History and exam

Key diagnostic factors

common

vitamin C deficiency upon dietary review

Nearly every reported case with a delay in scurvy diagnosis is due to inadequate or absent dietary history taken at presentation.

constitutional symptoms

Arthralgia, myalgia, weakness, lethargy, nausea, emesis, weight loss, dry skin, depression, and dyspnoea.[1][2][18]​ Fatigue has been suggested to be the earliest sensitive symptom.

easy bruising or bleeding

As vitamin C levels drop, the disease progresses, and symptoms of endothelial dysfunction and haemorrhage develop, including easy bruising or bleeding, myalgia, arthralgias, and joint swelling.

gait impairment or leg pain

The most common orthopaedic presentation in children is the refusal to bear weight.[63]​ This is most likely related to impaired bone growth. A frog-like leg positioning with little leg movement (probably caused by painful subperiosteal haemorrhages) has been described in infants and other children.[1][2][18][60]​ The most common radiographical sign is increased density of the metaphyseal line, which appears as a lucency. This is known as Frankel's sign.[63]

pedal oedema

May be a manifestation of cardiac failure or of local endothelial dysfunction.

petechial and perifollicular haemorrhages (legs and feet)

Caused by endothelial dysfunction and haemorrhage.[Figure caption and citation for the preceding image starts]: Corkscrew hair and perifollicular petechiae which are commonly seen in scurvyShah V, et al. Case Rep Med 2021 Mar 30; 2021: 5519937; used with permission [Citation ends].com.bmj.content.model.Caption@14cfb39b

poor wound healing

May be evident but overlooked by the patient.

bruising and nodular or black ecchymoses at non-traumatic sites

Caused by endothelial dysfunction and haemorrhage.

joint swelling

May be due to swelling or effusion.

oral mucosal petechiae

Caused by endothelial dysfunction and hemorrhage.

coiled hairs

A dermatological sign relating to endothelial dysfunction.[Figure caption and citation for the preceding image starts]: Corkscrew hair and perifollicular petechiae which are commonly seen in scurvyShah V, et al. Case Rep Med 2021 Mar 30; 2021: 5519937; used with permission [Citation ends].com.bmj.content.model.Caption@5c2a6920

follicular hyperkeratosis

A dermatological sign relating to endothelial dysfunction.

tooth loss

Dentate patients may have loose teeth with haemorrhagic gingivitis affecting interdental papillae.[1][2][18]

gingival discoloration

Gingival abnormalities have been suggested to be an early and highly sensitive sign.[1][2][18]

gum swelling

Gums are typically normal in edentulous patients. Gingival abnormalities have been suggested to be an early and highly sensitive sign.[1][2][18]

uncommon

lid petechiae and haemorrhages

Ophthalmological findings can occur as early as 74 days after vitamin C deprivation.[61]

proptosis

Proptosis can occur as a result of retrobulbar, periorbital, or orbital subperiosteal haemorrhage.[61] Ophthalmological findings can occur as early as 74 days after vitamin C deprivation.

conjunctival and subconjunctival haemorrhage

Small haemorrhages are punctuate, triangular, streaky, or linear. Also, linear and triangular varicosities of conjunctival venules have been reported.[61] Ophthalmological findings can occur as early as 74 days after vitamin C deprivation.

Other diagnostic factors

uncommon

dysphagia

A possible early, non-specific symptom.

alopecia

A dermatological sign relating to endothelial dysfunction.

sicca-like or Sjogren's-like syndrome

Xerostomia, xerophthalmia, keratoconjunctivitis.[1][2][18]

nail clubbing

May be present on examination.

peripheral (entrapment) neuropathy

Particularly likely to be present when peripheral oedema is evident.

cerebrovascular accident

Caused by haemorrhagic stroke.

cardiac failure

The aetiology of temporary cardiac dysfunction in scurvy is poorly understood, but in severe cases it may be related to endocardial haemorrhage.

haemorrhagic pleural effusion

Uncommon, but potentially life-threatening.

osteoporosis

May occasionally be present.

Risk factors

strong

famine and refugee populations

This group of people may have decreased access to sufficient vitamin C owing to insufficient amounts in food provisions, poor financial resources to purchase fruits and vegetables, and scarce land or water to grow fruits and vegetables. Within these groups, pregnant women and those with chronic infection may be at even greater risk; however, data from victims of the Irish potato famine suggested that young people and men were at greatest risk of scurvy.[36] Restricted access to camel's milk, which contains about 210 micromol/L (37 mg/L) vitamin C (3 times that of cow's milk), may have played a role in some African scurvy epidemics.[1][37]

In 2001-2002, the Afghanistan population was affected by scurvy due to famine. In April 2001, 6.5% of all deaths were due to scurvy. In April 2002, 4.5% of all children exhibited at least one sign or symptom of scurvy.[1][12][13]

The most recent refugee-based epidemic of scurvy occurred in 2017-2018, affecting 45 South Sudanese adolescents and young men living in Kenyan Turkana District Kakuma Refugee Camp. Paradoxically, this outbreak followed an attempt to allow for food diversification by offering e-cash instead of a portion of rations which included micronutrient fortification. The findings also suggested that adolescents and young males had a higher requirement for vitamin C, highlighting the inter-individual variation in vitamin C requirements.[15]

alcohol use disorder

Psychiatric disorders may preclude some patients from achieving balanced diets. Individuals with alcohol use disorder may have other nutritional deficiencies, such as thiamine deficiency, in addition to low levels of vitamin C.[1][3][17][18][19][20][39]

infants taking only cow's milk

A risk for scurvy due to the low vitamin C content of cow's milk. Of note, vitamin C amounts in human breast milk can be greater than the total amount of vitamin C consumed by the mother. Scurvy has not been reported in breast-fed infants.[1][3][17][18][19][20][45]

end stage renal disease, haemodialysis dependence, and/or post-renal transplant

Haemodialysis results in vitamin C removal from the bloodstream. Overall, scurvy is relatively infrequent among dialysis patients, but dialysis is associated with low levels of vitamin C in epidemiological studies. The risk for scurvy is unknown, but caregivers should assure adequate vitamin C intake.[20][46]​ Recipients of kidney transplants are frequently vitamin C deficient, regardless of time after transplant.[47]

smoking

Associated with low levels of vitamin C in epidemiological studies. The risk for scurvy is unknown.[7][20]

surgery

Associated with low levels of vitamin C in epidemiological studies. The risk for scurvy is unknown.[20]

Special consideration should be made for patients undergoing bariatric surgery, who may have low levels both preoperatively and postoperatively. Preoperative deficiency may stem from a longstanding diet low in fruit and vegetables. Given that most bariatric patients receive postoperative multivitamins, the aetiology of vitamin C deficiency postoperatively in these patients is uncertain, but has been proposed to be related to chronic iron deficiency. No cases of clinical scurvy in bariatric surgical patients have been reported.[48][49]

sepsis

Associated with low levels of vitamin C in epidemiological studies. The risk for scurvy is unknown.[20][24]​ Supplementation with vitamin C has not been shown to improve outcomes.[50][51]

HIV

Associated with low levels of vitamin C in epidemiological studies. The risk for scurvy is unknown.[20]

critical illness

Critical illness and acute hospitalisation are associated with rapid decreases in vitamin C levels.[52][53]​ Among patients with cardiac failure, poorer quality of life and a shorter duration of cardiac event-free survival have been associated with low levels of vitamin C.[54][55]​ Patients undergoing haematopoietic cell transplantation are also at risk for low levels of vitamin C.[56] The risk for clinical scurvy among these groups is unknown.[20]​ A 2023 retrospective paediatric study examined perioperative changes in vitamin C levels in critically ill children undergoing congenital heart surgery with cardiopulmonary bypass. The study found that postoperative vitamin C levels decreased, with 7% of patients experiencing hypovitaminosis C or vitamin C deficiency.[57]

pancreatitis

Associated with low levels of vitamin C in epidemiological studies. The risk for scurvy is unknown.[20]

inflammatory bowel disease (IBD)

Vitamin C deficiency has been seen in a number of patients with IBD, secondary to dietary restrictions. Signs and symptoms of scurvy were present in 80% of patients with IBD and vitamin C deficiency in a recent case series.[58]

weak

acute respiratory distress syndrome

Associated with low levels of vitamin C in epidemiological studies. The risk for scurvy is unknown.[20]​

older people

Older people may have restricted finances or be unable to maintain a balanced diet due to physical or cognitive impairment.[1][3][17][18][19][20]

living alone

People accustomed to having others prepare a balanced diet for them (e.g., widows, widowers) may lose certain micronutrients once tasked with preparing full meals for themselves.[1][3][17][18][19][20]

psychiatric disorders

Psychiatric disorders such as anorexia, depression, obsessive-compulsive disorder, or schizophrenia may preclude some patients from achieving balanced diets.[1][3][17][18][19][20][38]

dementia

Dementia may preclude some patients from achieving balanced diets.[38]

low income

Poor populations with restricted access to a complete diet (due to financial or geographical reasons) may be at risk.​[40]

atypical diets

Atypical diets, publicised or idiosyncratic, have been associated with scurvy.[1][3][17][18][19][20] Although rare, two cases of scurvy following a ketogenic diet (for epilepsy) have been reported.[41][42]

poor dentition or masticatory inefficiency

Most foods rich in vitamin C, such as fruits and vegetables, require sufficient mechanisms for chewing. This issue can be circumvented with supplements and juices.[1][3][17][18][19][20]

autistic spectrum disorder

Scurvy is one of several nutritional deficiency syndromes associated with autistic spectrum disorder. Several cases related to abnormal dietary preferences have been reported; however, estimates of prevalence may be low due to under-reporting.[43]​[44]​ One recent retrospective study showed that 27% of children with low vitamin C levels also carried a diagnosis of autism spectrum disorder.[16]​ Other childhood behavioural disorders (depression, idiosyncratic dietary patterns) may be a risk factor for scurvy in patients without otherwise identifiable risk factors.[1][3][17][18][19][20]

static encephalopathies of childhood

One review found 21 cases of scurvy related to idiosyncratic diets due to a variety of behavioural disturbances and static encephalopathies of childhood.[3]

graft versus host disease (GVHD)

Vitamin C deficiency has been observed in paediatric and adolescent patients with chronic GVHD and mucous membrane involvement.[59]

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