronkhite-Canada syndrome: a case report and review of literature. Gastroenterol Res Pract. 2009. 2009:619378. [QxMD MEDLINE Link].
Chen HM, Fang JY. Genetics of the hamartomatous polyposis syndromes: a molecular review. Int J Colorectal Dis. 2009 Aug. 24 (8):865-74. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Murata I, Yoshikawa I, Endo M, et al. Cronkhite-Canada syndrome: report of two cases. J Gastroenterol. 2000. 35(9):706-11. [QxMD MEDLINE Link].
Traussnigg S, Dolak W, Trauner M, Kazemi-Shirazi L. Difficult case of Cronkhite-Canada syndrome with small intestinal bacterial overgrowth, Clostridium difficile infection and polymyalgia rheumatica. BMJ Case Rep. 2016 Jan 27. 2016:[QxMD MEDLINE Link].
Fan RY, Wang XW, Xue LJ, An R, Sheng JQ. Cronkhite-Canada syndrome polyps infiltrated with IgG4-positive plasma cells. World J Clin Cases. 2016 Aug 16. 4 (8):248-52. [QxMD MEDLINE Link].
Li Y, Luo HQ, Wu D, Xue XW, Luo YF, Xiao YM, et al. [Clinicopathologic features of Cronkhite-Canada syndrome and the significance of IgG4-positive plasma cells infiltration]. Zhonghua Bing Li Xue Za Zhi. 2018 Oct 8. 47 (10):753-757. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Boland BS, Bagi P, Valasek MA, Chang JT, Bustamante R, Madlensky L, et al. Cronkhite Canada Syndrome: Significant Response to Infliximab and a Possible Clue to Pathogenesis. Am J Gastroenterol. 2016 May. 111 (5):746-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Ward EM, Wolfsen HC. Review article: the non-inherited gastrointestinal polyposis syndromes. Aliment Pharmacol Ther. 2002 Mar. 16 (3):333-42. [QxMD MEDLINE Link].
Sharma V, Mandavdhare HS, Prasad KK, Dutta U. Gastrointestinal: Esophageal squamous cell papilloma in a patient with Cronkhite-Canada syndrome. J Gastroenterol Hepatol. 2018 Dec. 33 (12):1937. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Scharf GM, Becker JH, Laage NJ. Juvenile gastrointestinal polyposis or the infantile Cronkhite-Canada syndrome. J Pediatr Surg. 1986 Nov. 21 (11):953-4. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Stefanaki C, Stratigos A. Alopecia in Cronkhite-Canada syndrome. Br J Dermatol. 2017 Aug. 177 (2):348-349. [QxMD MEDLINE Link].
Yamakawa K, Yoshino T, Watanabe K, Kawano K, Kurita A, Matsuzaki N, et al. Effectiveness of cyclosporine as a treatment for steroid-resistant Cronkhite-Canada syndrome; two case reports. BMC Gastroenterol. 2016 Oct 6. 16 (1):123. [QxMD MEDLINE Link].
Devulder F, Bouche O, Diebold MD, et al. [Cronkhite-Canada syndrome: a new French case]. Gastroenterol Clin Biol. 1999 Mar. 23(3):407-8. [QxMD MEDLINE Link].
Goto A. [Cronkhite-Canada syndrome; observation of 180 cases reported in Japan]. Nihon Rinsho. 1991 Dec. 49 (12):221-6. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Oberhuber G, Stolte M. Gastric polyps: an update of their pathology and biological significance. Virchows Arch. 2000 Dec. 437(6):581-90. [QxMD MEDLINE Link].
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. 2016 Apr. 51 (4):327-36. [QxMD MEDLINE Link].
Kindblom LG, Angervall L, Santesson B, Selander S. Cronkhite-Canada syndrome. Case report. Cancer. 1977 Jun. 39 (6):2651-7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Naoshima-Ishibashi Y, Murofushi T. A case of Cronkhite-Canada syndrome with vestibular disturbances. Eur Arch Otorhinolaryngol. 2004 Nov. 261(10):558-9. [QxMD MEDLINE Link].
Chalk JB, George J, McCombe PA, Tannenberg AE, Ward M, Pender MP. Cronkhite-Canada syndrome associated with peripheral neuropathy. Aust N Z J Med. 1991 Jun. 21 (3):379. [QxMD MEDLINE Link].
Firth C, Harris LA, Smith ML, Thomas LF. A Case Report of Cronkhite-Canada Syndrome Complicated by Membranous Nephropathy. Case Rep Nephrol Dial. 2018 Sep-Dec. 8 (3):261-267. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Hutnik CM, Nichols BD. Cataracts in systemic diseases and syndromes. Curr Opin Ophthalmol. 1999 Feb. 10(1):22-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Nakayama M, Muta H, Somada S, et al. Cronkhite-Canada syndrome associated with schizophrenia. Intern Med. 2007. 46(4):175-80. [QxMD MEDLINE Link].
Marinoni B, Tontini GE, Elli L, Bruni B, Maggioni M, Pastorelli L, et al. Major duodenal papilla prolapse in Cronkhite-Canada syndrome. Endoscopy. 2019 Feb 7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Wang J, Zhao L, Ma N, Che J, Li H, Cao B. Cronkhite-Canada syndrome associated with colon cancer metastatic to liver: A case report. Medicine (Baltimore). 2017 Sep. 96 (38):e7466. [QxMD MEDLINE Link].
Yamanouchi K, Sakata Y, Tsuruoka N, Shimoda R, Uchida M, Akutagawa T, et al. Cronkhite-Canada Syndrome Complicated by Triple Primary Cancers. Intern Med. 2016. 55 (12):1569-73. [QxMD MEDLINE Link].
Takeuchi Y, Yoshikawa M, Tsukamoto N, Shiroi A, Hoshida Y, Enomoto Y, et al. Cronkhite-Canada syndrome with colon cancer, portal thrombosis, high titer of antinuclear antibodies, and membranous glomerulonephritis. J Gastroenterol. 2003. 38 (8):791-5. [QxMD MEDLINE Link].
Gys B, Mertens J, Ruppert M, Hubens G. Cronkhite-Canada syndrome causing pouch outlet obstruction 5 years after roux-en-y gastric bypass. Acta Chir Belg. 2019 Feb. 119 (1):56-58. [QxMD MEDLINE Link].
Liu S, Ruan GC, You Y, Qian JM, Li J. A striking flail chest: a rare manifestation in Cronkhite-Canada syndrome. Intest Res. 2019 Jan. 17 (1):155-156. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Nemade NL, Shukla UB, Wagholikar GD. Cronkhite Canada syndrome complicated by pulmonary embolism-A case report. Int J Surg Case Rep. 2017. 30:17-22. [QxMD MEDLINE Link].
Morino K, Honma Y, Kumei S, Watanabe T, Kume K, Yoshikawa I, et al. Recombinant Thrombomodulin Used to Successfully Treat Cronkhite-Canada Syndrome with Disseminated Intravascular Coagulation due to Sepsis in a Compromised Patient. Intern Med. 2018 Nov 1. 57 (21):3079-3085. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Cao XC, Wang BM, Han ZC. Wireless capsule endoscopic finding in Cronkhite-Canada syndrome. Gut. 2006 Jun. 55(6):899-900. [QxMD MEDLINE Link].
Jha AK, Kumar A, Singh SK, Madhawi R. Panendoscopic characterization of Cronkhite-Canada syndrome. Med J Armed Forces India. 2018 Apr. 74 (2):196-200. [QxMD MEDLINE Link].
Misra SP, Misra V, Dwivedi M, Singh PA, Gupta SC. Cronkhite--Canada syndrome without colonic polyps. Endoscopy. 1997 May. 29 (4):333. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Ikeda K, Sannohe Y, Murayama H. A case of Cronkhite-Canada syndrome developing after hemi-colectomy. Endoscopy. 1981 Nov. 13(6):251-3. [QxMD MEDLINE Link].
Murata M, Bamba S, Takahashi K, Imaeda H, Nishida A, Inatomi O, et al. Application of novel magnified single balloon enteroscopy for a patient with Cronkhite-Canada syndrome. World J Gastroenterol. 2017 Jun 14. 23 (22):4121-4126. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Ong S, Rodriguez-Garcia C, Grabczynska S, Carton J, Osborn M, Walters J, et al. Alopecia areata incognita in Cronkhite-Canada syndrome. Br J Dermatol. 2017 Aug. 177 (2):531-534. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Chuamanochan M, Tovanabutra N, Mahanupab P, Kongkarnka S, Chiewchanvit S. Nail Matrix Pathology in Cronkhite-Canada Syndrome: The First Case Report. Am J Dermatopathol. 2017 Nov. 39 (11):860-862. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Langevin C, Chapdelaine H, Picard JM, Poitras P, Leduc R. Sirolimus in Refractory Cronkhite-Canada Syndrome and Focus on Standard Treatment. J Investig Med High Impact Case Rep. 2018 Jan-Dec. 6:2324709618765893. [QxMD MEDLINE Link].
Watanabe D, Ooi M, Hoshi N, Kohashi M, Yoshie T, Ikehara N, et al. Successful treatment of Cronkhite-Canada syndrome using anti-tumor necrosis factor antibody therapy. Endoscopy. 2014. 46 Suppl 1 UCTN:E476-7. [QxMD MEDLINE Link].
Tran VT, Reicher S, Chung DS, et al. M1252 Infliximab Therapy in Refractory Cronkhite Canada Syndrome [abstract]. Gastroenterol. 2010. 138:S-364. [Full Text].
Taylor SA, Kelly J, Loomes DE. Cronkhite-Canada Syndrome: Sustained Clinical Response with Anti-TNF Therapy. Case Rep Med. 2018. 2018:9409732. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Takahura M, Adachi H, Tsuchihashi N. A case of Cronkhite-Canada Syndrome markedly improved with mesalazine therapy. Digest Endos. 2004. 16:74-8.
Lo YL, Lim KH, Cheng XM, Mesenas S. Steroid Responsive Mononeuritis Multiplex in the Cronkhite-Canada Syndrome. Front Neurol. 2016. 7:207. [QxMD MEDLINE Link].

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Author

Melba Estrella, MD Research Fellow, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

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 Former 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: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Additional Contributors

Franklin Flowers, MD Professor Emeritus, Department of Dermatology, 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.

Kruti Parikh Rutgers Robert Wood Johnson Medical School

Disclosure: Nothing to disclose.

Acknowledgements

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

Disclosure: Nothing to disclose.

Cronkhite-Canada Syndrome Treatment & Management

Medical Care

Surgical Care

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Long-Term Monitoring

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