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Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

Journal of Oral and Maxillofacial Surgery,

Medicine, and Pathology
journal homepage: www.elsevier.com/locate/jomsmp

Case report

Necrotizing ulcerative stomatitis as initial presentation of

undiagnosed HIV infection: A case report and review of literature
Scott M. Peters a , Matthew J. Heinz b , David A. Koslovsky c,d , Angela J. Yoon a ,
Elizabeth M. Philipone a,∗
a
Division of Oral and Maxillofacial Pathology, Columbia University College of Dental Medicine, New York, NY, USA
b
Columbia University College of Dental Medicine, New York, NY, USA
c
Metropolitan Oral Surgery Associates, New York, NY 10022, USA
d
Division of Oral and Maxillofacial Surgery, Department of Surgery, Weill Cornell Medical Center, New York, NY 10065, USA

a r t i c l e i n f o a b s t r a c t

Article history: There are a multitude of oral manifestations of human immunodeficiency virus (HIV), many of which
Received 7 April 2017 have decreased in frequency following the introduction of combination antiretroviral therapy (cART) in
Received in revised form 5 July 2017 1996. Atypical periodontal disease is an example of an oral manifestation that is infrequently seen yet
Accepted 12 July 2017
strongly associated with HIV infection. HIV-associated periodontal disease can be classified into three
Available online xxx
categories, linear gingival erythema, necrotizing ulcerative gingivitis (NUG), and necrotizing ulcerative
periodontitis (NUP), which vary based on disease severity. When this disease process extends beyond
Keywords:
the alveolar ridges and causes massive tissue destruction, it is termed necrotizing ulcerative stomatitis
HIV
Necrotizing ulcerative stomatitis (NUS). Herein, we report a case of a 20-year-old male patient with undiagnosed HIV in whom necrotizing
Periodontal disease ulcerative stomatitis was the first presenting sign of underlying disease.
© 2017 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽

1. Introduction palatal tissues, thus resulting in exposure of bone [6]. Although

HIV-associated periodontal disease classically presents as one
(or more) of three atypical patterns. The first of these is linear gin-
gival erythema (LGE), which is characterized by a linear band of
erythema that involves the free gingival margin and can extend
apically for 2–3 mm [1–3]. The second pattern, necrotizing ulcera-
tive gingivitis (NUG) appears as ulceration or necrosis of interdental
papilla without attachment loss [4]. When attachment loss does
occur, the condition is referred to as necrotizing ulcerative peri-
odontitis (NUP) [2].
While these patterns are traditionally referred to as three dis-
tinct entities, they can be better understood as a single disease
process whose nomenclature varies based on clinical severity. As
a further extension of this process, when gingival necrosis extends
beyond the alveolar ridges and causes massive tissue destruction
within the oral cavity, the term necrotizing ulcerative stomatitis
(NUS) is used [5].
NUS was first reported in 1990 by Williams as an ulcero-necrotic
infection of gingiva that extends into contiguous mucosal and
∗ Corresponding author at: Columbia University Medical Center, 630 West 168th
Street, PH15W-1562, New York, NY 10032, USA.
E-mail address: ep2464@cumc.columbia.edu (E.M. Philipone).
NUS may be an extension of NUP, it can also begin in areas of
the oral mucosa other than the gingiva. Therefore, NUS was re-
defined as a painful ulceronecrotic lesion of the oral mucosa that
may expose underlying bone or extend into contiguous tissue [5].
A retrospective study aimed at delineating the histopathologic,
immunohistochemical, and virologic characteristics of NUS sup-
ported this updated definition and found that NUS does not always
progress as an extension of NUP, but may involve any oral mucosa
site [7]. In the absence of gingival involvement, however, the clin-
ical features of NUG are nonspecific, and biopsy is required for
diagnosis. Herein, we present a case of NUS in a 20-year-old male
patient with an undiagnosed HIV infection.
2. Case report
A 20-year-old Caucasian homosexual man was referred to a local
oral surgeon with a chief complaint of a burning sensation and
painful discomfort on his palate. The patient was in his baseline
state of health with no significant past medical history until January
2014, when he began to feel “a bubble” at the top of his mouth. He
initially denied pain but did complain of slight discomfort when
eating spicy food. As the lesion progressed in size, however, he
began to develop burning pain, chills, and night fevers.

http://dx.doi.org/10.1016/j.ajoms.2017.07.005
2212-5558/© 2017 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽

Please cite this article in press as: Peters SM, et al. Necrotizing ulcerative stomatitis as initial presentation of undiagnosed HIV infection:
A case report and review of literature. J Oral Maxillofac Surg Med Pathol (2017), http://dx.doi.org/10.1016/j.ajoms.2017.07.005
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Fig. 1. Initial presentation (July 2015). (a) Anterior maxilla with erythematous and edematous gingiva and blunting of papilla. (b) Ulcerative lesion of the palate.

The patient denied any other medical conditions or past surg-

eries. He reported that he was taking ibuprofen for pain relief, but
had not been prescribed any medications. He also denied smoking
or any illicit drug use. With regard to his social history, the patient
reported multiple sexual encounters with multiple male partners.
He had not been recently tested for HIV.
On clinical exam, the attached gingiva of the anterior maxilla
was edematous and erythematous with blunting of the papilla
(Fig. 1a). There was a large necrotic ulcerative lesion of the ante-
rior hard palate, extending from canine to canine, with exposure of
palatal bone (Fig. 1b). Teeth #7–10 were mobile and the oral cav-
ity was malodorous. Oropharyngeal candidiasis, which presented
as white, removable plaques on the uvula and left glossopalatine
fold, was identified (Fig. 2). The diagnosis was confirmed by fungal
culture. Radiographs were taken which showed extensive vertical
alveolar bone absorption of the anterior hard palate extending from
Fig. 2. Initial presentation (July 2015). White, removable plaques are present along
canine to canine (Fig. 3).
the uvula and left glossopalatine arch.
Clinical differential diagnosis included deep fungal ulcer (histo-
plasmosis, mucormycosis), NK-T cell lymphoma, tuberculosis,
syphilis, and HIV-associated periodontal disease. The patient was
were all negative. CD68 highlighted a prominent histiocytic com-
prescribed nystatin rinse for candidiasis, chlorhexidine 0.12% rinse,
ponent within the inflammatory infiltrate.
and pain medication. He consented to HIV testing and was referred
Bloodwork revealed a white blood count of 4.4 (nor-
for complete blood count (CBC), basic metabolic panel (BMP) and
mal = 3.5–9.1 × 109 /L), hemoglobin of 12.3 (normal = 12–15.8 g/dl),
liver function tests (LFTs). In addition, two incisional biopsies
and hematocrit of 38.3 (normal = 35.4–44.4%) [8]. His BMPs
were performed from the peripheral and central aspects of the
and LFTs were both normal. Panels (antibody titers) for
lesion, which showed ulceration with bacterial overgrowth and
hepatitis, syphilis, and toxoplasma were also negative. The
connective tissue necrosis, marked vasculitis, and acute and chronic
patient’s CD4 count, however, was reduced at 101 (nor-
inflammatory infiltrate (Fig. 4). Immunohistochemical stains for
mal = 393–1498 cells/mm3 ) and HIV was detected on rapid exam
intra-lesional fungal organisms (GMS and PAS), EBV, HSV1, HSV2,
[8]. HIV status was subsequently confirmed on western blot, and
and CMV stains were performed on paraffin-embedded tissue and
his HIV viral load was found to be 271,779 copies/mm3 . These
lab findings were discussed with the patient and he was referred

Fig. 3. Periapical radiographs (July 2015). Anterior maxilla with bone loss.

Please cite this article in press as: Peters SM, et al. Necrotizing ulcerative stomatitis as initial presentation of undiagnosed HIV infection:
A case report and review of literature. J Oral Maxillofac Surg Med Pathol (2017), http://dx.doi.org/10.1016/j.ajoms.2017.07.005
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Table 1
Patient Laboratory Values Pre and Post cART.

Initial Presentation (Pre-cART) One month post initiation of cART One year post initiation of cART Normal Value

WBC (x109 /L) 4.4 6.5 4.1 3.5–9.1

RBC (x109 /L) 4.25 4.25 4.90 4.3–5.6
Hemoglobin (g/dl) 12.3 13.0 15.4 12–15.8
Hematocrit (%) 38.3 39.9 44 35.4–44.4
Sodium (mmol/L) 140 143 140 135–145
Potassium (mmol/L) 5.0 4.5 4.8 3.5–5.1
Chloride (mmol/L) 102 105 102 95–105
CO2 -HCO3 (mmol/L) 31 30 30 22–28
BUN (mg/dL) 14 15 16 7–24
Creatinine (mg/dL) 0.94 0.93 1.36 0.7–1.4
Glucose (mg/dL) 73 87 70 60–120
CD4 (cells/mm3 ) 101 170 238 393–1498
HIV viral load (copies/mm3 ) 271,779 <20 <20 Undetectable

to the Infectious Disease department at NY-Presbyterian Hospi-

tal/Columbia Medical Center for management of newly diagnosed
HIV. He was also started on amoxicillin and flagyl.
Based on the patient’s clinical presentation, as well as the
histologic and laboratory findings, a diagnosis of HIV-associated
necrotizing ulcerative stomatitis of the maxilla was confirmed. The
patient began cART and returned approximately one month later
for follow-up. At that time, his viral load decreased to less than
20 copies/mm3 and his CD4 count also improved to 170 cells/mm3 .
A complete listing of the patient’s pre and post treatment labora-
tory values can be found in Table 1. He was subsequently seen for
necrotic tissue debridement and splinting of teeth #5–13 due to
gross mobility. A maxillofacial CT scan without contrast was sub-
sequently ordered and displayed loss of normal bony trabeculation
of the anterior maxilla, involving teeth #6–11, with erosion of the
buccal and palatal cortices (Fig. 5a) and destruction of the anterior
nasal floor (Fig. 5b).
Given the clinical findings and radiographic extent of bone loss,
the patient underwent anterior maxillary debridement, extrac-
tion of involved teeth, and obturator delivery. Teeth #5–11 were Fig. 4. Biopsy (July 2015). Marked vasculitis as well as acute and chronic inflamma-
extracted and a peripheral ostectomy was performed to encounter tion (H&E, ×200).

bleeding bone. A small perforation into the nasal cavity was noted
but the nasal mucosa remained intact. A rim of nasal aperture,
out tension and the maxillary obturator was delivered (Fig. 6b). A
as well as the anterior nasal spine, was maintained for structural
slight anterior open bite was maintained to alleviate pressure on
support (Fig. 6a). Primary closure of the mucosa was attained with-
the mucosa (Fig. 7).

Fig. 5. (August 2015): (a) CT scan (axial view). Anterior maxilla with bony erosion. (b) CT scan (coronal view). Destruction of the anterior nasal floor.

Please cite this article in press as: Peters SM, et al. Necrotizing ulcerative stomatitis as initial presentation of undiagnosed HIV infection:
A case report and review of literature. J Oral Maxillofac Surg Med Pathol (2017), http://dx.doi.org/10.1016/j.ajoms.2017.07.005
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Fig. 6. (October 2015): (a) Intra-operative photograph following extraction of teeth #5–11 and peripheral ostectomy. (b) Intra-operative insertion of obturator.
Fig. 7. (October 2015): Post-operative photograph with obturator in place. Note
that a slight anterior open bite was maintained to prevent anterior occlusal contact
and allow for healing of the surgical site.
The patient had an uncomplicated post-operative course and
was satisfied with the esthetics of his prosthesis. He remains on
anti-retroviral therapy. His most recent laboratory values, taken
at one year post initiation of cART, showed a CD4 count of 283
cells/mm3 and an undetectable viral load (Table 1). The patient is
interested in eventually replacing his obturator with a fixed dental
appliance. Pending long term compliance with his anti-retrovirals,
he will be evaluated as a candidate for hard and soft tissue recon-
struction via a vascularized osseocutaneous flap, osseointegrated
dental implants and a fixed dental prosthesis.
3. Discussion
According to the U.S. Centers for Disease Control and Prevention,
an estimated 1.2 million people in the United States are currently
living with HIV infection [9]. These individuals have compromised
immune function and are predisposed to a variety of systemic and
oral complications. Oral and maxillofacial lesions strongly associ-
ated with HIV infection include candidiasis, oral hairy leukoplakia,
Kaposi sarcoma, persistent generalized lymphadenopathy, non-
Hodgkin lymphoma, and atypical periodontal disease [2,10].
HIV-associated periodontal disease can be thought of as a sin-
gle disease process which is further classified into three categories
Please cite this article in press as: Peters SM, et al. Necrotizing ulcerative stomatitis as initial presentation of undiagnosed HIV infection:
A case report and review of literature. J Oral Maxillofac Surg Med Pathol (2017), http://dx.doi.org/10.1016/j.ajoms.2017.07.005
based on extent of clinical severity. Linear gingival erythema (LGE)
has been described as an early stage of HIV-associated periodontal
disease which presents as a fiery red, distinct linear erythema along
the free gingival margin, attached gingiva, and alveolar mucosa
[2]. Although some believe LGE to result from an abnormal host
immune response to subgingival bacteria, more recent data suggest
that it is in fact and unusual variant of candidiasis [3]. Necrotizing
ulcerative gingivitis (NUG) is a more severe condition, present-
ing with painful ulceration and necrosis of one or more dental
papilla [4]. Periodontal attachment loss is uncommon in both
LGE and NUG. Necrotizing ulcerative periodontitis (NUP), on the
other hand, is characterized by destruction of both hard and soft
tissue. Patients typically present with mobility of teeth, sponta-
neous bleeding, foul odor, and may also complain of deep jaw pain
[2].
Necrotizing ulcerative stomatitis (NUS) was first described as
the terminal progression of HIV-associated periodontal diseases.
In 1990, Williams et al. reported NUS as an ulceronecrotic infection
of the gingiva that extends into contiguous mucosal or palatal tis-
sues, resulting in exposure of bone [6,7]. This definition implies that
NUS must develop from pre-existing NUP. However, a retrospective
study aimed at delineating the histopathologic, immunohisto-
chemical, and virologic characteristics of NUS found that there
can be involvement originating from any oral mucosal site [7].
These findings, along with several others, resulted in NUS being
redefined as a painful ulceronecrotic lesion of the oral mucosa
that may expose underlying bone or extend into continuous tissue
[5].
The histopathologic features of NUS have been commonly
described as deep ulcerations overlying fibrous connective tis-
sue which exhibit areas of necrosis, leukocytoclasia, histiocytic
vasculitis with luminal fibrin clots, and extensive inflammatory
cell infiltrate [7,11]. This inflammatory infiltrate consists pri-
marily of large atypical cells with vesicular nuclei interspersed
throughout a background of more normal appearing histiocytes.
Expression of CD68 and HLA-DR4 in the inflammatory cell infil-
trate confirms that the large atypical cells are also histiocytes.
Often other viral pathogens, especially Herpes Simplex Virus (HSV),
Epstein Barr Virus (EBV) and Cytomegalovirus (CMV), can be iden-
tified histologically within the areas of ulceration and necrosis
[7].
With the advent of combination antiretroviral therapy (cART),
the prevalence and severity of HIV-associated periodontal disease
have decreased [12]. Management of NUP/NUS includes removal of
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dental plaque and calculus and debridement of hard and soft tissue
[13]. Chlorhexidine gluconate 0.12% rinse administered twice daily
and antibiotics are recommended to reduce the bacterial burden,
and typically a course of metronidazole or clindamycin in combi-
nation with amoxicillin is prescribed [13,14]. Pain management,
nutritional supplementation, counseling, and frequent follow-ups
are important factors to consider when treating a patient with
NUP/NUS. In cases of NUS where gingival involvement is absent,
clinical findings are non-specific and biopsy is required.
Following the advent of cART, there has been a decline in
the number of reported cases of HIV associated periodontitis and
NUS [12]. That being said, the literature base from the 1990s
and early 2000s provides documentation of the clinical and his-
tologic features of the disease. Patton and McKaig report a case
of NUS in a 23-year-old HIV positive man, who first presented
in 1992 with complaints of right upper quadrant pain and fetid
odor. Within 6 months of his initial presentation, the lesion had
spread to involve his palatal mucosa, and his overall alveolar bone
loss resulted in tooth mobility necessitating the extraction of two
involved teeth [13]. A retrospective study by Jones et al. in 2000
examined eighteen cases of necrotizing ulcerative stomatitis. The
patients in this study ranged from 20 to 52 years of age, were
predominately male (13 of 17), and were all HIV positive, with
3 demonstrating AIDS defining criteria. The most common loca-
tion of NUS was reported as the lower lip. The authors found
that in all patients the NUS, lesions possessed reproducible micro-
scopic and immunohistochemical features which also resembled
extranodal Kikuchi’s disease. A full listing of the clinical and
histologic features of these cases can be found in Jones et al.
[7].
4. Conclusion
Our case adds an additional report of NUS in an HIV positive indi-
vidual. This patient was initially undiagnosed and untreated, and
NUS was the first clinical manifestation of HIV in this patient. As
previously discussed, oral manifestations of HIV/AIDS have been
reported less frequently due to the efficacy of cART, and a pre-
sentation such as this is now considered rare. This report serves
as a reminder that clinicians must remain cognizant of the oral
manifestations of HIV, as they can help guide proper diagnosis and
treatment of systemic diseases. Consideration of and access to HIV
testing is important in the clinical setting.
Please cite this article in press as: Peters SM, et al. Necrotizing ulcerative stomatitis as initial presentation of undiagnosed HIV infection:
A case report and review of literature. J Oral Maxillofac Surg Med Pathol (2017), http://dx.doi.org/10.1016/j.ajoms.2017.07.005
5
Conflict of interest
The authors have no conflicts of interest to declare.
Ethical approval
Not needed.
Funding
The study received no commercial funding.
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