Vitamin C Deficiency (Scurvy)

Original Editors - Emily Buckingham, Martina Riney Students from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Martina Riney, Emily Buckingham, Kim Jackson, Lucinda hampton, Elaine Lonnemann, WikiSysop, 127.0.0.1 and Claire Knott  

Introduction

Vitamin C deficiency, also known as scurvy, is a disease primarily associated with socioeconomic status and access to food. Signs and symptoms are often readily visible in individuals who develop this disease. The classic constellation of corkscrew hairs, perifollicular hemorrhage, and gingival bleeding is highly suggestive of vitamin C deficiency. 

Image 1: Crystals of vitamin C

Etiology

Most animals require no exogenous vitamin C. For humans, however, vitamin C is an essential vitamin.

Humans lack the enzyme L-gulonolactone oxidase, and people must ingest it. A mutation in the gene coding for L-gulonolactone oxidase occurred, which no longer allows the human body to synthesize vitamin C. Thus, making it necessary for vitamin C to be taken in through the human diet to ensure the body is able to aid in wound healing, scar formation, repairing cartilage, bone, and teeth, and the ability to absorb iron.

• Vitamin C deficiency and its manifestations have largely been a product of inadequate dietary intake.
• Vitamin C is naturally found in fresh fruits and vegetables; for example, grapefruits, oranges, lemons, limes, potatoes, spinach, broccoli, red peppers, and tomatoes.
• Up to 90% of vitamin C is consumed in the form of vegetables and fruits. Lack of exposure to these foods has been the most frequent cause of the deficiency.
• Additionally, vitamin C is heat-sensitive, and historically, preparation (boiling or cooking) has removed the nutritional value.
• The vitamin C pool in the body is usually depleted in 4-12 weeks if one stops the intake of the vitamin.
• Total body storage of vitamin C is 1500 mg, and clinical features of deficiency occur after that level is reduced to less than 350 mg

Epidemiology

Vitamin C deficiency is defined as a serum concentration of less than 11.4 umol/L, and prevalence varies across the world

• As low as 7.1% in the United States
• Up to 73.9% in north India.

Although vitamin C deficiency is common, even in industrialized countries, overt scurvy is rare. Infantile incidence is also uncommon as both breast milk and fortified formula are an adequate source.

The following populations are at increased risk for a vitamin C inadequacy that could develop into a diagnosis of scurvy without appropriate dietary management.

• Smokers 
• Infants fed evaporated or boiled milk and Children with restricted diets 
• Children with autism, developmental delay, and cerebral palsy 
• Sailors at sea for months   
• Third world countries with limited foods
• Low income.
• Individuals with malabsorption 
• Individuals with cancer
• Individuals with chronic diseases such as end-stage renal disease or on hemodialysis

Pathophysiology

Scurvy as a clinical manifestation of severe vitamin C deficiency is caused by ascorbic acids role in collagen synthesis. Collagen type IV is the main constituent of blood vessel walls, skin, and specifically, the basement membrane zone separating the epidermis from the dermis. Changes include:

• Epigenetic DNA hypermethylation and inhibition of the transcription of various types of collagen found in skin, blood vessels, and tissue.
• Bone formation is altered and become brittle.
• The key feature of scurvy is hemorrhage which can occur in almost any organ.

Characteristics/Clinical Presentation

Vitamin C deficiency can lead to the following signs and symptoms:

• Anemia
• Bleeding gums
• Decreased ability to fight infection
• Decreased wound-healing rate
• Dry and splitting hair
• Easy bruising
• Gingivitis (inflammation of the gums)
• Nosebleeds
• Possible weight gain because of slowed metabolism
• Rough, dry, scaly skin
• Swollen and painful joints
• Weakened tooth enamel

Associated Co-morbidities

Osteopenia - osteopenia is defined by bone densitometry as a T score -1 to -2.5. There are many causes for osteopenia including calcium and vitamin D deficiency and inactivity. Genetics plays an important role in a person's bone mineral density and often Caucasian women with a thin body habitus who are premenopausal are found to have osteopenia. 

Iron deficiency - As the name implies, iron deficiency anemia is due to insufficient iron. Without enough iron, your body can't produce enough of a substance in red blood cells that enables them to carry oxygen (hemoglobin). As a result, iron deficiency anemia may leave you tired and short of breath.

Anemia

Folate deficiency - Folic acid (vitamin B9) works with vitamin B12 and vitamin C to help the body break down, use, and make new proteins. The vitamin helps form red and white blood cells. It also helps produce DNA. Folate is not stored in the body in large amounts, your blood levels will get low after only a few weeks of eating a diet low in folate. 

Vitamin K deficiency - Vitamin K (VK) deficiency can occur in any age group but is encountered most often in infancy. VK, an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins

Menagement

• 
  Direct replacement of vitamin C is standard, with up to 300 mg daily for children and 500 mg to 1000 mg daily for adults. The endpoint of replacement is one month or upon resolution of clinical sequelae.
• In addition to immediate supplementation, educate the patient on lifestyle modifications to ensure adequate intake, and recommend cessation of alcohol, and tobacco use.
• In the absence of a deficiency, daily requirements are up to 45 mg per day in children, 90 mg per day for men, 75 mg per day for women, and up to 120 mg per day for women who are lactating.

When choosing foods high in vitamin C, it is also important to consider how the food is prepared. Storing the food for long periods of time or cooking the product a certain way can reduce the amount of vitamin C the food contains. The best source of vitamin C is found most when consuming raw fruits and vegetables with high daily values. Cooking losses may be reduced by microwaving or steaming the food. Light exposure can also reduce the amount of vitamin C found in foods. According the NIH, juices kept in cartons should be chosen rather than juice contained in a clear bottle.

Dietary Management/Food Sources Vitamin C can be found in some foods naturally and other foods are fortified with vitamins. Table 2 lists the fruits and vegetables that contain naturally high in vitamin C content. Many cereals and beverages are fortified with vitamin C. Checking food labels can provide information on the amount of vitamin C contained in the product.

Table 2. Fruits and vegetables that contain high amounts of vitamin C. 

Fruits	Vegetables
Cantaloupe	Broccoli
Orange	Brussel Sprouts
Grapefruit	Cauliflower
Kiwi fruit	Spinach
Mango	Sweet and white potatoes
Papaya	Tomatoes and tomato juice
Pineapple	Winter squash
Strawberries	Green/red peppers
Raspberries	Turnip greens
Blueberries	Cabbage
Cranberries
Watermelon

Diagnostic Tests/Lab Tests/Lab Values

Plasma levels: A fasting serum ascorbic acid level greater than 0.6 mg/dL rules out scurvy. Scurvy generally occurs at levels below 0.1 mg/dL.
Leukocyte levels: The level of vitamin C in leukocytes more accurately correlates to tissue stores compared with serum levels, because these cells are not affected acutely by circadian rhythm or dietary changes. A level of zero indicates latent scurvy. Levels of 0-7 mg/dL reflect a state of deficiency.
Urinary levels: A more commonly used method is the ascorbic acid tolerance test, which quantitates urinary ascorbic acid over the 6 hours following an oral load of 1 g of ascorbic acid in water.
Radiographic findings: in infantile scurvy are diagnostic and may show any of the following:

• Subperiosteal elevation
• Fractures and dislocation
• Alveolar bone reabsorption
• Ground-glass appearance of cortex

Prognosis

Improvement of constitutional symptoms often occurs within 24 hours, with spontaneous bleeding improving over days to weeks. Corkscrew hairs take up to a month to resolve, and complete resolution is usually seen by three months. Bone abnormalities may require surgical intervention.

Differential Diagnosis

• Meningococcemia
• Osteomyelitis
• Pediatric Poliomyelitis
• Pediatric Syphilis
• Retinoblastoma Imaging
• Rheumatic Fever
• Rheumatoid Arthritis
• Rocky Mountain Spotted Fever
• Septic Arthritis