The present case demonstrated the following. First, poor oral hygiene and poor restoration outcomes combined with FS can lead to severe generalized periodontitis characterized by extensive alveolar bone resorption within a short timeframe. Second, a synergistic medical and dental treatment approach is important, when FS is accompanied by neutropenia.
Periodontitis is generally triggered and maintained by a subgingival biofilm adhering to tooth surfaces. Dysbiosis and the ensuing polymicrobial disruption of the host’s homeostasis were believed to be the causes of late-onset periodontitis [9, 10]. In the present case, leukopenia in addition to poor oral hygiene and poor restoration outcomes on mandibular molars resulted in rapid progression of the periodontal disease. Early-onset periodontitis generally occurs in patients with neutropenia and aberrant neutrophils, which are crucial for the management of bacterial infection [8]. They are the effector immune cells in charge of the gingival antimicrobial defense and the initial line of defense against bacterial invasion. Neutrophils are essential for maintaining periodontal health as evidenced by the early-onset periodontitis that occurs in patients with neutropenia and aberrant leukocyte adhesions [11]. Most genetic disorders that predispose an individual to severe periodontitis have been linked to abnormalities in the neutrophil immune cell subset, indicating the major role of this immune cell subtype in maintaining periodontal homeostasis [12]. Oral neutrophils may provide the cell subsets involved in periodontitis because they are located at the interface between the periodontal tissues and the oral environment. In contrast with neutrophils present in healthy periodontium, sites affected by periodontal disease show many gene alterations in neutrophils [13].
According to recent research, polymorphonuclear leukocytes (neutrophils) are the primary immune cells driving periodontal disease progression [14, 15]. A previous study demonstrated that patients with periodontitis have an increased number of neutrophils in the oral cavity [16]. Furthermore, some investigations have demonstrated that, compared to healthy controls, peripheral blood neutrophils from individuals with periodontitis have an improved capacity to phagocytose and eliminate bacteria, generating noticeably more reactive oxygen species and neutrophil elastase [17,18,19]. These results show that patients with periodontitis have altered neutrophil function. Thus, neutrophils are important in periodontitis, and in FS, particularly with extremely low neutrophil count, characterized by tissue destruction due to rapidly progressing periodontitis, as in this case.
Pancytopenia is a transient condition that can occur in various hematologic and autoimmune diseases and as a symptom of myelosuppression caused by cancer chemotherapy. Therefore, it is likely to be encountered in clinical practice. In FS, pancytopenia is associated with bacteremia, making periodontal therapy challenging. A more comprehensive diagnosis and dental treatment plan, along with close collaboration with the medical staff are essential, for management of such cases. Further, the combination of poor oral hygiene, poor restoration outcomes, and onset of FS induces severe alveolar bone resorption in a short period and over a wide area, that is, generalized severe chronic periodontitis. Poor oral hygiene and poor restoration outcomes, which are not major issues in patients with normal immunity, combined with FS may exacerbate existing periodontal diseases. Since alveolar bone resorption is considered to have progressed rapidly after the onset of FS in this case, it is also considered diagnosable as “Periodontitis as a direct manifestation of systemic diseases” according to the new classification of periodontitis [20]. In our case, the cause of the perioperative pancytopenia, including neutropenia, was not determined, and strict postoperative infection control was considered necessary. First, the patient underwent preoperative oral prophylaxis indicated by oral hygiene instruction to improve oral hygiene. There have been no reports on the perioperative period in the field of dentistry in patients with FS. The patient responded well after receiving antimicrobial agents following the “Guidelines for the Appropriate Use of Antimicrobial Agents for Prevention of Postoperative Infection” and the “Guidelines for the Treatment of Febrile Neutropenia.” If pancytopenia is not correctly diagnosed and treated, periodontal pockets in cases of severe periodontitis can become infected with oral bacteria and cause severe systemic infections. Thus, chronic and acute infections must be treated and controlled appropriately in patients with pancytopenia, including FS.
Augustus Roi Felty defined FS as a triad of RA, neutropenia, and splenomegaly in 1924. An absolute neutrophil count and persistent neutropenia of typically < 1500/mm3 is required to establish a diagnosis even if the complete triad is not present [1]. Patients with RA who have unexplained splenomegaly and neutropenia are clinically diagnosed with FS. Sometimes, the signs of inactive joints cause clinicians to focus on neutropenia and extra-articular illness, which leads to recurring and sometimes fatal infections. Therefore, establishing the right diagnosis can be difficult, and FS is frequently mistaken for hematological malignancy. In the present case, FS was not diagnosed until after the surgical tooth extractions, and the white blood count ranged from 0.3 to 0.6 × 103/µL. Comparison of the panoramic radiographs taken at the time of her visit to our department with the one taken by her family dentist 17 months earlier revealed rapid alveolar bone resorption. The patient was admitted to the hematology department in January 2016 with severe leukopenia and splenomegaly. Since rheumatic symptoms were absent, a definitive diagnosis of FS was not made.
In this case, all three criteria were present, and the characteristics of the systemic symptoms were consistent. Immunosuppressive therapy with corticosteroids is recommended for RA and leukopenia, and a strong antibacterial therapy is recommended for infection. The reason for the difficulty in the diagnosis of this case was believed to be the lack of RA symptoms and a focus on neutropenia alone.
In conclusion, severe periodontitis can be a significant outcome of pancytopenia combined with poor oral care. To prevent life-threatening situations and enhance the patient’s quality of life when both diseases co-exist, both the medical and dental teams need to work closely. We performed a pre- and postoperative antimicrobial administration procedure to prevent infection in this case of FS with neutropenia. Although this disease is relatively rare, it should be considered as a differential diagnosis when treating patients with leukopenia and neutropenia in clinical practice. Further, there are many causes of pancytopenia, and adequate collaborative measures with other relevant departments are necessary to prevent complications when performing invasive dental procedures. However, additional case studies and validation of this supposition are needed. Despite having severe chronic periodontitis and FS, a patient can still receive comprehensive dental therapy, including tooth preservation, extraction surgery, and comprehensive prosthetic treatment with control of the primary disease in collaboration with a hematologist, thus helping the patient achieve a better-quality lifestyle.
