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2010;141;47-51J Am Dent AssocFaizan AlawiScott S. DeRossi, Katharine N. Ciarrocca andasthmaOral ulcerations in a patient with severe
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Oral ulcerations in a patient
with severe asthmaScott S. DeRossi, DMD; Katharine N. Ciarrocca, DMD, MSEd; Faizan Alawi, DDS
CLINICAL PRACTICE DIAGNOSTIC CHALLENGE
JADA, Vol. 141 http://jada.ada.org January 2010 47
THE CHALLENGE
A general dentist referred a 69-year-old woman to
an otolaryngologist for evaluation and manage-
ment of multiple painful oral ulcerations that had
been present for seven months. The patients
symptoms began with mild but increasing
burning of the oral cavity, which developed into
discrete ulcerations of the tongue and buccalmucosa. The otolaryngologist performed a tongue
biopsy. According to the patient, the biopsy
results were benign and she was treated with sys-
temic antiviral therapy without relief. She was
referred to another otolaryngologist at the quater-
nary care medical center, Medical College of
Georgia, Augusta, where she received prescrip-
tions for both an antifungal and an anesthetic
mouthrinse, with minimal resolution of the
lesions. The otolaryngologist then referred her to
our office for evaluation by one of us (S.S.D.).
The patients medical history was significant
for hypertension and severe asthma. She was
treated with antihypertensive medications
including enalapril and furosemide, systemic
prednisone (7.5 milligrams per day) and both cor-
ticosteroid and -agonist inhalers in combination
with montelukast, a leukotriene inhibitor. She
had been admitted to the hospital several times
because of her asthma, with the most recent hos-
pitalization 18 months before her initial evalu-
ation in our office. The review of systems was sig-nificant only for pulmonary symptoms related to
asthma (that is, shortness of breath, coughing,
wheezing) and her complaint of oral sores.
The clinical examination revealed no cervical
lymphadenopathy, no lesions on exposed skin and
no conjunctival erythema. An oral soft-tissue
examination revealed a 1-centimeter, ovoid, shal-
low ulceration on the left buccal mucosa, areas of
which were surrounded by erythema and white
keratosis. The patients tongue was papillated nor-
mally, and an irregularly shaped deep ulceration
with indurated and hyperplastic margins was
located on the middorsum (Figures 1 and 2).
Can you make the diagnosis?
D. malignant neoplasm
E. herpetic viral infection
A. median rhomboid glossitis
B. recurrent aphthous stomatitis
C. deep fungal infection
Figure 1. A large nodular ulceration of the dorsal surface of thetongue.
Figure 2. Large, painful ulceration of the left buccal mucosademonstrating a white, raised and circinate border.
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CLINICAL PRACTICE DIAGNOSTIC CHALLENGE
THE DIAGNOSIS
C. Deep fungal infection
Deep fungal infections can be the cause of iso-
lated ulcerative lesions of the oral cavity and
should be considered in patients with known or
suspected immunosuppression.1 Deep fungal
infections can include histoplasmosis, blastomy-
cosis, mucormycosis, aspergillosis, cryptococcosis
and coccidioidomycosis. Histoplasmosis is caused
by the fungusHistoplasma capsulatum, which is
endemic to the Ohio and Mississippi River val-
leys. In the United States, approximately 40 mil-
lion people have been infected withH. capsu-
latum and about 500,000 new cases are reported
each year.2-4H. capsulatum is found most often inareas contaminated with bird or bat droppings,
such as caves, bird roosts and old houses or
barns, as well as in areas in which the soil is
being disrupted through farming or excavation.
Histoplasmosis results from inhalation of con-
taminated dust of droppings from infected birds;
consequently, the lungs are the primary entry for
this infection. The spectrum of illness ranges from
an asymptomatic infection to severe disseminated
disease, depending on the amount of inoculum
and the patients immune status.5 Most immuno-
competent people who develop histoplasmosis are
asymptomatic or have a mild form of the disease.
Patients with symptomatic histoplasmosis have a
flulike syndrome and pulmonary complaints
related to underlying pneumonia or other lung
involvement.6,7 In a small proportion of patients,
histoplasmosis may be widespread (disseminated
histoplasmosis), and it can involve blood,
meninges, adrenal glands and other organs.
Very young or very old people or those who have
underlying immune disorders such as AIDS are
at a higher risk of developing disseminated
histoplasmosis.
People with chronic lung disease (for example,emphysema, bronchiectasis) may be at a higher
risk of developing a more severe infection. Others
at risk include patients receiving corticosteroid
treatment, cytotoxic therapy and treatment with
immunosuppressive agents. Our patient had been
receiving long-term systemic corticosteroid
therapy for management of asthma, but she
denied any known exposure to bird droppings or
an occupational exposure. She was unaware of
any bat infestation in her home.
Oral involvement in histoplasmosis usually is
secondary to pulmonary disease or a manifesta-
tion of disseminated infection.7 Oral lesions can
appear papular, nodular, vegetative or ulcerative.
The oral lesions begin as an area of erythema
that becomes a papule, which eventually forms a
granulomatous-appearing ulcer. Up to 40 to 50
percent of patients with systemic histoplasmosis
have oral ulcerations.6 The major oral sites
affected are the mucosa, tongue, palate, gingiva
and periapical region of the teeth.The diagnosis of histoplasmosis depends on the
suspected location of infection. Tests may include
analysis of the organism in sputum, lung tissue,
blood, cerebrospinal fluid (CSF) or bone marrow
tissue, as well as antigen tests performed on
blood, urine or CSF.1
Histologic evaluation often reveals granuloma-
tous inflammation with small spore-form oval
yeasts within macrophages and reticuloendothe-
lial cells.7 Multinucleated giant cells and histio-
cytes usually are present and are interspersed
among other inflammatory cells. Although spores
can be seen with routine hematoxylin-eosin
staining, they are visualized more easily with
special staining such as periodic acidSchiff
(PAS) and methenamine silver.7 Our patients
biopsy specimen revealed numerous small cir-
cular and ovoid fungal organisms throughout the
submucosa and within the cytoplasm of histio-
cytes and giant cells (Figure 3).
The mainstay of treatment for histoplasmosis
is systemic antifungal therapy. In the case of pul-
monary histoplasmosis, treatment may include
systemic drugs such as itraconazole, voriconazole
or ketoconazole. Immunocompromised patientswith disseminated histoplasmosis often receive
treatment with intravenous amphotericin B.
Immunocompetent patients are treated with itra-
conazole or ketoconazole for six to 12 months. Our
patient was treated with a four-week course of
voriconazole (200 mg orally twice daily) in consul-
tation with an infectious disease specialist, who
ruled out disseminated disease via serologic tests
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CLINICAL PRACTICE DIAGNOSTIC CHALLENGE
and bronchoscopy. The patients oral lesions had
resolved completely at the one-month follow-up
visit after her four-week course of antifungal
therapy.
One of the challenging aspects of this case was
the multifocal and varied appearance of two dis-
tinct lesions, one on the tongue and the other on
the buccal mucosa. In this patient, the tongueulceration appeared deeper and more nodular
than its counterpart on the buccal mucosa. In
addition to deep fungal infections, the differential
diagnosis can include a variety of granulomatous
disease processes that may exhibit similar clinical
characteristics to those of fungal infections, such
as tuberculosis, syphilis or even a gastrointestinal
process like Crohn disease. Therefore, it is vital
for the clinician to rule out systemic complaints
that may indicate a more widespread process. In
addition, the prudent clinician should inform the
pathologist of his or her clinical impression (dif-
ferential diagnosis) so that the pathologist can
use appropriate special tissue stains on the
specimen to rule out infectious or granulomatous
processes.
DIFFERENTIAL DIAGNOSIS
The differential diagnosis for chronic, multiple
ulcerations of the oral cavity can be extensive and
requires careful history taking, physical exami-
nation, histologic evaluation and occasionally lab-
oratory testing to narrow down the diagnostic
possibilities.
JADA, Vol. 141 http://jada.ada.org January 2010 49
A
C D
B
Figure 3. Oral histoplasmosis histologic findings.A. Ulcerated, well-vascularized stroma containing a diffuse mixed inflammatory infiltrate
composed mainly of large, mononuclear histiocytes with epithelioid or vesicular-shaped nuclei and abundant cytoplasm and neutrophils, aswell as occasional multinucleated giant cells. No discrete granulomas were identified (hematoxylin-eosin stain, 40). B. Numerous organismscan be seen (arrows) amid the mononuclear histiocytes (hematoxylin-eosin stain, 400). C. Periodic acidSchiff stain highlights the organismsin magenta (arrows). D. Gomori methenamine silver stained the organisms black.
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CLINICAL PRACTICE DIAGNOSTIC CHALLENGE
Median rhomboid glossitis. Median rhom-boid glossitis (MRG) is an often asymptomatic
erythematous patch of atrophic mucosa on the
dorsal surface of the tongue secondary to chronic
candidal infection.1,8
Historically, researchers con-sidered MRG to be a developmental defect, and it
rarely was treated. The lesion often begins as a
narrow patch of redness on the medial fissure of
the dorsal surface of the tongue. It usually is
asymptomatic and enlarges gradually. Over time,
if untreated, the lesion can exhibit the erythema-
tous nodular hyperplasia characteristic of chronic
hyperplastic candidiasis.8
The diagnosis of MRG requires proper identifi-
cation of candidal organisms, which is accom-
plished most easily via microscopic examination
of cytologic scrapings with PAS staining, Gram
staining or potassium hydroxide preparation.Although carcinoma of the dorsal surface of the
tongue is rare, clinicians also should consider per-
forming a biopsy if there is any clinical suspicion
of malignancy. Treatment of patients with MRG
may involve long-term topical antifungal therapy
along with management of any predisposing fac-
tors, such as xerostomia.
Recurrent aphthous stomatitis. Recurrentaphthous stomatitis (RAS) is the most common
cause of ulcers in the oral cavity, affecting
approximately 20 percent of the population.
Although the etiology remains to be elucidated,
investigators have proposed several local, sys-
temic, immunologic, genetic, allergic, nutritional
and microbial factors.9 RAS usually affects adoles-
cents and young adults, but it can be seen in older
patients as well. Trauma often is a causative
factor in the development of aphthae in suscep-
tible people via disruption of the mucosal surface
barrier and induction of inflammation.9
The classic lesions of RAS are acute and recur-
ring single or multiple ulcerations associated with
prodromal burning before the ulcer appears.
These round, painful ulcers are covered by a
yellowish gray fibrinous pseudomembrane andare surrounded by an erythematous halo on less
heavily keratinized or movable mucosa.1
The three clinical categories of RAS are minor,
major and herpetiform. Minor aphthae account for
more than 80 percent of all aphthae cases; the
lesions generally are smaller than 1 cm in diam-
eter, last 10 to 14 days and heal without scarring.
Major aphthae are larger, more numerous and
longer lasting and they often heal with residual
scarring. Herpetiform aphthae usually consist of
numerous small ulcerations that appear in crops
and may develop on any oral mucosal surface.
Treatment of RAS ranges from topical emollients,topical corticosteroids and intralesional steroid
injections to systemic medications such as pentoxi-
fylline, colchicine or thalidomide for severe disease.1
Malignant neoplasm. Clinicians must con-sider malignant neoplasm in the differential diag-
nosis of persistent, nonhealing oral ulceration. In
most cases, the cancer manifests as a solitary
lesion; squamous cell carcinoma is the most fre-
quent diagnosis. In cases in which multiple or
multifocal ulcerations are present, clinicians less
commonly include malignancy in the differential
diagnosis. Nonetheless, they can consider cancers
such as leukemia and metastatic tumors. Leu-kemias, typically of myeloid lineages, can mani-
fest as oral ulceration, often with concomitant
gingival swelling or enlargement.10 Soft tissues,
including the gingiva and tongue, are the most
common sites of involvement. In the case of
metastatic disease, the gingival tissues are
affected most frequently; multifocal presentations
are uncommon but may occur. Treatment of
patients with such conditions requires the
involvement of oncologists and usually involves
some form of chemotherapy.
Herpetic viral infection.Viral infections cancause multiple painful ulcerations in the oral
cavity. In light of our patients clinical presenta-
tion, a differential diagnosis should include ulcers
secondary to herpes simplex virus or cyto-
megalovirus (CMV). Intraoral recurrent herpes
lesions almost always appear on heavily kera-
tinized tissue in the oral mucosa, which aids the
practitioner in distinguishing them from aphthae.
Clinically, these lesions can appear as shallow, ser-
pentine ulcerations or clusters of ulcerations that
coalesce. In some cases, they may appear similar to
tissue that has undergone local trauma or physical
irritation. An important distinguishing feature isthe presence of a vesicular eruption that precedes
the appearance of the lesions.
In immunocompromised patients, herpes
lesions can develop on any mucosal surface with
often uncharacteristic features that make clinical
diagnosis difficult. Although intraoral herpes
lesions are a self-limited process in immunocom-
petent patients, treatment with systemic antiviral
50 JADA, Vol. 141 http://jada.ada.org January 2010
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CLINICAL PRACTICE DIAGNOSTIC CHALLENGE
medications such as acyclovir, valacyclovir or fam-
ciclovir is effective if initiated within the first 48
to 72 hours of vesicular formation and eruption.
However, in many cases, the condition is diag-
nosed too late for systemic antiviral therapy to beeffective, but supportive measures, including anal-
gesics and hydration, are important.
CMV is a member of the herpes family of
viruses and occurs worldwide. Most people
infected with CMV have subclinical infections. In
fact, clinical oral manifestations of CMV rarely
are encountered. However, in immunocompro-
mised patients, CMV can cause salivary gland
disease and ulcerations in the oral cavity.
Immunocompromised patients often require
aggressive treatment with intravenous ganci-
clovir, foscarnet or cidofovir.
CONCLUSION
Patients receiving long-term treatment with
immunosuppressant medications are at risk of
developing a multitude of processes that can
cause chronic oral ulcerations. Clinicians should
include infectious processes of viral, bacterial and
fungal etiologies, as well as malignant processes,
in the differential diagnosis. Timely and accurate
diagnosis via thorough history taking and proper
diagnostic techniques, including biopsy, are of
utmost importance.
Dr. DeRossi is the chairman, Department of Oral Health and Diag-nostic Sciences, and an associate professor of oral medicine, MedicalCollege of Georgia School of Dentistry, 1120 15th St., Augusta, Ga.30912-1241, e-mail [email protected]. Address reprint requests toDr. DeRossi.
Dr. Ciarrocca is an instructor, Department of Oral Rehabilitation andDepartment of Oral Health and Diagnostic Sciences, Medical College ofGeorgia School of Dentistry, Augusta.
Dr. Alawi is an assistant professor, Department of Pathology, Schoolof Dental Medicine, University of Pennsylvania, Philadelphia.
Disclosure. None of the authors reported any disclosures.
Diagnostic Challenge is published in collaboration with the AmericanAcademy of Oral and Maxillofacial Pathology and the AmericanAcademy of Oral Medicine.
1. Greenberg MS, Glick M, Ship JA, eds. Burkets Oral Medicine.11th ed. Hamilton, Ontario, Canada: BC Decker; 2008.
2. Kurowski R, Ostapchuk M. Overview of histoplasmosis. Am FamPhysician 2002;66(12):2247-2252.
3. Narayana N, Gifford R, Giannini P, Casey J. Oral histoplasmosis:an unusual presentation. Head Neck 2009;31(2):274-277.
4. Psevdos G Jr, Tanowitz HB. Oral histoplasmosis. AIDS Read2008;18(4):217-218.5. Alcure ML, Di Hiplito Jnior O, Almeida OP, Bonilha H, Lopes
MA. Oral histoplasmosis in an HIV-negative patient. Oral Surg OralMed Oral Pathol Oral Radiol Endod 2006;101(2):e33-e36.
6. Rahman MT, Bakar NH, Philip R, Shamsudin AR. Oral histoplas-mosis presenting as oral ulcer in a non-HIV patient. Southeast Asian JTrop Med Public Health 2004;35(2):388-390.
7. Kauffman CA. Histoplasmosis: a clinical and laboratory update.Clin Microbiol Rev 2007;20(1):115-132.
8. Whitaker SB, Singh BB. Cause of median rhomboid glossitis. OralSurg Oral Med Oral Pathol Oral Radiol Endod 1996;81(4):379-380.
9. Scully C. Clinical practice: aphthous ulceration. N Engl J Med2006;355(2):165-172.
10. Parisi E, Draznin J, Stoopler E, Schuster SJ, Porter D, SollecitoTP. Acute myelogenous leukemia: advances and limitations of treat-ment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod2002;93(3):257-263.
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