Acute myocarditis secondary to Shigella sonnei gastroenteritis

Case Presentation: A 38-year-old female was presenting with chest pain and an increased level of troponins with the EKG (electrocardiogram) showing non-specific T-wave changes. Preceding the chest pain, the patient had Shigella sonnei gastroenteritis confirmed by stool culture. The patient’s cardiac catheterization showed normal findings. Thus a diagnosis of bacterial myocarditis was made. The event resolved after successful treatment of the gastroenteritis with ciprofloxacin.


Introduction
The most common cause of acute myocarditis in developed countries is viruses.Bacterial myocarditis is very rare and can be caused by multiple bacteria.Shigella sonnei has rarely been cited as one of the causes of bacterial myocarditis with only a handful of patients reported in the literature (Caraco et al., 1987;Rubenstein et al., 1993).

Case Presentation
A 38-year-old Caucasian female with no significant past medical history presented to the emergency room with typical chest pain of 3 days' duration.The chest pain was preceded by acute diarrhoea, fever, abdominal pain, nausea and vomiting over the previous week.On further inquiry, she mentioned that she had recently travelled to the Caribbean before the diarrhoea started.Four days after the diarrhoea onset and 3 days before admission, she then started experiencing intermittent pressure like chest pain, which was mid-sternal and associated with diaphoresis and nausea.She tried over-thecounter famotidine (Pepcid) with no relief.The primary care physician obtained an electrocardiogram (EKG) showing inverted T waves in leads V4 to V6 (Fig. 1), which is when she was sent to the emergency department for further evaluation.
The patient was not taking any other medications.Her family history was significant for hypertension and diabetes but not for coronary artery disease.Patient's vitals were stable on admission with a normal physical examination.Her laboratory workup showed an elevated troponin of 10.86 ng ml 21 (normal reference is 0.04 to 0.8 ng ml 21 ).Serum creatinine kinase was normal at 158 IU l 21 (normal reference is up to 170 IU l 21 ).Her blood count showed a haemoglobin level of 13.1 g dl 21 with a white cell count of 5900 mm 23 .Her electrolyte panel, liver and kidney function tests, lipid panel and thyroid profile were normal (Table 1).Her C-reactive protein (CRP) on admission was 66.1 mg l 21 .Her B-type natriuretic peptide (BNP) was 221 pg ml 21 .The troponins were trended as illustrated in Table 2.A preliminary diagnosis of non-ST elevated myocardial infarction was made.The patient was started on 81 mg aspirin tablet daily, 75 mg clopidogrel tablet daily, 1 mg enoxaparin kg 21 subcutaneous injections every 12 hours, 25 mg metoprolol succinate extended release tablet once daily and 2% nitrate topical ointment as needed for chest pain.Stool cultures were also sent to the lab because of persistent diarrhoea.Stool studies returned positive for Shigella sonnei that was sensitive to ciprofloxacin.Oral 500 mg ciprofloxacin tablet was started twice daily on the same day of admission to the hospital, at the same time the stool samples were sent to the lab.Blood cultures were also sent along with the stool studies but returned negative.Unfortunately, stool microscopy was never sent.It was preferred to start the oral ciprofloxacin empirically for fear of worsening condition, especially with the suspected myocarditis and the potential benefit that would be obtained from early antibiotic start.That is why the oral ciprofloxacin was started empirically and was continued when the stool culture result was concurring.Echocardiogram was performed the next day after admission showing ejection fraction of 74.9% with no significant valve lesion or chamber enlargement.Cardiac catheterization was performed with no coronary artery disease identified.Coxsackie and Trichinella antibodies were negative.Workup for autoimmune diseases was done including anti-phospholipid antibody panel (anti-phosphatidyl serine, glycerol, inositol and choline immunoglobulin IgG, M and A), and they were all negative.Anti-cephaline antibodies and anti-cardiolipin IgM were negative.Anti-nuclear antibody was weakly positive speckled (1 : 80, normal-1 : 40).At this point, due to absence of coronary artery disease a diagnosis of myocarditis secondary to a food-borne pathogen was made.Stool studies returned positive for Shigella sonnei that was sensitive to ciprofloxacin.By the end of the three-day stay in the hospital, diarrhoea completely resolved  Thus, the patient was discharged on a short course of oral ciprofloxacin tablets.The patient was discharged on 81 mg aspirin tablet once daily, 25 mg metoprolol succinate extended release tablet daily, 40 mg fluoxetine tablet once daily and 500 mg ciprofloxacin tablet twice daily for a total of 5 days of therapy.The patient stayed for 2 days so continued on oral antibiotic for 3 days after discharge.Follow-up was obtained in 3 weeks and the patient had no complaints, with a normal clinical exam and EKG showing sinus bradycardia without any ST-T-wave changes (Fig. 2).

Discussion
The most common presumed cause of myocarditis in developed countries is a viral infection.Coxsackie B viruses and enteroviruses are commonly associated with viral myocarditis (Feldman & McNamara, 2000).In the past 10 years, other viruses including adenovirus, parvovirus B19 and herpes virus 6 have emerged as important pathogens (Mahrholdt et al., 2006).Although histology remains the gold standard for establishing the diagnosis of myocarditis, low-risk patients are often presumed to have myocarditis on the basis of a compatible clinical scenario.
Acute bacterial myocarditis secondary to Shigella sonnei gastroenteritis is a rare phenomenon.An extensive literature search showed only three cases reported with a similar association.A case was reported in 1987 for a 19-year-old young adult who had myocarditis secondary to shigellosis in the form of acute EKG changes and a murmur that resolved in 5 days (Caraco et al., 1987).Two paediatric cases were also reported in 1993 where the patients presented with severe cardiovascular compromise due to myocarditis that required intensive care unit admission, and the patients were eventually discharged home after completing the course of antibiotic therapy, respiratory support and vasopressors (Rubenstein et al., 1993).In our case, a 38-year-old female presented with acute chest pain following gastroenteritis.Laboratory findings showed high troponins.The course was short and resolved well after treatment with oral ciprofloxacin.Given the exclusion of acute coronary syndrome after the cardiac catheterization, a clinical diagnosis of myocarditis was made.The temporal relation between the appearance of the gastrointestinal symptoms and chest pain and the simultaneous remission of all symptoms in response to the antibiotic treatment suggests an aetiological association between Shigella sonnei and myocarditis.
The mechanism by which Shigella sonnei toxin could cause myocardial injury could be similar to that of the diphtheria toxin, which works by reducing protein synthesis (Collier, 1975).Other potential mechanisms include direct invasion of myocardium, or immunologically mediated myocardial damage as occurs with other extra-intestinal manifestations of shigellosis, such as reactive inflammatory arthritis or Reiter's syndrome (Niyogi, 2005).A case of myocarditis has also been reported secondary to infection with Shigella boydii (Vieira et al., 2008).
The gold standard test to establish the diagnosis of myocarditis requires an endomyocardial biopsy, although this invasive examination is only recommended in rare circumstances (Yancy et al., 2013).No specific treatment regimens exist for these findings and medical management is usually dependent on the haemodynamic status of the patient and treating its complications (Westling & Evengard, 2001).
Our patient presented with initial signs and symptoms indicative of acute coronary syndrome.Further history regarding the diarrhoea and recent travel along with a negative cardiac catheterization pointed towards a more infectious source of the patient's aetiology.The antibiotic ciprofloxacin was started as oral tablet empirically to treat the diarrhoea, while cardiac workup was ongoing.
The chest pain, EKG changes and positive troponin associated with the diarrhoea pointed towards acute myocarditis.The cardiology and infectious disease consultants agreed that acute bacterial myocarditis was the cause of the patient's symptoms given the temporal relationship and the literature available with regard to the association.The patient thus finished the course of treatment and showed resolution of symptoms with a stable follow-up course.

Learning objective
Thus, in summary, we are reporting a very rare case of a 38-year-old female with Shigella sonnei gastroenteritis who developed acute chest pain and positive troponins with non-specific T-wave changes suggestive of acute myocarditis, given the workup that was negative for coronary artery disease.This demonstrates that acute myocarditis can occur secondary to very rare unexpected causes like enteric bacterial infection.Thus, clinicians need to be aware of such association of cardiac complaints after acute gastroenteritis, as promptly starting them on antibiotics will improve the prognosis and prevents complications.

Fig. 1 .
Fig. 1.EKG on day of admission showing non-specific T wave changes.

Fig. 2 .
Fig. 2. Follow up EKG 3 weeks after discharge from the hospital.

Table 2 .
Trend of troponin levels after admissionTroponin (ng ml 21 ) Time when blood specimen was drawn