Vitamin C Deficiency (Scurvy)


Article Author:
Luke Maxfield


Article Editor:
Jonathan Crane


Editors In Chief:
Sherry Gossman


Managing Editors:
Frank Smeeks
Scott Dulebohn
Erin Hughes
Sobhan Daneshfar
William Gossman
Pritesh Sheth
John Shell
Matthew Varacallo
Mark Pellegrini
James Hughes
Richard Ciresi
Phillip Hynes


Updated:
10/27/2018 12:31:51 PM

Introduction

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.

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. 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.

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. 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.

Pathophysiology

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.

Histopathology

Punch biopsy and subsequent histopathology are similar to clinical manifestations showing dilated hair follicles, keratin plugging by corkscrew hairs, and non-inflammatory perifollicular hemorrhages.

History and Physical

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.

Evaluation

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.

Treatment / Management

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

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.

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.

Complications

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.


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Vitamin C Deficiency (Scurvy) - Questions

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Vitamin C deficiency is associated with which of the following?



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A man with alcohol use disorder lives alone and is brought in with a leg wound that fails to heal. He is edentulous, has multiple ecchymoses, minute hemorrhages around hair follicles, and splinter hemorrhages in the nail beds. What food is likely deficient from his diet?



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A 2-year-old presents with bone pain. X-rays of the legs reveal generalized bony atrophy with epiphyseal separation. What is the most likely vitamin deficiency?



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A 64-year-old alcoholic lives alone and is admitted for a left leg wound that has failed to heal. He is edentulous, has multiple ecchymoses, minute hemorrhages around hair follicles, and splinter hemorrhages in the nail beds. What should be given to the patient?



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Which types of foods contain the highest level of vitamin C?



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Scurvy is associated with a deficiency of which vitamin?



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Periosteal elevation is commonly seen in which vitamin deficiency?



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Gingival swelling, bleeding, and loss of teeth may be signs of which vitamin deficiency?



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Scurvy is caused by a deficiency of what vitamin?



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A malnourished patient is diagnosed with scurvy characterized by hemorrhages, gum ulceration, and delayed bone growth. What molecule is deficient in this illness?



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What population is not likely to develop vitamin C deficiency?



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Which of the following is not a manifestation indicating vitamin C deficiency?



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What symptom would not be expected in a patient with a late diagnosis of scurvy?



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An 18-month-old child presents with irritability and refuses to walk. Both legs seem tender, there is a low-grade fever, and there are petechiae on the mucous membranes and skin. Leg x-rays show bony atrophy that is generalized with epiphyseal separation. What is the appropriate treatment?



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A 15-month-old female is noted to have sternal depression, outwardly projecting ribs, bruises on the legs, gingival hemorrhages, and bowing of the legs. What is the most likely diagnosis?



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Which of the following may be prolonged in patients with vitamin C deficiency?



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Perifollicular hyperkeratosis and petechiae suggest the diagnosis of which of the following?



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A 65-year-old female with a long history of alcohol abuse has a rash that has been present on her arms and thighs for a few weeks. The skin on bilateral arms shows hyperkeratotic, papules with perifollicular hemorrhage and corkscrew hairs as well as bleeding gums and multiple bruises on his legs. What is the most likely cause of these findings?



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A 47-year-old male with a long history of alcohol abuse presents for a rash that has been present for a few weeks. He admits the rash is non-pruritic and located on his arms and thighs. On examination, the skin showed hyperkeratotic, papules with perifollicular hemorrhage and corkscrew hairs as well as bleeding gums and multiple bruises on his legs. What can be offered as treatment?



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Vitamin C Deficiency (Scurvy) - References

References

Scurvy: past, present and future., Magiorkinis E,Beloukas A,Diamantis A,, European journal of internal medicine, 2011 Apr     [PubMed]
Scurvy in pediatric age group - A disease often forgotten?, Agarwal A,Shaharyar A,Kumar A,Bhat MS,Mishra M,, Journal of clinical orthopaedics and trauma, 2015 Jun     [PubMed]
Scurvy: a disease almost forgotten., Olmedo JM,Yiannias JA,Windgassen EB,Gornet MK,, International journal of dermatology, 2006 Aug     [PubMed]
Scurvy: reemergence of nutritional deficiencies., Léger D,, Canadian family physician Medecin de famille canadien, 2008 Oct     [PubMed]
Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES)., Schleicher RL,Carroll MD,Ford ES,Lacher DA,, The American journal of clinical nutrition, 2009 Nov     [PubMed]
Prevalence and risk factors for vitamin C deficiency in north and south India: a two centre population based study in people aged 60 years and over., Ravindran RD,Vashist P,Gupta SK,Young IS,Maraini G,Camparini M,Jayanthi R,John N,Fitzpatrick KE,Chakravarthy U,Ravilla TD,Fletcher AE,, PloS one, 2011     [PubMed]
The epigenetic role of vitamin C in health and disease., Camarena V,Wang G,, Cellular and molecular life sciences : CMLS, 2016 Apr     [PubMed]
Nutritional deficiencies during normal growth., Suskind DL,, Pediatric clinics of North America, 2009 Oct     [PubMed]
Dermoscopic diagnosis of scurvy., Wambier CG,Cappel MA,Werner B,Rodrigues E,Schumacher Welling MS,Montemór Netto MR,de Farias Wambier SP,, Journal of the American Academy of Dermatology, 2017 Feb     [PubMed]
Skin findings associated with nutritional deficiencies., Galimberti F,Mesinkovska NA,, Cleveland Clinic journal of medicine, 2016 Oct     [PubMed]
Measurement of intracellular vitamin C levels in human lymphocytes by reverse phase high performance liquid chromatography (HPLC)., Emadi-Konjin P,Verjee Z,Levin AV,Adeli K,, Clinical biochemistry, 2005 May     [PubMed]
Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients., Baxmann AC,De O G Mendonça C,Heilberg IP,, Kidney international, 2003 Mar     [PubMed]
Collagen IV in Normal Skin and in Pathological Processes., Abreu-Velez AM,Howard MS,, North American journal of medical sciences, 2012 Jan     [PubMed]
Scurvy identified in the emergency department: a case report., Stephen R,Utecht T,, The Journal of emergency medicine, 2001 Oct     [PubMed]

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