Scurvy is a clinical syndrome that results from vitamin C deficiency. Tales from pirates and British sailors made the disease infamous. This disease was first reported in 1550 BC when people accurately described the diagnosis and treatment using onions and vegetables. Hippocrates officially termed the disease "ileos ematitis" with the description, “the mouth feels bad; the gums are detached from the teeth; blood runs from the nostrils… ulcerations on the legs; some of these heal… skin is thin.” In the 1700s, James Lind of the British Royal Navy determined the consumption of lemons and oranges led to remission of the disease, and in 1927, the structure of ascorbic factor was published, with the synthesis of ascorbic acid named vitamin C not long after.
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. Therefore, 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. While a small amount of vitamin C is found within leukocytes, adrenal glands, or the pituitary, there is very little storage of vitamin C in the body, and therefore, plasma concentration is largely related to recent intake. 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.
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. Risk factors for deficiency include alcohol intake, tobacco use, low-income, male gender, patients on hemodialysis, and those with overall poor nutritional status. 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.
Scurvy as a clinical manifestation of severe vitamin C deficiency is caused by ascorbic acids role in collagen synthesis. Collagen type IV is a main constituent of blood vessel walls, skin, and specifically, the basement membrane zone separating the epidermis from the dermis. Vitamin C allows hydroxylation and crosslinking of pro-collagen catalyzed by lysyl hydroxylase. Lack of vitamin C decreases transcription of pro-collagen. Additionally, a lack of ascorbic acid leads to epigenetic DNA hypermethylation and inhibits the transcription of various types of collagen found in skin, blood vessels, and tissue.
Punch biopsy and subsequent histopathology are similar to clinical manifestations showing dilated hair follicles, keratin plugging by corkscrew hairs, and non-inflammatory perifollicular hemorrhages.
Vitamin C deficiency manifests symptomatically after 8 to 12 weeks of inadequate intake and presents as irritability and anorexia. After these initial symptoms, dermatologic findings include poor wound healing, gingival swelling with loss of teeth, mucocutaneous petechiae, ecchymosis, and hyperkeratosis. Because of the disruption of disulfide bond formation both corkscrew and swan-neck hairs occur. Perifollicular hemorrhages often are localized to the lower extremities, as capillary fragility is unable to withstand the gravity-dependent hydrostatic pressure. This can result in “woody edema.” Nail findings include koilonychia and splinter hemorrhages. Beyond mucocutaneous manifestations, multiple other organ systems also are involved. Rheumatologic problems occur, including painful hemarthrosis and subperiosteal hemorrhage. This bleeding results from vascular fragility from impaired collagen formation. Osseous pathology also occurs and presents with fractures in brittle bones from disrupted endochondral bone formation. A “scorbutic rosary” at the costochondral junction and sternal depression may occur. Ocular manifestations of hemorrhage include flame hemorrhages, cotton-wool spots, and retrobulbar bleeding into optic nerves, resulting in atrophy and papilledema. The late disease may be life-threatening with anasarca, hemolysis, jaundice, and convulsions.
Diagnosis begins with the evaluation of risk factors and a physical examination. Dermoscopy can be used to aid in diagnosis, confirming follicular purpura and corkscrew hairs with a 4 mm punch biopsy of affected areas showing similar findings by histopathology. Serum testing for low plasma vitamin C (less than 0.2 mg/dL) is usually consistent with scurvy; however, as stated above, recent intake or supplementation may elevate plasma levels and not be reflective of a prior prolonged deficit. The level of vitamin C in leukocytes is more accurate when assessing the sparse vitamin C stores as they are less affected by acute dietary changes. A leukocyte vitamin C level of 0 mg/dL is indicative of latent scurvy. Zero to 7 mg/dL is consistent with deficiency, and greater than 15 mg/dl is adequate.
In addition to assessing vitamin C levels, screening for concomitant other vitamin deficiencies should be undertaken. As deficiency is primarily related to poor intake, those affected also may have poor intake of other essential vitamins and minerals. Vitamin B12, folate, calcium, zinc, and iron have been notably low in this patient population. Additionally, vitamin C’s role in iron absorption cause those with scurvy to be more prone to bleeding and iron deficiency, in particular, should be assessed.
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. Alternative treatment regimens for adults include one to 2 g for up to 3 days followed by 500 mg daily for a week followed by 100 mg daily for up to 3 months. 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 abscence of 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.
Differential diagnosis includes many cutaneous purpuric pathologies including immune thrombocytopenic purpura, Henoch-Schonlein purpura, disseminated intravascular coagulation, Rocky Mountain spotted fever, meningococcemia, or hypersensitivity vasculitis. Mucosal involvement may mimic necrotizing gingivitis. Other vitamin deficiencies including niacin, biotin, and zinc may present with skin changes; however, a symmetric, hyperpigmented rash on sun exposed areas with the former and alopecia and lack of petechial and follicular findings in the latter two easily distinguish them from scurvy.
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.
As stated, vitamin C has very little storage in the body; however, uncommonly, toxicity from over-supplementation can occur. As vitamin C is excreted in the urine, its effect on other urinary metabolites has been explored. Notably, vitamin C has been shown to increase renal oxalate excretion and subsequent calcium oxalate crystals and stone formations.
All healthcare workers should encourage adequate nutrition in their patients. While scurvy is very rare in North America it may develop in people deprived of food or those with intestinal problems. Whenever deficiency of one vitamin is discovered, it is important to screen for concomitant other vitamin deficiencies. As deficiency is primarily related to poor intake, those affected also may have a poor intake of other essential vitamins and minerals. Vitamin B12, folate, calcium, zinc, and iron have been notably low in this patient population. Additionally, vitamin C’s role in iron absorption cause those with scurvy to be more prone to bleeding and iron deficiency, in particular, should be assessed.
When patients with Vitamin C deficiency are diagnosed, treatment is with supplements plus a change in diet. 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. (Level V)
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