Australian Dental Journal 1998;43:(1):9-13

A case of chronic severe neutropenia: Oral findings

and consequences of short-term g r a nulocyte
colony-stimulating factor treatment
Hatice Hastürk*
Ilhan Tezcan†
Leman Yel‡
Fügen Ersoy§
Özden Sanal§
Nermin Yamalık,
Ezel Berker¶

Abstract
Neutropenia is an absolute decrease in the number
of circulating neutrophils in the blood which results
in susceptibility to severe pyogenic infections.
Various oral findings such as periodontitis, alveolar
bone loss and ulceration may be seen in neutropenic
patients. A case is presented of a 6 year old girl with
chronic, probably congenital, severe neutropenia
with frequent respiratory tract infections, recurrent
oral ulcerations and significant periodontal break-
down resembling prepubertal periodontitis. She
was given granulocyte-colony stimulating factor
(G-CSF) treatment which resulted in an increase in
granulocyte count within two weeks and resolution
of the neutropenic ulceration. It is suggested that
G-CSF together with dental care regimens is a
promising treatment model in chronic severe
neutropenia cases presenting with oral
manifestations.
Key words: Neutropenia, granulocyte-colony stimulating
factor, periodontal breakdown, oral ulceration, paediatric
dentistry, case report.
(Received for publication September 1994. Revised
February 1995. Accepted March 1995.)
*Research Assistant, Department of Periodontology, Faculty of
Dentistry, University of Hacettepe, Ankara, Turkey.
†Associate Professor, Pediatrics, Immunology Division, Department
of Pediatrics, Children’s Hospital, University of Hacettepe, Ankara,
Turkey.
‡Research Assistant, Immunology Division, Department of
Pediatrics, Children’s Hospital, University of Hacettepe, Ankara,
Turkey.
§Professor, Pediatrics, Immunology Division, Department of
Pediatrics, Children’s Hospital, University of Hacettepe, Ankara,
Turkey.
,Associate Professor, Department of Periodontology, Faculty of
Dentistry, University of Hacettepe, Ankara, Turkey.
¶Professor, Department of Periodontology, Faculty of Dentistry,
University of Hacettepe, Ankara, Turkey.
Australian Dental Journal 1998;43:1.
Introduction
Neutropenia is defined as an absolute decrease in
the number of circulating neutrophils in the blood.
It can develop due to various aetiological factors or
can be congenital in nature. In cases of neutropenia
there is increased susceptibility to severe, life-
threatening pyogenic infections which make
therapeutic approaches problematic.1,2
Various oral features including gingival inflamma-
tion, gingival recession, tooth mobility, alveolar
bone loss and early tooth loss which may affect both
deciduous and permanent dentitions are frequently
encountered in neutropenia.3-9 Neutropenic ulcera-
tion is also common and may develop as the only
major clinical manifestation. 10-12 Periodontal features
may vary in appearance from marginal gingivitis to
severe alveolar bone loss affecting both deciduous
and permanent teeth, which in many aspects
resemble that of prepubertal periodontitis.13,14
A case of chronic severe neutropenia with typical
oral ulceration and severe periodontal breakdown
resembling prepubertal periodontitis is presented,
illustrating the benefit of granulocyte-colony
stimulating factor (G-CSF) treatment, even short-
term.
Case report
A 6 year old girl was referred to the Departments
of Pediatric Immunology and Periodontology,
Hacettepe University, with signs of severe tooth
mobility, recurrent oral ulceration and recurrent
respiratory system infection. Her medical history
9
 1 12

3 4

Fig. 1.–Caries and enamel hypoplasia at presentation. Gingival

inflammation is evident associated with calculus, plaque and
materia alba accumulation.
Fig. 2.–Deep, painful (recurrent) ulceration of the tongue at
presentation.
Fig. 3.–Periapical radiograph appearance of the mandibular incisor
teeth showing significant alveolar bone loss.
Fig. 4.–Panoramic radiograph showing alveolar bone loss affecting
nearly all teeth present.
Fig. 5.–Resolution of the neutropenic ulceration of the tongue
following short-term G-CSF treatment.

10 Australian Dental Journal 1998;43:1.

revealed that her chief complaint was recurrent oral
ulceration accompanied by fever lasting for 15-20
days since the age of 2 years. She had difficulty in
eating and failure to thrive due to painful recurrent
oral ulceration. In addition, she had suffered
frequent respiratory tract infections for which she
was given several courses of multiple antibiotics. She
was the child of healthy, consanguineous parents
(first cousins). Her two elder sisters had no similar
complaints
On physical examination, she had a weight of 12 kg
(under 5 percentile) and a height of 95 cm (under 5
percentile). Her body temperature was 38°C.
Systemic findings were unremarkable except for the
fine rales over the right lung.
Oral findings
All the deciduous teeth were present and the first
permanent molars were erupting. On oral examina-
tion the most striking feature was the severe carious
destruction of most of the teeth with the maxillary
and mandibular incisors most seriously affected. A
generalized enamel hypoplasia was also evident.
However, she did not suffer from any dental pain.
Abscess or pus formation was not noted. The
gingivae were bright red and severely oedematous
and inflamed. In most parts they tended to bleed
easily following provocation. On periodontal exami-
nation deep periodontal pockets (4-7 mm) were
noticed around most of the existing teeth, and nearly
all of the teeth presented various degrees of mobility.
A heavy amount of bacterial plaque, materia alba
and calculus formation was present due to the
child’s poor oral hygiene (Fig. 1). On her tongue
there was deep ulceration approximately 10 mm in
diameter (Fig. 2). Periapical radiographs showed
significant alveolar bone loss affecting nearly all of
the existing teeth, but the mandibular incisors were
affected more seriously (Fig. 3). Panoramic radio-
graphy confirmed the excessive alveolar bone loss
(Fig. 4).
Laboratory findings
The patient had a haemoglobin of 9.08 g/L with a
haematocrit of 27% and mild hypochromic and
microcytic red blood cells. The white blood cell
count was 5.000/mm3 with 4% segmented neutrophils
(absolute neutrophil count 200/min3), 81% lympho-
cytes, and 15% monocytes and the platelet number
was normal. Bone marrow aspiration revealed a
marked depletion of metamyelocytes and mature
neutrophils. There was a preponderance of the
earlier stages, namely myeloblasts, promyelocytes
and myelocytes. There was also a marked increase in
the number of plasma cells. Serum IgG, IgM and
IgA levels were 57.9 mg/mL (normal level: 7.45-
18.04 mg/mL), 4.53 mg/mL (normal level: 0.78-
Australian Dental Journal 1998;43:1.
2.61 mg/mL), and 6.15 mg/mL (normal level: 0.57-
2.82 mg/mL) respectively.
A chest X-ray indicated there was an infiltration of
the right lung.
Treatment
She was diagnosed as having severe neutropenia
and was started on 5 µg/kg/day subcutaneous G-
CSF and was also given sulbactam and ampicillin**
for pneumonia. No dental and/or periodontal treat-
ment could be performed because of the severe
neutropenic state of the patient until the recovery of
neutrophil count. However, the importance of
thorough oral hygiene attempts was discussed with
the parents and they and the patient were given
instruction in appropriate plaque elimination
techniques. Particular emphasis was placed on the
association between plaque accumulation and
gingival inflammation. The use of a soft toothbrush
and a disclosing solution to assist efficient plaque
removal was also recommended.
Two weeks of G-CSF treatment resulted in a
white cell count of 11200/mm3 (absolute count of
neutrophils: 2464/mm3 ) with 16% segmented
neutrophils, 6% stab cells, 6% myelocytes, 4%
promyelocytes, 4% eosinophils and 64% lympho-
cytes. Her chest was clear on auscultation and on X-
ray. Oral examination following two weeks of
G-CSF treatment revealed that the pre-existing
ulceration of the tongue had totally resolved (Fig. 5).
The amount of plaque accumulation also had
significantly decreased. Signs of gingival inflamma-
tion and bleeding on probing were less evident. She
also was much more comfortable upon tooth-
brushing and eating. It was recommended that she
be maintained on the G-CSF treatment and was put
on prophylactic trimethoprim-sulphamethoxazole
and elementary iron because of iron deficiency
anaemia, and she was given a professional perio-
dontal prophylaxis. Taking into account the continuing
development of the jaws, a treatment plan including
restoration of carious teeth, extraction of the teeth
with poor prognosis, and application of a removable
partial prosthesis and limitation of sucrose intake
was considered to be reasonable until the completion
of permanent dentition. In order to be able to deter-
mine any further dental-periodontal pathology in the
permanent dentition, a close monitoring of the
patient from a dental point of view was also
considered to be beneficial.
Discussion
Neutropenic disorders can be classified according
to the presence of an intrinsic defect in the myeloid
**Duocid, Pfizer, Turkey.
11
progenitors or extrinsic factors such as drugs, toxins,
infections and autoantibodies.1,2,15
There is involvement of stem cells of the myeloid
series with normal numbers of red blood cells and
platelet precursors in chronic neutropenia.
Neutrophil counts are frequently below 500/mm3
and peripheral monocytosis is often observed as in
this case of chronic neutropenia, probably of
congenital origin. The degree of susceptibility to
infection is roughly proportional to the blood
neutrophil count.16,17 The precise cause of the defec -
tive myelopoiesis is not known, although diminished
release of colony-stimulating activity or low affinity
of receptors has been considered to be responsible in
some instances.17,18
Recurrent, painful oral ulceration and prominent
periodontal destruction affecting most of the teeth
are common oral features of neutrophil disorders
and they may even be the first presenting symptoms.3,12
Severe and diffuse gi n gi val inflammation and
alveolar bone loss affecting both dentitions are also
frequently seen in neutropenia and the pattern of
this breakdown resembles prepubertal periodontitis.13,14
In the presented case, two frequently seen oral
characteristics of neutropenia, a prominent perio-
dontal breakdown and recurrent oral ulceration,
were both present. Furthermore, similar to the
previously reported cases, 13,14 the pattern was similar
to that of prepubertal periodontitis. Additionally, the
teeth presented a generalized enamel hypoplasia,
which has also been reported to be associated with
early severe infections.19 The presented case together
with the previously reported cases confirm that oral
manifestations may be the presenting symptoms of
most neutropenia cases and deserve particular
attention.
Various therapeutic approaches have been
attempted for long-term treatment in addition to
administration of antibiotics for acute infections.
Prophylactic antibiotics, corticosteroids, androgens,
splenectomy or cytotoxic therapy have all been
recommended.17 In recent years, recombinant
human G-CSF is considered to be a potential
effective therapy for promoting granulopoiesis and
in term elevating the circulating neutrophil count.7,20-24
The biological effects of G-CSF are mediated via
binding to high-affinity specific receptors mainly on
the surface of neutrophils.23,25 The present patient
was started on G-CSF with a dose of 5 µg/kg/day.
She showed an excellent response even with this
regimen in terms of clinical symptoms and increased
neutrophil counts.
While management directed to the primary
pathophysiology is maintained, symptomatic and
reconstructive therapy is essential because of the
severity of the additional oral manifestations.4,7,9,14
Even simple dental management may result in
12
bacteraemia because of the increased susceptibility
to infection. Scully and Gilmour11 suggested that
establishment of good oral hygiene is of utmost
importance in order to reduce the need for surgical
intervention. Mishkin et al.4 recommended a daily
application of 0.4% stannous fluoride gel in addition
to plaque elimination and limitation of sucrose
intake for prevention of carious breakdown of the
teeth. They also reported that the goal of perio-
dontal therapy for neutropenic patients should be to
aim to decrease gingival inflammation, make the
patient’s mouth more comfortable and to slow down
alveolar bone loss. Because of the high risk of
postoperative infection, surgery should be avoided
until sufficient absolute neutrophil counts are
attained and if emergency surgery is needed it is
recommended to be performed under appropriate
antibiotic coverage.4-6
Based on these suggestions and the patient’s age,
a professional prophylaxis was given to the patient
under antibiotic cover and oral hygiene instructions
were also given following G-CSF treatment which
resulted in an increase in neutrophil count and
resolution of the neutropenic ulceration. The
presented case may suggest that even a short-term
use of G-CSF is a promising medical therapy in
patients with severe neutropenia which in turn
makes the necessary dental treatment possible by
increasing the absolute neutrophil count and
decreasing the risk of postoperative infection.
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Address for correspondence/reprints:
Associate Professor I. Tezcan,
Immunology Division,
Department of Pediatrics,
Children’s Hospital,
Hacettepe University,
06100 Ankara, Turkey.
13