syndrome and agammaglobulinemia: a case report Yasuka Kusumoto1*, Kohsuke Imai2, Yoshio Ohyama3, Haruhisa Fukayama4 and Osamu Shinozuka1
Abstract Background: Down syndrome is characterized by a variety of dysmorphic features and congenital malformations, such as congenital heart disease, gastrointestinal disease, and other conditions like leukemia and autoimmune disorders. Patients with Down syndrome are highly prone to respiratory tract infections, which might be fatal to them. However, there are only few available data on patients diagnosed with Down syndrome and agammaglobulinemia. In this report, we describe a case of successful prevention of post-dental treatment complications (e.g., pneumonia and other bacterial infections) in a patient with Down syndrome and agammaglobulinemia. Case presentation: A 43-year-old man with Down syndrome, untreated agammaglobulinemia, and a history of recurrent pneumonia, was referred to our clinic for tooth mobility. To reduce the risk of post-operative infections, gammaglobulin treatment and prophylactic administration of antibiotics was scheduled before the dental procedure. Furthermore, the dental treatment, which included a filling and extractions, was conducted under general anesthesia and with the supervision of a hematologist. The dental procedures were successfully performed without any post-operative infection, and the patient is undergoing follow-up care. Conclusions: The purpose of this case report was to recommend a close liaison between physicians and dentists who may encounter a similar case, and to emphasize the importance of improving oral health of immunodeficient patients to prevent infections caused by oral microbial flora. Keywords: Down syndrome, Immunodeficiency, Oral management, Case report
Background [1, 2]. Agammaglobulinemia is one of the most common
treatment in patients with Down syndrome diagnosed perform a comprehensive evaluation and treatment with agammaglobulinemia. under general anesthesia as an in-patient procedure. Here, we report the successful prevention of post- After consultation with a hematologist, the patient re- dental treatment complications, such as pneumonia and ceived three courses of intravenous immunoglobulin other bacterial infections, in a 43-year-old man with (IVIG) therapy to restore and maintain his serum IgG Down syndrome and agammaglobulinemia, through levels above 500 mg/dL (Fig. 1). IVIG therapy was imple- immunoglobulin administrations and prophylactic mented at 4 weeks, 2 weeks, and 1 day before operation. antibiotherapy. The mandibular right first molar was restored with light-cured composite resin. The maxillary left first Case presentation molar, second molar, maxillary incisors, and mandibular Consent for publication in this report was obtained from left incisor were extracted. After extraction, sockets were the patient’s mother. sutured to prevent post-operative infection. Suture A 43-year old male patient was referred to the Clinic reduced the risk of rebleeding and relieved patient for Persons with Disabilities at the Dental Hospital of discomfort. Tokyo Medical and Dental University (Tokyo, Japan) Operating table was prepared in the usual fashion. For with a primary complaint of tooth mobility. He had a operative field, we used 0.025% benzalkonium chloride history of Down syndrome that was diagnosed at birth. solution and normal saline solution as usual. All proce- He lived alone with his mother. Family history was unre- dures were carried out under standard disinfection with- markable. He had experienced recurrent pneumonia and out any additional measures. chronic bronchitis since he was 34 years old. Subsequent Ampicillin sodium (6 g/day) was administered every immunological assessment revealed agammaglobulin- 12 h intravenously, beginning in the morning before the emia (Fig. 1) and B-cell deficiency (0.47%) associated operation and then for 4 days after the operation, follow- with decreased CD45 RA+ naive CD4+ T-cells (4.5% of ing which the patient was discharged without any infec- CD4+ T-cells) (Fig. 2). He had never received gamma- tion or complication. globulin treatment. At present, the patient is undergoing follow-up care, Oral and radiographic examinations revealed alveolar and the marginal gingivitis has improved. He is receiving bone resorption in maxillary incisors and several regular IVIG treatments under the care of his local decayed teeth (Fig. 3). Marginal gingivitis was observed physician. all around the teeth. The patient’s oral hygiene was very poor with dental plaque on all surfaces of his teeth. Discussion The patient had severe mental retardation and autistic The case reported here was successfully managed features, which included difficulty in communication. through the administration of gammaglobulin and Thus, with the consent of his family, it was decided to antibiotics. This report describes the management of
Fig. 1 Schedule of pre-operative intravenous immunoglobulin (IVIG) therapy. Hb = hemoglobin level (g/dL); IgA = immunoglobulin A (mg/dL); IgG = immunoglobulin G (mg/dL); IgM = immunoglobulin M (mg/dL); IVIG = intravenous immunoglobulin substitution; Plt = platelet count (10,000/μL); RBC = red blood cell count (10,000/μL); WBC = white blood cell count (/μL) Kusumoto et al. BMC Oral Health (2020) 20:71 Page 3 of 5
Fig. 2 Flow cytometric analysis of the patient’s peripheral blood mononuclear cells (PBMCs). PBMCs from the patient were stained with monoclonal antibodies for CD19, Cd3, CD4, CD45RA, and CD45RO. The B-cells and naive T-cells were remarkably decreased in the patient
agammaglobulinemia in a patient with Down syndrome IVIG therapy in patients with agammaglobulinemia re- during oral care procedures. Autoimmune diseases are duces the risk of infection [6, 7]. It involves therapeutic frequently observed in patients with Down syndrome, preparations of pooled polyspecific IgG, obtained from with prevalence of immune deficiency, mild to moderate the plasma of a large number of healthy individuals. T-cell and B-cell lymphopenia with decreased naive lym- IVIG approach had a significant and positive therapeutic phocytes, impaired mitogen-induced T-cell proliferation, impact in our patient (Fig. 1). reduced specific antibody responses to immunizations, IVIG therapy prevents many, though not all, pulmon- and defects in neutrophil chemotaxis [4, 5]. These ab- ary complications. Though they are receiving IVIG ther- normalities may contribute to increased susceptibility to apy, in some patients with relatively more severe viral infections, hematologic malignancies, and auto- antibody deficiencies, may be in high risk of chronic bac- immune diseases associated with Down syndrome [4, 5]. terial infections [8]. Then a standard course of antibi- For invasive dental procedures, such patients are at a otics for acute infections stemming from surgical high risk of severe infection and septicemia caused by treatment would not be sufficient in severely immunode- the spread of oral microorganisms and their toxins ficient patients and may lead to rapid relapse or recur- through circulating blood. Clinical use of IVIG therapy rence of infections and further morbidity, including has increased in the treatment of patients with PADS. permanent scarring and loss of function. Experienced
Fig. 3 Panoramic radiograph, radiographic examinations revealed alveolar bone resorption in maxillary incisors and several decayed teeth Kusumoto et al. BMC Oral Health (2020) 20:71 Page 4 of 5
clinical immunologists often prescribe a course of anti- and were major contributor in writing the manuscript. The authors read and microbials that are two to three times longer than stand- approved the final manuscript.
ard recommendations [9, 10]. In the case described here,
Funding antibiotic prophylaxis besides the induction of IVIG Not applicable. treatment was effective for dental treatment of the im- munodeficient patient. Availability of data and materials The datasets generated and analyzed during the current study are not Owing to their susceptibility to infection, immunodefi- publicly available since they contain medical information of the patient. cient patients require precautions during dental treatment. Dental treatment of patients with severe combined im- Ethics approval and consent to participate munodeficiency has not been previously reported in den- Not applicable. tal or medical literature. Based on our experience with Consent for publication this patient, we recommend that IgG, IgA, and IgM Written and signed consent to publish the images in this case report was should be evaluated in patients with Down syndrome be- obtained from the mother of the patient. A copy of the consent is available fore they undergo dental procedures. Delayed diagnosis of for review by the Editor of this journal. agammaglobulinemia and other PADs might result in fre- Competing interests quent hospitalizations owing to bacterial infections, The authors declare that they have no competing interests. including pneumonia, which could lead to chronic lung diseases. Author details 1 Department of Dentistry for Persons with Disabilities, Graduate School of In the current case, initial oral examination revealed Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, poor oral hygiene. Home care is essential for a patient’s Yushima, Bunkyo-ku, Tokyo, Japan. 2Department of Community Pediatrics, oral hygiene and dental health. However, this is difficult Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. 3Department of to achieve in patients with Down syndrome owing to the Oral and Maxillofacial Surgery, Shizuoka City Shizuoka Hospital, Shizuoka, intellectual impairment and decreased manual dexterity Japan. 4Department of Anesthesiology and Clinical Physiology, Graduate [11]. Since patients with Down syndrome frequently ex- School of Tokyo Medical and Dental University, Tokyo, Japan. perience respiratory infections, regular oral and dental Received: 30 December 2019 Accepted: 2 March 2020 examination should be performed to reduce the risk of aspiration pneumonia; it should be remembered that as they age, people with Down syndrome are more likely to References 1. 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