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. 

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, with rates as low as 7.1% in the United States and 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

Systemic Involvement

Circulatory System:

• Hypotension may be seen during the late stages of scurvy in response to vessels inability to constrict in response to stimuli. Complications in the heart can arise which include cardiac enlargement, electrocardiographic (ECG) changes, hemopericardium, and sudden death. Heart failure due to high-output can be seen in response to anemia.
• Anemia is present in 75% of the known cases of scurvy. Anemia appears in this population because of the blood loss into tissues, coexisting dietary deficiencies, malabsorption, and intravascular hemolysis.

Gastrointestinal System:'

If teeth have been erupted, gum hemorrhage is possible. The tissue surrounding the upper incisors are most commonly affected and present with a blue or purple color and a spongy feeling.

• Loose teeth can also be seen with a diagnosis of scurvy. Gum swelling, friability, bleeding, and infection can occur when loose teeth are present.
• Anorexia is sometimes seen with scurvy diagnoses; therefore, weight loss is commonly seen. A submucosal hemorrhage may be shown with an upper endoscopy.

Integumentary System/Skeletal: 

• Several skin problems can be noted with a diagnosis of scurvy. An early symptom is appearance bluish spots similar to bruises surrounding hair follicles on the shins, known as perifollicular hyperkeratotic papules. The hair is usually twisted like a corkscrew and very brittle susceptible to breakage. As the disease progresses, large patches of papules can form larger areas of bruising known as ecchymoses or purpura shown in the picture below.
• Vitamin C deficiency affects the production of collagen which can decrease efficiency of wound healing. This can affect new wounds and also decrease the integrity of old scars, leaving them at risk for skin breakdown.
• Sometimes bleeding within the joints can occur leading to painful hemarthroses. A subperiosteal hemorrhage can be palpable along the femur and sometimes the tibia in infants. If bleeding occurs in the femoral sheath, neuropathies can be seen and if there is bleeding into the muscles, woody edema can be present.

Nervous System:'

• Protrusion of the eyeball occurs due to an orbital hemorrhage and can be seen in the diagnosis of scurvy. Other ocular impairments can be seen which include dry eye similar to the diagnosis of Sjögren syndrome, subconjunctival hemorrhage, and bleeding in the eyelid, retrobulbar space, and periorbital are. Late in the diagnosis scleral icterus can be caused by hemolysis along with pale conjunctiva.

Physical Therapy Management

There are no direct physical therapy interventions for Scurvy. The patient may be referred to physical therapy for the treatment of impairments caused by Scurvy. These may include joint pain and stiffness, musculoskeletal pain, and musculoskeletal weakness, (particularly in the lower extremity).

Differential Diagnosis

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