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An unconventional case of scurvy

Subjects

In April 2012, a 29-year-old Caucasian man was admitted to our Department for worsening of chronic diarrhoea and the appearance of fatigue and lower limb oedema. During the previous 5 years, he had lost 50 kilos body weight (from 110 to 60, achieving a body mass index of 21.4) probably due to the malabsorption syndrome for which he had undergone extensive diagnostic work-up, including serological screening for endocrinopathies and immune-mediated enteropathies, stool tests, upper and lower endoscopy with biopsy sampling, despite which the underlying disease had not been identified. Moreover, previous tentative treatments with mesalamine, antibiotics and systemic steroids resulted only in transient benefit. No concomitant psychiatric or chronic illnesses, drug abuse, smoking or alcohol intake were reported. At admission, skin examination revealed multiple purpuric, non-scaling, follicular papules spread over the body and some ecchymotic patches with muscle wasting of the lower extremities and oedema of the calves (Figure 1). No organomegaly or lymphadenopathy were found. Blood tests showed moderate anaemia (haemoglobin 9.5 g/dl, red cell count 2.8 × 106, mean corpuscular volume 99.5 fl), lymphopenia (850 cells/μl, whose immunophenotype assessment pointed to a depletion of CD3+ T cells), hypo-albuminaemia (2.7 g/dl), hypo-γ-globulinemia (0.9 g/dl), hypo-ferritinaemia (12.0 ng/ml), increase of the erythrocyte sedimentation rate (34 mm/h), normal levels of folic acid, vitamin B12 and negativity of the D-xylose test (36 mg/dl, normal value 30 mg). Other investigations concerning systemic and organ-related autoantibodies, viral and bacterial tests, cryoglobulins, complement levels and coagulation (including prothrombin time, international normalized ratio and factors II, V, VII, IX and X) were all within normal ranges. Faecal occult blood test, calprotectin and stool tests for pathogens were repeatedly negative, while human immunodeficiency virus infection was ruled out by both specific antibody search and RNA analysis. A colour-Doppler ultrasound excluded deep vein thrombosis. The dermatologist consultation highlighted the presence of perifollicular haemorrhages and corkscrew hairs on careful inspection, while oral mucosa had normal appearance, thus raising the suspicion of scurvy, which was confirmed through a skin biopsy1 whose histological examination2 showed a scant, perifollicular and perivascular lymphocytic infiltrate in the superficial dermis with extravasated erythrocytes, and an overlying follicular hyperkeratosis (Figure 2). Meanwhile, following a further unremarkable upper and lower endoscopy, a wireless capsule enteroscopy was carried out which showed several areas with blunted and whitish villi scattered throughout the jejunum supporting the diagnosis of protein-losing enteropathy due to intestinal lymphangiectasia. Subsequent direct questioning revealed a two-year self-imposed diet completely devoid of vegetables and fruit in an attempt to reduce the number of bowel movements. Measurement of plasma level of vitamin C was not performed due to the unavailability in the laboratory; however, it should be considered that it is affected by recent intakes of vitamin C and may be normal despite a depleted body store.3 Moreover, laboratory investigations are usually not necessary in the diagnosis of scurvy, especially if histologic findings show the characteristic lesions and vitamin C administration promptly recovers the lesions.4 High-dosage supplementation was then administered (500 mg intravenously twice daily) for two weeks in order to replace the body store, followed by oral replacement at the same dose for a further two weeks, and was maintained with a daily intake of citrus fruits and green leafy vegetables.5 The follicular purpura improved rapidly after 2–3 days, and the ecchymotic patches faded almost completely within 7 days, while the lower limb oedema had already disappeared following a mild diuretic therapy and anaemia ameliorated after a month, when the patient was referred to a tertiary centre of intestinal microsurgery for the appropriate treatment of lymphangiectasia.

Figure 1
figure1

Skin lesions. Pinpoint follicular purpuric macules (black head arrows) and large ecchymotic patch (white arrows) on the right calf with follicular plugs (vertical black arrows).

Figure 2
figure2

Histological features. Follicular hyperkeratosis (black thin arrow) and sparse perivascular superficial infiltrate of lymphocytes (black head arrows) with perivascular, periadnexal and interstitial extravasation of erythrocytes in the dermis (white arrows). Haematoxylin and eosin, original magnifications × 20 and × 40 in the box.

Unlike most animals that do not require exogenous source of ascorbic acid since they derive it by the glucose metabolism, humans lack this skill, so they need a regular dietary intake5 with the citrus fruits, green vegetables, tomatoes, and peppers being very rich in vitamin C. This latter plays a crucial role in collagen biosynthesis where it is needed for proline hydroxylation. Mature collagen, indeed, is composed of three polypeptide molecules arranged in a triple helix, which are initially synthesized as procollagen molecules. The lysyl and prolyl residues are then hydroxylated using vitamin C as a cofactor. The absence of hydroxylysyl and hydroxyprolyl residues renders the polypeptide unstable and unable to self-assemble into rigid triple helices. This defect results in blood vessel fragility and easy bruising especially on the legs where the hydrostatic pressure is highest.3 Furthermore, vitamin C acts also as a potent redox agent which further protects blood vessels by removing free radicals.1, 3 Historically, scurvy is known as an illness affecting sailors on lengthy voyages deprived of citrus fruit and vegetables, whilst more recently it has been recognized as occurring in people with low socio-economic status and in alcoholics, caused by poorly balanced diets and because alcohol decreases the absorption of vitamin C, as well as in those undergoing chemotherapy, or those with psychiatric disturbances.3, 6, 7 The singularity of our case lies in the lack of these usual risk factors, except for diarrhoea due to lymphangiectasia. However, the possibility that this protein-losing enteropathy was the cause of the severe vitamin C deficiency appeared marginal, since ascorbic acid is not protein bound in the plasma and is excreted by the kidneys.3 On the other hand, the possibility of a dangerous self-imposed dietary restriction represents a new emergency in the Western world, where a growing number of people are susceptible to food faddism, resulting in the re-emergence of forgotten nutritional deficiencies.3, 8 Scurvy is a multifaceted disease ranging from severe multiorgan disfunction9 to slight symptoms including fatigue and arthralgias.3 Its diagnosis is therefore primarily based on clinical suspicion and dietary history of inadequate vitamin C intake, and then confirmed by a rapid resolution of signs and symptoms after vitamin C supplementation.

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Acknowledgements

This study was funded by a grant from: Fondazione Celiachia Italia, project entitled: ‘Studio di possibili fattori ambientali e sviluppo di nuove strategie terapeutiche nelle complicanze della malattia celiaca’ to GRC.

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Correspondence to R Ciccocioppo.

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Ciccocioppo, R., Gallia, A., Carugno, A. et al. An unconventional case of scurvy. Eur J Clin Nutr 67, 1336–1337 (2013). https://doi.org/10.1038/ejcn.2013.181

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