Case of autoimmune neutropenia with severe marginal periodontitis


Early onset periodontitis is rarely seen in infants, though often leads to an acute and serious clinical course when encountered in such patients. Autoimmune neutropenia presents systemic and dental symptoms, as depressed resistance to bacterial infection is caused by a disorder that reduces the number of neutrophils. This disease can result in not only gingival inflammation but also destruction of periodontal tissues, such as attachment loss, alveolar bone absorption, and early tooth loss in primary as well as mixed dentition. Here, we report treatment of a child with marginal periodontitis from the age of 3 years–7 years 9 months. No systemic manifestations were noted until 3 years of age, thus the patient had never received a detailed examination or medication related to the disease. Following examinations at our department, we referred the patient to a pediatrician at our university hospital for possible systemic disease, who made a diagnosis of autoimmune neutropenia. Although administration of antibiotics and professional dental care were continued, neutrophil count was not increased and progressive periodontal destruction was observed. Extraction of teeth with poor prognosis was performed and a prosthetic strategy for the missing teeth developed. It is important to recognize that periodontitis along with autoimmune neutropenia can appear in infants, even though the incidence is quite low. Early detection and early treatment of this disease is necessary for delaying progression of periodontitis and optimal occlusal induction of permanent teeth.


Autoimmune neutropenia (AN) is a disorder caused by severely reduced neutrophils (0–500/mm a result of an intrinsic immune cell defect, or genetic defect, or virus infection , or a manifestation of 22q 11.2 deletion syndrome , Evans syndrome , or hyper IgM syndrome .

In individuals affected by AN, attacks by autoantibodies against neutrophils cause their destruction. Such neutrophil defects and other immune cell functions can play roles in increased susceptibility to periodontitis and other systematic infection .

Human neutrophil antigen (HNA)-1a, 1b, and -1C are principal antigens implicated in the development of AN . Antibodies in the majority of diagnosed patients show reactions against antigens located on IgG Fc receptor type 3b(FcRⅢb), though other involved antigens have yet to be elucidated .

AN is quite rare, with an absolute rate of incidence ranging from as low as 0.001%–0.3% , with a clear gender difference related to incidence rates reported . The age of diagnosis ranges from 3 to 30 months. In spite of a lack of neutrophils, the primary clinical symptoms of AN are mild and generally presented as fever, upper respiratory tract infection, or tympanitis . Neutrophil count recovers spontaneously when most patients become 4–5 years old, after which they gain resistance to infection . However, the epidemiology is not fully understood, because of the early age of onset and generally benign attributes of the disease.

On the other hand, in contrast to general symptoms, severe oral manifestations have been observed in children affected by AN , with gingivitis, oral ulceration, stomatitis, and periodontitis shown to be prominent features resulting from susceptibility to infection . Periodontal problems are recognized as a characteristic features of other types in cases of innate, postnatal, and acquired neutropenia, as represented by congenital , familial benign chronic , and cyclic neutropenia.

Here, we present clinical findings and dental management of a patient with AN. Written and verbal consent for the use of patient-related documentation and information for the purpose of publication were provided by the parents.

Case report

A Japanese girl aged 3 years 7 months was referred to our university hospital for oral and gingival problems in primary dentition. A medical history revealed that she had suffered oral stomatitis about once a month and a slight fever up to 37 °C about once a week since the age of 11 months. The patient had not suffered from a respiratory tract infection or middle ear inflammation. The family medical history was unremarkable and the patient had not received any type of medication up to that time.

All primary teeth were present and no evidence of dental caries was seen. An intraoral examination revealed redness and recession, as well as unusual marginal gingiva bleeding, which was hemorrhagic and painful. Plaque accumulation and gingival inflammation were noted in the upper and lower primary incisors. There was no ulcerative gingiva or pus formation ( Fig. 1 A). A periodontal examination showed 3-mm periodontal pockets in the upper primary incisors, while slight mobility and calculus deposits were seen in the lower primary incisors. Dental radiography of the upper primary incisors revealed horizontal alveolar bone loss up to nearly half of the root length ( Fig. 1 B). Oral hygiene was locally inadequate, especially in tooth cervical areas.

Fig. 1
A. Intraoral photograph obtained at first visit (age 3 years 7 months). B. Periapical radiographs obtained at the age of 4 years 4 months. The upper primary incisors revealed horizontal alveolar bone loss extending to nearly half of the root length.

Laboratory findings showed haemoglobin and haematocrit concentrations of 12.6 g/L and 38.1%, respectively, while the white blood cell count was 3640/mm 3 with 0.5% segmented neutrophils (absolute neutrophil count 91/min 3 ), composed of 70.5% lymphocytes and 19.0% monocytes, and the number of platelets was 299,000/mm 3 ( Table 1 ). The human neutrophil alloantigen (HNA)-1a antibody against white blood cells was identified as the cause of neutropenia.

Table 1
Results of clinical blood examination at age of 3 years 9 months.
Complete blood count Value Normal
Hemoglobin (g/dl) 12.6 males 14–18, females 12–16, newborns, 16–19, adolescents, 11-16
Hematocrit (%) 38.1 males 40–54, females 37–47, newborns 49–54, adolescents 35-49
White blood cells 3640 5000-10,000 cells/mm 3
Platelets 299,000 150,000–400,000 cells/mm 3
Differential blood count
Neutrophils 2.5% 50–70%
Lymphocytes 70.5% 30–40%
Monocytes 19.0% 3–7%
Eosinophils 7.5% 0–5%
Basophils 0.5% 0–1%

The patient was diagnosed with autoimmune neutropenia and trimethoprim-sulfamethoxazole and tosufloxacin at 0.04 g/kg/day was started, with amoxicillin temporarily added when infection was noted. Granulocyte-colony stimulating factor (G-CSF) injections were considered should the patient become extremely febrile or neutropenic. Instructions regarding oral hygiene were given to the patient and her mother, with daily brushing and use of dental floss recommended. Periodontal treatments in the clinic were also performed twice a month, including scaling with an ultrasonic scaler, professional mechanical tooth cleaning (PMTC), and chemical cleaning with acrinol hydrate, in order to remove dental plaque and calculus.

Following those initial treatments, the amount of plaque accumulation was reduced to half that seen prior to treatment ( Fig. 2 ). Bleeding on probing and gingival inflammation also showed lower degrees of intensity. The twice-a-month periodontal treatments were continued and a medical checkup was also conducted once a month including blood cell monitoring. Neutrophil count did not increase, except when an upper respiratory tract inflammation or a virus infection was present, which cause an increase to 100–329/mm 3 .

Fig. 2
Intraoral photograph obtained at the age of 5 years 9 months. Plaque accumulation was reduced as compared to the first visit. However, bleeding from the marginal gingiva and gingival recession were observed in the lower and upper bilateral primary molars.

Regular professional treatments as well as self-care measures resulted in improvement to the plaque control record and bleeding index. Nevertheless, generalized severe acute and chronic gingivitis continued, including periodontal pockets 3–4 mm in depth noted in the lower primary molars at the age of 6 years 3 months ( Fig. 3 A), though periodontal pocket depth for the upper incisors remained less than 3 mm. Attachment loss and severe tooth mobility were also detected in the lower bilateral first and second primary molars. Orthopantomography findings revealed severe periodontal bone loss around the bilateral lower molars ( Fig. 3 B). Extraction of the lower left first primary molar was performed because of severe occlusal pain. Although we recommended extraction of other teeth with poor prognosis, that was rejected by the patient and her parents. Surgical treatment was not considered because of systemic condition and age. We continued to provide professional tooth cleaning and applied minocycline ointment to the periodontal pockets. Interdental brushing and flossing were provided for interproximal areas of the dentition, gingival lesions, and root furcation areas. Occlusal adjustment was also performed. The neutrophil count gradually increased from the age of 6–7 years up to 307/mm 3 and the general condition of the patient was stable. At that time, long-term administrations of trimethoprim-sulfamethoxazole and tosufloxacin was changed to a single administration of macrolide.

Jan 12, 2020 | Posted by in General Dentistry | Comments Off on Case of autoimmune neutropenia with severe marginal periodontitis
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