International Journal of Oral & Maxillofacial Pathology. 2012;3(4):34-38 ISSN 2231 – 2250 Available online at http://www.journalgateway.com or www.ijomp.org

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

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. Some of which evolved into target lesions.

1

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 identical.

2 Erythema multiforme regarded by

Shklar and McCarthy as a "Symptom complex".

3 The etiology is obscure, although

a number of agents are known to precipitate the attacks; herpes simplex infection.

4 Other

viral infection, bacterial and fungal infection, drug hypersensitivity, vaccination, radiation therapy, food product allergy, emotional tension.

3,4

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 may also be seen.

1 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 involvement is multiple.

5

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 same disease.

6 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

Case Report

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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). On intraoral examination, approximately 1 x 1mm vesicle (Fig 1f) was present on palatal

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.

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. ISSN 2231 - 2250

Discussion Erythema multiforme is an acute inflammatory disease of the skin and mucous membrane that cause a variety of skin lesions.

7 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 seen.

8 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 in severe cases.

7

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 and bands of erythema.

7 Additionally bullae

and vesicles may also be seen.5 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 trunk, the face, and on the extremities.

9 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

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 by drugs.

10

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 tetracyclines.

11 Sulfa drugs are the most

common triggers.9 Co-trimoxazole is in the

upper third of the table of drugs which certainly, probably or possibly induced Lyell’s syndrome and in the middle of the table of those that induced Stevens-Johnson syndrome.

12 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 of the oral mucosa are denuded.

8 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 characteristic.

7

Skin biopsy of erythema multiforme may show in the epidermis/epithelium apoptotic individual keratinocytes (cellular self-destruction, 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 Stevens-Johnson 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 vessels.

13 Histopathology is not diagnostic

and the immunopathologic features are also nonspecific, the diagnosis is often based on the clinical presentation and the exclusion of other vesiculobullous disorders.

8 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 Stevens-Johnson syndrome.

9

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 SJS.

6,14

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 serologic tests have to be performed.

9

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 such drugs may be detrimental.

8

For all forms of EM, symptomatic treatment, including oral antihistamines, analgesics, local skin care, soothing mouthwash are of

great importance. Oral antacids may be useful for discrete oral ulcers.

9 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.