Acute Necrotizing Ulcerative Gingivitis

Etiology

ANUG is typically an opportunistic bacterial infection caused by spirochetes or gram-negative bacteria.[1] Results from a study identified spirochetes and predominantly gram-negative bacteria, including Bacteroides intermedius and Fusobacterium spp., as the most common causes.[4][5] Furthermore, results from another study primarily implicated species of Treponema, Selenomonas, Fusobacterium, and Prevotella intermedia.[6]

Epidemiology

Historians have documented cases of ANUG since the fourth century BCE. Most reports from the ancient world came from fighting troops, and studies of ANUG in the modern world continue to highlight soldiers as a prominent demographic affected by the disease.[1][7] ANUG is more common in younger individuals, particularly severely malnourished children and young adults with HIV infection.[1][8] In the United States, ANUG appears to occur primarily in White individuals.[9] Results from prospective clinical studies have also found psychological stress, immunosuppression, and tobacco use to be strongly associated epidemiologically with the development of ANUG.[10]

Pathophysiology

Many physiologic factors play a central role in the development of ANUG, including psychological stress, malnutrition, insufficient sleep, use of alcohol or tobacco, poor oral hygiene, preexisting gingivitis, and HIV infection. These factors have been shown to impair the host immune response, which facilitates bacterial virulence. Psychological stress reduces gingival microcirculation and salivary flow; it also increases adrenocortical secretion, thereby modifying the function of polymorphonuclear leukocytes (PMNs) and lymphocytes and altering the efficacy of the host immune response. In addition, psychological stress can influence the patient's behavior and mood, leading to poor oral hygiene, malnutrition, and increased tobacco use, further increasing their susceptibility to infection.[6] Similarly, a poor diet increases histamine levels and capillary permeability in the gingiva, thereby reducing PMN chemotaxis.[6]

Histopathology

The clinical appearance of ANUG reflects its histopathology.[6] Four distinct layers have been described. Most superficial is a bacterial area within a fibrous mesh composed of epithelial cells, leukocytes, and various bacteria, including rods, fusiforms, and spirochetes. Deep to that layer lies a neutrophil-rich zone with a higher density of leukocytes, spirochetes, and other bacterial cells. Next lies a necrotic zone containing disintegrated cells, spirochetes, and fusiform bacteria. The deepest layer contains spirochete infiltration.[6] Often, microbiological testing does not provide relevant diagnostic information, as the microbial profile of ANUG can also be typical of healthy gingiva, gingivitis, and periodontitis.[6] A few case series have demonstrated the utility of Gram staining to support the diagnosis, which is otherwise purely clinical.[5] 

History and Physical

ANUG is primarily a clinical diagnosis, making the history and physical examination essential. Three core findings establish the diagnosis: sudden-onset oral pain, gingival bleeding, and the characteristic necrosis and ulceration of the interdental papillae.[1][10] Additional features may include lymphadenopathy; malaise; a strong, fetid odor on the breath; and a gingival pseudomembrane.

Several predisposing factors are thought to contribute to the development of ANUG.[6] Poor oral hygiene and compromised immune function, particularly in individuals with HIV infection, are strongly linked to the diagnosis of ANUG.[6] Nutritional deficiencies, inadequate living conditions, and significant psychological stress have also been frequently noted as contributing risk factors.[1][6]

Evaluation

As discussed in the History and Physical section, ANUG is primarily a clinical diagnosis based on a detailed history and physical examination. There are 3 essential clinical components required to confirm the diagnosis: sudden-onset oral pain, gingival bleeding, and the characteristic necrosis and ulceration of the interdental papillae. A Gram stain of the gingival tissue supports the diagnosis; however, this test is not always performed and is not required.[5]

Treatment / Management

The treatment of ANUG should be approached in successive stages: acute-phase management, treatment of any preexisting conditions, management of disease sequelae, and transition to the supportive or maintenance phase.[6] Treatment of the acute phase aims to halt tissue destruction and to control the patient's discomfort. Gentle ultrasonic debridement is used for superficial gingival plaques and calculi, in conjunction with localized oxygen therapy directed at necrotic lesions.[6] The use of 0.12% chlorhexidine gluconate mouth rinse should be considered, with a suggested regimen of twice-daily use for 30 days.[11] (B3)

Systemic antimicrobials are considered in the acute phase in cases with poor response to debridement or with symptoms of systemic involvement, including fever, malaise, and vomiting.[6] Metronidazole (250 mg 3 times daily) is a common first-choice agent due to its activity against anaerobes. Penicillin, tetracyclines, clindamycin, amoxicillin, and amoxicillin-clavulanate have been shown to produce acceptable results and are considered on a case-by-case basis. Results from a study of oral penicillin, for example, showed significant clinical improvement within 3 to 6 days.[5] Although oral antibiotics are beneficial, topical antimicrobials are not recommended. The high bacterial density in the tissue impairs the ability to achieve adequate drug concentrations. Significantly, antifungal agents should be added for patients with immunosuppression who are undergoing antibiotic therapy.[6](B3)

After the acute phase has been controlled, treatment of any preexisting conditions, such as chronic gingivitis, should be initiated. This stage involves procedural prophylaxis, such as scaling and root planing, and the establishment of oral hygiene maintenance methods with the patient.[11] Gingivectomy or gingivoplasty procedures can treat any superficial craters.[6] Predisposing factors, including smoking, poor sleep hygiene, and stress, should also be addressed.(B3)

The main goals of the maintenance phase are to promote patient adherence to oral hygiene practices and to control any predisposing factors.[6] If proper maintenance is not carried out, relapses are likely to occur. Treating ANUG requires a multifactorial approach that includes superficial debridement, oral hygiene instruction, use of antimicrobial mouthwash, and, potentially, oral antibiotics, as well as initiation of a comprehensive prophylaxis plan that provides for root planing and management of predisposing factors.[4]

Differential Diagnosis

ANUG may be mistaken for other infectious or inflammatory conditions. Considerations for a differential diagnosis should include bacterial causes, such as gonococcal or streptococcal gingivitis, and viral causes, such as acute herpetic gingivostomatitis and infectious mononucleosis, in addition to mucocutaneous conditions such as desquamative gingivitis, multiforme erythema, and pemphigus vulgaris.[6] Clinicians should consider ANUG in individuals with HIV, even if their CD4+ T-lymphocyte counts have remained stable.

Pertinent Studies and Ongoing Trials

While numerous studies have examined suspected risk factors for ANUG, research on the condition remains limited. Approximately two-thirds of the observed studies on ANUG have been surveys or case reports, with the remainder being case-control studies. Only a few longitudinal and population-based studies are available, most of which are conducted in high-risk populations. Furthermore, the results of many of these studies pertain to gingivitis in general rather than ANUG specifically. Other existing studies are based on small numbers or on case histories alone, without including control subjects, which leaves much to be desired in this field of research. However, the extremely low incidence of ANUG in the population severely limits the feasibility of most longitudinal studies at this time.[9]

Prognosis

Appropriate multifactorial management of ANUG usually prevents disease progression, and ulcer healing can be expected within a few days after initiating treatment. However, untreated ANUG can rapidly deteriorate into potentially fatal conditions such as sepsis, necrotizing ulcerative periodontitis, and cancrum oris (noma).[1]

Complications

Acute necrotizing ulcerative gingivitis may result in severe tissue destruction, including necrotizing periodontitis, necrotizing stomatitis, and cancrum oris (noma), which is often fatal. Developing the knowledge necessary to identify and manage ANUG promptly is essential for both adult and pediatric clinicians.[12]