In many cases, the symptoms appear in the following order:

• Gastrointestinal symptoms
• Weight loss
• Weakness
• Edema
• Ectodermal changes

The ectodermal changes occur after a few weeks or a few months. The first and major complaint from patients is that of periodic or constant pain in the upper or lower abdomen. The intensity varies greatly from mild and localized to generalized and severe [8]. The pain comes with recurrent watery diarrhea or chronic diarrhea and in some cases, melena.

The watery bowel movements may be reported 7 times or more each day. In some cases, stool volume as high as 4-6 L/d are reported. Following the diarrhea is progressive weight loss.

Anorexia have been reported in some patients and loss of smell and change in taste sensations have equally been reported
Other gastrointestinal symptoms are nausea and vomiting and this is more readily seen in female patients.

Typically, the patients experience hair loss and swallowing difficulties have been reported as well. The hair loss happens in tandem across the extremities, pubic areas, axillae, face, eyebrows and scalp. However, some patients have presented loss of hair in only the scalp area. Alopecia takes place very fast with reports of total hair loss with a few days common [9].

Other ectodermal changes that happen in many cases include hyperpigmentation of the skin, vitiligo, discoloured and ragged fingernails (nail dystrophy) which often results in onycholysis. Some neurologoc symptoms have been reported as well and these include sensory neuropathy, syncope, seizures, vestibular disturbances (ie, gaze-evoked nystagmus, dysequilibrium) and sensory neuropathy.

All of the symptoms reported above do not appear in all cases and in two reported cases there was a blistering episode before the Cronkhite-Canada syndrome fully set in.

• Weight Loss

  Description CCS is a very rare sporadic condition that involves gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation weight loss, abdominal pain, and watery diarrhea. [medigoo.com]

  In this report, a 74 year old man is described who had dysgeusia, skin hyperpigmentation, onycholysis, abdominal pain, chronic diarrhea, progressive weight loss and episodic melena since one year ago. He underwent upper endoscopy and colonoscopy. [govaresh.org]

  CASE REPORT A 68-year-old white man presented with a 7-month history of anorexia, hypogeusia, and watery diarrhea, with an estimated weight loss of 40 lb during this period. [thefreelibrary.com]

  The disease is characterized by diffuse gastrointestinal polyposis, dystrophic changes of the fingernails, alopecia, cutaneous hyperpigmentation, diarrhea, weight loss, and abdominal pain. An autoimmune etiology is suspected. [ncbi.nlm.nih.gov]

• Anemia

  […] for characteristic sparing of the esophagus. (3) Presenting symptoms in CCS include diarrhea, weight loss, abdominal pain, hematochezia, and hypogeusia. (3) Laboratory evaluation usually reveals evidence of gastrointestinal malabsorption, including anemia [thefreelibrary.com]

  The blood test showed mild anemia and hypoalbuminemia. The esophagogastroduodenoscopy and colonoscopy revealed diffuse and reddened sessile to semi-pedunculated polyps, resulting in the diagnosis of CCS. [ncbi.nlm.nih.gov]

  Labs were remarkable for microcytic anemia and severe hypoalbuminemia. Endoscopy showed numerous polyps scattered throughout the colon. [unboundmedicine.com]

• Familial Adenomatous Polyposis

  Related polyposis conditions are familial adenomatous polyposis, attenuated familial adenomatous polyposis, Birt–Hogg–Dubé syndrome and MUTYH.[citation needed] Diagnosis[edit] There is no specific test to diagnose Cronkhite–Canada syndrome. [en.wikipedia.org]

  Related polyposis conditions are familial adenomatous polyposis, attenuated familial adenomatous polyposis, Birt–Hogg–Dubé syndrome and MUTYH. [ipfs.io]

• Pallor

  On physical examination, he had pallor, hyperpigmentation of both hands and feet involving both soles and feet [Table/Fig-1,2], alopecia, and dystrophic nail changes [Table/Fig-3,4]. However, pigmentation within oral cavity was not noted. [ncbi.nlm.nih.gov]

• Diarrhea

  Description CCS is a very rare sporadic condition that involves gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation weight loss, abdominal pain, and watery diarrhea. [medigoo.com]

  Diagnosis of a rare Syndrome: Cronkhite-Canada Syndrome Abstract Cronkhite-Canada syndrome (CCS) is a rare, non-familial disorder of unknown etiology associated with alopecia, cutaneous hyperpigmentation, gastrointestinal polyposis, onychodystrophy, diarrhea [govaresh.org]

  Cronkhite-Canada syndrome (CCS) is a noninherited condition, associated with high morbidity, and characterized by gastrointestinal inflammatory polyposis, alopecia, onychodystrophy, hyperpigmentation, and diarrhea. [mayoclinic.pure.elsevier.com]

  CASE REPORT A 68-year-old white man presented with a 7-month history of anorexia, hypogeusia, and watery diarrhea, with an estimated weight loss of 40 lb during this period. [thefreelibrary.com]

  Patients typically present with watery diarrhea and protein losing enteropathy and associated nail atrophy, brownish skin pigmentation, and alopecia 3. [radiopaedia.org]

• Abdominal Pain

  In this report, a 74 year old man is described who had dysgeusia, skin hyperpigmentation, onycholysis, abdominal pain, chronic diarrhea, progressive weight loss and episodic melena since one year ago. He underwent upper endoscopy and colonoscopy. [govaresh.org]

  An 83-year-old woman was admitted to our hospital with a 4 week history of abdominal pain, diarrhoea, and dysgeusia. [thelancet.com]

  These changes lead to the clinical symptoms, including diarrhea, abdominal pain, and profound malnutrition. Dermatologic signs accompany the GI symptoms. [japi.org]

  This condition is characterized by diffuse GI polyposis, dystrophic changes in the fingernails, alopecia, cutaneous pigmentation, diarrhea, weight loss and abdominal pain. [ijhas.in]

• Nausea

  Other symptoms include severe vomiting and nausea (more common for females). Some of the patients develop difficulties during swallowing. Diarrhea causes loss of protein and electrolytes and respectively cachexia (exhaustion). [medigoo.com]

  A 66-year-old male patient presented with nausea, abdominal pain, occasional rectal bleeding, progressive dysgeusia, onicodystrophy, and alopecia. [ncbi.nlm.nih.gov]

• Chronic Diarrhea

  […] by chronic diarrhea, diffuse intestinal polyposis and onychodystrophy. [unboundmedicine.com]

  Cronkhite-Canada Syndrome: A Rare Cause of Chronic Diarrhea Abstract Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease characterized by chronic diarrhea, diffuse intestinal polyposis and onychodystrophy. [gastrores.org]

  In this report, a 74 year old man is described who had dysgeusia, skin hyperpigmentation, onycholysis, abdominal pain, chronic diarrhea, progressive weight loss and episodic melena since one year ago. He underwent upper endoscopy and colonoscopy. [govaresh.org]

  He lacked chronic diarrhea and ectodermal abnormalities, which were seen in the typical CCS cases. [karger.com]

  This report describes a 60-year-old female who was diagnosed with Cronkhite-Canada syndrome with hypothyroidism after presenting with chronic diarrhea, alopecia, intermittent abdominal pain, generalized gastrointestinal polyposis, hyperpigmentation, and [ncbi.nlm.nih.gov]

• Hematochezia

  We report a case of a 58-year-old man who was admitted to our hospital with a 6-month history of frequent diarrhea, intermittent hematochezia and a weight loss of 13 kg. [ncbi.nlm.nih.gov]

  […] disorder with diffuse GI polyposis, alopecia, hyperpigmentation, dystrophic changes in fingernails and toenails Nonhereditary, unknown etiology Onset usually in middle age adults Patients may have diarrhea, weight loss, abdominal pain, anorexia, weakness, hematochezia [pathologyoutlines.com]

  The symptoms of diarrhea, hematochezia and abdominal pain released but polyps burden did not reduce significantly. The Nutritional condition of body improved. [biomedres.us]

  Consistent with this, in the present case study, the patient initially experienced diarrhea and hematochezia, followed by abdominal pain, nail and toenail loss, onychatrophy and hyperpigmentation. [spandidos-publications.com]

• Alopecia

  Cronkhite-Canada Syndrome (CCS) is an extremely rare noninherited disease characterized by the generalized gastrointestinal polyps, cutaneous pigmentation, alopecia, and onychodystrophy. [medigoo.com]

  This condition is characterized by diffuse GI polyposis, dystrophic changes in the fingernails, alopecia, cutaneous pigmentation, diarrhea, weight loss and abdominal pain. [ijhas.in]

  Cronkhite-Canada syndrome (CCS) is a noninherited condition, associated with high morbidity, and characterized by gastrointestinal inflammatory polyposis, alopecia, onychodystrophy, hyperpigmentation, and diarrhea. [mayoclinic.pure.elsevier.com]

  Syndrome Gastrointestinal polyposis-skin pigmentation-alopecia-fingernail changes syndrome Cronkhite-Canada disease Gastrointestinal polyposis-ectodermal changes syndrome Polyposis skin pigmentation alopecia fingernail changes edit English Cronkhite-Canada [wikidata.org]

  Physical examination showed diffuse hyperpigmentation, alopecia, and onychodystrophy of the nails of the hands and feet. [thefreelibrary.com]

• Hyperpigmentation

  Description CCS is a very rare sporadic condition that involves gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation weight loss, abdominal pain, and watery diarrhea. [medigoo.com]

  Cronkhite-Canada syndrome (CCS) is a noninherited condition, associated with high morbidity, and characterized by gastrointestinal inflammatory polyposis, alopecia, onychodystrophy, hyperpigmentation, and diarrhea. [mayoclinic.pure.elsevier.com]

  Diagnosis of a rare Syndrome: Cronkhite-Canada Syndrome Abstract Cronkhite-Canada syndrome (CCS) is a rare, non-familial disorder of unknown etiology associated with alopecia, cutaneous hyperpigmentation, gastrointestinal polyposis, onychodystrophy, diarrhea [govaresh.org]

  Cronkhite–Canada syndrome is a rare, sporadic disorder characterised by generalised gastrointestinal polyposis and dermatological manifestations consisting of hyperpigmentation, hair loss, and nail dystrophy. [dermnetnz.org]

  […] son who was asymptomatic, with mild alopecia and hyperpigmentation over his face and hands. [ncbi.nlm.nih.gov]

• Ulcer

  Pathologically, the ulcerated rectal tumor was a moderately differentiated adenocarcinoma with invasion into the muscularis propria. [ncbi.nlm.nih.gov]

  Bryophyllum pinnatumleaf extracts exhibits in vivo gastroprotective activity by markedly decreasing the incidence of ulcers in ethanol induced ulcer rats [33]. [peertechz.com]

• Cutaneous Manifestation

  The cutaneous manifestations of CCS have been attributed to malabsorption and malnutrition caused by the GI pathology. [orpha.net]

  However, cutaneous manifestation precedes onset of diarrhea in some patients with Cronkhite-Canada syndrome. [flipper.diff.org]

• Partial Alopecia

  On examination she had titubation, partial alopecia and severe onycholysis. BP 140/80 mm Hg, HR 70/min. Rectal examination showed a palpable mass. She had normal U&E-s, Calcium, Magnesium, Phosphate, thyroid and adrenal function. [endocrine-abstracts.org]

  The manifestations of the integuments (partial alopecia and onychotrophia), associated with gastric polyposis, support the diagnosis of Cronkhite-Canada syndrome raised during the anatomopathology examination. [em-consulte.com]

Electrolyte and micronutrient determination is carried out to check for hypokalemia, hypocalcemia and depressed serum levels of Vitamin B-12, magnesium, copper, iron and zinc [10].

Hematology tests are carried out to check for hematocrit, red blood cell count, hemoglobin and depressed white blood cell count.

Serum protein tests aid in checking hypoalbuminemia, hypoproteinamia and increase in alpha 1 globulin level.

Endoscopic tests procedures show polyps lesions of the sessile or semipedunculated type within the stomach, colon, Ileum and duodenum. The endoscopic procedures to be carried out include gastroscopy, colonoscopy and sigmoidoscopy.

• Multiple Colonic Polyps

  We herein present a 66-year-old-male patient with Cronkhite-Canada syndrome who had a carcinoma of the sigmoid colon along with multiple colonic polyps, which included juvenile-type polyps, adenomas, and hyperplastic polyps. [ncbi.nlm.nih.gov]

  Figure 12 Multiple colonic polyps; juvenile polyps/hamartomas, tubular adenomas, traditional serrated adenomas. [pubmed.ncbi.nlm.nih.gov]

  He took a colonoscopy examination at a private clinic showing multiple colonic polyps of varying sizes. He was referred to the Gastrointestinal Department of Presbyterian Medical Center. [e-ce.org]

  Turcot syndrome Turcot et al first described an association between colonic polyps and tumors. The colonic/rectal polyps are adenomatous, usually multiple, and 1-30 mm in diameter. [suprepkit.com]

• Polyps

  This was suspicious of polyposis syndrome in this patient and was subjected to colonoscopy which also revealed entire colon studded with polyps. Histopathological examination of biopsies taken from the polyps showed hyperplastic polyps [Figure 4]. [ijhas.in]

  Surgical removal of the polypes has also been suggested. [medigoo.com]

  Endoscopy of Upper GI and Lower GI tract revealed severe gastroduodenitis with polyp in duodenum and multiple polyps whole throughout the colon respectively. [japi.org]

  polyp of the sigmoid (arrow). [em-consulte.com]

  […] and histologic features of CCS polyps and polyps in other polyposis syndromes makes CCS a clinicopathologic diagnosis that cannot be made solely based on polyp histology. [ncbi.nlm.nih.gov]

• Occult Blood Positive

  He had occult- blood positive stool. The laboratory parameters including renal and liver function tests, serum electrolytes were within normal limits except hypoalbuminemia (2 g/dl; normal 3.5 -5 g/dl). [ncbi.nlm.nih.gov]

Treatment remains predominantly symptomatic due to the unknown etiology. Management aims at correcting the fluid, electrolyte, and protein loss.

Cronkhite-Canada syndrome is considered a progressive disease with a variable course and poor prognosis.

The cause of this condition is not known. Formerly, it was thought that the epidermal changes were secondary to profound malnutrition due to enteropathy which leads to loss of protein.

Newer findings have disputed this hypothesis however as hair and nail changes often do not show signs of improvement even with improved nutrition [4].

There are other conditions which show multiple harmartomatous polyps of the digestive system. These include Cowden disease, juvenile polyposis and Peutz-Jeghers syndrome. Related polyposis conditions include MUTYH, Birt–Hogg–Dubé syndrome, attenuated familial adenomatous polyposis and familial adenomatous polyposis [5].

The CCS has a worldwide distribution but 75% of reports come from Japan. The Cronkhite Syndrome is a rare disorder because by the end of 2002, only 467 cases have been reported in literature across the world with 354 of those coming from groups in Japan.

Mortality/Morbidity

The CCS is regarded as a progressive condition which has poor prognosis and runs a variable course and is dependent mainly on the control of electrolyte balance and protein [2]. Regardless of therapy used, the mortality rate is more than 50%. Co-existing gastrointestinal bleeding, the possibility of intussusception and malignant changes in the polyps all lead to an increase in mortality rate.

The first two patients who were described to have the Cronkhite-Canada syndrome died of starvation 7-8 months after the beginning of symptoms. There have been reported cases of spontaneous remission after nutritional support. In children, the prognosis is often less optimistic than what is obtainable amongst adults [3].

Although majority of cases come from Japan, there is no data to prove any racial predisposition. Therefore the condition is treated as a worldwide condition.

Sex

Sex-wise, the male to female ratio is 1.5-1.31 approximately so the condition is believed to affect both sexes equally.

Age

The Cronkhite-Canda syndrome often sets in between middle age and old age with average age being 55 years. The age rang at which this condition is seen mostly is 31-86 years of age. The disease may stay asymptomatic and therefore it may not be diagnosed for quite a while. Many patients are aged 50 and above by the time of presentation. There have been very scanty reports regarding cases of infantile Cronkhite-Canada Syndrome .

There is no evidence to show the existence of familial predisposition. There is equally the possibility of afflicted patients and offspring that are asymptomatic. The most important risk factors for the CCS are mental stress and physical stress [6].
This stress brings about a local inflammatory reaction since it acts on the gastrointestinal mucosa.

Two weeks after the start of taking oral thyroxine, some patients with the CCS develop ectodermal lesions. At cessation of treatment, the cutaneous signs improved.

The involvement of the immune system in the pathogenesis of the Cronkhite-Canada syndrome is supported by the effectiveness of corticosteroid therapy in many cases of the condition.

The gastrointestinal lesions in CCS are polyps of the harmatomatous type and these histologically show pseudopolypoid-inflammatory changes. Malabsorption is believed to be what leads to the cutaneous symptoms. Changes that occur in the ectorderm do not happen in tandem with other activities of the disease and so it improved in some cases despite gut dysfunction [7].

There are no guidelines for prevention of Cronkhite-Canda syndrome.

Cronkhite-Canada syndrome (CCS) is a rare non-inherited disorder that was reported for the first time in 1955 by Leonard W. Cronkhite Jr and Wilma J. Canada [1].

The condition occurs sporadically. It was seen for the first time as a separate condition within 2 female patients who have onychodystrophy, alopecia, cutaneous pigmentation and generalized gastrointestinal polyps.

If diagnosed for this condition, one way to deal with it is to judiciously stick to medical regimes reporting anything unusual as soon as possible.

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10. 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.