Clinical Manifestations and Pathology

Pellagra usually appears in the winter or spring and seems to disappear a few months later, only to recur the following year. Symptoms become progressively worse. In the early stages of the disease, patients feel weak, tire easily, lose their appetites, and cannot sleep. The first definite sign of the disease, however, is a reddening of the skin, frequently mistaken for sunburn. In severe cases, the skin manifestation progresses rapidly and makes the disease easy to distinguish. It may appear on the feet and ankles, hands and forearms ("pellagra gloves"), or around the neck, and across the face. Lesions on the neck are called Casal's necklace, after the Spanish physi-

cian Gaspar Casai, who first identified mal de la rosa in 1735. In ail cases, the skin manifestations are symmetrical and bilateral.

The first published description of pellagra, written by the French physician François Thièry in 1755, was graphic. The skin, he wrote, is "a horrible crust, dry, scabby, blackish, crossed with cracks, which causes much pain to the sufferer and throws off a very foetid odor." Although lesions usually occur on those parts of the body exposed to the sun, the genitals and pressure points may be affected. There is a clear demarcation between the affected and normal skin. Pellagra lesions sometimes peel, beginning from the center and spreading to the edges. In acute cases blisters occur. These may rupture, leaving weeping areas that resemble third-degree burns.

Although dermatitis is the diagnostic feature, the disease also affects the gastrointestinal tract. Patients may be nauseated or suffer from excessive salivation, have a reddened tongue, or experience a burning sensation in the abdomen. These symptoms, although associated with pellagra, are usually due to deficiencies of B-complex vitamins other than niacin. Diarrhea, sometimes intense, is characteristic of the disease.

Particularly distressing are the neurological symptoms. Insomnia is an early complaint, and patients are often apprehensive. Peripheral neuritis makes the movements of pellagrins uncertain. Mental aberrations are varied. Some patients suffer only mild depression, confusion, or loss of memory. Others manifest psychotic changes severe enough for admission to a mental hospital. Some are suicidal. All these symptoms are caused by biochemical changes still imperfectly understood. The amino acid composition of the skin is altered, and the collagen markedly reduced. The low level of urocanic acid in the skin may be related to pellagra's characteristic photosensitive rash since urocanic acid acts as an ultraviolet ray trap. There are also changes in the electrical rhythms of the brain, even if mental symptoms are not present. The majority of pellagra victims show an absence of normal alpha rhythms, but theta wave activity and high-voltage delta wave activity are found. These changes are believed to be related to an altered metabolism, in the brain, of serotonin, which is synthesized from tryptophan. Serotonin is one of the biogenic amines that modulate behavior.

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