American Journal of Emergency Medicine (2009) 27, 132.e3–132.e5
www.elsevier.com/locate/ajem
Case Report Myocarditis due to oral flurbiprofen use Abstract We report a 23-year-old man presenting with chest pain. He denoted skin eruptions on his hands, lips, mouth, and penis 24 to 36 hours after he had taken flurbiprofen 10 days ago. Detailed examination showed an ulcerated, pitching lesion with a dimension of approximately 2 × 2 cm on his penis; however, other explained skin lesions were ameliorated. ST elevations were present in the electrocardiogram. Cardiac biomarkers gradually rose. The scintigraphy showed myocardial hypoperfusion in the inferoseptal wall. This phenomenon is a rare case of myocarditis due to hypersensitivity reaction. In the case of nonspecific angina pectoris accompanied by electrocardiogram changes, drug-induced myocarditis must hold a place in differential diagnoses. Complications because of therapeutic doses of nonsteroidal anti-inflammatory drugs (NSAIDs) are not usual. The most common reported adverse reactions include cholestasis, fixed eruptions, asthma, and cutaneous vasculitis [1,2]. Compared with other NSAIDs, flurbiprofen is a well-tolerated drug [3-5]. Fixed drug eruption begins with nummular erythematous lesions. Later, an erythema fades and pigmentation remains. If the same drug is taken repeatedly, an erythema may occur again on the same location. The skin reaction can be severe enough to form edema, vesicle, and bullae. Among men, glans penis is one of the most effected areas [6]. Usually, viral infections play a huge role in the etiology of myocarditis, but drug use may cause it as well [7]. In the literature review, there are only a few reports on the NSAIDs leading to myocarditis; however, we could not find any paper about the use of flurbiprofen causing myocarditis. We think that this case is the first one in the literature. Therefore, we aimed to present such an interesting case. A 23-year old man was admitted to emergency service because of chest pain lasting for 2 days. The patient described resting angina without any history of cardiac pathology of himself or his family. On examination, there was only mild sensitivity of the chest with palpation. The vitals were in the reference range. By investigating the details of the patient's history, it was understood that he had taken 2 pills of 0735-6757/$ – see front matter © 2009 Elsevier Inc. All rights reserved.
flurbiprofen (Majezik, Sanovel, Istanbul, Turkey) because of headache 10 days ago. He denoted skin eruptions on his hands, lips, mouth, and penis 24 to 36 hours after he had taken the drug. Detailed examination showed an ulcerated, pitching lesion with a dimension of approximately 2 × 2 cm on his penis; however, other explained skin lesions were ameliorated (Fig. 1). The electrocardiogram (ECG) showed sinus rhythm with a cardiac rate of 50 beats/min and an ST elevation of 0.5 to 1 mV in all derivations (Fig. 2). The chest x-ray was normal. The echocardiography (ECHO) showed normal cardiac cavities, valvular motions, and systolic and diastolic functions, with an ejection fraction of 58%. The laboratory parameters were in reference ranges, except cardiac biomarkers (troponin I, 3.41 μg/L [reference range, b0.1 μg/L]; creatine kinase (CK), 689 U/L [reference range, b190 U/L]; creatine kinase-MB form (CK-MB), 76 U/L [reference range, b25 U/L); and myoglobin, 221 μg/L [reference range, 10-46 μg/L]) and hematocrit (47%). The blood cultures were negative. After hospitalization with the
Fig. 1
The penile lesions due to fixed drug eruption.
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Fig. 2
The patient's derived 12-lead ECG.
diagnosis of drug-induced myocarditis, the cardiac biomarkers kept rising (CK, 1634 U/L; CK-MB, 179 U/L; and troponin I, 18.82 μg/L). In the fourth day of hospitalization, the cardiac biomarkers began to decline, and they reached reference levels in the eighth day. On the seventh day, Tl-201 rest-redistribution myocardial perfusion single photon emission computed tomography (SPECT) was planned to prove the diagnosis. It showed an ischemia as a perfusion defect during rest that totally resolved at redistribution in the inferoseptal wall (Fig. 3). Supportive care was given to the patient. He was discharged on the ninth day without any complication. Drug-induced reactions are one of the common complaints of emergency service admissions. Allergic reactions range from insignificant urticaria to fatal anaphylaxis. Clinical features range from local organ involvement to serious multisystem effects and even to death [8]. Drug-induced skin eruptions manifest with various morphologic characteristics. One of this is fixed drug eruptions. These eruptions may occur on the same side or sides when the drug is used. In an acute episode, the lesions are erythematous and bordered sharply. After healing, hyperpigmentation is constituted and may last for years. Lesions placed on glans penis are typical
and they may be bullous. In our case, the eruptions began with erythematous lesions and transformed into vesicular and bullous lesions, especially on penis. Development of these lesions caused skin erosions (Fig. 1). Most urticarial and/or angioedematous reactions to NSAIDs are thought to appear because of pseudoallergic phenomena, but there is also evidence that during use of these drugs, the occurrence of maculopapular rashes may well be manifestations of type IV hypersensitivity [1]. The time consequence between drug and skin eruptions has vital importance so as to clarify the blamed drug. If the drug has not been used before and if the erythema is a hypersensitivity reaction, then it may last a few weeks to gain sensitivity to the drug, so to the eruption. In our case, the eruption occurrence in 24 to 36 hours after drug intake may show that this drug had been used by the patient before. Careful interview gave us the patient's history of previous flurbiprofen (Majezik) use naturally. Another clinical manifestation of drug-induced organ reaction is myocarditis. It is characterized by inflammatory infiltration of myocardium due to infective or noninfective etiology. Although most of the myocarditis is because of viral infections, drugs can be a reason of noninfective causes
Fig. 3 Sequential short-axis images from Tl-201 rest-redistribution myocardial perfusion SPECT. Upper row, rest Tl-201 images show an inferoseptal wall defect. Lower row, redistribution Tl-201 images show total redistribution of the inferoseptal wall.
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[9]. Over the past few years, the cardiac adverse effects of clozapine have become increasingly recognized and reported. Some cases have been related to a peripheral and/ or cardiac eosinophilia that is suggestive of an immunoglobulin E–mediated hypersensitivity reaction. The greatest risk of cardiac involvement is seen during the first month of use, but the risk persists throughout its use [10]. In our case, we suppose that myocarditis occurred because of flurbiprofen (Majezik), an NSAID. In drug-induced myocarditis, an active infiltration of the myocardium by eosinophils, lymphocytes, and histiocytes is pathologically recognized. According to recent immunopathologic techniques, it is offered that several toxic proteins derived from degranulation of eosinophils may play a considerable role in the pathogenesis of the cardiac disorder [11]. The beginning symptoms and findings may include rash, fever, eosinophilia, and markers of cardiac involvement like sinus tachycardia, mild cardiomegaly, slightly increased cardiac enzymes, and ST or T changes in the ECG [12]. Our patient presented with chest pain. Because of late presentation (10th day), no skin eruption was found other than penile lesions. Moreover, no eosinophilia or fever was present. ST elevations were present in the ECG. The ECHO did not show cardiomegaly. Cardiac biomarkers gradually rose. A myocardial biopsy is required to establish the definite diagnosis. The risk of complications, sampling error, and costs of this procedure do not make it the first choice. The SPECT is a noninvasive but sensitive method of imaging. In the previous studies, SPECT was safely used to show myocardial damage in myocarditis [13]. In our case, it showed myocardial hypoperfusion in the inferoseptal wall. In conclusion, in the case of skin eruptions with unknown cause, fixed drug eruptions must be kept in mind in differential diagnoses. Furthermore, when nonspecific angina pectoris accompanied by ECG changes do happen, drug-induced myocarditis must hold a place in differential diagnoses, and further investigations such as ECHO and scintigraphy should be planned so as to put definite diagnosis. Mustafa Uzkeser MD Mucahit Emet MD Sahin Aslan MD Zeynep Cakir MD Sule Turkyılmaz MD Department of Emergency Medicine Ataturk University, School of Medicine 25090 Erzurum, Turkey E-mail addresses:
[email protected] [email protected]
Enbiya Aksakal MD Department of Cardiology Ataturk University, School of Medicine 25090 Erzurum, Turkey
Bedri Seven MD Department of Nucleer Medicine Ataturk University, School of Medicine 25090 Erzurum, Turkey
doi:10.1016/j.ajem.2008.04.030
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