Rashes, diarrhea, and neuropsychiatric issues
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Rashes, diarrhea, and neuropsychiatric issues


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A man, aged 42 years, presents with a 6-month history of a painful, scaly skin rash. The eruption is symmetrically distributed over photosensitive areas, affecting his face, neck, upper back, forearms, and hands. The dorsal surfaces of his hands and forearms exhibit a dusky brown coloration over rough and cracked skin. He complains of itching and burning and reports intermittent vomiting and diarrhea. He admits to heavy alcohol intake for the last 2 decades and denies taking any medications. Neuropsychiatric evaluation reveals short-term memory loss, speech problems, and poor concentration. 


Pellagra is a systemic disease observed in chronic severe deficiency of niacin (also known as nicotinic acid or vitamin B3). Pellagra means rough skin and is a clinical syndrome characterized by symmetric photosensitive rashes, gastrointestinal symptoms, and neuropsychiatric disturbances.1,2 It...

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Pellagra is a systemic disease observed in chronic severe deficiency of niacin (also known as nicotinic acid or vitamin B3). Pellagra means rough skin and is a clinical syndrome characterized by symmetric photosensitive rashes, gastrointestinal symptoms, and neuropsychiatric disturbances.1,2 It is traditionally described by the “four Ds”: dermatitis, diarrhea, dementia, and death, if left untreated.

Niacin can be synthesized from tryptophan or obtained from food sources such as meat, poultry, dry beans, nuts, and dairy products. Pellagra develops as soon as 60 days in someone on a niacin-deficient diet.2,3 Niacin is a constituent of coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which function in essential oxidation-reduction reactions; NAD is involved in cell signaling and macronutrient catabolism, and NADP functions in anabolic processes.2 Manifestations of pellagra result from the insufficiency of these coenzymes, which are found throughout the body, which in turn explains the multisystem involvement. Tissues with high-energy requirements (brain) or high turnover rates (skin and gut) are most affected by the impaired cellular energy transfer reactions.2

Although the exact incidence of pellagra is unknown, in developed countries, it is a rare condition that is confined to groups at risk for malnutrition, such as alcoholics and psychiatric patients.4 Pellagra remains endemic in poverty-stricken areas of Africa and Asia where the staple diet primarily consists of corn or maize, which contain bound niacin that cannot be absorbed; an exception is the maize prepared in Mexico, where the limewater washing process liberates bound niacin.1,2,4 Pellagra has no sex or race predilection and occurs infrequently in children.4

Pellagra may arise secondary to underlying conditions that interfere with niacin absorption and processing. Patients with gastrointestinal disorders are predisposed to pellagra due to impaired absorption of tryptophan and niacin; examples include Crohn disease, gastrectomy, severe ulcerative colitis, and jejunoileitis.1 Metabolic disorders such as Hartnup disease, in which pellagra-like symptoms develop in childhood, and carcinoid syndrome, may lead to pellagra. Drugs that are known to interfere with niacin metabolism include isoniazid, pyrazinamide, 6-mercaptopurine, 5-fluorouracil, phenytoin, azathioprine, and chloramphenicol.1 Chronic alcoholics are at risk for pellagra due to a combination of poor diet, malabsorption, liver cirrhosis, and hepatic cell injury.3

The dermatitis seen in pellagra begins as painful, erythematous, pruritic patches in a bilaterally symmetrical eruption in areas exposed to sunlight, heat, and friction.1,5 Initially, the affected skin resembles an acute sunburn with erythema and progressively becomes more edematous; it may develop vesicles and bullae, which can rupture and leave crusted erosions, or develop into a hyperpigmented scaly rash.4,5 Patients may complain of a burning sensation and exacerbation following exposure to sunlight. Photosensitivity is thought to be caused by a deficiency of urocanic acid or cutaneous accumulation of kynurenic acid, which induces phototoxic changes.2

The dorsal surfaces of the hands are the most commonly affected sites (observed in up to 97% of cases); when the rash extends proximally to the radial aspects of the forearms, it forms the characteristic gauntlet of pellagra.1,4,5 An eruption localized to the upper central portion of the chest and neck is known as Casal necklace or Casal collar.1 Typically, a sharply demarcated border between affected and normal skin is evident.

Over time, the skin thickens into hyperkeratotic and parchment-like plaques that are dry and scaly, giving rise to the term goose skin.1,5 A symmetric butterfly eruption with fine scaling over the malar area is frequently observed.1 One-third of patients have oral mucous membrane involvement, manifesting as cheilitis, angular stomatitis, and glossitis.5

The pathologic changes of hyperkeratosis, parakeratosis, and acanthosis in pellagrous skin are nonspecific. Possible histologic findings include epidermal atrophy overlying dermal fibrosis, vacuolar change, sebaceous gland atrophy, and a lymphocytic perivascular infiltrate.2,5

Although the characteristic dermatitis of pellagra is the key to diagnosis, the earliest manifestation of the disease is gastrointestinal disturbance. Patients often report decreased appetite, epigastric discomfort, abdominal pain, vomiting, and watery diarrhea.1,5 Signs of neurologic damage occur late in the disease. Common complaints include insomnia, fatigue, anxiety, and depression. Neuropsychiatric examination may reveal impaired memory, poor concentration, irritability, apathy, sensorimotor neuropathy, tremor, and ataxia.2,5 As pellagra advances, patients become increasingly disoriented and delirious, ultimately slipping into a coma.5

The diagnosis of pellagra is based on clinical presentation, with focus on the first three Ds and localization of skin lesions, and rapid response to oral vitamin supplementation.1,5 There are no tests that definitively diagnose pellagra, but measurements of low serum niacin and low urinary niacin metabolites may provide supportive evidence.1,5 The differential diagnosis should include phototoxic and photoallergic skin reactions, polymorphous light eruption, porphyria, and lupus erythematosus.

If pellagra is diagnosed and treated appropriately, the prognosis for recovery is excellent. However, untreated pellagra will progressively worsen as neurologic function declines, leading to death within 4 to 5 years.5

The treatment of pellagra consists of oral nicotinamide or niacin (100-300 mg daily in 3-4 separate doses) until resolution of the major symptoms.2,5 Nicotinamide is preferred because it does not cause the headache and flushing associated with niacin.1,2 Severe cases may require parenteral niacin. For secondary pellagra, the underlying pathology must be addressed and offending drugs removed. Most patients require concomitant administration of riboflavin, pyridoxine, zinc, and magnesium, and a protein-rich diet for a full recovery.2 Neuropsychiatric symptoms disappear after 1 to 2 days, whereas skin lesions take 3 to 4 weeks to resolve.1,2 Topical emollients for the dermatitis may reduce discomfort.5

In our case, the patient was treated with oral niacin supplementation for 1 week, at which point his symptoms completely resolved. The patient was advised to avoid sun exposure during treatment and received alcohol counseling as well. 


Julie Nguyen, BS, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston.

References 


  1. Jen M, Yan AC. Cutaneous changes in nutritional disease. In: Goldsmith L, Katz S, Gilchrest B, Paller A, Leffell D, Wolff K, eds.Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York, NY: McGraw-Hill, 2012:1499-1524.
  2. Karthikeyan K, Thappa DM. Pellagra and skin. Int J Dermatol. 2002;41(8):476-481.
  3. Oldham MA, Ivkovic A. Pellagrous encephalopathy presenting as alcohol withdrawal delirium: a case series and literature review.Addict Sci Clin Pract. 2012;7:12.
  4. Wan P, Moat S, Anstey A. Pellagra: a review with emphasis on photosensitivity. Br J Dermatol. 2011;164(6):1188-1200.
  5. Hegyi J, Schwartz RA, Hegyi V. Pellagra: dermatitis, dementia, and diarrhea. Int J Dermatol. 2004;43(1):1-5.
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