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Comparing the Effect of Phenytoin Syrup and Triamcinolone Acetonide

Ointment on Aphthous Ulcers in Patients with Behcet’s Syndrome

Article  in  Iranian Red Crescent Medical Journal · February 2012

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Iranian Red Crescent Medical Journal
ORIGINAL ARTICLE

Comparing the Effect of Phenytoin Syrup and Triamcinolone

Acetonide Ointment on Aphthous Ulcers in Patients with
Behcet’s Syndrome

MM Fani1, H Ebrahimi1, S Pourshahidi1*, E Aflaki2, S Shafiee Sarvestani3

1
Department of Oral Medicine, Dental School, Shiraz University of Medical Sciences, Shiraz, Iran
2
Department of Rheumatology, Shiraz University of Medical Sciences, Shiraz, Iran 3Dentist, Shiraz Uni-
versity of Medical Sciences, Shiraz, Iran

Abstract

Background: Recurrent aphthous stomatitis (RAS) appears to be the most common type of oral ulcers. The
lesion is usually self limited but its painful presentation results in some difficulties. Therefore, an efficient thera-
peutic strategy is required and currently existing therapies seem to be inadequate because of its unclear etiology.
Here the therapeutic effect of triamcinolone acetonide ointment as a relatively expensive medication has been
compared with phenytoin syrup on aphthous ulcers in patients with Behcet’s syndrome.

Methods: Thirty out of 60 our patients with Behcet’s syndrome were randomly treated by phenytoin syrup and
the remaining were advised to use 0.1% triamcinolone acetonide ointment. After a week, they were visited again
to determine the status of aphthous ulcers.

Result: Positive response in the triamcinolone acetonide group and phenytoin group was 86.7% and 53.3%,
respectively.

Conclusion: The effectiveness of triamcinolone acetonide ointment was more than phenytoin on aphthous
ulcers in patients with Behcet’s syndrome.
Keywords: Phenytoin; Triamcinolone Acetonide; Aphthous ulcer; Behcet’s syndrome

Introduction erythema, often appear on labial or buccal mucosa,

heal within 7-10 days and leave no scar.1,2,8,11
Recurrent aphthous stomatitis (RAS) appears to be Major aphthous ulcers are presented as larger and
the most common type of oral ulcers. Typically it is deeper ulcers, mostly seen on soft palate, tonsils,
presented as self limited ulcers affecting non- tongue or pharynx, heal within several weeks and
keratinized oral mucosa.1 The first lesions often ap- usually leave scar. Herpetiform aphthous usually pre-
pear when the patient is a child.2 It has a higher sent as ulcers of 1-3 mm in diameter and occur in
prevalence in younger adults and the incidence and groups. They heal within 1-4 weeks.1,2,8,12-17
severity would decrease with age.3-7 No gender predi- The cause of RAS is still unknown, although there
lection has been detected.3 are many promoting and exacerbating factors such as
Minor, major and herpetiform aphthous ulcers are positive family history, trauma, nutritional deficiency
the subdivisions. Minor ones, seen in 80% of patients8- (iron, vitamin B12, folate), food hypersensitivity,
10
are less than 10 mm in diameter. The round or ovoid immune disturbance, smoking cessation and psycho-
ulcers with a pseudo membranous base surrounded by logical stress.1,2,8,12-16 RAS generally is not associated
with systemic disorders but aphthous like ulcers may
be the presentation of some disorders such as
*Correspondence: Sara Pourshahidi, DMD, MSc, Assistant Professor Behcet’s and Reiter’s syndrome.2,17
of Oral Medicine, Dental School, Shiraz University of Medical Sciences,
Shiraz, Iran. Tel: +98-912-4760970, e-mail: purshahidi@sums.ac.ir Although the lesion is usually self limited, its
Received: July 24, 2011 Accepted: October 12, 2011 painful presentation leads to difficulty in eating,

Iran Red Crescent Med J 2012; 14(2):75-78 ©Iranian Red Crescent Medical Journal
Fani et al.

speaking and swallowing and decreased quality of ml), cream (1%) and capsule (50 and 100 mg) . The
life. Patients may suffer from its high frequency, too.1 classic form of topical application is suspension (30
So an efficient therapeutic strategy is needed and be- mg/5 ml).23
cause of its unclear etiology, current available thera- In this study, the therapeutic effect of triamcino-
pies seem to be inadequate.1,13 lone acetonide ointment as a relatively expensive
The therapeutic strategies for minor aphthous le- medication was compared with phenytoin syrup on
sions include concurrent oral hygiene, coating agents, aphthous ulcers in patients with Behcet’s syndrome.
antiseptics, antibiotics, hormones, topical anesthesia
and steroids. These methods mostly relieve symptoms
and accelerate healing but systemic ones, although Materials and Methods
effective, have side effects. Therefore, topical thera-
pies are the first choice.8 Here, we are to compare the Sixty patients with Behcet’s Syndrome who had
therapeutic effect of triamcinolone acetonide oint- oral aphthous lesions were assessed for eligibility
ment as a relatively expensive and not easily availa- to participate in this trial (IRCT code:
ble medication in Iran, with phenytoin syrup on aph- IRCT201107036920N2). It was their first visit and did
thous ulcers in patients with Behcet’s syndrome. not have any medication for the disease. All were vis-
Triamcinolone acetonide is a fluoride synthetic ited by a rheumatologist and a dentist. They all an-
corticosteroid. Its cream (0.1%) and ointment (0.1%) swered a questionnaire about demographic data, the
forms are available for topical use. The absorption age of Behcet’s syndrome onset, the most affected
rate varies from 1% in palms and knee to 36% in oral site with the aphthous ulcers, duration of ulcers
face, eyelash and genital area. Its absorption increases and severity of pain and burning. Then the dentist
via damaged, inflammed or dressed skin. Steroids visited them and recorded the site of aphthous lesions,
may have systemic absorption via oral mucosa.18 their size and number.
Metabolism of triamcinolone after topical applica- Thirty patients were randomly selected and treated
tion is dermal. The small amount which may enter by phenytoin syrup and other 30 ones were advised to
systemic circulation is metabolized in liver. Topical use 0.1% triamcinolone acetonide ointment. Those in
application’s side effects are burning, itching, irrita- triamcinolone group applied the ointment three times
tion, dryness, folliculitis, hirsutism, hyperpigmenta- a day on the lesions and had been advised not to have
tion, perioral dermatitis, contact allergic dermatitis, water or meal till 30 minutes. Those in phenytoin
secondary infections and atrophy.18 group used 2 teaspoon of syrup in half a glass of
Phenytoin was first made in 1908 and its anticon- warm water as mouthwash for 4-5 minutes, three
valescent effect was detected in 1938. The most times a day and had been advised not to have water or
common side effect of phenytoin is gingival hyper- meal till 30 minutes. After a week, they were visited
plasia. These effects were reported in 1939.19 Dill and again to determine the status of aphthous ulcers.
Iacopino reported a case of skin thickening due to In this study, the group treating by triamcinolone
long term application of phenytoin. Thickening oc- was named “ T” and the other named “P”. The
curred in face and Talon which revealed the prolifera- statistical analysis was performed using SPSS
tive effect of the medication on connective tissue software (Version 14.0, Chicago, IL, USA). We used
cells in whole body.20 Fisher’s Exact test and Independent t test to compare
In an animal study, the angiogenesis effect of positive response of the groups and the mean of
phenytoin was shown. It also led to decreased in- patients’ age, respectively.
flammation and bacterial colonies, necrosis and pro-
liferation of fibroblasts.21 Phenytoin affected epitheli-
um via keratinocyte growth factors and their receptors Results
which may have a significant role on wound healing.
Ghapanchi et al. applied phenytoin powder on wound There were 8 men and 22 women in each group
secondary to flap and reported less edema and in- (Table 1). The mean age in “T” group was
flammation and more granulation tissue and fibrosis. 35.47+8.85 years and in “P” group was 38.77+9.4
It also led to less pain and burning sensation and ac- years (Table 1). So the mean age and gender in these
celerated wound healing clinically.22 Phenytoin can two groups were almost equal and could not interfere
be used as syrup (125 mg/5 ml), ampule (250 mg/5 in the results (p>0.05). Among 30 patients in “T”

76 WWW.ircmj.com Vol 14 February 2012

 Phenytoin and triamcinolone in aphthous

Table 1: The demographic characteristics of patients treated with phenytoin (P group) and triamcinolone ace-
tonide (T group) a.

Sex Age (years)

Men Women Min Max Mean+-SD
P group 8 (26.7%) 22 (73.3%) 17 65 38.77+-9.4
T group 8 (26.7%) 22 (73.3%) 15 57 35.47+-8.85
a
p=0.167
group, 4 of them (13.3%) did not respond to the findings which shows that corticosteroids are effective
medication and 26 of them (86.7%) had a positive in treatment of aphthous lesions.
response. In “p” group, 14 of them (46.7%) did not In an animal study, Ghapanchi and colleagues applied
respond to the medication and 16 of them (53.3%) phenytoin powder on wound secondary to flap and
had a positive response. Statistical tests revealed that reported less edema and inflammation and more granu-
triamcinolone ointment had a better therapeutic effect lation tissue and fibrosis. It also led to less pain and
on aphthous lesions in patients with Behcet’s burning sensation and clinically an accelerated wound
syndrome (p=0.01). healing.22 In our study, healing of most aphthous ulcers
with phenytoin application resembled their results.
Discussion There was not any study to compare the effect of these
tow medications. In our study, the positive response to
Aphthous ulcer is the chief complain of a significant triamcinolone acetonide (86.7%) was more than phen-
percentage of patients visited by physicians or dentists. ytoin (53.3%) (p<0.05). So it is not logical to replace
It sometimes interferes with patients’ activities and phenytoin instead of triamcinolone; although triamcin-
decreases their quality of life because of severe pain olone ointment is more expensive and less available.
and burning. Some specialists have immunomodulative Triamcinolone acetonide ointment was shown to be
strategy. Brown and Bott applied combination of more effective than phenytoin on aphthous ulcers in
azathioprine and dexamethasone on aphthous ulcers, patients with Behcet’s syndrome.
topically and had a good result.24 Miles and Steven
revealed that triamcinolone acetonide is a useful
medication for aphthous lesion.24 This is similar to our Conflict of interest: None declared.

References

1 Gallo Cde B, Mimura MA, Sugaya aphthous stomatitis. Literature mucosal conditions--methodologic
NN. Psychological stress and review and open clinical trial issues. Community Dent Oral
recurrent aphthous stomatitis. employing steroids. Oral Surg Oral Epidemiol 1991;19:129-40. [186406
Clinics (Sao Paulo) 2009;64:645-8. Med Oral Pathol 1992;74:79-86. 4] [http://dx.doi.org/10.1111/j.1600-
[19606240] [1508514] [http://dx.doi.org/10.1016/ 0528.1991.tb00128.x]
2 Keogan MT. Clinical Immunology 0030-4220(92)90219-G] 8 Meng W, Dong Y, Liu J, Wang Z,
Review Series: an approach to the 5 Natah SS, Konttinen YT, Enattah Zhong X, Chen R , Zhou H, Lin M,
patient with recurrent orogenital NS, Ashammakhi N, Sharkey KA, Jiang L, Gao F, Xu T, Chen Q, Zeng
ulceration, including Behçet's Häyrinen-Immonen R. Recurrent X. A clinical evaluation of
syndrome. Clin Exp Immunol 2009; aphthous ulcers today: a review of ameloxanox oral adhesive pellicles
156:1-11. [19210521] [http://dx.doi.org/ the growing knowledge. Int J Oral in the treatment of recurrent
10.1111/j.1365-2249.2008.03857.x] Maxillofac Surg 2004;33:221-34. aphthous stomatitis and comparison
3 Mimura MA, Hirota SK, Sugaya NN, [15287304] [http://dx.doi.org/10. with ameloxanox oral tablets: a
Sanches Jr JA, Migliari DA. Systemic 1006/ijom.2002.0446] randomized, placebo controlled,
treatments in severe cases of 6 Reichart PA. Oral mucosal lesions blinded, multicenter clinical trial. Bio
recurrent aphthous stomatitis: an in a representative cross-sectional Med Central. http://www.trialsjournal.
open trial. Clinics (Sao Paulo) study of aging Germans. Community com/content/10/1/30. ( 6 May 2009)
2009;64:193-8. [19330244] [http:// Dent Oral Epidemiol 2000;28:390-8. 9 Barrons RW. Treatment strategies
dx.doi.org/10.1590/S1807-5932200 [11014516] [http://dx.doi.org/10.10 for recurrent oral aphthous ulcers.
9000300008] 34/j.1600-0528.2000.028005390.x] Am J Health Syst Pharm 2001;
4 Vincent SD, Lilly GE. Clinical, 7 Kleinman DV, Swango PA, Niessen 58:41-5. [11194135]
historic and therapeutic features of LC. Epidemiologic studies of oral

WWW.ircmj.com Vol 14 February 2012 77

 Fani et al.

10 Akintoye SO, Greenberg MS. 16 Natah SS, Konttinen YT, Enattah 20 Dill RE, Iacopino AM. Myofibroblasts
Recurrent aphthous stomatitis. Dent NS, Ashammakhi N, Sharkey KA, in phenytoin-induced hyperplastic
Clin North Am 2005;49:31-47, vii- Häyrinen-Immonen R. Recurrent connective tissue in the rat and in
viii. [15567359] [http://dx.doi.org/ aphthous ulcers today: a review of human gingival overgrowth. J
10.1016/j.cden.2004.08.001] the growing knowledge. Int J Oral Periodontol 1997;68:375-80. [915
11 Femiano F, Lanza A, Buonaiuto C, Maxillofac Surg 2004;33:221-34. [152 0043]
Gombos F, Nunziata M, Piccolo S, 87304] [http://dx.doi.org/10.1006/ 21 Vernillo AT, Schwartz NB. The effects
Cirillo N. Guidelines for diagnosis ijom.2002.0446] of phenytoin (5,5-diphenylhydantoin)
and management of aphthous 17 Scully C. Aphthous ulceration. N on human gingival fibroblasts in
stomatitis. Pediatr Infect Dis J 2007; Engl J Med 2006;355:165-72. [1683 culture. J Periodontal Res 1987;
26:728-32. [17848886] [http://dx. 7680] [http://dx.doi.org/10.1056/NE 22:307-12. [2957484] [http://dx.doi.
doi.org/10.1097/INF.0b013e318062 JMcp054630] org/10.1111/j.1600-0765.1987.tb01
15f9] 18 Khandwala A, Van Inwegen RG, 590.x]
12 Woo SB, Sonis ST. Recurrent Alfano MC. 5% amlexanox oral 22 Ghapanchi J,Haghighati F, Dehpoor
aphthous ulcers: a review of paste, a new treatment for recurrent GH. The reparative effect of
diagnosis and treatment. J Am Dent minor aphthous ulcers: I. Clinical Phenytoin on ulcers secondary to
Assoc 1996;127:1202-13. [8803396] demonstration of acceleration of gingival surgery. Journal of Dentistry
13 Ship JA, Chavez EM, Doerr PA, healing and resolution of pain. Oral 1999;131-35. [Persian]
Henson BS, Sarmadi M. Recurrent Surg Oral Med Oral Pathol Oral 23 Saber M.Iranian generic medication
aphthous stomatitis. Quintessence Radiol Endod 1997;83:222-30. [91 and classification of them. 1th ed.
Int 2000;31:95-112. [11203919] 17754] [http://dx.doi.org/10.1016/ Iran, Tehran, Noore Danesh; 2002.
14 Casiglia JM. Recurrent aphthous S1079-2104(97)90009-3] 24 Miles DA, Bricker SL, Razmus TF,
stomatitis: etiology, diagnosis, and 19 Laurence L. Brunton, John S. Lazo, Potter RH. Triamcinolone acetonide
treatment. Gen Dent 2002;50:157- Keith L. Parker. Drugs Acting on the versus chlorhexidine for treatment of
66. [12004710] central nervous system in: Goodman recurrent aphthous stomatitis. Oral
15 Scully C, Gorsky M, Lozada-Nur F. & Gilman’s The pharmacological Surg Oral Med Oral Pathol 1993;75:
th
The diagnosis and management of basis of therapeutics. 11 ed. New 397-402. [8469556] [http://dx.doi.org/
recurrent aphthous stomatitis: a York, Chicago, San Francisco, 2006: 10.1016/0030-4220(93)90158-Z]
consensus approach. J Am Dent p. 508-10.
Assoc 2003;134:200-7. [12636124]

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