Вы находитесь на странице: 1из 8


Oral mucosal fixed drug eruption: Characteristics and

differential diagnosis

Esen Ozkaya, MD
Istanbul, Turkey

Background: Little is known about the characteristic features of oral mucosal fixed drug eruption (FDE).

Objective: To present the clinical highlights and the differential diagnosis of oral mucosal FDE in a
relatively large group of patients from Turkey.

Methods: This was a methodological, retrospective, cross-sectional study of 61 patients with oral mucosal
FDE. The causative drug was established mainly by oral provocation test.

Results: The age range of 61 patients (38 females, 23 males) was 7 to 62 years. Naproxen and
cotrimoxazole were the main inducers. Fourteen patients (23%) had a solitary oral lesion predominantly
located on the dorsum of the tongue, or on the hard palate, the former statistically significantly associated
with cotrimoxazole. Bullous/erosive (n = 47), aphthous (n = 12), and erythematous (n = 2) morphology
were observed. A considerable number of patients were referred with a prior clinical diagnosis of herpes
simplex and Behcets disease; some of them were already receiving long-term treatment with acyclovir and
colchicine, respectively.

Limitations: The main limitation of the present study resides in its retrospective design.

Conclusions: Isolated oral lesions, aphthous lesions, severe bullous/erosive lesions, and the absence of
residual pigmentation are the main features that may cause difficulties in the differential diagnosis. It is
important to differentiate dysmenorrhea-related monthly attacks of oral FDE in female patients caused by
nonsteroidal anti-inflammatory drugs from menstruation-triggered attacks of herpes simplex infection, and
isolated orogenital aphthous FDE from Behcets disease, especially in countries with a high frequency of
the disease in order to prevent irrelevant therapies. ( J Am Acad Dermatol 10.1016/j.jaad.2012.08.019.)

Key words: behcets disease; bullous; differential diagnosis; erosive; fixed drug eruption; gingival; herpes;
mucosal; oral; palate; tongue.

Abbreviations used:
Fixed drug eruption (FDE) is characterized by
recurrent site-specific lesions on the skin and/or EM: erythema multiforme
FDE: fixed drug eruption
mucosa each time the responsible drug is taken. Oral NSAID: nonsteroidal anti-inflammatory drug
mucosal lesions often accompany the characteristic
skin lesions, but sometimes they may occur alone or in
combination with genital/other mucosal involvement. different clinical manifestations of oral mucosal FDE is
The absence of skin lesions is a diagnostic challenge mainly based on case reports, and a few clinical studies
to the physician because of the wide spectrum of with a relatively small number of cases. The aim of this
differential diagnostic conditions. Our knowledge of study is to present the clinical highlights and the

From the Department of Dermatology and Venereology, Istanbul Correspondence to: Esen Ozkaya, MD, _Istanbul Universitesi

University, _Istanbul Medical Faculty. _Istanbul Tp Fak ultesi, Deri ve Z
uhrevi Hastalklar Anabilim
Funding sources: None. Dal, 34093 _Istanbul, Turkey. E-mail: profeo@istanbul.edu.tr.
Conflicts of interest: None declared. Published online October 5, 2012.
Accepted for publication August 12, 2012. 0190-9622/$36.00
Reprints not available from the authors. 2012 by the American Academy of Dermatology, Inc.



differential diagnosis of oral mucosal FDE in with regard to age, gender, responsible drug, local-
a relatively large number of patients from Turkey, a ization, number and morphology of oral lesions,
country with a high frequency of the disease.1 additional mucosal and/or skin involvement, num-
ber of attacks, and prior diagnoses of the condition.
METHODS Patients with lip involvement without oral mucosal
This was a methodological, retrospective, cross- lesions were not included.
sectional study based on the analysis of patients data Histopathologic examination was performed
derived from the standard only in the presence of ad-
medical history forms pre- ditional skin lesions. Among
pared for the precise clinical CAPSULE SUMMARY 61 patients, 37 had addi-
documentation of FDE pa- tional skin involvement.
d The literature lacks a comprehensive
tients in our clinic. Skin punch biopsy and
study on oral mucosal FDE.
Between January 1996 and histopathologic examination
May 2011, 269 patients with d Oral FDE presents with bullous/erosive, was performed in 15 of these
suspected FDE were seen. Of aphthous, or erythematous morphology. 37 patients.
them, 78 did not revisit us. In The hard palate and dorsum of the Data were stored and
184 of the remaining 191 pa- tongue are the preferred sites. Aphthous assessed using SPSS for
tients, an oral provocation lesions, severe bullous/erosive lesions, Windows Release 15.0 ver-
test was performed as de- isolated oral involvement, and lack of sion. The chi-square test was
scribed previously,2 after residual pigmentation cause difficulties used for the comparisons. A
written or oral consent of in the differential diagnosis. two-tailed P value less than
patients and of parents or d Recurrent oral lesions in patients with a .05 was taken to indicate a
legal guardians in children, prior diagnosis of menstruation- statistically significant associ-
to establish the causative triggered herpes simplex or Behcets ation. The study was
agent. First, a list of suspected disease should be evaluated carefully assessed and approved by
drugs was prepared for each with regard to FDE. the institutional ethics
individual patient according committee.
to a detailed history of drug
intake. Four weeks after the clearance of the lesions, RESULTS
the oral challenge was performed starting with the The age range of 61 patients (38 females, 23
least suspected drug. Drug challenge was started with males; female/male = 1.7) was 7 to 62 years (median:
one-eighth of a single dose. Doses were increased at 32). Two patients were younger than 10 years old.
12- to 24-hour intervals to one-fourth, one-half, and The occurrence of drug hypersensitivity ranged from
one full dose, if necessary. The test was considered 1 month to more than 10 years (median: 12 months).
positive if the previously involved sites reactivated The number of attacks ranged between one and
with marked erythema/edema, accompanied by more than 10 times. At the time of diagnosis, 6
itching or burning. If no reaction occurred with that patients (9.8%) had had their first attack, whereas 8
drug, the next suspected drug, according to the (13.1%) had had more than 10 attacks. Oral mucosal
patients history, was tested in the same manner after lesions were present since the first FDE attack in 52
an interval of 2 to 3 days. If reactivation occurred with patients (85.2%), whereas 9 patients (14.8%) had
the first drug, the next suspected drug was tested only developed lesions during subsequent attacks. Pain
after the complete subsidence of the first reaction. A and burning were the major symptoms.
drug was considered causative if the challenge test Histopathologic examination, performed in 15 of
was positive. 37 patients with additional skin involvement showed
The diagnosis of FDE could be confirmed in 169 an interface dermatitis characterized by dyskeratosis,
patients, whereas oral provocation test with sus- hydropic degeneration of the basal cells, melano-
pected drugs remained negative in 15 patients. An phages in the papillary dermis, and mononuclear
additional 7 patients were diagnosed according to a perivascular inflammatory infiltration, that was con-
definite history of a single specific drug intake prior sistent with the diagnosis of FDE.
to the eruption and site-specific recurrence.
Photodocumentation was performed in a majority Localization
of patients. Oral mucosal lesions were part of orogenital FDE
Among a total of 176 patients with established in 42 patients (68.8%), either seen as isolated
FDE, 61 patients with oral mucosal involvement orogenital FDE in 14 patients or as orogenital and
comprised the study group. Their files were analyzed skin lesions in 28 patients. Conjunctival and nasal
Ozkaya e3

Table I. Involved FDE sites by the causative drugs with special regard to solitary oral lesions
Localization (no.) Causative agent (no.) Significance
Orogenital 1 skin (28) Cotrimoxazole (13), naproxen (11), piroxicam (2), dipyrone (1), NS
etodolac (1)
Orogenital only (14) Naproxen (7), cotrimoxazole (6), piroxicam (1) NS
Oral 1 skin (10) Naproxen (7), cotrimoxazole (2), piroxicam (1) NS
Oral only (9) Naproxen (5), cotrimoxazole (2), phenobarbital (1), ornidazole (1) NS
Oral solitary lesion (14) Cotrimoxazole (8), naproxen (4), piroxicam (1), ornidazole (1) NS
Dorsum of the tongue* (8) Cotrimoxazole* (7), naproxen (1) P = .009 (Fishers
exact test)
Hard palate (5) Naproxen (3), cotrimoxazole (1), piroxicam (1) NS
Inner lip (1) Ornidazole (1)

FDE, Fixed drug eruption; NS, not statistically significant.

*Solitary FDE on dorsum of the tongue was almost exclusively induced by cotrimoxazole.

mucosal involvement accompanied the lesions in 2 other drugs (22%). The differences were statistically
patients. Ten patients (16.4%) had oral mucosal and not significant.
skin lesions, whereas 9 (14.8%) had only oral muco- Solitary lesions on the tongue (n = 8) were almost
sal involvement. Lips were involved in 33 patients exclusively induced by cotrimoxazole (n = 7; Fishers
(54.1%). There was no statistically significant rela- exact test, P \ .05) with a female predominance of
tionship between lip involvement and accompany- 80%. Solitary lesions on the hard palate (n = 5) were
ing oral mucosal involvement. caused by naproxen (n = 3), cotrimoxazole (n = 1)
Fourteen patients (23%) had a solitary oral lesion. and piroxicam (n = 1). Involved FDE sites and the
Solitary oral mucosal lesions (n = 14) were most causative drugs are shown in Table I.
frequently located on the dorsum of the tongue
(n = 6), on the hard palate (n = 5), inner lip mucosa Morphology
(n = 1), on the ventral (n = 1), and on the lateral side Three major morphological forms were observed
of the tongue (n = 1). Multiple oral lesions in the (Table II): Bullous/erosive (n = 47, 77.1%) (Figs 1
remaining patients were mainly located on the and 2), aphthous (n = 12, 19.7%) (Fig 3, A and B),
inner lip and buccal mucosa followed by gingival and erythematous (n = 2, 3.2%) (Fig 3, C and D).
mucosa. Bullous/erosive lesions were mainly located on the
inner lip and buccal mucosa (n = 27, 57.4%).
Causative agent Solitary lesions on the dorsum of the tongue and
The causative agent was verified by oral provo- on the hard palate were almost exclusively bullous/
cation test in 54 patients (89%) and clinically by the erosive (Fig 2). Bullous/erosive lesions of the dor-
presence of a definite history of a single specific drug sum of the tongue were almost exclusively induced
intake prior to the eruption and site-specific recur- by cotrimoxazole (P \.001). Aphthous lesions were
rence in 7 patients (11%). In a majority of patients, mainly located on the inner lip mucosa (83.4%).
positive results were achieved with one-eighth of a Erythematous lesions were located on the inner lip
single dose. The time required for the positive mucosa (n = 1) and the dorsum of the tongue (n =
reaction to start ranged between 10 minutes and 12 1). Oral mucosal lesions healed without residual
hours. Dissemination of the lesions did not occur pigmentation.
following oral provocation.
Naproxen was the cause of FDE in 30 patients Prior diagnoses
(49.2%), followed by trimethoprim-sulfamethoxazole Twenty-seven patients (44.3%) were referred to
(cotrimoxazole) in 23 patients (37.7%), piroxicam in our clinic with a prior clinical diagnosis of the
4 patients (6.6%), dipyrone in 1 patient (1.6%), following conditions: Behcets disease in 10 pa-
etodolac in 1 patient (1.6%), phenobarbital in 1 patient tients with recurrent aphthous oral FDE and addi-
(1.6%), and ornidazole in 1 patient (1.6%). Sensitivity tional genital involvement, menstruation-triggered
to more than one drug was not observed. herpes simplex infection in 9 female patients with
Orogenital lesions were mainly induced by co- oral FDE of bullous/erosive (n = 5) or aphthous
trimoxazole (45.2%) and naproxen (42.9%). Isolated morphology (n = 4) recurring monthly during
oral mucosal lesions were mainly induced by na- menstruation due to oral intake of nonsteroidal
proxen (56%), followed by cotrimoxazole (22%) and anti-inflammatory drugs (NSAIDs) because of


Table II. Different morphologic types of FDE lesions causing difficulties in the clinical differential diagnosis
Morphology (%) Mainly involved site Prior clinical diagnoses (no.)
Bullous/erosive (77.1) Inner lip/buccal mucosa/gingiva Herpes simplex* (5), pemphigus vulgaris (2), erythema
multiforme major (2), erosive oral lichen planus (1),
oral candidiasis (1), food allergy (1), vitamin deficiency (1)
Aphthous (19.7) Inner lip mucosa Behcets diseasey (10; 2 of them received colchicine), herpes
simplex* (4; 2 of them were receiving long-term oral
acyclovir therapy)
Erythematous (3.2) Inner lip mucosa/dorsum of tongue None

FDE, Fixed drug eruption.

*Those patients with a prior clinical diagnosis of herpes simplex infection were female patients who were taking non-steroidal anti-
inflammatory drugs because of dysmenorrhea. The monthly recurrence of lesions during menstruation was erroneously attributed to herpes
simplex infection.
Patients with a prior clinical diagnosis of Behcets disease were those with recurrent aphthous orogenital FDE.

Fig 1. Oral mucosal FDE. Mild erosive lesions on the lower lip mucosa (A), severe bullous/
erosive lesions on the upper lip mucosa (B), on the lower lip mucosa (C), and on the palatal
and inner lip mucosa (D). Disseminated bullous/erosive lesions deserve special attention in
order to differentiate the condition from pemphigus vulgaris as well as severe drug eruptions
such as EM major or Stevens-Johnson syndrome.

dysmenorrhea, pemphigus vulgaris in 2 patients colchicine, and 2 of 9 patients with the prior clinical
with disseminated bullous/erosive FDE on the diagnosis of menstruation-triggered herpes sim-
cheek or inner lip mucosa, erythema multiforme plex were receiving long-term oral acyclovir ther-
(EM) major in 2 patients, erosive oral lichen planus, apy. However, none of the patients improved on
oral candidiasis, food allergy, and vitamin defi- therapy with colchicine or acyclovir. In these pa-
ciency in 1 patient each mainly with bullous/ tients, the correct diagnosis of FDE was made by
erosive FDE (Table II). There was no correlation establishing the causative drug by oral provocation.
between the prior diagnosis and the number of No other attack was observed upon avoidance of the
attacks. causative drug. The medications, prescribed by the
Two of 10 patients with the prior clinical referring physician, were stopped after the correct
diagnosis of Behcets disease were given diagnosis of FDE.
Ozkaya e5

Fig 2. Oral mucosal FDE. Solitary bullous/erosive lesion on dorsum of the tongue (A and B)
and on the hard palate (C and D) (arrows). Solitary oral lesions in these locations seem to be
highly suggestive of oral mucosal FDE.

DISCUSSION cotrimoxazole in our study. Moreover, naproxen

A review of the literature primarily focused on was the main inducer of solitary FDE on the
oral mucosal FDE revealed less than 40 cases palatal mucosa. Cotrimoxazole and naproxen are
mainly reported as single case reports from India known as the leading causes of FDE in our
and Spain (Table III).3-19 Similar to our findings, country.2,20
the considerable number of solitary oral FDE The bullous/erosive type of lesions predominated
mainly involving the hard palate and the dorsum in previous reports, followed by erythematous le-
of the tongue was striking. However, the inducer sions. In our study, however, aphthous lesions were
drugs were variable. Solitary FDE on the dorsum the second most frequent morphologic type that had
of the tongue was almost exclusively induced by not been reported previously.


Fig 3. Oral mucosal FDE. Multiple aphthous lesions on lower lip mucosa (A), solitary aphthous
lesion on buccal mucosa (B), solitary erythematous lesion on lower lip mucosa (C), and solitary
erythematous lesion on dorsum of tongue with central bullae (D). Aphthous lesions deserve
special attention in order to differentiate the condition, especially from herpes simplex
infection or Behcets disease.

A previous study from Pakistan reported 17 of 450 history of site-specific attacks, and reactivation of old
FDE cases with oral mucosal involvement.21 Buccal lesions upon oral challenge helped to diagnose
mucosa, gums, soft and hard palate, floor of the our cases as FDE and to differentiate it from
mouth, undersurface of the tongue, and posterior drug-induced recurrent EM or a lichenoid drug
pharyngeal wall were affected, but other character- eruption with similar histopathologic findings.
istic features of these patients were not mentioned.21 Round to oval, sharply demarcated, red to livid,
Residual pigmentation was not observed in our slightly elevated plaques of 4 to 5 cm in diameter
study, and it has been reported rarely previously.5,6 were characteristic skin lesions for FDE, whereas
Indeed, it is usually absent in oral mucosal FDE numerous, smaller, typical or atypical targetoid le-
lesions or less obvious than in skin lesions.22 The sions, or shiny flat papules would be expected in
lingual mucosa is known as the rarest site to show drug-induced EM or lichenoid drug eruption, re-
melanin.23 spectively. Oral mucosal lesions may accompany as
Isolated mucosal FDE without additional skin reticular and/or erosive lesions in lichenoid drug
involvement is a rare finding.3,4 The diagnosis of eruption, or as disseminated bullous/erosive lesions
FDE with isolated oral mucosal involvement is al- accompanied by fever and often malaise in more
ways a challenge to the physician. A solitary bullous/ severe forms of drug-induced EM, that is EM major,
erosive lesion should be distinguished from major Stevens-Johnson syndrome. In our patients, the
aphthous ulcer, primary or secondary syphilitic le- course was uncomplicated with lack of fever and
sions (eg, chancre, mucous plaque) or irritant lesions systemic symptoms. Site-specific recurrence of the
such as thermal burns. On the other hand, it might be lesions by therapeutic or diagnostic rechallenge with
difficult to differentiate multiple erosive FDE from the inducer drug is the main differential diagnostic
pemphigus vulgaris or bullous drug eruptions such finding of FDE. In contrast, recurrent lesions in drug-
as EM major or Stevens-Johnson syndrome. induced EM or lichenoid drug eruption show no
Histopathologic examination of skin lesions, per- predilection for previously involved sites.
formed in 15 patients, showed an interface derma- The most striking finding in our study was that
titis. Characteristic morphology of the skin lesions, female patients with dysmenorrhea-related recurrent
Table III. Overview of the previously reported cases with oral mucosal FDE (excluding lips)
Additional involvement Inducer established
Author (country) No. of cases No. of lesions Localization (no. of cases) Morphology (S/G/O) (no. of cases) Inducer by (no. of cases) RP
Kanwar (India) 1 Solitary Junction of hard/soft palate B/E No Novalgin tablet OPT NM
Browne4 (Nigeria) 20 NM Hard palate (2), gingival (1), NM S, O (conjunctival, NM History/TPT/OPT *NM
tongue (1), buccal (16) nasal mucosa)
Tagami5 (Japan) 1 Multiple Dorsum of tongue Erythematous No Aminopyrine OPT Yes
Westerhof6 (Holland) 1 Multiple Dorsum of tongue B/E (ulcerations) No Heroin No Yes
Jain7 (India) 2 NM Tongue (1), hard palate (1) B/E No NM OPT NM
Mahendra8 (India) 1 Solitary Hard palate B/E No Fluconazole OPT NM
Heikkila9 (Finland) 1 Multiple Oral mucosa B/E S Fluconazole TPT NM
Handisurya10 (Austria) 2 Multiple Oral mucosa and tongue B/E S (2), O (1: conjunctival) Mefenamic acid TPT (1), OPT (1) NM
Montoro11 (Spain) 1 Multiple Oral mucosa B/E (ulcerations) S, G Piroxicam TPT No
Gupta12 (India) 1 Solitary Lower lip mucosa B/E No Ornidazole OPT NM
Gazquez13 (Spain) 1 Multiple Oral mucosa, tongue Erythematous S Quinine OPT No
Alonso14 (Spain) 1 Solitary Dorsum of tongue Erythematous No Clarithromycin OPT Yes
Alvarez Santullano15 1 Multiple Oral mucosa, tongue, palate B/E, erythematous S Ibuprofen TPT NM
Gupta16 (India) 1 Solitary Hard palate B/E No Gabapentin OPT NM
Moreno Escobosa17 1 Solitary Hard palate Erythematous S Trimethoprim OPT NM
Murray18 (USA) 1 Solitary Hard palate B/E No Tetracycline Definite history NM
Naik19 (India) 1 2 Dorsum of tongue B/E S Erithromycin No NM
This study (Turkey) 61 Multiple (47), See Tables I and II B/E (47), aphthous (12), See Table I See Table I OPT (54)/Definite No
solitary (14) erythematous (2) history (7)

B/E, Bullous/erosive; G, genital mucosa; NM, not mentioned; O, other mucosa; OPT, oral provocation test; RP, residual pigmentation; S, skin; TPT, topical provocation tests; these were performed in
healed skin lesions.
*Difficult to establish in deeply pigmented patients.



oral FDE from NSAIDs were frequently misdiag- countries with a high frequency of the disease,
nosed as menstruation-triggered herpes simplex. such as Turkey. Therefore, a high degree of suspi-
The monthly attacks had even led to long-term oral cion and exclusion of other differential diagnostic
acyclovir therapy in 2 patients. Recurrent orogenital conditions are sine qua non for a correct diagnosis of
aphthous lesions, on the other hand, were misdiag- oral mucosal FDE to prevent patients from receiving
nosed as Behcets disease in 10 patients, leading to irrelevant treatments.
the start of treatment with colchicine in 2 patients. In
all these patients, the correct diagnosis of FDE was REFERENCES
made by establishing the causative drug by oral 1. Ozkaya E, Akar U. Fixed drug eruption induced by
provocation. trimethoprim-sulfamethoxazole: evidence for a link to HLA-A30
Systemic provocation is the gold standard for B13 Cw6 haplotype. J Am Acad Dermatol 2001;45:712-7.
identifying the causative drug in FDE. It is a safe and 2. Ozkaya E. Fixed drug eruption: state of the art. J Dtsch
Dermatol Ges 2008;6:181-8.
still the most reliable method for the diagnosis of FDE 3. Kanwar AJ, Dhar S, Ghosh S, Kaur S. Mucosal fixed drug
with a high sensitivity and specificity. However, it eruption. Dermatology 1994;188:171.
may lead to generalized bullous lesions in some 4. Browne SG. Fixed eruption in deeply pigmented subjects:
cases. Therefore the suspected drug should be clinical observations on 350 patients. Br Med J 1964;2:1041-4.
5. Tagami H. Pigmented macules of the tongue following fixed
administered in graded doses starting with a sub-
drug eruption. Dermatologica 1973;147:157-60.
therapeutic dose (eg, one-eighth of a single dose) 6. Westerhof W, Wolters EC, Brookbakker JT, Boelen RE, Schipper
until the full therapeutic dose is achieved. This would ME. Pigmented lesions of the tongue in heroin addictsfixed
elicit a positive reaction at the lowest possible dose. drug eruption. Br J Dermatol 1983;109:605-10.
When multiple drugs are suspected, it is advisable to 7. Jain VK, Dixit VB, Archana. Fixed drug eruption of the oral
start with the least susceptible drug. Only one drug mucous membrane. Ann Dent 1991;50:9-11.
8. Mahendra A, Gupta S, Gupta S, Sood S, Kumar P. Oral fixed
should be tested at a time. The optimal time point for drug eruption due to fluconazole. Indian J Dermatol Venereol
systemic provocation is not defined, but it is recom- Leprol 2006;72:391.
mended to wait at least 4 weeks after resolution of 9. Heikkila H, Timonen K, Stubb S. Fixed drug eruption due to
signs and symptoms to avoid false-negative results fluconazole. J Am Acad Dermatol 2000;42(5 Pt 2):883-4.
because of a refractory period.2 Topical provocation 10. Handisurya A, Moritz KB, Riedl E, Reinisch C, Stingl G, W ohrl S.
Fixed drug eruption caused by mefenamic acid: a case series
in previously involved FDE sites would be a safer and diagnostic algorithms. J Dtsch Dermatol Ges 2011;9:374-8.
first-step method, especially for children and in cases 11. Montoro J, Daz M, Gens C, Lozano A, Bertomeu F. Non-
of generalized bullous FDE; however, it is not stan- pigmenting cutaneous-mucosal fixed drug eruption due to
dardized and has a variable sensitivity. piroxicam. Allergol Immunopathol (Madr) 2003;31:53-5.
12. Gupta S, Jain VK, Aggarwal K, Gupta S, Mahendra A. Fixed
In conclusion, this was a comprehensive study
drug eruption caused by ornidazole. Contact Dermatitis 2005;
investigating different clinical forms of oral mucosal 53:300-1.
FDE which cause difficulties in establishing the 13. Gazquez V, G omez C, Daimau G, Gaig P, Landeyo J. A case of
correct diagnosis. As a first step, one should always fixed drug eruption due to quinine. Clin Exp Dermatol 2009;
look for additional skin involvement that is usually 34:95-7.
more characteristic for FDE. In the absence of addi- 14. Alonso JC, Melgosa AC, Gonzalo MJ, Garca CM. Fixed drug
eruption on the tongue due to clarithromycin. Contact Der-
tional skin involvement, the location and morphol- matitis 2005;53:121-2.
ogy of the oral mucosal lesion might help: Solitary 15. Alvarez Santullano CV, Tover Flores V, De Barrio Fernandez M,
bullous/erosive lesions on the dorsum of the tongue Tornero Molina P, Prieto Garcia A. Fixed drug eruption due to
or on the hard palate might be highly suggestive of ibuprofen. Allergol Immunopathol (Madr) 2006;34:280-1.
FDE. Naproxen and co-trimoxazole were the main 16. Gupta S, Gupta S, Mittal A, David S. Oral fixed drug eruption caused
by gabapentin. J Eur Acad Dermatol Venereol 2009;23:1207-8.
inducers, the latter significantly associated with sol- 17. Moreno Escobosa MC, Cruz Granados S, Moya Quesada MC,
itary FDE on the dorsum of the tongue. However, the Amat L opez J. Enanthema and fixed drug eruption caused by
inducer drugs may vary from country to country. trimethoprim. J Investig Allergol Clin Immunol 2009;19:249-50.
Isolated oral involvement, aphthous lesions, se- 18. Murray VK, DeFeo CP. Intraoral fixed drug eruption following
vere bullous/erosive lesions, the absence of residual tetracycline administration. J Periodontol 1982;53:267-8.
19. Naik RP, Singh G. Bullous fixed drug eruption presumably due
pigmentation, and the wide spectrum of differential to erythromycin. Dermatologica 1976;152:177-80.
diagnostic conditions may cause difficulties in the 20. Ozkaya E. Specific site involvement in fixed drug eruption.
diagnosis of oral mucosal FDE. It is important to J Am Acad Dermatol 2003;49:1003-7.
differentiate dysmenorrhea-related monthly attacks 21. Mahboob A, Haroon TS. Drugs causing fixed eruptions: a study
of oral mucosal FDE due to NSAIDs in female of 450 cases. Int J Dermatol 1998;37:833-8.
22. Gomez B, Sastre J. Fixed drug eruption. Allergol Immunopa-
patients from menstruation-triggered attacks of her- thol 1985;13:87-91.
pes simplex infection and isolated orogenital aph- 23. Dummett CO, Barens G. Pigmentation of the oral tissues: a
thous FDE from Behcets disease, especially in review of the literature. J Periodontol 1967;38:369-78.