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A Case Report of Pernicious Anemia and Recurrent Aphthous Stomatitis

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Painful recurrent ulcers covered with a grayish pseudomembrane surrounded by an erythematous margin were identified on the tongue and in the buccal mucosa of a 71-year-old woman. The patient also presented with depapilation of the tongue. The clinical diagnosis was RAS. Laboratory tests including a hemogram were ordered to determine existing levels of folic acid, iron, ferritin, and vitamins B2, B6, and B12. Levels of serum vitamin B12 and serum hemoglobin were low. The laboratory investigation also showed a medium corpuscular volume of 104.1 fl. A gastroduodenoscopy revealed no macroscopic abnormality. A gastric biopsy showed mucosal atrophy in the gastric corpus with evidence of intestinal metaplasia. Antibodies against an intrinsic factor were negative. The diagnosis pernicious anemia was made, with RAS caused by vitamin B12 malabsorption. Treatment consisted of the administration of 1.0 ml of hydroxocolabamin intramuscularly twice weekly over four weeks followed by 1.0 ml once weekly for four weeks. Clinical resolution was observed after two months.
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A Case Report of Pernicious Anemia
and Recurrent Aphthous Stomatitis
Bruna Gonçalves Garcia, MS; Marcelo Ferreira Pinto Cardoso;
Omar de Faria, MS; Ricardo Santiago Gomez, DDS, PhD;
Ricardo Alves Mesquita, DDS, PhD
Abstract
Aim: The aim of this report is to present the management of a patient with pernicious anemia afflicted with
recurrent aphthous stomatitis (RAS).
Background: RAS is one of the most common lesions of the oral mucosa. Although the exact etiology of RAS
is still unknown different hematinic deficiencies have been proposed.
Case Report: Painful recurrent ulcers covered with a grayish pseudomembrane surrounded by an
erythematous margin were identified on the tongue and in the buccal mucosa of a 71-year-old woman. The
patient also presented with depapilation of the tongue. The clinical diagnosis was RAS. Laboratory tests
including a hemogram were ordered to determine existing levels of folic acid, iron, ferritin, and vitamins B2,
B6, and B12. Levels of serum vitamin B12 and serum hemoglobin were low. The laboratory investigation also
showed a medium corpuscular volume of 104.1 fl. A gastroduodenoscopy revealed no macroscopic abnormality.
A gastric biopsy showed mucosal atrophy in the gastric corpus with evidence of intestinal metaplasia.
Antibodies against an intrinsic factor were negative. The diagnosis pernicious anemia was made, with RAS
caused by vitamin B12 malabsorption. Treatment consisted of the administration of 1.0 ml of hydroxocolabamin
intramuscularly twice weekly over four weeks followed by 1.0 ml once weekly for four weeks. Clinical resolution
was observed after two months.
FREE full text provided by P&G Professional Oral Health.
1
The Journal of Contemporary Dental Practice, Volume 10, No. 2, March 1, 2009

Summary: The association of RAS with vitamin B12 malabsorption is a rare event. However, along with
conventional RAS clinical management, iron, folic acid, vitamin B deficiencies, and nutritional intolerance must
be considered. Evaluation of the predisposing factors is imperative in treating patients with RAS including
vitamin B12 malabsorption.
Clinical Significance: Determination of the levels of vitamin B12 should be the basis for replacement therapy.
Such therapy can be considered a benefit to the patients with RAS as its etiology remains unclear. Clinicians
must be alert to the possibility this lesion could be a signal of systemic disease.
Keywords: Chronic gastritis, malabsorption, pernicious anemia, recurrent aphthous stomatitis, RAS,
vitamin B12
Citation: Garcia BG, Cardoso MFP, Faria O, Gomez RS, Mesquita RA. A Case Report of Pernicious Anemia
and Recurrent Aphthous Stomatitis. J Contemp Dent Pract 2009 March; (10)2:083-089.
Introduction
Recurrent aphthous stomatitis (RAS) is an
Broides et al.5 reported patients with Imerslun-
inflammatory ulcerative condition of the oral
Grabeck syndrome had a vitamin B12 deficiency
mucosa characterized by painful and recurrent
associated with a neutrophil chemotactic defect
ulcers. It is one of the most common oral diseases
that may cause RAS.
worldwide and has been the subject of many
studies. RAS affects up to 25% of the general
Chronic gastritis is an inflammation of the lining of
population and three-month recurrence rates are
the stomach occurring gradually and persisting for
as high as 50%.1
a prolonged time.6 Pernicious anemia is the result
of vitamin B12 malabsorption induced by chronic
RAS is classified according to clinical features as
gastritis. The relation between deficiency of vitamin
minor, major, and herpetiform. The most common
B12 and RAS have been rarely reported in the
presentation is minor RAS with round, clearly
literature.4 Wray et al.7 demonstrated RAS can be
defined, small, painful ulcers that heal in 10 to
caused by a deficiency of vitamin B12 although
14 days without scarring. In major RAS (Sutton’s
only 3.8% of the patients presented this condition.
disease) the lesions are larger (>1.0 cm), can
Piskin et al.8 observed 35 patients with RAS and
last for six weeks, and frequently scar. The third
concluded serum vitamin B12 levels were low in
variety of RAS is the herpetiform, which presents
eight patients (22.8%). In other studies Koybasi et
as multiple clusters of pinpoint lesions that
al.9 and Burgan et al.10 observed 35.2% and 26.6%
coalesce to form large irregular ulcers and last
of the patients, respectively, had RAS and a vitamin
seven to ten days.2
B12 deficiency. In the current report the clinical
features and management of a case of RAS related
While the exact pathophisiology of RAS remains
to vitamin B12 malabsorption are described.
unclear, factors contributing to this clinical entity
include the following:3,4
Case Report
• Local trauma
• Smoking
Diagnosis
• Stress
A 71-year-old-woman was referred to the Oral
• Hormonal status
Medicine Clinic of the School of Dentistry at the
• Genetics
Universidade Federal de Minas Gerais in Belo
• Hematinic deficiencies (iron, folic acid,
Horizonte, Brazil for evaluation and treatment in
vitamins B2, B3, B6, B12, and C)
April 2006. She complained of painful recurrent oral
• Immunological factors
ulcers evolving over the past three years. Multiple
• Microorganisms
ulcers covered with a grayish pseudomenbrane
• Systemic diseases
surrounded by an erythematous margin located
2
The Journal of Contemporary Dental Practice, Volume 10, No. 2, March 1, 2009

Figure 1. A. Depapilation of the tongue and multiples ulcers covered with a grayish pseudomenbrane located
in the apex of the tongue. B and C. Ulcers covered with a grayish pseudomenbrane located in the right and
left erythematous buccal mucosa. D, E and F. Clinical resolution of the ulcers and improvement of the tongue's
depapilation.
in the tongue and in the buccal mucosa
Treatment
were identified during the oral examination.
Treatment consisted of the administration of 1.0
Depapilation of the tongue and erythemathous
ml of hydroxocolabamin intramuscularly twice
buccal mucosa was also noted (Figures 1A, 1B,
weekly over four weeks followed by 1.0 ml once
and 1C).
weekly for four weeks. Clinical resolution of the
RAS and improvement of the tongue depapilation
Laboratory tests including a hemogram were
and buccal mucosa (Figures 1D, 1E, and 1F) was
ordered to determine folic acid, iron, ferritin,
apparent after two months.
vitamins B2, B6, and B12 levels, serum
hemoglobin, and medium corpuscular volume
At 12 months the patient was free of the RAS
(MCV). A low serum vitamin B12 (133 pg/ml) and
with normal levels of hemoglobin, MCV, and
a low serum hemoglobin (3,670,000/mm3) along
vitamin B12, but continued with intramuscular
with a MCV of 104.1 fl were identified.
administration of vitamin B12 and 2 ml of
hydroxocolabamin for 60 more days.
A gastroduodenoscopy revealed no macroscopic
abnormality. A gastric biopsy revealed mucosal
Discussion
atrophy in the gastric corpus with evidence of
A great deal of progress has been made during
intestinal metaplasia. Antibodies against an
the last three decades regarding the epidemiology,
intrinsic factor and Helicobacter pylorii detection
description, causes, and treatment of RAS.
were negative. The diagnosis of pernicious
Systemic conditions, genetic, immunologic,
anemia was made along with RAS caused by
microbial factors, and hematinic deficiencies have
malabsorption of vitamin B12.
been found to be related to the pathogenesis
3
The Journal of Contemporary Dental Practice, Volume 10, No. 2, March 1, 2009

of RAS. However, no principal cause has been
Patients with RAS generally do not require
discovered to date.2,3 The clinical features along
treatment. On the other hand, some RAS lesions
with the patient response to the management of
can be painful in a recurrent or constant pattern.
the case reported here supported a diagnosis of
As a result, it is important to determine possible
RAS related to vitamin B12 malabsorption.
hematinic deficiencies or allergies in order to
provide appropriate therapies.15 Like the case
Chronic gastritis can induce malabsorption of
reported by Weusten and Van de Wiel4 the patient
vitamin B12. In the present case the gastritis was
in the present case responded to treatment with
an auto-immune phenomenon. The deficiency
parenteral vitamin B12 after which the RAS did
of vitamin B12 is frequently associated with
not recur and serum vitamin B12, hemoglobin,
glossitis but not generally thought to induce
and MCV levels returned to normal levels.
RAS.7,8,11,12 While the precise role of vitamin B12
deficiency in the pathogenesis of RAS is unclear,
Summary
the suppression of cell-mediated immunity and
The association of RAS with vitamin B12
changes in the cells of the tongue and oral
malabsorption is a rare event. However, along
mucosa have been described.13-15 Studies from
with conventional RAS clinical management, iron,
the United Kingdom, United States, and Spain
folic acid, vitamin B deficiencies, and nutritional
have demonstrated hematinic deficiency is twice
intolerance must be considered. Evaluation
as common in RAS patients than in controls.7 In
of the predisposing factors is imperative in
the present case the disease started when the
treating patients with RAS including vitamin B12
patient was 71 years old, which is not common.
malabsorption.
The patient also presented with erythemathous
mucosa and depapilation of the tongue which are
Clinical Significance
characteristic symptoms of other problems.
Determination of the levels of vitamin B12
should be the basis for replacement therapy.
Differentiation between RAS and other forms
Such therapy can be considered a benefit to the
of oral ulcers seldom pose a major clinical or
patients with RAS as its etiology remains unclear.
diagnostic problem,4 although similar-appearing
Clinicians must alert to the possibility this lesion
lesions may arise in systemic disorders. Rarely,
could be a signal of systemic disease.
drugs such as non-steroidal anti-inflammatory
drugs (NSAIDS) or nicorandil can give rise to oral
ulcers, similar to RAS.15
4
The Journal of Contemporary Dental Practice, Volume 10, No. 2, March 1, 2009

References
1. Barrons RW. Treatment stratagies for recurrent oral aphthous ulcers. Am J Health Syst Pharm.
2001; 58(1):41-50.
2. Ship JA. Recurrent aphthous stomatitis. An update. Oral Sug Oral Med Oral Pathol Oral Radio
Endod. 1996; 81(2):141-7.
3. Scully C, Porter SR. Recurrent aphthous stomatitis: current concepts of etiology, pathogenesis, and
management. J Oral Pathol Med. 1989; 18(1):21-7.
4. Weusten BL, Van de Wiel A. Aphthous ulcers and vitamin B12 deficiency. Neth J Med. 1998;
53(4):172-5.
5. Broides A, Yerushalmi B, Levy R, Hadad N, Kaplun N, Tanner SM, Chapelle Ade L, Levy J.
Imerslund-Grasbeck syndrome associated with recurrent aphthous stomatitis and defective
neutrophil function. J Pediatr Hematol Oncol. 2006; 28(11):715-9.
6. Rugge M, Genta RM. Staging and grading of chronic gastritis. Hum Pathol. 2005; 36(3):228-233.
7. Wray D, Ferguson MM, Mason DK, Hutcheon AW, Dagg JH. Recurrent aphtae treatment with
vitamin B12, folic acid and iron. Br Med J. 1975; 2(5969):490-3.
8. Piskin
S,
Sayan C, Durukan N, Senol M. Serum iron, ferritin. Folic acid, and vitamin B12 levels in
recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol. 2002; 16(1):66-7.
9. Koybasi
S, Parlak AH, Serin E, Yilmaz F, Serin D. Recurrent aphthous stomatitis: investigation of
possible factors. Am J Otolaryngol. 2006; 27(4):229-32.
10. Burgan SZ, Sawair FA, Amarin ZO. Hematologic status in patients with recurrent aphthous stomatitis
in Jordan. Saudi Med J. 2006; 27(3):381-4.
11. Barnadas MA, Remacha A, Condomines J, de Moragas JM. Hematologic deficiencies in patients
with recurrent oral aphtae. Med Clin (Barc). 1997; 109(3):85-7.
12. Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis:
a consensus approach. J Am Dent Assoc. 2003; 134(2):200-7.
13. Carrozzo M, Carbone M, Gandolfo S. Recurrent aphthous stomatitis: current etiopathogenetic and
therapeutic concepts. Minerva Stomatol. 1995; 44(10):467-75.
14. Porter SR, Hegarty A, Kaliakatsou F, Hodgson TA, Scully, C. Recurrent Aphtous Stomatitis Clin
Dermatol. 2000; 18(5):569-78.
15. Macphail L. Topical and systemic therapy for recurrent aphtous stomatitis. Semin Cut Med Sur.
1997; 16(4):301-7.
About the Authors
Bruna Gonçalves Garcia, DDS
Dr. Garcia is a graduate student in the Department of Oral Surgery, Oral Medicine and
Oral Pathology of the School of Dentistry at the Universidade Federal de Minas Gerais
in Belo Horizonte, Brazil.
e-mail: bgg104@hotmail.com
Marcelo Ferreira Pinto Cardoso
Mr. Cardoso is an undergraduate student in the Department of Oral Surgery, Oral
Medicine and Oral Pathology of the School of Dentistry at the Universidade Federal
de Minas Gerais in Belo Horizonte, Brazil.
5
The Journal of Contemporary Dental Practice, Volume 10, No. 2, March 1, 2009

Omar de Faria, MS
Mr. Faria is a graduate student in the Department of Oral Surgery, Oral Medicine
and Oral Pathology of the School of Dentistry at the Universidade Federal de Minas
Gerais in Belo Horizonte, Brazil.
Ricardo Santiago Gomez, DDS, PhD
Dr. Gomez is an Associate Professor in the Department of Oral Surgery, Oral
Medicine and Oral Pathology of the School of Dentistry at the Universidade Federal
de Minas Gerais in Belo Horizonte, Brazil.
Ricardo Alves Mesquita, DDS, PhD
Dr. Mesquita is an Adjunct Professor in the Department of Oral Surgery, Oral Medicine
and Oral Pathology of the School of Dentistry at the Universidade Federal de Minas
Gerais in Belo Horizonte, Brazil.
Acknowledgments
The authors appreciate the support provided by the National Council for Scientific and Technological
Development (CNPq) (484974/2006-8; 301490/2007-4) for this project.
6
The Journal of Contemporary Dental Practice, Volume 10, No. 2, March 1, 2009

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