Global Research Journal of Public Health and Epidemiology: ISSN-2360-7920, Vol. 2(3): pp 071-074, May, 2015.

Copyright 2015 Spring Journals

Review

Recurrent erythema multiforme: A dental case report

1
Jitender Solanki and 2Sarika Gupta
1
Associate Professor, Department of Public Health Dentistry, Vyas Dental College and Hospital, India
2
Postgraduate Student, Oral Medicine and Radiology, Vyas dental college & Hospital

Corresponding Authors E-mail: solankijitender@gmail.com

Accepted 27th April

Erythema multiforme is a rare acute mucocutaneous condition caused by a hypersensitivity

reaction. It can be triggered with the use of certain drugs or infectious agents, mainly Herpes
Simplex virus. It is important to know the etiological factor behind the disease in order to cure the
disease or even to prevent attacks in case of recurrent form. This article illustrates a case report of
patient with recurrent form of erythema multiforme who responded to antiviral treatment after taking
ineffective steroid treatment.

Keywords: Acyclovir, Dapsone, Ulcers, Erythema

INTRODUCTION

Erythema multiforme (EM) is a rare acute increased in size with blood crustations. He gives
mucocutaneous condition caused by a hypersensitivity history of similar ulcers which had developed for the last
reaction with the appearance of cytotoxic T lymphocytes 2 years in summers, but now they have appeared in
in the epithelium that induce apoptosis in keratinocytes, winters and are worse. He got relieved with the
leading to satellite cell necrosis. A number of factors can treatment that he had taken for those ulcers. But this
be associated with EM, but it is found to be mostly time no relief was achieved. Although ulcers are not
associated with preceding infection with herpes simplex associated with pain or burning sensation but were
virus (HSV). Most other cases are initiated by drugs predisposed with an episode of fever for 2 days, patient
(Scully and Began, 2008). When recurrent herpes gives no history of any change in toothpaste or lip
simplex is an important etiologic factor in EM minor, EM cosmetic in the past one month. Patient is under
major is often preceded with mycoplasmal infections and systemic and topical steroids since 5 days but no relief is
drug intake. The various etiological factors are given in achieved (tab. Betnisol fort 1 TDSx 5 days, cefadox
table 1: ( Sokumbi and Wetter, 2012; Rafael Lima Verde 500mg 1 BDx 5days, tab. Bfolien plus 1 BDx 7 days,
Osterne et al., 2009) flutibact ointment T/A x7 days). He smokes occassionaly
Other than these, Nasabzadeh TJ et al in his case (1-2 cigerettes a day) since 1 year. All his vital signs
report have stated that the precise trigger of a given were within normal limits. Lymph nodes were non tender
patient's recurrent EM often remains elusive. He has and non palpable. On inspection lower lip was grossly
pointed towards a hormonal influence interpreted as swollen, cracked, with split crusted bleeding.
autoimmune progesterone dermatitis (APD), Widespread fibrin covered erosions were seen with
Nasabzadeh et al., 2010. surrounding erythematous area. (Figure 1) Similar lesion
was seen on the upper lip but involvement of the lower
lip was more. On palpation, the lesion was tender on
Care report touch and bleeded profusely. Labial mucosa was
Reddish and erythematous. Posteriorly on hard palate a
An 18 year old male patient came to the OPD with the reddish erythematous area was seen which was non
complaint of ulcers on lower lip since 15 days. Patient tender on palpation ((Figure 2).
was apparently alright uptill 15 days back when he
noticed 2 pin point size ulcers on lower lip in the night.
Next morning when he got up, the ulcers had markedly
072. Glob. Res. J. Public Health and Epidemiol.

Table 1: various etiological factors

Causative agent Type

Drugs Antibacterial; anticonvulsants; analgesics; nonsteroidal antiinflammatory drugs; antifungals
Infectious agents Virus; Herpes simplex, Epstein-Barr virus, Cytomegalovirus, varicella-zoster virus, Mycoplasma
pneumonia, hepatitis viruses, Bacterial; Mycobacterium, streptococci, Fungal; parasites

Figure 1: Widespread fibrin covered erosions with surrounding erythematous area seen on lower lip.

Figure 2: Reddish erythematous area seen on hard palate

DISCUSSION treatment of 65 patients with recurrent EM, noted that

the mean number of attacks per year was six with the
Based upon its clinical spectrum, erythema multiforme mean duration of 9.5 years, which reflected its chronicity.
has been further grouped into recurrent erythema Maximum patients had oral mucous membrane
multiforme and the rare persistent erythema multiforme involvement with mostly viral etiology. Therefore,
(Table 2, Drago et al., 1995). According to a study by antiviral drugs, mostly acyclovir was found to be the
Schofield JK et al who reviewed the clinical features and most effective first-line treatment. Patients who did not
 073. Solanki and Gupta

Table 2: Clinical features of various types of EM (3)

CATEGORY OF EM Features FEATURES

Erythema multiforme minor Typical target lesions or raised atypical target lesions.
< 10% of the body surface area is affected.
May affect only the oral mucosa with mild to severe erythema, erosions
and ulcers.
Erythema multiforme major Cutaneous lesions and at least 2 mucosal sites (typically oral mucosa)
affected.
< 10% of the body surface area involved.
Typical target lesions or raised atypical target lesions or both;
symmetrically distributed.
Severe, widespread oral lesions.
Stevens-Johnson syndrome Differs from erythema multiforme major in terms of typology and location of
lesions and the presence of systemic symptoms. < 10% of the body
surface area is involved.
Primarily atypical flat target lesions and macules.
Widespread lesions involving multiple mucosal sites with scarring.
Prodromal flu-like systemic symptoms are common.
Overlapping Stevens-Johnson No typical targets; flat atypical targets are present. Up to 10%30% of the
syndrome and toxic epidermal body surface area affected. Prodromal flu-like systemic symptoms
necrolysis common.
Toxic epidermal necrolysis When spots are present, characterized by epidermal detachment of > 30%
of the body surface and widespread purpuric macules or flat atypical
targets. In the absence of spots, characterized by epidermal detachment >
10% of the
body surface, large epidermal sheets and no macules or target lesions.

respond to acyclovir responded to a small proportion of 5. Expression of HSV DNA in keratinocytes. The length
dapsone. The most resistant patients were treated with of HAEM eruption depends upon the duration of gene
azathioprine with complete disease suppression in all expression.
+
cases (Schofield et al., 1993). On the other hand, a 6. Infiltration of HSV-specific CD4 Th1 cells in the
study by Tatnall FM et al have shown that continuous dermis/epidermis of HAEM lesions Activated T cells
acyclovir therapy can completely suppress attacks of have a restricted TCR repertoire and include increased
recurrent EM and may even lead to disease remission proportion of Vb 2 cells.
(Tatnall et al., 1993). 7. HSV-specific T cells respond to HSV antigens and
The pathophysiology behind herpes simplex virus generate IFN-g
associated EM (HSV-EM) is cell-mediated immune 8. Generation of cytokine and chemokines amplification
reaction against viral antigen-positive cells that contain cascade, including TGF-b, Mig, IP10 and RANTES and
the HSV DNA polymerase gene (pol). It is associated recruitment of NK cells, monocytes and leukocytes
with typical target lesion showing concentric zones of 9. Recruitment of auto reactive T cells to the lesion site
color change (Sokumbi andWetter, 0012). resulting in an autoimmune amplification loop
Histopathologic testing and other laboratory 10. Epidermal cell damage results from attacks by
investigations may be used to confirm the diagnosis of cytotoxic T cells, NK cells and monocytes and/or
EM and to differentiate it from other similar clinical chermokines in varying combinations
waf
conditions (Sokumbi andWetter, 0012). The 11. TGF-b and p21 are expressed in
pathogenesis of Herpes associated EM includes a virus- keratinocytes at the site and adjacent to the epidermal
triggered autoimmune component (Aurelian et al., 2003). damage, thereby possibly contributing to apoptotic cell
1. Primary or recurrent HSV infection which may be death
subclinical or accompanied by visible vesicular lesions. Clinically, EM can be confused with urticaria, Stevens-
+
2. Macrophages and/or CD34 hematopoetic progenitors Johnson syndrome, fixed drug eruption, paraneoplastic
engulf HSV and DNA is fragmented resulting in pemphigus, bullous pemphigoid, Sweet's syndrome,
generation of DNA fragments that encompass HSV polymorphus light eruption, Rowell's syndrome and
genes including pol. cutaneous small-vessel vasculitis. Antiviral prophylaxis is
3. Peripheral extravasation of PBMC carrying HSV DNA required for patients with HSV-associated recurrent EM
fragments possibly related to ICAM-1 expression on and idiopathic recurrent EM. For patients with severe
endothelial cells mucosal involvement, hospitalization is considered since
4. Deposition of HSV DNA at distant skin sites it leads to poor oral intake and subsequent fluid and
074. Glob. Res. J. Public Health and Epidemiol.

electrolyte imbalance (Sokumbi andWetter, 0012). REFERENCES

Studies have proven the efficacy of corticosteroids in
the treatment of EM but their use as maintenance Scully C, Began J (2008). Oral mucosal diseases: Erythema
therapy is not clearly indicated because of the multiforme. British Journal of Oral and Maxillofacial
associated side effects. Remission of herpes associated Surgery;46(2):9095.
EM can occur by oral acyclovir with short-course which Sokumbi O, Wetter DA (20012). Clinical features, diagnosis,
and treatment of erythema multiforme: a review for the
represents a safer, more effective treatment for many practicing dermatologist. Int. J. Dermatol.; 51(8):889902.
patients with recurrent EM. However, EM cannot be Rafael Lima Verde Osterne et al (2009). Management of
prevented if administered after a herpes simplex Erythema Multiforme Associated with Recurrent Herpes
recurrence has occurred. Repeated topical treatment Infection: A Case Report. JCDA.;79:597-601.
with acyclovir to sites of recurrent herpes infection is Nasabzadeh TJ, Stefanato CM, Doole JE, Radfar A, Bhawan
said to prevent erythema multiforme. It has been seen in J, Venna S (2010). Recurrent erythema multiforme triggered
several studies that acyclovir completely suppress by progesterone sensitivity. J. Cutaneous
recurrent EM in the majority of patients and produce Pathol.;37(11):11641167.
partial suppression in others (Huff et al., 1983). Drago F, Parodi A, Rebora A (1995). Persistent erythema
multiforme: Report of two new cases and review of
Continuous acyclovir therapy in patients who have a literature.;33(2):366-369.
clear-cut relationship between HSV and EM are often Schofield JK, Tatnall FM, Leigh IM (1993). Recurrent erythema
effectively treated with acyclovir (200 mg 5x/day for 5 multiforme: clinical features and treatment in a large series
days) started at the earliest sign of a herpes attack. But of patients. Brit. J. Dermatol.;128(5):542545.
patients who have frequent attacks of EM, whether HSV- Tatnall FM, Schofield JK, Leigh IM (1993). A double-blind,
related or not, should receive a trial of continuous placebo-controlled trial of continuous acyclovir therapy in
acyclovir before alternative therapies are tried. It is not recurrent erythema multiforme. Brit. J.
clear whether failures of acyclovir are related to viral Dermatol.;132(2):267270.
resistance to acyclovir or to non-HSV-induced recurrent Aurelian L, Ono F, Burnett J (2003). Herpes simplex virus
(HSV)-associated erythema multiforme (HAEM): A viral
EM. One case report discussed a patient with frequent disease with an autoimmune component. Dermatology
post-herpetic recurrent EM resistant to continuous Online J.; 9(1):1-12.
acyclovir treatment but responsive to valacyclovir (Huff Huff JC, Weston WL, Tonnesen MG (1983). Erythema
et al., 1983). The use of thalidomide should be reserved multiforme: A critical review of characteristics, diagnostic
for severe cases(Leaute-Labreze et al., 2000). The criteria, and causes. J. Am. Acad. Dermatol.;8(6):763775.
efficacy of dapsone in treating recurrent EM has been Leaute-Labreze C, Lamireau T, Chawki D, Maleville J, Taieb A
reported earlier. Antimalarials (mepacrine or (2000). Diagnosis, classification, and management of
hydroxychloroquine) have also resulted in disease erythema multiforme and StevensJohnson syndrome. Arch
suppression where acyclovir treatment has failed. But it Dis Child;83:347352.
Sen P, Chua SH (2004). A Case of Recurrent Erythema
is recommended as a second line treatment due to the Multiforme and its Therapeutic Complications. Ann Acad
associated side effects. Mycophenolate mofetil has been Med Singapore.
shown to be an effective and relatively safe
immunosuppressive agent in recurrent EM in case of
failure to anti malarias. However, its high cost limits its
use (Sen and Chua, 2004).

CONCLUSION

The most important step in the management of erythema

multiforme or similar cutaneous lesions is proper history
taking. This is done to rule out the correct etiology of the
disease. Treatment is aimed based upon the causative
factors like virus or drug related. The use of
corticosteroids is most prevalent in case of erythema
multiforme. However, many side effects have been
reported with its use for a longer duration. In the present
case report when the patient could not be cured with
steroids a treatment plan consisting of antiviral drug
helped. Therefore, it is important to rule out the etiology
before forming a proper treatment plan.