Cronkhite-Canada Syndrome Clinical Presentation

In most cases, symptoms appear in the sequence of gastrointestinal symptoms, weight loss, weakness, edema, and then ectodermal changes after a few weeks or a few months.

• Patients' principal complaints start with a constant or episodic pain in the lower or upper abdomen.

  • Intensity varies from mild and localized to severe and generalized.
  • Pain is accompanied by chronic or recurrent watery diarrhea, sometimes melena.
  • Watery bowel movements may occur 5-7 times per day, and stool volume as high as 4-6 L/d were reported.
  • Progressive weight loss follows the diarrhea.
• Change in taste sensation and loss of smell, with or without hypogeusia, also were reported as early symptoms.
• Most patients lose more than 20 kg during the course of the disease.
• Progressive anorexia has been reported in several patients.
• Other gastrointestinal symptoms are nausea and vomiting, apparently more frequent in female patients.
• A case of a patient with Cronkhite-Canada syndrome and severe recurrent acute pancreatitis owing to a polyp on the ampulla of Vater has been described.^[12]
• Swallowing difficulties are reported.
• Patients typically experience hair loss.

  • In most patients, hair loss takes place simultaneously from the scalp, eyebrows, face, axillae, pubic areas, and extremities.
  • In some cases, loss of scalp hair only was described.
  • Alopecia usually occurs rapidly; total hair loss within a few days was reported.
  • Hair loss was specially denied in 1 reported patient.
• Other ectodermal changes include skin hyperpigmentation, vitiligo, and nail dystrophy (discoloration, ragged fingernails) leading to onycholysis.
• Neurologic symptoms may include sensory neuropathy, seizures, syncope, and/or vestibular disturbances (ie, gaze-evoked nystagmus, dysequilibrium).^[13]
• In some reported cases, not all of the symptoms described above were present.
• In 2 cases, Cronkhite-Canada syndrome was preceded by a blistering episode.^[14]

  • One case described subepidermal blisters and antibasement membrane zone antibodies in direct immunofluorescence, suggesting epidermolysis bullosa acquisita.
  • The second case reported blistering eruption as a form of drug-induced erythema multiforme.
  • In another reported case, the characteristic changes of Cronkhite-Canada syndrome developed 2 months after hemicolectomy of the descending colon for a carcinoma and 3 neighboring polyps, followed by 4 weeks of chemotherapy.

Physical examination typically reveals the following ectodermal and gastrointestinal changes:

• Ectodermal lesions

  • Skin - spotty (lentigolike macules ranging from a few millimeters to 10 cm in diameter) and diffuse hyperpigmentation notably localized on the dorsal surface of the hands, palms, arms, neck, face, scalp, anterior chest region, and body folds; ill-defined brown patches on the perioral and buccal areas; reported cases without hyperpigmentation; patchy vitiligo
  • Buccal mucosa - Brownish pigmentation and swollen tongue with loss of papillae
  • Fingernails and toenails^[15] - Discoloration; proximal nail plate separation and shedding; soft and spongy look of proximal nails; ragged distal fingernails; often irregular regenerated distal plate; onychoschizia (splitting of nails into layers); onychomadesis (nail shedding staring at the base and extending forward)
  • Hair loss on the scalp and other body areas
• Gastrointestinal symptoms

  • Multiple sessile or semipedunculated polyps ranging from 0.5-2 cm in diameter located principally in the colon but also in the stomach ("carpetlike" polyposis) and small intestine
  • Rough granular changes of stomach mucosa with edematous giant rugae
  • Almost 40 cases of colorectal cancer have been reported in association with Cronkhite-Canada syndrome (adenocarcinoma arising from the mucosal hyperplasia). Cronkhite-Canada syndrome associated with colorectal cancer frequently (40%) includes polyps containing serrated adenoma lesions.^[16]
• Other

  • Edema ranging from mild and peripheral edema to massive anasarca
  • Wasting of muscle
  • Streaks of tan pigment in the retina
  • Cataract^[17]
  • Xanthelasmas, cheilosis papillary atrophy of the tongue
  • Positive Chvostek and Trousseau signs
  • Acute psychotic symptoms, possibly caused by electrolyte loss, and, possibly schizophrenia^{[18, 19]}
• Children

  • A symmetric desquamating rash on the lower back, buttocks, genital area, lips, and perioral region, similar to skin lesions in acrodermatitis enteropathica (zinc deficiency), also is present.
  • Macrocephaly is a typical sign of infantile Cronkhite-Canada syndrome.

The pathogenesis of the disease is unknown.

• The principal gastrointestinal symptoms, weight loss, and weakness probably are due to altered digestive, motive, absorptive, and secretory functions of the gut and bacterial overgrowth. (Clostridium difficile is isolated quite frequently in the stool.)

  • The exact etiology of diarrhea is not clear.
  • The symptom is likely related to the presence of polyps; however, the impaired bowel motility may cease without alteration of the size and number of polyps. Gastric polyps have been found to be infected with Helicobacter pylori.^[20]
  • Elevated gastric acid secretion also was found in one reported case.
• Ectodermal changes (ie, hyperpigmentation, alopecia, nail dystrophy) are believed to be due to protein loss and malabsorption; however, cutaneous manifestation preceded onset of diarrhea in some patients with Cronkhite-Canada syndrome.

  • Authors suggest that ectodermal changes are an inherent part of the syndrome, not secondary to malabsorption, because similar ectodermal lesions do not appear in other protein-losing gastroenteropathies.^[21]
  • Regrowth of hair was noted after treatment, during spontaneous remission, and even during active disease.
  • Hyperpigmentation also was noted to be reversible after and without any specific therapy.
• Presence of edema correlates well to hypoalbuminemia.
• Neurologic or psychotic symptoms occurred as a cause of hypocalcemia, hypomagnesemia, and hypokalemia.
• Mild-to-moderate anemia is secondary to malabsorption (ie, iron, vitamin B-12, folate deficiency), blood loss, or both.
• Cataract progression probably is associated with hypoproteinemia and hypocalcemia.

  • Low calcium levels in the aqueous humor were believed to promote changes in lens membrane permeability and subsequent membrane disruption.
  • A flux of sodium ions was postulated to occur from the aqueous into the lens, resulting in overhydration and production of a cortical lens opacity.
• The cause of macrocephaly, typically present in cases of the juvenile Cronkhite-Canada syndrome, is unknown. An increase of arachnoid cysts was demonstrated.