Υποτροπιάζουσα αφθώδης στοματίτιδα: Τοπικοί και συστηματικοί προδιαθεσικοί παράγοντες
Ερωφίλη ΠΑΠΑΔΟΠΟΥΛΟΥ1, Νικόλαος ΝΙΚΗΤΑΚΗΣ2, Αλεξάνδρα ΣΚΛΑΒΟΥΝΟΥ-ANΔΡΙΚΟΠΟΥΛΟΥ3
Εργαστήριο Στοματολογίας, Οδοντιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
(Διευθύντρια: Καθηγήτρια Α. Σκλαβούνου-Ανδρικοπούλου)
Αρχεία Ελληνικής Στοματικής και Γναθοπροσωπικής Χειρουργικής (2009) 1, 35-45
ΠΕΡΙΛΗΨΗ: Ως υποτροπιάζουσα αφθώδης στοματίτιδα ορίζεται μία φλεγμονώδης κατάσταση
αγνώστου αιτιολογίας, η οποία χαρακτηρίζεται από επώδυνα, υποτροπιάζοντα, μονήρη ή πολλαπλά
έλκη του στοματικού βλεννογόνου. Ένας μεγάλος αριθμός τοπικών και συστηματικών παραγόντων
προδιαθέτει στην ανάπτυξη αφθωδών ελκώσεων καθιστώντας την ανεύρεση και άρση τους απαραί-
τητη προϋπόθεση για την αντιμετώπιση και αποφυγή υποτροπών.
Σκοπός της παρούσας εργασίας είναι η ανασκόπηση της βιβλιογραφίας σχετικά με την κλινική εικό-
να, την αιτιοπαθογένεια και τη θεραπευτική αντιμετώπιση των αφθωδών ελκώσεων, με ιδιαίτερη
έμφαση στην παράθεση των προδιαθεσικών παραγόντων.
Οι άφθες διακρίνονται κλινικά στις μικρές, τις μεγάλες και τα ερπητόμορφα έλκη. Η αιτιολογία τους
παραμένει άγνωστη μέχρι σήμερα και οι παθογενετικοί μηχανισμοί που εμπλέκονται δεν έχουν πλή-
ρως διαλευκανθεί. Στους τοπικούς προδιαθεσικούς παράγοντες ανήκουν το τραύμα, το κάπνισμα και
οι αντιδράσεις σε τροφές και χημικές ουσίες. Οι κυριότεροι συστηματικοί προδιαθεσικοί παράγο-
ντες μπορούν να ταξινομηθούν σε αιματολογικά νοσήματα, νοσήματα του γαστρεντερικού, διάφο-
ρα σύνδρομα και σε καταστάσεις που προκαλούν ανοσοκαταστολή. Στόχος της θεραπευτικής αντι-
μετώπισης είναι η ανακούφιση των συμπτωμάτων και η αποφυγή των υποτροπών, η οποία προϋπο-
θέτει την άρση των προδιαθεσικών παραγόντων.
ΛΕΞΕΙΣ ΚΛΕΙΔΙΑ: Άφθες, Υποτροπιάζοντα έλκη, Στοματικός βλεννογόνος, Προδιαθεσικοί παράγο-
ντες.
REFERENCES
Αγγελόπουλος A, Παπανικολάου Σ, Αγγελοπούλου E:
Σύγχρονη Στοματική και Γναθοπροσωπική Παθο-
λογία. Λίτσας 2000, σελ 679-681, 715-716.
Axell T, Henricsson V: Association between recurrent
aphthous ulcers and tobacco habits. Scand J Dent Res
93:239-242, 1985a
Axell T, Henricsson V: The occurence of recurrent aphthous
ulcers in an adult Swedish population. Acta
Odontol Scand 43:121-125, 1985b
Barrons RW: Treatment strategies for recurrent oral aphthous
ulcers. AJHP 58:41-53, 2001
Behcet H: Uber rezidivierende Aphthose, durch ein Virus
verursante Geschwure am Mund, am Auge und an
Genitalien. Dermatol Wochenschr 105: 1152-1157,
1937
Bhattacharyya A, Patel MK, Tymms DJ: Celiac disease in
adults. J R Soc Med 92:286-289, 1999
Boulingez S, Reix S, Bedane C, Debrock C, Bouyssou-
Gauthier ML, Sparsa A et al: Role of drug exposure in
aphthous ulcers: a case-control study. Br J Dermatol
143:1261-1265, 2000
Bruce AJ, Rogers RS 3rd: Acute oral ulcers. Dermatol Clin
21:1-15, 2003
Buno IJ, Huff JC, Weston WL, Cook DT, Brice SL: Elevated
levels of interferon gamma, tumor necrosis factor
alpha, interleukins 2, 4 and 5, but not interleukin 10,
are present in recurrent aphthous stomatitis. Arch
Dermatol 134:827-831, 1998
Castellini JL, Diaz-Guzman L: Lesions of the oral mucosa:
an epidemiological study of 23785 Mexican patients.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
105:79-85, 2008
Catassi C, Fabriani E, Corrao G, Barbato M, De Renzo A,
Carella AM: Risk of non-Hodgkin lymphoma in celiac
disease. JAMA 287:1413-1419, 2002
Chalacombe JJ, Batchelor JR, Kennedy LA, Lehner T: HLAantigens in recurrent oral ulcerations. Arch Dermatol
113:1717-1719, 1977
Chin S, Hoyan P, McKenzie S, Gibbs H, Strutton G, Wong
R: Mouth and Genital ulcers with inflammed cartilage
(MAGIC). Syndrome complicated by Aneurysmal
Aortitis. J Clin Rheumatol 13:221-223, 2007
Crivelli MR, Aguas S, Adler I, Quarracino C, Bazerque P:
Influence of sosioeconomic status on oral mucosa
lesion prevalence in schoolchildren. Com Dent Oral
Epidemiol 16:58-60, 1998
Dorsey C: More observations on relief of aphthous stomatitis
on resumption of cigarette smoking. Calif Med
101:377-378, 1964
Embil JA, Stephens RE, Mauriel R: Prevalence of recurrent
herpes labialis and aphthous ulcers among young adults
on six continents. CMAJ 113:630-637, 1975
Escudier M, Bagan J, Scully C: Behcet’s disease (Adamantiades
syndrome). Oral Dis 12:78-84, 2006
Evereklioglu C: Current concepts in the etiology and treatment
of Behcet disease. Surv Ophthalmol 50:297-
350, 2005
Fergusson MM, McKay HD, Lindsay R, Stephen KW: Progestin
therapy for menstrual related aphthae. Int J Oral
Surg 7:463-470, 1978
Fergusson MM, Wray D, Carmichael HA, Russel RI, Lee
FD: Coeliac disease associated with recurrent aphthae.
Gut 21:223-226, 1980
Fujimura Y, Kamoi R, Iida M: Pathogenesis of aphthoid
ulcers in Crohn’s disease: correlative findings by magnifying
colonoscopy, electron microscopy and immunohistochemistry.
Gut 38:724-732, 1996
Graykowski EA, Barile MF, Lee WB, Stanley HR: Recurrent
aphthous stomatitis. Clinical, therapeutic, histopathologic
and hypersensitivity aspects. JAMA 196:129-136,
1966
Healy CM, Thornhill MH: An association between recurrent
oro-genital ulceration and non-steroidal antiinflammatory
drugs. J Oral Pathol Med 24:46-48, 1995
International Study Group for Behcet’s Disease. Criteria
for diagnosis for Behcet’s disease. Lancet 335:1078-
1080, 1990
Jurge S, Kuffer R, Scully C, Porter SR: Recurrent aphthous
stomatitis. Oral Dis 12:1-21, 2006
Krause I, Rosen Y, Kaplan I, Milo G, Guedj D, Molad Y,
Weinberger A: Recurrent aphthous stomatitis in
Behcet’s disease: clinical features and correlation with
systemic disease expression and severity. J Oral Pathol
Med 28:193-196, 1999
Lahteenoja H, Toivanen A, Viander M, Maki M, Irjana K,
Raiha I: Oral mucosal changes in celiac patients on a
gluten-free diet. Eur J Oral Sci 106:899-906, 1998
Letsinger JA, McCarthy MA, Jorizzo J: Complex aphthosis:
a large case series with evaluation algorithm and therapeutic
ladder from topical to thalidomide. J Am Acad
Dermatol 52:500-508, 1996
Lindemann RA, Riviere GR, Sapp JR: Serum antibody responses
to indigenous oral mucosal antigens and selected
laboratory-maintained bacteria in recurrent
aphthous ulceration. Oral Surg Oral Med Oral Pathol
59:585-589, 1985
MacPhail LA, Greenspan D, Feigal DW, Lennette ET,
Greenspan JS: Recurrent aphthous ulcers in association
with HIV infection: description of ulcer types and
analysis of T-Lymphocyte subsets. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 71:678-683,1991
MacPhail LA, Greenspan D, Greenspan JS: Recurrent aphthous
ulcers in association with HIV infection. Diagnosis
and treatment. Oral Surg Oral Med Oral Pathol
73:283-288, 1992
Marshall GS, Edwards KM, Lawton AR: PFAPA syndrome.
Pediatr Infect Dis J 8:658-659, 1989
Martin DK, Nelms DC, Mackler BF, Peavy DL: Lymphoproliferative
responses induced by streptococcal
antigens in recurrent aphthous stomatitis and Behcet’s
syndrome. Clin Immunol Immunopathol 13:146-155,
1979
Miller MF, Garfunkel AA, Ram CA, Ship II: The inheritance
of recurrent aphthous stomatitis. Observations on
susceptibility. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 49:409-412, 1980
Miller MF, Ship II: A retrospective study of the prevalence
and incidence of recurrent aphthous ulcers in a professional
population, 1958-1971. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 43:532-537, 1977
Miziara I, Filbo, Weber R: AIDS and recurrent aphthous
stomatitis. Br J Otorhinolaryng 71:517-520, 2005
Muzyca BC, Glick M: Major aphthous ulcers in patients
with HIV disease. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 77:116-120, 1994
Natah SS, Hayrinen-Immonen R, Hietanen J, Malmstrom
M, Kontinen TT: Immunolocalization of tumor necrosis
factor-a expressing cells in recurrent aphthous ulcer
lesions. J Oral Pathol Med 29:19-25, 2000
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KA, Hayrinen-Immonen R: Recurrent aphthous
ulcers today: a review of the growing knowledge. Int J
Oral Maxillofac Surg 33:221-234, 2004
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Nolan A, McIntosh WB, Allam BF, Lamey PJ: Recurrent
aphthous ulceration: Vitamin B1, B2 and B6 status and
response to replacement therapy. J Oral Pathol Med
20:389-391, 1991a
Nolan A, Lamey PJ, Milligan KA, Forsyth A: Recurrent
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Med 20:473-475, 1991b
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syndrome (Mouth and Genital ulcers with Inflammed
Cartilage). Arch Dermatol 126:940-944, 1990
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Endod 83:325-328, 1997
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Porter SR, Flint S, Scully C, Keith O: Recurrent aphthous
stomatitis: the efficacy of replacement therapy in patients
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51:14-16, 1992
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lesions, the influence of tobacco habits and an
estimate of treatment time in a Swedish population. J
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Scully C, Gorsky M, Lozada-Nur F: The diagnosis and
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Εργαστήριο Στοματολογίας, Οδοντιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
(Διευθύντρια: Καθηγήτρια Α. Σκλαβούνου-Ανδρικοπούλου)
Αρχεία Ελληνικής Στοματικής και Γναθοπροσωπικής Χειρουργικής (2009) 1, 35-45
ΠΕΡΙΛΗΨΗ: Ως υποτροπιάζουσα αφθώδης στοματίτιδα ορίζεται μία φλεγμονώδης κατάσταση
αγνώστου αιτιολογίας, η οποία χαρακτηρίζεται από επώδυνα, υποτροπιάζοντα, μονήρη ή πολλαπλά
έλκη του στοματικού βλεννογόνου. Ένας μεγάλος αριθμός τοπικών και συστηματικών παραγόντων
προδιαθέτει στην ανάπτυξη αφθωδών ελκώσεων καθιστώντας την ανεύρεση και άρση τους απαραί-
τητη προϋπόθεση για την αντιμετώπιση και αποφυγή υποτροπών.
Σκοπός της παρούσας εργασίας είναι η ανασκόπηση της βιβλιογραφίας σχετικά με την κλινική εικό-
να, την αιτιοπαθογένεια και τη θεραπευτική αντιμετώπιση των αφθωδών ελκώσεων, με ιδιαίτερη
έμφαση στην παράθεση των προδιαθεσικών παραγόντων.
Οι άφθες διακρίνονται κλινικά στις μικρές, τις μεγάλες και τα ερπητόμορφα έλκη. Η αιτιολογία τους
παραμένει άγνωστη μέχρι σήμερα και οι παθογενετικοί μηχανισμοί που εμπλέκονται δεν έχουν πλή-
ρως διαλευκανθεί. Στους τοπικούς προδιαθεσικούς παράγοντες ανήκουν το τραύμα, το κάπνισμα και
οι αντιδράσεις σε τροφές και χημικές ουσίες. Οι κυριότεροι συστηματικοί προδιαθεσικοί παράγο-
ντες μπορούν να ταξινομηθούν σε αιματολογικά νοσήματα, νοσήματα του γαστρεντερικού, διάφο-
ρα σύνδρομα και σε καταστάσεις που προκαλούν ανοσοκαταστολή. Στόχος της θεραπευτικής αντι-
μετώπισης είναι η ανακούφιση των συμπτωμάτων και η αποφυγή των υποτροπών, η οποία προϋπο-
θέτει την άρση των προδιαθεσικών παραγόντων.
ΛΕΞΕΙΣ ΚΛΕΙΔΙΑ: Άφθες, Υποτροπιάζοντα έλκη, Στοματικός βλεννογόνος, Προδιαθεσικοί παράγο-
ντες.
REFERENCES
Αγγελόπουλος A, Παπανικολάου Σ, Αγγελοπούλου E:
Σύγχρονη Στοματική και Γναθοπροσωπική Παθο-
λογία. Λίτσας 2000, σελ 679-681, 715-716.
Axell T, Henricsson V: Association between recurrent
aphthous ulcers and tobacco habits. Scand J Dent Res
93:239-242, 1985a
Axell T, Henricsson V: The occurence of recurrent aphthous
ulcers in an adult Swedish population. Acta
Odontol Scand 43:121-125, 1985b
Barrons RW: Treatment strategies for recurrent oral aphthous
ulcers. AJHP 58:41-53, 2001
Behcet H: Uber rezidivierende Aphthose, durch ein Virus
verursante Geschwure am Mund, am Auge und an
Genitalien. Dermatol Wochenschr 105: 1152-1157,
1937
Bhattacharyya A, Patel MK, Tymms DJ: Celiac disease in
adults. J R Soc Med 92:286-289, 1999
Boulingez S, Reix S, Bedane C, Debrock C, Bouyssou-
Gauthier ML, Sparsa A et al: Role of drug exposure in
aphthous ulcers: a case-control study. Br J Dermatol
143:1261-1265, 2000
Bruce AJ, Rogers RS 3rd: Acute oral ulcers. Dermatol Clin
21:1-15, 2003
Buno IJ, Huff JC, Weston WL, Cook DT, Brice SL: Elevated
levels of interferon gamma, tumor necrosis factor
alpha, interleukins 2, 4 and 5, but not interleukin 10,
are present in recurrent aphthous stomatitis. Arch
Dermatol 134:827-831, 1998
Castellini JL, Diaz-Guzman L: Lesions of the oral mucosa:
an epidemiological study of 23785 Mexican patients.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
105:79-85, 2008
Catassi C, Fabriani E, Corrao G, Barbato M, De Renzo A,
Carella AM: Risk of non-Hodgkin lymphoma in celiac
disease. JAMA 287:1413-1419, 2002
Chalacombe JJ, Batchelor JR, Kennedy LA, Lehner T: HLAantigens in recurrent oral ulcerations. Arch Dermatol
113:1717-1719, 1977
Chin S, Hoyan P, McKenzie S, Gibbs H, Strutton G, Wong
R: Mouth and Genital ulcers with inflammed cartilage
(MAGIC). Syndrome complicated by Aneurysmal
Aortitis. J Clin Rheumatol 13:221-223, 2007
Crivelli MR, Aguas S, Adler I, Quarracino C, Bazerque P:
Influence of sosioeconomic status on oral mucosa
lesion prevalence in schoolchildren. Com Dent Oral
Epidemiol 16:58-60, 1998
Dorsey C: More observations on relief of aphthous stomatitis
on resumption of cigarette smoking. Calif Med
101:377-378, 1964
Embil JA, Stephens RE, Mauriel R: Prevalence of recurrent
herpes labialis and aphthous ulcers among young adults
on six continents. CMAJ 113:630-637, 1975
Escudier M, Bagan J, Scully C: Behcet’s disease (Adamantiades
syndrome). Oral Dis 12:78-84, 2006
Evereklioglu C: Current concepts in the etiology and treatment
of Behcet disease. Surv Ophthalmol 50:297-
350, 2005
Fergusson MM, McKay HD, Lindsay R, Stephen KW: Progestin
therapy for menstrual related aphthae. Int J Oral
Surg 7:463-470, 1978
Fergusson MM, Wray D, Carmichael HA, Russel RI, Lee
FD: Coeliac disease associated with recurrent aphthae.
Gut 21:223-226, 1980
Fujimura Y, Kamoi R, Iida M: Pathogenesis of aphthoid
ulcers in Crohn’s disease: correlative findings by magnifying
colonoscopy, electron microscopy and immunohistochemistry.
Gut 38:724-732, 1996
Graykowski EA, Barile MF, Lee WB, Stanley HR: Recurrent
aphthous stomatitis. Clinical, therapeutic, histopathologic
and hypersensitivity aspects. JAMA 196:129-136,
1966
Healy CM, Thornhill MH: An association between recurrent
oro-genital ulceration and non-steroidal antiinflammatory
drugs. J Oral Pathol Med 24:46-48, 1995
International Study Group for Behcet’s Disease. Criteria
for diagnosis for Behcet’s disease. Lancet 335:1078-
1080, 1990
Jurge S, Kuffer R, Scully C, Porter SR: Recurrent aphthous
stomatitis. Oral Dis 12:1-21, 2006
Krause I, Rosen Y, Kaplan I, Milo G, Guedj D, Molad Y,
Weinberger A: Recurrent aphthous stomatitis in
Behcet’s disease: clinical features and correlation with
systemic disease expression and severity. J Oral Pathol
Med 28:193-196, 1999
Lahteenoja H, Toivanen A, Viander M, Maki M, Irjana K,
Raiha I: Oral mucosal changes in celiac patients on a
gluten-free diet. Eur J Oral Sci 106:899-906, 1998
Letsinger JA, McCarthy MA, Jorizzo J: Complex aphthosis:
a large case series with evaluation algorithm and therapeutic
ladder from topical to thalidomide. J Am Acad
Dermatol 52:500-508, 1996
Lindemann RA, Riviere GR, Sapp JR: Serum antibody responses
to indigenous oral mucosal antigens and selected
laboratory-maintained bacteria in recurrent
aphthous ulceration. Oral Surg Oral Med Oral Pathol
59:585-589, 1985
MacPhail LA, Greenspan D, Feigal DW, Lennette ET,
Greenspan JS: Recurrent aphthous ulcers in association
with HIV infection: description of ulcer types and
analysis of T-Lymphocyte subsets. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 71:678-683,1991
MacPhail LA, Greenspan D, Greenspan JS: Recurrent aphthous
ulcers in association with HIV infection. Diagnosis
and treatment. Oral Surg Oral Med Oral Pathol
73:283-288, 1992
Marshall GS, Edwards KM, Lawton AR: PFAPA syndrome.
Pediatr Infect Dis J 8:658-659, 1989
Martin DK, Nelms DC, Mackler BF, Peavy DL: Lymphoproliferative
responses induced by streptococcal
antigens in recurrent aphthous stomatitis and Behcet’s
syndrome. Clin Immunol Immunopathol 13:146-155,
1979
Miller MF, Garfunkel AA, Ram CA, Ship II: The inheritance
of recurrent aphthous stomatitis. Observations on
susceptibility. Oral Surg Oral Med Oral Pathol Oral
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