Vitamin C Deficiency (Scurvy): Difference between revisions

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== Introduction  ==
== Introduction  ==
 
[[File:Crystals of vitamin C.jpeg|alt=|thumb|Crystals of vitamin C]]
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. <ref name=":0">Maxfield L, Crane JS. [https://www.statpearls.com/articlelibrary/viewarticle/28798/ Vitamin C deficiency (scurvy).] StatPearls [Internet]. 2019 Nov 19.Available from: https://www.statpearls.com/articlelibrary/viewarticle/28798/<nowiki/>(accessed 5.3.2021)</ref>
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. <ref name=":0">Maxfield L, Crane JS. [https://www.statpearls.com/articlelibrary/viewarticle/28798/ Vitamin C deficiency (scurvy).] StatPearls [Internet]. 2019 Nov 19.Available from: https://www.statpearls.com/articlelibrary/viewarticle/28798/<nowiki/>(accessed 5.3.2021)</ref>


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Most animals require no exogenous vitamin C. For humans, however, vitamin C is an essential vitamin.  
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. A mutation in the gene coding for L-gulonolactone oxidase occurred, which no longer allows the human body to synthesize vitamin C. Thus, making it necessary for vitamin C to be taken in through the human diet to ensure the body is able to aid in wound healing, scar formation, repairing cartilage, bone, and teeth, and the ability to absorb iron.
Humans lack the [[Enzymes|enzyme]] L-gulonolactone oxidase, and people must ingest it. A mutation in the gene coding for L-gulonolactone oxidase occurred, which no longer allows the human body to synthesize vitamin C. Thus, making it necessary for vitamin C to be taken in through the human [[Nutrition|diet]] to ensure the body is able to aid in [[Wound Healing|wound healing]], [[Scar Management|scar]] formation, repairing [[cartilage]], [[bone]], and teeth, and the ability to absorb [[iron]].
* Vitamin C deficiency and its manifestations have largely been a product of inadequate dietary intake.  
* 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.  
* Vitamin C is naturally found in fresh fruits and vegetables; for example, grapefruits, oranges, lemons, limes, potatoes, spinach, broccoli, red peppers, and tomatoes.  
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== Epidemiology  ==
== 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.   
Vitamin C deficiency is defined as a serum concentration of less than 11.4 umol/L, and prevalence varies across the world
 
* As low as 7.1% in the United States
* Up to 73.9% in north India.   
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.  
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.  


The following populations are at increased risk for a vitamin C inadequacy that could develop into a diagnosis of scurvy without appropriate dietary management.  
The following populations are at increased risk for a vitamin C inadequacy that could develop into a diagnosis of scurvy without appropriate dietary management.  


*Smokers<ref name="Wax">Wax E, Zieve D, Ogilvie I. Vitamin C [updated Feb 2, 2015; cited 2016 April 8]. Available from: https://www.nlm.nih/gov/medlineplus/ency/article/002404.htm.</ref>&nbsp;  
*[[Smoking Cessation and Brief Intervention|Smoker]]<nowiki/>s<ref name="Wax">Wax E, Zieve D, Ogilvie I. Vitamin C [updated Feb 2, 2015; cited 2016 April 8]. Available from: https://www.nlm.nih/gov/medlineplus/ency/article/002404.htm.</ref>&nbsp;
*Infants fed evaporated or boiled milk<ref name="Wax" />&nbsp;and Children with restricted diets<ref name="Alqanatish">Alqanatish JT, Alqahtani F, Alsewairi WM, Al-kenaizan S. Childhood scurvy: an unusual cause of refusal to walk in a child. Pediatric rheumatology online journal. 2015;13-23.</ref>&nbsp;  
*Infants fed evaporated or boiled milk<ref name="Wax" />&nbsp;and Children with restricted diets<ref name="Alqanatish">Alqanatish JT, Alqahtani F, Alsewairi WM, Al-kenaizan S. Childhood scurvy: an unusual cause of refusal to walk in a child. Pediatric rheumatology online journal. 2015;13-23.</ref>&nbsp;  
*Children with autism, developmental delay, and cerebral palsy<ref name="Alqanatish" />&nbsp;  
*Children with autism, [[Child Development|developmental delay]], and [[Cerebral Palsy Introduction|cerebral palsy]]<ref name="Alqanatish" />&nbsp;  
*Sailors at sea for months<ref name="Alqanatish" />'''&nbsp;<ref name="Chaudhry">Chaudhry SI, Newell EL, Lewis RR, Black MM. Scurvy: a forgotten disease. Clinical &amp; Experimental Dermatology. 2005;30(6):735-6</ref>&nbsp;&nbsp;'''  
*Sailors at sea for months<ref name="Alqanatish" />'''&nbsp;<ref name="Chaudhry">Chaudhry SI, Newell EL, Lewis RR, Black MM. Scurvy: a forgotten disease. Clinical &amp; Experimental Dermatology. 2005;30(6):735-6</ref>&nbsp;&nbsp;'''  
*Third world countries with limited foods <ref name="Wax" />   
*Third world countries with limited foods <ref name="Wax" />   
*Low income.  
*Low income.  
*Individuals with malabsorption&nbsp;<ref name="Wax" />  
*Individuals with malabsorption&nbsp;<ref name="Wax" />  
*Individuals with cancer <ref name="Wax" />   
*Individuals with [[Oncology|cancer]] <ref name="Wax" />   
*Individuals with chronic diseases such as end-stage renal disease or on hemodialysis<ref name=":0" /> <ref name="Wax" />
*Individuals with [[Chronic Disease|chronic diseases]] such as [[Chronic Kidney Disease|end-stage renal disease]] or on hemodialysis<ref name=":0" /> <ref name="Wax" />


== Pathophysiology ==
== Pathophysiology ==
Scurvy as a clinical manifestation of severe vitamin C deficiency is caused by ascorbic acids 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. Changes include:
[[File:Collagen 03.png|right|frameless]]
* Epigenetic DNA hypermethylation and inhibition of the transcription of various types of collagen found in skin, blood vessels, and tissue.  
Scurvy as a clinical manifestation of severe vitamin C deficiency is caused by ascorbic acids 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. Changes include:
* [[Epigenetics|Epigenetic]] DNA hypermethylation and inhibition of the transcription of various types of collagen found in skin, blood vessels, and tissue.
* Bone formation is altered and become brittle.
* Bone formation is altered and become brittle.
* The key feature of scurvy is hemorrhage which can occur in almost any organ.<ref name=":0" />  
* The key feature of scurvy is hemorrhage which can occur in almost any organ.<ref name=":0" />  
== Vitamin C and [[Muscle Function: Effects of Aging|Sarcopenia]] ==
[[File:Muscle-up.gif|right|frameless]]
Insufficient dietary vitamin C intake may have effects on muscles.
* Around two-thirds of our body’s total vitamin C is found in skeletal [[muscle]]. It’s used for making carnitine, a crucial substance that provides energy for muscles to function, and collagen, which is an essential structural component of muscle.
* In addition, vitamin C is a strong antioxidant that can help to counteract free radical molecules, which increase when we age. Unopposed, these free radicals can contribute to the destruction of muscle cells.
Studies have found the people  who consumed the highest amount of vitamin C in their diet had the greatest muscle mass.
* The biggest difference was seen in women: those women in the highest category of vitamin C consumption had muscle mass 3% greater than those in the lowest category.
* These differences are likely to be clinically relevant, especially given that most people are estimated to lose 0.5% to 1% of muscle mass every year after age 50.
* These findings build on the concept that optimal nutrition may help reduce the decline in muscle. We should encourage all people to follow the healthy eating guidelines and eat a wide variety of vegetables and fruits each day, not only for general health but to protect their muscles.<ref>The Conversation [https://theconversation.com/vitamin-c-could-help-older-adults-retain-muscle-mass-new-research-145125 Vitamin C could help older adults retain muscle mass – new research] Available from: https://theconversation.com/vitamin-c-could-help-older-adults-retain-muscle-mass-new-research-145125<nowiki/>(accessed 6.3.2021)</ref>


== Characteristics/Clinical Presentation ==
== Characteristics/Clinical Presentation ==
Vitamin C deficiency can lead to the following signs and symptoms:<ref name="Wax" />  
Vitamin C deficiency can lead to the following signs and symptoms:<ref name="Wax" />  


*Anemia
*[[Anaemia]]
*Bleeding gums  
*Bleeding gums  
*Decreased ability to fight infection  
*Decreased ability to fight [[Infectious Disease|infection]]
*Decreased wound-healing rate  
*Decreased wound-healing rate  
*Dry and splitting hair  
*Dry and splitting hair  
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== Associated Co-morbidities  ==
== Associated Co-morbidities  ==
 
'''[[Osteopenia]]''' - osteopenia is defined by bone densitometry as a T score -1 to -2.5. There are many causes for osteopenia including calcium and vitamin D deficiency and inactivity. Genetics plays an important role in a person's bone mineral density and often Caucasian women with a thin body habitus who are premenopausal are found to have osteopenia.<ref name="Karaguzel">Karaguzel G, Holick MF. Diagnosis and treatment of osteopenia. Reviews in endocrine &amp; metabolic disorders. 2010;11(4):237-51.</ref>&nbsp;  
'''<ref name="Goebel">Goebel L, July M. Scurvy Overview: Prognosis 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-overview#a7.</ref>'''
 
'''Osteopenia''' - osteopenia is defined by bone densitometry as a T score -1 to -2.5. There are many causes for osteopenia including calcium and vitamin D deficiency and inactivity. Genetics plays an important role in a person's bone mineral density and often Caucasian women with a thin body habitus who are premenopausal are found to have osteopenia.<ref name="Karaguzel">Karaguzel G, Holick MF. Diagnosis and treatment of osteopenia. Reviews in endocrine &amp; metabolic disorders. 2010;11(4):237-51.</ref>&nbsp;  


'''Iron deficiency''' - As the name implies, iron deficiency anemia is due to insufficient iron. Without enough iron, your body can't produce enough of a substance in red blood cells that enables them to carry oxygen (hemoglobin). As a result, iron deficiency anemia may leave you tired and short of breath.<ref name="Mayo clinic">Mayo Clinic Staff. Iron Deficiency Anemia 2014 [updated Jan. 2, 2014; cited 2016 April 8]. Available from: http://www.mayoclinic.org/diseases-conditions/iron-deficiency-anemia/basics/definition/con-20019327.</ref>   
'''Iron deficiency''' - As the name implies, iron deficiency anemia is due to insufficient iron. Without enough iron, your body can't produce enough of a substance in red blood cells that enables them to carry oxygen (hemoglobin). As a result, iron deficiency anemia may leave you tired and short of breath.<ref name="Mayo clinic">Mayo Clinic Staff. Iron Deficiency Anemia 2014 [updated Jan. 2, 2014; cited 2016 April 8]. Available from: http://www.mayoclinic.org/diseases-conditions/iron-deficiency-anemia/basics/definition/con-20019327.</ref>   


'''Anemia'''  
'''[[Anaemia]]'''  


'''Folate deficiency''' - Folic acid (vitamin B9) works with vitamin B12 and vitamin C to help the body break down, use, and make new proteins. The vitamin helps form red and white blood cells. It also helps produce DNA. Folate is not stored in the body in large amounts, your blood levels will get low after only a few weeks of eating a diet low in folate.<ref name="Wax2">Wax E, Zieve D, Ogilvie I. Folate Deficiency [updated July 14, 2015; cited 2016 APril 8]. Available from: https://www.nlm.nih.gov/medlineplus/ency/article/000354.htm.</ref>&nbsp;  
'''Folate deficiency''' - Folic acid (vitamin B9) works with vitamin B12 and vitamin C to help the body break down, use, and make new proteins. The vitamin helps form red and white blood cells. It also helps produce DNA. Folate is not stored in the body in large amounts, your blood levels will get low after only a few weeks of eating a diet low in folate.<ref name="Wax2">Wax E, Zieve D, Ogilvie I. Folate Deficiency [updated July 14, 2015; cited 2016 APril 8]. Available from: https://www.nlm.nih.gov/medlineplus/ency/article/000354.htm.</ref>&nbsp;  


'''Vitamin K deficiency''' - Vitamin K (VK) deficiency can occur in any age group but is encountered most often in infancy. VK, an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins<ref name="Nguyen">Nguyen-Khoa D-T, Patel P. Vitamin K Deficiency [updated Dec. 18, 2015; cited 2016 April 8]. Available from: http://emedicine.medscape.com/article/126354-overview.</ref>  
'''Vitamin K deficiency''' - Vitamin K (VK) deficiency can occur in any age group but is encountered most often in infancy. VK, an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins<ref name="Nguyen">Nguyen-Khoa D-T, Patel P. Vitamin K Deficiency [updated Dec. 18, 2015; cited 2016 April 8]. Available from: http://emedicine.medscape.com/article/126354-overview.</ref>'''<ref name="Goebel">Goebel L, July M. Scurvy Overview: Prognosis 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-overview#a7.</ref>'''


== Menagement  ==
== Menagement  ==
* 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.  
*[[File:Citrus food Vit C.jpg|right|frameless]]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.  
* In addition to immediate supplementation, educate the patient on lifestyle modifications to ensure adequate intake, and recommend cessation of alcohol, and tobacco use.
* 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 women who are lactating<ref name=":0" />.
* 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 women who are lactating<ref name=":0" />.
When choosing foods high in vitamin C, it is also important to consider how the food is prepared. Storing the food for long periods of time or cooking the product a certain way can reduce the amount of vitamin C the food contains. The best source of vitamin C is found most when consuming raw fruits and vegetables with high daily values. Cooking losses may be reduced by microwaving or steaming the food. Light exposure can also reduce the amount of vitamin C found in foods. According the NIH, juices kept in cartons should be chosen rather than juice contained in a clear bottle.<ref />
When choosing foods high in vitamin C, it is also important to consider how the food is prepared. Storing the food for long periods of time or cooking the product a certain way can reduce the amount of vitamin C the food contains. The best source of vitamin C is found most when consuming raw fruits and vegetables with high daily values. Cooking losses may be reduced by microwaving or steaming the food. Light exposure can also reduce the amount of vitamin C found in foods. According the NIH, juices kept in cartons should be chosen rather than juice contained in a clear bottle.


'''Dietary Management/Food Sources''' Vitamin C can be found in some foods naturally and other foods are fortified with vitamins. '''Table 2'''&nbsp;lists the&nbsp;fruits and vegetables that contain naturally high in vitamin C content. Many cereals and beverages are fortified with vitamin C. Checking food labels can provide information on the amount of vitamin C contained in the product.
'''Dietary Management/Food Sources''' Vitamin C can be found in some foods naturally and other foods are fortified with vitamins. '''Table 2'''&nbsp;lists the&nbsp;fruits and vegetables that contain naturally high in vitamin C content. Many cereals and beverages are fortified with vitamin C. Checking food labels can provide information on the amount of vitamin C contained in the product.
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== Diagnostic Tests/Lab Tests/Lab Values==
== Diagnostic Tests/Lab Tests/Lab Values==


'''Plasma levels: '''A fasting serum ascorbic acid level greater than 0.6 mg/dL rules out scurvy. Scurvy generally occurs at levels below 0.1 mg/dL.<ref name="Goebel-workup">Goebel L. July M. Scurvy Workup 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-workup#showall.</ref><br>'''Leukocyte levels:''' The level of vitamin C in leukocytes more accurately correlates to tissue stores compared with serum levels, because these cells are not affected acutely by circadian rhythm or dietary changes. A level of zero indicates latent scurvy. Levels of 0-7 mg/dL reflect a state of deficiency.<ref name="Goebel-workup" /><br>'''Urinary levels:''' A more commonly used method is the ascorbic acid tolerance test, which quantitates urinary ascorbic acid over the 6 hours following an oral load of 1 g of ascorbic acid in water.<ref name="Goebel-workup" /><br>'''Radiographic findings:''' in infantile scurvy are diagnostic and may show any of the following:<ref name="Goebel-workup" />  
'''[[Blood|Plasma]] levels: '''A fasting serum ascorbic acid level greater than 0.6 mg/dL rules out scurvy. Scurvy generally occurs at levels below 0.1 mg/dL.<ref name="Goebel-workup">Goebel L. July M. Scurvy Workup 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-workup#showall.</ref><br>'''[[Leukocytes|Leukocyte]] levels:''' The level of vitamin C in leukocytes more accurately correlates to tissue stores compared with serum levels, because these cells are not affected acutely by circadian rhythm or dietary changes. A level of zero indicates latent scurvy. Levels of 0-7 mg/dL reflect a state of deficiency.<ref name="Goebel-workup" /><br>'''Urinary levels:''' A more commonly used method is the ascorbic acid tolerance test, which quantitates urinary ascorbic acid over the 6 hours following an oral load of 1 g of ascorbic acid in water.<ref name="Goebel-workup" /><br>'''Radiographic findings:''' in infantile scurvy are diagnostic and may show any of the following:<ref name="Goebel-workup" />  


*Subperiosteal elevation  
*Subperiosteal elevation  
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*Ground-glass appearance of cortex  
*Ground-glass appearance of cortex  


== Systemic Involvement ==
== ''<nowiki/><nowiki/>''Prognosis ==
'''Circulatory System:<ref name="Goebel-clinicalpresentation">Goebel L, July M. Scurvy Clinical Presentation 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-clinical.</ref>'''
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.


*Hypotension may be seen during the late stages of scurvy in response to vessels inability to constrict in response to stimuli. Complications in the heart can arise which include cardiac enlargement, electrocardiographic (ECG) changes, hemopericardium, and sudden death. Heart failure due to high-output can be seen in response to anemia.  
== Differential Diagnosis  ==
*Anemia is present in 75% of the known cases of scurvy. Anemia appears in this population because of the blood loss into tissues, coexisting dietary deficiencies, malabsorption, and intravascular hemolysis.
Differential diagnosis includes many cutaneous purpuric pathologies including:
 
* Immune thrombocytopenic purpura, Henoch-Schonlein purpura, disseminated intravascular coagulation, [[Rocky Mountain Spotted Fever|Rocky Mountain spotted fever]], meningococcemia, or hypersensitivity vasculitis.  
'''Gastrointestinal System''''':<ref name="Goebel-clinicalpresentation" />'<nowiki/>''
* Mucosal involvement may mimic necrotizing gingivitis.  
* Other vitamin deficiencies including niacin (B3), biotin (B7), and zinc may present with skin changes.<ref name="Wax" />


If teeth have been erupted, gum hemorrhage is possible. The tissue surrounding the upper incisors are most commonly affected and present with a blue or purple color and a spongy feeling.
*Loose teeth can also be seen with a diagnosis of scurvy. Gum swelling, friability, bleeding, and infection can occur when loose teeth are present.
*Anorexia is sometimes seen with scurvy diagnoses; therefore, weight loss is commonly seen. A submucosal hemorrhage may be shown with an upper endoscopy.
[[Image:Purpura.JPG|50x50px|Purpura [Internet]. Wikipedia. 2016 [cited 5 April 2016]. Available from: https://en.m.wikipedia.org/wiki/Purpura|right|frameless]]'''Integumentary System/Skeletal:<ref name="Ngan">Ngan V. Scury 2005 [updated Nov. 9, 2015; cited 2016 April 8]. Available from: http://www.dermnetnz.org/systemic/scurvy.html.</ref>'''&nbsp;
*Several skin problems can be noted with a diagnosis of scurvy. An early symptom is appearance bluish spots similar to bruises surrounding hair follicles on the shins, known as perifollicular hyperkeratotic papules. The hair is usually twisted like a corkscrew and very brittle susceptible to breakage. As the disease progresses, large patches of papules can form larger areas of bruising known as ecchymoses or purpura shown in the picture below.
*Vitamin C deficiency affects the production of collagen which can decrease efficiency of wound healing. This can affect new wounds and also decrease the integrity of old scars, leaving them at risk for skin breakdown.
*Sometimes bleeding within the joints can occur leading to painful hemarthroses. A subperiosteal hemorrhage can be palpable along the femur and sometimes the tibia in infants. If bleeding occurs in the femoral sheath, neuropathies can be seen and if there is bleeding into the muscles, woody edema can be present.
'''Nervous System''''':<ref name="Goebel-clinicalpresentation" />'<nowiki/>''
*Protrusion of the eyeball occurs due to an orbital hemorrhage and can be seen in the diagnosis of scurvy. Other ocular impairments can be seen which include dry eye similar to the diagnosis of Sjögren syndrome, subconjunctival hemorrhage, and bleeding in the eyelid, retrobulbar space, and periorbital are. Late in the diagnosis scleral icterus can be caused by hemolysis along with pale conjunctiva.
== Physical Therapy Management  ==
There are no direct physical therapy interventions for Scurvy. The patient may be referred to physical therapy for the treatment of impairments caused by Scurvy. These may include joint pain and stiffness, musculoskeletal pain, and musculoskeletal weakness, (particularly in the lower extremity).<ref name="Wax" /> 
== Differential Diagnosis  ==
*Meningococcemia
*Osteomyelitis
*Pediatric Poliomyelitis
*Pediatric Syphilis
*Retinoblastoma Imaging
*Rheumatic Fever
*Rheumatoid Arthritis
*Rocky Mountain Spotted Fever
*Septic Arthritis'''<ref name="Goebel-differential">Goebel L, July M. Scurvy Differential Diagnosis 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-differential.</ref>'''
== References  ==  
== References  ==  


Latest revision as of 05:33, 27 July 2022

Original Editors - Emily Buckingham, Martina Riney Students from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Martina Riney, Emily Buckingham, Kim Jackson, Lucinda hampton, Elaine Lonnemann, WikiSysop, 127.0.0.1 and Claire Knott  

Introduction[edit | edit source]

Crystals of vitamin C

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. [1]

Etiology[edit | edit source]

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. A mutation in the gene coding for L-gulonolactone oxidase occurred, which no longer allows the human body to synthesize vitamin C. Thus, making it necessary for vitamin C to be taken in through the human diet to ensure the body is able to aid in wound healing, scar formation, repairing cartilage, bone, and teeth, and the ability to absorb iron.

  • 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.
  • The vitamin C pool in the body is usually depleted in 4-12 weeks if one stops the intake of the vitamin.
  • 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[1]

Epidemiology[edit | edit source]

Vitamin C deficiency is defined as a serum concentration of less than 11.4 umol/L, and prevalence varies across the world

  • As low as 7.1% in the United States
  • Up to 73.9% in north India.

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.

The following populations are at increased risk for a vitamin C inadequacy that could develop into a diagnosis of scurvy without appropriate dietary management.

Pathophysiology[edit | edit source]

Collagen 03.png

Scurvy as a clinical manifestation of severe vitamin C deficiency is caused by ascorbic acids 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. Changes include:

  • Epigenetic DNA hypermethylation and inhibition of the transcription of various types of collagen found in skin, blood vessels, and tissue.
  • Bone formation is altered and become brittle.
  • The key feature of scurvy is hemorrhage which can occur in almost any organ.[1]

Vitamin C and Sarcopenia[edit | edit source]

Muscle-up.gif

Insufficient dietary vitamin C intake may have effects on muscles.

  • Around two-thirds of our body’s total vitamin C is found in skeletal muscle. It’s used for making carnitine, a crucial substance that provides energy for muscles to function, and collagen, which is an essential structural component of muscle.
  • In addition, vitamin C is a strong antioxidant that can help to counteract free radical molecules, which increase when we age. Unopposed, these free radicals can contribute to the destruction of muscle cells.

Studies have found the people who consumed the highest amount of vitamin C in their diet had the greatest muscle mass.

  • The biggest difference was seen in women: those women in the highest category of vitamin C consumption had muscle mass 3% greater than those in the lowest category.
  • These differences are likely to be clinically relevant, especially given that most people are estimated to lose 0.5% to 1% of muscle mass every year after age 50.
  • These findings build on the concept that optimal nutrition may help reduce the decline in muscle. We should encourage all people to follow the healthy eating guidelines and eat a wide variety of vegetables and fruits each day, not only for general health but to protect their muscles.[5]

Characteristics/Clinical Presentation[edit | edit source]

Vitamin C deficiency can lead to the following signs and symptoms:[2]

  • Anaemia
  • Bleeding gums
  • Decreased ability to fight infection
  • Decreased wound-healing rate
  • Dry and splitting hair
  • Easy bruising
  • Gingivitis (inflammation of the gums)
  • Nosebleeds
  • Possible weight gain because of slowed metabolism
  • Rough, dry, scaly skin
  • Swollen and painful joints
  • Weakened tooth enamel

Associated Co-morbidities[edit | edit source]

Osteopenia - osteopenia is defined by bone densitometry as a T score -1 to -2.5. There are many causes for osteopenia including calcium and vitamin D deficiency and inactivity. Genetics plays an important role in a person's bone mineral density and often Caucasian women with a thin body habitus who are premenopausal are found to have osteopenia.[6] 

Iron deficiency - As the name implies, iron deficiency anemia is due to insufficient iron. Without enough iron, your body can't produce enough of a substance in red blood cells that enables them to carry oxygen (hemoglobin). As a result, iron deficiency anemia may leave you tired and short of breath.[7]

Anaemia

Folate deficiency - Folic acid (vitamin B9) works with vitamin B12 and vitamin C to help the body break down, use, and make new proteins. The vitamin helps form red and white blood cells. It also helps produce DNA. Folate is not stored in the body in large amounts, your blood levels will get low after only a few weeks of eating a diet low in folate.[8] 

Vitamin K deficiency - Vitamin K (VK) deficiency can occur in any age group but is encountered most often in infancy. VK, an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins[9][10]

Menagement[edit | edit source]

  • Citrus food Vit C.jpg
    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.
  • 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 women who are lactating[1].

When choosing foods high in vitamin C, it is also important to consider how the food is prepared. Storing the food for long periods of time or cooking the product a certain way can reduce the amount of vitamin C the food contains. The best source of vitamin C is found most when consuming raw fruits and vegetables with high daily values. Cooking losses may be reduced by microwaving or steaming the food. Light exposure can also reduce the amount of vitamin C found in foods. According the NIH, juices kept in cartons should be chosen rather than juice contained in a clear bottle.

Dietary Management/Food Sources Vitamin C can be found in some foods naturally and other foods are fortified with vitamins. Table 2 lists the fruits and vegetables that contain naturally high in vitamin C content. Many cereals and beverages are fortified with vitamin C. Checking food labels can provide information on the amount of vitamin C contained in the product.

Table 2. Fruits and vegetables that contain high amounts of vitamin C. 

Fruits Vegetables
Cantaloupe Broccoli
Orange Brussel Sprouts
Grapefruit Cauliflower
Kiwi fruit
 Spinach
Mango Sweet and white potatoes
Papaya
 Tomatoes and tomato juice
Pineapple Winter squash
Strawberries
 Green/red peppers
Raspberries
 Turnip greens
Blueberries Cabbage
Cranberries
Watermelon

Diagnostic Tests/Lab Tests/Lab Values[edit | edit source]

Plasma levels: A fasting serum ascorbic acid level greater than 0.6 mg/dL rules out scurvy. Scurvy generally occurs at levels below 0.1 mg/dL.[11]
Leukocyte levels: The level of vitamin C in leukocytes more accurately correlates to tissue stores compared with serum levels, because these cells are not affected acutely by circadian rhythm or dietary changes. A level of zero indicates latent scurvy. Levels of 0-7 mg/dL reflect a state of deficiency.[11]
Urinary levels: A more commonly used method is the ascorbic acid tolerance test, which quantitates urinary ascorbic acid over the 6 hours following an oral load of 1 g of ascorbic acid in water.[11]
Radiographic findings: in infantile scurvy are diagnostic and may show any of the following:[11]

  • Subperiosteal elevation
  • Fractures and dislocation
  • Alveolar bone reabsorption
  • Ground-glass appearance of cortex

Prognosis[edit | edit source]

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.

Differential Diagnosis[edit | edit source]

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 (B3), biotin (B7), and zinc may present with skin changes.[2]

References[edit | edit source]

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Maxfield L, Crane JS. Vitamin C deficiency (scurvy). StatPearls [Internet]. 2019 Nov 19.Available from: https://www.statpearls.com/articlelibrary/viewarticle/28798/(accessed 5.3.2021)
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Wax E, Zieve D, Ogilvie I. Vitamin C [updated Feb 2, 2015; cited 2016 April 8]. Available from: https://www.nlm.nih/gov/medlineplus/ency/article/002404.htm.
  3. ↑ 3.0 3.1 3.2 Alqanatish JT, Alqahtani F, Alsewairi WM, Al-kenaizan S. Childhood scurvy: an unusual cause of refusal to walk in a child. Pediatric rheumatology online journal. 2015;13-23.
  4. ↑ Chaudhry SI, Newell EL, Lewis RR, Black MM. Scurvy: a forgotten disease. Clinical & Experimental Dermatology. 2005;30(6):735-6
  5. ↑ The Conversation Vitamin C could help older adults retain muscle mass – new research Available from: https://theconversation.com/vitamin-c-could-help-older-adults-retain-muscle-mass-new-research-145125(accessed 6.3.2021)
  6. ↑ Karaguzel G, Holick MF. Diagnosis and treatment of osteopenia. Reviews in endocrine & metabolic disorders. 2010;11(4):237-51.
  7. ↑ Mayo Clinic Staff. Iron Deficiency Anemia 2014 [updated Jan. 2, 2014; cited 2016 April 8]. Available from: http://www.mayoclinic.org/diseases-conditions/iron-deficiency-anemia/basics/definition/con-20019327.
  8. ↑ Wax E, Zieve D, Ogilvie I. Folate Deficiency [updated July 14, 2015; cited 2016 APril 8]. Available from: https://www.nlm.nih.gov/medlineplus/ency/article/000354.htm.
  9. ↑ Nguyen-Khoa D-T, Patel P. Vitamin K Deficiency [updated Dec. 18, 2015; cited 2016 April 8]. Available from: http://emedicine.medscape.com/article/126354-overview.
  10. ↑ Goebel L, July M. Scurvy Overview: Prognosis 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-overview#a7.
  11. ↑ 11.0 11.1 11.2 11.3 Goebel L. July M. Scurvy Workup 2015 [updated Sep 23, 2015; cited 2016 April 5]. Available from: http://emedicine.medscape.com/article/125350-workup#showall.
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