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Volume 4 Number 1 December 1999
Necrotizing Ulcerative Periodontitis
M. John Novak*
* University of Pittsburgh, Pittsburgh, Pennsylvania.
In patients with no known systemic disease or immune dys-
function, necrotizing periodontitis (NUP) appears to share many
of the clinical and etiologic characteristics of necrotizing ulcer-
ative gingivitis (NUG) except that patients with NUP demon-
strate loss of clinical attachment and alveolar bone at affected
sites. In these patients, NUP may be a sequela of a single or mul-
tiple episodes of NUG or may be the result of the occurrence of
necrotizing disease at a previously periodontitis-affected site.
The existence of immune dysfunction may predispose patients
to NUG and NUP, especially when associated with an infection
of microorganisms frequently associated with periodontal disease
such as Treponema and Selenomonas species, Fuscobacterium
nucleatum, Prevotella intermedia, and Porphyromonas gingi-
valis. The role of immune dysfunction is exemplified by the
occasionally aggressive nature of necrotic forms of periodontal
disease seen in patients with HIV infection or malnutrition, both
of which may impact host defenses. Clinical studies of HIV-
infected patients have shown that patients with NUP are 20.8
times more likely to have CD4+ cell counts below 200 cells/mm3.
However, these same studies have demonstrated that most
patients with CD4+ cell counts below 200 cells/mm do not have
NUP,3 suggesting that other factors, in addition to immuno-
compromisation, are involved. Further studies are needed to
define the complex interactions between the microbial, or viral,
etiology of necrotic lesions and the immunocompromised host.
It is, therefore, recommended that NUG and NUP be classified
together under the grouping of necrotizing periodontal diseases
based on their clinical characteristics. Ann Periodontol 1999;4:74-
77.
KEY WORDS
Gingivitis, necrotizing ulcerative/etiology; gingivitis,
necrotizing ulcerative/pathogenesis; periodontitis/necrotizing
ulcerative/etiology; periodontology, necrotizing, ulcerative/
classification; periodontitis, necrotizing ulcerative/
pathogenesis.
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SYSTEMIC DETERMINANTS
UNKNOWN
At the 1989 World Workshop on Clincial
Periodontics, the classification was changed
from necrotizing ulcerative gingivo-peri-
odontitis to necrotizing ulcerative peri-
odontitis (NUP).1 These changes were made
without any supporting evidence from the
literature other than the clinical observa-
tion that recurrent episodes of necrotizing
ulcerative gingivitis (NUG) may lead to peri-
odontitis. It was stated in the consensus
report on Periodontal Diagnosis that with-
out treatment, NUG may progress to an
associated periodontitis (NUP).1 The 1992
edition of the Glossary of Periodontal Terms
defines NUP as severe and rapidly pro-
gressive disease that has a distinctive ery-
thema of the free gingiva, attached gingiva,
and alveolar mucosa; extensive soft tissue
necrosis; severe loss of periodontal attach-
ment; deep pocket formation is not evi-
dent.2 NUG is not defined in the 1992 Glos-
sary and refers the reader to the definition
for NUP.2 It appears from these statements
that NUP, in patients with no known sys-
temic disease or immune dysfunction, has
the same clinical appearance as NUG
except that sites with NUP demonstrate loss
of clinical attachment and alveolar bone
and that these events are the normal seque-
lae of NUG. This conclusion has been sup-
ported by the observation that sites, previ-
ously affected by NUG, demonstrated more
clinical attachment loss than previously
unaffected sites in a population of 13 sub-
jects, 18 to 27 years of age.3 The increased
attachment loss associated with prior expo-
sure to NUG was not associated with a con-
comitant increase in probing depth. The
clinical characteristics of NUG may include,
but are not limited to, ulcerated and necrotic
papillary and marginal gingiva covered by
a yellowish-white or grayish slough or
pseudomembrane, blunting and cratering
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Ann Periodontol
of papillae, bleeding on provocation and/or sponta-
neous bleeding, pain, and fetid breath.4-6 NUG may
be accompanied by fever, malaise, and lympha-
denopathy but these are not consistent characteris-
tics.7-9
The prevalence of NUP in a systemically healthy
population is unclear and the demographics of patients
affected by NUP have not been defined since most
studies of necrotic oral lesions have failed to differen-
tiate between NUG and NUP based on the presence or
absence of attachment and bone loss at affected sites.
However, clinical opinion would suggest that NUP is a
natural progression of untreated NUG1,3 and therefore
would share similar clinical, microbiologic, and
immunologic characteristics. Clinical studies have sug-
gested that patients with NUG are usually younger than
most patients presenting with periodontitis4,5,9 and that
smoking is more common.5,9 Microbiologic studies of
NUG have demonstrated the presence of an anaero-
bic microflora consisting of Treponema and Seleno-
monas species, Fusobacterium nucleatum, Prevotella
intermedia, and Porphyromonas gingivalis.5,10 Elec-
tron microscopic studies of microbial samples from
NUG lesions support the observation of large numbers
of spirochetes with morphologic heterogeneity within
the lesion.5,11 It has also been suggested that NUG
patients have alterations in their immune function mak-
ing them more susceptible to microbial attack.12 Since
NUG and periodontitis share many of the same risk fac-
tors such as a Gram-negative microflora and smoking,
it is distinctly possible that NUG may occur in the pres-
ence of an existing periodontitis and that the 2 dis-
eases occur independently of one another since not
all NUG-affected sites progress to NUP. From the lit-
erature currently available, there is no evidence to sup-
port the concept that NUP is a natural progression of
NUG other than the occurrence of incidental attach-
ment loss occurring in young individuals as a result of
interdental soft tissue destruction associated with
NUG.3 NUP may indeed have social and clinical demo-
graphics and microbiologic and immunologic charac-
teristics, that are distinct from NUG and that predis-
pose subjects to a more progressively destructive
disease. However, since there is currently insufficient
information to suggest that NUP is a distinct clinical
entity, this reviewer believes that it would be more
appropriate at this time to combine the clinical man-
ifestations of NUP and NUG into a distinct cluster of
diseases described by the term necrotizing periodon-
tal diseases as previously suggested.13
NUP: SYSTEMATICALLY AGGRAVATED
Immunosuppression
It has been observed that some form of immune dys-
function exists in NUG patients who are otherwise sys-
temically healthy and this is exemplified by the occa-
Novak
sionally aggressive nature of necrotic forms of peri-
odontal disease in subjects that are systemically com-
promised as a result of infection by HIV.12 In an HIV-
infected population with NUP, defined as local
ulcerations and necrosis of gingival tissue with expo-
sure and rapid destruction of underlying bone, spon-
taneous bleeding, and severe pain, patients were 20.8
times more likely to have CD4+ cell counts below 200
cells/mm3 than patients without NUP.14 These data
suggest that the extent of periodontal destruction dur-
ing necrotizing ulcerative periodontal disease may, in
part, be a function of the level of immunocompromi-
sation of the host. This conclusion is supported by the
observation that for HIV-infected individuals with NUP,
the predictive value of NUP patients having CD4+ cell
counts below 200 cells/mm3 was 95.1% and a cumu-
lative probability of death within 24 months of a NUP
diagnosis was 72.9%.14 However, the observation by
the same authors that most HIV-infected individuals
with CD4+ cell counts below 200 cells/mm3 do not
have NUP suggests that factors, other than immuno-
compromisation, are involved in the etiology and
pathogenesis of NUP. Of HIV-infected individuals with
CD4+ cell counts below 400 cells/mm3 only 2 of 163
patients were diagnosed with NUP, whereas 37 were
diagnosed with adult periodontitis, 51 with gingivitis,
and 71 subjects were periodontally healthy.15 Further
studies have indicated that immunosuppression (CD4+
cell counts <200 cells/mm3), especially in combina-
tion with older age (>35 years), may be a significant
risk factor for attachment loss.16 These data suggest
that immunocompromisation may alter the rate of dis-
ease progression but the initial clinical presentation of
disease may be a function of its microbial etiology.
Microbiologic studies suggest that HIV-infected indi-
viduals with gingivitis and periodontitis harbor similar
microorganisms to non-HIV-infected individuals with
the same periodontal conditions except for the
increased prevalence of Candida albicans.17,18 Fur-
ther studies are needed, therefore, to define the com-
plex interactions between microbial etiology and
immunocompromisation that may lead to the devel-
opment of necrotic lesions. Since longitudinal studies
have demonstrated that attachment loss of >3 mm is
likely to occur 6.16 times more frequently in subjects
with CD4+ cell counts of <200 cells/mm,3,16 it is rea-
sonable to suggest a classification based on systemic
aggravation of periodontal disease progression. How-
ever, to suggest that NUP is a distinct form of peri-
odontitis lacks scientific support. It implies that the
destructive process that leads to tissue necrosis and
ulceration in systemically compromised individuals is
similar to that observed in periodontitis. The presence
of tissue necrosis in NUP suggests that periodontitis
and necrotizing lesions that affect the periodontium
may have distinct and separate etiologies. Since NUG
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Necrotizing Ulcerative Periodontitis
and NUP are necrotic lesions that occur in the presence
of some form of modulation of the immune system, this
reviewer suggests that NUG and NUP be classified under
the common term of necrotizing periodontal diseases
without the modifier of being aggravated by systemic
factors.
Malnutrition
An association has been made in developing coun-
tries between malnutrition, poor oral hygiene, and the
development of NUG.19-21 These reports have indi-
cated that a severe destructive disease, leading to
necrosis and sequestration of bone, is also observed
in this population and this condition has been termed
cancrum oris or noma. It has also been suggested that
this condition is an extension of NUG. The descrip-
tions provided from these studies suggest that can-
crum oris or noma is similar to the NUP lesions
described in HIV-infected patients and may be due to
an alteration of immune function through malnutri-
tion19,22 or systemic disease.23 The potential for HIV-
infection to be involved in the development of necrotic
periodontal lesions in young children of developing
countries has been suggested but not explored.20 From
the evidence provided, it appears that necrotic lesions,
including lesions of NUP, may occur in young individ-
uals who may be immunocompromised through mal-
nutrition and/or systemic disease. There is insufficient
evidence to support a distinct classification of NUP
associated with malnutrition since these subjects
appear to have systemic determinants that would place
them under the classification of necrotizing periodon-
tal diseases.
Refractory Necrotizing Ulcerative Periodontitis
There are no controlled clinical studies available to
suggest that necrotizing periodontal disease is refrac-
tory to treatment. Considering its microbial etiology,
there is ample evidence to suggest that the disease
can be controlled with effective oral hygiene measures
combined with the use of systemic antibiotics directed
at the invading microbial infection. The adjunctive
administration of systemic metronidazole has been
reported to be effective in the management of HIV-
associated periodontitis.24 and in spirochetal infection
control.10 However, the risk of superinfection with oral
Candida must be considered when using systemic
antibiotics especially in HIV-infected patients. Although
necrotic lesions may recur in the absence of effective
oral hygiene and the persistence of immunocompro-
misation, there are no studies that would support a
classification of refractory NUP.
SUMMARY
Because of the lack of appropriate clinical and basic
scientific studies, there is insufficient information avail-
able that would support the classification of necrotiz-
76
Volume 4 Number 1 December 1999
ing ulcerative periodontitis (NUP) in the group of dis-
eases defined by the term periodontitis. The use of the
term NUP would suggest that the pathologic process
observed in NUP is similar to that observed in peri-
odontitis, but with the addition of tissue necrosis. There
are currently no microbiologic or immunologic data to
support this. It is clear, however, that individuals
demonstrating necrotic lesions associated with the peri-
odontium may be immunocompromised through sys-
temic disease or malnutrition and the level of immuno-
compromisation may affect the clinical manifestations
of the necrotic lesion. This reviewer suggests that, until
more of the etiology and pathogenesis of the lesion is
known, NUP be reclassified as a necrotizing form of
periodontal disease and that NUG be included as a
component of this classification since necrotic lesions
can affect the gingiva as well as the periodontal liga-
ment and alveolar bone. The classification of necro-
tizing periodontal diseases should be distinct from the
classifications of gingivitis and periodontitis since tis-
sue necrosis is the common distinctive clinical feature
of NUG and NUP. In addition, neither lesion shares eti-
ologic or histologic characteristics that are currently
consistent with the classification of gingivitis or peri-
odontitis.
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3. MacCarthy D, Claffey N. Acute necrotizing ulcerative
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4. Barnes GP, Bowles WF, Carter HG. Acute necrotizing
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10. Loesche WJ, Syed SA, Laughon BE, Stoll J. The bac-
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