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Report

Oxford, UK
International
IJD
Blackwell
1365-4632
45 Publishing,
Publishing
Journal Ltd,
of
Ltd.
Dermatology
2005

Scurvy: a disease almost forgotten


Olmedo et al.
Scurvy
Report

Jesse M. Olmedo, MD, James A. Yiannias, MD, Elizabeth B. Windgassen, MD, and
Michael K. Gornet, MD

From the Department of Dermatology, Abstract


Division of Regional and International Background Although much decreased in prevalence, scurvy still exists in industrialized
Medicine, and Division of Hematology/ societies. Few recent large studies have examined its pathogenesis, signs, and symptoms.
Oncology, Mayo Clinic, Scottsdale, Arizona
Methods After we diagnosed scurvy in a 77-year-old female patient in 2003, we conducted a
Correspondence retrospective records review to identify patients with scurvy treated between 1976 and 2002 at
James A. Yiannias, MD Mayo Clinic (Scottsdale, Arizona; Rochester, Minnesota; or Jacksonville, Florida). We also
Department of Dermatology searched the English-language medical literature for published reports on scurvy.
Mayo Clinic
Results In addition to our patient, seven of 11 patients whose records in the institutional
13400 East Shea Boulevard
Scottsdale database mentioned vitamin C deficiency were women. The age ranged from a neonate to
AZ 85259 77 years (mean, 48 years). The most common associated causes were concomitant
gastrointestinal disease, poor dentition, food faddism, and alcoholism. Vitamin or mineral
deficiencies other than vitamin C deficiency were also found in our patients who had scurvy.
The most common symptoms were bruising, arthralgias, or joint swelling. The most common
signs were pedal edema, bruising, or mucosal changes. Four patients had vague symptoms of
myalgias and fatigue without classic findings, and five had concomitant nutritional deficiencies.
Follow-up available for six of 12 patients treated by vitamin C supplementation showed complete
resolution of symptoms in five.
Conclusions Patients with scurvy may present with classic symptoms and signs or with
nonspecific clinical symptoms and an absence of diagnostically suggestive physical findings.
Concomitant deficiency states occur not uncommonly. Taking a thorough dietary history and
measuring serum ascorbic acid levels should be considered for patients with classic signs and
symptoms, nonspecific musculoskeletal complaints, or other vitamin or mineral deficiencies.

identified by this method, we first describe one patient who


Introduction
presented in 2003 to our clinic. This patient was also included
Scurvy is a disease historically associated with sailors on in our statistical analysis.
lengthy voyages. Although much decreased in prevalence, the
disease still exists today, even in industrialized societies.
Case Report
Scurvy occurs as a result of decreased vitamin C consumption
or absorption. We report a case of profound scurvy identified A 77-year-old woman with a 10-year history of hives that she
in a patient treated in 2003 at Mayo Clinic, Scottsdale, Ari- attributed to all types of fruits and vegetables presented with
zona. We then present a retrospective records review of all fatigue, bruising, gingival bleeding, and anemia. For the preceding
patients with scurvy who were treated at Mayo Clinic (Scotts- 2 years, the patient’s diet had consisted only of bread, olive
dale, Arizona; Rochester, Minnesota; or Jacksonville, oil, and red meat because of the perceived food allergy. In the
Florida) between 1976 and 2002, and review the medical preceding 3–5 months, she had experienced increased fatigue
literature on scurvy. and extensive bruising on her arms and legs. She had also noticed
a grayish discoloration of her face. For weeks, she had experienced
occasional nosebleeds, bleeding of the gums while brushing
Materials and Methods
her teeth, and soreness of the tongue. On the day the patient
The medical records of Mayo Clinic patients treated between 1976 presented for treatment at our tertiary-care clinic, she noticed
and 2002 were searched electronically. Search terms were bright red blood from the rectum during a bowel movement.
diagnoses such as scurvy, ascorbic acid deficiency, vitamin C Her face and “vee” of the neck were noticeably slate gray
deficiency, avitaminosis C, and scorbutus. In addition to patients (Fig. 1). Her arms and legs demonstrated circumferential, 909

© 2006 The International Society of Dermatology International Journal of Dermatology 2006, 45, 909–913
910 Report Scurvy Olmedo et al.

masticatory mucosa had dilated tortuous vessels. No joint


abnormalities were identified.
Workup revealed normocytic anemia with a hemoglobin
of 8.8 g /dL (reference range, 11.5–15.5 g /dL), hematocrit of
26.4% (reference range, 33.3–43.3%), and mean corpuscu-
lar volume of 86.1 fL (reference range, 82.7–96.8 fL). Iron
studies, prothrombin time, and international normalized
ratio were within normal ranges. A bone marrow biopsy
identified ineffective erythropoiesis. Values for vitamin B12
and folate were within normal ranges, whereas the concentra-
tion of vitamin C was undetectable. The zinc level was
0.56 µg /mL (reference range, 0.66–1.10 µg /mL).
A 6-mm punch biopsy on a violaceous nodule on the left
lower leg showed dermal and subcutaneous hemosiderin
deposition with fibrosis, suggestive of a resolving hematoma.
Findings of an external biopsy specimen from the right neck
were suggestive of ochronosis, and findings of a biopsy
specimen from the right upper alveolus indicated a pyogenic
granuloma.
A diagnosis of scurvy was established and the patient was
Figure 1 Slate gray discoloration of the patient’s face and “vee”
of the neck started on vitamin C, 100 mg three times a day for 2 weeks,
and then continued on 100 mg a day. Additional information
from the patient about her suspected food allergies revealed
that the urticarial lesions did not cease completely when she
avoided all fruits and vegetables, and so we recommended the
addition of doxepin hydrochloride, 10–20 mg once a day at
bedtime. As the urticarial lesions improved, the patient was
able to expand the types of foods she ate.
The patient was also diagnosed with a concomitant zinc
deficiency that most probably accounted for her sore tongue,
and she was started on oral zinc sulfate, 220 mg twice a day.
After only 3 days of supplementation, the patient had an
increase in the concentration of vitamin C to 0.4 mg /dL (ref-
erence range, 0.6–2 mg /dL), and signs of new bruising and
gingival bleeding resolved. On physical examination, the
ecchymoses, petechiae, and gingival tenderness were also
found to have improved.
Although, clinically, the slate gray pigmentation was
suspicious for pellagra, the patient said that she had been
applying large quantities of topical hydroquinone to her face
for years. This self-treatment seemed to account for her gray
pigmentation and for other histologic features suggestive of
ochronosis.

Figure 2 Deep, tender, ill-defined nodules (ranging in color from


Results
flesh tones to violaceous) may accompany ecchymotic patches
with perifollicular petechiae and red nonscaling papules In addition to our patient, the retrospective records review
identified 11 patients, 10 from Rochester and 1 from Scottsdale,
whose charts made reference to a vitamin C deficiency. Eight
ecchymotic patches with perifollicular petechiae and red of the overall total of 12 patients were women, and the age
nonscaling papules. Deep, tender, ill-defined, flesh-colored to range overall was from a neonate to 77 years (average, 48 years).
violaceous nodules accompanied these lesions (Fig. 2). The The causes of scurvy in the 12 patients included absorption
patient’s gums were hypertrophied and tender. The non- maladies, such as severe reflux, colitis, strictures, or nonspecific

International Journal of Dermatology 2006, 45, 909–913 © 2006 The International Society of Dermatology
Olmedo et al. Scurvy Report 911

Table 1 Pathogenesis of scurvy* Complete resolution of symptoms was noted as early as


1 week and as late as 1 month. One male patient did not
Cause No. of patients respond to 5 weeks of vitamin C supplementation. Because
this patient was lost to further follow-up, the pathogenesis of
Gastrointestinal disease 4 his symptoms and the reason for his lack of response to vita-
Dentition abnormalities 4
min C supplementation could not be ascertained.
Food faddism (avoidance) 5
Alcohol or illicit drug use 4
Concomitant deficiency (e.g. calcium, vitamin B12, iron) 5
Discussion
Mental disorder 2
Prematurity 1 Scurvy was first described in the Ebers papyrus written about
1500 bc. Historically, scurvy has been known as an illness
*n = 12 (individual patients may have had more than one cause
affecting sea voyagers. Between 1500 bc and ad 1800, scurvy
of vitamin C deficiency).
killed more sailors than all other diseases and disasters com-
bined.1 In 1753, Sir James Lind, a ship’s surgeon in the British
malabsorption, that resulted in an inadequate intake of vita- Navy, recognized that citrus fruits could prevent and treat
min C (Table 1). Poor dentition complicating mastication scurvy on long sea voyages. Unfortunately, for many years,
also resulted in inadequate vitamin C consumption in four “sea scurvy” was not associated with “land scurvy.”
patients. Alcohol abuse, illicit drug use, and severe mental dis- For example, the Great Famine of Ireland was precipitated
orders (e.g. depression or dementia) were related to 10 cases by the failure in 1845 of the crops of potatoes, a rich source
of vitamin C deficiency. Food faddism or avoidance of prod- of vitamin C that was the mainstay of the peasants’ diet.
ucts containing vitamin C because of an alleged intolerance or Many deaths from scurvy also occurred during the Crimean
allergy was present in five patients. War, the U.S. Civil War, the California gold rush, and the
journey of settlers westward along the Mormon Trail to
Symptoms and signs Utah. It was not until 1931 that Albert Szent-Györgyi, a bio-
The most common symptoms were bruising, arthralgias, and chemist and Nobel laureate, discovered and identified the
joint swelling (Table 2). Four patients, however, exhibited antiscorbutic factor in citrus fruits and potatoes. The
less common symptoms that included fatigue and myalgias. antiscorbutic factor was initially called hexuronic acid and
The most common signs of vitamin C deficiency were non- subsequently was renamed vitamin C.1
specific pedal edema and bruising (11 patients; Table 2). Also Vitamin C serves various functions in the human body. It
commonly present was oral mucosal involvement with is responsible for the hydroxylation of collagen, the bio-
petechiae or gingival swelling. Of note, three patients demon- synthesis of carnitine and norepinephrine, the metabolism of
strated no physical signs suggestive of scurvy, but their his- tyrosine, and the amidation of peptide hormones. Vitamin C
tory suggested poor intake of vitamin C, thereby prompting functions as an antioxidant and is therefore decreased in
the physician to screen for its deficiency. oxidative states associated with diabetes, smoking, or myo-
cardial infarction. Vitamin C also promotes iron absorption
Response to treatment by reducing dietary iron from the ferric to the ferrous form.2
Six patients had subsequent follow-up that mentioned their It is also important in disulfide bonding of hair.3
response to vitamin C supplementation. Five patients The function of vitamin C in collagen synthesis is extremely
responded to vitamin C supplementation (500 mg daily). important; the abnormality in collagen synthesis is responsible

Table 2 Symptoms and signs of scurvy*


Symptom No. of patients Sign No. of patients

Bruising 5 Pedal edema 5


Arthralgias 5 Bruising 6
Joint swelling 4 Mucosal changes (petechia /gum swelling) 5
Dysphagia 2 Normal examination 3
Nausea 2 Joint swelling 2
Fatigue 3 Alopecia 1
Depression 1 Nail clubbing 1
Myalgias 1 Emesis 1

*n = 12 (individual patients may have had more than one physical examination finding
indicative of vitamin C deficiency).

© 2006 The International Society of Dermatology International Journal of Dermatology 2006, 45, 909–913
912 Report Scurvy Olmedo et al.

for most manifestations of scurvy. Mature collagen is com- or myalgias) may be secondary to anemia, which develops in
posed of three polypeptide molecules in a triple helix. The 75% of patients because of blood loss, concomitant folate
polypeptides are initially synthesized in the ribosome as deficiency, or altered iron absorption. The anemia is most
procollagen molecules; the lysyl and prolyl residues are then commonly normochromic normocytic.5 Myalgias occur
hydroxylated using vitamin C as a cofactor. The absence because of the reduced production of carnitine.6
of hydroxylysyl and hydroxyprolyl residues renders the Scurvy causes changes in the skin as a result of defective
polypeptide unstable and unable to self-assemble into rigid collagen synthesis. Classic changes on the legs and buttocks,
triple helices. This defect in collagen results in blood vessel where hydrostatic pressure is greatest, are hyperkeratotic
fragility and poor wound healing.3 papules with corkscrew hairs and perifollicular hemorrhage.
The pharmacokinetics of vitamin C have been studied Petechiae becoming confluent into large ecchymoses and
extensively. Ascorbic acid is absorbed well at lower doses, but the even palpable purpura may occur on the lower legs because
percentage of absorption decreases as the dose is increased. of blood vessel fragility. The legs can become edematous
For a 30-mg dose, 87% is absorbed, whereas only 50% of a because of soft tissue hemorrhage or heart failure secondary
1250-mg dose is absorbed. Ascorbic acid is not protein bound, to anemia. The nails may develop splinter hemorrhages.
and is excreted by the kidneys. In healthy persons, vitamin C can Alopecia can occur because of defective disulfide bonding.
be reabsorbed by the kidneys, but it is lost during hemodialysis, Because of defective collagen production, wounds heal poorly
making patients with end-stage renal disease at particular risk and even old scars can break down.3
for scurvy. Circulating white blood cells contain 10 –30 times Patients with scurvy may also develop oral complications.
the plasma concentration of vitamin C, which concentrates in The gingivae often bleed with minor trauma. The gums
the brain, adrenal cortex, liver, spleen, pancreas, and kidney become red, smooth, swollen, and shiny. Eventually, the
tissues;2 the mechanism behind this process is not known. gums may recede or become necrotic. As alveolar bone
Most animals require no exogenous source of vitamin C; absorption occurs, tooth loss may occur.3
however, guinea pigs, fruit bats, and humans do not have the Rheumatologic problems, such as painful hemarthrosis
ability to synthesize vitamin C. Humans obtain 90% of their and subperiosteal hemorrhage, may develop in persons with
intake from fruits and vegetables. Cooking reduces vitamin C scurvy. Subperiosteal hemorrhage in infants may cause
content by 20–40%.3 The total body pool of vitamin C is Barlow syndrome, which is associated with extreme pain and
1500 mg, and clinical manifestations of scurvy occur when an immobilized posture (hips and knees in semiflexion).5
this pool is reduced to less than 350 mg. To reach such a low Scurvy can also have an impact on the heart. Cardiac
level, vitamin C must be completely eliminated from the diet enlargement may occur because of congestive heart failure
for 60–90 days. Yet, as little as 6 –10 mg of vitamin C each secondary to high-output anemia. Hemopericardium result-
day is sufficient to maintain a level of 350 mg. A single orange ing in sudden death has been reported.5
contains 50 mg of vitamin C.4 The recommended dietary Ophthalmic manifestations include conjunctival hemor-
allowance for vitamin C was recently increased by the Food rhage and fundus changes, including flame-shaped hemor-
and Drug Administration to 75 mg per day for women and rhages and cotton-wool spots. Bleeding into the retrobulbar
90 mg per day for men. Notably, the vitamin C intake in 2001 space and into the optic nerve sheaths can cause papilledema
was less than 60 mg in 20 –30% of US adults, a level that can and optic nerve atrophy. Sjögren-like symptoms have also
result in subclinical vitamin C deficiency.2 been noted.3
Scurvy occurs because of reduced intake or absorption of The diagnosis of scurvy is generally based on clinical fea-
vitamin C. At-risk groups include the poor (because of tures and dietary history, and there is rapid resolution of signs
reduced access to groceries), food faddists, widowers, and and symptoms after vitamin C supplementation. Laboratory
individuals with purported allergies to multiple fruit and investigations may not be necessary to diagnose scurvy, but
vegetable products. Other at-risk groups include persons with are useful to confirm less typical cases. The concentration of
gastrointestinal disease (e.g. colitis), anatomical abnormali- ascorbic acid may be checked, but this value tends to reflect
ties, or poor dentition. Cancer patients on chemotherapy who recent dietary intake rather than actual vitamin C.5 A serum
have increased nausea and diarrhea are also at risk, as are level below 11 µmol/L suggests scurvy.6 A leukocyte ascor-
patients on hemodialysis. Psychiatric disorders (e.g. depres- bate level more accurately reveals tissue stores of vitamin C,
sion, schizophrenia, or anorexia) have also been recognized but the test is difficult to perform and not readily available.5
as putting patients at risk for reduced intake of vitamin C. An ascorbic acid tolerance test can be used to assess vitamin
Alcoholic persons represent one of the largest groups at risk C status. The test is simple to administer and suitable for
for scurvy because they may have poorly balanced diets and patients. It involves giving an oral load of 1 g of ascorbic acid
because alcohol decreases the absorption of vitamin C.3 in water and then measuring the urinary excretion of vitamin
Patients with scurvy exhibit various systemic manifesta- C during the next 6 hours.7 Biopsy of a follicular lesion
tions. Severe constitutional symptoms (e.g. weakness, fatigue, characteristically shows a dilated hair follicle with keratin

International Journal of Dermatology 2006, 45, 909–913 © 2006 The International Society of Dermatology
Olmedo et al. Scurvy Report 913

plugging and perifollicular hemorrhage. Occasionally, a cork- screening for vitamin C deficiency by dietary history and,
screw hair may be found;6 however, biopsy specimens of lesions, possibly, by evaluating serum ascorbic acid levels should be
such as the hemorrhagic cutaneous lesions of our patient, may considered for patients with classic signs and symptoms of
be nonspecific (e.g. showing only hemorrhage and fibrosis). scurvy, as well as for those with common, nonspecific,
The treatment of scurvy involves increased vitamin C chronic musculoskeletal complaints.
intake. Correcting the deficit and repleting body stores Concomitant nutritional deficiencies were also identified
requires 100 mg three times daily. Subjective improvement in in this study population. Five (42%) of the 12 patients had
fatigue, pain, and anorexia typically occurs within 24 hours. concomitant deficiencies in calcium, vitamin B12, or iron. We
Joint swelling resolves in days. The ecchymoses resolve in 1– therefore recommend screening broadly for other nutritional
2 weeks. By 4 weeks, the corkscrew hairs regain normal deficiencies in patients identified with vitamin C deficiency.
growth. The gums heal within 1–2 weeks, and complete Specifically, screening should include vitamin B12, folate, iron,
recovery occurs after about 3 months of treatment.3 and zinc levels. The corollary of this concept is that clinicians
Our study clearly shows that scurvy continues to exist, should be aware of possible vitamin C deficiency when defi-
even in industrialized nations such as the USA. Our findings ciencies in other minerals or vitamins are identified.
also indicate that decreased vitamin C consumption can be All physicians should be aware of the clinical presentations
associated with gastrointestinal disease, poor dentition, food of vitamin C deficiency, because the presentation of the patient
faddism, alcoholism, or mental disorders such as major with scurvy may be subtle. Recognizing the disease requires
depression. Thus, a thorough dietary review to detect both heightened vigilance; however, when patients with scurvy are
clinical and subclinical cases of scurvy should be part of every diagnosed early, the condition can be readily treated.
review of systems.
The patients in our study reported the classic symptoms of
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© 2006 The International Society of Dermatology International Journal of Dermatology 2006, 45, 909–913