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International Journal of Oral & Maxillofacial Pathology. 2012;3(4):34-38

Available online at http://www.journalgateway.com or www.ijomp.org

Case Report
Erythema Multiforme Major: Case Report
Kedar Saraf, Shashikanth MC, Mahendra Patait, Anuja Saraf

Abstract
Erythema Multiforme is an acute inflammatory disease of the skin and mucous membranes that
causes a variety of skin lesions hence the name "multiforme". It is a blistering, ulcerative
condition of uncertain etiopathogenesis. Hall mark of this is the iris or target lesion. Erythema
multiforme may present within a wide spectrum of severity. Among the many etiologic factors the
most common triggers for episodes of erythema multiforme are herpes simplex virus and drug
reactions. Drugs are reported in many documented cases of Stevens-Johnson syndrome and
Toxic Epidermal Necrolysis. Sulfa drugs are the most common triggers. Here is the case of
erythema multiforme major secondary to drug reaction with oral, skin and genital manifestations.
Keywords : Erythema multiforme; Stevens-Johnson syndrome; Sulfa drugs; Skin Diseases;
Erythema; Vesiculobullous.
Kedar Saraf, Shashikanth MC, Mahendra Patait, Anuja Sarf. Erythema Multiforme Major: Case Report.
International Journal of Oral & Maxillofacial Pathology; 2012:3(4):34-38. International Journal of Oral and
Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights
Reserved.
Received on: 05/02/2012 Accepted on: 17/10/2012

Introduction
The
initial
description
of
erythema
multiforme (EM) is attributed to Ferdinand
Von Hebra who in 1860 first described a
self-limited condition characterized by the
abrupt appearance of round red papules.
1
Some of which evolved into target lesions.
In 1916, Rendu described an acute febrile
illness (later named ectodermosis erosive
pluriorificialis), characterized by severe
erosions of all mucous membranes and a
vesicular skin eruption. In 1922, Stevens
and Johnson described two boys who were
febrile with erosive stomatitis, severe
purulent conjunctivitis and a disseminated
cutaneous
eruption.
This
disorders
described by Rendu and Stevens and
Johnson were probably very close, if not
2
identical. Erythema multiforme regarded by
Shklar and McCarthy as a "Symptom
3
complex". The etiology is obscure, although
a number of agents are known to precipitate
4
the attacks; herpes simplex infection. Other
viral infection, bacterial and fungal infection,
drug hypersensitivity, vaccination, radiation
therapy, food product allergy, emotional
3,4
tension.
The diagnostic criteria include symmetrical
lesions
which
initially
comprise
erythematous papules but later develop into
typical "target" or "iris" lesions with an
erythematous periphery and a central zone
of necrosis. Additionally, bullae and vesicles
1
may also be seen. The mucous membranes
of the oral cavity, nose, eyes and genitalia

may also be affected in EM and the degree

of mucosal involvement has been used to
classify the disease into EM minor and
major. In the former only mucous
membrane, usually the mouth is affected,
whereas in EM major mucous membrane
5
involvement is multiple.
In past 30 years, it became widely accepted
that EM minor, EM major, Stevens-Johnson
syndrome (SJS) and toxic epidermal
necrolysis (TEN) were all parts of a single
spectrum. Within that spectrum EM major,
ectodermosis
erosive
pluriorificialis,
mucocutaneous syndrome and SJS are
usually considered as synonyms for the
6
same disease. Here is a case of erythema
multiforme major which was developed
secondary to drug intake cotrimoxazole
involving oral, skin and genitalia.
Case Report
A 47 year old, male patient presented to the
Department of Oral Medicine and Radiology
with the chief complaint of bleeding from lips
since six days. Bleeding was associated with
mild pain. The medical history revealed that
the patient had taken Tab. Cotrimoxazole six
days back prescribed by the physician for
upper respiratory tract infection and
following which he started generalized
blisters on face, lips, neck, extremities and
genital region. He discontinued medication
after three days on medical advice. Patient
was diabetic and was under medication

2012 International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved

ISSN 2231 2250

since two year for the same. His past dental

history was non contributory.
On clinical examination, hemorrhagic
encrustations were seen on vermillion
border of the upper and lower lip (Fig 1a).
Diffuse erythematous lesions were present
on palms (Fig 1b), arm, neck, chest and
axillary region. On right hand between
thumb and
index finger concentric
erythematous target or bull's eye lesion (Fig
1c) was present. On right foot, an irregular
shaped bulla (Fig 1d) was present extending
from anterior part of the ventral aspect of
root to the ankle of the medial side
approximately 9 x 3 cm in size. Overlying
skin was wrinkled; surrounding skin was
yellowish in colour. On left foot, busted bulla
was seen. On genital examination,
ulceration with hemorrhagic crusting was
seen on penis (Fig 1e).

Erythema Multiforme... 35

mucosa at the junction of hard and soft

palate. Tongue was fissured. Considering
the history of drug intake followed by the
lesions the clinical diagnosis of drug induced
erythema multiforme major was made. His
complete hemogram report showed patient
was
anemic
(9.0gm%),
erythrocyte
sedimentation rate was increased, random
blood sugar was 150mg%. Tridot test for
screening of human immunodeficiency virus
(HIV) was negative. Patient was prescribed
oral prednisolone at an initial dose of 15mg
in a divided dose followed by gradual
tapering of the dosage over a period of eight
days
along
with
antiallergic
Chlorphenylamine maleate 4mg, once daily
and ointment 0.1% triamcinolone acetonide
was prescribed for topical application.
Patient reported after eight days, signs of
healing lesions on lips, palate, hands, palms,
chest, feet, and genital (Fig 1g, h, & i) were
seen.

On intraoral examination, approximately 1 x

1mm vesicle (Fig 1f) was present on palatal

Figure 1: The clinical photographs showing encrustations on vermillion border of the upper and
lower lip (a), erythematous lesions on palms (b), target or bull's eye lesion on hands (c), irregular
shaped bulla on right foot (d), ulceration with hemorrhagic crusting on the penis (e), vesicle on
palatal mucosa at the junction of hard and soft palate (f), the healed lesion on lips (g), on genitals
(h) and on the foot (i).

36 Kedar Saraf, et al.

Discussion
Erythema
multiforme
is
an
acute
inflammatory disease of the skin and
mucous membrane that cause a variety of
7
skin lesions. It may display wide spectrum
of clinical disease. On the mild end of
spectrum ulcerations develop, affecting the
oral mucosa primarily. In its most severe
from, diffuse sloughing and ulceration of the
entire skin and mucosal surfaces may be
8
seen. Erythema multiforme is seen most
frequently in children and young adults and
is rare after age 50 years. It has an acute or
even an explosive onset; generalized
symptoms such as fever and malaise appear
7
in severe cases.
The most common cutaneous areas
involved are the hands, feet and extensor
surface of the elbows and knees. The face
and neck are commonly involved, but only
severe cases affect the trunk. Typical skin
lesions of erythema multiforme may be
nonspecific macules, papules and vesicles.
The pathognomic lesion is the "target" or
"iris" lesion which consist of a central bulla
or pale clearing area surrounded by edema
7
and bands of erythema. Additionally bullae
5
and vesicles may also be seen. Different
workers have suggested that EM and SJS
could be separated from as two different
clinical disorders with similar mucosal
reactions but different patterns of cutaneous
lesions.
Erythema multiforme major is characterized
by mucosal erosions of raised atypical target
lesions usually on extremities and/or face.
The characteristic findings of SJS are
mucosal
erosions
plus
widespread
distribution of flat atypical target or purpuric
macules. The lesions may be present on the
9
trunk, the face, and on the extremities. In
our case concentric erythematous macular
lesion was present on the right hand
resembling
target
eye
and
other
erythematous lesion on palms, arm, neck,
chest and axillary region.
The relationship of TEN with Stevens Johnson syndrome and erythema multiforme
has been an issue of confusion and debate.
There is a growing evidence that SJS and
TEN constitute a spectrum of disease that is
distinct from erythema multiforme but with
similar
histopathologic
characteristics,
overlapping patients and cases of transition
from SJS to TEN. Cases with widespread
purpuric macules and epidermal attachment
below 10% are called SJS. Those with

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cutaneous detachment between 10% and

30% are called transitional "SJS-TEN" and
those with more than 30% epidermal
detachment are designated or TEN. Both
diseases are primarily, but not solely caused
10
by drugs.
The drugs which are found to be associated
with SJS are antibacterial, sulfonamides,
anticonvulsants (Phenobarbital, phenytoin,
carbamazepine, valporic acid) oxicam
nonsteroidal
anti-inflammatory
drugs,
chlormezanone, allopurinol, acitomenophen,
imidazole antifungal drugs, corticosteroids
for
systemic
use,
aminopenicillins,
cephalosporins,
quinolones
and
11
tetracyclines. Sulfa drugs are the most
9
common triggers. Co-trimoxazole is in the
upper third of the table of drugs which
certainly, probably or possibly induced
Lyells syndrome and in the middle of the
table of those that induced Stevens-Johnson
12
syndrome. Our case was typical example
of drug induced erythema multiforme as
patient gave history of rashes on skin and
oral lesions started after taking medication.
Oral lesions commonly appear along with
skin lesion in approximately 70% of EM
patients Oral lesion has seemingly started in
oral cavity on the buccal mucosa, palate,
lips, tongue. In full flow clinical cases, the
lips are extensively eroded and large portion
8
of the oral mucosa are denuded. In the
present case, characteristic encrustations
and bleeding from the lips and also palatal
vesicle were present. The diagnosis was
made on the basis of the total clinical
picture, including the rapid onset of lesions.
The oral lesions start as bullae on an
erythematous base, but intact bullae are
rarely seen by the clinician as they break
rapidly into irregular ulcers. Viral lesions are
small, round, symmetric, and shallow, but
EM lesions are larger, irregular, deeper, and
often bleed. Lesions may occur anywhere on
the oral mucosa with EM, but involvement of
the lips is especially prominent, and gingival
involvement is rare. This is an important
criterion for distinguishing EM from primary
herpes
simplex
infection,
in
which
generalized
gingival
involvement
is
7
characteristic.
Skin biopsy of erythema multiforme may
show in the epidermis/epithelium apoptotic
individual keratinocytes (cellular selfdestruction, earliest histological change),
hydropic
degeneration
of
basal
keratinocytes,
intercellular
oedema

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(spongiosis), blisters within and under the

epidermis/epithelium,
epithelial/epidermal
necrosis but there are no large sheets of
epidermal necrosis as seen in StevensJohnson syndrome / toxic epidermal
necrolysis. Direct immunofluorescence may
show deposition of immune proteins C3 and
fibrin along the dermo-epidermal junction
and IgM, C3 and fibrin around blood
13
vessels. Histopathology is not diagnostic
and the immunopathologic features are also
nonspecific, the diagnosis is often based on
the clinical presentation and the exclusion of
8
other vesiculobullous disorders. In our case
diagnosis was made on the basis on
characteristic clinical feature only.
The varied nature of the disease may
present difficulty in diagnosis, particularly
when the occurrence of cutaneous lesion is
minimal also in serious often bullous drug
eruption, so severe that large sheets of skin
peel off giving the appearance of a
widespread scalding burn. Oral erosions
may also occur and have been described by
Giallorenzi and Goldstein. It is not
considered to be a confluent form of
9
Stevens-Johnson syndrome.
A retrospective study demonstrated a
correlation between two pattern and cause
of EM major and Stevens-Johnson
syndrome. The findings suggested that
typical and atypical popular target lesions,
distributed on the extremities and the face
characterized herpes induced EM major,
whereas flat atypical target lesions or
purpuric macules, widespread or distributed
on the trunk are found in drug-induced
6,14
SJS.
Identification of the cause should be made if
possible. If a drug is suspected, it must be
withdrawn,
infections
should
be
appropriately treated after cultures and/or
9
serologic tests have to be performed.
Management of erythema multiforme
particularly the minor and major forms,
includes use of systemic corticosteroids,
especially in the early stages of the disease.
Sometimes oral lesions in minor forms of the
condition may be managed effectively with
topical corticosteroid syrup or elixirs.
Corticosteroids in the management of TEN,
because some investigators have found that
8
such drugs may be detrimental.
For all forms of EM, symptomatic treatment,
including oral antihistamines, analgesics,
local skin care, soothing mouthwash are of

Erythema Multiforme... 37

great importance. Oral antacids may be

9
useful for discrete oral ulcers. In present
case patient responded to topical and
systemic
corticosteroids
and
no
complications were seen.
Conclusion
Generally, EM is not life threatening except
in its most severe form. By recognizing the
early EM oral lesions along with skin lesions
if any, the dentist has a responsibility in the
early diagnosis of the disease, which is of
utmost prognostic importance.
Acknowledgement
We would like to thank all the staff members of
the department of oral medicine for their constant
support and encouragement.
Author Affiliations
1. Dr.Kedar Saraf, Senior lecturer, SMBT Dental
College & Hospital, Sangamner, Maharashtra. 2.
Dr.Shashikanth MC, Professor, UP Dental
College & Hospital, Lucknow, Uttar Pradesh, 3.
Dr.Mahendra Patait, Professor, SMBT Dental
College & Hospital, 4. Dr.Anuja Saraf, Dental
Surgeon, Sangamner, Maharashtra, India.

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Corresponding Author
Dr.Kedar saraf,
Senior lecturer,
SMBT Dental College & Hospital,
Sangamner, Maharashtra, India.
Email: kedarvs@yahoo.co.in
Ph: +91 9730638060

Source of Support: Nil, Conflict of Interest: None Declared.