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Necrotizing Ulcerative Gingivitis

Randal W. Rowland*
* University of California San Francisco, San Francisco, California.

Necrotizing periodontal diseases are unique in their clinical presentation and course. Data suggest that the etiology and pathogenesis of necrotizing periodontal diseases may also be distinctive from other periodontal diseases. Necrotizing ulcerative
gingivitis (NUG) is a type of necrotizing periodontal disease in
which the necrosis is limited to the gingival tissues. Three specific clinical characteristics must be present to diagnose NUG,
pain (usually of rapid onset) interdental necrosis, and bleeding.
Epidemiological and prospective clinical studies have found an
altered ability to cope with psychological stress, immunosuppression, and tobacco use to be strongly associated with the
onset of NUG. Ann Periodontol 1999;4:65-73.
KEY WORDS
Gingivitis, necrotizing ulcerative/etiology; gingivitis,
necrotizing ulcerative/pathogenesis; gingivitis, necrotizing
ulcerative/classification.

ecrotizing ulcerative gingivitis

(NUG) is unique among the periodontal diseases. It has an acute
clinical presentation with the distinctive
characteristics of rapid onset of gingival
pain, interdental gingival necrosis, and
bleeding. Necrotizing ulcerative gingivitis has been recognized for centuries. It
has been known by many names: Vincents disease, fusospirochetal gingivitis,
trench mouth, acute ulcerative gingivitis, necrotizing gingivitis, and acute
necrotizing ulcerative gingivitis or ANUG,
to name a few.1-6 The onset of NUG is
associated with increased psychological
stress, increased physical demand, and
decreased nutrient intake.1-10 It is not
surprising that early historical documentations of NUG were made in the military and especially at times of war. The
first reference to an oral disease distinguished by these clinical signs and symptoms is credited to the historical war
records of Xenophons troops during the
fourth century BC.11-13 These records
included descriptions of painful decaying tissue between the teeth which
allowed for the distinction between NUG
and scurvy, another common gingival
lesion of that era.13 A NUG-like condition
was also reported in the Roman army of
the first century AD.12 In general, this
clinical description is still in use today in
the diagnosis of NUG. John Hunter first
delineated the clinical differences between NUG, scurvy, and chronic periodontitis in 1778.12,14 Necrotizing ulcerative gingivitis was commonly found
among the French soldiers in the nine65

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teenth century. Hirsch added secondary findings to the

clinical presentation of NUG in 1886 and Bergeron
described both acute and chronic forms of the disease
in 1895.12
Although its clinical signs are easy to identify, much
is still not understood regarding the etiology and pathogenesis of NUG. For example, with such a profound
bacterial mass and concomitant inflammation, why is
NUG usually self-limited to the interdental and marginal
gingiva? Does NUG in the immunocompromised host
(e.g., acquired immune deficiency syndrome [AIDS])
progress to include much of the periodontium resulting in severe loss of clinical attachment and bone?
Does NUG in extremely nutritionally deficient children
(e.g., Kwashiorkor) progress to include the external
structures of the face sometimes leading to death? The
literature concerning the clinical diagnosis, pathogenic
mechanisms, and progression of NUG is often in conflict. The purpose of this paper is to critically review
data that exist in relation to NUG as a clinical diagnosis.
A comprehensive understanding of NUG will assist in
clinical diagnosis and delivery of appropriate therapy
for this infrequent, yet clinically significant, periodontal condition.
DEFINING CHARACTERISTICS OF NUG
Clinical Presentation
Necrotizing ulcerative gingivitis is different from the
other periodontal diseases, in that it presents with interdental gingival necrosis as often described by punched
out ulcerated papillae, gingival bleeding, and pain.1-6
Interproximal gingival necrosis is easy to detect. However, tooth shape, size, and alignment may alter the
form of papillae. Consequently, these factors must be
considered when assessing interdental papillae. It is
possible for inexperienced clinicians to misclassify
papillae as necrotic when in fact the papillae are
blunted due to the presence of a diastema and inflamed
due to bacterial plaque. Loss of attachment and bone
in NUG are infrequent findings, but can occur after
multiple recurrences of the disease. Gingival bleeding
associated with NUG is probably the least distinctive
of the clinical signs of NUG, since it is a frequent finding in other periodontal diseases. However in other
periodontal diseases, a substantial stimulus such as
tooth brushing or periodontal probing is required to
elicit bleeding. In comparison, gingival bleeding in NUG
occurs with little or no provocation. Pain is the hallmark
of NUG. The quality of pain in NUG is intense and
results in patients seeking treatment. Typical gingivitis and periodontitis are not associated with severe gingival pain. Periodontal abscesses and herpetic infections are painful but can be easily distinguished from
NUG. If any of the 3 criteria (interproximal necrosis,
bleeding, and pain) are absent, a diagnosis of NUG
cannot be made. Other signs and symptoms that have
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been reported to occur in NUG include lymphadenopathy, fetor ex ore, fever, and malaise.15-17
However, none of these are pathognomonic since they
frequently occur in many other forms of periodontal
disease. Lymphadenopathy is an infrequent finding in
NUG. Its presence is probably related to the severity
of the disease since it is usually observed in severe,
advanced cases.3,18 The strong malodor (fetor ex ore)
that has often been associated with NUG is not always
noted4,18 and may be associated with many other oral
diseases such as chronic periodontitis. While there are
reports that fever and malaise are common clinical
features of NUG,1,16 most clinical studies have indicated that their presence may suggest primary herpetic gingivostomatitis or mononucleosis.2,4,19,20 If one
compares the features that are unique to NUG to those
that are common, it is easy to distinguish NUG clinically from other gingival and periodontal diseases.
It has been suggested that there are acute and
chronic forms of NUG.21,22 Patients presenting with
NUG are indeed often susceptible to future recurrences.1-6,23 However, the historical terminology of
chronic should be considered a misidentification of
a recurrence of disease. In addition, the rapid onset
of NUG has led many, especially in the United States,
to refer to NUG as ANUG. The term acute in ANUG
is a clinical descriptive term and should not be used
as a diagnostic classification. As there is no chronic
form of NUG, it is also best to consider ANUG a misnomer.
Necrotizing ulcerative gingivitis is diagnosed at the
onset of specific clinical signs and symptoms.5,6,24
Episodes of NUG will usually resolve within a few days
after receiving adequate treatment. Such response is
extraordinary among plaque-associated periodontal
diseases. Furthermore, unlike other forms of periodontal infection, NUG primarily affects the interdental and marginal soft tissue with little osseous involvement. It may be superimposed upon periodontitis and
complicate the diagnosis.2,6 Some reports indicate that
NUG is associated with attachment loss. In a study of
13 patients with a history of NUG, it was found that
mean probing attachment loss in the interdental crater
sites were significantly greater than the mean for all
other sites. The presence of interdental craters was
assumed to be the previous sites of NUG. An association between NUG and attachment loss was made in
this report.25 Attachment loss has also been noted
upon recurrences of NUG.17 Such findings have led
some to support the surgical treatment of any residual interdental soft tissue craters.2,3,17
Even if clinical attachment loss is associated with
NUG, it is obvious that this disease presents with a
different response to therapy than other forms of periodontal disease. Resolution is quick upon removing
the bacterial challenge.2,20,23,26 In addition, it has been

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reported that even with conservative treatment, regeneration of the affected interdental sites is possible.27
Using periodic scaling, root planing, and antimicrobial
rinses, this study showed that the disease process was
not only halted, but that regeneration of the necrotic
papillae was possible.27 In contrast, longitudinal studies involving similar therapeutic regimens in the maintenance of post-therapy periodontitis sites found stabilization, but not necessarily regeneration, of the lost
periodontium.28 The clinical presentation, course, and
response to therapy for NUG are specific among the
periodontal diseases and support a unique clinical disease category.
Etiology
Necrotizing ulcerative gingivitis is an infectious disease. Dramatic resolution of signs and symptoms can
be affected by reduction of the microbial plaque either
by antibiotic therapy,3,26,29 mechanical debridement,2,17,20 or both.1,5,6,27 A specific infectious disease should be associated with a specific etiology. The
bacterial etiology of NUG provides one of our strongest
examples of a primary bacterial etiology in a periodontal disease.30 This bacterial etiology was first
proposed by Plaut in 189431 and Vincent in 1896.32
Working independently, they both reported that
fusiform-spirochete bacterial flora were associated with
the lesions of necrotizing ulcerative gingivitis. Even
though fusiforms and spirochetes are commonly found
in patients who do not have NUG,33 it does appear
that these and perhaps other bacteria play a major
role in the pathogenesis of NUG. First, electron microscopic studies of gingival biopsies from NUG patients
have provided some of the most well known findings
in support of bacterial invasion in a periodontal disease.
In a classic electron microscopic investigation in 1965,
four zones associated with the gingival lesion of NUG
were identified.34
1. Bacterial zone: composed of a large mass of bacteria with varying morphotypes, including some spirochetes.
2. Neutrophil rich zone: underlies the bacterial zone,
contains many leukocytes with neutrophils predominating. Bacteria, including many spirochetes, are
located between the cells.
3. Necrotic zone: characterized by disintegrating
cells and many spirochetes (large and intermediate)
and other bacteria that appear to be fusiforms.
4. Spirochetal infiltration zone: tissue elements
appear well preserved but are infiltrated by spirochetes,
both large and intermediate in size. No other bacteria
were observed.
Essentially the same findings were reported in
another study 2 years later.35 A later study also found
cocci and rods in addition to the spirochetes, within the
adjacent non-necrotic connective tissue region.36 The

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neutrophil rich, necrotic, and spirochetal infiltration

zones are unique to NUG. The histologic appearance
of NUG is different from other gingival and periodontal
diseases,37-39 but it is complex and may be misleading, as cells associated with chronic lesions such as
lymphocytes may be present also. These are probably
due in part to a preexisting established gingivitis.39
Microbial studies have also characterized the genera and species of the cultivable flora in NUG.24,40 In
one study, the cultivable flora and microscopic findings
were evaluated on the same plaque samples.40 It was
reported that both the cultivable and microscopic flora
had what the authors identified as constant and variable components. The constant cultivable flora consisted of a limited number of predominant organisms,
B. melaninogenicus ssp. intermedius, now known as
Prevotella intermedia, and Fusobacterium sp. Microscopically, Treponema and Selenomonas sp. comprised
the constant flora. The concept of a predominant constant flora suggests an association of these flora with
the disease. As with other periodontal diseases however, this association does not necessarily demonstrate
an etiologic role for these bacteria in the initiation of
NUG. Attempts to satisfy Kochs postulates by transfer of the disease from one animal to another have
been attempted. When inoculated subcutaneously into
the groin of guinea pigs, scrapings from lesions of NUG
have produced fusospirochetal infections.41 It was also
possible to pass this infection from animal to animal
by the same route. Skin abscesses have been produced in guinea pigs by injecting pure cultures of T.
vincentii and T. buccalis separately and in combination with other oral isolates.42 However, several different organisms singly or in combination have been
demonstrated to be capable of producing similar
lesions.43 Using a steroid-induced immunosuppression
in the beagle dog, it has been possible to transmit NUG
from animal to animal.44-48 Some histologic differences were noted in the dog model compared to the
earlier studies of human specimens; however, spirochetes were seen penetrating normal epithelium, which
may suggest that spirochetes were involved in the initiation of the pathogenesis in NUG.48 In other forms of
periodontal disease, spirochetes are involved in
advanced gingivitis and periodontitis lesions but are
not associated with sites of early periodontitis or gingival health.24,49,50 Studies of the bacterial etiology of
NUG indicate that NUG is different from other periodontal diseases.
For many years, NUG was considered a communicable disease. A diagnosis of NUG often required a
report to community health departments in a similar
fashion as a venereal disease. A particularly insightful discussion of the data in regards to the communicability of NUG led the American Dental Association
to conclude that NUG was not communicable.51
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Predisposing Factors
Psychological stress. Development of NUG is closely
associated with specific predisposing secondary factors such as psychological stress, immune suppression, smoking, malnutrition, pre-existing gingivitis, and
tissue trauma. Acute psychological stress in particular appears to be associated with the onset of NUG.7
It is well documented that the prevalence of NUG in
the military increases under conditions which produce
high levels of acute stress4,19,22,52 and in drug addicts
during periods of drug withdrawal.8 Additionally, it is
not uncommon to have outbreaks of NUG among college students during examinations.9
During periods of psychological stress, oral hygiene
measures may decrease, nutrition may become inadequate, tobacco smoking may increase, and immune
function may be suppressed. Stressful life events may
lead to an activation of the hypothalamic-pituitaryadrenal axis, resulting in an elevation of serum and
urine corticosteroid levels.53 Increases in urinary levels of 17 hydroxycorticosteroid (17-OHCS) have been
associated with psychological stress. Accordingly, significantly higher levels of urinary 17-OHCS have been
reported in NUG patients when compared with levels
measured after resolution of the disease.54 Another
study reported significantly higher levels of urinary
cortisol in NUG patients in comparison to control subjects.55 Increased corticosteroid levels may play several roles in the development of NUG such as immunosuppression.
Immunosuppression. Increased cortisol levels have
been associated with a depression of polymorphonuclear leukocyte (PMN) function.56 Depressed PMN
function as measured by chemotactic, phagocytic, and
bactericidal abilities has been reported in NUG
patients.57-59 In addition, altered lymphocyte function
has been reported in NUG and will be discussed
below.57,60,61 Further evidence to support the relationship of immune suppression via increased levels of
corticosteroids was demonstrated by the transfer of
NUG in the beagle dog after pretreatment with steroids
as previously discussed.44-48 Furthermore, it has also
been suggested that elevated steroid levels may provide essential nutrients for specific bacterial growth
(Prevotella intermedia).40,62
Studies of immune responses in NUG have found, for
the most part, a lack of protective functions. One of
the earliest studies found no differences in antibody
levels to Fusobacterium fusiforme, B. melaninogenicus, and Borrelia vincentii of NUG patients compared
to control subjects.63 A follow-up study using a different methodology from the same laboratory looked
at the immune response to Actinomyces viscosus, F.
fusiforme, Veillonella alcalescens, and B. melaninogenicus. They also found no differences in serum antibody levels between patients and control subjects. This
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was true on the first day of attendance and up to one

month after the disease started.64 In another study,
saliva was assayed for all 5 classes of immunoglobulins as well as secretory IgA. A decrease in total
immunoglobulin levels but an increase in secretory
IgA was found in NUG subjects when compared to the
control subjects.65 Another study of the humoral
response reported a depressed total serum IgG and
increased total serum IgM concentrations in patients
with NUG and patients with recurrent NUG compared
to the control subjects.66 Taken together, these early
reports provide interesting findings. The onset of NUG
is associated with a large microbial plaque load. Furthermore an established or pre-existing gingivitis is
considered necessary for the onset of NUG. Therefore
these early studies of the immune response indicate
that a lack of protective antibodies may be involved
in the development of NUG.
In contrast to these early studies, two more recent
investigations of antibody response have reported conflicting findings.24,67 Both studies used specific bacterial strains and measured antibody levels by an enzymelinked immunosorbent assay. One study found
significantly higher IgG and IgM levels to an intermediate size spirochete and higher IgG levels to B. intermedius (P. intermedia) in NUG subjects compared to
healthy and gingivitis subjects.67 Examination of the
results, however, indicated that significantly higher IgG
titers were present against only 1 of 2 P. intermedia
strains tested. In addition, the source for the intermediate size spirochete in this study was reported to have
been deep periodontal pockets. The other study was
carefully controlled for confounding factors: plaque levels, age, race, gender, and socio-economic status. In
this study, a depressed IgG and IgM response in NUG
subjects compared to control subjects was reported for
4 isolates of P. intermedia (2 from NUG patients, 2 from
control subjects). In addition, no differences in IgG levels to spirochetes isolated from NUG subjects or control subjects, or IgM levels to the spirochetes from NUG
individuals were found.24 It is arguable that antibody levels, both non-specific and specific, are either similar
or depressed in NUG patients compared to control subjects. However, lymphocyte function as measured by
mitogenic response is severely depressed in NUG.57,60,61
It is apparent that regardless of the mechanisms
involved, a general immune suppression (PMN function,
antibody response, and lymphocyte mitogenesis) is
associated with the onset of NUG.
Thus, it is not surprising that NUG has been associated with infection by human immunodeficiency virus
(HIV) and acquired immune deficiency syndrome
(AIDS).6,7,60 Moreover, it has been reported that NUG
may be the first sign of HIV infection.60 Several controversies regarding the association of HIV disease and
NUG exist. Early in the AIDS epidemic, atypical forms

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of gingivitis and periodontitis were reported to be associated with HIV infection.68 The gingivitis was described
as a distinct erythematous band of the marginal gingiva with either diffuse or punctate erythema of the
attached gingiva with little dental plaque. It was named
HIV-associated gingivitis (HIV-G).68 Spontaneous bleeding was often present in HIV-G. Unlike conventional
gingivitis, it was reported that HIV-G did not respond
to oral hygiene measures. It may be due at least in
part to a candidal infection.69 These early studies from
San Francisco also reported a progression from HIVG to NUG to a necrotizing ulcerative periodontitis.68 In
1993, HIV-G was renamed as linear gingival erythema
(LGE) by a collaboration of the EC-Clearinghouse on
Oral Problems related to HIV infection and the WHO
Collaboration Centre on Oral Manifestations of the
Immunodeficiency Virus.69
The distinct periodontitis in the San Francisco HIVinfected population was described as an ANUG type
of lesion (i.e., NUG) superimposed upon a rapidly progressing periodontitis; a lesion in which severe loss of
attachment and bone was noted. Patients presenting
with this disease did not have a history of NUG in these
areas.68 The authors referred to this disease as HIVassociated periodontitis (HIV-P). HIV-associated periodontitis was subsequently renamed as necrotizing
ulcerative periodontitis or NUP.69 Necrotizing stomatitis (NS) occurs when the necrosis extends into the
mucosa and bone outside the periodontium.68,69
Through the years NUP in HIV-infected patients has
been either misinterpreted as NUG or as a NUG-like
lesion, which quickly progressed to a necrosis of
bone.70-72 This has occurred in spite of the original
report and subsequent attempts to clearly define these
entities.73-75 It is important to note that these early
findings were generated from essentially non-medically
treated HIV-infected patients. In a sense the actual disease process of NUG and NUP could be studied. Studies of the bacterial etiology of NUP (HIV-P) found the
flora to be different from adult periodontitis76 and the
same as adult periodontitis.77 Both studies however
found the flora to be different from that associated with
NUG.40 The issue of periodontal disease in HIV-infected
individuals has become much more complex than warranted.78 There have been attempts to address this
problem. One approach is to clearly define small clinical differences for use in clinical studies of periodontal disease.79 This approach is time consuming, but
would be useful in specific situations; e.g., assessment
of disease progression and treatment outcomes. Others have sought to broadly group clinical findings.69,80
Such an approach would be applicable for use in epidemiologic studies of oral manifestations but would
lack sensitivity for identification of periodontal diseases
such as NUG and NUP. Excellent reviews of periodontal
diseases in HIV infection have been written by peri-

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odontists and others experienced with this area of HIV

manifestations.73-75,81,82
Malnutrition. Malnutrition also has been reported to
be a predisposing factor in the onset of NUG.1-6 Necrotizing ulcerative gingivitis is considered to be a disease of young adults in Europe and the United States.
In contrast, NUG occurs in very young children in
developing countries.83-89 The development of NUG
in children appears to be related to poor nutritional
status especially in protein intake83,84 and secondary
to viral infections such as measles.85 Necrotizing ulcerative gingivitis, which occurs in malnourished children,
especially after viral and protozoal infections, may also
progress to a fulminating disfiguring and often lethal
infection known as noma.1-6 Noma has been known
by other names such as cancrum oris in Africa, and
dzo-ma-gan in China. Dzo-ma-gan, which translates as
running horse gangrene, is a historical name and is
a reference to the rapid progression noma exhibits.5,90
While it is generally accepted that NUG will progress
to noma in the compromised patient,1-6 a review of
the literature finds only rare cases that clearly began
as NUG and progressed to noma.88 Moreover, reports
purported to document the progression of NUG to
noma contain photographs of initial presentation that
appear to indicate that patients had more than interproximal gingival necrosis. These included cellulitis of
the external facial structures, advanced lesions involving the entire periodontium (necrotizing ulcerative periodontitis), or lesions extending past the periodontium
into surrounding bone (necrotizing stomatitis).83-89
While it may seem appropriate to consider noma as
an extension of NUG, this is not well documented. A
recent study indicates that noma is associated with
elevated cortisol levels and reduced levels of zinc and
amino acids in children previously infected with
measles or herpesviruses in consort with F. necrophorum infection.91 This finding is in agreement with earlier studies that reported the association of viral infections with the development of noma.83,86 The
underlying mechanisms of the pathogenesis of noma,
however, still need to be identified.
Other Predisposing Factors. Tobacco smoking,
pre-existing gingivitis, and trauma have been reported
as predisposing factors in NUG also. Tobacco smoking in particular is associated with the onset of
NUG.10,92-94 An earlier report suggested an association between NUG and venereal disease.95
SYSTEMIC DETERMINANTS UNKNOWN
The majority of patients with NUG will still present with
systemic determinants unknown. In other words, the
clinician will make a presumption of the etiologic and
pathogenic mechanisms that are ongoing based upon
the identification of predisposing factors. A smaller
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Volume 4 Number 1 December 1999

Psychological Stress and Anxiety

Pre-Existing Gingivitis
Increased Corticosteroid Production
Immunosuppression
Increased Bacteria Growth and Invasion
Viral Infection

Immunosuppression
Necrotizing Ulcerative Gingivitis
HIV Infection

Deficient Nutrition

Candida Infection

Viral Infections
Protozoal Infections

Linear Gingival Erythema

Noma
Necrotizing
Ulcerative
Periodontitis

Necrotizing
Stomatitis

Figure 1. Necrotizing ulcerative gingivitis: possible etiological mechanisms and sequelae.

percentage of NUG cases will be attributable to systemic determinants known; e.g., immunosuppression
secondary to HIV infection.
SUMMARY
Necrotizing ulcerative gingivitis is a distinct painful
infectious disease primarily of the interdental and marginal gingiva. These clinical signs and symptoms of
NUG will usually resolve within a few days after receiving adequate treatment; however, patients remain at
risk for recurrences of disease. As with other plaqueassociated periodontal diseases, opportunistic bacteria are the primary etiologic agents in NUG. There are
also non-specific predisposing factors for the development of NUG: acute psychological stress, tobacco
smoke, and pre-existing gingivitis. From this review
of the literature it is evident that the predominant factor in the development of NUG is immunosuppression.
Furthermore, immunosuppression may be associated
with all of the predisposing factors.
70

The epidemiology and etiology of NUG have interested the research community for many years. Several excellent reviews are available for reference.1,15,96
While this interest has led to an extensive body of
knowledge in regards to NUG, there is still much
not known. It has been proposed by many that NUG
may progress to involve the periodontium (NUP) and
surrounding oral tissues (necrotizing stomatitis and
noma) depending upon the health status of the
patient. While the clinical presentation of NUG may
be modified by the systemic health status of the
patient, it has a unique presentation, etiology, and
pathogenesis and warrants a separate disease classification. Figure 1 depicts the various interactions
thought to occur in NUG.
REFERENCES
1. Johnson BD, Engel D. Acute necrotizing ulcerative gingivitis. A review of diagnosis, etiology, and treatment. J
Periodontol 1986;57:141-150.

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2. Goldhaber P, Giddon DB. Present concepts concerning

the etiology and treatment of acute necrotizing ulcerative gingivitis. Int Dent J 1964;14:468-496.
3. Shinn DL. Vincents disease and its treatment. In: Finegold SM ed. Metronidazole, Proceedings of the International Metronidazole Conference Montreal, Quebec,
Canada. Amsterdam: Excerpta Medica; 1977:334-340.
4. Grupe HE, Wilder LS. Observations of necrotizing gingivitis in 870 military trainees. J Periodontol 1956;
27:255-261.
5. Armitage GC. Acute periodontal lesions. In: Biologic
Basis of Periodontal Maintenance Therapy. Berkeley, CA:
Praxis Publishing Company; 1980:145-164.
6. Cogen RB. Acute necrotizing ulcerative gingivitis. In:
Genco RJ, Goldman HM, Cohen DW, eds. Contemporary Periodontics. St. Louis: The C.V. Mosby Company;
1990:459-465.
7. Moulton R, Ewen S, Thieman W. Emotional factors in
periodontal disease. Oral Surg Oral Med Oral Pathol
1952;5:833-860.
8. Davis RK, Baer PN. Necrotic ulcerative gingivitis in drug
addict patients being withdrawn from drugs. Report of
two cases Oral Surg Surg Oral Med Oral Pathol 1971;31:
200-204.
9. Giddon DB, Zackin SJ, Goldhaber P. Acute necrotizing
gingivitis in college students. J Am Dent Assoc 1964;
68:381-386.
10. Stevens AW Jr., Cogen RB, Cohen-Cole S, Freeman A.
Demographic and clinical data associated with acute
necrotizing ulcerative gingivitis in a dental school population. (ANUGdemographic and clinical data). J Clin
Periodontol 1984;11:487-93.
11. Prinz H, Greenbaum SS. In: Diseases of the Mouth and
Their Treatment. Philadelphia: Lea & Febinger; 1935:153166.
12. Hirschfeld I, Beube F, Siegel EH. The history of Vincents infection. J Periodontol 1940;11:89-98.
13. Pickard HM. Historical aspects of Vincents disease. Proc
Royal Soc Med 1973;66:695-699.
14. Hunter J. A treatise on the natural history and diseases
of the human teeth (1778). In: Complete Works of John
Hunter, Philadelphia, 1841:81.
15. Murayama Y, Kurihara H, Nagai A, Dompkowski D, Van
Dyke TE. Acute necrotizing ulcerative gingivitis: risk
factors involving host defense mechanisms. Periodontol
2000 1994;6:116-124.
16. Wilson JR. Etiology and diagnosis of bacterial gingivitis including Vincents disease. J Am Dent Assoc 1952;
44:671-679.
17. Schluger S. The etiology and treatment of Vincents
infection. J Am Dent Assoc 1943;30:524-532.
18. Manson JD, Rand H. Recurrent Vincents disease. A survey of 61 cases. Br Dent J 1961;110:386-390.
19. Shields WD. Acute necrotizing ulcerative gingivitis. A
study of some of the contributing factors and their
validity in an army population. J Periodontol 1977;48:
346-349.
20. Stammers AF. Vincents infection: Observations and conclusions regarding the aetiology and treatment of 1,017
civilian cases. Br Dent J 1944;76:147-155, 171-177,
205-209.
21. Kristoffersen T, Lie T. Necrotizing gingivitis. In: Lindhe
J, ed. Textbook of Clinical Periodontology, 2nd ed.
Copenhagen: Munksgaard; 1989:202-218.
22. Pindborg JJ. Influence of service in armed forces on the
incidence of gingivitis. J Am Dent Assoc 1951;42:517522.

Rowland

23. Silver JG, Southcott RJ, Wade AB. Acute necrotizing

ulcerative gingivitisan evaluation of the ulcer improvement index. J Periodontol 1974;45:308-311.
24. Rowland RW, Mestecky J, Gunsolley JC, Cogen RB.
Serum IgG and IgM levels to bacterial antigens in necrotizing ulcerative gingivitis. J Periodontol 1993;64:195201.
25. MacCarthy D, Claffey N. Acute necrotizing ulcerative
gingivitis is associated with attachment loss. J Clin Periodontol 1991;18:776-779.
26. Duckworth R, Waterhouse JP, Britton DER, et al. Acute
ulcerative gingivitis: A double-blind controlled clinical
trial of metronidazole. Br Dent J 1966;120:599-602.
27. Hartnett AC, Shiloah J. The treatment of acute necrotizing ulcerative gingivitis. Quintessence Int 1991;22:95100.
28. Axelsson P, Lindhe J. Effect of controlled oral hygiene
procedures on caries and periodontal disease in adults.
Results after 6 years. J Clin Periodontol 1981;8:239-248.
29. Loesche WJ. Chemotherapy of dental plaque infections.
Oral Sci Rev 1976;9:65-107.
30. Socransky SS, Haffajee AD. Evidence of bacterial etiology: a historical perspective. Periodontol 2000 1994;
5:7-25.
31. Plaut HC. Bacterial diagnostic studies of diphtheria and
oral diseases. (Studien zur bakteriellen Diagnostik der
Diphtherie und der Anginen). Dtsch Med Wochnschr,
1894;20:920-923.
32. Vincent H. The etiology and the histopathology of hospital rot. (Sur letiolgie et surn les lesions anatomopathologiques, de la pourriture dhopital). Ann de lInsti Pasteur, 1896;10:488-510.
33. Loesche WJ, Laughon BE. Role of spirochetes in periodontal disease. In: Genco RJ, Mergenhagen, SE, eds.
Host-Parasite Interactions in Periodontal Diseases, Washington, DC: American Society for Microbiology; 1982:6275.
34. Listgarten MA. Electron microscopic observations on
the bacterial flora of acute necrotizing ulcerative gingivitis. J Periodontol 1965;36:328-339.
35. Heylings RT. Electron microscopy of acute ulcerative
gingivitis (Vincents type). Demonstration of the
fusospirochaetal complex of bacteria within pre-necrotic
gingival epithelium. Br Dent J 1967;122:51-56.
36. Courtois GJ, Cobb CM, Killoy WJ. Acute necrotizing
ulcerative gingivitis. A transmission electron microscope
study. J Periodontol 1983;54:671-679.
37. Freedman HL, Listgarten MA, Taichman NS. Electron
microscopic features of chronically inflamed human gingiva. J Periodont Res 1968;3:313-327.
38. Melcher AH. Some histological and histochemical observations on the connective tissue of chronically inflamed
human gingiva. J Periodont Res 1967;2:127-146.
39. Hooper PA, Seymour GJ. The histopathogenesis of acute
ulcerative gingivitis. J Periodontol 1979;50:419-423.
40. Loesche WJ, Syed SA, Laughon BE, Stoall J. The bacteriology of acute necrotizing ulcerative gingivitis. J Periodontol 1982;53:223-230.
41. Rosebury T, MacDonald JB, Clark AR. A bacteriologic
survey of gingival scrapings from periodontal infections
by direct examination, guinea pig inoculation and anaerobic cultivation. J Dent Res 1950;29:718-731.
42. Hamp EG, Mergenhagen SE. Experimental intracutaneous fusobacterial and fusospirochetal infections. J
Infect Dis 1963; 112:84-99.
43. MacDonald JB, Socransky SS, Gibbons RJ. Aspects of
the pathogenesis of mixed anaerobic infections of
71

A12_IPC_AAP_Annals_553640

6/7/00

8:54 AM

Page 72

Necrotizing Ulcerative Gingivitis

mucous membranes. J Dent Res 1963;42:529-544.

44. Mikx F, van Campen GJ. Preliminary evaluation of the
microflora in spontaneous and induced necrotizing ulcerative gingivitis in the beagle dog. J Periodont Res 1982;
17:460-461.
45. Mikx FHM, van Campen GJ. Microscopical evaluation of
the microflora in relation to necrotizing ulcerative gingivitis in the beagle dog. J Periodont Res 1982;17:576584.
46. Mikx FHM, Hug HU, Maltha JC. Necrotizing ulcerative gingivitis in beagle dogs. I. Attempts at unilateral
induction and intraoral transmission of NUG, a microbiological and clinical study. J Periodont Res 1984;19:
76-88.
47. Hug HU, Maltha JC, Mikx FHM. Necrotizing ulcerative
gingivitis in beagle dogs. II. Histologic characteristics of
NUG in relation to interproximal contacts. J Periodont Res
1984;19:89-99.
48. Maltha JC, Mikx FHM, Kuijpers FJ, Necrotizing ulcerative gingivitis in beagle dogs. III. Distribution of spirochetes in interdental gingival tissue. J Periodont Res
1985; 20:522-531
49. Armitage GC, Dickinson WR, Jenderseck RS, Levine
SM, Chambers DW. Relationship between the percentage of subgingival spirochetes and the severity of periodontal disease. J Periodontol 1982;53:550-556.
50. Zappa UE, Polson AM, Eisenberg AD, Espeland MA
Microbial populations and active tissue destruction in
experimental periodontitis. J Clin Periodontol 1986;
13:117-125.
51. Rosebury T. Is Vincents infection a communicable disease? J Am Dent Assoc 1942;29:823-834.
52. Pindborg JJ. The epidemiology of ulceromembranous
gingivitis showing the influence of service in the armed
forces. Parodontol 1956;10:114-118.
53. Rose RM. Endocrine responses to stressful psychological events. Psychiatr Clin North Am 1980;3:251-276.
54. Maupin CC, Bell WB. The relationship of 17-hydroxycorticosteroid to acute necrotizing ulcerative gingivitis.
J Periodontol 1975;46:721-722.
55. Cohen-Cole S, Cogen RB, Stevens AW Jr., et al. Psychiatric, psychosocial, and endocrine correlates of acute
necrotizing ulcerative gingivitis (trench mouth): A preliminary report. Psychiatr Med 1983;1:215-225.
56. Rubin RH. Infection in the immune-suppressed host. In:
Rubenstein E, Federman E, eds. Scientific American
Medicine, Vol. 10. New York: Scientific American; 1981;
1-27.
57. Cogen RB, Stevens AW Jr., Cohen-Cole S, Kirk K, Freeman, A. Leukocyte function in the etiology of acute
necrotizing ulcerative gingivitis. J Periodontol 1983;
54:402-407.
58. Claffey N, Russell R, Shanley D. Peripheral blood phagocyte function in acute necrotizing ulcerative gingivitis. J
Periodont Res 1986;21:288-297.
59. Cutler CW, Wasfy MO, Ghaffar K, Hosni M, Lloyd DR.
Impaired bactericidal activity of PMN from two brothers
with necrotizing ulcerative gingivo-periodontitis. J Periodontol 1994;65:357-363.
60. Rowland RW, Escobar MR, Friedman RB, Kaplowitz LG.
Painful gingivitis may be an early sign of infection with
the human immunodeficiency virus. Clin Infect Dis
1993;16:233-236.
61. Rowland RW. Relationship between race and lymphocyte function during acute gingival inflammation. J Periodont Res 1993;28:514-516.
62. Kornman KS, Loesche WJ. Effects of estradiol and prog72

Volume 4 Number 1 December 1999

63.
64.
65.
66.
67.
68.

69.

70.

71.
72.
73.
74.
75.
76.
77.
78.
79.

80.
81.

82.

esterone on Bacteroides melaninogenicus and Bacteroides gingivalis. Infect Immun 1982;35:256-263.

Lehner T, Clarry ED. Acute ulcerative gingivitis. An
immunofluorescent investigation. Br Dent J 1966; 121:
366-370.
Wilton JMA, Ivanyi L, Lehner T. Cell-mediated immunity
and humoral antibodies in acute ulcerative gingivitis. J
Periodont Res 1971;6:9-16.
Harding J, Berry WC Jr., Marsh C, Jolliff CR. Salivary
antibodies in acute gingivitis. J Periodontol 1980;51:
63-69.
Lehner T. Immunoglobulin abnormalities in ulcerative
gingivitis. Br Dent J 1969;127:165-169.
Chung CP, Nisengard RJ, Slots J, Genco RJ. Bacterial
IgG and IgM antibody titers in acute necrotizing ulcerative gingivitis. J Periodontol 1983;54:557-562.
Winkler JR, Grassi M, Murray PA. Clinical description
and etiology of HIV-associated periodontal diseases. In:
Robertson PB, Greenspan JS, eds. Perspectives on Oral
Manifestations of AIDS. Littleton, MA: PSG Publishing
Company; 1988:49-70.
EC-Clearinghouse on Oral Problems Related to HIV infection and WHO Collaborating Centre on Oral Manifestations of the Human Immunodeficiency Virus. Classification and diagnostic criteria for oral lesions in HIV
infection. J Oral Pathol Med 1993;22:289-291.
San Giacomo TR, Tan PM, Loggi DG, Itkin AB. Progressive osseous destruction as a complication of HIVperiodontitis. Oral Surg Oral Med Oral Pathol 1990;
70:476-479.
Robinson PG, Sheiham A, Challacombe SJ, Zakrzewska
JM. Periodontal health and HIV infection. Oral Dis
1997;3(Suppl. 1):S149-S152.
Patton LL, McKaig R. Rapid progression of bone loss in
HIV-associated necrotizing ulcerative stomatitis. J Periodontol 1998;69:710-716.
Winkler JR, Robertson PB. Periodontal disease associated with HIV infection. Oral Surg Oral Med Oral Pathol
1992;73:145-150.
Greenspan JS. Periodontal complications of HIV infection. Compendium Cont Educ Dent 1994;(Suppl. 18):
S694-S698.
Holmstrup P, Westergaard J. Periodontal diseases in
HIV-infected patients. J Clin Periodontol 1994;21:270280.
Murray PA, Grassi M, Winkler JR. The microbiology of
HIV-associated periodontal lesions. J Clin Periodontol
1989;16:636-642.
Rams TE, Andriolo M Jr., Feik D, Abel SN, McGivern TM,
Slots J. Microbiological study of HIV-related periodontitis. J Periodontol 1991;62:74-81.
Johnson NW. Essential questions concerning periodontal diseases in HIV infection. Oral Dis 1997;3(Suppl 1):
S138-S140.
Robinson PG, Winkler JR, Palmer G, Westenhouse J,
Hilton JF, Greenspan JS. The diagnosis of periodontal
conditions associated with HIV infection. J Periodontol
1994;65:236-243.
Horning GM. Necrotizing gingivostomatitis: NUG to
noma. Compendium Contin Educ Dent 1996;17:951954,956-958.
Lamster IB, Grbic JT, Bucklan RS, Mitchell-Lewis D,
Reynolds HS, Zambon JJ. Epidemiology and diagnosis
of HIV-associated periodontal diseases. Oral Dis 1997;
3(Suppl. 1):S141-S148.
Murray PA. Periodontal diseases in patients infected by
human immunodeficiency virus. Periodontol 2000 1994;

A12_IPC_AAP_Annals_553640

6/7/00

8:54 AM

Page 73

Ann Periodontol

6:50-67.
83. Enwonwu CO. Epidemiological and biochemical studies
of necrotizing ulcerative gingivitis and noma (cancrum
oris) in Nigerian children. Arch Oral Biol 1972;17:13571371.
84. Pindborg JJ, Bhat M, Roed-Petersen B. Oral changes in
South Indian children with severe protein deficiency. J
Periodontol 1967;38:218-221.
85. Osuji OO. Necrotizing ulcerative gingivitis and cancrum
oris (noma) in Ibadan, Nigeria. J Periodontol 1990;61:
769-772.
86. Malberger E. Acute infectious oral necrosis among young
children in the Gambia, West Africa. J Periodont Res
1967;2:154-162.
87. Sheiham A. An epidemiological survey of acute ulcerative gingivitis in Nigerians. Arch Oral Biol 1966;11:937942.
88. Uohara GI, Knapp MJ. Oral fusospirochetosis and associated lesions. Oral Surg Oral Med Oral Pathol 1967;
24:113-123.
89. Taiwo JO. Severity of necrotizing ulcerative gingivitis in
Nigerian children. Periodontal Clin Investig 1995;17:2427.
90. Sung CCW, Sung RY. Some clinical observations concerning noma. Am J Orthodont Oral Surg 1947;33:284287.
91. Enwonwu CO, Falkler WA Jr, Idigbe EO, et al. Pathogenesis of cancrum oris (noma): confounding interactions of malnutrition with infection. Am J Trop Med Hyg
1999;60:223-232.
92. Pindborg JJ. Tobacco and gingivitis. I. Statistical examination of the significance of tobacco in the development of ulceromembranous gingivitis and in the formation of calculus. J Dent Res 1947;26:261-264.

Rowland

93. Pindborg JJ. Tobacco and gingivitis. II. Correlation

between consumption of tobacco, ulceromembranous
gingivitis and calculus. J Dent Res 1949;28:460-463.
94. The American Academy of Periodontology. Tobacco use
and the periodontal patient (Position Paper). J Periodontol 1996;67:51-56.
95. Wirthlin MR, Devine L. Venery and Vincents? 15 case
reports and discussion. J Periodontol 1978;49:449-456.
96. Melnick SL, Roseman JM, Engel D, Cogen RB., Epidemiology of acute necrotizing ulcerative gingivitis. Epidemiol Rev 1988;10:191-211.
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