Pediatric Pellagra Clinical Presentation

Updated: Feb 11, 2016
  • Author: Simon S Rabinowitz, MD, PhD, FAAP; Chief Editor: Jatinder Bhatia, MBBS, FAAP  more...
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Presentation

History

Pellagra can be induced experimentally in 6-8 weeks with exposure to a pellagragenic diet.

In endemic cases, pellagra tends to be seasonal and occurs during spring and early summer. Early symptoms are nonspecific. Patients express weakness, lassitude, and anorexia. Soon, classic symptoms of GI involvement, dermatitis, and disturbed mental state follow.

A small US series reported that less than a quarter of patients with pellagra had a syndrome that included diarrhea, dermatitis, and dementia. [7] Isolated dermatitis and dementia were both slightly more common, whereas a combination of dermatitis and diarrhea was seen in nearly 20%.

A small Romanian series published in 1994 also described a slightly different clinical presentation for modern pellagra. [8] Sun exposure causes the skin to rapidly move from sunburn to pigmented and parched. Parched lips and angular stomatitis were also observed. GI symptoms suggest irritable bowel syndrome, with either constipation or diarrhea and abdominal discomfort. Dementia in this cohort was characterized by an unexpressive look, abnormal facial expressions, difficulty sleeping and headaches.

  • GI findings
    • Pellagra begins in the gut, where metabolically active mucosal tissue is constantly turning over.
    • Patients with pellagra tend to suffer from poor appetite, nausea, epigastric discomfort, abdominal pain, and increased salivation.
    • Gastritis can be present and may result in achlorhydria.
    • Glossitis typically causes soreness of the mouth and dysphagia.
    • Diarrhea is the manifestation of intestinal inflammation. Diarrhea is typically watery (enteritis) but is occasionally bloody and mucoid (colitis).
    • A single case has been reported of a young woman who presented with pellagra secondary to megaduodenum. [9]
  • Skin findings
    • Affected skin lesions are initially erythematous and are associated with a burning sensation.
    • The distribution of the cutaneous eruption is typically symmetrical and bilateral in parts of the body exposed to sun. There can be acute presentation with bullae, which has been referred to as wet pellagra. Dorsum of the hands and feet, neck area, and a malar rash are typical areas of involvement.
    • As the dermatitis progresses, the affected skin becomes hyperpigmented and thickened.
    • The dermatologic findings of pellagra, which responded to niacin supplementation, have been reported as an initial presentation of Crohn disease. [10]
    • For more detailed information, see the Medscape Reference article Dermatologic Manifestations of Pellagra.
  • Neuropsychiatric findings
    • Early neuropsychiatric symptoms of pellagra include lethargy, apathy, depression, anxiety, irritability, and poor concentration.
    • As the disease advances, patients become disoriented, confused, and delirious. Eventually, the patient becomes stuporous and comatose.
  • Death: Death is the result of the depletion of the coenzyme required to generate sufficient energy to support vital body functions.
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Physical

See the list below:

  • GI symptoms
    • Anorexia and malabsorptive diarrhea lead to a state of malnutrition. The picture may initially be confusing because other B vitamin deficiencies may also be present. If severe enough, a kwashiorkor phenotype may be observed.
    • Often, the glossitis is severe and is associated with swelling and tenderness of the tongue. The tongue becomes beefy red and has a raw appearance secondary to atrophy of the papillae.
  • Skin symptoms
    • Initially, the skin lesions of pellagra resemble a typical sunburn noted over parts of the body that have been exposed to the sun. They tend to be bilateral, tender and symmetrical in distribution.
    • Lesions may blister, vesiculate, and denude.
    • Eventually, the affected skin thickens and becomes hyperpigmented.
    • Parts of the body most commonly involved include the dorsum of the hands, feet, forearms, and legs. The face presents with a butterfly distribution over the cheeks, forehead, tip of the nose, and front V of the neck. The neck lesion is referred to as the Casal necklace, named after Don Gasper Casal who first described pellagra. Facial seborrheic dermatitis is noted in some patients. The scrotum, perineum [2] , and pressure points may also be involved.
  • Neurologic symptoms
    • Muscle weakness leads to gait problems.
    • Paraesthesia and a burning sensation are noted in some patients.
    • Mental status changes are early signs and become profound over time.
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Causes

Dietary deficiency of bioavailable niacin and of its precursor, tryptophan, or malabsorption of these nutrients results in pellagra. Other mechanisms can lead to the deficiency by compromising conversion of tryptophan to niacin. Certain peculiar dietary amino acid imbalances can affect the body's ability to synthesize niacin and also cause pellagra.

  • Primary: Compromised intake of niacin or tryptophan
    • Poverty
    • Poor nutrition
    • Chronic alcoholism
    • Neglect and abuse, resulting in malnutrition
    • Famine
    • HIV
    • Anorexia nervosa: This association needs to be kept in mind as the relationship of these conditions is symbiotic. Deficiency of NAD leads to the manufacture of hunger–suppressive endorphins eliminating normal satiety signals making it easier to starve one self.
    • Sometimes persons with alcoholism can develop secondary issues that combine to yield pellagra. [11]
  • Primary: Compromised ability to absorb ingested niacin and tryptophan
    • Malabsorptive states
    • Prolonged diarrhea
  • Secondary: Altered intermediary metabolism impacting niacin synthesis
    • Hartnup disease: This is an autosomal recessive disorder that compromises renal and intestinal transport of neutral amino acids. [12] The gene for this condition, which severely depletes tryptophan (the substrate for niacin synthesis), has been found by homozygosity mapping to be located on chromosome 5p15.
    • Fad diets: Individuals following diets high in leucine and low in tryptophan (eg, rich in yogurt, gelatin) or groups who consume large amounts of the grain sorghum may develop pellagra. [13] Excessive leucine alters the normal metabolism of tryptophan and thereby contributes to low levels of niacin.
    • Isoniazid therapy: Treatment with the antituberculosis drug isoniazid can lead to pyridoxine depletion. Pyridoxine, another B vitamin, is required as a coenzyme for the conversion of tryptophan to niacin. Isoniazid therapy is a well-recognized contributor to pellagra.
    • Carcinoid tumors: Niacin and serotonin are alternative pathways of tryptophan metabolism. Normally, serotonin production only represents a small fraction of tryptophan degradation. Patients with carcinomas have excessive serotonin production. Increased diversion of tryptophan toward serotonin production results in a deficiency of substrate available for niacin synthesis. [14]
    • Medications: Like isoniazid, most of the medications associated with pellagra disrupt its endogenous synthesis from tryptophan. These include 5-flurouracil, pyrazinamide, 6-mercaptopurine, hydantoins, ethionamide, phenobarbital, azathioprine, and chloramphenicol.
  • Multifactorial, miscellaneous, or unknown mechanism
    • Liver cirrhosis
    • Diabetes mellitus
    • Prolonged febrile illness, possibly leading to increased energy hence niacin requirements
    • Human immunodeficiency virus (HIV) disease: Besides simply malnutrition, diarrhea, and febrile state, plasma tryptophan levels are decreased in patients with HIV, inducing a pellagralike state. [15] Certain authors have recommended niacin supplementation as a general therapeutic principle for HIV in the third world. However, a recent report on a cohort of well-nourished HIV positive children without diarrhea found no evidence for niacin depletion in this group. [16]
    • The clinical features in a group of patients with alcoholism and pellagra included confusion and/or clouding of consciousness, marked oppositional hypertonus (gegenhalten), and myoclonus.
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