Acute Necrotizing Ulcerative Gingivitis

Etiology

ANUG is commonly due to an opportunistic bacterial infection and is predominantly associated with fusiform and spirochete bacteria. One study identified spirochetes and a majority of Gram-negative bacteria, including Bacteroides intermedius and Fusobacterium spp. as the most common causes.[3][4] Another study described the microbiota associated with ANUG to include Treponema spp., Selenomonas spp., Fusobacterium spp., and Prevotella intermedia.[5] In summary, ANUG is closely associated with spirochetes and gram-negative bacteria, which can be identified on gram stain (if performed).[1]

Epidemiology

ANUG has been documented by historians since the fourth century BC. Most of the reports from the ancient world were among fighting troops, and studies of ANUG in the modern world are still finding it common among soldiers.[1] ANUG is more common in the young, particularly severely malnourished children and young adults with human immunodeficiency virus (HIV) infection.[1][6] It appears that in the United States, the distribution is limited primarily to Whites.[7] Prospective clinical studies have found a disrupted ability to cope with psychological stress, immunosuppression, and tobacco use to be strongly associated epidemiologically with the development of ANUG.[8]

Pathophysiology

Physiologic factors that play a main role in ANUG include psychological stress, poor diet, insufficient sleep, alcohol, tobacco, poor oral hygiene, preexisting gingivitis, and HIV infection. These factors have been shown to impair the host immune response, which facilitates bacterial pathogenicity. Psychological stress reduces the gingival microcirculation and salivary flow and increases adrenocortical secretions, which can modify the function of polymorphonuclear leukocytes and lymphocytes. This alters the immune response as well as the patient's behavior and mood, resulting in insufficient oral hygiene, malnutrition, and increased tobacco consumption.[5] Similarly, poor diet results in increased histamine concentration and increased capillary permeability of the gingiva, which leads to decreased PMN leukocyte chemotaxis.[5]

Histopathology

Often, the use of microbiological testing does not provide relevant diagnostic information, as the microbiological description of ANUG can also be typical of healthy gingiva, gingivitis, and periodontitis.[5] A few case series have demonstrated the usefulness of Gram staining in supporting the diagnosis, which would otherwise rest solely on clinical grounds.[4] The clinical appearance of ANUG reflects its histopathology.[5] 

Four distinct layers have been described. Most superficial is a bacterial area of fibrous mesh composed of epithelial cells, leukocytes, and a variety of bacterial cells, including rods, fusiform bacteria, and spirochetes. Deep to that layer exists a neutrophil-rich zone composed of a higher number of leukocytes, spirochetes, and bacterial cells. Next lies a necrotic zone containing disintegrated cells, spirochetes, and fusiform bacteria. The deepest layer contains spirochete infiltration.[5]

History and Physical

ANUG remains largely a clinical diagnosis; thus, the physical exam is critical. The diagnosis is based on three essential findings. Necessary findings include mouth pain, usually of rapid onset, gum bleeding, and, most specifically, ulceration and necrosis of the interdental papillae.[1][8] Systemic symptoms such as lymphadenopathy and malaise can also be found on physical exam, as well as a fetid odor of the breath and pseudomembrane formation on the gums. There are various predisposing factors that seem to play a role in the pathogenesis of ANUG.[5] 

The diagnosis of ANUG is associated with poor oral hygiene and weakening of the host immune system, particularly in the setting of HIV infection.[5] Nutritional deficiencies, poor living conditions, as well as the context of psychological stress, have commonly been observed as predisposing factors.[1][5]

Evaluation

As mentioned above, the diagnosis of ANUG is largely based on a detailed history and physical exam. A gram stain of gingival tissue has been shown to be useful in supporting the diagnosis, but it is not required and is not always performed.[4]

Treatment / Management

The treatment of ANUG should be approached in successive stages, including treatment of the acute phase, treatment of any preexisting condition, treatment of disease sequelae, and transition to supportive or maintenance phase.[5]

Treatment of the acute phase aims to halt tissue destruction and to control the patient's discomfort. This involves gentle, ultrasonic debridement of superficial gingival plaques and calculi along with localized oxygen therapy, directed at necrotic lesions.[5] The use of 0.12% chlorhexidine gluconate mouth rinse should be considered, a suggested regimen being twice a day for 30 days.[9] Systemic antimicrobials are considered in the acute phase in cases with poor response to debridement or those with symptoms of systemic involvement, including fever, malaise, vomiting, etc.[5] (B3)

Metronidazole (250 mg 3 times a day) is a common first drug choice due to its activity against anaerobes. Penicillin, tetracyclines, clindamycin, amoxicillin, and amoxicillin with clavulanate have been shown to produce "acceptable" results and are considered on a case-by-case basis. Oral penicillin, for example, was demonstrated in one study to show significant clinical improvement in three to six days.[4] Although oral antibiotics have been shown to be beneficial, topical antimicrobials are not recommended. The large number of bacteria present within the tissues impairs the ability to achieve adequate drug concentrations. Importantly, the addition of antifungal agents is indicated in immunosuppressed patients who undergo antibiotic therapy.[5](B3)

After the acute phase has been controlled, treatment of any preexisting condition, such as chronic gingivitis, should be initiated. This stage involves professional prophylaxis in the form of scaling and root planning and the establishment of maintenance of oral hygiene methods by the patient.[9] Predisposing factors, including smoking, poor sleep hygiene, and stress, should be addressed. Gingivectomy and/or gingivoplasty procedures can treat any superficial craters.[5](B3)

The main goal of the maintenance phase is to comply with oral hygiene practices and control any predisposing factors.[5] If proper maintenance is not carried out, relapses are likely to occur.

In summary, the treatment of ANUG consists of a multifactorial approach involving superficial debridement, oral hygiene instruction, utilization of antimicrobial mouthwash and oral antibiotics, and initiation of a comprehensive prophylaxis plan involving root planning and predisposing factor management.[3]

Differential Diagnosis

ANUG diagnosis may be confused with other bacterial conditions and also many viral conditions. Considerations for a differential diagnosis should include bacterial infections like gonococcal or streptococcal gingivitis, acute herpetic gingivostomatitis, infectious mononucleosis, and also with some mucocutaneous conditions such as desquamative gingivitis, multiforme erythema, and pemphigus vulgaris.[5] Clinicians should consider ANUG in HIV-infected individuals, even if CD4+ T-lymphocyte counts have remained stable.

Pertinent Studies and Ongoing Trials

There have been studies of various suspected risk factors associated with acute necrotizing ulcerative gingivitis. Approximately two-thirds of the observed studies on ANUG have been surveys or case reports, the remaining being case-control studies. Only a few longitudinal and population-based studies are available, mostly in high-risk populations. The findings of many of these studies pertain to gingivitis in general rather than acute necrotizing ulcerative gingivitis specifically. Other existing studies are based on small numbers or solely on case histories without the inclusion of control subjects, which leaves much to be desired in this field of research. However, as mentioned above, the epidemiology and low observed prevalence of ANUG in the population severely limits most longitudinal studies at this time.[7]

Prognosis

Adequate treatment usually prevents the progression of the disease, and ulcer healing can be expected in a few days utilizing this treatment approach. Nevertheless, lack of treatment can lead to deterioration in the form of potentially fatal conditions such as necrotizing ulcerative periodontitis (NUP) and even cancrum oris (noma).[1]

Complications

Acute necrotizing ulcerative gingivitis may lead to devastating tissue damage in the form of necrotizing periodontitis, necrotizing stomatitis, and cancrum oris (noma), which is frequently fatal. Its identification and treatment is a challenge, but a necessity, for adult and pediatric practitioners alike.[10]