Are You Confident of the Diagnosis?

What to be alert for in the history

Patients with scurvy may have a history of unusual or restrictive diets, particularly those deficient in citrus fruits.

Characteristic findings on physical examination

Mucosal findings (gingival hemorrhage, tooth loss and poor dentition), cutaneous lesions (petechiae, purpura especially in response to minor trauma, separation of previously healed scars, poor wound healing, phrynoderma), hair findings (corkscrew hairs on the extremities), and nail findings (splinter hemorrhages) (Figure 1).

Figure 1.

Scurvy. Note the perifollicular purpura and the corkscrew hairs characteristic of severe vitamin C deficiency in this patient on chronic total parenteral nutrition. (Photo courtesy of Albert Yan, MD, and the Section of Pediatric Dermatology at the Children’s Hospital of Philadelphia.)

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Bone pain is often a presenting sign in children. A scorbutic rosary may be present (thickening of the costochondral junctions of the ribs).

Expected results of diagnostic studies

While the diagnosis is often evident from the clinical examination, confirmation can be obtained from a blood sample to obtain a plasma or leukocyte ascorbic acid level (2.5 to 5mg/L indicates depletion of stores of vitamin C; 0.1 to 2.5mg/L indicates deficiency; less than 0.1mg/L indicates severe deficiency and symptoms of scurvy are typically manifest).

Hess’ sign may be present: development of petechial lesions distal to the site of blood pressure cuff use to measure blood pressure.

Histopathology of scurvy lesions may show findings indicative of impaired collagen formation, including decreased collagen, capillary ectasia, and hemorrhage from capillary rupture.

Imaging studies of the long bones may reveal a pathognomonic sclerotic area near the metaphyses indicating scurvy (Wimberger sign). This widening of the zone of provisional calcification results from suppression of osteoblastic activity but while cartilage formation is decreased, mineralization continues leading to these changes. Periosteal elevation may also occur as a result of subperiosteal hemorrhage from capillary fragility as a direct result of ascorbic acid deficiency. “Ground glass” changes may be present in the epiphyseal areas.

Diagnosis confirmation

Differential diagnoses include conditions that predispose to findings of petechiae, purpura, arthralgias, arthritis, bone pain, periosteal changes from hemorrhage, and visceral hemorrhage: petechiae/purpura (idiopathic thrombocytopenic purpura, bleeding diatheses, leukemia, bacterial septicemia; non-accidental trauma); arthralgias/arthritis/bone pain (osteomyelitis, rheumatic fever, syphilis).

Who is at Risk for Developing this Disease?

Scurvy, as with other nutritional deficiency disorders, is associated with deprivation states, such as poverty, war, and famine.

Historically, scurvy as a disease has been known as early as 1550 BC. The Ebers papyrus describes onion as remedy for a condition resembling scurvy. Onions contain between 5 and 32mg of vitamin C per 100 grams onion. Hippocrates also reported on a condition consistent with scurvy characterized by “foetid breath, lax gums, and hemorrhage from the nose” (as quoted by the 18th century British physician James Lind).

Between the late 15th century through the mid-19th century during the so-called Age of Sail, seafarers were at particular risk for scurvy due to a lack of information about the causes of the disease and the inability to maintain stocks of fresh citrus fruits during long voyages. During this period, the mortality from scurvy was estimated to be about 50% among those aboard, and ship captains often doubled their staffing needs to compensate for anticipated losses. In fact, an estimated 2 million sailors died of scurvy during the Age of Sail and the mortality from scurvy exceeded deaths from storms, shipwrecks, warfare, and all other diseases combined.

Today, national rates of vitamin C deficiency are estimated around 7% in the United States.

Patient populations at special risk where vitamin C deficiency has been reported in association include:

– Patients with eating disorders, including those with anorexia nervosa with vitamin C deficiency resulting from globally restricted diets

– Children with autism-spectrum disorders who tend to have self-restricted diets that often are lacking in foods rich in vitamin C

– Patients receiving chronic total parenteral nutrition (TPN) using protocols or equipment that may predispose to premature degradation of vitamin C

– Patients after bariatric surgery (up to 34%) at 2-year follow-up in one study, due to problems of malabsorption

– Patients with liver transplantation have recently been reported to have vitamin C deficiency.

What is the Cause of the Disease?

Vitamin C or ascorbic acid is not natively synthesized by human organisms because we lack the enzyme L-gulonolactone oxidase, which in other organisms allows native hepatic conversion of glucose to ascorbic acid.

Vitamin C is a necessary cofactor in the synthesis of collagen. It is involved in collagen polypeptide synthesis, post-translational hydroxylation, and specifically interacts as a cofactor for lysyl and prolyl hydroxylase.

Systemic Implications and Complications

Because collagen is a key structural protein for blood vessels, bone, and skin, deficiency of vitamin C resulting in impaired collagen synthesis manifests as problems in tissues containing collagen.

– Skin: petechiae and purpura, wound dehiscence, phrynoderma, edema, corkscrew hairs

– Oral mucosal: Poor dentition, gingival hemorrhage

– Musculoskeletal: bone pain, arthralgias, arthritis, hemarthrosis, pathologic fracture, scorbutic rosary, myalgia, muscular hematomas

– Neurologic: strokes

– Hematologic: anemia, visceral hemorrhage

Treatment Options

Vitamin C supplementation either intravenously (for severe cases) or orally (for mild to moderate cases) is advised. Once supplementation is completed, maintenance therapy is needed to prevent recurrence of the disease.

Treatment Doses

Vitamin C 100mg 3 times daily, orally or intravenously until symptoms and signs resolve; then switch to maintenance doses using Recommended Daily Allowances (RDAs) as a minimum.

– Oral route is reasonable for mild to moderate disease.

– Intravenous route is necessary for those with gastrointestinal malabsorption.

RDA for Maintenance of Adequate Stores of Vitamin C (Food and Nutrition Board, Institute of Medicine)

0-6 months: 40mg per day

7-12 months: 50mg per day

1-3 years: 15mg per day

4-8 years: 25mg per day

9-13 years: 45mg per day

14-18 years: 75mg per day (male) or 65 mg per day (female)

Note: The average orange has about 70 mg of vitamin C.

Patients with scurvy due to degradation of vitamin C in those receiving chronic TPN:

– Vitamin C degradation is oxygen-dependent and requires photoexcitation.

– Ascorbic acid is degraded to dehydroascorbic acid, which is biologically inactive.

– To minimize problems related to depletion of vitamin C from oxidation within TPN bags, TPN should be placed in airtight, oxygen-impermeable containers, kept protected from light, kept refrigerated, and promptly dispensed.

Optimal Therapeutic Approach for this Disease

Treatment responses are rapid and often remit within 24 hours of initiating therapy. Once vitamin C levels are repleted, symptoms often resolve within about a week of adequate repletion. Once symptoms resolve, maintenance therapy should be instituted.

Patient Management

Dietary maneuvers to incorporate foods containing vitamin C are often sufficient to maintain vitamin C stores. These include citrus fruits and green leafy vegetables such as broccoli and spinach.

Unusual Clinical Scenarios to Consider in Patient Management

While scurvy is caused by a deficiency of vitamin C, the causes of this deficiency are highly varied, and some detective work is often necessary to identify the underlying cause. Causes can be divided into:

– Decreased intake

– Increased utilization

– Increased losses

Unusual scenarios that have been recently described in the literature were noted above and include:

– Anorexia nervosa due to globally restricted diets

– Children with autism-spectrum disorders who tend to have self-restricted diets, which often are lacking in foods rich in vitamin C

– Patients receiving chronic TPN using protocols or equipment that may predispose to premature degradation of vitamin C

– Patients after bariatric surgery (up to 34%) at 2-year follow-up in one study

– Patients with liver transplantation have recently been reported to have vitamin C deficiency

What is the Evidence?

Bown, SR. Scurvy: How a surgeon, a mariner, and a gentleman solved the greatest medical mystery of the age of sail. 2003. (A wonderful historical recounting of scurvy during the Age of Sail, with a focus on the work of James Lind and other physicians who helped characterize the cause and treatment of scurvy.)

Buckler, BS. Pediatric scurvy. Emedicine. (An excellent overview of pediatric scurvy)

Dupertuis, YM, Ramseyer, S, Fathi, M, Pichard, C. “Assessment of ascorbic acid stability in different multilayered parenteral nutrition bags: critical influence of the bag wall material”. JPEN J Parenter Enteral Nutr. vol. 29. 2005. pp. 125-30. (A paper describing the effects of layering and protection from oxygen on vitamin C integrity in TPN)

Goebel, L. Scurvy. Emedicine. (An excellent review of scurvy)

Hatuel, H, Buffet, M, Mateus, C, Calmus, Y, Carlotti, A, Dupin, N. “Scurvy in liver transplant patients”. J Am Acad Dermatol.. vol. 55. 2006. pp. 154-6. (Highlights the association of scurvy among liver transplant patients)

Levine, M, Eck, P. “Vitamin C: working on the x-axis”. Am J Clin Nutr. vol. 90. 2009. pp. 1121-3. (A summary of more recent epidemiology of scurvy in the United States)

Murad, S, Grove, D, Lindberg, KA, Reynolds, G, Sivarajah, A, Pinell, SR. “Regulation of collagen synthesis by ascorbic acid”. Proc Natl Acad Sci USA. vol. 78. 1981. pp. 2879-82. (A concise paper describing the role of ascorbic acid in collagen synthesis.)

Noble, JM, Mandel, A, Patterson, MC. “Scurvy and rickets masked by chronic neurologic illness: revisiting “psychologic malnutrition.””. Pediatrics. vol. 119. 2007. pp. e783-90. (A case report of scurvy in a child with autism-spectrum disorder)

Olmedo, JM, Yiannias, JA, Windgassen, EB, Gornet, MK. “Scurvy: a disease almost forgotten”. Int J Dermatol. vol. 45. 2006. pp. 909-13. (A nice recent review of scurvy)

Schleicher, RL, Carroll, MD, Ford, ES, Lacher, DA. “Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES)”. Am J Clin Nutr. vol. 90. 2009. pp. 1252-63. (National data on scurvy in the United States)

Tamura, Y, Welch, DC, Zic, JA, Cooper, WO, Stein, SM, Hummell, DS. “Scurvy presenting as painful gait with bruising in a young boy”. Arch Pediatr Adolesc Med. vol. 154. 2000. pp. 732-5. (Case report of scurvy in a child with a self-restricted diet)

Weinstein, M, Babyn, P, Zlotkin, S. “An orange a day keeps the doctor away: scurvy in the year 2000”. Pediatrics. vol. 108. 2001. pp. E55(Case report of scurvy in a child with a self-restricted diet)