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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 30  |  Issue : 3  |  Page : 306-309

Drug induced erythema multiforme: Reporting 2 cases


1 Department of Oral Medicine and Radiology, Mar Baselios Dental College, Kothamangalam, Kerala, India
2 Department of General Surgery, ESIC-MC PGIMSR, Bengaluru, Karnataka, India

Date of Submission08-May-2018
Date of Acceptance07-Jul-2018
Date of Web Publication18-Oct-2018

Correspondence Address:
Dr. Kamala Rawson
Department of Oral Medicine and Radiology, Mar Baselios Dental College, Kothamangalam, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaomr.jiaomr_73_18

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   Abstract 


Erythema multiforme (EM) is a rare, acute, inflammatory mucocutaneous condition caused by a hypersensitivity reaction with the appearance of cytotoxic T lymphocytes in the epithelium that induce apoptosis in keratinocytes, which leads to satellite cell necrosis. Reactions to drugs are quite common and are generally mild, hence not reported. However, occasionally life-threatening reactions including EM major (Steven–Johnson syndrome) and toxic epidermal necrolysis may occur. A wide spectrum of drugs can sometimes give rise to EM. We report two cases of EM following administration of non-steroidal anti-inflammatory drugs.

Keywords: Drug reaction, erythema multiforme, hypersensitivity reaction


How to cite this article:
Rawson K, Rani R U, Susan S, Roy G, Gupta N. Drug induced erythema multiforme: Reporting 2 cases. J Indian Acad Oral Med Radiol 2018;30:306-9

How to cite this URL:
Rawson K, Rani R U, Susan S, Roy G, Gupta N. Drug induced erythema multiforme: Reporting 2 cases. J Indian Acad Oral Med Radiol [serial online] 2018 [cited 2019 Jan 23];30:306-9. Available from: http://www.jiaomr.in/text.asp?2018/30/3/306/243664




   Introduction Top


Erythema multiforme (EM) is an acute inflammatory disease that affects skin and/or mucous membranes that cause a variety of skin lesions, hence the name multiforme. EM usually affects apparently healthy young individuals with the peak age of 20–40 years although 20% of cases are young children.[1]

It has been classified into several variants, mainly minor, major, and severe forms, as it may involve the mouth alone, or may present with a skin eruption, with or without lesions of oral or other mucous membranes. EM minor typically affects only one mucosa and may be associated with symmetrical target skin lesions on the extremities. EM major typically involves two or more mucous membranes with more variable skin involvement termed Stevens–Johnson syndrome usually involve the skin extensively.[2] A severe variant of the disease is TEN (toxic epidermal necrolysis, Lyell's disease), which results in sloughing of skin and mucosa in large sheets. Morbidity is high and patients with this form of disease are managed in burn centers where necrotic skin is removed under general anesthesia. Herpes-associated EM is common enough to be categorized by some authors as distinct form of the disease.[3]

Drug-related EM – A wide range of drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs), barbiturates, cephalosporins, estrogens, phenothiazines, progestrones, protease inhibitors, sulphonamides, sulphonylurea derivatives, and tetracyclines may give rise to EM, and it may be clinically impossible to distinguish drug-induced EM from disease due to other causes.[4]


   Case Reports Top


Case I

A 4-year-old female child reported to the Department of Oral Medicine and Radiology, with the chief complaint of painful ulcers on the tongue, lips, and palate since 2 days due to which she was unable to open her mouth and eat anything. Her mother informed that when she tried to clean the patient's mouth with her finger, fresh bleeding occurred. Medical history revealed that patient took medication for fever and throat pain from a physician 4 days back. On the second day of medication, she developed ulcers on the lips and in the mouth along with fever. No previous history of uncontrolled bleeding was reported. Personal history and family history were non-contributory. On general physical examination, all vital signs were normal except temperature which was 99.5 degrees F. Extraoral examination of the lesion revealed diffuse erythematous areas on the vermilion borders of the upper as well as lower lip, which were covered by pseudomembranous slough and crustations on the lips and left corner of the mouth. Bleeding areas were present on the right corner of the mouth [Figure 1]a. As the patient was unable to open her mouth, the intraoral examination was compromised at the time of her first visit. When the patient reported after 3 days of medication, she was able to open her mouth and diffuse areas of ulcerations were seen on her tongue [Figure 1]b. Hence, on the basis of history and clinical examination, a diagnosis of drug-induced EM was given. Management was done by giving 15 mg of prednisolone once daily for 3 days and subsequently the dose was reduced to 10 mg for the next 3 days, the 5 mg for next 3 days. After 10 days of medication, intra as well as extraoral bleeding had stopped and the lesions were completely healed [Figure 1]c and [Figure 1]d.
Figure 1: (a) Cr ustations on lips. (b) Ulcerations on tongue (3 days after medication). (c) Postmedication (crustations healed). (d) Postmedication (ulcers healed)

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Case II

A 50-year-old male patient reported to the department with the chief complaint of pain, bleeding from the mouth, and rashes all over the body since 2 days. The history of present illness revealed that 4 days back patient felt pain in the gums for which he took medication from a quack. After 2 days of the medication, when he got up in the morning, he noticed rashes all over the body and continuous bleeding from his mouth. Severe, continuous pain in the lips, gums, and palate was present since 2 days due to which he was unable to eat or drink anything. The past medical and the dental history were non-contributory as well as the personal and the family histories were non-significant. The general physical examination was unremarkable except temperature which was 99 degree F. On extraoral examination, multiple erythematous, macular target lesions measuring about 0.5–1 cm in diameter were present all over the face of the patient [Figure 2]a. Similar concentric, macular target lesions measuring were present on the chest, arms, and thighs of the patient [Figure 2]b and [Figure 2]c. On palpation, these lesions were flat, non-tender, and not ulcerative. On the vermillion border of the upper and lower lips there were diffuse bleeding areas covered by crustations [Figure 2]d.
Figure 2: (a) Target lesions on the face. (b) Lesions on chest. (c) Lesions on forearm. (d) Bleeding areas covered by crustations on the lip. (e) Intraoral bleeding. (f) Crustations on lips and ulcerations on palate. (g) Extraoral lesions on chest healed after medication. (h) Intraoral lesions healed after medication

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On intraoral examination, there was fresh bleeding from the tongue as well as the maxillary and the mandibular gingival margin [Figure 2]e. Ulcers measuring 2–3 mm in diameter were present on the tip of the tongue and the hard palate as well as the soft palate region [Figure 2]f. On palpation, the ulcers were highly tender with profuse bleeding. On the basis of history and clinical examination similar to the first case a diagnosis of drug-induced EM involving the oral mucosa and skin. Management was done by giving 40 mg of prednisolone once daily for 5 days and subsequently the dose was reduced to 20 mg for the next 5 days, the 10 mg for next 5 days, and then 5 mg for next 5 days. For the skin lesions on the face, chest, arms, and legs we prescribed him ointment clobetasol propionate 0.05% to apply twice daily. After 20 days of medication, the extraoral lesions were completely healed [Figure 2]g and intraoral bleeding had subsided [Figure 2]h. In both cases symptomatic relief was given by topical anesthetic mouth rinse (benzyadamine hydrochloride) twice a day. A complete hemogram was advised in both the patients who reported absolutely normal counts of the blood cells. Differential diagnosis given were thrombocytopenic purpura, allergic stomatitis, pemphigus, and herpes simplex virus (HSV) infection.


   Discussion Top


EM is a typically mild, self-limiting, and recurring mucocutaneous rection characterized by target or iris lesions of the skin or mucous membranes which resolve within 1–6 weeks.[5] The best documented trigger factors for EM are drugs and microorganisms in 80%–90% of cases. The drugs most frequently associated with EM are sulfonamides, non-steroidal anti-inflammatory agents, penicillins, trimethoprim, barbiturates, and carbamazepine. The most frequently documented microorganisms are mycoplasma pneumonia and HSV-1 and II in 70%–80% of the cases. Both HSV-I and HSV-II have been shown to trigger EM. Despite this well-established clinical association, not all EM episodes are preceded by HSV infection and not all HSV episodes are followed by EM.[6] Other triggers for EM include benign and malignant tumors, radiotherapy, Crohn's disease, sarcoidosis, histoplasmosis, and infectious mononucleosis.

The pathology of EM is that there is a per vascular infiltrate of CD4 and CD8 lymphocytes surrounding swollen blood vessels in the upper dermis with papillary dermal edema and vacuolar degeneration of the basal layer, subdermal blister formation, and epidermal necrosis of keratinocytes that increases with older lesions. The individual necrotic keratinocytes are surrounded by CD8 cells, termed “satellite cell necrosis”.[7]

Clinical presentation

EM is characterized by multiple target or iris lesions. All lesions typically present within approximately 3 days of onset. The lesions have a symmetric distribution. They present as circular erythematous plaques in a concentric array with lesion size ranging from 2 to 20 mm. A central blister or area of necrosis may be present. Initially the lesions are seen acrally (extensor surfaces of hands, feet, elbows, and knees). Less commonly, lesions may also be seen on the palms, sole, thighs, and buttocks.[8] Lesions may appear at sites of trauma or physical irritation and at sites of sun exposure.[7] EM is known to cause alterations in skin color.[9] Prodromal symptoms are rare, when present are typically mild and non-specific (cough, rhinitis, low-grade fever, malaise, diarrhea, myalgia, and arthritis). The lesions are usually asymptomatic, although burning or itching sensations have occasionally been reported. Complete recovery from an individual EM attack ranges from 1 to 4 weeks with individual lesions typically resolving in 10 to 14 days.

Oral mucosal lesions occur in >70% of cases of EM. Although less well-recognized EM does present as oral mucosal ulcerations with few or no skin lesions. Preferred sites of involvement include the lips, alveolar mucosa, and palate. Lip involvement is almost universal. Although target or iris lesions may be seen, superficial ulcerations or crusted lesions are more common.[10]

Management

Mild cases of oral EM may be treated with supportive measures only, including topical anesthetic mouthwashes and a soft or liquid diet. Moderate-to-severe oral EM may be treated with a short course of systemic corticosteroids in patients without significant contraindications to their use. An initial dose of 30 mg/day to 50 mg/day prednisolone or methylprednisolone for several days and then tapered is considered helpful in shortening the healing time. Higher doses of steroids are considered necessary for severe cases. Prophylactically, acyclovir can be used to prevent HSV-related EM.[3]


   Conclusion Top


Drug-induced oral EM is a rare and less described variant of EM. EM is often triggered by HSV infections and rarely by adverse drug reactions. Even though primary attack of drug-induced EM is confined to the oral mucosa the subsequent attack can produce more severe forms of EM (EM minor and EM major) involving their skin. It is important for stomatologists, oral pathologists, and general dentists to differentiate from other vesicullobullous lesions from drug-induced EM for prompt management and proper follow-up.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Scully C, Bagan J. Oral mucosal diseases: Erythema multiforme. Br J Oral Maxillofac Surg 2008;46:90-5.  Back to cited text no. 1
    
2.
Dubey NK, Jajoo D, Gupta A, Sharma D. Antipyretics induced erythema multiforme. Indian Pediatr 1995;32:1117-9.  Back to cited text no. 2
    
3.
Greenberg MS. Ulcerative, vesicular, and bullous lesions. Burkett's Oral Medicine. 9th ed., Ch. 2. Philadelphia: J.B. Lippincott Company; 1994. p. 20-2.  Back to cited text no. 3
    
4.
Scully C, Bagan JV. Adverse drug reactions in the orofacial region. Crit Rev Oral Biol Med 2004;15:221-39.  Back to cited text no. 4
    
5.
Sen P, Chua SH. A case of recurrent erythema multiforme and its therapeutic complications. Ann Acad Med Singapore 2004;33:793-6.  Back to cited text no. 5
    
6.
Léauté-Labrèze C, Lamireau T, Chawki D, Maleville J, Taïeb A. Diagnosis, classification, and management of erythema multiforme and Stevens-Johnson syndrome. Arch Dis Child 2000;83:347-52.  Back to cited text no. 6
    
7.
Chan LY, Tang WY, Leung CY, Lo KK. Recurrent erythema multiforme in a child. Hong Kong Med J 2000;6:331.  Back to cited text no. 7
    
8.
Williams PM, Conklin RJ. Erythema multiforme: A review and contrast from Stevens-Johnson syndrome/toxic epidermal necrolysis. Dent Clin North Am 2005;49:67-76, viii.  Back to cited text no. 8
    
9.
De Silva DA, Seah AB. A “tattoo” of erythema multiforme. Ann Acad Med Singapore 2007;36:226.  Back to cited text no. 9
    
10.
Neville BW, Damm DD, Allen CM, Bouquot JE. Immune Mediated Diseases and Their Evaluation. Oral and Maxillofacial Pathology. 3rd edition. Chapter 16. 2009:1:776-9.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]



 

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