bubble_chart Overview

Niacin deficiency disease, also known as pellagra, is primarily caused by a deficiency of niacin vitamins. Its clinical manifestations include neurotrophic disorders, dermatitis, and gastrointestinal and neuropsychiatric symptoms.

Niacin is pyridine β-carboxylic acid (in the structural formula above, R=OH), and niacinamide is the corresponding amine (R=NH2). Both niacin and niacinamide are white crystalline substances soluble in water. They are heat-stable and insensitive to light, air, or alkali. Since both share the same vitamin activity, they are often used interchangeably in the literature, with the term "P.P. factor" or niacin commonly used as a general designation.

Niacin is found in a wide variety of foods, particularly meat, fish, and wheat. However, it often exists in an unabsorbable bound form in foods, especially in corn. As a result, severe niacin deficiency primarily occurs in regions where corn is the staple food. Although Mexicans rely on corn as their staple, the incidence of deficiency is often lower than expected. This is due to a local practice of treating corn with lime water before preparing certain foods, which releases the bound niacin, making it absorbable.

Currently, there is insufficient experimental evidence to determine the precise human requirement. Generally, adults require approximately 0.5 mg per 1000 kcal, with a minimum of no less than 13 mg per person per day. Intake should be increased during pregnancy and lactation.

The amide of niacin is an absolutely essential component of hydrogen-carrying coenzymes. These coenzymes are coenzyme I—nicotinamide adenine dinucleotide (NAD, formerly called diphosphopyridine nucleotide, DPN) and coenzyme II—nicotinamide adenine dinucleotide phosphate (NADP, formerly called triphosphopyridine nucleotide, TPN). In both coenzymes, niacin is the group directly involved in hydrogen transfer.

The hydrogen transfer catalyzed by coenzymes I and II plays a decisive role in intermediate metabolism. The hydrogen acceptor function of these two coenzymes occurs at the para position of nicotinamide.

bubble_chart Etiology

Niacin deficiency can result from insufficient intake, malabsorption, increased demand, and other causes. Additionally, in normal individuals, tryptophan is converted into a portion of niacin, whereas in patients with carcinoid syndrome, tryptophan is diverted toward increased serotonin production, reducing endogenous niacin synthesis. Intestinal bacteria can also synthesize niacin, but synthesis decreases when bacterial activity is inhibited. Certain drugs, such as isoniazid, thioisonicotinamide, and 6-mercaptopurine, have structural similarities to niacin and competitively inhibit its utilization. Hereditary amino acid metabolic disorders and Hartnup disease are caused by defects in intestinal absorption and renal tubular reabsorption of tryptophan.

Vitamin PP includes two substances: niacin (nicotinic acid) and niacinamide (nicotinamide). These are absorbed in the small intestine, and in the body, niacin is converted into niacinamide, which is a crucial component of coenzyme I and coenzyme II. The niacinamide moiety in these coenzymes exhibits reversible hydrogenation and dehydrogenation properties, acting as a hydrogen carrier in biological oxidation and participating in numerous metabolic processes. Therefore, deficiency of niacin-related vitamins can lead to various pathological processes, most commonly affecting ectodermal tissues such as the skin, nervous system, and gastrointestinal tract.

Since sun exposure is a factor that induces skin lesions, some suggest that increased levels of porphyrins or similar substances in the body may sensitize the skin to sunlight and trigger the disease.

bubble_chart Clinical Manifestations

This disease can occur in various age groups, with males more affected than females, and is more prevalent in summer and autumn. The classic clinical triad consists of dermatitis, diarrhea, and mental disorders. These symptoms often appear sequentially, and it is rare for all three to coexist simultaneously. Typically, one or two manifestations are present, with skin and gastrointestinal symptoms being the most common, though cases with only mental disorders have also been observed.

Before the onset of the rash, patients often experience prolonged prodromal symptoms such as fatigue, insomnia, memory loss, and weight loss, which are frequently overlooked.

The typical skin lesions are symmetrically distributed on exposed areas of the limbs, primarily the back of the hands, fingers, wrists, outer forearms, back of the feet, ankles, extensor surfaces of the lower legs, face, neck, and upper chest. They may also appear on friction-prone areas of the limbs, while clothed areas are rarely affected. In the acute stage of attack, the lesions resemble sunburn, presenting as bright red or purplish-red patches accompanied by cutaneous pruritus or a burning sensation. The rash has clearly defined borders with adjacent skin. Later, the lesions turn reddish-brown with noticeable edema. In severe cases, large blisters may form on the erythema, which can rupture and exude serous fluid or dry into crusts, making them prone to secondary infections and pustules. After 2-3 weeks, the rash darkens to a deep reddish-brown or blackish-brown, and the skin gradually thickens with hyperkeratosis and scaling. During acute episodes, systemic symptoms such as high fever and weakness may occur.

In chronic sexually transmitted disease cases, the skin lesions become hard and rough, with increased brittleness and dark pigmentation, appearing almost black. They may develop rhagades and dry scales, often covered with black crusts due to bleeding. Areas prone to friction, such as the elbows, knees, and finger joints, often exhibit thickened skin and hyperkeratosis. The extensor surfaces of the lower legs may show ichthyosis-like changes.

The healing of skin lesions occurs centrifugally, with large-scale desquamation in the center and residual inflammation at the edges. Newly healed areas often appear atrophic.

Gastrointestinal symptoms include glossitis, loss of appetite, nausea, vomiting, abdominal distension and fullness, abdominal pain, and diarrhea, with glossitis and diarrhea being the most prominent. Early signs include redness of the tongue tip and margins, along with hypertrophic fungiform papillae. Later, the entire tongue, oral mucosa, pharynx, and esophagus become red and swollen, with superficial ulcers causing pain and dysphagia. Salivation increases, and over time, the tongue papillae atrophy, leaving the tongue dry, smooth, and red, resembling beef. Early stages often present with constipation, while the late stage (third stage) is marked by increased bowel movements, occurring several to over a dozen times a day. The stool is copious, watery, or pasty, with a foul odor. A few cases may experience tenesmus and bloody stools.

Neuropsychiatric symptoms may include dysphoria, anxiety, depression, disorientation, forgetfulness, paresthesia, suspicion, delusions, mania, tremor, limb stiffness or paralysis, and ataxia. Severe cases may exhibit lethargy, delirium, confusion, limb rigidity, and abnormal reflexes. Peripheral neuropathy may manifest as limb numbness and burning sensations. Myelitis is occasionally observed.

Other possible symptoms include angular cheilitis, vulvitis, vaginitis, and rashes in the perianal and scrotal areas, which are associated with concurrent vitamin B2 deficiency.

Cases with severe neuropsychiatric symptoms have a poorer prognosis. If left untreated, the mortality rate can be as high as 15-50%, with some deaths resulting from severe diarrhea leading to systemic exhaustion.

bubble_chart Diagnosis

The diagnosis is not difficult based on the triad of dermatitis, diarrhea, and mental disturbances, combined with nutritional status, laboratory tests, and therapeutic trials.

bubble_chart Treatment Measures

For special treatment, niacin or niacinamide is supplemented. Niacin has the side effect of vasodilation, so niacinamide is preferred. The therapeutic dose of niacinamide ranges from 100–150 mg/day to 300–1000 mg/day depending on the severity of the condition. For cases with diarrhea, uncooperative patients, ineffective oral administration, or difficulties, 50–100 mg can be administered via intramuscular or intravenous injection once daily. In pellagra, symptoms of peripheral neuritis and ocular issues typically respond better to vitamin B1 and riboflavin, respectively. Niacinamide has also been used to treat certain gastrointestinal disorders and sprue-like diarrhea syndrome, as well as stomatitis and glossitis caused by various factors. For preventive purposes, the daily dose can be up to 50 mg.

For glossitis, stomatitis, diarrhea, and concurrent infections, symptomatic treatment should be administered accordingly. For dermatitis, mild protective agents and keratolytic topical medications can be used.

bubble_chart Differentiation

This disease needs to be differentiated from the following diseases:

1. Vegetable solar dermatitis: There is a history of consuming certain vegetables and exposure to sunlight, often occurring in spring. The lesions present as diffuse, substantial edema accompanied by petechiae and ecchymoses, with subjective numbness and pain, and no other systemic disorders.
2. Photosensitive drug dermatitis: There is a clear history of medication use, without hyperkeratosis or hyperpigmentation.
3. Porphyria cutanea tarda: There is a history of exposure to chemicals and long-term alcohol consumption, without gastrointestinal or neurological symptoms.