What is Cronkite-Canada syndrome?

What is Cronkhite-Canada Syndrome?

Cronkhite-Canada syndrome (CCS) is a rare, non-hereditary gastrointestinal polyposis syndrome characterized by diffuse hamartomatous polyps throughout the GI tract (sparing the esophagus) combined with distinctive ectodermal abnormalities including alopecia, skin hyperpigmentation, and nail dystrophy. 1

Clinical Features

Gastrointestinal Manifestations

• Diffuse polyposis distributed throughout the stomach (90%), colon (90%), small intestine (80%), and rectum (67%), with the esophagus characteristically spared 2, 3
• Polyps are hamartomatous and non-neoplastic in nature, distinguishing CCS from hereditary polyposis syndromes 4, 5
• Patients present with chronic diarrhea, weight loss, abdominal pain, protein-losing enteropathy, and malnutrition 2, 5, 3
• Dysgeusia (taste abnormalities) and atrophic glossitis are common accompanying symptoms 4, 2

Ectodermal Abnormalities

• Alopecia (hair loss) affecting scalp and body 2, 5
• Cutaneous hyperpigmentation, particularly of the upper limbs and trunk 2, 3
• Nail dystrophy with malnourishment of fingernails and toenails 2, 3

Epidemiology and Demographics

• Extremely rare condition with approximately 450 cases reported worldwide since first description in 1955 6, 3
• Predominantly affects middle-aged and older adults, typically over age 50 years 2, 5
• More common in males, though females can be affected 2
• Non-hereditary with no familial pattern, distinguishing it from FAP, PJS, and other inherited polyposis syndromes 1, 4

Pathophysiology

• Etiology remains unknown, though an autoimmune process is suspected 3
• Pathological analysis shows increasing eosinophil and mast cell infiltration from upper to lower GI tract, with positive IgG results suggesting immune-mediated pathology 2
• Lesions in the middle and lower GI tract demonstrate greater extent and severity compared to upper tract 2

Diagnosis

Endoscopic Findings

• Upper endoscopy reveals diffuse gastric mucosal nodularity with multiple polypoidal and carpet-like lesions in fundus, body, and antrum 6
• Colonoscopy shows circumferential nodular pancolitis with multiple sessile and pedunculated polyps 6, 4
• Capsule endoscopy can identify small intestinal involvement 2
• Important pitfall: Endoscopic appearance may initially mimic inflammatory bowel disease, leading to diagnostic delay 4

Histopathology

• Biopsies confirm hamartomatous polyps with characteristic inflammatory infiltrate 4, 2
• Histological examination is essential to exclude malignancy and differentiate from other polyposis syndromes 6, 4

Complications and Prognosis

• Mortality rate of 55% if untreated, primarily due to severe malnutrition and protein-losing enteropathy 6
• Malignant transformation of polyps can occur, requiring surveillance 6, 5
• Thromboembolic complications including pulmonary embolism represent significant risk, appearing to occur irrespective of surgical intervention 6
• Patients should be categorized as highest risk for thromboembolism with thrombophilia profile, fibrinogen level, and Factor VIII testing before any intervention 6

Treatment Approach

Medical Management

• Corticosteroids represent first-line therapy with demonstrated efficacy 4, 2, 5
• Combination therapy with azathioprine for steroid-sparing effect and sustained remission 5
• Antiallergic medications, acid-suppressing drugs, and salicylates as adjunctive therapy 2
• Nutritional support is critical, including total parenteral nutrition in severe cases, with zinc sulfate supplementation, trace elements, and amino acids 6, 2

Thromboprophylaxis

• Mechanical and pharmacological thromboprophylaxis should be instituted immediately upon diagnosis, given the highest risk categorization for thromboembolic events 6
• This applies regardless of whether surgical intervention is planned 6

Surgical Intervention

• Reserved for complications such as malignancy or obstruction 6
• Carries high risk of postoperative complications including anastomotic leak and pulmonary embolism 6

Response to Treatment

• Hormone therapy demonstrates significant efficacy with improvement in appetite, taste, atrophic glossitis, pigmentation, and diarrhea frequency 2
• Endoscopic re-examination after 3 months typically shows substantial decrease in number and size of polyps 2
• Lesions in middle and lower GI tract resolve faster than upper tract lesions 2

Surveillance and Follow-up

• Long-term surveillance is necessary due to potential for polyp recurrence and malignant transformation 5
• Regular endoscopic follow-up to monitor polyp burden and detect early malignant changes 5
• One-year follow-up without recurrence has been documented with appropriate immunosuppressive therapy 5

Key Clinical Pearls

• Consider CCS in the differential diagnosis of any middle-aged or older patient presenting with multiple GI polyps accompanied by ectodermal symptoms 5
• Early recognition and treatment reduce risk of cancerous changes and complications 2
• The combination of GI polyposis with ectodermal changes is pathognomonic and should prompt immediate consideration of CCS 5, 3
• Unlike hereditary syndromes, there is no genetic testing available as CCS is non-hereditary 4, 5