What is Scurvy?
- Get link
- Other Apps
Vitamin C Deficiency
Luke Maxfield; Jonathan S. Crane.Author Information
Last Update: July 18, 2021.
Continuing Education Activity
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. This activity reviews the history, clinical manifestations, diagnosis, and treatment of vitamin C deficiency. This activity highlights the role of the interprofessional team in caring for affected patients and promoting awareness regarding nutritional deficiencies.
- Review common exam findings associated with vitamin C deficiency.
- Describe the pathophysiology of vitamin C deficiency.
- Summarize the steps to diagnose vitamin C deficiency.
- Explain the importance of improving care coordination, with particular emphasis on communication between interprofessional medical teams, to enhance both preventative management and prompt delivery of care to patients with vitamin C deficiency.
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.
The vitamin C pool in the body is usually depleted in 4 to 12 weeks if one stops the intake of the vitamin. Ascorbic acid is affected by many factors that can impair absorption and its functions. The best way to prevent vitamin C deficiency is to consume fruits and vegetables regularly.
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.
Risk factors for Vitamin C deficiency include:
- Babies only fed cow's milk
- Seniors only consuming tea and toast diet
- Poor people who are not able to afford fruits and vegetables
- Individuals with eating disorders
- Type 1 diabetes who have high vitamin C requirements
- Individuals with disorders of the GI tract like inflammatory bowel disease.
- Individuals with iron overload, which leads to wasting of vitamin C by the kidneys
- Individuals with restrictive diets, food allergies
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 as high as 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 adequate sources.
As a clinical manifestation of severe vitamin C deficiency, scurvy is caused by ascorbic acid's 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. 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. Finally, the key feature of scurvy is hemorrhage which can occur in almost any organ. Further, bone formation is altered and becomes brittle.
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 are often localized to the lower extremities, as capillary fragility cannot 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 the 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.
Ocular symptoms include dry eyes, subconjunctival hemorrhage, and scleral icterus. Alopecia is common, and bleeding into the joints occurs with minimal trauma.
Recent studies show that Vitamin C deficiency may be associated with non-alcoholic fatty liver disease.
Diagnosis begins with the evaluation of risk factors and a physical examination. Dermoscopy can be used to aid in the 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 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 causes those with scurvy to be more prone to bleeding, and iron deficiency, in particular, should be assessed.
Imaging studies will reveal the following:
- Fractures, dislocations
- Subperiosteal elevation
- Alveolar bone resorption
- Early imaging features of scurvy are observed at the distal ends of the radius, which has fuzziness over the lateral aspect of the cortex. Progression to osteoporosis is common.
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 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 lactating women.
The key is to treat the primary condition causing scurvy.
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.
Deterrence and Patient Education
Patient education will depend on the source of vitamin C deficiency. If it is secondary to a malabsorptive condition, such as ulcerative colitis for Crohn disease, management of the underlying condition will require patient compliance and education.
If it is due to modifiable factors, the patient should receive counsel to abstain from smoking and limit alcohol consumption if these are factors. They can also receive instruction on proper dietary habits, including which foods are rich in vitamin C, such as citrus fruits, berries, and certain kinds of melon, as well as Vegetables such as spinach, red and green peppers, tomatoes, cabbage, cauliflower, broccoli, and Brussels sprouts. Lastly, they can receive instruction on appropriate vitamin C dietary supplementation.
Enhancing Healthcare Team Outcomes
All healthcare workers should encourage adequate nutrition for their patients. While scurvy is very rare in North America, it may develop in people deprived of food or those with intestinal problems. Whenever a deficiency of one vitamin is discovered, it is important to screen for other concomitant 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 causes those with scurvy to be more prone to bleeding, and iron deficiency, in particular, should be assessed.
The primary care provider, nurse practitioner, dietician, and pharmacist, operating as a cohesive interprofessional team, should educate patients about a healthy diet rich in fruits and vegetables. In addition, patients should be encouraged to stop smoking and quit alcohol. Any patient that fails to improve within a few weeks should be referred to a specialist to determine the primary cause of vitamin C deficiency. Only through an interprofessional team approach can the morbidity of vitamin C deficiency be lowered and patient outcomes optimized. [Level 5]
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 5]
- Shaikh H, Faisal MS, Mewawalla P. Vitamin C deficiency: rare cause of severe anemia with hemolysis. Int J Hematol. 2019 May;109(5):618-621. [PubMed]
- Callus CA, Vella S, Ferry P. Scurvy is Back. Nutr Metab Insights. 2018;11:1178638818809097. [PMC free article] [PubMed]
- Lux-Battistelli C, Battistelli D. Alcohol Withdrawal: Possible Risk of Latent Scurvy Appearing as Tiredness: A STROBE-Compliant Study. J Clin Med Res. 2019 Jan;11(1):26-34. [PMC free article] [PubMed]
- Byard RW, Maxwell-Stewart H. Scurvy-Characteristic Features and Forensic Issues. Am J Forensic Med Pathol. 2019 Mar;40(1):43-46. [PubMed]
- Panchal S, Schneider C, Malhotra K. Scurvy in a hemodialysis patient. Rare or ignored? Hemodial Int. 2018 Oct;22(S2):S83-S87. [PubMed]
- Irvine I, Walshe T, Capra M, Hayes R. Scurvy: an unusual complication of paediatric cancer treatment. Skeletal Radiol. 2019 Jun;48(6):995-998. [PubMed]
- Ravindran P, Wiltshire S, Das K, Wilson RB. Vitamin C deficiency in an Australian cohort of metropolitan surgical patients. Pathology. 2018 Oct;50(6):654-658. [PubMed]
- Lipner S. A classic case of scurvy. Lancet. 2018 Aug 04;392(10145):431. [PubMed]
- Ceglie G, Macchiarulo G, Marchili MR, Marchesi A, Rotondi Aufiero L, Di Camillo C, Villani A. Scurvy: still a threat in the well-fed first world? Arch Dis Child. 2019 Apr;104(4):381-383. [PubMed]
- Antonelli M, Burzo ML, Pecorini G, Massi G, Landolfi R, Flex A. Scurvy as cause of purpura in the XXI century: a review on this "ancient" disease. Eur Rev Med Pharmacol Sci. 2018 Jul;22(13):4355-4358. [PubMed]
This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to the Creative Commons license, and any changes made are indicated.
- Get link
- Other Apps
Post a Comment