PEDIATRIC DENTISTRY V 3 4 í NO 4 J U L ; A U G 12

Case ReDort
Misdiagnosis of Erythema Multiforme: A Literature Review and Case Report
John Kempton, DDS, MS' • John iVl. Wright, DDS, MS^ • Caroiyn Kerins, DDS, PhD^ • David i-iaie, DDS, MSD^

Abstract: Erythema multiforme is primarily considered a disease of the skin. Diagnosis tends to be centered on dermatoiogic iesions of the extremities,
with mouth uicers regarded as a secondary finding. The purpose of this paper was to report a case of an 8-year-oid maie diagnosed with erythema
muitiforme iimited to the orai cavity. The patient was referred to Texas A&M Health Science Center's Bayior Coiiege of Dentistry for biopsy of recurrent
mouth ulcers following an outbreak of a fever blister. Previous hospitaiization occurred twice due to severe mouth uicers causing dehydration and ioss
of nutrition. He was treated with 10 mg of prednisone twice daiiy and was abie to eat and drink without pain within 48 hours. Nearly aii iesions
heaied within 5 days of therapy. Aithough rare, erythema multiforme shouid aiways be considered in the differential diagnosis in the event of acute onset
stomatitis. (Pediatr Dent 2012:34:337-42) Received December 14,2009 I Last Revision July 20, 2011 i Accepted Juiy 25,2011

KEYWORDS: ERYTHEiViA MULTiFORiViE, DiFFERENTiAL DIAGNOSIS, PEDiATRiC PATHOLOGY

Erythema multiforme (EM) is a reactive mucocutaneous disot-
der affecting the skin, mucous membtanes, or both, and is
often characterized by target- (or iris-) shaped lesions disttibuted
symmetrically on the extremities. EM includes a spectrum of
reactions that are acute and self-limiting. It generally results
from an immune-mediated reaction to various antigenic chal-
lenges and has a tendency to recur.''^ The extent of the tesponse
can vary widely, which has resulted in further classifications and
subcategories known as EM minor, EM major (traditionally also
called Stevens-Johnson syndrome [SJS]), and toxic epidermal
necrolysis depending on the severity where multiple mucous
membranes and significant portions of the skin are involved.^'^
While there is considerable overlap in the clinical features
of EM major and SJS and some authorities consider them syn-
onymous, there is some evidence suggesting that EM majot is
clinically and etiologically distinct from SJS. EM major is more
commonly caused by herpes simplex virus (HSV), while SJS is
more commonly drug induced.'"'' Minor EM cases are usually
associated with the herpes virus, while more severe episodes of
the spectrum commonly follow drug administration.''''' SJS and
toxic epidetmal nectolysis are less common and represent the
mote severe end of the specttum that typically occurs in adults."
EM was otiginally defmed in 1866 by Von Hebra to in-
clude the presence of true target lesions of the skin, with no
mucosal lesions ot a lesion involving the mucosa in only one
site. This definition (which limits the disease to primarily in-
volving the skin), now constitutes what is known as EM minor.
It has now been reported that apptoximately 70% of pa-
tients with either minor or major forms of EM have oral
lesions.' These may be isolated or precede lesions on other
' Dr. Kempton is a dentist in private practice in Phoenix, Arizona; ^Dr. Wright is a
regents professor and chairman. Department of Diagnostic Sciences, and ^Dr. Kerins is
an associate professor and 'Dr. Hale is an assistant professor. Department of Pédiatrie
Dentistry, all in Baylor College of Dentistry, The Texas A&M University System, Health
Science Center, Dallas. Texas.
Correspond with Dr. John Wright at JWri^t@bcd. tamhsc.edu
Stratified squamous epithelia and progress as diffuse and wide-
spread erosions to blistets and ulcération. Intraotal lesions arise
typically on nonkeratinized mucosa in the antetior parts of the
mouth. Oral manifestations are characterized by rapid onset
with panoral ulcerative stomatitis, necrotic tags of epithelium,
and lips that charactetistically crack, bleed, swell, and crust
but heal without scatring.^'" EM primarily affects patients in
the second to third decades of life; however, reports have doc-
umented EM in older patients as well as children. " ' '
The typical target lesions, with their wheel-like appear-
ance, are the result of intense dermal infiammation mediated
by CD4+ T lymphocytes and monocytes. In herpes-associated
EM, the inHammation is likely associated with microvascular
damage that is caused by HSV-containing mononuclear cells
binding to the endothelium.^ The erosions and inflammation
associated with EM occur by a T-cell mediated immune teac-
tion to antigen expressing keratinocytes. This cell-mediated
immune response results in apoptosis and satellite-cell necrosis
of these cells, with ensuing subepithelial and intraepithelial
vesiculation.'
A less-known group of EM involves only the oral mucosa.
It presents as an acute, vesiculobuUous stomatitis with erosions
of the oral mucosa that can also involve the vermillion of the
lips in some patients. While often described as vesiculobuUous,
vesicles and buUae are rarely seen and lesions present as areas
of erythema, erosions, and ulcers. Pain is usually severe and
morbidity is considerable, as it can interfere with oral intake
and speech over a period of time. Oral EM is not accepted
by all authors^; however, it is well documented in the current
litetature,'''*"'^ with several cases reported. "''"•'^•'^•"* Diagnosis of
oral EM is difficult due to the similar clinical presentation of
other inflammatory and vesiculobuUous diseases.'•^''° Typical
cutaneous involvement for EM minor, however, is seen in 25%
of patients, making the diagnosis more clear.'
EM can affect patients of all ages; however, it is most
commonly seen in healthy young adults ranging from 20
to 40 years old, with an incidence of up to 1% per year."

ERYTHEMA MULTIFORME IN PEDIATRIC PATIENTS 337

PEDIATRIC DENTISTRY V 3 4 ' NO 4 |UL;AUG

Approximately 20% of EM cases are found in children and ado-
lescents younger than 20 years old.'"'''"'"''''^ Overall, the rate
of illness affects fewer than 1 in 100,000.^°
Several variables have been implicated as possible etiologic
factors, including viral and bacterial infections, drugs, and sev-
eral associated neoplastic conditions.'^ The more severe and
widespread the reaction, the more likely it is drug-induced.^"
HSVs I and II are both considered the primary trigger for EM
in adults and children.'^''''^ A possible genetic predisposition
has also been implieated, along with many other viral and bac-
terial possibilities.'-' Food and drug-associated cases are also
numerous.'" Medicines most commonly antecedent reported
are cephalosporins, amoxicillin, sulfamethaoxazole, and tetra-
cyclines. Nonsteroidal anti-inflammatory drugs and antieon-
vulsants have been implieated as well.^' Possible triggering
agents are presented in Table 1.
Diagnosis ean be ehallenging in these patients due to the
variable features of the disease, espeeially when it is limited to
the oral eavity.'•'•''•''' A diagnosis is primarily made elinieally,
with the related history with treatment outcome confirming the
The purpose of this case report was to present a case of
erythema multiforme in which only oral lesions were seen, re-
sulting in misdiagnosis and mismanagement that required
hospitalization.
Case report
In early 2007, an otherwise healthy 8-year-old Caucasian male
with a history of fever blisters presented to a community health
clinic due to perioral vesicular lesions, a sore mouth, swelling of
the lips, and a temperature of 2 days duration. The physician
reeorded multiple lesions and uleers on the patient's mouth and
lips and made a provisional diagnosis of fever blisters. A strep-
toeoeeal test resulted negative, and tbe physician's clinical im-
pression was an HSV infection. Valtrex lg orally for 5 days was
prescribed along with amoxicillin. A Benadryl/Maalox solution
(1:1) was also prescribed for palliative treatment of the gingivo-
stomatis. A complete blood count was ordered. Four days later,
tbe patient returned with an increase in temperature, decreased
appetite, malaise, and a cough. The complete blood count re-
turned with no signifieant findings, and the patient was direeted
to eontinue with the eurrent preseriptions. After another 4
days, the patient returned—still not feeling well. His appetite
eontinued to deerease and mouth uleerations had inereased.
The patient was referred to the Emergeney Department
of Children's Medieal Center in Dallas, Texas, for dehydration
and weight loss of 4 to 6 lbs. Monospot and direet fiuorescent
antibody tests were negative. A differential diagnosis of "mouth
blisters" was eonsidered, but the patient began tolerating
liquids by mouth, beeame eomfortable, rested, and was dis-
eharged with a final diagnosis of "viral syndrome."

Table 1. POSSIBLE TRIGGERING AGENTS OF ERYTHEMA MULTIFORME

Drugs Drug groups Viral infections Bacterial infections Fungal infections Other Vaccines

Acarbose Aminopenicillins Human immuno- B-hemolytic Coccidioidomycosis Emotional stress DTAP

Allopurinol Anti-epileptics deficiency streptococci Dermatophytosis Food additives: vaccine
Antlpyrene AntiRingals virus Brucellosis Histoplasmosis benzoates. Hep B
Arsenic Antimalarials Herpes simplex 1 Diptheria Sporotrichosis nitrobenzene, vaccine
Bactrim Barbiturates and 2 Mycobacteria Trichomonas perftimes, terpenes MMR
Bezafibrate Bromides Mumps (avium, leprae, Toxoplasma gond Immunosuppression vaccine
Bupropion Cancer Variola (small pox) tuberculosis) Tattoos
Busulfan chemotherapeutic Adenovirus Mycoplasma Immune/other
Carbarn azepine agents Herpes zoster pneumonia conditions: GVHD,
Chlorpropamide Cephalosporins Poliomyelitis Tularemia immunization
Cimetidine Fluoquinolones Ecthyma Typhoid Fever (BCG, hepatitis B,
Clindamycin Gold salts contagiosum Group A smallpox)
Clonazepam Herbal remedies Parvovirus B19 streptococcus Inflammatory bowel
Cocaine Hydantoins Influenza type A Borreliosis disease
Co-triamzole Iodides Psittacosis Cat scratch disease Polyarteritis nodosa
Digitalis NSAIDs Enteroviruses: Chlamydia Pregnancy
Ethambutol Mercurials (poliovirus. Corynebacterium Sarcoidosis
Furosemide Oestrogens coxsackie virus Legionellosis Systemic lupus
Gabapentin Oral B5, echoviruses) Lymphogranuloma erythematosus
Hydralazine contraceptives Epstein-Barr virus Venereum Malaria
Nevirapine Phenothiazines Cytomegalovirus Lymphogranuloma Tuberculin skin test
Phcnolphthalein Progestogens Rickettsiae Inguinale Radiation therapy
Progesterone Protease Paramyxovirus Neisseria Nitrogen mustard
Rifampin inhibitors Hepatitis A, B, meningitidis
Sertraline Sulfonamides and C Proteobacteria
Simvastatin Tetracyclines Paravaccinia (Pseudomonas,
Suramin Vaccinia vibrio, salmonella)
Theophylline Psittacosis
Thidbendazole Rickettsia
Ticlopidine Staphylococcus
Thibendazole Streptococcus
Tolbutamide Pneumonia
Trichloroethylene Treponema pallidum
Trimethadione Yersinia
Vancomycin
Verapamil

338 ERYTHEMA MULTIFORME IN PEDIATRIC PATIENTS


Ten months later, in December 2007, the patient sought
care for another episode of sores that would not heal in his
mouth. He tested negative for group A streptococcus, and was
given Zithromax and Valtrex. He returned 3 days later with
decreased fiuid intake and no improvement of his "aphthous
ulcers." There was crusting, fissuring, and swelling of his lips,
with mild erythema of the posterior pharynx. Due to dehydra-
tion, he was admitted to a local hospital, placed on IV fluid
resuscitation, and given Zithromax. Eighteen days following
the onset, the patient felt better and his appetite improved. He
was referred to an immunologist who recorded the following:
"The description by history is that of two different processes:
history of herpes simplex reactivation on his lips, and an inter-
mittent process of sores in his mouth that are unclear to me as
to the etiology."
In May 2008, the patient returned for treatment of the
same condition. The physician's notes describe multiple yellow
crusted lesions on both lips and ulcérations on the left side of
the tongue and buccal mucosa. The patient was referred to the
immunology clinic of Children's Medical Center for treatment
and was given Valtrex, Zovirax, Tylenol no. 3, and a Maalox/
Benadryl 1:1 solution for relief.
Later that month, the patient was referred to the Baylor
College of Dentistry at Texas A&M University Health Science
Center, Dallas, Texas, for a biopsy of the ulcerated lesions. A
clinical examination was performed along with a detailed his-
tory. A family history of recurrent fever blisters was teported
extending from the patient's maternal grandparents, mother,
and 17-year-old sister; however, none had developed significant
mouth sores. The clinical examination and health history given
by the patient's mother resulted in no hand, skin, eye, or genital
lesions. Swollen, cracked, crusted, and bleeding lips were
noted, along with ulcérations of nonkeratinized mucosa in the
anterior parts of the mouth (Figures la-5a). A diagnosis of
Figure 1. (a) Initiai presentation of patient with erythema multiforme including swollen, encrusted, and hemorrhagic lips, (b) Five days following treatment with pred-
nisone, showing nearly complete resolution of lesions.
Figure 2. (a) Pre-treatment photo of erythema multiforme patient with showing maxillary labial mucosainvolvement. Note the patients inability to maintain oral hygiene,
(b) Post-treatment resolution following administration of prednisone.
Figure 3. (a) Pretreatment involvement of mandibular labial mucosa in a patient with erythema n:iultiforme. (b) Post-treatment photo depicting nearly complete resolution
of erythematous lesions in the same patient with erythema multiforme.
PEDIATRIC DENTISTRY V 34 i NO 4 JUL I AUG 12
erythema multiforme was suggested by the oral pathology de-
partment, and the patient was given prednisone 10 mg twice
a day for 5 days. The patient reported back for a follow-up
exam 5 days later. All lesions at this time were resolved, with
the exception of 2 on the lower lip (Figures lb-5b). The patient
was 100% compliant with treatment recommendations and
was able to eat and drink without pain 48 hours after the start
of prednisone. The patient continued on 10 mg of prednisone
twice daily for 2 more days (7 days total), then was reduced to
10 mg once per day for 9 more days.Future outbreaks were
to be treated in the same manner.
In August 2008, the patient sought treatment from his
primary care physician for swollen lips and mouth ulcérations
following a fever blister. He was prescribed a Z-pack and pred-
nisone 10 mg twice a day for 5 days, then 10 mg/day for 10
days. The mother reported that relief was immediate, with the
lip swelling resolving over night.
Discussion
EM is primarily consideted a disease of the skin. Diagnosis tends
to be centered on dermatologie lesions of the extremities, with
mouth ulcers being regarded as a secondary finding.'•^•'"•^^'^^
As the name suggests, EM is a disease that can exhibit varying
signs and symptoms, making diagnosis difficult. EM's typical
clinical presentation consists of acrally distributed target lesions,
which are considered the landmark feature.'•'''^^•^'* Skin lesions
have been emphasized for diagnosis and are regarded as a com-
mon feature of all variants, as well as "the sine qua non fot the
diagnosis of EM."''' Some authors have defined EM patients
as not having oral lesions.''•''•^' Current authors, however, re-
port the existence of EM limited to the oral cavity."''''^''^''* As
skin lesions are a major component in diagnosing the disease,
cases where skin lesions are absent makes diagnosis much
more difficult.'".5.>3.30
ERYTHEMA MULTIFORME IN PEDIATRIC PATIENTS 339
PEDIATRIC DENTISTRY V 34 : NO 4 J U L / A U G 12

The severe forms of EM are often characterized by a pro- ulcerative necrotizing gingivitis primarily affects and is limited
drome of nonspecific malaise, headache, and sometimes fever to the gingiva, although other parts of the mouth can be
as much as 1 week before the mucocutaneous eruption. One involved.
of the most characteristic features of EM is its acute onset, The most obvious differential diagnosis, primary herpetic
often within 1 or 2 days. This distinguishes it from many of gingivostomatitis, can closely resemble oral manifestations
the other conditions in the differential diagnosis, which are of EM. Both vesiculo-ulcerative diseases are acute, affect
more chronic in their onset. The oral severity is variable, and younger populations, and resolve spontaneously. The ulcers
the condition tends to be generalized and somewhat symme- indicative of primary herpes, however, tend to be small, round,
trical in its distribution because of the reaction's systemic shallow, and affect the palate and gingiva. Gingival edema is
nature. Lesions range from erythema to full thickness ulcéra- also seen in primary herpes, and the disease is not recurrent.^"
tion. Gonsiderable tissue sloughing may be seen in severe cases. EM lesions are larger, irregular, and exhibit a pattern of
Lesions tend to preferentially affect nonkeratinized mucosa, recurrences and generally spare the gingiva.'''" With herpetic
but occasionally the gingiva and hard palate show involvement. infections, patients are always febrile, while in EM they are
One of the most characteristic features is the hemorrhagic afebrile or the fever is lower.
crusting of the lip vermilions. If untreated, the reac-
tion is self-limited within 2 to 8 weeks. Up to 37%
of patients experience recurrent episodes."
Aphthous ulcers, toxic epidermal necrolysis,
pemphigus vulgaris, subepithelial immune dis-
orders (pemphigoid and others), primary herpes,
Behcet's disease, buUous or ulcerative lichen planus,
diphtheria, systemic lupus erythematosus, acute
ulcerative necrotizing gingivitis, cyclic neutropenia,
and allergies have all been included in the differen-
tial diagnosis for the oral lesions of EM.''"'^''*'"'''*
A summary of distinguishing features of conditions
simulating EM is presented inTable 2.
Pemphigus and pemphigoid are typically seen
in older populations, but both are well docu-
mented in children. They show characteristic bound
autoantibodies in tissues and exhibit signs of des-
quamative gingivitis, are chronic, and do not resolve
spontaneously.'''' Behcet's disease is characterized
by the presence of recurrent aphthous ulcers of
the oral cavity, which last 7 to 14 days along with Figure 4. (a) Precreatment photo of the right buccal mucosa in a patient with erythema multiforme,
other hallmark symptoms. These include erythema (b) Five-day post-treatment follow-up showing complete resolution of buccal lesions in the same patient
nodosum-like nodules on the legs, superficial and/ with erythema muitiforme.
or deep thrombophlebitis, and acral purpuric papu- Figure 5. (a) Pretreatment photo depicting lesions of the tongue's dorsal surface in a patient with erythema
multiforme, (b) Five-day post-treatment follow-up showing marked improvement of erythematous
londular lesions. It is most often seen in young lesion of the same patient with erythema multiforme.
adult males and is uncommon in children.-'' Acute

iiible 2. SUMMARY OF DISTINGUISHING FEATURES OF DIFFERENTIAL DIAGNOSES FOR ERYTHEMA MULTIFORME

Diagnosis Sex pref Acute Initiating Recurs Lip Gingival Blisters/ Ulcers Sores
onset factor/etiology involvement involvement vessicles

Erythema Male Medications, •

multiforme Herpes Simplex
virus
Primary herpetic None Herpes Simplex
gingivostomatitis virus
Beçhet's Male Autoimmune
syndrome
Systemic allergy None Allergen • • •
Impetigo None Staph/Strep •
infection
Pemphigus None Autoimmune • •
Epidermolysis None Heredity
buUosa

340 ERYTHEMA MULTIFORME IN PEDIATRIC PATIENTS


Anothet diflFetential diagnosis, minot aphthous ulcets, can
be diffetentiated ftom EM by their distribution. The dotsum of
the tongue and othet ketatinized sites affected by EM ate tate-
ly involved by minor aphthae, and the ulcets ate bettet defined
and do not fotm areas of confluent ulcération. The extent of
oral mucosal involvement is usually considetably mote limited
in aphthous ulcets than in EM. Major aphthae differ by more
limited disttibution and scatting of tissues, and they do not
have the acute, explosive onset of EM.
The limited and vatiable nature of EM has led to symp-
tomatic management of the disease. An attempt should be made
to detetmine the undetlying cause, patticulatly dtugs which
should be discontinued and not represctibed. Liquid antacids,
antihistimines, topical cotticostetoid suspensions and anes-
thetics may teduce subjective symptoms; howevet, they have
limited impact on its course.^'* Soft liquid diets devoid of acidic
and spicy foods have been tecommended, along with emphasis
on adequate fluid intake.''^ Systemic cotticostetoid thetapy has
been controversial. Many authots have consideted them the
standatd of cate fot yeats and included them as patt of a rec-
ommended treatment of SJS and Toxic Epidetmal Nectolysis
(TEN)^'''^-''"'^^ Some authots have shown, howevet, through
tetrospective reviews of SJS and TEN, that the disease coutse
was not shortened via corticostetoid thetapy, and medical com-
plications ensued.^^'^^ Conflict in teporting has led some authors
to not recommend the toutine use of systemic cotticostetoids
fot management of EM, SJS, otTEN."''''-^''
In a prospective study by Kakourou et al., it was con-
eluded that eatly and short course corticosteroid tteatment of
etythema multifotme majot in childten is favotable.^* The use
of systemic cotticostetoids has been advocated in mote sevete
EM cases.^'^''^' In discussion of this conttovetsy, Renfto et al.,
suggested that cotticostetoid treatment might be most appto-
ptiate in eatly stages of the disease (ptiot to maximal tissue
damage), and in patients with complicated and potentially se-
rious cases of EM major.''
Much focus has been placed on the prevention of EM as-
sociated with the HSV. It has been shown that oral Zovirax
(200 mg 5 times daily for 5 days) may prevent EM and that
continuous ptophylaxis of Zovirax (10 mg/kg) fot a 6- to 12-
month period is highly effective at limiting episodes of both
HSV and EM."'^"'""''*'
Etythema multifotme traditionally affects young adults, but
pédiatrie dentists may not be awate that as many as 20% of
cases affect childten and can be limited to the otal cavity. This
paper presented a case of EM in an 8-year-old child who was
hospitalized on 2 occasions because the diagnosis was nevet
considered. In the event of acute onset stomatitis, EM (al-
though täte) should always be consideted in the diffetential
diagnosis.
References
1. Ayangco L, Rogets RS III. Otal manifestations of ety-
thema multifotme. Detmatol Chn 2003;21:195-205.
2. Fteedbetg IM, Fitzpattick TB. Fitzpattick's Detmatology
in General Medicine. New York: McGraw-Hill, Medical
Publishing Division; 2003.
3. Lozada F, Silvetman S Jt. Etythema multifotme: Clinical
chatactetistics and natutal histoty in 50 patients. Otal Sutg
Otal Med Oral Pathol 1978;46:628-36.
PEDIATRIC DENTISTRY V 34 í NO 4 )UL i AUG 12
4. Huff JC, Weston WL, Tonnesen MG. Erythema multi-
forme: A critical teview of chatacteristics, diagnostic ctitetia,
and causes. J Am Acad Detmatol 1983;8:763-75.
5. Wetter DA, Camilleri MJ. Clinical, etiologic, and histo-
pathologic features of Stevens-Johnson syndtome duting
an 8-yeat period at Mayo Clinic. Mayo Clin Proc 2010;
85:131-8.
6. Bastuji-Garin S, Rzany B, Stetn RS, Sheat NH, Naldi L,
Roujeau JC. Clinical classification of cases of toxic epidet-
mal nectolysis, Stevens-Johnson syndrome, and erythema
multifotme. Atch Detmatol 1993;129:92-6.
7. Scully C, Bagan J. Otal mucosal diseases: Etythema multi-
fotme. Bt J Otal Maxillofac Surg 2008;46:90-5.
8. Williams PM, Conklin RJ. Erythema multifotme: A te-
view and conttast ftom Stevens-Johnson syndtome/toxic
epidetmal necrolysis. Dent Clin Notth Am 2005;49:67-
76, viii.
9. Fatthing PM, Matagou P, Coates M, Tatnall F, Leigh IM,
Williams DM. Chatactetistics of the otal lesions in pa-
tients with cutaneous recurrent etythema multifotme. J
Otal Pathol Med 1995;24:9-13.
10. Fatthing P, Bagan JV, Scully C. Mucosal disease seties. No.
IV. Etythema multifotme. Oral Dis 2005;ll:26l-7.
11. Ledesma GN, McCotmack PC. Etythema multifotme.
Clin Dermatol 1986;4:70-80.
12. Kennett S. Etythema multifotme affecting the otal cavity.
Otal Sutg Otal Med Otal Pathol 1968;25:366-73.
13. Lozada-Nut F, Gotsky M, Silvetman S Jt. Otal erythema
multifotme: Clinical obsetvations and tteatment of 95
patients. Oral Sutg Otal Med Otal Pathol 1989;67:36-40.
14. Bean SF, Quezada RK. Recuttent oral erythema multi-
fotme. Clinical expetience with 11 patients. JAMA 1983;
249:2810-2.
15. Buchnet A, Lozada F, Silverman S Jt. Histopathologic
specttum of otal etythema multifotme. Otal Sutg Oral
Med Otal Pathol 1980;49:221-8.
16. Jawetz RE, Elkin A, Michael L, Jawetz SA, Shin HT. Ery-
thema multifotme limited to the otal mucosa in a teenager
on oral conttaceptive thetapy. J Pediatt Adolesc Gynecol
2007;20:309-13.
17. Nesbit SP, Gobetti JP. Multiple recurrence of oral erythema
multifotme aftet secondaty herpes simplex: Report of
case and review of literatute. J Am Dent Assoc 1986; 112:
348-52.
18. Manganato AM. Erythema multifotme. Gen Dent 1996;
44:164-6.
19. Schopick E, Cavanaugh K. Cases from the Oslet Medical
Setvice at Johns Hopkins Univetsity. Am J Med 2004;
116:349-51.
20. Chan HL, Stetn RS, Atndt KA, et al. The incidence of
etythema multifotme, Stevens-Johnson syndtome, and
toxic epidetmal nectolysis. A population-based study with
patticulat tefetence to reactions caused by dtugs among
outpatients. Arch Detmatol Res 1990; 126:43-7.
21. Howland WW, Golitz LE, Weston WL, Huff JC. Etythema
multifotme: Clinical, histopathologic, and immunologie
study J Am Acad Detmatol 1984;10:438-46.
22. Schofield JK, Tatnall FM, Leigh IM. Recuttent etythema
multifotme: Clinical featutes and tteatment in a large seties
of patients. Br J Dermatol 1993; 128:542-5.
ERYTHEMA MULTIFORME IN PEDIATRIC PATIENTS 341
PEDIATRIC DENTISTRY V 34 ! NO 4 )UL I AUG 12
23. Stewart MG, Duncan NO III, Franklin DJ, Friedman
EM, Suiek M. Head and neck manifestations of erythema
multifotme in childten. J Otolaryngol Head Neck Surg
1994;111:236-42.
24. Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. London,
UK: Mosby; 2003.
25. Rook AWDS, Ebling FJG. Textbook of Detmatology. 3""
ed. Oxford, UK: Blackwell Scientific Publications; 1979.
26. Weedon D, Strutton G. Skin Pathology. 2"** ed. London,
UK: Mosby; 2002.
27. Aurelian L, Ono F, Burnett J. Herpes simplex virus (HSV)-
associated etythema multiforme (HAEM): A viral disease
with an autoimmune component. Detmatol Online J
2003;9:l.
28. Weston JA, Weston WL. The overdiagnosis of etythema
multiforme. Pediatrics 1992;89:802.
29. Roujeau JC. Stevens-Johnson syndtome and toxic epi-
detmal necrolysis are severity variants of the same disease
which differs from erythema multifotme. J Detmatol 1997;
24:726-9.
30. Schneider LC, Schneider AE. Diagnosis of oral ulcers. Mt
Sinai J Med 1998;65:383-7.
31. Patterson R, Dykewicz MS, Gonzalzles A, et al. Erythema
multiforme and Stevens-Johnson syndrome: Descriptive
and therapeutic controversy. Chest 1990;98:331-6.
32. Renfro L, Grant-Kels JM, Feder HM Jr, Daman LA. Con-
ttoversy: Are systemic steroids indicated in the treatment
of erythema multifotme? Pediatr Dermatol 1989;6:43-50.
33. Halebian PH, Corder VJ, Madden MR, Finklestein JL,
Shites CT. Improved burn center survival of patients with
toxic epidermal necrolysis managed without corticosteroids.
Ann Surg 1986;204:503-12.
342 ERYTHEMA MULTIFORME IN PEDIATRIC PATIENTS
34. Nethercott JR, Choi BC. Erythema multiforme (Stevens-
Johnson syndtome): Chart review of 123 hospitalized pa-
tients. Dermatológica 1985;171:383-96.
35. Rasmussen JE. Erythema multiforme in children: Response
to tteatment with systemic cotticostetoids. Br J Dermatol
1976;95:181-6.
36. Marvin JA, Heimbach DM, Engrav LH, Harnar TJ. Im-
proved treatment of the Stevens-Johnson syndrome. Arch
Surg 1984;119:601-5.
37. Revuz J, Roujeau JC, Guillaume JC, Penso D, Touraine
R. Treatment of toxic epidermal necrolysis: Creteil's expe-
rience. Arch Dermatol 1987; 123:1136-8.
38. Kakourou T, Klontza D, Soteropoulou F, Kattamis C.
Corticosteroid tteatment of erythema multiforme major
(Stevens-Johnson syndrome) in children. Eur J Pediatr
1997;156:90-3.
39. Burket LW, Greenberg MS, Glick M, Ship JA. Burket's
Oral Medicine. 11''' ed. Greenberg MS, Glick M, Ship JA,
eds. Hamilton, Ontatio, BC: Decker; 2008.
40. Lemak MA, Duvic M, Bean SF. Oral acyclovir for the
ptevention of herpes-associated erythema multiforme. J
Am Acad Dermatol 1986; 15:50-4.
41. Tatnall FM, Schofield JK, Leigh IM. A double-blind,
placebo-controlled trial of continuous acyclovir therapy in
recurrent erythema multiforme. Br J Dermatol 1995;132:
267-70.
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