Myocarditis in a Child with Crimean-Congo Hemorrhagic Fever

Introduction

Crimean–Congo hemorrhagic fever (CCHF) is a viral, tick-borne disease that can be fatal, especially in the adult patient population. After a short incubation period, CCHF the most common presenting symptoms are a sudden onset of high fever, malaise, nausea and vomiting, diarrhea, tonsillopharyngitis, headache, and myalgia. Additional symptoms can include neuropsychiatric and cardiovascular changes (Ergonul 2006). CCHF involves multiple organ systems. Pericardial effusion, cardiac hypokinesia, T-wave changes, and bundle branch block have been reported previous studies in adult patients with CCHF (Engin et al. 2009, Yilmaz et al. 2011). Although myocardial involvement had been shown in adult patients, it is not clear that cardiac involvement is present in children with CCHF. We report a 13-year-old boy patient with myocarditis during the course of CCHF who has completely resolved after the convalescent period of the disease.

Case report

A 13-year-old healthy male patient was admitted to emergency department with fever and vomiting. About 15 days before admission, he was bitten by a tick, and a friend removed the tick. He was hospitalized with a suspicion of CCHF. At admission, physical examination was normal and white blood cell count was 2300/μL, hemoglobin was 11 grams/dL, and platelet count was 43,000/μL. Coagulation tests were as follows; Prothrombin time (PT) 18.7 s (9.4–12.5), activated partial thromboplastin time (aPTT) 39.6 s (25–38), and international normalized ratio (INR) was 1.7 (0.8–1.2). Aspartate aminotransferase (AST) level was 450 U/L, alanine aminotransferase (ALT) was 150 U/L, D-dimer 28.6 mg/L (<2.0 mg/L), creatine phosphokinase (CPK) was 243 U/L (55–170 U/L), and lactate dehydrogenase (LDH) was 603 U/L. PCR for CCHF was positive. Immediately fresh frozen plasma was initiated at a dose of 10 mL/kg per day because of the coagulation abnormality. Ribavirin treatment was started 2 grams/day initial loading dose on first day and 1 gram four times a day for maintanence. After initiation of ribavirin treatment, the patient developed bradycardia and hypotension. Electrocardiography showed nonspesific ST segment depression and sinus bradycardia. Cardiac enzymes were as follows: Creatine kinase MB (CK-MB) 35 ng/mL (0–4.3), troponin I 0.42 ng/mL (0–0.4), and brain natriuretic peptide (BNP) was 471 pg/mL (0–100) elevated.

Echocardiography showed mild mitral valve regurgitation and minimal septal hypertrophy with an ejection fraction of 65%. The patient was diagnosed with myocarditis with the help of clinical findings and echocardiographic and laboratory studies. Thrombocytes were administered because of intermittent epistaxis and gingival bleeding. Ribavirin was stopped at the fourth day of treatment because of bradycardia. At the third day of admission, fever decreased. After cessation of ribavirin, bradycardia resolved. Fresh frozen plasma was continued for 9 days. The troponin I level decreased to 0.04 ng/mL and the CK-MB level decreased to <1 ng/mL. Mitral valve regurgitation and septal thickness of the interventricular septum resolved completely. After 14 days of hospitalization, the patient's leukocyte, platelet, and coagulation tests were within normal range and he was discharged.

Discussion

The pathogenesis of CCHF is poorly understood, but it is known that infection of the endothelium has an important role in CCHF pathogenesis (Ergonul 2006). Direct invasion of the heart muscles by the virus or endothelial damage of cardiac structures may have a role in cardiac involvement. Several different viruses, like Coxsackie A/B and adenovirus, may cause myocarditis and cardiomyopathy, but myocardial involvement of CCHF in children has been rarely reported (Gül et al. 2011). Previously, experimental clinical studies have shown that hemorrhagic fever viruses are able to cause cardiac involvement. Echocardiography is a helpful tool for evaluating cardiac involvement, and it showed mitral valve failure and minimal septal hypertrophy in our patient. (Wali et al. 1998, Savoia et al. 2005).

Mortality in CCHF is characterized by refractory shock, severe coagulopathy, and multifocal necrosis of the liver and other viscera. Fatal outcome in CCHF might be due to severe gastrointestinal hemorrhage, severe anemia, cerebral hemorrhage, shock associated with prolonged diarrhea, myocardial infarction, lung edema, and pleural effusion (Ergonul 2006). Our previous study showed that low serum cytokine levels could be associated with a mild disease course and low mortality rate in children compared to adult patients (Tezer et al. 2014b). Cardiac involvement of CCHF has been mentioned in a few studies. Engin et al. studied cardiac involvement in 52 adult patients with echocardiograpy, and they found that cardiac involvement influenced mortality rate. Patients were classified as severe and nonsevere according to their clinical status. Lower left ventricular ejection fraction, higher systolic pulmonary artery pressure, and more frequent pericardial effusion (p<0.01) was observed in the severe group (n=17; 38.6%). These investigators suggested that cardiac impairment is more frequent in the severe patients group (Engin et al. 2009). The current study has shown that pericardial effusion and low ventricular ejection fraction could be due to myocardial impairment. (Engin et al. 2009).

Yilmaz et al. evaluated electrocardiograms of 49 adult CCHF patients. Thirty-one patients survived and 18 patients died of CCHF. T-wave changes and bundle branch block were more frequently observed in patients who died. Presence of T-wave negativity or bundle branch block in that cohort of patients with CCHF predicted death with a sensitivity of 72.7%, specificity of 92.6%, positive predictive value of 88.9%, and negative predictive value of 80.6%. (Yilmaz et al. 2011).

Gül et al. investigated cardiac involvement in 23 pediatric CCHF patients. A standard 12-lead electrocardiography and echocardiography were performed. Electrocardiographic (ECG) parameters were within normal ranges, and seven patients (30%) had minimal (<1 cm) pericardial effusion. Fifteen (65%) patients had segmental wall motion abnormalities (hypokinesia). After the disease had resolved, all cardiac wall hypokinesia had disappeared. Neither valvular nor ECG abnormality was observed in that population. Patients were not diagnosed as having myocarditis. These investigators concluded that cardiac involvement appeared to be more frequent in children with CCHF disease than in adults (Gül et al. 2011).

Oflaz et al. studied resting heart rate of CCHF patients in children. They evaluated 84 male patients. Twenty-six patients were in the severe group. In this group, resting heart rate was higher compared to nonsevere group. The optimal cutoff value of resting heart rate (RHR) to predict disease severity was >96 beats per minute (bpm), with 70.6% sensitivity and 50.1% specificity. (Oflaz et al. 2014)

Bradycardia could be seen as a side effect in patients receiving ribavirin treatment for CCHF disease (Oflaz et al. 2013, Tezer et al. 2014a). Our patient also developed bradycardia associated with ribavirin treatment, and for that reason he was diagnosed as having myocarditis according to clinical, echocardiographic, and laboratory findings. The incubation period of our patient was 15 days. The incubation period for CCHF could differ depending on several factors, including viral dose and route of exposure. The incubation period of 3–12 days is followed by a febrile period of 5–12 days and a prolonged convalescence (Halstead 2011).

In conclusion, it should be kept in mind that myocarditis could be seen in children with CCHF. Close monitoring of the patients is necessary because all clinical symptoms of myocarditis may not be seen; hypotension could be an alerting symptom of in CCHF patients.