Non‐typhoidal Salmonella myocarditis: a disease manifestation not to be missed

Clinical record

In April 2021, a 19‐year‐old man presented with a two‐day history of intermittent pleuritic chest pain and associated fevers. He reported symptoms of diarrhoea and vomiting 48 hours after consuming tandoori chicken pizza eight days previously.

The patient had no significant past medical history and did not use regular medications. He had not yet received a coronavirus disease 2019 (COVID‐19) vaccination and had not travelled recently. On examination, he was febrile with a temperature of 38°C; otherwise, there were no significant findings. His full blood count revealed a normal white cell count of 8.7×10⁹/L (reference interval [RI], 3.5–11×10⁹/L), and C‐reactive protein was 62.0mg/L (RI, <5.0mg/L). Creatine kinase was elevated at 515U/L (RI, 45–250U/L), and troponin T was raised at 916ng/L (RI, <14ng/L). An electrocardiogram (ECG) showed diffuse T wave inversion. A transthoracic echocardiogram revealed a mildly enlarged left ventricle, with left ventricular ejection fraction of 45% and some mild basal hypokinesis without pericardial effusion. The patient was initially investigated for viral causes of myocarditis. An extended respiratory polymerase chain reaction (PCR) panel was sent to the laboratory and, given the preceding diarrhoea, enteroviruses, adenoviruses, COVID‐19, and atypical bacterial causes such as Mycoplasma spp infection were investigated. Furthermore, parvovirus B19 and human herpes virus 6 serology, a stool culture, and a BioFire (BioFire Diagnostics) gastrointestinal panel were analysed.

Blood cultures isolated Salmonella enterica, serotype Saintpaul and the stool culture grew the same strain. The Salmonella spp isolate was sensitive to ciprofloxacin, ceftriaxone and azithromycin, and intravenous ceftriaxone 2g daily was commenced. A cardiac magnetic resonance imaging (MRI) scan revealed a mildly enlarged left ventricle with impairment of systolic function (left ventricular ejection fraction 40%), and patchy mid‐wall late gadolinium enhancement in the basal and inferolateral walls.

Within 72 hours, his chest pain and fevers settled and troponin T decreased to 212ng/L (day 5). His antibiotic was changed to oral ciprofloxacin after 72 hours, and he completed a ten‐day antibiotic course. He was commenced on an angiotensin‐converting enzyme (ACE) inhibitor and a low dose cardio‐selective β‐blocker. Investigations for underlying diabetes mellitus, human immunodeficiency virus (HIV) infection, hepatitis B and C, and immunoglobulin deficiency were unremarkable.

On follow‐up at six and 12 weeks after therapy, he remained well with no relapse of symptoms. His repeat echocardiography and MRI scan demonstrated normalisation of previous left ventricular dysfunction. His stool culture and PCR test were negative, demonstrating clearance of carriage within 12 weeks.

Discussion

Non‐typhoidal Salmonella (NTS) is the second most common cause of bacterial gastroenteritis in Australia,1 with 14146–18009 notifications of salmonellosis per year from 2015 to 2019.2 Most cases of NTS infections worldwide are attributable to Salmonella Enteritidis, which is not endemic in Australia. Nationally, Salmonella Typhimurium is the most common serotype, mostly acquired from poultry.3 NTS causes a wide spectrum of clinical syndromes; even though gastroenteritis is the most common, invasive NTS infections resulting in bacteraemia, osteomyelitis, or endovascular infections have all been well documented.4,5,6,7 Risk factors for development of invasive infections include immunocompromised states, malnutrition, recent malaria, or HIV infection.4,5,6,7

This case highlights that cardiac involvement with myocarditis and/or pericarditis is an emerging (and likely underdiagnosed) manifestation of invasive NTS. Viral causes of myocarditis commonly include human herpes virus 6, parvovirus B19, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), influenza virus, and enteroviruses.4 Even though this patient had myocarditis, pericarditis has been a more commonly reported pathology in NTS infection, with myopericarditis being rarer.4,5,6,7 The most implicated serovars are S. Enteritidis followed by S. Typhimurium.1,2,5 In previously published case series, 71–80% of NTS myocarditis and/or pericarditis cases have occurred in men, with a median age of 30.8–48.3 years.6,7 To our knowledge, there is only one other published case in Australia.7

Although impaired innate immunity is linked to NTS myocarditis (and it is important to exclude risk factors such as HIV infection, diabetes mellitus or viral hepatitis) there are also many other cases reported in immunocompetent and otherwise healthy patients.4,5,6,7 The pathogenesis of this disease is unclear; it appears associated with testosterone (reflective in the prevalence of predominantly younger male patients affected), and molecular mimicry, with immune‐mediated injury to myosin, has been hypothesised.4,5,6

The diagnosis should be suspected when there are clinical symptoms of chest pain associated with raised cardiac biomarkers, ECG findings of myocarditis (sinus tachycardia and non‐specific T wave and ST segment changes in myocarditis) or pericarditis (PR depression, diffuse ST segment concave elevations and flattened/inverted T waves) in patients with concurrent or recent NTS infection.4,5,6 Normal cardiac biomarkers in early illness do not preclude the diagnosis. The use of cardiac MRI, where available, is a useful adjunct to echocardiography and more accurately characterises myocardial tissue and determines the extent of myocardial inflammation.4,6 It is recommended to treat concurrent NTS invasive infection with empiric ceftriaxone and subsequently with azithromycin or ciprofloxacin orally (pending susceptibility) for a minimum duration of 5 days; altered longer courses are recommended depending on the treatment of associated complications (ie, osteomyelitis, endovascular infection, bacteraemia).4,5,6,7,8,9 However, there is no clear consensus regarding the optimum duration of antimicrobial therapy in cases of NTS myocarditis or pericarditis. The management of myocarditis in NTS infection is aimed at addressing heart failure and cardiomyopathy with pharmacological therapies such as β‐blockers and ACE‐inhibitors, where appropriate, and close cardiac monitoring for developing conduction defects or ventricular dysrhythmias.4,5,6,7,8

The onset of NTS‐associated myocarditis and/or pericarditis can follow resolution of symptoms of gastroenteritis and, hence, careful history taking, including that of potential sick contacts, is vital. Importantly, this NTS clinical syndrome carries a mortality of 20–40% in documented cases, and the implications for missed diagnosis can be significant.6,7 Our patient had resolution of symptoms, with normalisation of cardiac biomarkers and MRI findings; however, death (in the setting of cardiogenic shock), dilated cardiomyopathy, fulminant cardiac failure, conduction defects, and ventricular rupture are reported sequelae of severe presentations.4,5,6,7,8 We suggest that screening with stool culture and/or PCR tests, as well as blood cultures, be considered in younger patients with a relevant history of gastrointestinal illness who present with myocarditis of unclear aetiology.