Cronkhite–Canada syndrome

Overview

Cronkhite–Canada syndrome (CCS) is a rare, non-hereditary gastrointestinal disorder characterized by widespread polyps in the digestive tract, along with distinctive skin and nail changes. First described in 1955 by Leonard Cronkhite and Wilma Canada, this syndrome is primarily seen in adults over the age of 50. In addition to gastrointestinal symptoms, patients often experience alopecia (hair loss), nail dystrophy, hyperpigmentation of the skin, and weight loss. CCS is considered a potentially serious condition due to its complications, including malnutrition, chronic diarrhea, and an increased risk of gastrointestinal cancer.

Causes

The exact cause of Cronkhite–Canada syndrome remains unknown, but it is believed to involve an autoimmune component. Unlike many gastrointestinal polyposis syndromes, CCS is not inherited and does not have a clear genetic pattern. Factors that may contribute to the syndrome include:

• Autoimmune dysfunction: Immune-mediated damage may lead to inflammation and polyp formation.

• Chronic inflammation: May play a role in gastrointestinal mucosal changes.

• Stress or environmental triggers: Though not proven, they may act as contributing factors.

There is no known familial link, and most cases appear sporadically in individuals without a family history of similar symptoms.

Symptoms

The hallmark features of Cronkhite–Canada syndrome include both gastrointestinal and ectodermal symptoms. Common signs and symptoms include:

• Chronic diarrhea: Often severe and persistent

• Gastrointestinal polyps: Found throughout the stomach, small intestine, and colon (sparing the esophagus)

• Abdominal pain and cramping

• Weight loss: Due to malabsorption and reduced appetite

• Loss of taste or appetite (ageusia or anorexia)

• Alopecia: Hair loss, especially of eyebrows and scalp hair

• Nail dystrophy: Thinning, ridging, or shedding of nails

• Hyperpigmentation: Darkening of the skin, especially on the face and extremities

• Fatigue and weakness: From chronic nutrient deficiencies

Diagnosis

Diagnosis of CCS is based on clinical findings, endoscopic evaluation, and histopathological confirmation. The steps involved in diagnosis include:

• Endoscopy and colonoscopy: Reveal widespread sessile polyps throughout the gastrointestinal tract

• Biopsy of polyps: Typically shows non-neoplastic inflammatory or hamartomatous tissue

• Blood tests: May reveal anemia, low albumin, and vitamin deficiencies

• Stool studies: To rule out infections and assess malabsorption

• Clinical evaluation: Noting ectodermal changes such as hair loss and nail changes helps support diagnosis

Differentiating CCS from inherited polyposis syndromes (like Peutz-Jeghers or juvenile polyposis) is crucial, as CCS is non-hereditary and typically adult-onset.

Treatment

Treatment of Cronkhite–Canada syndrome is supportive and aimed at managing symptoms, reducing inflammation, and preventing complications. Common treatments include:

• Nutritional support: High-protein, high-calorie diet, vitamin supplementation, and sometimes parenteral nutrition

• Corticosteroids: Prednisone or similar drugs to reduce inflammation and immune response

• Immunosuppressive agents: Such as azathioprine or cyclosporine, in refractory cases

• Antibiotics: For secondary infections or bacterial overgrowth

• Proton pump inhibitors: To manage gastric symptoms and reduce polyp burden

• Endoscopic surveillance: Regular monitoring of polyps due to increased cancer risk

Prognosis

The prognosis of Cronkhite–Canada syndrome is variable. With early diagnosis and aggressive treatment, many patients show improvement or remission. However, the condition can be life-threatening if left untreated due to complications such as:

• Severe malnutrition

• Electrolyte imbalances

• Sepsis from infections

• Increased risk of gastrointestinal cancers

Mortality rates have improved with better supportive care and immunosuppressive therapies. Lifelong follow-up and regular endoscopic monitoring are essential for managing the disease and detecting malignancies early.