Necrotizing Periodontal Diseases

Etiology

Although necrotizing periodontal diseases are infectious conditions, immunosuppression is the most critical predisposing factor. Cases of necrotizing gingivitis and necrotizing periodontitis are almost always found in patients with an immunosuppressed condition, most notably HIV. A CD4 count of less than 200 in an HIV-positive patient is more strongly linked to necrotizing periodontitis than any other risk factor.[4][5][4] But, other diseases such as leukemia, neutropenia, diabetes mellitus, and long-term immunosuppressant therapy have also been noted.[6][7][8]

Other contributing factors include tobacco smoking, unusual psychological stress, severe malnutrition, poor sleeping habits, and poor oral hygiene. Most cases of NPDs are seen in patients that are tobacco smokers. Malnutrition has been shown to be an important risk factor. In developed countries, NPDs are associated with populations who display poor eating habits, such as college students, whereas, in developing countries, they are associated with young children with deficient protein intake.[9] Also, patients with a history of necrotizing gingivitis are considered at increased risk of developing necrotizing periodontitis.[4]

Virulent bacteria, specifically Fusobacteria, Prevotella intermedia, Porphyromonas gingivalis, and Treponema sp, have been identified in the necrotic lesions associated with NPDs.[4] Additionally, antibiotics have been shown to alleviate symptoms in the acute phase, indicating a bacterial involvement in the disease process. However, it is unclear whether these organisms are the causative agent in the disease process or if they represent a secondary overgrowth due to the immunosuppressed condition. Furthermore, the disease is not known to be transmissible, indicating that the etiology is not due to exogenous factors but rather due to preexisting host factors.[8]

A limited understanding exists surrounding the actual cause of necrotizing periodontal diseases; however, evidence points to an existing periodontal condition that is given the opportunity to proliferate into a more rapid and destructive state.[10]

Epidemiology

The worldwide prevalence of necrotizing periodontal diseases is less than 1%.[2] The most affected age group is young adults aged 18 to 30, malnourished children, or immunocompromised patients.[2] NPDs are more commonly found in countries with lower socioeconomic status and are rarely seen in developed countries.[2] 

A major epidemiologic risk factor is malnutrition. NPDs are most commonly associated with very young children in developing countries due to severe malnourishment, specifically a low protein intake.[11] Additional risk factors most widely associated with emerging countries include tobacco smoking and poor oral hygiene.[12]

Pathophysiology

The exact pathogenesis of necrotizing periodontal diseases is not fully understood. However, the initial stage of NG is believed to be caused by commensal oral organisms that become pathogenic in response to reduced host response.[13] Fusobacteria and spirochete species have commonly been implicated in NPDs; however, it is unclear whether these are causative organisms or represent a secondary or opportunistic infection due to the patient's immunosuppressed condition.[14] These bacteroids, in addition to other primarily gram-negative species, produce a vast array of metabolites (collagenases, endotoxins, hydrogen sulfide, and fibrinolysin) responsible for the destruction seen in NPDs: rapid destruction of the periodontium, including the gingiva, periodontal ligament, and alveolar bone.[8][15]

Histopathology

In 1965, Listgarten provided electron microscopy (EM) data of the invasion of spirochetes in what was previously referred to as necrotizing ulcerative gingivitis (NUG) and differentiated between various zones within NUG. The zones are listed in order of increasing depth.

1. Bacterial zone
2. Neutrophil-rich zone
3. Necrotic zone
4. Zone of spirochete infiltration

The most superficial bacterial zone contains a variety of bacterial species. The neutrophil-rich zone contains various leukocytes, with the most prominent cell type being the neutrophil. In the next deeper zone, the necrotic zone, an abundance of dead cells and fragmented connective tissue can be found. Up until this final zone, a variety of bacteria species could be found, including spirochetes. However, in the zone of spirochete infiltration, spirochetes are the sole organism present and can be found in the deep, preserved tissue.[16]

History and Physical

As previously mentioned, necrotizing periodontal diseases are almost always found in patients with immunosuppression or psychological stress.[4] A history of tobacco smoking is a significant risk factor for developing an NPD.

Patients will usually report excruciating pain, fetid oral odor, and rapid onset of the condition, characteristic of necrotizing periodontal diseases - necrotizing periodontitis can lead to loss of periodontal attachment in as short as a few days.[4][17] In some NPDs, systemic involvement can be seen via swelling of regional lymph nodes. Fever and malaise are associated with more advanced stages of NPDs, e.g., necrotizing periodontitis.[17] NPD lesions are extremely painful, which provides a good differentiating feature from regular periodontal diseases that do not elicit pain. As a result of the pain, patients tend to stop their oral hygiene practices, contributing to halitosis. Additionally, patients may decrease their drink and food intake, potentially becoming malnourished, exacerbating symptoms of fever or malaise.[18]

The most typical clinical sign of NPDs is tissue necrosis, seen as ulcerated and necrotic gingiva, with a distinctive “punched-out” or “cratered” appearance.[15][18] These necrotic gingival tissues are covered by a pseudomembrane containing plasma proteins and white blood cells. When NG progresses to NP, loss of periodontal ligament and alveolar bone occurs. A linear erythematous area demarcates the ulcerated zone from the attached gingiva, alveolar mucosa, and free gingiva.[4] Provoked or spontaneous bleeding may be evident. Loss of attachment is the key feature of necrotizing periodontitis; however, deep periodontal pockets are uncommon (junctional epithelium is necrotized).[4] The disease progresses so rapidly that there is little time for pocket formation.[10][15] In necrotizing stomatitis, there is a destruction of the oral mucosa beyond the mucogingival junction and bone exposure, with alveolar bone necrosis and possible sequestration.[3][4]

Evaluation

NPDs are a clinical diagnosis, and intraoral examination should be accompanied by extraoral examination searching for lymphadenopathy or facial asymmetry [4]. A biopsy is unhelpful, as it will present as non-specific inflammation. Radiographs can be used to demonstrate the extent of alveolar bone loss.

On radiographic examination, the bone may show extensive changes or very little. Osteonecrosis of the bone may be seen as “moth-eaten” patchy radiolucency, resembling other conditions such as medication-related osteonecrosis of the jaw, osteoradionecrosis, and osteomyelitis.[2] Radiopaque areas corresponding to necrotic bone sequestra may be visualized. CT scans may be more helpful in differentiating between different conditions of the bone. But ultimately, elements of the history and clinical examination will determine a definitive diagnosis.[2]

Blood tests are recommended to investigate predisposing illnesses such as leukemia, neutropenia, and agranulocytosis.[18][9]

Treatment / Management

Necrotizing gingivitis and necrotizing periodontitis are mainly managed using local measures. The treatment of NPDs depends on the extent and severity of the disease, but in general, initial management includes:

1. Gentle mechanical debridement under local anesthesia,
2. Removing pseudomembrane with the help of a cotton pellet embedded in 0.12% chlorhexidine,
3. Providing oral hygiene instructions
4. Indicating either a 0.12% chlorhexidine mouthwash or hydrogen peroxide mouth rinse[4]

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) as needed should be advised to the patient to help alleviate the pain.[4] Antibiotics are recommended as an adjuvant to local measures when there is evidence of systemic involvement, e.g., pyrexia, malaise, and lymphadenopathy.[19][4] Metronidazole is the antibiotic of choice due to the anaerobic bacteria involved in the condition. Amoxicillin is another option when metronidazole is contraindicated.

Modifying risk factors and treating underlying systemic conditions are key in managing NPDs. Tobacco smoking, psychological stress, and malnutrition should be managed to reduce the risk of future disease.[9][14] Patients with NP may require a medical consultation as the patient may have an underlying immunocompromising condition like HIV. These underlying or concurrent conditions need to be treated simultaneously with the required dental therapy.(B2)

Further advice may include taking vitamin supplements, avoiding spicy food, observing appropriate fluid intake, and improving sleep.[4] Finally, reviewing for further treatment and maintenance is vital in improving the disease prognosis.

Necrotizing periodontitis is a disease of tissue destruction of both soft tissue (gums) and hard tissue (alveolar bone). As a result of the disease, both soft and hard tissue defects can make oral hygiene difficult. After completing the acute treatment phase, patients may undergo treatments to surgically correct any defects, such as a gingivoplasty for smaller soft tissue defects or osteoplasty to repair larger, bony defects.[4]

Differential Diagnosis

Necrotizing periodontal diseases should be differentiated from the following:

1. Oral mucositis 
2. HIV-associate periodontitis
3. Herpes simplex virus (HSV)
4. Scurvy
5. Gingivostomatitis
6. Desquamative gingivitis
7. Invasive fungal disease 
8. Illicit-drug related gingival disease
9. Agranulocytosis
10. Leukemia
11. Chronic periodontitis

Appropriate testing and history taking must be performed for an accurate diagnosis.[20][17]

Staging

According to the 2017 classification system put forth by the American Academy of Periodontology, necrotizing periodontal disease is a category of diseases that affects the periodontium through the extent of ulceration and necrosis. Within this group, there are three major subsets:

1. Necrotizing gingivitis
2. Necrotizing periodontitis
3. Necrotizing stomatitis

The differences between these subsets are based on the extent and site of damage. Necrotizing gingivitis is used to describe necrosis and ulceration limited to the gingiva (gums). A progression of that condition is necrotizing periodontitis, where there is damage to and loss of the periodontium surrounding each tooth, including the gingival tissues, alveolar bone, and periodontal ligament. Lastly, necrotizing stomatitis is a term used to describe the destruction of the mucous membranes in the mouth and the areas beyond the mucogingival junction, such as the cheek, tongue, and palate.[21]

Prognosis

Recurrence of necrotizing periodontal diseases is not uncommon, and therefore regular recalls are recommended to monitor for signs of future illness. Additionally, a critical factor in the prognosis of NPDs is the management of risk factors. The prognosis is more favorable if patients improve their risk factors such as oral hygiene, nutrition, psychological stress, or smoking cessation. Additionally, treatment of underlying conditions, such as therapy for HIV, may reduce the patient's immunosuppressed state, thus improving their prognosis.[7][17]

Complications

There are several noted complications of necrotizing periodontal diseases, most of which are related to the destructive nature of the disease.[10] These complications include:

• Tooth loss
• Further loss of attachment
• Extensive soft tissue necrosis
• Alveolar bone exposure
• Sequestration of bone fragments
• Bacteremia
• Weight loss and dehydration[4][22]