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JDC CASE REPORT

Severe Gingivitis Associated with Ascorbic


Acid-Deficiency in a Pediatric Patient

Allison J. Brand, DMD 1 Michael B. Lieberman, DDS 2


Evlambia Hajishengallis, DDS, DMD, MSc, PhD 3

ABSTRACT
Plaque-induced gingivitis, a common condition in children, responds well to
proper oral hygiene practices. Persistent severe gingivitis, on the other hand, should
prompt investigation of etiological factors. Nutritional elements are implicated in
periodontal health. This case report describes a pediatric patient with severe persistent
gingivitis caused by vitamin C deficiency. The events that led to a diagnosis of
scurvy and a resolution of the systemic and localized manifestations of the disease,
after vitamin C administration, are presented. It is recommended that vitamin C
deficiency be considered in cases of refractory gingivitis, especially in pediatric patients
with special health care needs who have aversion to foods rich in ascorbic acid.
(J Dent Child 2019;86(2):125-8)
Received February 14, 2019; Last Revision March 23, 2019; Accepted March 25, 2019.
Keywords: vitamin c, scurvy, periodontal disease

P
laque-induced gingivitis, characterized by gingival connective tissues high in collagen, such as the gingiva.
inflammation with no attachment or bone loss, Those at risk for vitamin C deficiency usually include
is the most common periodontal disease in chil- elderly individuals, adults with smoking or other addic-
dren. Uncommon in early primary dentition, gingivitis tions, individuals from lower-income households or
is found in approximately 50 percent of four- to five- with stressful lives, pregnant women, and individuals
year-old children and young adults, and 100 percent of who are treated in hospitals (e.g., patients on main-
adolescents.1 tenance hemodialysis).8
Inadequate oral hygiene is the most frequent cause The purposes of this paper are to present an unusual
of gingivitis. However, local or systemic factors, includ- case of a 10-year-old girl with persistent severe gingi-
ing malnutrition, can exacerbate the severity of plaque- vitis caused by vitamin C deficiency, and discuss the
induced gingivitis. 2-5 One of the nutritional factors symptoms and events that led to the diagnosis and the
implicated in periodontal health is vitamin C (ascor- treatment rendered.
bic acid).6 Vitamin C-dependent enzymes catalyze the
hydroxylation of lysine and proline, which is necessary
for the folding of collagen into its functional structure.7 CASE REPORT
Thus, vitamin C deficiency can particularly affect A 10-year-old Caucasian girl presented to the Dental
Medicine (PDM) Pediatric Clinic of the University of
Pennsylvania, Philadelphia, Pa., USA, one week follow-
1
Dr. Brand is a resident, 2Dr. Lieberman is a clinical associate, and 3Dr. ing an anaphylactic reaction to milk proteins. Her chief
Hajishengallis is a professor, graduate program director and chief, all complaint was excessive bleeding and swollen and pain-
in the Division of Pediatric Dentistry, Department of Preventive and
ful gingiva. A review of the patient’s medical history
Restorative Sciences, The University of Pennsylvania School of Dental
Medicine, University of Pennsylvania, Philadelphia, Pa., USA. revealed extreme prematurity (23-week), ligated patent
Correspond with Dr. Hajishengallis at evalmbia@upenn.edu ductus arteriosus, bronchopulmonary dysplasia, asthma,

Journal of Dentistry for Children-86:2, 2019 Severe gingivitis and scurvy Brand et al. 125
performed but found to be normal (Table).
Table. Patient’s Blood Test Results Improvement of oral hygiene and utili-
zation of chlorhexidine gluconate mouth-
Date of testing Reference
range rinse would significantly resolve the
1/5/2017 3/29/2018 4/9/2018 4/19/2018 patient’s oral condition; therefore, a diag-
nosis of severe gingivitis due to poor oral
WBC (x103/µL) 8.2 7.0 4.8 5.9 3.7-10.5 hygiene was not excluded.
RBC (x10 /µL)
6
5.06 4.63 3.41 3.16 3.9-5.45 The patient presented with irritability,
Hemoglobin g/dL 13.3 11.8 8.7 8.1 11.7-15.7 left leg limp, petechiae on both legs, and
hematoma on the left thigh in the location
Hematocrit (%) 39.8 36.5 26.7 26.0 34.8-45.8
where an Epi-pen injection was admin-
Platelet (x103/µL) 276 315 232 321 176-407
istered during her allergic reaction. Due
PT/INR (seconds) 13.2 111.6-13.8 to her poor cooperation, a limited intra-
PTT (seconds) 21 22.0-36.0 oral examination revealed edematous,
Factor VIII (%) 184 49-191 spontaneously-bleeding granulomatous
lesions and hematomas on the mandibular
Ferritin (ng/mL) 55.4 10-82
and maxillary anterior gingiva (Figure 1).
Iron Profile (mg/dL) 43 25-140
The patient was diagnosed again with
Vitamin B12 (pg/mL) 413 168 247-1,174 severe gingivitis; oral hygiene, including
Vitamin E (mg/L) 7.6 4.8 5.5- 9.0 the use of chlorohexidine gluconate mouth-
Vitamin A (mg/L) 0.36 0.20-0.50 rinse, was reemphasized.
At the one-week follow up, her deteri-
Vitamin C (µmol/L) <5 23-114
orating oral condition, especially after her
recent stressor event (allergic reaction),
WBC: White blood cells. µL: microliter. RBC: Red blood cells.
g/dL: grams/deciliter. PT/INR: Prothrombin time/International normalized ratio.
suggested diagnosis of acute necrotizing
PTT: Partial thromboplastin time. ng/mL: nanograms/milliliter. ulcerative gingivitis (Figure 2), which
mg/dL: milligrams/deciliter. pg/mL: picograms/milliliter. prompted us to prescribe metronidazole
mg/L: milligrams/Liter. µmol/L:micromoles/Liter.
(200 mg every eight hours) for five days;
however, this did not improve the patient’s condition.
gastroesophageal reflux, milk allergy, autism, develop- Concurrently, the patient’s limping increased and her
mental delay, swallowing difficulty, food aversions, and a pediatrician suggested a leg radiograph and orthopedic
diet consisting of a limited selection of fruits and vegeta- evaluation, both of which were unremarkable. The pa-
bles, soy yogurt, and chicken nuggets. tient’s condition continued to decline, leading to an
A review of the patient’s dental history showed mul- emergency room visit and hospitalization for a hemato-
tiple visits to the PDM, during which she was diagnosed logical evaluation. On that admission, the patient was
with poor oral hygiene and, at times, severe gingivitis. found to have normal factor VIII, ferritin, prothrombin,
To rule out systemic contributing factors, blood meta- partial thromboplastin time, Von Willebrand factor and
bolic and vitamin (excluding vitamin C) testing was iron, and low hemoglobin and hematocrit levels (Table).
An ultrasound exam showed subcutaneous edema and
hemorrhage behind her left knee, probably caused by

Figure 1. Edematous, spontane­o usly bleeding Figure 2. Clinical aspect similar to acute necrotizing ulcerative
granulomatous lesions and hematomas on the gingivitis.
maxillary anterior gingiva.

126 Brand et al. Severe gingivitis and scurvy Journal of Dentistry for Children-86:2, 2019
the Epi-pen injection. The patient was released and into her diet. At 10 days post-admission, the patient’s
prescribed iron supplements based on the fact that the periodontal health (Figure 4), temperament, leg move-
patient’s hematocrit and hemoglobin levels were low. ment, leg hematoma, and petechiae had improved
Five days later, the patient was readmitted to the hos- significantly. The patient is now monitored regularly
pital due to spontaneous oral bleeding, increase in by hematologists and our dental team for her systemic
petechiae on both legs (Figure 3), inability to ambulate, and oral health.
and bruising on her arms and elbows. At that time, the
differential diagnosis included scurvy, Von Willebrand
disease, Glanzmann’s thrombasthenia, and Henoch- DISCUSSION
Schoniein purpura. A complete vitamin-panel testing, Ascorbic acid is a water-soluble vitamin synthesized by
including vitamin C, was ordered, and the patient was plants and most animals but not by humans; it is found
released and prescribed vitamin C supplements due to a mainly in citrus fruits and vegetables.8,9 Vitamin C is an
high suspicion of scurvy based on the symptoms, clini- electron donor/reducing agent; thus, it is considered an
cal manifestations and the fact that any other disease on antioxidant.7 It acts as an enzyme co-factor/co-substrate
the differential diagnosis the medical team considered for 15 mammalian enzymes involved in important meta-
was eliminated upon testing. bolic pathways, such as the norepinephrine biosyn-
thesis, collagen hydroxylation, tyrosine metabolism,
carnitine biosynthesis, and histone demethylation.9 The
reducing action of ascorbic acid in the small intestine
appears to be involved in iron absorption, whereas in
the stomach it may prevent formation of N-nitroso
compounds.9 Intracellularly, vitamin C regulates gene
expression, mRNA translation, and prevention of oxida-
tion damage to DNA and proteins. In plasma, it increases
endothelium-dependent vasodilation, reduces extracellular
oxidants from neutrophils and oxidation of low-density
lipoproteins, and quenches aqueous peroxyl radicals and
lipid peroxidation products.9 Following ingestion, vitamin
C is absorbed from the small intestine and distributed
quickly to extracellular spaces, predominantly in the liver,
brain, and skeletal muscles.9
While vitamin C deficiency is considered at a blood
Figure 3. Petechiae and hematomas in legs. concentration below 23 µmol per liter, the critical level
for development of scurvy is 10 µmol per liter.10 Latent
scurvy symptoms include fatigue, irritability, vague/dull
Test results confirmed the diagnosis of scurvy (Table). aching pains, and weight loss, which often lead to mis-
The patient’s vitamin C supplementation was increased, diagnosis such as myopathy, neuropathic conditions, or
and she was placed on a strawberry-sweet potato-banana- hematological malignancy.10 After one to three months
chicken diet as a way to reintroduce fruits and vegetables of severe vitamin C deficiency, the potentially lethal
disease scurvy may develop. The sign/symptoms of
scurvy include depression, confusion, anemia, fever,
shortness of breath, infections, coiled hair, severe gingi-
vitis, petechiae, erythema, purpura, arthralgia, bleeding
into the skin, subcutaneous tissues, muscles, and joints.11
Patients may present with only some symptoms/signs of
scurvy, making the diagnosis difficult. Some, but not all,
of the signs/symptoms can be explained based on the
enzyme malfunction caused by vitamin C deficiency. For
example, the tiredness and signs of autonomic dysfunc-
tion might be due to impaired norepinephrine biosyn-
thesis and the breakdown of wounds and the bleeding
gingiva might be due to impaired hydroxylation of
collagen.7 Moreover, the role of vitamin C in the synthesis
of carnitine, which is involved in the oxidation of fatty
acids, may account for the muscle weakness observed in
Figure 4. Significant improvement of perio- scurvy.8,12 Additionally, since ascorbic acid is important
dontal health after vitamin C supplementation. in iron absorption, its deficiency may lead to anemia.13

Journal of Dentistry for Children-86:2, 2019 Severe gingivitis and scurvy Brand et al. 127
In our patient, blood levels of vitamin C were not ditions on an intact and a reduced periodontium:
tested initially, as deficiency of this vitamin is extremely consensus report of workgroup 1 of the 2017 World
rare. Furthermore, our patient did not have and could Workshop on the Classification of Periodontal and
not express other symptoms (i.e., muscle weakness) sug- Peri-Implant Diseases and Conditions. J Clin Perio-
gestive of vitamin C deficiency. In addition to that, her dontol 2018;45(20):S68-S77.
poor oral hygiene was consistent with the diagnosis of 5. Albandar JM, Susin C, Hughes FJ. Manifestations
severe gingivitis. It was not until her allergic reaction of systemic diseases and conditions that affect the
that other signs/symptoms of scurvy (bruising, petechiae, periodontal attachment apparatus: case definitions
limping) surfaced and led to the correct diagnosis and and diagnostic considerations. J Clin Periodontol
treatment. Therefore, in the search of systemic factors4,5,14 2018;45(20):S171-S189.
that could account for the persistence of gingivitis, the 6. Woolfe SN, Hume WR, Kenney EB. Ascorbic acid
patient’s diet should be considered. If it is restrictive, and periodontal disease: a review of the literature.
vitamin C blood analysis is important. J West Soc Periodontol 1980;28(2):44-56.
The recommended dietary daily allowance (RDA) 7. Grosso G, Bei R, Mistretta A, et al. Effects of vita-
for vitamin C is 15 mg at one to three years of age, min C on health: a review of evidence. Front
25 mg at four to eight years of age, 45 mg at nine to Biosci 2013;18:1017-29
13 years of age, and 75 mg for boys and 65 mg for girls 8. Pacier C, Martirosyan D. Vitamin C: optimal
at 14 to 18 years of age.15 For adults, the RDA is 90 mg dosages, supplementation and use in disease pre-
per day for males and 75 mg/day for females. Con- vention. Funct Foods Health Dis 2015;5(3):
sumption of the daily-recommended five servings of 89-107.
fruits and vegetables provides plenty of vitamin C (210 9. Padayatty SJ, Levine M. Vitamin C: the known and
to 280 mg).8,15 the unknown and Goldilocks. Oral Dis 2016;22
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C supplementation in deficient patients can quickly Serum vitamin C and the prevalence of vitamin C
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(NHANES). Am J Clin Nutr 2009;90(5):1252-63.
13. Ems T, Huecker MR. Iron absorption. In: StatPearls
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128 Brand et al. Severe gingivitis and scurvy Journal of Dentistry for Children-86:2, 2019
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