Twenty-first century pellagra

By Warren R. Heymann, MD, FAAD
Sept. 10, 2025
Vol. 7, No. 36

With obesity (defined as a body mass index > 30) affecting more than 40% of the adult population of the United States (1), it is difficult to fathom that nutritional deficiencies still exist. Kiani et al. expertly review the main nutritional deficiencies. (2) The following abstract summarizes their manuscript:

Nutrition is the source of energy that is required to carry out all the processes of human body. A balanced diet is a combination of both macro- and micronutrients. “Nutritional inadequacy” involves an intake of nutrients that is lower than the estimated average requirement, whereas “nutritional deficiency” consists of severely reduced levels of one or more nutrients, making the body unable to normally perform its functions and thus leading to an increased risk of several diseases like cancer, diabetes, and heart disease. Malnutrition could be caused by environmental factors, like food scarcity, as well as disease conditions, like anorexia nervosa, fasting, swallowing inability, persistent vomiting, impaired digestion, intestinal malabsorption, or other chronic diseases. Nutritional biomarkers — like serum or plasma levels of nutrients such as folate, vitamin C, B vitamins, vitamin D, selenium, copper, zinc — could be used for the evaluation of nutrient intake and dietary exposure. Macronutrients deficiencies could cause kwashiorkor, marasmus, ketosis, growth retardation, wound healing, and increased infection susceptibility, whereas micronutrient — like iron, folate, zinc, iodine, and vitamin A — deficiencies lead to intellectual impairment, poor growth, perinatal complications, degenerative diseases associated with aging and higher morbidity and mortality. Preventing macro- and micronutrient deficiency is crucial and this could be achieved through supplementation and food-based approaches.

The cutaneous manifestations of nutritional deficiency often enter our differential diagnosis, especially in hospitalized patients. Dermatologists know that the presentation is usually due to multiple nutritional deficiencies. This commentary will focus exclusively on pellagra due to niacin (vitamin B3) deficiency.

In 1914, the public health pioneer Joseph Goldberger challenged the prevailing theory that pellagra was an infectious disease. He observed that prisoners and children in orphanages were often affected while staff members at these institutions were spared. Confirming his hypothesis that diet was responsible, he arranged for children in two Mississippi orphanages to receive a more balanced diet — nearly all afflicted children were cured. (3)

Niacin (vitamin B3) is an essential water-soluble vitamin within the B complex group. Niacin is rich in eggs, peanuts, poultry, red meat, fish, bran, whole-grain cereals, and legumes. Niacin is involved in cellular metabolism as a vital component in the oxidized state of nicotinamide adenine dinucleotide (NAD, or coenzyme 1) and the reduced form of nicotinamide adenine dinucleotide phosphate (NADP, or coenzyme 2). These coenzymes play key roles in glycolysis, pyruvate metabolism, protein and amino acid metabolism, pentose biosynthesis, glycerol metabolism, synthesis of high-energy phosphate bonds, and fatty acid metabolism. (4)

Niacin deficiency can occur from a lack of consuming dietary sources containing niacin. In some foods, such as corn, niacin can covalently bind to carbohydrates or small peptides, decreasing the bioavailability for absorption in the small intestines. This binding explains why some of the earliest signs of pellagra occur in populations consuming a high corn-based diet. In addition to dietary sources, the liver can synthesize niacin from tryptophan; thus, a diet containing both niacin and tryptophan is necessary to maintain adequate niacin levels.

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Niacin deficiency is uncommon in industrialized countries because of adequate dietary intake. Most cases of pellagra are secondary to drugs, alcoholism, gastrointestinal tract diseases, and malignancies. The increased serotonin production in carcinoid tumors utilizes more tryptophan, resulting in the deficiency of substrate left for niacin synthesis. Excessive and chronic alcohol intake may be accompanied by malnutrition, thus impairing the conversion of tryptophan to niacin. Because niacin is primarily absorbed in the small intestine, malabsorptive disorders such as chronic diarrhea, inflammatory bowel disease, and malignancy can impair niacin absorption. Hartnup disease causes pellagra because of impaired tryptophan absorption. Medications, such as isoniazid, may cause niacin deficiency by binding with vitamin B6 and reducing PLP-dependent kynureninase activity, a required substance for niacin synthesis. (5) Isoniazid also decreases niacin levels by inhibiting its intestinal absorption and endogenous production from tryptophan. Chemotherapeutic agents such as fluorouracil and 6-mercaptopurine can also lead to niacin deficiency.

Pellagra is characterized by the “three D’s” — dermatitis, diarrhea, and dementia, which may culminate in the fourth “D” — death due to inadequate energy to support critical functions. (6) According to Dhattarwal and Singh, “Characteristic cutaneous findings are symmetrical, well-demarcated photosensitive eruption on face (butterfly rash), neck (Casal’s necklace), dorsa of hands (gauntlet/glove of pellagra) and feet. The back of the hands is the commonest site. Initially, there is intense erythema, pain, burning sensation and sometimes, even vesicles and bulla formation (wet pellagra). Thereafter, thick, dry and scaly hyperpigmented ‘goose’ like skin develops. Oral cavity may be involved in one-third patients in the form of cheilitis, angular stomatitis, glossitis, fissures and/or ulceration. Perineal lesions (pellagrous scrotal dermatitis and pellagrous vulvitis), thickening and pigmentation of skin over bony prominences, follicular hyperkeratosis on face and half and half nails are some uncommonly seen features.” (7)

Dermoscopy of pellagra may show a pink background, double-edged white scales, reddish brown structures, red and brown dots and globules, perifollicular scaling, follicular white dots, and plugs. Histopathological features are eczematous, with the upper half of the stratum malpighi showing changes (pallor, necrosis) that may be seen in other nutritional deficiencies such as acrodermatitis enteropathica and necrolytic migratory erythema. Chronic cases demonstrate acanthosis, hyperkeratosis, and increased epidermal pigment. (8)

The cutaneous hallmark of pellagra — photosensitivity — is likely due to excess production of the photosensitizer, kynurenic acid, and diminished production of the photoprotective compound, urocanic acid. These changes will respond to the standard treatment of pellagra — oral nicotinamide (niacinamide) supplementation (with other supplements because of the multifactorial nature of nutritional deficiency) dosed 300 mg daily divided into 3-4 doses for 3-4 weeks. (9)

Pellagra is not a relic of history. While secondary pellagra is noted in industrialized countries, Fernandez-Gonzalez’s classical cases may be more widespread than recognized. They detailed five cases in Gambo, Ethiopia, all of which were linked to exclusive maize consumption. (10) Joseph Goldberger’s work continues in the twenty-first century.

Point to Remember: Pellagra due to niacin deficiency still exists as a primary disorder in less developed countries and as a secondary disorder in industrialized countries.

Our expert’s viewpoint

Dr. Niharika Dhattarwal, MD, DNB
Specialist
Deen Dayal Upadhyay Hospital, Delhi (India)

Pellagra is a well-known clinical syndrome caused by deficiency of niacin (vitamin B3). It can be due to dietary factors or drugs, gastrointestinal diseases and malignancy. As mentioned in this paper, nutritional deficiencies are no longer the leading cause of pellagra in industrialized countries and thus, secondary causes must be ruled out and addressed in all cases. Even in a developing country like India, I have encountered more cases of drug-induced pellagra rather than nutritional deficiencies, especially in adults. Antitubercular drug Isoniazid is the most commonly seen culprit drug, probably due to high tuberculosis incidence in India, but I had a patient with phenytoin-induced pellagra as well. So history and temporal corelation with other drugs like ethionamide, pyrazinamide, chemotherapeutic drugs, azathioprine etc. should be carefully taken.

Clinical manifestations may not be classical in all cases. Photodistributed dermatitic (in early stage) or hyperpigmented and hyperkeratotic lesions (in late stage) is characteristically noted and dermatologists should suspect pellagra in these cases. Sometimes, mucosal involvement may be the presenting feature as reported and published in our case. In pediatric age group, multiple nutritional deficiencies are more common rather than just one macro or micronutrient deficiency. This leads to a mixed clinical picture showing cutaneous, hair, and nail changes of zinc, iron, or other vitamin deficiencies along with growth retardation. Therefore, apart from the mentioned clinical presentations, nutritional deficiency can also be suspected when there are widespread dermatitic lesions which are not responding to standard treatments like emollients, topical steroids or topical steroid sparing immunosuppressants.

Treatment consists of oral supplementation as mentioned as well as removal of the inciting cause.

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References

1. https://www.cdc.gov/obesity/adult-obesity-facts/index.html (accessed Nov 11, 2024)

2. Kiani AK, Dhuli K, Donato K, Aquilanti B, Velluti V, Matera G, Iaconelli A, Connelly ST, Bellinato F, Gisondi P, Bertelli M. Main nutritional deficiencies. J Prev Med Hyg. 2022 Oct 17;63(2 Suppl 3):E93-E101. doi: 10.15167/2421-4248/jpmh2022.63.2S3.2752. PMID: 36479498; PMCID: PMC9710417.

3. Jayakumar KL, Micheletti RG. Joseph Goldberger-Public Health Champion and Investigator of Pellagra. JAMA Dermatol. 2017 Dec 1;153(12):1262. doi: 10.1001/jamadermatol.2017.4044. PMID: 29238837.

4. Peechakara BV, Gupta M. Vitamin B3. 2024 Feb 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 30252363.

5. Prabhu D, Dawe RS, Mponda K. Pellagra a review exploring causes and mechanisms, including isoniazid-induced pellagra. Photodermatol Photoimmunol Photomed. 2021 Mar;37(2):99-104. doi: 10.1111/phpp.12659. Epub 2021 Feb 2. PMID: 33471377.

6. Redzic S, Hashmi MF, Gupta V. Niacin Deficiency. 2023 Jul 25. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 32491660.

7. Dhattarwal N, Singh V. Perianal rash: An uncommon presenting complaint of pellagra. J Eur Acad Dermatol Venereol. 2024 Nov;38(11):e1005-e1006. doi: 10.1111/jdv.20057. Epub 2024 May 2. PMID: 38695739.

8. Murthy SC, Shankar M. Pellagra dermatitis: five cases with dermoscopic findings. Int J Dermatol. 2022 Feb;61(2):e56-e58. doi: 10.1111/ijd.15610. Epub 2021 May 24. PMID: 34029401.

9. Hołubiec P, Leończyk M, Staszewski F, Łazarczyk A, Jaworek AK, Wojas-Pelc A. Pathophysiology and clinical management of pellagra - a review. Folia Med Cracov. 2021 Sep 29;61(3):125-137. doi: 10.24425/fmc.2021.138956. PMID: 34882669.

10. Fernandez-Gonzalez P, Seijas-Pereda L, Tefasmariam A, Balcha S, Fernandez-Zarzoso M, Onoda M, Quiles-Recuenco A, Pérez-Tanoira R, Malmierca E. Pellagra linked to maize consumption in Gambo, Ethiopia: A call for awareness. J Eur Acad Dermatol Venereol. 2024 Jul;38(7):e617-e619. doi: 10.1111/jdv.19829. Epub 2024 Feb 9. PMID: 38334189.

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