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]

  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]

  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]

• Malnutrition

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

  Therefore, it could be one of the plausible explanations that ectodermal changes in CCS generally occur due to malnutrition caused by protein-losing enteropathy. [karger.com]

  One month later, the patient suffered from aggravating multiple rib fractures due to the ineffective treatment, persistent hypocalcaemia and malnutrition. This is the first case of a CCS patient with multiple rib fractures. [ncbi.nlm.nih.gov]

  Common complications include GI bleeding, malabsorption, malnutrition, and infection. [orpha.net]

• Anemia

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

  […] 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]

• 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]

  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]

  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]

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

• 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]

  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

  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]

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

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

  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

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

  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]

  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]

• Dysgeusia

  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]

  Fingerprint Alopecia Canada syndrome Cronkhite Cutaneous hyperpigmentation Diarrhea Dysgeusia Gastrointestinal IgG4 autoimmunity Onychodystrophy Polyposis syndromes Cite this APA Standard Harvard Vancouver Author BIBTEX RIS [mayoclinic.pure.elsevier.com]

  The manifest include watery diarrhea with stool volumes of 4-6 L (sometimes accompanied by steatorrhea and melena), dysgeusia (distorted sense of taste), dry mouth, partial or total lack of appetite, weight loss (usually up to 20 kg), constant or episodic [medigoo.com]

  He also had alopecia, onychatrophia, and dysgeusia. The presence of multiple polyps and associated symptoms of alopecia, onychatrophia, pigmentation, and dysgeusia informed the diagnosis of CCS. [ncbi.nlm.nih.gov]

  The patient's dysgeusia improved with zinc supplementation, he gained 8 kg of weight with eventual improvement in nail dystrophy (Figure C) and endoscopic resolution of the lesions (Figure D). [cghjournal.org]

• 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]

  Synonym(s) Alopecia and fingernail changes; Diffuse gastrointestinal with ectodermal changes; Polyposis diffuse gastrointestinal with ectodermal changes; Polyposis skin pigmentation alopecia and fingernail changes History This section has been translated [altmeyers.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]

  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]

• 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]

• 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]

• Erythema

  Upper endoscopy showed mucosal erythema and nodularity with polypoid-like lesions. Biopsies showed cystic glandular dilatation, lamina propria oedema and chronic inflammation consistent with Cronkhite-Canada syndrome (CCS). [ncbi.nlm.nih.gov]

  Esophagogastroduodenoscopy (EGD) and colonoscopy revealed antral erythema and 2 colonic polyps. [journals.lww.com]

  The second case reported blistering eruption as a form of drug-induced erythema multiforme. [flipper.diff.org]

  Upper endoscopy was also performed showing erythema, congestive gastropathy, gastric polyps, and nodular, diffusely polypoid appearing small bowel with fissuring and scalloping. [karger.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]

• Hypoalbuminemia

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

  Here we report a 63-year-old male presenting with diffuse gastrointestinal polyposis, onychodystrophy, cutaneous pigmentation, alopecia, diarrhea, hypoalbuminemia and lower leg edema. [ncbi.nlm.nih.gov]

  Cronkhite-Canada syndrome has a high mortality rate up to 45∼60% due to nutritional absorption disturbance, hypoalbuminemia, recurrent infection, sepsis, heart failure and gastrointestinal bleeding. [e-ce.org]

• 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]

  Thousands of little grape-like polyps that were less than 10 mm in size and some colon polyps of more than 1 cm in size were observed during colonoscopy. [e-ce.org]

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

  Colonoscopy showed numerous sessile polyps scattered through the colon (Figure 2B). The polyps were ranged in size of 2mm to 3 cm in size. Ileal polyps were also present. Capsule endoscopy showed normal small intestine. [biomedres.us]

  Nearly 10% of cases may be complicated by malignant transformation of the polyps. [japi.org]

• 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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3. Sweetser S, Ahlquist DA, Osborn NK, et al. Clinicopathologic features and treatment outcomes in Cronkhite-Canada syndrome: support for autoimmunity. Dig Dis Sci 2012; 57:496.
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