Cronkhite-Canada Syndrome Clinical Presentation

Updated: Feb 22, 2019
  • Author: Melba Estrella, MD; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

In most cases, symptoms of Cronkhite-Canada syndrome (CCS) 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. [30]

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. [31]

Swallowing difficulties are reported.

Ectodermal changes are present in nearly all patients. Generally, ectodermal changes follow gastrointestinal symptoms by weeks to months; however, cases have been reported in which the ectodermal findings are present years before the gastrointestinal pathology. [26] 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, only scalp hair loss is described. Alopecia usually occurs rapidly; total hair loss within a few days is reported. Hair loss was specially denied in one reported patient. Other ectodermal changes include skin hyperpigmentation, vitiligo, and nail dystrophy (discoloration, ragged fingernails) leading to onycholysis.

In some reported cases, not all of the symptoms described above were present.

Neurologic symptoms may include sensory neuropathy, seizures, syncope, and/or vestibular disturbances (ie, gaze-evoked nystagmus, dysequilibrium). [32] Two cases of Cronkhite-Canada syndrome have been described in association with peripheral neuropathy, one of which was diagnosed as mononeuritis multiplex. [8, 33]

Approximately four cases of Cronkhite-Canada syndrome  associated with membranous nephropathy have been reported in the literature. Within these cases, the first case of Cronkhite-Canada syndrome treated with rituximab was reported, with subsequent remission of both conditions (Cronkhite-Canada syndrome and membranous neuropathy). [34]

In two cases, Cronkhite-Canada syndrome was preceded by a blistering episode. [35] One case described subepidermal blisters and antibasement membrane zone antibodies on 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.

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Physical Examination

Physical examination in Cronkhite-Canada syndrome (CCS) typically reveals ectodermal and gastrointestinal changes.

Ectodermal lesions are as follows:

  • 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 [36] - 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 are as follows:

  • 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. [37]

Other findings are as follows:

  • Edema ranging from mild and peripheral edema to massive anasarca

  • Wasting of muscle

  • Streaks of tan pigment in the retina

  • Cataract [38]

  • Xanthelasmas, cheilosis papillary atrophy of the tongue

  • Positive Chvostek and Trousseau signs

  • Acute psychotic symptoms, possibly caused by electrolyte loss, and, possibly schizophrenia [39, 40]

  • Thrombosis and coagulation disorders [26]

  • Cardiac failure [26]

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

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Complications

Principal complications in Cronkhite-Canada syndrome (CCS) are related to gastrointestinal involvement (number, size, location of polyps); other complications may include the following:

  • Water, protein, and electrolyte loss
  • Gastrointestinal bleeding (due to erosions on the surface of polyps)
  • Bacterial overgrowth syndrome
  • Small intestinal bacterial overgrowth
  • C difficile enterocolitis [7]
  • Intussusception
  • Prolapse of gastric polyp–bearing mucosa
  • Duodenal papillary prolapse [41]
  • Thromboembolic episodes due to dehydration
  • Cachexia
  • Heart failure

Nagata et al suggest that Cronkhite-Canada syndrome has definite malignant potential, although the rate of malignant transformation is thought to be low, observed in up to 15% of patients with Cronkhite-Canada syndrome; colon, gastric, and bile duct primary malignancies have been reported in Cronkhite-Canada syndrome, with rare cases of liver metastasis. [42, 43, 44]

Uncommon complications of Cronkhite-Canada syndrome with membranous neuropathy have been reported. [34, 45]

Diffuse polyposis in Cronkhite-Canada syndrome was identified as a rare cause of pouch outlet obstruction after a Roux-en-Y gastric bypass in one patient. [46]

A unique manifestation of flail chest in a Cronkhite-Canada syndrome patient with severe osteoporosis and osteomalacia secondary to vitamin D deficiency was reported. [47]

An unusual reported complication of Cronkhite-Canada syndrome is the occurrence of both arterial and venous thromboses, in the setting of elevated circulating factor VIIIc and fibrinogen. [48] Nemade et al reported a case of Cronkhite-Canada syndrome complicated by pulmonary embolism following surgery. [49] There is also a report of severe sepsis and disseminated intravascular coagulation successfully treated with recombinant human soluble thrombomodulin. [50]

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