Introduction
Background
Scurvy is a condition that has been described for at least 500 years. In 1753, Sir James Lind demonstrated that the condition could be prevented in British sailors by adding citrus fruits to their diets. Forty years later, Sir Gilbert Blane convinced the admiralty of the British Navy to approve a preventive dietary regimen for sailors. Prior to that, all sea voyages had to be limited to 10 weeks or less to rehabilitate the crews. Scurvy produces characteristic perifollicular hemorrhages and gingival changes as well as hematologic, joint, and cardiac complications.
Pathophysiology
Scurvy is caused by a prolonged deficiency of vitamin C intake that results in defective collagen synthesis, tissue repair, and synthesis of lipids and proteins. It functions both as a reducing agent and as an antioxidant and is required for many physiologic functions, including metabolism of iron and folic acid, resistance to infection, and integrity of blood vessels.
The clinical manifestations of scurvy are primarily due to abnormal collagen synthesis resulting from a lack of vitamin C. Vitamin C is a cofactor required for the function of several hydroxylases. The absence of vitamin C reduces the function of prolyl hydroxylase, which is required to form hydroxyproline, an amino acid found in collagen but rarely found in other proteins. The presence of hydroxyproline in collagen stabilizes the collagen triple-helix structure by forming interstrand hydrogen bonds. Collagen lacking hydroxyproline is more fragile and contributes to the clinical manifestations of scurvy, including purpura due to vessel wall fragility. In addition, osteoid matrix formation is defective and bone resorption is increased in persons with vitamin C deficiency.
Frequency
United States
Scurvy is rare in the United States. Vitamin C deficiency, however, was reported in 10-14% of adults in the Third National Health and Nutrition Survey in 1994, emphasizing the importance of recognizing this disorder.1 Patients at risk include those with chronic malnutrition, such as persons with alcoholism, elderly people, and men who live alone (widower scurvy). Other reported cases include people with monotonous or peculiar diets, including patients undergoing dialysis and those with cognitive disorders,2,3 psychiatric illnesses,4 malabsorption, inflammatory bowel disease, cancer on chemotherapy, Whipple disease, or dyspepsia (those who avoid acidic foods). Scurvy may occur in infants fed evaporated or condensed milk formulas.
Infantile scurvy was fairly common in the United States during the 1950s, but changes in feeding practices in the next decade almost completely eliminated the disorder. If a mother has an adequate diet, breast milk contains sufficient vitamin C for a baby's needs. Commercially available formulas and many prepared fruit juices are fortified with vitamin C.
International
Scurvy is a problem when general malnutrition exists, as in some impoverished, underdeveloped third world countries. Scurvy also occurs in epidemic proportions in international refugee camps and in populations that subsist mainly on cereal grains.
Mortality/Morbidity
Until minimal daily requirements of vitamin C were supplied, scurvy plagued prolonged naval voyages and military campaigns as personnel succumbed to its devastating effects. Lethargy, fatigue, and hemorrhagic manifestations of impaired collagen synthesis affecting oral, ophthalmic, musculoskeletal, cardiac, and gastrointestinal structures and functions incapacitated or killed more people than enemy action in many cases. Manifestations of scurvy tend to dramatically improve, resolving within weeks, if adequate vitamin C is given in daily doses to recoup body stores.
Race
No racial predilection for scurvy has been sited in the literature
Sex
No sex predilection for scurvy has been sited in the literature.
Clinical
History
- Symptoms of scurvy develop after 3 months of severe or total vitamin C deficiency.
- Patients may complain of weakness, fatigue, shortness of breath, and aching limbs. Left untreated scurvy progresses, with potentially fatal complications, including cerebral hemorrhage or hemopericardium.
- Infantile scurvy is uncommon before age 7 months, and clinical and radiographic manifestations rarely occur in infants younger than 3 months. Early clinical manifestations consist of pallor, irritability, and poor weight gain.
- In advanced infantile scurvy, the major clinical manifestation is extreme pain and tenderness of the arms and, particularly, the legs. The baby is miserable and tends to remain in a characteristic immobilized posture from subperiosteal pain, with semiflexion of the hips and the knees, as described by Thomas Barlow in 1884. The body is both wasted and edematous, and petechiae and ecchymoses are commonly present.
Physical
- Symptoms and signs of scurvy may be remembered by the 4 Hs: hemorrhage, hyperkeratosis, hypochondriasis, and hematologic abnormalities. Patients may be miserable, irritable, depressed, resentful, and full of aches and pains. The body is both wasted and edematous, and petechiae and ecchymoses are commonly present.
- The earliest signs are found on the skin, often on the shins, after 3 months of severe or total vitamin C deprivation. Perifollicular hyperkeratotic papules are surrounded by hemorrhagic halos. The central hairs are twisted like corkscrews, and they may become fragmented. The posterior parts of the legs develop purpura that may coalesce.
- Soft, spongy swelling of the gums and gingival interdental papillae is followed by gingival hemorrhage, which is accentuated by coexistent poor oral hygiene and periodontal disease. Disrupted tooth formation and loosening of teeth may result in permanent defects of dentition.
- Ocular features include those of Sjögren syndrome, subconjunctival hemorrhage, and bleeding within the optic nerve sheath. Funduscopic changes include cotton wool spots and flame-shaped hemorrhages.
- Bleeding into the joints causes exquisitely painful hemarthroses. Subperiosteal hemorrhage may be palpable, especially along the distal portions of the femurs and the proximal parts of the tibias of infants. In advanced cases, clinically detectable beading may be present at the costochondral junctions of the ribs. This finding is known as the scorbutic rosary. Bleeding into the femoral sheaths may cause femoral neuropathies, and bleeding into the muscles of the arms and the legs may cause woody edema.
- Heart complications include cardiac enlargement, ECG changes (reversible ST-segment and T-wave changes), hemopericardium, and sudden death.
- Anemia develops in 75% of patients, resulting from blood loss into tissue, coexistent dietary deficiencies (folate deficiency), altered absorption and metabolism of iron and folate, gastrointestinal blood loss, and intravascular hemolysis. The anemia is most often characterized as normochromic and normocytic. Vitamin C enhances iron absorption by reducing dietary iron from the ferric form to the ferrous form. Thus, vitamin C deficiency may reduce the availability of intracellular iron. Vitamin C is also necessary to convert folic acid to its active metabolite, folinic acid.
- Other problems include increased redness and swelling in recently healed wounds and the failure of new wounds to heal.
Causes
- Scurvy is caused by a prolonged deficiency of vitamin C intake.
- Most animals can convert gluconate into ascorbate. Primates, including humans, and guinea pigs as well as a few other species cannot convert gluconate into ascorbate and, therefore, require exogenous ascorbic acid, otherwise known as vitamin C. Humans obtain 90% of their intake of vitamin C from fruits and vegetables, and cooking these sources decreases vitamin C content 20-40%. The US Food and Drug Administration recommends a daily dietary allowance of vitamin C of 75 mg for women and 90 mg for men.
- The total body pool of vitamin C is approximately 1500 mg. The absorbed vitamin is found ubiquitously in body tissues, with the highest concentrations in glandular tissue and the lowest concentrations in muscle and stored fat. Ascorbic acid is metabolized in the liver by oxidation and sulfation. The renal threshold for excretion by the kidney in urine is approximately 1.4 mg/100 mL plasma. Excess amounts of ascorbic acid are excreted unchanged or as metabolites. When body tissue or plasma concentrations of vitamin C are low, excretion of the vitamin is decreased. Scurvy occurs after vitamin C has been eliminated from the diet for at least 3 months and when the body pool falls below 350 mg.
- Ascorbic acid is prone to oxidation in vivo, and body stores are affected by environmental and lifestyle factors (eg, smoking), biological conditions (eg, inflammation, iron excess), and pathological conditions (eg, malabsorption) that may alter its oxidation. One study identified a genetic polymorphism of the human plasma protein haptoglobin, Hp 2, that may be an important non-nutritional modifying factor in the pathogenesis of vitamin C deficiency. The Hp 2-2 polymers are less efficient inhibitors of hemoglobin-driven oxidative stress, leading to ascorbic acid depletion. The Hp 2-2 phenotype is present in 35% of whites and 50% of South Asians and East Asians and may help identify patients who are more prone to develop clinically significant vitamin C deficiency.5
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Further Reading
Keywords
infantile scurvy, Barlow disease, Barlow's disease, vitamin C deficiency, ascorbic acid, widower scurvy, chronic malnutrition
