Disease of the past re-emerging in modern Australian society

Abstract

A 28-year-old man with fever, atraumatic lower limb pain and rash was noted to have multiple areas of ecchymosis involving both lower limbs. He was anaemic and also had a grossly swollen left leg. Differential diagnoses of compartment syndrome, vascular tear, platelet and clotting factor disorders, vasculitis and myositis were ruled out. Scurvy was only considered after failing to reach a diagnosis. A dietary history revealed consumption of a restricted diet with no fresh fruits or vegetables. Diagnosis was supported by an undetectable vitamin C level in blood and a rapid improvement of symptoms on oral vitamin C replacement. Prevalence of vitamin C deficiency in developed countries is also discussed.

Background

This case highlights a presentation of a condition that was more prevalent in the past. Though easily missed, diagnosis and treatment is inexpensive and safe. The key to making this diagnosis is a good clinical history.

Case presentation

A 28-year-old male Caucasian was referred to the emergency department (ED) by his general practitioner with intermittent fevers and progressive bilateral leg bruising. He took regular pantoprazole but no other medications. There was no family history of bleeding disorders.

He described a 4-week history of gradually worsening atraumatic left leg pain and swelling with associated large areas of bruising on his both lower limbs and intermittent fevers up to 38.6°C (figure 1). He also reported a non-healing ulcer of his right great toe following an ingrown toe nail excision. On examination, he was of normal built with a weight of 75.6 kg. His left thigh, knee and calf were swollen without erythema, warmth or tenderness. There were multiple ecchymoses involving both of his lower limbs. Both dorsalis pedis pulses were readily palpable. There were no bruises on his mucosal surfaces, upper limbs or trunk. His right great toe had a small non-healing ulcer without any obvious signs of infection. He did not have follicular haemorrhage or corkscrew hairs. Cardiovascular, respiratory and abdominal examinations were unremarkable.

Figure 1.

Ecchymoses of the lower limbs on presentation.

Within the first 2 days of his hospitalisation, we noted a gradual haemoglobin drop from 11.6 g/dL to 8.2 g/dL over 2 days and progression of the ecchymoses and the swelling of the left calf. On further questioning, he reported some tissue loss from around his gums while brushing his teeth a few weeks prior but had no gingival swelling or bleeding. There was no history of night sweats or recent weight loss. It was noted that his diet consisted primarily of one main meal per day of homemade carbonara sauce with pasta for many years. He consumed no fruit or vegetables and rarely ate meat. Spontaneous bleeding and poor wound healing secondary to symptomatic vitamin C deficiency was suspected.

Investigations

Initial investigations revealed a microcytic anaemia with haemoglobin of 11.6 g/dL (13–18 g/dL), mean corpuscular volume 79 fL (82–98 fL), platelets 407×10⁹/L (150–400/L), bilirubin 38 µmol/L (≤20 µmol/L), albumin 29 g/L (35–50 g/L), lactate dehydrogenase 177 U/L (120–250 U/L) and a prothrombin time of 15 s (11–18 s).

White cell count was normal at 7.0×10⁹/L (2.7×10⁹–90.5×10⁹/L), but C reactive protein was elevated to 36 mg/L (<3 mg/L). Blood cultures were negative. Creatine kinase was not elevated at 53 U/L (55–170 U/L). Antinuclear cytoplasmic antibodies (ANA) were detected with a speckled pattern but a low titre of 1:80. Cytoplasmic ANCA and perinuclear ANCA were not elevated at 3 U/mL (≤5 U/mL) and 0 U/mL (≤10 U/mL), respectively. Haematological investigations revealed normal von Willebrand factor studies.

MRI of the lower limbs demonstrated haemorrhage into the posterior compartment musculature without evidence of an arterial tear, muscle tear or myositis.

A sample collected several days into the patient’s admission demonstrated an undetectable vitamin C level in blood of <5 µmol/L (40–100 µmol/L) which confirmed the diagnosis of scurvy. He was also deficient in vitamin B₁₂ and folic acid with a level of 103 pmol/L (>150 pmol/L) and 5.7 nmol/L (>10.0 nmol/L), respectively. Iron studies showed a relatively low level of body iron with serum levels of 7.8 µmol/L (7.0–29.0 µmol/L), transferrin 1.8 g/L (1.8–3.3 g/L), transferrin saturation 30% (10%–45%) and ferritin 70 ug/L (30–300 ug/L).

Differential diagnosis

Given a presentation with atraumatic spontaneous bleeding and fever, multiple diagnoses were considered including vasculitis, myositis, von Willebrand disease, haemophilia, platelet disorders, compartment syndrome and muscle tear. Compartment syndrome of the left leg was ruled out clinically and on imaging.

It was speculated that the patient’s fever was secondary to an infected right toe ulcer.

Ultimately, it was not the extensive investigations that led to his diagnosis but focused history taking which uncovered his restricted diet and a consideration of symptomatic vitamin C deficiency.

Treatment

With the advice of a haematologist, he was commenced on supplemental vitamin C 1 g daily. Within 48 hours, there was an evidence of improvement, with resolution of fever, reduced myalgias and no evidence of new petechiae or ecchymoses. Dietary advice and iron and folic acid supplementation were also provided for his nutritional deficiencies.

Outcome and follow-up

At 1-month follow-up, the patient was asymptomatic, with complete resolution of the ecchymoses (figure 2).

Figure 2.

Complete resolution at 1 month follow-up post vitamin C replacement.

Discussion

Scurvy is a condition that arises from a deficiency in vitamin C. Unlike many other animals, humans are unable to produce vitamin C endogenously through metabolising glucose, thus, diet is often the primary source, with a recommended daily intake of at least 30 mg.¹ Signs and symptoms of scurvy typically include anaemia, gingivitis, bruising, arthralgia, lethargy and impaired wound healing. The haemorrhagic manifestations of scurvy can be attributed to a deficiency in collagen synthesis as a consequence of low vitamin C levels.¹

The history of scurvy in Australia can be traced back to Captain James Cook who, aboard his vessel HMS Endeavour, was among the first to show that sailors could prevent or treat scurvy by consuming a diet rich in green vegetables.² Modern industrialised society has brought with it the advent of processed foods leading to reduced amounts of available vitamin C in various products.³

Patients at risk of vitamin C deficiency include those with poor dietary intake, alcoholism, lower socioeconomic status, smoking and those who had not used nutrient supplements in the last month.^{4 5} Vitamin C deficiency in Australia has been noted to be present in patients attending tertiary diabetes clinics and EDs. A diabetes clinic in western Sydney found that 7 of 11 patients in a retrospective cohort study over a 2-year period had vitamin C deficiency.⁴ These patients were similar to our patient in that they also had diets devoid of fruits and vegetables. In contrast, most of the patients in this study were overweight or obese. A similar case to ours was described in Gosford, Australia in 2009.⁶ A recent observational study involving medical inpatients at an urban tertiary hospital in Australia highlighted that vitamin C deficiency was common; 114 of 149 tested (76.5%) had deficient vitamin C levels (level <28 µmol/L was classified as low). Such deficiency was associated with a longer length of stay (6 days vs 4 days, p 0.02).⁷ A study of inpatients in a Canadian hospital showed that 61 of 149 patients (60%) had suboptimal levels of serum vitamin C concentration (<28.4 µmol/L) while 29 of 149 patients (19%) were deficient (<11.4 µmol/L).⁸ Comparatively, a study of inpatients in a Paris hospital found that 87 of 184 patients (47.3%) had reduced vitamin C levels (<5 mg/L) with 31 of those patients (16.9%) having a vitamin C deficiency (<2 mg/L).⁹

Furthermore, a UK study showed that 25% of men and 16% of women in the low socioeconomic population had vitamin C plasma levels which were consistent with a deficiency.¹⁰ In the USA, a study of 15 769 individuals aged 12–75 years, from 1988 to 1994, found that 5%–17% had reduced vitamin C levels (<11 µmol/L) and 13%–23% were vitamin C deficient (11–28 µmol/L).¹¹ Data published by the Australian Bureau of Statistics as part of the Australian Health Survey 2011–2012 found that <5% of the population had inadequate intake of vitamin C.¹² Thus, an awareness of the high prevalence of vitamin C deficiency among patients, especially the elderly, is essential as it can cause the manifestation of orthostatic hypotension and skin bruising.¹³

Our case acts as a reminder that we need to regularly ask our patients about their diet, and to suspect scurvy when there is history of a restricted diet. An increased awareness of scurvy and its presentation means that diagnosis can be made based on history and thus avoid over investigation and prolonged hospital admissions. This lesson is especially pertinent given the high prevalence of vitamin C deficiency in developed countries and that the treatment of dietary deficiencies is inexpensive and safe.^{1 7–9}

Learning points.

• Scurvy is likely under-recognised in developed countries.

• It should be considered in the differential diagnosis of patients presenting with a new bleeding diathesis.

• The diagnosis can be confirmed by a thorough history and serological testing is often unnecessary.

• Rapid clinical improvement occurs on vitamin C supplementation, which is safe and inexpensive.