Literature

Clinical Pearls & Morning Reports

Posted by Carla Rothaus, MD

Published December 20, 2023

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What is the mainstay of treatment for the Cronkhite-Canada syndrome?

The Cronkhite-Canada syndrome (CCS) is a rare, apparently noninherited hamartomatous polyposis syndrome. This syndrome was first reported in 1955, and since then, only approximately 500 cases have been reported worldwide. Read the NEJM Case Records of the Massachusetts General Hospital here.

Clinical Pearls

Q: What are the features of CCS?

A:CCS is characterized by the presence of multiple hamartomatous polyps throughout the gastrointestinal tract (apart from the esophagus), as well as multiple cutaneous changes, including loss of the hair and nails and hyperpigmentation of the skin. Patients with CCS usually present with diarrhea and protein-losing enteropathy as the dominant gastrointestinal symptoms.

Q: How is CCS diagnosed and what is its prognosis?

A: There are no established diagnostic criteria for CCS, and the diagnosis should be considered when compatible clinical characteristics are present and when other conditions are ruled out. Unfortunately, the overall prognosis of CCS is poor, with a reported 5-year mortality of 55%, mostly due to complications such as sepsis and gastrointestinal bleeding.

Morning Report Questions

Q: What is the mainstay of treatment for CCS?

A: Data from prospective trials investigating the treatment of CCS are lacking, given the rarity of this disease; treatment choices are mainly guided by case reports and case series. Immunosuppression is the mainstay of treatment of CCS. The most commonly reported immunosuppressive treatment is systemic glucocorticoids; in case series and retrospective cohort studies, more than half of patients had a treatment response. However, there is no agreement regarding the choice, route, dose, or duration of glucocorticoid therapy. In patients with glucocorticoid-refractory disease who remain symptomatic with persistent skin changes and no regression of gastrointestinal polyposis, the use of nonsteroidal immunosuppressants such as azathioprine and cyclosporine A can be considered. In patients with disease that is refractory to all these treatments, infliximab may be a possible treatment option.

Q: Describe additional treatment considerations for patients with CCS.

A: The initial approach to the management of CCS includes treating Helicobacter pylori infection in patients who have a positive test; this strategy has been shown to result in regression of polyposis in the gastrointestinal tract and a reduction in skin changes. It is important that patients with gastroesophageal reflux disease also be treated with histamine type 2 receptor antagonists or proton-pump inhibitors. The hypercoagulable state associated with CCS is due to a loss of intrinsic anticoagulants, such as protein C and protein S, along with elevated fibrinogen and factor VIII levels. Hence, it is important to consider prophylactic anticoagulation in patients with CCS. In addition to the described specific treatments for coexisting conditions and the administration of immunosuppressive therapy, general supportive measures are of paramount importance in caring for patients with CCS. Patients with CCS are susceptible to infections because of weakened immunity associated with a loss of immunoglobulins caused by protein-losing enteropathy and because of the use of immunosuppressants as the mainstay of treatment. It is vital that patients receive maximal nutritional support and electrolyte replacement.

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