An Overview of Pellagra

Pellagra is a condition that occurs when a person develops a deficiency in vitamin B3, also called niacin. There are two types of deficiency a person can have. A primary deficiency occurs when a person is not getting enough niacin in their diet, and a secondary deficiency is when the body isn't able to use the nutrient properly.

Pellagra used to be a very common condition, especially in parts of the world that were dependent on corn-based diets. Today, most cases of pellagra occur in poverty-stricken areas, in people with health conditions that impair the body's ability to absorb nutrients, and also in people with chronic alcoholism. While the condition can be cured if diagnosed, pellagra can be fatal if left untreated.

Symptoms

Vitamin B3 (also known as niacin) is essential to good health. Niacin helps our bodies convert the food we eat into energy. Two coenzymes produced by niacin, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), also have important roles in the body. These coenzymes are integral to functions like gene expression and cellular processes such as cholesterol synthesis.

Niacin can be consumed directly through the foods we eat—these are either foods that are fortified or naturally-rich in vitamin B3, such as meat, dairy, and nuts. Our bodies can also convert an amino acid protein called tryptophan into niacin. Turkey is a very rich dietary source of tryptophan and therefore can help stave off niacin deficiency.

The adult Dietary Reference Intakes (DRIs) recommendations for niacin is 14 to 16 milligrams of niacin equivalents (mg/NE). If a person does not get enough niacin, or if they have a health condition that impairs the body's ability to use niacin or convert tryptophan into niacin, they are at risk for developing a deficiency. Severe niacin deficiency results in a disorder called pellagra.

There are three common symptoms of pellagra referred to as the "three Ds."

Untreated pellagra will lead to death, sometimes called the "fourth D," within a few years.

In the early stages, pellagra symptoms may be vague. Patients with the condition may only have one or two of the "Ds" along with other nonspecific symptoms. The rash and diarrhea, however, are seen in the majority of cases.

Watery diarrhea is usually the first symptom and is the result of inflammation of the gastrointestinal mucosa. Sometimes diarrhea may have blood or mucus, especially if a patient has a condition like Crohn's disease. In some cases, pellagra may lead to the diagnosis of inflammatory bowel disease.

As the condition goes on, people with pellagra also tend to have no appetite (sometimes leading to anorexia), feel sick to their stomach (nauseated), or have stomach pain. These symptoms can cause a cycle where a person who is already in a state of malnourishment leading to nutritional deficiency does not feel well enough to eat, or the person has a health condition that impacts their ability to adhere to a well-rounded diet.

In turn, the person will become more malnourished. A weakened state may predispose them to other health problems, such as viral illness, that their body can not effectively fight against due to lowered immunity.

Dermatitis, or skin inflammation, typically appears in the form of a rash in sun-exposed areas of the body. In fact, it often looks like a sunburn. The rash may become more intense, with skin peeling and changing in skin color (pigmentation) that can be permanent.

As the rash begins to blister, the skin may become rough and scaly, especially on the bottom part of the hands and feet, as well as on the face (a pattern known as a butterfly or malar rash).

Areas of affected skin may be itchy, painful, and sensitive to the sun.

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The neurological signs and symptoms occur later when the deficiency has become severe and has been going on for a prolonged period of time. At first, a person may experience memory loss, trouble sleeping, and mood changes.

As the deficiency gets worse, the neurological symptoms can be severe: a person may become disoriented or not know where they are, begin to have hallucinations, or even be in a stupor, failing to respond to their surroundings.

As the condition worsens and body systems begin to shut down, other symptoms may develop, including:

• Loss of coordination
• Glossitis (tongue swelling) that can obstruct a person's airway
• Dementia
• Paralysis
• Heart conditions such as dilated cardiomyopathy
• Stupor
• Coma

Left untreated, multi-organ failure from pellagra can be fatal in three to five years.

Causes

People have been suffering the effects of niacin deficiency for centuries. The name pellagra (from the Italian pelle agra for "rough skin") was used to describe the condition by scholars in the early 18th century. At first, people were not sure what caused pellagra.

They noticed that one thing many people who became sick with the condition had in common was that their diet was primarily maize (corn). For many years, people believed that corn crops carried a pest or toxin that was making people sick.

As people began to travel to other cultures around the world, it became clear that many communities were able to subsist on corn crops without getting pellagra. The key was in how corn was prepared, which seemed to determine how nutritious the diet was. When the corn crops were treated with a certain alkalizing process, called nixtamalization, it allowed the niacin to be released.

As long as people were eating corn that had been prepared this way, such as corn tortillas, they wouldn't develop pellagra.

However, in some cases, even though a person is getting enough niacin from the food they eat, their body is not able to use it properly. This may be due to an underlying condition or caused by a medication. Reasons people develop secondary pellagra include:

• Genetic conditions like Hartnup disease, which inhibits the body's ability to absorb tryptophan from the intestines
• Treatment with drugs that affect how the body uses B vitamins, such as the antituberculosis drug isoniazid or phenobarbital
• Types of tumors that produce excessive serotonin (carcinomas) leading to a condition called carcinoid syndrome
• Adhering to very restricted diets ("fad diets") or maize-based diets that have not been nixtamalized

Additionally, conditions that put stress on the body (thereby increasing nutritional needs) can also lead to pellagra. Patients may be at increased risk of developing the deficiency if they have:

• A prolonged febrile illness
• Diabetes mellitus
• Human Immunodeficiency Virus (HIV)
• Chronic alcoholism and/or drug abuse
• Anorexia nervosa
• Liver cirrhosis  
• Patients receiving long-term dialysis

A person's socioeconomic circumstances can also place them at risk for developing pellagra. People living in poverty who don't have adequate access to nutritious food, those living in famine conditions, and refugees are more likely to become severely malnourished.

While pellagra mostly develops in adults, children who are living in countries experiencing famine, whose families are homeless, or who are being neglected may also be at risk.

In many parts of the world where pellagra still occurs, it follows a predictable seasonal pattern. People tend to develop pellagra in the late spring or summer months after having limited access to food over the winter. More exposure to sunlight during the lighter months of the year can also make the characteristic rash of pellagra more apparent.

Often, people will recover from pellagra during the months of the year when they have access to nutritious food, only to have the condition recur when the season changes.

Pellagra occurs equally in men and women. It primarily occurs in adults but in some cases, infants and children may be at risk. People of all races can develop pellagra, though it is seen more often in developing countries and poverty-stricken regions of developed nations.

Diagnosis

If a doctor suspects a person has pellagra, there are several ways to confirm the diagnosis. They will perform a physical exam and ask the person about diet and lifestyle.

Findings that support a clinical diagnosis of pellagra include the characteristic skin changes, rash, and accompanying symptoms of itching or pain. Patients often report diarrhea or other gastrointestinal symptoms, including swelling of the tongue. In some cases (but not all), patients will have started to experience changes to their moods, developed trouble sleeping, started to feel depressed, or have early symptoms of dementia.

Pellagra is uncommon in children, but it does occur. Younger patients may not present with the typical symptoms of pellagra, however, which can make diagnosis tricky.

To confirm the diagnosis of pellagra, doctors will want to take a blood sample to test for low levels of niacin. They may also be looking for other abnormalities, such as low tryptophan, NAD, and NADP levels. The presence of other nutritional deficiencies, inflammatory markers, or low immunity may also provide helpful insight and help rule out other conditions, such as Lupus, that can have similar symptoms.

If a person is found to have pellagra, the next step will be determining the cause. Sometimes the answer will be fairly obvious, such as if a person reports eating a limited diet or are clearly malnourished. Other patients may need additional tests to determine the reason for the deficiency. These tests may include:

• Additional blood tests to check for infections or markers of certain illnesses
• Urine tests to see how much niacin a person is excreting
• Imaging, such as an X-ray or CT scan, to assess the organs or look for tumors
• Special tests, like a colonoscopy, to look at the gastrointestinal system if a condition like Crohn's is suspected
• Examining samples from skin lesions under a microscope

Diagnosing pellagra and figuring out what caused a person to develop the condition is very important. It can also cause a number of complications, including:

• Mental changes, such as confusion, depression, and anxiety
• Trouble swallowing due to swelling of the tongue and inflammation
• Hallucinations and delusions
• Permanent changes to the skin's texture and color

Untreated niacin deficiency can cause a person to go into a coma. After several years, the condition causes major damage to the internal organs, which is ultimately fatal.

Treatment

While pellagra that goes undetected and untreated can be serious, if diagnosed and promptly treated, a person can make a full recovery. One of the key ways a doctor knows a person definitely has pellagra is by administering niacin and/or tryptophan supplements. A person with pellagra will immediately respond to this relatively simple intervention.

Adequate nutrition can quickly reverse the skin symptoms of pellagra if they are not advanced.

When recovery begins, many people with pellagra will be very sick. Usually, they are put on mandatory bed rest. If a person has inflammation in the mouth or a gastrointestinal condition that is making it hard for them to eat, they may be given intravenous nutrition (feeding tube) and other forms of liquid supplementation. A high-calorie, nutritious diet with plenty of hydration is essential to helping the body heal and to prevent a recurrence of pellagra.

People who have an active rash are usually advised to avoid the sun until it has started to heal.

Once a person is able to resume a diet of solid foods, they may work with a dietician or nutritionist to ensure they are getting plenty of niacin in their diet. Meat, dairy, and nuts are good sources of niacin, as are green, leafy, vegetables. People can also take a supplemental form of vitamin B3, especially if they are also deficient in other B vitamins (such as in the case of malabsorption) or are taking medications that affect how their body can use niacin.

At first, a person with pellagra may need to take a large amount of a niacin supplement, often for a few weeks. Then, they can then taper off to a maintenance dose along with a niacin-rich diet. A doctor or dietician can help a person decide what regimen they need.

A person with chronic, severe, pellagra will take longer to recover than a person with a milder case. If a person is high-risk for developing pellagra again (such as those who are homeless, have certain medical conditions or abuse alcohol) they will need close follow-up with their medical team to ensure they are getting adequate nutrition.