105

Journal of Oral Science, Vol. 60, No. 1, 105-114, 2018

Original

Gingival enlargement in children with sickle cell disease

Mine Ö. Tonguç1), Selma Ünal2), and Rabia B. Arpaci3)
1)Department of Periodontology, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey
2)Depatment of Pediatrics, Faculty of Medicine, Mersin University, Mersin, Turkey
3)Depatment of Pathology, Faculty of Medicine, Mersin University, Mersin, Turkey

(Received November 15, 2016; Accepted March 27, 2017)

Abstract: The purpose of the present study was

to evaluate periodontal health status in children
with sickle cell disease (SCD). Forty-nine children
with SCD and 39 systemically healthy sex- and age-
matched children were enrolled in the study. Plaque
index, gingival index, bleeding on probing, pocket
depth, salivary volume, and hyperplastic index were
recorded. In addition, the histopathological evalua-
tion of gingiva was made in a child with SCD. There
were significant differences between the groups with
regard to hyperplastic index (P < 0.05), whereas there
were no differences in other parameters. Gingival
enlargement was detected in 27 children (55.1%) in
the SCD group and 6 children (15.4%) in the control
group (P < 0.001). However, there were no differences
in periodontal health status of children in the SCD
and control groups, the most important finding of
this study that the gingival enlargement was more
prevalent in children with SCD. Sickling and chronic
inflammation seen in SCD may affect gingival tissues.
Therefore, physicians and dentists must be aware of
the effects of SCD on gingival tissues.
Keywords: sickle cell disease; gingiva; gingival
enlargement; histopathology.
Correspondence to Dr. Mine Öztürk Tonguç, Department
of Periodontology, Faculty of Dentistry, Suleyman Demirel
University, Cunur 32260, Isparta, Turkey
Fax: +90-246-2370607 E-mail: mineperio@gmail.com
Color figures can be viewed in the online issue at J-STAGE.
doi.org/10.2334/josnusd.16-0796
DN/JST.JSTAGE/josnusd/16-0796
Introduction
Sickle cell disease (SCD) is a fatal hereditary disease in
which acute illness attacks and detrimental organ damage
are observed. A point mutation in the hemoglobin (Hb)
β chain gene leads to SCD. The electrophoretic abnor-
malities in sickle hemoglobin (HbS) are pathognomonic
for SCD (1). The estimated prevalence of SCD in the
world is 7%. While the disease is mostly seen in Africa,
it has spread over the whole world as a consequence of
migration. The major hemoglobinopathy seen in Turkey
is HbS, with a prevalence of 0.37-0.6%, but it is more
prevalent in the East Mediterranean region (3-44%) (2).
The pathogenesis of SCD originates from the polym-
erization of deoxygenated HbS. This polymer formation
alters the normal biconcave disc shape into a rigid,
irregularly-shaped, unstable cell (3). Abnormal structured
sickle hemoglobin, which results in the sickle shape of
erythrocytes, polymerizes within the cell. Sickled eryth-
rocytes create a thin occlusion within vessels, resulting in
tissue ischemia (3).
The two important features of SCD are chronic hemo-
lytic anemia and vaso-occlusion, resulting in ischemic
tissue injury (1). The essential feature of the disease is
“sickle crisis”, resulting in life-threatening complica-
tions including acute pain, infection, stroke, acute chest
syndrome, growth retardation, organ damage, and osteo-
myelitis (1).
SCD is a chronic inflammatory disease characterized by
elevated leukocyte counts, hyper-reactive granulocytes,
monocytes, and endothelial cells, and increased levels
of pro-inflammatory mediators (4,5). Chronic inflamma-
tion is observed in patients who are in the steady state,
whereas elevated acute inflammatory cytokines are one
of the important causes of vaso-occlusion in SCD (6).
106
Some oro-facial changes including mid-facial over-
growth, facial swelling, and osteonecrosis were reported
in SCD patients (7-9). Few studies exist regarding the
periodontal status of patients with SCD (10-13), but
their results are conflicting. In one study, it was reported
that patients with SCD have greater periodontal pocket
depths than those of their healthy counterparts (10).
However, other studies stated that there were no differ-
ences between patients with SCD and controls with
regard to probing depth or attachment loss (11-13). In
addition, higher plaque index (PI), gingival index (GI),
and bleeding on probing (11,12) scores in subjects with
SCD were reported.
The present study aimed to explore the periodontal
health status of 5-18 year-old children with SCD and
compare them with those of their healthy counterparts.
Materials and Methods
The present study was performed in cooperation with
the Department of Pediatric Hematology at Mersin
University, Faculty of Medicine and the Department of
Periodontology at Süleyman Demirel University, Faculty
of Dentistry. The research protocol was independently
reviewed and approved by the Mersin University Faculty
of Medicine Ethical Committee (date: 10 January 2013;
number: 2013/15). The study was performed in accor-
dance with the ethical standards established in the 1964
Declaration of Helsinki which was revised in 2008. This
study was carried out from October 2013 to October
2014.
Study groups
The study population consisted of 49 children with SCD
(18 girls and 31 boys, age range 5-18) (SCD group) who
were followed by the Pediatric Hematology Clinic in
Mersin University, Faculty of Medicine, Department of
Pediatrics and 39 systemically healthy children (19 girls
and 20 boys, age range 5-18) (control group), who had
been admitted to Mersin University, Faculty of Medicine,
Department of Pediatrics for routine control and the
patients subsequently volunteered for the study. Informed
written consent was obtained from all the children and
their parents.
Individuals using medication affecting gingival status,
such as phenytoin derivatives, cyclosporine, or calcium-
channel blockers, were excluded from the study. None
of the participants had received periodontal therapy
and orthodontic treatment or used antibiotics and non-
steroidal analgesics in the month prior to the study.
All the children with SCD were physically examined
by an experienced pediatrician (S.Ü.). Medical status of
the SCD patients was evaluated to identify the subjects
meeting the inclusion criteria. The type of SCD (geno-
types of the subjects with SCD were confirmed by β-gene
mutation analysis), the frequency of blood transfusions,
and vaso-occlusive painful crisis in the last year, the
history of acute chest syndrome, splenic sequestration,
splenectomy, and stroke and the usage of hydroxyurea,
penicillin prophylaxis, chelating agents, and other medi-
cation were evaluated and recorded in children with SCD.
Participants with SCD who had taken penicillin
prophylaxis (1,200,000 IU Benzathine- Penicillin G/
month) within the last 30 days before enrolment were
included in the study after completion of 30 days of
antibiotic usage (14). In addition, participants with SCD
receiving a blood transfusion or having a vaso-occlusive
crisis in the previous month were excluded from the
study.
The study included children aged 5-18 years with
different dentitions (deciduous, mixed, and permanent).
Therefore, the SCD and control groups were categorized
and sub-grouped according to their dentition status.
The study groups formed were as follows: SCDd, SCD
patients with deciduous or mixed dentition; SCDp, SCD
patients with permanent dentition; controld, healthy
children with deciduous or mixed dentition; and controlp,
healthy children with permanent dentition.
Periodontal evaluation
All the examinations were performed at the Pediatric
Hematology Clinic of Mersin University, Faculty of
Medicine and Department of Pediatrics during morning
hours after overnight fasting. All clinical periodontal
and dental measurements were performed by the same
experienced examiner (M.Ö.T.). Unstimulated saliva
was collected for a period of 10 min, and its volume was
recorded. Dental examinations were performed using
the Williams periodontal probe (Henry Schein Inc.,
Melville, NY, USA) and a dental mirror in daylight and
an additional portable light source (Keeler Instruments
Inc. Windsor, UK). Clinical measurements of periodontal
parameters, including plaque index (PI) (15), gingival
index (GI) (16), bleeding on probing (BOP) (17), and
probing pocket depth (PPD) were recorded. In addition,
nasal or oral breathing status of the children was evalu-
ated using a dental mirror.
Gingival enlargement was assessed using hyperplastic
index (HI) (18). This index has been used frequently
in recent studies (19,20). After examination, the peri-
odontal health status of the subjects was evaluated using
a biofilm-gingival interface (BGI) classification system
(21).
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Fig. 1   The clinical appearances of gingival enlargements in 3 children with sickle cell disease (a-c) and a systemi-
cally and periodontally healthy child (d). (a) 9 year-old girl with SCD who underwent gingival biopsy. A horizontal
marginal gingival enlargement is noticeable throughout the entire oral cavity, especially the right maxillary posterior
region. Loss of the marginal gingiva’s knife-edge border is visible (arrow). (b) Mild gingival enlargement in hori-
zontal direction in maxillary permanent incisors of a 10 year-old boy with SCD. (c) Horizontal gingival enlargement
in maxillary and mandibular permanent first incisors of an 11 year-old boy with SCD. (d) Clinical appearance of
systemically and periodontally healthy 9 year-old girl.

Analysis of intra-examiner reproducibility Sample size calculation

The intragroup reproducibility for all the data (PI, GI,
PPD, HI) was determined by the examiner (MÖT) by
assessing six patients. Each patient was evaluated twice
during one visit over a 1-h interval, and all data measure-
ments were repeated in these subjects in a blinded manner
for the first assessment. The reproducibility was defined
by a Kappa score. Kappa scores were calculate with non-
weighted Kappa index with a 95% confidence interval
(95% CI) and reported as 0.82, 0.83, 0.80, and 0.85 for
PI, GI, PPD, and HI, respectively.
Histopathological evaluation
Since physical trauma, ache, and stress may induce
painful vaso-occlusive SCD crisis, histopathological
evaluation of the enlarged gingiva was performed for
only one child (a 9 year-old girl) who needed extrac-
tion of the left maxillary first molar because of gingival
enlargement and deep caries and volunteered for gingival
biopsy (Fig. 1a). The gingival tissue biopsy (sized 0.4 ×
0.3 × 0.1 mm) was obtained during the tooth extraction.
Additionally, as control, a healthy gingival sample (sized
0.2 × 0.3 × 0.1 mm) was obtained from a systemically
healthy 9 year-old child during maxillary first deciduous
molar tooth extraction because of deep occlusal caries.
The gingival tissue samples were embedded in paraffin
and stained with hematoxylin-eosin (HE) and evaluated
microscopically for inflammatory and fibrous changes in
gingival tissue.
According to the 2013 data of the Turkish Statistical
Institute, 430,836 children aged 5-18 years are present
in the Mersin province (www.tuik.gov.tr/ilGostergeleri/
iller/MERSIN.pdf). Of these, 60 children were diag-
nosed and registered with SCD by the hospitals present
in Mersin. Therefore, the proportion of children having
SCD was calculated as 0.014%; 49 of these 60 children
with SCD were included in the present study.
The relevance of the study was calculated using a
package program (NCSS/PASS 2011, Dawson Edition;
NCSS, Kaysville, UT, USA) for α = 0.01; β/α ratio = 1
using the means and standard deviations (SD) of all the
periodontal parameters. Post hoc power of the present
study for HI was determined to be 0.97 (effect size =
0.78, α = 0.05) in SCD and control groups. The post hoc
power of the permanent and deciduous/mixed dentition
subgroups for HI was 0.88 (effect size = 0.83, α = 0.05),
and 0.78 (effect size = 0.78, α = 0.05), respectively.
Statistical analyses
All comparisons were made between the SCD and control
groups, the matched subgroups SCDd and controld, SCDp
and controlp were compared statistically for study param-
eters as well. The sex differences between the groups
were determined by using the Chi-square test. Normality
of the data was determined by the Shapiro-Wilk’s test.
The normally distributed data were age, PI, GI, and BOP.
These normally distributed data were expressed as mean
± SD and group comparisons were made using indepen-
108

Table 1 Demographic and dental characteristics of the study groups

Demographic and dental SCD Control SCDd Controld SCDp Controlp
characteristics n = 49 n = 39 n = 17 n = 20 n = 32 n = 19
Age (mean ± SD) 12.6 ± 3.34 11.3 ± 3.44 9 ± 2.23 8.55 ± 2.04 14.5 ± 1.96 14.26 ± 1.76
Sex (F/M) (n) 18/31 19/20 6/11 8/12 12/20 11/8
Number of teeth
26 (15-28) 24 (20-28) 24 (15-28) 23 (20-25) 27 (22-28) 27 (24-28)
Median (min-max)
BGI (n) (BGI-H/BGI-G) 6/43 5/34 2/15 4/16 4/28 1/18
SCD: Sickle cell disease, SCDd: SCD patients with deciduous or mixed dentition, SCDp: SCD patients with permanent dentition. Controld: healthy children
with deciduous or mixed dentition, Controlp: healthy children with permanent dentition. F/M: female/ male, BGI: biofilm-gingival interface index, H:
healthy, G: gingivitis

Table 2 The clinical characteristics of the sickle cell disease (SCD) groups
SCD n = 49 SCDd n = 17 SCDp n = 32
Clinical Characteristics
n (%) n (%) n (%)
Type of SCD
HbSS 28 (57.1) 11(64.7) 17 (53.1)
HbSB 21 (42.9) 6 (35.3) 15 (46.9)
Frequency of vaso-occlusive crisis in the last year
0 32 (65.3) 10 (58.8) 22 (68.8)
1-5 14 (28.6) 6 (35.3) 3 (25)
>5 3 (6.1) 1 (5.9) 2 (6.3)
Frequency of blood transfusion in the last year
0 25 (51.1) 5 (29.4) 20 (62.5)
1-5 18 (36.7) 10 (58.8) 8 (25)
>5 6 (12.2) 2 (11.8) 4 (12.5)
History of acute chest syndrome 15 (30.6) 2 (11.8) 13 (40.6)*
History of splenic sequestration 13 (26.5) 5 (29.4) 8 (25)
History of splenectomy 11 (22.4) 2 (11.8) 9 (28.1)
History of stroke 5 (10.2) 1 (5.9) 4 (12.5)
Usage of hydroxyurea 40 (81.6) 14 (82.4) 26 (81.3)
Usage of chelating agent 9 (18.4) 5 (29.4) 4 (12.5)
Usage of penicillin 45 (91.8) 16 (94.1) 29 (90.6)
Usage of folic acid 49 (100) 17 (100) 32 (100)
SCDd: SCD patients with deciduous or mixed dentition, SCDp: SCD patients with permanent dentition. *: statistically
significant differences between the SCDd and the SCDp subgroups (P < 0.05, Chi-square test)

dent sample t-test. The other non-normally distributed
data were presented as median (min-max) values. The
Mann-Whitney U test was used for group comparisons
for the non-normally distributed data. Because the data
regarding medical parameters in SCD group were not
distributed normally, Spearman correlation coefficient
(rho) was used to analyze the relationships between
periodontal and medical parameters in the whole SCD
group. Multivariate analysis of variance (MANOVA)
was used to investigate of the interaction of the indepen-
dent variables; P < 0.001 and P < 0.05 were considered to
be significant. All statistical calculations were performed
using a software package program (SPSS 10, SPSS Inc.,
Chicago, IL, USA).
Results
Clinical findings
Demographic and oral health related parameters of the
study groups are shown in Table 1. There were no statisti-
cally significant differences between the SCD and control
groups and between the matched subgroups with regard
to age, gender, number of teeth, periodontal health status,
and unstimulated salivary volume (P > 0.05). There were
no subjects with periodontitis in the study groups. The
majority of the study participants had gingivitis.
In the SCD group, 28 patients (57.1%) had the SS
genotype, and 21 patients (42.9%) had the SB genotype.
The frequencies of the evaluated medical parameters of
the SCD groups are given in Table 2. Statistically signifi-
cant difference between the SCDd and SCDp was noted
with regard to the history of acute chest syndrome (P <
0.05).
There were no statistically significant differences
between the study groups and between the subgroups
with regard to all of the periodontal parameters except
HI and gingival enlargement frequency (GE) (P < 0.05).
GE frequency and the mean ± SD values of the PI, GI
and BOP, HI, and PPD in the study groups are shown in
 109

Table 3 Intergroup comparisons of the clinical parameters; plaque index (PI), gingival index (GI), probing pocket depth (PPD),
bleeding on probing (BOP), gingival enlargement (GE) frequency, and hyperplastic index (HI)
SCD Control SCDd Controld SCDp Controlp
Clinical Parameters
n = 49 n = 39 n = 17 n = 20 n = 32 n = 19
GE frequency
27 (55.1) 6 (15.3)**a 10 (58.8) 4 (20) §a 17 (53.1) 2 (10.5) ‡ a
n (%)
HI
0.29 ± 0.38 0.07 ± 0.19**b 0.37 ± 0.46 0.09 ± 0.24§b 0.24 ± 0.34 0.03 ± 0.11‡ b
(mean ± SD)
PI
1.14 ± 1.04 1.10 ± 0.54 1.18 ± 0.38 1.21 ± 0.63 1.11 ± 0.59 0.95 ± 0.37
(mean ± SD)
GI
0.96 ± 0.54 0.87 ± 0.47 0.98 ± 0.52 0.98 ± 0.50 0.95 ± 0.57 0.72 ± 0.39
(mean ± SD)
PPD
1.19 (1-1.88) 1.17 (1-2.15) 1.14 (1-1.79) 1.16 (1-2.15) 1.23 (1-1.88) 1.18 (1-2.02)
Median (min-max)
BOP %
40 ± 24 35 ± 22 40 ± 26 38 ± 24 41 ± 23 31 ± 19
(mean ± SD)
Unstimulated Salivary volume
2.95 ± 2.08 3.12 ± 3.06 2.86 ± 2.43 3.02 ± 1.82 3.60 ± 3.91 2.47 ± 1.03
(mean ± SD)
SCD: Sickle cell disease, SCDd: SCD patients with deciduous or mixed dentition, SCDp: SCD patients with permanent dentition, Controld: healthy children
with deciduous or mixed dentition, Controlp: healthy children with permanent dentition, *: significant differences between the SCD and the Control groups
(P < 0.05), **: significant differences between the SCD and the Control groups (P < 0.001), §: significant differences between the SCDd and the Controld
groups (P < 0.05), ‡: significant differences between the SCDp and the Controlp groups (P < 0.05), a: Chi-Square test, b: Mann-Whitney U test

Table 4 The gender distribution, location of GE and mean ± SD values of plaque index, gingival index and bleeding of probing
in enlargement region (PI-E, GI-E, BOP-E) of the subjects having GE in the groups and subgroups
SCD Control SCDd Controld SCDp Controlp
Characteristics of GE
n = 27 n=6 n = 10 n=4 n = 17 n=2
Gender distribution
n (F/M) 27 (8/19) 6 (1/5) 10 (2/8) 0/4 17 (6/11) 1/1
Location of GE (n) * § ‡

Anterior 16 5 5 4 11 1
Posterior 1 1 1 0 0 1
Whole mouth 10 0 4 0 6 0
PI-E (mean ± SD) 1.11 ± 1.03 1.09 ± 0.69 1.20 ± 0.26 1.24 ± 0.59 1.13 ± 052 1.16 ± 0.55
GI-E (mean ± SD) 1.07 ± 0.45 1.52 ± 0.35 1.02 ± 0.32 1.47 ± 0.48 1.10 ± 0.51 1.61 ± 0.39
BOP-E (%)
(mean ± SD) 47.8 ± 21.8 49.3 ± 19.5 41.6 ± 25.2 51.5 ± 14.1 51.4 ± 19.5 47.0 ± 22.6
PPD-E
Median (min-max) 1.30 (1-2.57) 1 (1-1.70) 1.40 (1-2.57) 1 (1-1.30) 1.25 (1-2.50) 1.35 (1-1.70)
SCD: Sickle cell disease, SCDd: SCD patients with deciduous or mixed dentition, SCDp: SCD patients with permanent dentition. Controld: healthy children
with deciduous or mixed dentition, Controlp: healthy children with permanent dentition, *: statistically significant differences between the SCD and the
Control groups (P < 0.001, Chi-Square test), §: statistically significant differences between the SCDd and the Controld groups (P < 0.05, Chi-Square test),
‡: statistically significant differences between the SCDp and the Controlp groups (P < 0.05, Chi-Square test)

Table 3.
GE was detected in 27 children (55.1%) in the SCD
group and 6 children (15.4%) in the control group (P <
0.001). GE was observed more frequently in boys than
in girls in both study groups and the dentition subgroups
(P < 0.05) (Table 4). The gender distribution, location
of GE and mean ± SD values of PI, GI, PPD, and BOP
in enlargement region (PI-E, GI-E, PPD-E, BOP-E) of
the subjects having GE in the groups and subgroups are
shown in Table 4. However, there were no statistically
significant differences between the groups and subgroups
regarding PI, GI, PPD, and the BOP values of the enlarge-
ment regions. The PPD-E values were higher in the SCD
group and subgroups except the SCDp group (Table 4).
The location of the tooth with GE in the SCD group was
significantly different from that in the control group (P
< 0.001); moreover, this significance was valid for the
subgroups as well (P < 0.05).
The GE observed in SCD group reached from gingival
margin to the muco-gingival junction. The thickened and
shelf-like contour of the marginal gingiva in this region
was remarkable in several SCD patients. The clinical
appearances of the three SCD patients (9-11 years old)
are presented in Fig. 1a-c. The enlargements were espe-
cially in the horizontal direction and had most a more
pronounced fibrotic appearance in children with SCD.
110

Fig. 3   Hyalinized, fibrotic, dense scar-like stroma (arrow) of the

gingival mucosa (HE, 100×).

Fig. 2   Histological findings of gingival tissue samples harvested

from gingival enlargement regions of a child with sickle cell
disease. (a) Hyperplastic epithelium (white arrow) and lympho-
cyte and plasma cell infiltration (black arrow) in a fibrotic stroma
(HE, 100×), (b) Russell bodies (arrow) are among the plasma cells
and lymphocytes (HE, 400×), (c) Intraepithelial vessels filled with
erythrocytes (arrow) and vessels entering the epithelium (HE,
100×), (d) Abnormally shaped erythrocytes are in some vessels
(HE, 400×).

Figure 1d represents the knife-edge contour of healthy Fig. 4   Histopathological findings of gingival tissue samples of a
systemically and periodontally healthy child.
marginal gingiva in a systemically healthy 9 year-old
child from the control group (Fig. 1a-c).
When the correlations between the medical and the
dental/periodontal parameters were assessed in the whole
SCD group, there were significant positive correlations
between the history of splenic sequestration and HI (rho
= 0.368, P < 0.01), between the history of acute chest
syndrome and the number of teeth (rho = 0.363, P <
0.01), and between the presence of GE and some peri-
odontal parameters like BGI (rho = 0.289, P < 0.01) and
BOP (rho = 0.341, P < 0.05). In addition, HI values were
positively associated with GI (rho = 0.295, P < 0.05) and Fig. 5   Panoramic radiographs of patients with sickle cell disease
BOP (rho = 0.315, P < 0.05). who underwent gingival biopsy.
When the effects of all parameters were evaluated
together, the interaction between groups and age groups
was not statistically significant (P > 0.05), the differences Focal dense scar-like fibrotic areas in connective tissue
between the groups were also not significant (P > 0.05). were noted. Some Russell bodies were also seen among
The number of teeth was the only significantly different the chronic mononuclear inflammatory cells (Fig. 2b).
variable between the age groups in MANOVA analysis Some of the sections also suggested that blood vessels
(P < 0.05). filled with erythrocytes entered the epithelium (Fig. 2c),
especially in the basal layer. The shape of erythrocytes was
Histopathological findings abnormal and some of them were seen in blood vessels,
Paraffin-embedded samples stained with HE from the while others were seen in the erythrocyte extravasation
GE region showed hyperplastic epithelium and slight areas (Fig. 2d). Hyalinization and fibrosis (arrow) were
lymphocyte and plasma cell infiltration in a fibrotic detected in the connective tissue of the gingival mucosa
connective tissue stroma of the gingival mucosa (Fig. 2a). (Fig. 3). Figure 4 shows the histopathologic appearance
 111

Table 5 Previous studies on the literature regarding periodontal health status of the subjects with sickle cell disease
Study n Ethnicity Age (years) Parameters Results
Crawford et al. 45 HbSS African American 18-64 Plaque index (PI) No associations between SCD and
1988 (22) 19 HbSC Gingival index (GI) periodontal disease
14 thalassemia Pocket depth (PD)
46 healthy Clinical attachment level
(CAL), calculus
Arowojolu 50 SCD Nigerian 11-19 PD PD levels were significantly higher
1999 (10) 50 healthy in adolescents with SCD
Güzeldemir et al. 55 SCD Turkish >18 PI, GI and BOP, Higher PI, GI, and BOP in SCD
2011 (11) 41 healthy Mandibular cortex index, patients
bone quality index
Passos et al. 99 SCD Brazilians of 16-68 CPI The number of decayed teeth was
2012 (12) 91 healthy African descent higher in SCD
No significant difference in CPI
Veiga et al. 10 SCD Brazilians of 6-12 PI and BOP No differences between the PI and
2013 (25) 15 healthy African descent BOP in all groups
Singh et al. 250 thalassemia Indian 3-15 GI and PI Subjects with thalassemia and SCD
2013 (24) 250 SCD have higher GI scores compared to
250 healthy the controls
Mahmoud et al. 59 SCD Sudanese 12-16 GI and PD SCD is not associated with
2013 (23) 54 healthy periodontal diseases
de Caravalho et al. 246 SCD Brazilians of >12 PI, GI, PD,CAL, Sickle cell trait was associated with
2015 (39) 123 healthy African descent calculus, mobility, gingivitis, SCD may be a risk factor
gingival recession and for periodontal diseases
furcation involvements
Al-Alawi et al. 33 SCD Saudi 18-38 CPI and PI No difference between the groups in
2015 (13) 33 healthy CPI and PI

of a healthy gingiva from a systemically healthy child. A
small number of leukocytes, normally structured vessels
and connective tissue were observed in healthy gingival
tissue. There were no radiographic abnormalities except
for deep caries in the left maxillary first molar (Fig. 5).
Discussion
In the present study, we evaluated the periodontal health
status in children with SCD and compared it to that of
healthy children. To our knowledge, this is the first study
evaluating the GE status in addition to periodontal health
parameters in a group of children with SCD. Our findings
revealed that there was a significant difference between
children with SCD and healthy controls regarding the
frequency and location of GE; however, there were no
differences between the groups in terms of other peri-
odontal parameters.
There are few studies in the literature associated
with the periodontal health status of subjects with SCD
(10-13,22-25). Previous studies focusing on the peri-
odontal health status of patients with SCD are presented in
Table 5. Two of these studies were conducted in children
(10,25). The majority of these studies reported that there
were no significant differences between SCD patients
and healthy controls in terms of periodontal parameters
(12,13,22-25). In agreement with those results, the oral
health status of children with SCD was similar to those
of their healthy counterparts in our study. The majority of
individuals in both groups had gingivitis. Veiga et al. (25)
reported that children with SCD had gingivitis with high
levels of dental plaque and gingival bleeding similar to
that observed in healthy children. In another study, higher
GI values were observed in children with SCD compared
to their healthy counterparts (23). Although the GI values
of the SCD group were slightly higher than those of the
control group, the difference was not significant in the
present study.
GE was observed in a large number of patients with
SCD (27 children, 55.1%), whereas it was noted in only 6
(15.4%) participants in the control group. Moreover, the
whole-mouth GE was observed in 10 patients in the SCD
group, whereas it was not observed in the control group.
There was only one case report in the literature
regarding GE in SCD patients (7). The case report
presented a 14 year-old Afro-Trinidadian boy with SCA
having enlarged mandibular gingiva. It was reported
that histopathologic assessment of the gingiva showed a
hemorrhagic and fibrotic lamina propria with inflamma-
tory cell infiltration.
The gingival samples harvested from the GE regions
of a subject with SCD were evaluated histopathologi-
cally (Figs. 2, 3). Similar to the results of the case report
112
mentioned above (7), we observed focal dense scar-like
areas and fibrosis in the connective tissue stroma (Fig. 3).
Fibrosis was characterized as an increased accumulation
of fibroblasts, collagen, and other extracellular matrix
components (26). The classical features of GE include
greatly elongated epithelial rete pegs extending deep
into the connective tissue as well as gingival lesions
containing fibrotic or expanded connective tissue with
characteristic levels of inflammation (27). The histo-
pathological observations in the present study conform
to the findings associated with gingival overgrowth.
In addition, it was observed that blood vessels filled
with abnormally shaped erythrocytes in close proximity
to the epithelium were present. Russell bodies were
observed among the chronic mononuclear inflammatory
cells (Fig. 2b). Abnormal plasma cells called Mott cells,
containing immunoglobulin aggregates termed Russell
bodies, have been found in non-secretory myeloma,
inflammatory diseases, and autoimmune disorders (28).
Furthermore, histopathologic signs of chronic inflamma-
tion include elongated rete pegs, fibrosis, and abnormal
plasma cells, Russel bodies or abnormally shaped eryth-
rocytes resulting from sickling and vaso-occlusion were
not observed in histopathologic evaluation of the healthy
gingival sample (Fig. 4). These findings give rise to the
notion that the gingiva in patients with SCD was affected
by chronic sickling and inflammation.
All patients with SCD in this study were administered
1 mg folic acid daily. This approach aims to keep a stable
hemoglobin level. In addition, folate medication in SCD
patients prevents hyperhomocysteinemia and thrombotic
events leading to painful crises (29). The GE observed in
the SCD group was mild. This may be as a result of daily
folic acid intake by SCD patients. It was reported that
systemic folic acid supplementation decreases phenytoin
induced gingival overgrowth (30). Similarly, daily folic
acid supplementation may be repressing the GE caused
by chronic inflammation and sickling observed in SCD.
Patients with SCD are more susceptible to pulmonary
infections and bacteremia. The etiologies of these infec-
tions involve functional defects in spleen, and tissue
damage resulting from SCD. Therefore, antibiotics are
essential to avoid infections in patients with SCD (31).
Since periodontal diseases are chronic inflammatory and
infectious diseases, the administration of systemic anti-
biotics reduces periodontal inflammation and improves
clinical outcomes (32). Systemic amoxicillin and metro-
nidazole combination is an effective adjunctive treatment
along with mechanical periodontal therapy for periodontal
diseases (32). Conversely, systemic penicillin regimen
by itself cannot eliminate periodontal infection. In the
present study, children with SCD who were administered
penicillin prophylactically were included in the study 30
days after antibiotic usage in order to exclude the effects
of penicillin on periodontal inflammation (14).
Puberty produces some changes in the physical appear-
ance and behavior of adolescents. Sex steroid hormones
have direct and indirect effects on proliferation, differ-
entiation, and growth of keratinocytes and fibroblasts in
the gingiva. During puberty, under the influence of sex
hormones, periodontal tissues may mount an exaggerated
response to local factors (33). Two cases were reported in
the literature linking GE to puberty (34,35). In contrast,
it was reported that hypogonadism, endocrine organ
dysfunction, delayed growth, and pubertal development
are frequently observed in children and adolescents with
SCD (36). In addition, in another study conducted on the
same population as this study, growth and pubertal devel-
opment retardation were found to be more frequent in
children with SCD compared to their healthy counterparts
(37). Although the pubertal status of the participants was
not assessed in this study, delayed sexual development
has been recorded in their medical records for most of the
SCD patients participating in this study.
Adenoid hypertrophy and tonsillitis are common in
patients with SCD. It has been speculated that recurrent
upper respiratory tract infections and chronic inflam-
mation cause adenotonsillar hypertrophy. They are also
associated with mouth breathing and hypoxia which
trigger sickling, inflammation, and vaso-occlusive crises
(38).
The nasal or oral respiratory status of the participants
was evaluated using a dental mirror in this study. We did
not observe mouth breathing in any subjects. In addi-
tion, the upper and lower lips of the subjects closed in
the rest position. Since xerostomia and mouth breathing
may increase dental plaque accumulation and induce
gingival changes, the unstimulated salivary volume of
the subjects was also evaluated. No differences were
observed between the SCD and the control groups and
subgroups regarding PI and salivary volume.
The present study has several limitations. The gingival
tissue samples were not obtained from all the study
participants. Histopathological evaluations of the gingiva
were performed in only one subject from each group for
ethical reasons. Furthermore, evaluating the effects of
adenoid hypertrophy on GE was not possible owing to
the lack of adenoid examination in this study.
The results of the present study revealed that although
periodontal health and oral hygiene status were similar
to those of their healthy counterparts, marginal GE was
observed more frequently in children with SCD. There-

fore, we conclude that SCD may predispose children
to GE and that gingival tissues are affected by chronic
inflammation and hemoglobin sickling that is also seen
in SCD. Furthermore, folic acid supplementation may be
repress GE observed in children with SCD.
Acknowledgments
The authors are grateful to The Scientific and Technological
Research Council of Turkey (TUBITAK) for supporting the study
(project number 113S271).
Conflict of interest
The authors declare that they have no conflicts of interest related
to this study.
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