bubble_chart Overview

Vitamin A deficiency is a systemic disease caused by a lack of vitamin A in the body, characterized primarily by keratinizing metaplasia of epithelial tissues throughout the body. Ocular symptoms appear early and prominently, including reduced dark adaptation, followed by dryness of the conjunctiva and cornea, and eventually corneal softening or even perforation. Hence, it is also referred to as night blindness, xerophthalmia, or keratomalacia. This condition is commonly seen in malnourished infants and young children with chronic diarrhea, with the peak incidence occurring between 1 to 4 years of age. It is rare in children over 6 years old. The disease is prevalent in developing countries in Asia and Africa and remains relatively common in remote areas of China.

bubble_chart Etiology

1. Improper Diet: At birth, infants have very little vitamin A stored in their liver, which is quickly depleted. However, colostrum is extremely rich in vitamin A, and both human milk and cow's milk are the primary sources of vitamin A for infants. Other foods such as vegetables, fruits, eggs, and liver can also provide sufficient vitamin A. Therefore, a proper diet can supply enough vitamin A to prevent deficiency. However, during infancy, if the diet is too simplistic—such as insufficient milk intake without supplementary foods—it can easily lead to subclinical vitamin A deficiency. After weaning, if infants are fed only rice cakes, flour paste, porridge, or skimmed milk for an extended period without adding protein- and fat-rich complementary foods, deficiency can occur.

2. Digestive System Diseases: Chronic digestive disorders such as prolonged diarrhea, chronic dysentery, intestinal tuberculosis, and pancreatic diseases can impair vitamin A absorption. The liver is the main organ for vitamin A metabolism and storage, and bile salts in the gallbladder emulsify lipids, promoting vitamin A absorption while enhancing the activity of β-carotene-15,15´-oxygenase, facilitating its conversion into retinol. Therefore, hepatobiliary diseases such as congenital biliary atresia and chronic hepatitis can easily lead to vitamin A deficiency. Toxic hepatitis caused by viral infections or concurrent infectious diseases can also result in vitamin A deficiency and should be closely monitored.

3. Consumptive Diseases: Conditions such as chronic respiratory infections, protracted pneumonia, and measles can exacerbate vitamin A deficiency when intake is already insufficient due to increased consumption. Additionally, long-term use of mineral oil (e.g., liquid paraffin), neomycin, and methotrexate can interfere with vitamin A absorption. Malignant tumors and urinary system diseases may increase vitamin A excretion. Protein deficiency affects the synthesis of retinol-binding protein, leading to reduced plasma vitamin A levels and deficiency symptoms.

4. Hypothyroidism and Diabetes: Both conditions can impair the conversion of β-carotene to retinol, resulting in vitamin A deficiency. Meanwhile, large amounts of carotene accumulate in the blood and skin, resembling jaundice, though the bulbar conjunctiva does not appear yellow.

5. Zinc Deficiency: Reduced levels of prealbumin (which binds vitamin A) and vitamin A reductase lead to the inability to utilize vitamin A, causing its excretion and subsequent deficiency. Recent reports suggest that changes in nutritional status can also affect vitamin A utilization. {|104|}

bubble_chart Pathogenesis

Vitamin A exists in two forms, namely β-ionone and its derivatives, and provitamin A, also known as carotenoids, both of which are fat-soluble. The former are unsaturated monohydric alcohols, which function in the body as retinol (vitamin A₁) and 3-dehydroretinol (vitamin A₂). Vitamin A₁ is found in the liver, fat, milk, and egg yolks of mammals and marine fish; vitamin A₂ is found in the liver of freshwater fish and in birds that consume these fish, with the latter's biological potency being only 40% of the former. Carotenoids are polyene compounds primarily derived from plants, the most important of which is β-carotene, which is cleaved by 15,15´-oxygenase to form two molecules of retinol, transported via the lymphatic vessels of the intestinal mucosa to the liver for storage. Retinol from food combines with palmitic acid in the small intestinal mucosa to form retinyl palmitate, which is then incorporated into chylomicrons and transported via the lymphatic system to the liver for uptake and storage. As needed by the body, it is hydrolyzed into free retinol, which binds with specific transport proteins in the plasma, namely retinol-binding protein (RBP) and prealbumin, to be transported to other tissues. Both vitamin A and carotenoids are relatively stable compounds. They are heat-, acid-, and alkali-resistant, insoluble in water, stable in oils, and minimally affected by general cooking processes. Antioxidants such as vitamin C and E may enhance their stability.

The main functions of vitamin A are: ① Formation of photosensitive substances in visual cells, maintaining visual function in low light. The rod cells in the human retina contain the photosensitive substance rhodopsin, which is composed of 11-cis-retinal and opsin and is essential for vision in dim light. This binding is a continuous reaction requiring enzymes and energy. Each rhodopsin molecule contains only one retinal molecule. Upon exposure to light, 11-cis-retinal is converted to all-trans-retinal, which cannot bind with opsin and separates from it—a process called bleaching. At this point, objects cannot be seen clearly in the dark. Through a series of chemical reactions, it is converted back to 11-cis-retinal, which recombines with opsin to form rhodopsin, the substance sensitive to dim light. When its synthesis decreases, the body's sensitivity to low light diminishes, dark adaptation weakens, and in severe cases, night blindness occurs. Rhodopsin requires constant regeneration and renewal, necessitating continuous vitamin A supplementation to maintain dark adaptation ability. ② Maintaining the stability of cell membranes and ensuring the integrity and health of skin and mucosal epithelial cells; ③ Promoting normal growth of bones and teeth; ④ Enhancing immune function and the body's disease resistance; ⑤ Maintaining normal reproductive system function; ⑥ β-carotene can reduce light sensitivity in children with erythropoietic protoporphyria, thereby alleviating symptoms.

When vitamin A is deficient, these physiological processes cannot proceed normally, leading to a series of clinical manifestations.

bubble_chart Pathological Changes

The main pathological changes of vitamin A deficiency are alterations in epithelial cells, initially showing atrophy followed by a hyperplastic response. The original cuboidal or columnar epithelium undergoes metaplasia into stratified squamous epithelium, with excessive keratinization of the surface layer and a tendency to desquamate. Epithelial tissues in various parts of the body do not transform simultaneously, and the degree of transformation varies. Generally, lesions in the conjunctiva and cornea are most prominent, followed by the respiratory tract, lacrimal glands, salivary glands, esophageal mucosa, pancreatic ducts, and epithelial cells of the urinary and reproductive systems, which can all undergo similar changes. When the skin becomes excessively keratinized, the sebaceous and sweat glands atrophy. With treatment, these pathological changes gradually disappear.

bubble_chart Clinical Manifestations

If there is a deficiency or malabsorption of vitamin A in the diet, symptoms may appear within a few weeks. In infants with congenital biliary obstruction or infantile hepatitis syndrome, if complicated by pneumonia, ocular xerosis can develop rapidly and should be noted early.

1. Ocular symptoms The earliest symptom is difficulty seeing in dim light and disorientation, leading to night blindness, which can easily be overlooked without careful examination. After several weeks to months, the conjunctiva and cornea gradually lose their luster and become abnormally dry when exposed to air. The conjunctiva near the cornea is the first to show changes, becoming dry and wrinkled, with keratinized epithelium gradually forming irregularly sized, foam-like white spots, known as conjunctival xerotic plaques or Bitot's spots. At this stage, the lacrimal gland epithelial cells degenerate, reducing tear secretion, and the lacrimal ducts become blocked by shed epithelial cells, further decreasing tear production. The child experiences photophobia, a sensation of dryness and discomfort in the eyes, pain, and a gritty feeling, frequently blinking or rubbing their eyes, which can lead to secondary infections. The cornea gradually becomes dry, cloudy, and develops white nebulae, softening as the condition progresses. In advanced cases, corneal ulcers may form, leading to necrosis, perforation, iris prolapse, and corneal scarring within days to weeks, ultimately resulting in blindness. The retina is also affected, showing signs of fundus xerosis. Both eyes are usually affected simultaneously, though sometimes sequentially; unilateral involvement is rare. Although ocular symptoms appear early in most cases, older children often develop eye symptoms after other manifestations.

2. Skin manifestations The skin becomes dry, hyperkeratotic, and scaly. Keratinized material fills the hair follicles and protrudes from the epidermis, giving a goosebump or rough sandpaper-like texture when touched. These changes are most prominent on the extensor surfaces of the limbs and shoulders and are uncommon in infants under 4 years old. Other signs include ridged, dull, brittle, and cracked nails, as well as dry, brittle hair that falls out easily.

3. Other manifestations Due to epithelial hyperplasia and keratinization of the respiratory and urinary tracts caused by vitamin A deficiency, along with weakened immune function, secondary respiratory infections and pyuria are common. The taste buds on the tongue become keratinized, leading to loss of taste and reduced appetite, and some children may experience vomiting. Delayed physical growth may be observed during infancy and early childhood. Severe vitamin A deficiency can impair hematopoiesis, resulting in anemia that does not respond to iron therapy. Some reports indicate that infants may experience choking during feeding, which can be alleviated with vitamin A supplementation.

bubble_chart Diagnosis

In cases with obvious ocular symptoms, diagnosis is not difficult when combined with feeding history, chronic digestive system disorders, or a history of wasting diseases. Since vitamin A deficiency often presents with complications, a thorough eye examination should be conducted for children with malnutrition, chronic diarrhea, chronic dysentery, or prolonged dietary restrictions after measles, especially if they exhibit photophobia or frequent blinking. Older children should also be assessed for skin changes. Early or atypical cases may show mild ocular changes, which can be easily overlooked, particularly in infants and young children. For suspected cases, the following tests can aid diagnosis: 1. Gently scrape a small amount of material from the conjunctival membrane with a cotton swab moistened with saline and examine under a microscope for keratinized epithelial cells. 2. Serum vitamin A measurement is the most reliable indicator. Normal levels in children range from 300–500 μg/L, while deficiency is indicated by levels below 200 μg/L or even 100 μg/L. 3. Collect approximately 10 mg of fresh midstream urine, add a few drops of 1% gentian violet solution, mix well, and perform an epithelial cell count. Normal urine contains no more than three epithelial cells per cubic millimeter; higher counts may indicate vitamin A deficiency, excluding urinary tract infections. Examination of urine sediment under high-power microscopy can further assess the degree of keratinization in epithelial cells.

bubble_chart Treatment Measures

1. General Therapy: Improve diet by adding milk, egg yolk, liver, and foods rich in carotenoids. Actively treat underlying conditions such as intestinal infections, liver and gallbladder diseases, and other systemic disorders to restore normal metabolism in the body, thereby facilitating the absorption and utilization of carotenoids and vitamin A.

2. Vitamin A Therapy: ① Administer cod liver oil or other concentrated vitamin A preparations. Initially, give concentrated cod liver oil three times daily, with a total daily dose containing approximately 25,000 IU of vitamin A. After significant improvement in ocular symptoms, gradually reduce the dosage as appropriate. Following this treatment, night blindness usually improves within hours, while xerophthalmia may take 2–3 days to show improvement. Skin keratosis papules respond even more slowly, requiring 1–2 months of treatment to return to normal. ② For severe or rapidly progressing ocular symptoms, or cases accompanied by diarrhea or liver disease, begin with an intramuscular injection of vitamin AD solution (0.5–1 ml per dose, containing 25,000 IU of vitamin A and 2,500 IU of vitamin D per 0.5 ml) once daily. Symptoms typically improve significantly after 2–3 injections, after which oral concentrated preparations can be administered as needed. For critically ill patients or those with digestive disorders, if oil-based preparations are poorly absorbed, a water-soluble vitamin A formulation can be given in larger doses for emergency treatment. Both oral and injectable water-soluble forms act faster than oil-based preparations.

3. Local Therapy for Eye Disease: Regularly cleanse the eyes with a boric acid solution or apply antibiotic eye ointments (e.g., chlortetracycline or erythromycin) to control infection. Additionally, instill 1% atropine to dilate the pupil and prevent iris prolapse or adhesions. Exercise caution during eye care: when applying eye drops, place the thumb on the upper orbital rim and gently lift the eyelid, avoiding pressure on the eyeball to prevent corneal perforation. If ulcers are deep, even high doses of vitamin A may not prevent vision loss or blindness. Therefore, local treatment should be initiated as early as possible.

bubble_chart Prevention

The primary goal is to provide children with sufficient vitamin A. The methods of supply vary depending on age. During the fetal period, pregnant women should be given ample amounts of vitamin A-rich foods. During infancy, emphasis should be placed on breastfeeding, supplemented with whole milk, legume-based foods, carrot puree, egg yolks, etc. Additionally, spinach soup and tomato juice can be added. Premature infants have a weaker ability to absorb fats and vitamin A, so concentrated vitamin A should be administered early, but care must be taken to avoid overdose and toxicity. For older children who can consume a variety of foods, vitamin A deficiency is generally not a concern. Infants require approximately 1,500–2,000 international units (IU) of vitamin A daily (1 IU of vitamin A is equivalent to 0.3 μg of retinol, and 1 μg of retinol is equivalent to 6 μg of β-carotene). Children require 2,000–4,500 IU. In cases of chronic illness where absorption is reduced and consumption is increased, 3,000–5,000 IU can be given daily, but dosage should be adjusted promptly, as prolonged excess can lead to chronic toxicity. Preventing vitamin A deficiency not only prevents night blindness and xerophthalmia, avoiding blindness, but also ensures normal child development and reduces the risk of infections in various epithelial tissues. According to a 1986 study by the Tianjin Children's Health Institute and others on serum vitamin A levels in 774 rural children, 39.3% had levels below 200 μg/L, with the highest deficiency rate observed in the 6-month age group. The study also showed a positive correlation between serum vitamin A levels and growth indicators, indicating that subclinical vitamin A deficiency is widespread in rural China and requires urgent attention. In impoverished border areas and regions with high blindness rates, three key measures should be prioritized: ① Raising awareness of the link between vitamin A supply and blindness; ② Strengthening prevention and treatment of diarrhea and measles; ③ Ensuring adequate daily vitamin A intake.