What Deficiency Disease Produces the Symptoms Known as the Four DS?

December 31, 2025 •

2 min read

Historically responsible for over 100,000 deaths in the early 20th century U.S., pellagra is the deficiency disease that produces the symptoms known as the four Ds: dermatitis, diarrhea, dementia, and death. It is caused by a severe lack of niacin (vitamin B3) or its precursor, tryptophan.

Quick Summary

Pellagra is a disease caused by severe niacin deficiency, presenting with a distinct set of symptoms known as the four Ds. It affects the skin, digestive system, and nervous system.

Key Points

Pellagra is the four Ds disease: The classic symptoms of pellagra—dermatitis, diarrhea, dementia, and death—result from severe niacin (vitamin B3) deficiency.
Niacin is vital for metabolism: As a precursor to NAD and NADP, niacin is crucial for energy production in cells, particularly those in the skin, gut, and brain.
Causes can be primary or secondary: Primary pellagra is from a poor diet, often maize-heavy, while secondary pellagra is caused by underlying conditions affecting nutrient absorption.
Symptoms affect multiple systems: Pellagra presents with skin lesions on sun-exposed areas, gastrointestinal issues like diarrhea, and neuropsychiatric problems ranging from confusion to psychosis.
Treatment is straightforward but urgent: Early intervention with niacin supplementation and dietary changes can reverse symptoms, but delayed treatment may cause permanent damage.
Prevention is key: A balanced diet with niacin-rich foods or enriched grains is the best way to prevent pellagra.

What is Pellagra?

Pellagra is a nutritional disorder resulting from a severe deficiency of niacin, also known as vitamin B3. The name, meaning "rough skin" in Italian, points to one of its main symptoms. While rare in many countries today due to food fortification, it can still affect people in areas with limited food diversity or those with specific health issues. Niacin is essential for cellular metabolism, and its lack impacts rapidly renewing tissues like the skin, gut, and brain.

The Four Ds Explained

Pellagra's classic symptoms are often summarized as the four Ds:

Dermatitis: A characteristic skin rash, similar to a sunburn, typically appears symmetrically on sun-exposed areas. A band-like rash around the neck is sometimes called Casal's collar. The affected skin can become thick and discolored.
Diarrhea: Niacin deficiency affects the gastrointestinal tract lining, leading to chronic diarrhea, abdominal pain, nausea, and vomiting.
Dementia: The central nervous system is impacted, causing symptoms like fatigue, depression, anxiety, confusion, memory loss, and in severe cases, psychosis. Permanent neurological damage is possible.
Death: Without treatment, the systemic effects of pellagra can ultimately be fatal.

Causes of Pellagra

Pellagra can be primary, due to insufficient niacin or tryptophan intake, or secondary, resulting from problems absorbing or using niacin.

Primary Pellagra This type is linked to diets low in niacin and tryptophan, historically common in populations relying heavily on corn. Niacin in corn is bound and unavailable unless processed with alkali, a method called nixtamalization.

Secondary Pellagra Secondary pellagra occurs when underlying conditions interfere with niacin absorption or metabolism. Common causes include chronic alcoholism, malabsorption disorders like Crohn's disease, certain medications (e.g., isoniazid), and genetic conditions like Hartnup disease. Other risk factors include advanced cancer and HIV.

Treatment and Prevention

Pellagra is treatable with niacin or nicotinamide supplements, often showing symptom improvement quickly. Prevention focuses on ensuring adequate niacin intake through diet.

List of Niacin-Rich Foods

Poultry (chicken, turkey)
Red meat (beef, liver)
Fish (tuna, salmon)
Legumes (peanuts, lentils)
Seeds (sunflower seeds)
Enriched bread and cereals
Mushrooms
Avocado

Comparison of Pellagra with Other Deficiency Diseases


Feature	Pellagra (Niacin/B3)	Beriberi (Thiamin/B1)	Scurvy (Vitamin C)
Classic Symptoms	Dermatitis, Diarrhea, Dementia	Wet beriberi (cardiovascular) or Dry beriberi (neurological)	Fatigue, swollen gums, joint pain, poor wound healing
Affected Systems	Skin, gastrointestinal, nervous	Nervous, cardiovascular	Connective tissue, immune system
Key Cause	Deficiency of Niacin or Tryptophan	Deficiency of Thiamin	Deficiency of Ascorbic Acid
Historical Context	Epidemic in maize-dependent populations	Epidemic in polished rice-dependent populations	Historical disease of sailors on long voyages
Treatment	Niacin/Nicotinamide supplements	Thiamin supplementation	Vitamin C supplementation

Conclusion

Pellagra, caused by a severe lack of niacin or tryptophan, is characterized by the four Ds: dermatitis, diarrhea, dementia, and death. Its history highlights the importance of diet and socioeconomic factors in health. While fortification has reduced primary pellagra in many places, risk remains for groups like chronic alcoholics and those with malabsorption. Early treatment with niacin can reverse symptoms and prevent serious complications. For more information, consult medical resources.

Frequently Asked Questions

Pellagra is caused by a severe deficiency of niacin (vitamin B3), or a lack of the amino acid tryptophan, which the body can convert into niacin.

The four Ds stand for dermatitis (skin rash), diarrhea (digestive problems), dementia (neurological issues), and death (if left untreated).

No, pellagra is rare in developed countries due to food fortification. It is still a problem in developing nations and for at-risk individuals, such as chronic alcoholics.

In many maize-dependent populations, pellagra arose because the niacin in corn is in a bound form that is poorly absorbed unless prepared using an alkaline process like nixtamalization.

Yes, pellagra is curable with niacin or nicotinamide supplementation, as well as a nutritious diet. Recovery is often quick with early treatment.

Risk factors for secondary pellagra include chronic alcoholism, malabsorption disorders like Crohn's disease, and certain medications that interfere with niacin metabolism.

Good sources of niacin include meat, fish, poultry, eggs, legumes, peanuts, seeds, and fortified cereals and breads.