Pellagra is characterized classically by the triad of dermatitis, diarrhea and dementia.

• The dermatitis is essentially a photosensitive rash. It is typified by bilaterally symmetrical erythema at sites of sun exposure, resembling sunburn. Vesicles and bullae can also be seen and can become exudative, crusted and desquamating. Casal's necklace (named after Don Gaspar Casal) describes a symmetrical, desquamating rash in the neck area. The mucous membranes can also be involved with stomatitis of the tongue and mucositis of the urethra and vagina occurring. Stomatitis of the tongue is a sign of acute deficiency.
• The gastrointestinal symptoms are anorexia, nausea, abdominal pain and diarrhea. The diarrhea is generally watery but can be bloody and mucoid.
• The neurologic manifestations are varied and can include depression, hallucinations, psychosis, memory loss and may progress to disorientation and delirium.

• Malnutrition

  Pellagra due to malnutrition occurred in an Ottawa women in 1973. She was given a normal diet with supplements of riboflavin, thiamine, niacin and ascorbic acid. The clinical response was striking. [ncbi.nlm.nih.gov]

  However, a widespread problem of malnutrition soon arose wherever corn became the main staple. This was a mystery since these types of malnutrition were not normally seen among the Native Americans to whom corn was the principal staple food. [preparednessadvice.com]

• Weight Loss

  She reported a 45-kg (100-lb) weight loss during the past four months and no diarrhea or neurologic symptoms. [nejm.org]

  Pellagra may also develop due to: Gastrointestinal diseases Weight loss (bariatric) surgery Anorexia Excessive alcohol use Carcinoid syndrome (group of symptoms associated with tumors of the small intestine, colon, appendix, and bronchial tubes in the [nlm.nih.gov]

  He presented impaired general condition with moderate asthenia and weight loss. Physical examination showed mitral holosystolic murmur and lower limbs edema. [pubs.sciepub.com]

• Anemia

  Laboratory investigation revealed mild anemia and serum niacin level was found to be low. The diagnosis of a classical pellagra was established. [panafrican-med-journal.com]

  Anemia. Dietary management for Pellagra Avoid:. Avoid alcohol consumption.. Avoid excess consumption of maize (corn) and sorghum (jowar), they hinder in absorption of niacin. Consume:. [specialityclinic.com]

  Other vitamin deficiency diseases besides scurvy and pellagra include rickets, a bone disease caused by too little vitamin D; night blindness, or difficulty seeing in dim light, which is caused by a lack of vitamin A; and pernicious anemia, a condition [pbslearningmedia.org]

  In anemia, the tissues aren't getting enough oxygen and the person feels bad, tired, and exertion quickly becomes exhausting. [blatner.com]

• Fever

  There was no history of fever, seizures or jerky movements or weakness of limbs. His family was on stable diet of maize and was also an occasional alcohol consumer. [panafrican-med-journal.com]

  ‘The troops suffered from malaria, dengue fever, beriberi, hookworm and pellagra.’ [en.oxforddictionaries.com]

  Joseph Goldberger (1874-1929), a physician who served in the United States Public Health Service, fought epidemics of typhoid, dengue, typhus, and yellow fevers, as well as measles and diphtheria—but it is his campaign against pellagra in the Southern [doi.org]

• Burning Feet

  In Africa the mouth lesions of riboflavin deficiency and tropical ulcers commonly occur; in prisoners of war in East Asia during the Second World War the burning feet syndrome (intense burning of the soles) was a marked feature, but almost any symptom [fao.org]

• Diarrhea

  ‘Deficiency leads to pellagra, a condition characterized by dermatitis, diarrhea and certain mental health problems.’ ‘The severe symptoms, depression, dermatitis and diarrhea, are associated with the condition known as pellagra.’ [en.oxforddictionaries.com]

  SYMPTOMS Pellagra is classically described by "the three D's": diarrhea, dermatitis and dementia. [flipper.diff.org]

  Classically, it manifests with triad of diarrhea, dermatitis and dementia and if not treated in time leading to death. Thus, it´s a disorder affecting the skin, nervous system, and gastrointestinal. [panafrican-med-journal.com]

• Abdominal Pain

  Early symptoms include: Loss of appetite Generalised weakness Irritability and aggression Abdominal pain Vomiting Continued deficiency leads to epithelial changes leading to: Stomatitis. Bright red glossitis. Vaginitis. Oesophagitis. [patient.info]

  Diarrhea with nausea, vomiting, abdominal pain.. Dementia (memory disorder, confusion, disorientation etc).. Hallucination.. Fatigue, dizziness.. Insomnia (loss of sleep).. Glossitis (inflammation of tongue).. [specialityclinic.com]

• Loss of Appetite

  ‘Inadequate amounts of this vitamin cause a disease called pellagra, which is characterized by skin disorders, weak muscles, diarrhea, and loss of appetite.’ [en.oxforddictionaries.com]

  Symptoms of pellagra include: Delusions or mental confusion Diarrhea Weakness Loss of appetite Pain in abdomen Inflamed mucous membrane Scaly skin sores, especially in sun-exposed areas of the skin Your health care provider will perform a physical exam [nlm.nih.gov]

  Early symptoms include: Loss of appetite Generalised weakness Irritability and aggression Abdominal pain Vomiting Continued deficiency leads to epithelial changes leading to: Stomatitis. Bright red glossitis. Vaginitis. Oesophagitis. [patient.info]

• Constipation

  Other symptoms include nausea, vomiting, abdominal discomfort, constipation, and diarrhea (which may be bloody). Later, fatigue, insomnia, and apathy develop. Malfunction of the brain (encephalopathy) usually follows. [merckmanuals.com]

  Constipation is common. Later, nausea, vomiting, and diarrhea may occur. Diarrhea is often bloody because of bowel hyperemia and ulceration. [msdmanuals.com]

  Other side effects include nausea, vomiting, pruritus, hives, abnormally high liver enzymes, and constipation. However, too much nicotinic acid or niacin can be harmful. Avoid taking more than your doctor prescribes or recommends. [webmd.com]

• Chronic Diarrhea

  Diets of chronic alcoholics.. Occasionally seen in patients suffering from cirrhosis, chronic diarrhea, diabetes and cancerous growth. Sign and symptoms of Pellagra. [specialityclinic.com]

  He reported also chronic diarrhea with 4 or more watery stools/ day for several months. He presented impaired general condition with moderate asthenia and weight loss. Physical examination showed mitral holosystolic murmur and lower limbs edema. [pubs.sciepub.com]

  Examples of these conditions include prolonged diarrhea; chronic alcoholism; chronic dialysis treatment; chronic colitis, particularly ulcerative colitis or regional enteritis; cirrhosis of the liver; tuberculosis of the GI tract; malignant carcinoid [emedicine.medscape.com]

  Chronic diarrhea can be the part of the presentations of a number of chronic medical conditions affecting the intestine. [en.wikipedia.org]

  Causes include: (1, 4) Alcoholism Cirrhosis of the liver Chronic diarrhea Gastrointestinal diseases such as Crohn’s disease, ulcerative colitis and GI tuberculosis Problems metabolizing tryptophan, such as Hartnup syndrome Carcinoid tumors Certain medications [draxe.com]

• Cheilitis

  MUCOSAL INVOLVEMENT ANGULAR STOMATITIS GLOSSITIS CHEILITIS ULCERATIONS (BUCCAL / VULVAL) 15. GI MANIFESTATIONS • Precedence • • • • Nausea / Vomiting Anorexia Diarrhoea Pain Abdo 16. [slideshare.net]

  Cellulitis of lips Cheilitis NOS Cheilodynia Cheilosis Exfoliative cheilitis Fistula of lips Glandular cheilitis Hypertrophy of lips Perlèche NEC Type 1 Excludes ariboflavinosis ( E53.0 ) cheilitis due to radiation-related disorders ( L55-L59 ) congenital [icd10data.com]

  Images in Clinical Medicine Neda Ashourian, M.D., and Nico Mousdicas, M.D. 10 Citing Articles Three months after undergoing Roux-en-Y bariatric surgery, a 32-year-old woman presented with glossitis, angular cheilitis, and an erythematous, desquamative [nejm.org]

• Tongue Ulcer

  Ulcerations may appear, especially under the tongue, on the mucosa of the lower lip, and opposite the molar teeth. [msdmanuals.com]

  Ulceration (traumatic) of tongue Type 1 Excludes atrophic glossitis ( K14.4 ) pellagrous E52 Niacin E52 (amide) Nicotinic acid deficiency E52 Pellagra E52 (alcoholic) (with polyneuropathy) Polioencephalopathy, superior hemorrhagic E51.2 ICD-10-CM Diagnosis [icd10data.com]

• Bleeding Gums

  FEX: Use of case definitions and awareness of micronutrient deficiencies Summary of Unpublished Study* Afgani boy with swollen and bleeding gums typical of scurvy. [ennonline.net]

  Plaque between the teeth and close to the gums may lead to secondary infection, to receding and bleeding gums and eventually to loss of supporting bone and loss of teeth. [fao.org]

• Sore Mouth

  Abstract In the first few years of the present century there suddenly appeared in the Alabama Insane Hospital a new disease of unknown nature, the salient characteristics of which were a violent dermatitis of the exposed parts, sore mouth, profuse diarrhea [annals.org]

  Locations of involvement include dorsal hands especially, as well as other photodistributed areas; frictional areas like perineum and inframammary folds; oral/ gastrointestinal with sore mouth, red tongue, flat papillae on tongue and gastrointestinal [clinicaladvisor.com]

  In persons with severe skin lesions, a sore mouth and severe diarrhoea with frequent watery stools, dramatic improvements occur within 48 hours. [fao.org]

• Aphthous Stomatitis

  Differential Diagnosis Other Rash Acute generalized exanthematous pustulosis Allergic reaction Aphthous stomatitis Atopic dermatitis Coxsackie Dermatitis herpetiformis Exfoliative erythroderma Impetigo Pellagra Psoriasis Pityriasis rosea Seborrheic dermatitis [wikem.org]

• Dermatitis

  DDx • • • • • • • • • • • PMLE ATOPIC DERMATITIS DRUG RASH SCLE PCT KAVA DERMOPATHY (Piper Methysticus) SEBORRHEIC DERMATITIS CONTACT DERMATITIS HYDROA VACCINIFORME PHYTOPHOTODERMATITIS ACTINIC LP 18. [slideshare.net]

  ‘Deficiency leads to pellagra, a condition characterized by dermatitis, diarrhea and certain mental health problems.’ ‘The severe symptoms, depression, dermatitis and diarrhea, are associated with the condition known as pellagra.’ [en.oxforddictionaries.com]

• Skin Rash

  The condition manifests as a pellagra-like skin rash within 8 weeks after birth, with signs of cerebellar ataxia and developmental retardation. [ncbi.nlm.nih.gov]

  The World's Healthiest Foods Deficiency results in a condition called pellagra, the symptoms of which are a dark, scaly skin rash, a bright red tongue, vomiting, diarrhea, apathy, depression, disorientation, and memory loss. [wordnik.com]

  While early patients may simply have a light skin rash, over time the skin becomes increasingly thickened, pigmented, and may slough off in places. Areas of the skin may become prone to bacterial infection. [encyclopedia.com]

• Blister

  Histopathological examination showed paucicellular interface dermatitis with subepidermal blistering and epidermal pallor. Direct immunofluorescence for immunoglobulin and complement proteins was negative. [mja.com.au]

  PCT presents with as blisters erythema particularly on the wrist of a photodistributed area and may have recurrent flares. However, these flares do not typically exhibit the amount of dyschromia and hyperkeratosis seen with pellagra. [clinicaladvisor.com]

  Denudation of the vesiculated and blistered skin lesions can potentially become infected secondarily. Severe glossitis causes dysphagia. GI tract involvement leads to a mal-absorptive state. [infonet-biovision.org]

  In some patients, blisters appear after several days of erythema, lesions coalesce into vesicles and then rupture. In other cases, dry brown scales appear. 2nd stage: Skin lesions become hard, dry, brittle, brownish in color. [vinmec.com]

• Hyperpigmentation

  Pellagra was suspected because of the classic appearance of Casal's necklace (i.e., erythema, hyperpigmentation, and scales around the neck) (Panel B). [nejm.org]

  Beneficial effects of topically applied nicotinamide in aging skin, such as improvement in barrier functions in atopic dry skin and decreased appearance of signs of facial photoaging (eg, skin texture changes and hyperpigmentation), have been noted. [emedicine.medscape.com]

  After the second cycle, she had hyperpigmentation on her hands and chest. Niacin levels were tested and found to be undetectable. Diarrhea, dermatitis, and undetectable niacin concentrations were consistent with pellagra. [ascopubs.org]

  After 3 months of supplementation, only mild postinflammatory hyperpigmentation remained, subjective skin sensation had returned, mood had improved and diarrhoea had abated. [mja.com.au]

  The complications of Pellagra include: Permeant hyperpigmentation of the skin Difficulty swallowing due to mouth inflammation Depression and anxiety Delusion, hallucination Dilated cardiomyopathy: It is a heart muscle disorder that leads to enlarged and [dovemed.com]

• Cutaneous Manifestation

  The most common features of pellagra in patients with anorexia nervosa are cutaneous manifestations such as erythema on sun-exposed areas, glossitis, and stomatitis. [ncbi.nlm.nih.gov]

  CUTANEOUS MANIFESTATIONS • Erythematous, Pruritic, Painful Photosensitive dermatitis • Edematous, Vesiculobullous lesions • Hyperkeratotic, hyperpigmented, sharply demarcated plaques • Painful fissured palms, soles with goose-flesh 10. • aaa 11. • Butterfly [slideshare.net]

  Scott McNutt, Susan Kindel and Jorge Lugo, Cutaneous manifestations of measles in AIDS, Journal of Cutaneous Pathology, 19, 4, (315-324), (2006). Otto Braun-Falco, Gerd Plewig, Helmut H. Wolff and Richard K. [doi.org]

• Malar Rash

  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). [verywellhealth.com]

• Visual Hallucination

  A historical and conceptual review of the psychopathological aspects of this condition is offered, followed by the report of a patient with a history of chronic alcohol consumption showing signs of pellagra, delusions and visual hallucinations, which [ncbi.nlm.nih.gov]

  In this case the patient presented fantastic, mystic and megalomaniac delusions and visual hallucinations. [doi.org]

  Cognitive symptoms included mental confusion, short-term memory loss, and visual hallucinations of parasites crawling out of his skin. [consultant360.com]

• Psychiatric Manifestation

  The cardinal manifestations have been popularly known as the three D's, which are dementia, dermatitis and diarrhea. Psychiatric manifestations are fairly common but are easily overlooked due to their non specific nature. [ncbi.nlm.nih.gov]

• Mood Swings

  Swings, Irritability, and Other Problems Disorientation and Delusions Restlessness or Anxiety Some Other Symptoms might Include: Sores on the gums and lips Vomiting and nausea Trouble in drinking and eating Decreased appetite What is Pellagra Caused [vedantu.com]

• Confusion

  More symptoms are: High sensitivity to sunlight • Aggression • Dermatitis, alopecia, oedema • Smooth, beefy red glossitis • Red skin lesions • Insomnia • Weakness • Mental confusion • Ataxia, paralysis of extremities, peripheral neuritis • Diarrhea • [flipper.diff.org]

  Results and factors identified in Llopis's analysis (75 female patients) Loadings Factor 1 ‘Stupor-confusion’ (after rotation) variance 23% Emotionalism 0.644 Depression 0.710 Confusion 0.600 Delusions 0.800 Stupor 0.724 Factor 2 ‘Hallucinatory-confused [doi.org]

  The clinical features included confusion and/or clouding of consciousness, marked oppositional hypertonus ('gegenhalten') and myoclonus. [ncbi.nlm.nih.gov]

  A forty-two-year farmer from hilly area of central Nepal, presented with pruritic and eczematous skin lesions over dorsum of hands and forearms, face, neck (A) and lower leg with mild confusion state and diarrhea of 2 months duration. [panafrican-med-journal.com]

• Apathy

  NEUROLOGICAL INVOLVEMENT • • • • • • • • Insomnia Fatigue Nervousness Apathy Impaired Memory Depression Psychosis Dementia 17. [slideshare.net]

  At the same time, there was noticeable improvement in the patient's depression and apathy. We suggest that all of these changes could be due to percutaneous absorption of niacinamide. [ncbi.nlm.nih.gov]

  […] and gums may be sore and peeling Gastrointestinal Diarrhoea occurs in 50% of cases Poor appetite, abdominal pain, nausea and vomiting are common It may be difficult to eat and drink, leading to further malnutrition Neurological Initially symptoms of apathy [web.archive.org]

• Irritability

  A few weeks later, the patient developed nervousness, irritability, insomnia and, consequently, delusional ideas and hallucinations, for which he had to be hospitalized. [ncbi.nlm.nih.gov]

  […] appetite, abdominal pain, nausea and vomiting are common It may be difficult to eat and drink, leading to further malnutrition Neurological Initially symptoms of apathy and slight depression may go unnoticed Other symptoms include headache, confusion, irritability [web.archive.org]

  Avoid other things that can irritate damaged or painful skin, such as hot showers or baths, hot tubs, too much time in the shower, swimming in chlorinated water, makeup with irritating chemicals, perfumes or deodorants on affected skin, etc. [draxe.com]

  Early symptoms include: Loss of appetite Generalised weakness Irritability and aggression Abdominal pain Vomiting Continued deficiency leads to epithelial changes leading to: Stomatitis. Bright red glossitis. Vaginitis. Oesophagitis. [patient.info]

• Insomnia

  NEUROLOGICAL INVOLVEMENT • • • • • • • • Insomnia Fatigue Nervousness Apathy Impaired Memory Depression Psychosis Dementia 17. [slideshare.net]

  A few weeks later, the patient developed nervousness, irritability, insomnia and, consequently, delusional ideas and hallucinations, for which he had to be hospitalized. [ncbi.nlm.nih.gov]

  Insomnia (loss of sleep).. Glossitis (inflammation of tongue).. Stomatitis (inflammation of mucous lining of the mouth).. Vaginitis (inflammation of mucous lining of the vagina) in females.. Anemia. Dietary management for Pellagra Avoid:. [specialityclinic.com]

  Some of the symptoms include sore skin, fatigue, mental disorders, diarrhea, inflamed mucous membranes, aggression, insomnia, sensitivity to sunlight, etc. [cookinggodsway.com]

• Tremor

  […] vomiting are common It may be difficult to eat and drink, leading to further malnutrition Neurological Initially symptoms of apathy and slight depression may go unnoticed Other symptoms include headache, confusion, irritability, restlessness, anxiety, tremor [web.archive.org]

  Various neurologic and gastrointestinal complaints such as dizziness, tremors, insomnia, fatigue, mood symptoms, nausea, vomiting, and diarrhea can be present and may precede skin manifestations. [visualdx.com]

  Anxiety, headaches, and tremors were also present. He had been consuming 6 to 8 liters of wine every day for the past 11 years. He used to wear a hooded sweatshirt, not having other photoexposed areas. [mayoclinicproceedings.org]

In addition to obtaining a dietary history, low levels of urinary excretion of N-methyl nicotinamide and pyridone can be used to diagnose niacin deficiency and support the diagnosis of pellagra.

Treatment of pellagra consists primarily of exogenous replacement of niacin or nicotinamide. However, patients with pellagra are frequently deficient in other B vitamins too and are generally prescribed B vitamin complexes. Prescription of a balanced diet and replenishment of calories is also frequently required due to the fact that pellagra patients are generally malnourished.

The dermatitis component can be treated with emolients and topical corticosteroids. Treatment of concurrent conditions such as psychiatric disorders and malabsorption syndromes should also be undertaken.

Prognosis of pellagra is generally good if recognized and treated early with niacin supplementation. The dermatological and diarrheal symptoms of pellagra subside over a period of 2 weeks and the neurologic symptoms following thereafter. Untreated pellagra can result in death however, due to cardiomyopathy resulting from impairment of cellular metabolic functions.

Pellagra is caused by niacin deficiency. Niacin deficiency may occur as a result of poor dietary intake, as seen in areas corn is a staple food. Corn is deficient in niacin. However, niacin deficiency can occur as a result of deficiency in intake of its precursor molecule tryptophan. Hence, a diet poor in amino acid balance can also result in pellagra. Medical conditions in which a poor diet is a usual component, particularly anorexia nervosa and alcoholism, can manifest in pellagra.

Following on from this, excess metabolic demand for tryptophan can also cause pellagra as seen in carcinoid syndrome. Carcinoid syndrome, which is caused by excess serotonin production, diverts tryptophan towards the production of serotonin. Malabsorption disorders can also lead to pellagra due to inadequate absorption of amino acids. Hartnup disease, which is a congenital disorder of amino acid absorption, can also result in pellagra due to deficiency in tryptophan absorption.

Certain medications such as 5-fluoro-uracil, isoniazid, pyrazinamide, 6-mercaptopurine, hydantoins, phenobarbital and chloramphenicol can also induce pellagra. These medications inhibit the biosynthesis of niacin by inhibiting the conversion of tryptophan to niacin.

Pellagra afflicts young adults commonly and affects both males and females equally. Historically, rural areas of the United States with high levels of poverty saw epidemic proportions of pellagra during the depression era. Although Central American cultures depend on corn as a staple, pellagra does not occur in Central America due to differences in preparation methods of the corn. Fortification of bread and flour with niacin occurred in 1941 making pellagra a rare entity in modern times. Nonetheless, pellagra remains a common entity in developing countries.

Niacin is the precursor for nicotinamide which in turn is the precursor for nicotinamide adenine dinucleotiode (NAD). NAD in its oxidized and reduced form are known as NAD+ and NADH respectively. These two molecules play a key role in electron transfer reactions such as oxidative phosphorylation. Hence a deficiency in niacin has widespread consequences on whole body cell metabolism thereby underlying the widespread systemic symptoms pellagra. The skin photosensitivity seen in pellagra is possibly due to an indirectly induced zinc deficiency. The depression seen in pellagra may be a result of serotonin deficiency.

Prevention of pellagra primarily depends on consumption of a balanced diet. Since 1941, flour and bread have been fortified in the United States with niacin which helped to virtually eliminate dietary-related pellagra in the United States. Primary prevention efforts are especially important in those who are at risk for poor nutrition – e.g. schizophrenics, anorexics, patients with Crohn disease or short gut syndrome. Such patients would benefit from a focus on dietary counseling and education.

Pellagra was initially described by Don Gaspar Casal in 1735 in Spanish peasants. The word "pellagra" is derived from the Latin words "pelle" - skin and "agra" - rough. Thereby describing one of the three cardinal symptoms of pellagra i.e. dermatitis, which is the most easily recognizable outward symptom of the disease. Historically, pellagra was initially recognized as caused by poor nutrition seen in poor populations living in regions where corn is the staple food. More recently, pellagra is recognized as a complication of poor nutrition secondary to other medical conditions such as alcoholism, eating disorders and schizophrenia.

• Definition: Pellagra is a disease caused by niacin deficiency or tryptophan (an amino acid) deficiency. Niacin is a type of vitamin B which is important for normal metabolism. 
• Cause: Pellagra can be caused by any condition which causes poor dietary intake, particularly of vitamins and protein. Eating as corn as a staple diet classically caused pellagra, but nowadays pellagra can occur in association with eating disorders, alcoholism, gastrointestinal diseases and other conditions where nutrition is poor.
• Symptoms: Pellagra commonly presents with three symptoms: rash, diarrhea and mental changes.
• Diagnosis: Pellagra is generally diagnosed clinically by asking about the symptoms of pellagra and a dietary history. Physical exam will focus on looking for the rash. A urine test may be ordered to help support the diagnosis.
• Treatment and follow-up: Pellagra is treated with niacin supplementation as well improvement in nutrition levels overall. Dietary counseling and education is important to prevent recurrences.

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