Cronkhite-Canada syndrome (CCS) is a rare, non-hereditary condition that causes multiple noncancerous polyps in the digestive tract and changes in the skin, hair, and nails.

Cronkhite-Canada syndrome (CCS) is a rare, nonhereditary condition that affects the digestive system and other parts of the body, including the skin, hair, and nails.

It causes multiple noncancerous polyps in the gastrointestinal (GI) tract, which can lead to severe diarrhea, malnutrition, and other complications if not treated early.

Cronkhite-Canada syndrome is a rare, noninherited gastrointestinal disorder that causes multiple noncancerous polyps to form throughout the digestive tract.

These polyps or small growths can appear in the stomach, small intestine, and colon, leading to inflammation, diarrhea, weight loss, and issues with nutrient absorption.

CCS affects not only the digestive system. It’s a multisystem condition, and in addition to digestive symptoms, it can also cause changes in the skin, hair, and nails.

Research shows around 500 case reports worldwide. Most diagnoses occur in adults over 50, and people assigned male at birth seem to experience the condition more often.

While CCS can occur in people of any background, it appears more common in people of Japanese descent, with about 75% of reported cases coming from Japan.

Because the condition is so rare, CCS is sometimes mistaken for conditions such as inflammatory bowel disease (IBD) or familial adenomatous polyposis (FAP).

Unlike hereditary polyposis syndromes such as FAP, CCS does not run in families. Researchers believe that immune system dysfunction and chronic inflammation may contribute to the development of the condition.

Symptoms of Cronkhite-Canada syndrome can affect the digestive system as well as the skin, hair, and nails. They may develop gradually or appear suddenly.

For many people, an early sign is a change or loss of taste or hypogeusia, or a reduced sense of smell. These changes may link to zinc deficiency in some cases.

CCS can affect the gastrointestinal tract and may cause:

CCS can also cause visible changes outside the digestive system, including:

  • skin darkening or patchy discoloration
  • thinning or complete loss of hair or alopecia
  • brittle, thinning, or spoon-shaped nails
  • fatigue or weakness
  • swelling in the legs or ankles or edema
  • unusual mouth sensations, such as dryness or burning

Because CCS varies from person to person, some people develop skin or nail changes before any digestive symptoms.

Others may have very mild symptoms or none at all in the early stages, while some may experience one or several of these symptoms.

If you notice persistent digestive problems along with changes in your skin, hair, or nails, consider talking with a doctor for a proper evaluation.

You may want to see a doctor if you experience:

  • frequent diarrhea lasting more than a few days
  • unexplained weight loss
  • persistent abdominal discomfort or bloating
  • signs of dehydration, such as dizziness or dry mouth
  • fatigue or weakness that doesn’t improve
  • a combination of digestive problems with skin, hair, or nail changes

A gastroenterologist, a doctor specializing in digestive conditions, can help determine whether your symptoms are due to Cronkhite-Canada syndrome or another underlying cause.

If you’re losing weight quickly, feeling very weak, or having trouble staying hydrated, seek medical care right away. These symptoms can become serious without prompt treatment.

The exact cause of Cronkhite-Canada syndrome is not fully understood; however, current evidence suggests that the immune system may play a role.

In some people, the immune system appears to mistakenly damage healthy tissues, triggering inflammation and polyp formation in the digestive tract.

A 2024 case report also noted that some people with CCS test positive for autoantibodies such as ANA, which further supports a possible autoimmune mechanism.

Several factors may contribute to or trigger the condition:

  • Immune and inflammatory changes: Studies have shown signs of immune system activation in some individuals with CCS, including the presence of autoantibodies and IgG4-positive cells in polyps, which serve as markers of increased immune activity.
  • Chronic inflammation: When the lining of the digestive tract remains irritated for an extended period, the body may respond by producing abnormal tissue growth and forming polyps.
  • Infections: Some studies link CCS to Helicobacter pylori (H. pylori), a bacterium that causes stomach inflammation. In a few reports, symptoms improved after treating the infection.
  • Allergic reactions: A few case reports suggest CCS may develop after allergic reactions to certain medications, such as oral thyroxine, though research has not confirmed this as a cause.
  • Hormonal imbalance of serotonin: Studies have found that individuals with CSS tend to have hormonal imbalances related to serotonin, a neurotransmitter in the brain responsible for various bodily functions, including mood and sleep.

Even with these findings, the exact mechanism behind CCS remains unclear, and researchers continue to investigate how these factors interact.

Cronkhite-Canada syndrome can be challenging to diagnose early due to its rarity and the similarity of its symptoms to those of other gastrointestinal conditions.

Because of this, your doctor may need to run several tests to confirm CCS and rule out other conditions. These may include:

  • Physical exam: Your doctor checks your skin, hair, and nails for changes such as hyperpigmentation, hair thinning, or brittle nails, as these can appear alongside the digestive symptoms seen in CCS.
  • Blood tests: These tests can help your doctor check for low protein levels, anemia, vitamin deficiencies, and electrolyte imbalances, all of which are common when CCS causes issues with nutrient absorption.
  • Endoscopy or colonoscopy: A flexible camera allows your doctor to examine the stomach, small intestine, or colon for polyps. During this procedure, they may also take small tissue samples, which they examine under a microscope to confirm the type of polyp.
  • Stool tests: These tests can show signs of malabsorption, such as excess fat or protein loss, as well as inflammation or blood in the stool. They also help rule out infections that can mimic CCS symptoms.
  • Imaging tests: Your doctor may order a CT scan or MRI to assess the extent of polyps and check for inflammation or other complications in the digestive tract.

Early diagnosis is important. Without treatment, CCS may cause severe malnutrition and increase the risk of gastrointestinal cancers such as stomach or colon cancer.

There’s no single standard treatment for Cronkhite-Canada syndrome. Treatment typically focuses on reducing inflammation, restoring nutritional balance, and preventing complications.

Common treatment options include:

  • Corticosteroids: Doctors may prescribe oral prednisone first to lower inflammation and suppress an overactive immune response. Many people improve with steroid therapy.
  • Nutritional support: Nutrition specialists recommend high protein diets, vitamin and mineral supplements, or intravenous nutrition to correct deficiencies and prevent severe malnutrition.
  • Antibiotics: Doctors may prescribe antibiotics if tests indicate bacterial overgrowth or the presence of H. pylori. Treating infections helps reduce inflammation and improve digestive symptoms.
  • Immunosuppressive therapy: If steroids are not enough, doctors may prescribe drugs like azathioprine or cyclosporine to further suppress immune activity and manage symptoms.
  • Polyp management: Doctors remove large or concerning polyps during colonoscopy to prevent bleeding or obstruction. They recommend surgery only if severe complications develop.

The outlook for Cronkhite-Canada syndrome was once considered unfavorable; however, recent research suggests more favorable outcomes. According to a 2023 study, the 5-year overall survival is 93.3%.

These findings suggest that with timely diagnosis and appropriate treatment, many people with CCS improve significantly, though some may need long-term steroid therapy or slower dose reductions to prevent relapse.

Without treatment, CCS can progress and lead to serious, potentially life threatening complications, including:

Because of these risks, most people with CCS need regular follow-up, repeat endoscopies, and long-term monitoring to help catch complications early.

Cronkhite-Canada syndrome is a rare but serious condition that affects multiple bodily systems, including the digestive system, as well as the skin, hair, and nails. While it isn’t genetic, it requires medical treatment and long-term follow-up.

If you experience persistent diarrhea, weight loss, or unusual changes in your hair or nails, talk with your doctor. Early diagnosis and treatment can help manage symptoms, prevent complications, and improve quality of life.