TYPE Original Research

PUBLISHED 14 September 2022

DOI 10.3389/fped.2022.981908

When the limp has a dietary

OPEN ACCESS cause: A retrospective study on
scurvy in a tertiary Italian
EDITED BY
Ozgur Karcioglu,
Taksim Training and Research
Hospital, Turkey

REVIEWED BY
pediatric hospital
Andrea Taddio,
Institute for Maternal and Child Health
Burlo Garofolo (IRCCS), Italy Daniela Masci1 , Chiara Rubino2*, Massimo Basile3 ,
Douglas Lanska,
University of Wisconsin-Madison, Giuseppe Indolfi2,4 and Sandra Trapani2,5
United States 1
Post-graduate School of Pediatrics, University of Florence, Florence, Italy, 2 Pediatric Unit, Meyer
*CORRESPONDENCE Children’s University Hospital, Florence, Italy, 3 Radiology Unit, Meyer Children’s University Hospital,
Chiara Rubino Florence, Italy, 4 Department of NEUROFARBA, University of Florence, Florence, Italy, 5 Department
[email protected] of Health Sciences, Meyer Children’s University Hospital, University of Florence, Florence, Italy
SPECIALTY SECTION
This article was submitted to
General Pediatrics and Pediatric The limping child frequently represents a diagnostic challenge. The differential
Emergency Care,
a section of the journal
diagnosis is broad and should include vitamin C deficiency. Scurvy, resulting
Frontiers in Pediatrics from vitamin C deficiency, is the oldest-known nutritional disorder. Despite
RECEIVED 29 June 2022 its rarity in developed countries, scurvy has been increasingly reported in
ACCEPTED 18 August 2022 recent years in pediatric patients, particularly those with autism or neurological
PUBLISHED 14 September 2022
disabilities. In the present retrospective study, we describe the clinical,
CITATION
Masci D, Rubino C, Basile M, Indolfi G
laboratory, and radiological features of 8 patients diagnosed with scurvy in the
and Trapani S (2022) When the limp Pediatrics Unit of Meyer Children’s University Hospital, between January 2016
has a dietary cause: A retrospective and December 2021. The majority (87%) were males, and the median age was
study on scurvy in a tertiary Italian
pediatric hospital. 3.7 years. Half of the patients had comorbidities known to be risk factors for
Front. Pediatr. 10:981908. scurvy, while the remaining patients were previously healthy. All the children
doi: 10.3389/fped.2022.981908
were admitted for musculoskeletal symptoms, ranging from lower limb pain
COPYRIGHT (87%) to overt limping (87%). Mucocutaneous involvement was observed in 75%
© 2022 Masci, Rubino, Basile, Indolfi
and Trapani. This is an open-access cases. Microcytic anemia and elevated inflammatory markers were common
article distributed under the terms of laboratory findings. Bone radiographs, performed on all patients, were often
the Creative Commons Attribution
interpreted as normal at first, with osteopenia (62%) as the most frequent
License (CC BY). The use, distribution
or reproduction in other forums is finding; notably, after re-examination, they were reported as consistent with
permitted, provided the original scurvy in four patients. The most common magnetic resonance imaging
author(s) and the copyright owner(s)
are credited and that the original findings were multifocal symmetrical increased signal on STIR sequence
publication in this journal is cited, in within metaphysis, with varying degrees of bone marrow enhancement,
accordance with accepted academic
adjacent periosteal elevation and soft tissue swelling. Differential diagnosis
practice. No use, distribution or
reproduction is permitted which does was challenging and frequently required invasive diagnostic procedures like
not comply with these terms. bone marrow biopsy, performed in the first three patients of our series. The
median time frame between clinical onset and the final diagnosis was 35
days. Notably, the interval times between admission and diagnosis become
progressively shorter during the study period, ranging from 44 to 2 days.
Treatment with oral vitamin C led to improvement/resolution of symptoms
in all cases. In conclusion, scurvy should be considered in the differential

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diagnosis in a limping child, performing a detailed dietary history and careful

physical examination, looking for mucocutaneous lesions. A quick and correct
diagnostic path avoids invasive diagnostic procedures and reduces the risk of
long-term complications.

KEYWORDS

scurvy, vitamin C, children, limping, musculoskeletal pain

Introduction records. Patients were included using “scurvy” as discharge

diagnosis keyword in Diagnosis Related Groups (DRG) database
Scurvy, resulting from vitamin C deficiency, is the search. The study describes the authors’ experience with
oldest-known nutritional disorder (1). Nowadays it is eight patients (observational, descriptive research design).
considered a rare disease confined to low- or middle-income Their medical charts were reviewed, in order to collect
countries (2). Recently, however, cases of scurvy are epidemiological and clinical data, laboratory and radiological
re-emerging also in developed countries in wealthy families. features, diagnostic work up, treatment and outcome, as
Autism spectrum disorders, neurological impairment and well as time-frame between onset and diagnosis, length
malabsorption are considered the main predisposing conditions of hospitalization and resolution of symptoms. Laboratory
in children in the modern age (3, 4). investigations including hemoglobin (Hb), Mean Corpuscular
The earliest manifestations of scurvy are non-specific Volume (MCV), C–reactive protein (CRP), white cell count,
systemic symptoms; however, in the pediatric population, it platelet blood count, ferritin, coagulation tests, vitamin D levels
usually presents with musculoskeletal complaints such as severe on admission were recorded. For each laboratory study, the
lower limb pain, limping and refusal to walk (4–6). Despite range, median and interquartile range (IQR) were calculated.
this, scurvy is rarely included in the differential diagnosis of Diagnosis of scurvy was based on clinical presentation,
a limping child. This often leads to prolonged workup and radiological findings, vitamin C serum levels lower than 200
unnecessary interventions before the right diagnosis is made. In µg/dL, and response to treatment. Four cases have been
addition, scurvy’s clinical features mimic more common diseases previously reported (7).
such as osteoarticular infectious, malignancy and autoimmune
diseases, frequently resulting in misdiagnosis. The diagnosis is
based on a combination of clinical and radiographic findings, Results
in a child with a dietary history indicating insufficient intake
of vitamin C. A low plasma level of vitamin C is specific for Seven of the eight patients were male, with a median
scurvy, though insensitive, as it can be normal if there has been age of 3.7 years (IQR 2.7, range 18 months - 12 years).
a recent vitamin C consumption in any form. Once started Four cases (50%) had comorbidities: two patients had autism
on vitamin C supplementation, patients recover quickly and spectrum disorder (#1 and #6), one patient had cerebral palsy
symptoms usually resolve in 2–4 weeks (5). Resolution of disease and focal epilepsy (#4), and one had spastic tetraparesis with
manifestations after vitamin C supplementation remains the severe neuro-developmental delay in Micro syndrome and
best evidence of scurvy. coenzyme q10 deficiency (#8). The remaining four children were
In the present study, we described the clinical characteristics previously healthy.
and the diagnostic work up of 8 patients diagnosed with scurvy Before being admitted to our hospital, patients had a
over the last 6 years in a pediatric tertiary care center. We aimed long duration of symptoms, the median time-frame between
to highlight the common clinical, laboratory and radiological clinical onset and hospital admission was 30 days (range 16–241
features of these children, in order to provide useful findings for days), with previous hospitalizations (#2, #3, #8) and access
a correct diagnostic approach. to the emergency department (ED) (range 1–4 accesses to ED
before admission).
All patients were admitted for musculoskeletal complaints.
Materials and methods Leg pain was the most common presenting symptom (7/8, 87%),
associated with low back pain in two patients (2/8, 25%). A
We performed a retrospective study on children diagnosed limping gait was present in seven out of eight patients (in
with scurvy in the Pediatrics Unit of Meyer Children’s University patient #8 gait was not assessable since she was unable to
Hospital in Florence, Italy, between 1st January 2016 and 31st walk), with complete refusal to bear weight in five patients
December 2021. Cases were identified among inpatient hospital (5/8, 62%). While three patients reported recent trauma, there

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was no preceding history of trauma in the remaining five. On

admission, three patients presented with fever (#2, #3, and #4).
Systemic symptoms, such as fatigue or malaise, were reported in
five patients; three had reduced appetite, and almost all patients
presented as highly irritable (7/8, 87%). One of the children
reported a history of gingival bleeding in the previous weeks, not
found on admission.
The clinical examination at admission revealed petechiae
and ecchymosis in three patients (#2, #3, and #4), and swollen
and bleeding gums in three (#4, #5, and #8). Four patients
presented cachectic and pale, with BMI below 5th percentile (#1,
#2, #5, #8); in contrast, the nutritional status of the other four
was good. Articular examination revealed a swollen limb in four
children (#1, #2, #4, and #5), no restriction in range of motion
FIGURE 1
was identified in almost all cases, except for patient #3 who
Frontal radiograph of right leg demonstrates multiple transverse
showed restricted hip mobility, keeping a “pithed frog’s posture” growth recovery lines (solid arrow) and inhomogeneous density
with semi-flexed knees and hips. Neurological examination of tibial diaphysis (open arrow). These findings were not initially
appreciated.
revealed reduced patellar tendon reflexes in four patients (#1,
#2, #3, and #6), without other abnormal findings, whereas it was
normal in the other patients.
During hospitalization, low-grade fever was detected in
other two patients (#5 and #8), and three patients developed metaphyseal bands (Trümmerfeld zone, 4/8, 50%) and dense
mucocutaneous involvement with swollen or bleeding gums or metaphyseal line (Frankel’s line, 4/8, 50%).
petechiae and ecchymosis without evidence of trauma. Magnetic resonance imaging (MRI) was performed in seven
Blood tests detected microcytic anemia in seven out of patients (focused on lower limbs in 5, pelvis in 6, whole body
eight patients (median Hb 9.9 g/dL, IQR 1.95, range: 6.9– in 1). Common MRI findings were multifocal symmetrical
11.8; median MCV 71.9 fl, IQR 2.42, range: 66.8–74), that increased signal on STIR sequence within metaphyses (6 cases),
in one case required blood transfusion (#2); leukocyte and with varying degrees of bone marrow enhancement (4 cases),
platelet blood count were normal in all patients. Inflammatory soft tissue swelling (4 cases), and adjacent periosteal elevation
markers were increased in all patients. Median CRP was (3 cases). A negative MRI of the spine ruled out spinal cord
1.08 mg/dL (negative if lower than 0,5 mg/dL, IQR 0.95, involvement in 4 patients.
range: 0.51–8.13); median ESR was 68 mm/h (negative if As an example, Figures 1, 2 show radiograph and MRI of
lower than 20 mm/h, IQR 29.5, range 23–109); median patient #5.
ferritin was 60.5 ng/mL (IQR 31, range 42–164). Fibrinogen In patients #1, #2, #3, and #6, in whom hypoelicitable tendon
was increased in five patients (median 478 mg/dL, IQR 59, reflexes were detected, electroneurography was performed and
range 438–598); lactate dehydrogenase was elevated only in resulted negative in all.
patient #3. Coagulation tests were normal in all patients. Other The patients #1 and #2 underwent bone biopsy, which was
laboratory findings were unremarkable. All patients underwent negative in patient #1, whereas it suggested the diagnosis of
an extensive infectious and autoimmune work up, with negative myosarcoma in patient #2. Consequently, this patient underwent
results. Antinuclear antibodies (ANA) were found positive (titer muscle biopsy, bone marrow aspiration, and a second bone
1:160) in patient #3. biopsy that ruled out malignancies. Bone marrow aspiration was
Hip ultrasound was performed on six patients and performed also in patients #1 and #3 and excluded malignancy.
interpreted as normal, except for patient #6 in which effusion Patient #2 refused to feed, therefore, given his cachectic
was found in the left hip. The ultrasound was performed before condition, enteral feeding via nasogastric tube was started. Non-
admission to the pediatric ED, when the patient was apyretic steroidal anti-inflammatory drugs (NSAIDS) were administered
and in good general condition; therefore, he was first treated as to all patients to ease pain, without significant improvement.
transient synovitis. In 4 cases, the use of opioid analgesics was necessary, with
Bone radiographs of lower limbs and pelvis, performed in mild improvement of musculoskeletal pain. Empiric intravenous
all patients, were often referred as normal at first, except for antibiotic therapy was administered to all patients in the
osteopenia (5/8, 62%) that was the most frequent finding. After initial suspicion of osteoarticular infection (osteomyelitis or
reexamination, they were reported as consistent with scurvy in septic arthritis).
four patients, documenting metaphyseal spurs with concomitant In all patients an accurate dietary history highlighted
cupping of the metaphyses (Pelkan spurs, 3/8, 37%), lucent restrictive and unbalanced diet, mainly based on carbohydrates.

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FIGURE 2
MRI with large field of view. Coronal (a,b) and sagittal (c) T2-weighted fat saturated views demonstrate abnormal marrow signal of femoral, tibia
and wrist metaphyses (white arrows) bilaterally, with more evident involvement of right tibia diaphysis, showing abnormal inhomogeneous signal
intensity (curved arrows). Coronal and axial views (d,e) after contrast administration show inhomogeneous enhancement of bone marrow
(white star) and periosteal tissue (black star), without periosteal collections.

In patients with neurological disabilities (#4 and #8), swallowing tested. Vitamin A (tested in 3/8), vitamin B12 (tested in 4/8),
difficulties had limited intake to smoothie or homogenized vitamin E (tested in 2/8) were normal in the small group of
foods; in the year prior to admission both children had excluded patients tested.
or severely limited fruit and vegetable intake. Patients with Treatment was started with 500 mg of vitamin C daily,
autism spectrum disorder (#1 and #6) had a history of food administered orally. The supplementation led to improvement
aversion of fruits and vegetables started after weaning. In the of symptoms in all cases, with resolution of cutaneous
group without comorbidities, two children started a selective and mucosal manifestations, improved general conditions
diet after a suspicious reaction to food during weaning; the other and nutritional status, alleviation of pain, and disappearance
two had developed an eating disorder rejecting new foods, in of limping. Spontaneous bleeding and systemic symptoms
particular fruits and vegetables. (irritability, loss of appetite) recovered quicker, within days, with
The dietary history, combined with clinical and radiological full recovery in one month in all patients (median three weeks).
features, raised the suspicion of scurvy. Thus, vitamin C serum This was associated with dietary improvement with introduction
levels were tested and resulted in insufficient concentrations of new foods in three children. In three patients, laboratory tests
(median 14.50 µg/dL, IQR 38.5, reference range: 460–1,400 were repeated after seven days of treatment, showing CRP and
µg/dL) in all patients. The median time-frame between ESR normalization.
admission and vitamin C dosage was six days (IQR 5.5). The treatment was continued for three months
The interval time between admission and diagnosis become at the same dosage in five patients, the dosage was
progressively shorter during the study period, ranging from 44 reduced to 300 mg after the first month in three cases. In
to two days. The average length of hospitalization was found to addition, in some patients vitamin D (5/8), multivitamin
be 21 days (median 18.5 days, IQR 14.2, range 7–52 days). supplementation (3/8), iron supplementation (6/8) were
Patients were studied for other micronutrient deficiencies: administered orally.
vitamin D was found to be at the lower limits of the normal range The prompt response to vitamin C supplementation
in two patients, insufficient in three patients, deficient in three together with the finding of deficient serum vitamin C levels
patients. Folate was found to be deficient in all three patients confirmed the clinical suspicion of scurvy.

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Discussion However, scurvy can also occur in healthy children

without known risk factors, only due to impaired diet (20–
The limping child frequently represents a diagnostic 24). Accordingly, half of our patients were previously healthy
challenge. The differential diagnosis is broad, ranging children with incorrect eating habits. Parental reports of
from benign and self-limiting to life-threatening diseases. selective eating are frequent in pediatric practice and may be
Trauma and infections are the most common causes, but disregarded; picky eating is in fact a common behavior in early
also inflammatory, oncological, neuromuscular, congenital, childhood that resolves spontaneously for most children (25).
and hematological pathologies may present with limping. However, an overly unbalanced diet can lead to micronutrient
Among unusual etiologies, nutritional deficiencies should also deficiencies, as in our cases, so it must be detected and
be considered. corrected early.
Scurvy, resulting from vitamin C deficiency, is the The recommended daily allowance (RDA) of vitamin C
oldest-known nutritional disorder. Nevertheless, due to its is 25 mg for children aged 1–3 years, 30 mg for 4–6 years,
rarity in the current era, the diagnosis of scurvy is often 45 mg for 7–10 years, 55–75 mg for 11–18 years, according
forgotten. Pediatric cases of scurvy have been increasingly to the Italian Society for Human Nutrition (26). The global
described in recent years. However, most studies report recommendations for vitamin C intake vary greatly between
single or few cases. In the present study, we describe 8 various health authorities, reflecting the different criteria
cases diagnosed with scurvy in a tertiary care pediatric used (27).
hospital in a 6-year period. The above-described cases The best sources of vitamin C are citrus fruits and fresh
are representative of the diagnostic challenges and pitfalls vegetables, though cooking and food storage can reduce their
of scurvy. vitamin C content. Breast milk and baby formulas also contain
Vitamin C is an essential water-soluble micronutrient, an adequate amount of ascorbic acid for infants, around 50–
it is involved in several body functions, including collagen 90 mg/L. Cow’s milk, on the other hand, has significantly less
biosynthesis, absorption of iron, wound healing and vitamin C. Therefore, the risk of ascorbic acid deficiency is lower
maintenance of blood vessels, cartilage, and bones. Humans during the first year of life, since infant feeding is predominantly
are unable to synthesize it, as a result of the loss of an enzyme based on breast milk or formula (25, 28).
required in the biosynthetic process, therefore vitamin C must Most of our patients were around 3 and a half years old. The
be orally introduced (8, 9). peak prevalence of picky eating occurs at this age, according to
Insufficient dietary intake may lead to impaired bone Taylor et al. (25).
formation and vascular fragility, clinically manifesting as In our case series, the majority of patients were male. This
scurvy (5). gender distribution, coherent with other data reported (5), is
The prevalence of scurvy in children in developed countries unexplained. Epidemiological studies have frequently reported
is not known. In the United States, the prevalence of vitamin C higher vitamin C concentrations in females than in males, but
deficiency in the general population is about 5.9%, according to no conclusive gender-related difference in the pharmacokinetics
the cross-sectional study by the National Health and Nutritional of vitamin C was observed (10, 29, 30).
Examination Survey (NHANES) conducted in 2017–2018 on The first clinical manifestations of scurvy usually appear
civilians aged more than six years, albeit the majority were after 1–3 months of inadequate vitamin C intake (4). The
clinically asymptomatic. The prevalence of deficiency in the earliest manifestations are non-specific systemic symptoms,
United States is lower in the pediatric population than in adults, such as malaise, asthenia, irritability, loss of appetite and low-
though this does not occur in developing countries where low grade fever. Later, mucocutaneous signs can appear, including
vitamin C deficiency is more frequently observed in children hyperkeratosis, the characteristic perifollicular hemorrhages,
(2, 10–12). petechiae, ecchymosis, corkscrew hairs, gingival swelling and
Certain groups of children have a higher risk of ascorbic bleeding with teeth loosening. Capillaries become fragile and
acid deficiency. The large majority of children with scurvy there is a bleeding tendency. In addition to mucocutaneous
have underlying conditions predisposing them to nutritional bleeding, the bleeding tendency may also manifest as hematuria
imbalances. Neuropsychiatric or developmental disorders, such (31). Musculoskeletal manifestations are the most frequent
as autism spectrum disorders, cerebral palsy and developmental presenting symptoms in children (5, 6, 32, 33), inducing
delay, are the most common, as these patients are more prone patients to seek medical attention. Symptoms include arthralgia,
to restrictive diets owing to sensory issues (3, 13–15). Other myalgia, limb or joint swelling, affecting mainly knees and
diseases may increase the risk of vitamin C deficiency by ankles, hemarthrosis, and muscular hematomas; subperiosteal
reducing its absorption (Crohn’s, Whipple’s, and celiac disease) hematoma can occur during the healing phase. Lower
(16), increasing its requirement (chemotherapy, bone marrow extremities are affected more often, even though any joint can
transplant, hemodialysis) (17–19), or accelerating its catabolism be involved. Leg pain can be so severe that children develop a
(iron overload) (19). limping gait, with refusal to walk and inability to bear weight.

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Infants may present with pseudoparalysis, lying in a “pithed frog seems even to an expert radiologist (5). As a confirmation of
position” with semi-flexed hips and knees (34). Defective osteoid this, imaging studies showed typical alterations only in half of
matrix and enhanced bone reabsorption, caused by vitamin C our patients and mostly upon the second review.
deficiency, may lead to spontaneous or inadequate healing of While the classical radiographic signs of scurvy are well-
fractures (4). described in the medical literature, MRI findings are not so well-
Scurvy’s manifestations may appear discontinuously, and delineated and specific. Common MRI features are hypointense
the presence of isolated symptoms can be misleading. In signals in T1-weighted sequences and hyperintense in T2-
addition, patients may have a good nutritional status, which can weighted and STIR sequences, mainly within metaphyses. The
further contribute to the diagnostic delay (4, 5). metaphysis is a site of high turnover, therefore, as a result of
Other rare clinical signs of scurvy have been poor collagen formation needed for bone growth and repair,
described, such as proptosis due to orbital hemorrhage it may be affected first in patients with vitamin C deficiency
(35), cardiac hypertrophy, pulmonary hypertension, and (44). These alterations are often multifocal and symmetrical,
diminished adrenal and bone marrow functions. Scurvy, suggesting a systemic process. Bone marrow enhancement
if untreated, can be lethal, mainly due to the hemorrhagic has been described in several cases. These alterations on
diathesis and the difficulty in wound healing, with deaths MRI might be due to the gelatinous transformation of bone
reported from cerebral hemorrhage and hemopericardium marrow, owing to the replacement of normal marrow elements
(4, 36–38). with hyaluronic acid and water (45). Periosteal elevation
Microcytic anemia and elevation of inflammatory markers and soft tissue alterations may be present, secondary to
are common laboratory findings, as seen in our patients subperiosteal hemorrhage or edema. These findings, though,
in which all but one had microcytic anemia and all had are non-specific and can overlap with features of other diseases
elevated inflammatory markers, especially ESR with slightly such as hematological malignancies, metastatic disease, and
altered CRP. Anemia may be secondary to a combination infectious and non-infectious osteomyelitis; therefore, it is
of bleeding and decreased iron absorption, or abnormal important to keep scurvy in the differential to avoid invasive
folate metabolism (5, 39–41). Indeed, folate levels should be diagnostic procedures. MRI alterations may be noticeable
checked in patients with scurvy, regardless of hemoglobin earlier than radiographic changes and, in the appropriate
and mean corpuscular volume values. The inflammatory state clinical scenario, may point toward the diagnosis of nutritional
may be due to the loss of the antioxidant effect provided by deficiency (44–46).
ascorbic acid (14). Anemia with low hematocrit and increased The differential diagnosis in a limping child with these
fibrinogen, as seen in our patients, can counteract increasing clinical, laboratory and radiological features may be challenging,
ESR levels. making the diagnostic pathway full of pitfalls.
These laboratory results may be misleading. In a limping According to the history of lower limbs pain and limping,
child, elevation of inflammatory markers and anemia might associated in some patients with swollen limb, fever, and
suggest more common diagnoses, such as infectious, elevated inflammatory markers, an osteoarticular infection
inflammatory and oncological diseases. However, these was initially suspected in all of our patients, thus empiric
findings should not deter pediatricians from including scurvy intravenous antibiotic therapy was administered. Metaphyseal
in their differential diagnosis. Complete nutritional blood tests signal abnormalities on MRI may be misinterpreted. Two
should be performed and may reveal further multiple vitamin patients underwent a bone biopsy, but biopsies and blood
deficiencies, vitamin D and folate deficiency being the most cultures were negative; however, it is not uncommon for
frequent (42, 43). infectious osteomyelitis to show no growth of organisms (47).
Scurvy has typical radiographic findings, especially Our patients, against this diagnosis, presented low-grade
occurring at the distal ends of the long bones, due to alterations fever, no alterations in white blood count, a slight alteration of
in the osteoid matrix caused by vitamin C deficiency. These CRP with no response to antibiotic therapy. The mucocutaneous
include the Frankel line, an irregular but thickened white line signs and the dietary history suggested a diagnosis other than
in the metaphyseal area, representing the zone of well-calcified an osteoarticular infection. When performed on an extended
cartilage, and the Trümmerfeld zone, a rarefied area secondary field, MRI showed multifocal and symmetrical signal alterations,
to poorly formed trabeculae. Other typical findings are Pelkan indicating a systemic process rather than a focal lesion as acute
spur, resulting from a healed metaphyseal pathological fracture, osteomyelitis (45).
and the Wimberger ring sign, a thin sclerotic rim surrounding The association of symptoms such as limb pain, also during
a small lucent epiphysis. Osteopenia is the most common night-time, cachectic appearance and pallor, petechiae, and
radiographic sign detected in patients with scurvy, though it is ecchymosis, gingival hypertrophy, with diffuse bone marrow
not specific (4). These typical imaging findings usually appear signal abnormalities on MRI, raised the suspicion of oncologic
after 3–6 months of vitamin C-deficiency, thus they may not diseases (48, 49). Therefore, a peripheral blood smear and a bone
be present in the earliest stage, and could not be as clear as it marrow aspiration were performed in the first three patients to

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exclude malignancy. Leukemia was also suspected in patient #7. and systemic symptoms usually recover within a few days,
In that case the dietary history collected from the beginning with full resolution of clinical manifestations in several
raised the suspicion of nutritional deficiency earlier, therefore weeks (4, 54).
bone marrow aspiration was postponed after vitamin C dosage. Dietetic regimens should be re-assessed following
In the meantime, the patient underwent chest radiography and the acute phase. Indeed, pediatricians and dieticians
abdomen ultrasound, which were negative for organomegaly, should verify that the child and the family modify their
lymphadenopathy or masses, and a peripheral blood smear nutritional intakes. Otherwise, normal vitamin levels are
showed no blast cells. at risk to restore back to insufficient levels after the period
As a result of the finding of hypoelicitable reflexes in patients of supplementation.
#1, #2, #3 and #6, with gait abnormalities, a neuropathy or a As in other reports (55, 56), our patients had a significant
spinal cord disorder were suspected. Electroneurography was diagnostic delay, with a time-frame between onset and final
normal in all four patients and spine MRI ruled out spinal diagnosis of about 2 months. Notably, the interval times became
cord involvement. progressively shorter during the study period, showing that if we
Juvenile idiopathic arthritis (JIA) was suspected in patient consider scurvy among the causes of limping, a final diagnosis
#3, considering the long history of pain with restricted mobility can be made in a few days.
of the hips, laboratory findings with microcytic anemia, elevated
inflammatory markers and ANA positivity. He was treated with
NSAIDS (naproxen), without any improvement. Conclusion
MRI findings of multifocal and symmetric bone marrow
abnormalities with periosteal reaction were interpreted as In pediatric scurvy, the presenting complaints are typically
consistent with chronic nonbacterial osteomyelitis (CNO) in musculoskeletal symptoms. Scurvy must be considered in the
patients #1 and #5. This hypothesis was also supported by differential diagnosis of a child with a limp, not only in children
clinical findings of bone pain and limping associated with with known risk factors but also in healthy ones. During the
elevation of ESR without significantly raised CRP on blood assessment of a limping child, an accurate dietary history is
tests (50). A treatment with naproxen was started, without fundamental in order to detect potential nutritional deficiency,
significant improvement. The bone marrow abnormalities and together with a careful physical examination looking for
the metaphyseal predilection seen on MRI in scurvy MAY typical mucocutaneous signs of scurvy such as hyperkeratosis,
overlap with the imaging findings of CNO (51). perifollicular hemorrhages, petechiae, ecchymosis, corkscrew
Bone biopsy, performed in patient #1, did not show any hairs, gingival swelling and bleeding. Microcytic anemia
bacterial growth, but nor inflammatory changes that should and ESR elevation with only slight alteration of CRP are
be present in CNO. It is important to consider scurvy in common laboratory findings. Imaging studies, if performed
the differential diagnosis to avoid an invasive procedure such by expert radiologists, may reveal the typical features of
as bone biopsy (50). In patient #5, the history of selective scurvy. Common MRI findings are multifocal symmetrical
and unbalanced diet together with gingival swelling at the increased signal on STIR sequence within metaphyses, with
physical examination raised the suspicion of scurvy, confirmed varying degrees of bone marrow enhancement, with adjacent
by insufficient serum vitamin C levels. periosteal elevation and soft tissue swelling. Although not
Determination of serum vitamin C levels is the diagnostic as specific as radiographic changes, MRI alterations may be
gold standard for scurvy: levels lower than 200 µg/dL are noticeable earlier. Differential diagnosis can be challenging
considered insufficient and confirm the diagnosis. The test is because scurvy can mimic common and severe infectious,
specific but insensitive, as it may be normal in case of recent oncologic, inflammatory conditions. This often leads to
ascorbic acid intake in any form. Other ways to estimate long hospitalization and unnecessary procedures. Scurvy’s
the vitamin C body stores are measuring the acid ascorbic manifestations are reversible with vitamin C supplementation,
level in the buffy-coat of the leukocytes (deficient if lower so any delay in diagnosis contributes to unnecessary pain
than 10 mg/108 WBCs), or measuring the urinary excretion and clinical morbidity. A correct diagnostic path avoids
of ascorbic acid after parenteral vitamin C infusion. These invasive diagnostic procedures and reduces the risk of
methods, though, are not readily available. The best evidence long-term complications.
of scurvy, in presence of a consistent clinical scenario, remains
the resolution of the disease manifestations after vitamin C
supplementation (4, 52, 53). Data availability statement
The dosage and length of treatment should be
individualized, as there are no standard regimens. Children The raw data supporting the conclusions of this
are usually treated with 100–500 mg of vitamin C daily, article will be made available by the authors, without
for 1 month or until full recovery. Spontaneous bleeding undue reservation.

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Ethics statement Conflict of interest

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