Salmonella typhimurium myopericarditis: A case report and review of literature

Abstract

BACKGROUND

Non-typhoidal salmonella (NTS) is a rare, but well-established cause of myopericarditis. Presenting symptoms may be varied, however often revolve around the dual presentation of both myopericarditis and infectious diarrhoea. Given the rarity of NTS related myopericarditis, we conducted a systematic review of the literature, identifying 41 previously reported cases.

CASE SUMMARY

We present the case of an otherwise healthy 39-year old male, presenting with chest pain in the setting of documented Salmonella typhimurium infection. After further investigation with echocardiogram and laboratory blood tests, a diagnosis of NTS associated myopericarditis was made, and the patient received antibiotic treatment with an excellent clinical outcome. Overall, myopericarditis is rare in NTS. Although treatment for myopericarditis has not been well established, there are guidelines for the treatment of NTS infection. In our review, we found that the majority of NTS cases has been pericarditis (27/42, 64.3%), with an average age of 48.3 years, and 71.4% being male. The average mortality across all cases was 31%.

CONCLUSION

Myopericarditis is a rare, but potentially serious complication of NTS infection, associated with an increased morbidity and mortality.

Key Words: Salmonella typhimurium, Pericarditis, Myocarditis, Myopericarditis, Non-typhoidal salmonella, Case report

Core tip: Myopericarditis symptoms can be variable but generally presents with ischaemic sounding chest pain or pleuritic chest pain and cardiac biomarker elevation (troponin I and T). Non-typhoidal salmonella (NTS) generally presents as a non-bloody infectious diarrhoea. Salmonella enterica has multiple subtypes, with Salmonella typhi and paratyphi causing typhoid fever. However, there are a large number of NTS, which may include Salmonella choleraesuis, enteritidis, and typhimurium. Relevant investigations may consist of laboratory blood tests, electrocardiogram, echocardiography, coronary angiography, cardiac magnetic resonance imaging, cardiac biopsy, and faecal culture for Salmonella. Salmonella is a rare cause of myopericarditis; however, it should be considered when patients with symptoms of myocarditis or pericarditis present with a history of diarrhoea, abdominal pain and fever.

INTRODUCTION

Myocarditis is defined as an inflammatory disorder of the myocardium, formally diagnosed on clinical biopsy, however many cases are often diagnosed clinically[1]. Pericarditis, also inflammatory, is when the inflammation primarily involves the pericardial sac. Given their close anatomical relation, co-inflammation can occur as part of a syndrome known as myopericarditis, however, clinical manifestations are predominantly myocarditic or pericarditic[2]. The aetiology of myopericarditis is varied, ranging from infections (viral being the most common), autoinflammatory conditions, neoplasms, trauma, metabolic and idiopathic[3]. A rare, but potentially serious cause is as a sequelae of Salmonella infection.

Most cases of Salmonella myocarditis are associated with typhoid fever (Salmonella typhi/paratyphi), complicating up to 5% of all infections, and is well described in literature[4]. We conducted a systematic review of all case studies and case series published on nontyphoidal salmonella (NTS) associated pericarditis and/or myocarditis from January 1970 to March 2019. Both authors (Jin D and Kao CY) searched on PubMed and EMBASE using the search terms “Salmonella AND myocarditis” and “Salmonella AND pericarditis”. PubMed was further searched for the combined MeSH values of “Myocarditis” as well as “Salmonella (excluding typhi and paratyphi)”. Paediatric and non-human cases were excluded. References of articles were then further reviewed. We aim to discuss a case NTS myopericarditis, as well as reviewing the relevant literature.

CASE PRESENTATION

Chief complaints

We report a case of a 39-year old male, with no previous medical history, presenting with Salmonella typhimurium myopericarditis.

Personal and family history

The patient initially presented to our emergency department (ED) with acute chest discomfort, on the background of a four-day history of persistent, watery diarrhoea, occurring three to four times per day. On Day 0 (four days prior to admission), he noticed diffused abdominal cramps, bloating, nausea without vomiting, and fever. There was no history of recent travel, however he had a seven-year-old daughter, who had a one-week history of the same symptoms which had resolved prior to the patient’s presentation. There was no report of blood in the diarrhoea, which was beginning to decrease and form solid motions by Day 4.

However, it was during this stage (Day 4) that the patient noted central chest discomfort, described as a burning sensation, radiating to the axilla and neck, associated with diaphoresis and self-resolving shortness of breath. This was not exacerbated by exercise, however there was some relief with leaning forwards. He initially presented to his General Practitioner (GP), who organised for faecal cultures, before referring onto ED.

Laboratory examinations

At presentation to ED, his observations were within normal limits, with no documented fevers or tachycardia. Physical exam was unremarkable. Serial electrocardiogram (ECG, Figure 1) revealed prominent ST elevation (> 2 mm in leads V2-V6, > 1 mm in II/aVF), as well as ST depression in aVR. Investigations revealed a white cell count (WCC) of 7.3 × 10⁹/L, C-reactive protein (CRP) of 84 mg/L, as well as a Troponin I (Abbott Architect) of 14,757 ng/L and a creatinine kinase of 594 units/L. Other blood tests such as electrolytes, creatinine and liver function tests were unremarkable.

Figure 1 Electrocardiography from admission, showing diffuse ST elevation and mild ST depression in automatic voltage regulator.

Imaging examinations

Chest X-ray showed mild cardiac enlargement, without signs of pulmonary oedema or pneumonia. Faeces microscopy and culture, along with blood cultures were taken, and the patient was admitted without specific antimicrobial treatment. An echocardiogram conducted the next day showed a trivial amount of pericardial fluid. The was no clinical or echocardiographic evidence of tamponade, ventricular dysfunction, or thrombus formation.

During Day 5, we were notified of a Salmonella species from the faecal culture organised by the GP. Treatment was commenced with 1 g of ceftriaxone daily. Later that night there was an associated, asymptomatic rise in the Troponin I from the previous nadir of 8,915 to 15,114 ng/L. Ceftriaxone was increased to 2 g daily, and the Infectious Diseases Unit were consulted. At this stage the repeat faecal culture also identified Salmonella species, with negative blood cultures at 48 h. Joint decision at this stage was made to change to azithromycin 500 mg daily for 5 d and to not initiate non-steroidal therapy, given that the initial presenting symptoms had fully resolved. There had been no clinical events of arterial or venous thrombus, combined with no significant echocardiography changes, therefore no anticoagulation was prescribed. After a further period of observation over 24 h, during which the troponin decreased to 11,327 ng/L, the patient was discharged home.

Post discharge, at Day 7, the initial presenting blood culture was positive for gram negative bacilli in one aerobic bottle, out of two sets, also identified as Salmonella typhimurium, however by this stage the patient was convalescing well at home.

FINAL DIAGNOSIS

Myopericarditis in the setting of Salmonella typhimurium gastroenteritis and bacteraemia.

TREATMENT

Two days of ceftriaxone 2 g IV daily followed by azithromycin 500 mg orally daily for 5 days.

OUTCOME AND FOLLOW-UP

Clinical and biochemical resolution of myopericarditis and Salmonella typhimurium infection. Patient well with no further complaints at routine one-month follow-up.

DISCUSSION

The presentation of NTS myopericarditis can be varied, but generally is divided into two categories, the symptoms of myopericarditis, and the diarrhoeal syndrome. Although the manifestations of myopericarditis are commonly a spectrum between myocarditis and pericarditis, there is often a predominance of on[2]. Myocarditis typically presents with chest pain, often of a varied nature, and can be impossible to differentiate on history from ischaemic chest pain. Otherwise heart failure symptoms, flu-like symptoms, fatigue, palpitations, syncope, or even sudden cardiac death may be the presenting symptom[5]. Pericarditis is associated with a pleuritic chest pain, often relieved by learning forward, as well as fatigue, palpitations, dyspnoea, and potentially tamponade[5]. The classic exam finding is the pericardial friction rub, often described as a scratching sound best heard over the left sternal edge. Purulent pericarditis, a rare subset in the antibiotic era, should nevertheless be considered given its high morbidity and mortality. Presenting symptoms may include signs of pericarditis, especially if associated with sepsis or bacteraemia, with Salmonella aureus being the most commonly identified organism.

Investigations of relevance in myopericarditis include ECG, echocardiography, laboratory blood tests, biopsy, coronary angiography and cardiac magnetic resonance imaging. ECG changes are varied[6], but typically involve diffuse ST elevation and PR depression, progressing to normalization of segments with subsequent T-wave inversion. However, given this can also manifest as focal ST elevation, combined with the fact that the pain can be ischaemic in nature, differentiation from acute coronary syndromes (ACS) is often required. This is most frequently done with interventional angiography, or more recently computed tomography coronary angiography. Aside from raised troponin, inflammatory markers such as WCC and CRP are often raised, however this has not been shown to help differentiate NTS as a cause[7]. Echocardiography is another critical area of investigation, as this can help identify ventricular dysfunction, valvular incompetence and thrombus in myocarditis[8], as well as the extent of pericardial involvement, ranging from completely normal to cardiac tamponade in pericarditis[9]. Cardiac magnetic resonance imaging is another investigation that can be potentially used, as it can accurately assess inflammation in either the pericardium or myocardium, as well as help differentiate between ACS[10]. Definitive diagnosis of myocarditis requires endocardial biopsy, however indication revolves around whether a biopsy result would change patient management, and thus is rarely conducted in those with normal or only mildly impaired ventricular function[11]. Biopsy is most frequently performed in cases of fulminant heart failure, heart failure with rhythm disturbance, or when there is peripheral eosinophilia, suggestive of eosinophilic myocarditis.

The most recognised infection from Salmonella is typhoid fever, also known as enteric fever, caused by Salmonella enterica serotype Typhi (formerly Salmonella typhi), as well as Salmonella paratyphi (Salmonella enterica serotype paratyphi). Due to a nomenclature change, within Salmonella there are now two species; bongori and enteric[12]. Salmonella enterica, which causes the majority of infections, contains 6 subspecies, of which the most clinically relevant is Salmonella enterica subspecies enterica. These are then further divided into serovars, with the most common including: Salmonella choleraesuis, Salmonella enteritidis, and Salmonella typhimurium. These organisms make up the group known as NTS.

NTS often manifests within 72 h of exposure to the offending pathogen and is usually associated with faecal-oral contamination. The most common presenting symptoms by far is gastroenteritis[13], associated with watery, non-bloody diarrhoea, abdominal cramps, nausea and vomiting, as well as fever.

In our review of the literature (Table 1), we found 42 reported cases of NTS (Table 2), with 9 myocarditis, 6 myopericarditis and 27 cases of pericarditis. Overall, we found that Salmonella enteritidis was the most common organism, representing 18 (42.9%) of all reported cases, with Salmonella typhimurium at 31.7%. Males consisted 71.4% of the cases, and the average age of patients was 48.3 years. In the case studies that we have identified, the overall mortality rate was 31%, and up to 77.8% in myocarditis cases, compared to 14.8% in pericarditis. Tamponade was the most commonly reported complication, especially in pericarditis, at 54.3%, whilst ventricular rupture was the most commonly reported complication of myocarditis. However, this is limited by both reporting and publication bias, and by the fact that most deaths and myocarditis cases occurred earlier in time, prior to modern diagnostic techniques and treatment.

Table 1 Non-typhoidal salmonella pericarditis and myocarditis.

Author	Relevant medical history	Age and sex	Cardiac manifestation	Organism	Complications	Outcome
Bengtsson et al[20], 1955	NA	50F	Myocarditis	Salmonella typhimurium	NA	Deceased
Bengtsson et al[20], 1955	NA	51M	Myocarditis	Salmonella typhimurium	NA	Deceased
Sanders et al[21], 1964	NA	62F	Myocarditis	Salmonella choleraesuis	Ventricular Rupture	Deceased
Shilkin et al[22], 1969	SLE	61M	Myopericarditis	Salmonella typhimurium	Endocarditis	Deceased
Schatz et al[23], 1973	NA	62M	Myopericarditis	Salmonella typhimurium	Tamponade	Deceased
Webster et al[24], 1977	NA	19F	Myopericarditis	Salmonella agona	NA	Survived
Simonsen et al[25], 1980	NA	24M	Myocarditis	Salmonella typhimurium	NA	Deceased
Götz et al[26], 1983	NA	53M	Myocarditis	Salmonella typhimurium	NA	Deceased
Martínez-Martínez et al[27], 1989	NA	60M	Myocarditis	Salmonella enteritidis	Mycotic aneurysms of aorta	Deceased
Burt et al[28], 1990	NA	29M	Myocarditis	Salmonella Heidelberg	VF	Deceased
Dunbabin et al[29], 1990	Chemotherapy	52F	Pericarditis	Salmonella Dublin	Tamponade	Deceased
Doig et al[30], 1991	NA	36F	Pericarditis	Salmonella enteritidis	Tamponade	Survived
Clesham et al[31], 1993	NA	45M	Pericarditis	Salmonella enteritidis	Tamponade	Survived
Li et al[32], 1993	NA	22F	Pericarditis	Salmonella enteritidis	NA	Survived
Yang et al[33], 1995	NA	54F	Pericarditis	Salmonella typhimurium	NA	Survived
Victor et al[34], 1997	NA	71M	Pericarditis	Salmonella enteritidis	NA	Survived
Kiuchi et al[35], 1998	ITP (prednisolone)	39M	Pericarditis	Salmonella enteritidis	Tamponade	Survived
Badawi et al[36], 2002	NA	48M	Pericarditis	Salmonella typhimurium	NA	Survived
Pace et al[37], 2002	NA	65M	Pericarditis	Salmonella enteritidis	Tamponade	Survived
Salavert et al[38], 2002	NA	61M	Pericarditis	Salmonella arizonae	Tamponade	Survived
Candel et al[39], 2003	HIV	37M	Pericarditis	Salmonella Derby	NA	Survived
Yoshioka et al[40], 2003	NA	40M	Pericarditis	Salmonella enteritidis	NA	Survived
Arruvito et al[41], 2004	Arthritis (steroids)	75M	Pericarditis	Salmonella enterica	Tamponade	Deceased
Can et al[42], 2004	NA	42M	Pericarditis	Salmonella typhimurium	NA	Deceased
Fernández Guerrero et al[43], 2004	SLE (prednisolone and azathioprine)	23F	Pericarditis	Salmonella typhimurium	Tamponade	Survived
Fernández Guerrero et al[43], 2004	NA	66M	Myopericarditis	Salmonella enteritidis	NA	Survived
Hoag et al[44], 2005	HIV	47F	Pericarditis	Salmonella arizonae	Tamponade	Survived
Górecki et al[45], 2008	RA (steroids) ESRF (on HDx)	64M	Pericarditis	Salmonella enteritidis	Tamponade	Survived
Sahu et al[46], 2008	Hodgkin’s lymphoma	23M	Pericarditis	Salmonella typhimurium	NA	Survived
Takamiya et al[47], 2008	CD4/CD8 depression (ratio = 0.81)	65M	Pericarditis	Salmonella enteritidis	NA	Survived
Hibbert et al[48], 2010	NA	25M	Myopericarditis	Salmonella enteritidis	NA	Survived
Tseng et al[49], 2010	ESRF	66M	Pericarditis	Salmonella enterica	Tamponade	Survived
Tseng et al[49], 2010	ESRF	82M	Pericarditis	Salmonella enteritidis	Tamponade	Deceased
Ortiz et al[50], 2014	SLE (prednisolone)	62M	Pericarditis	Salmonella enteritidis	Tamponade	Survived
Chand et al[51], 2015	NA	67M	Pericarditis	Salmonella enteritidis	Tamponade	Survived
Zaman et al[52], 2015	NA	67M	Myopericarditis	Salmonella enteritidis	Tamponade	Survived
Dawar et al[53], 2017	NA	46F	Pericarditis	Salmonella typhimurium	NA	Survived
Kuo et al[54], 2017	Adult onset Still’s disease (methylprednisolone/prednisolone)	30F	Pericarditis	Salmonella enteritidis	Tamponade	Survived
Suzuki et al[55], 2017	NA	31M	Pericarditis	Salmonella arizonae	Tamponade	Survived
Ezad et al[56], 2018	NA	29F	Myocarditis	Salmonella typhimurium	NA	Survived
Sundbom et al[57], 2018	NA	22M	Myocarditis	Salmonella enteritidis	NA	Survived
Saddler et al[58], 2019	Crohn’s disease (Infliximab)	57M	Pericarditis	Salmonella enterica	Tamponade	Survived

NA: Not applicable; SLE: Systemic lupus erythematosus; ESRF: End-stage renal failure; HIV: Human immunodeficiency virus; RA: Rheumatoid arthritis; ITP: Idiopathic thrombocytopenic purpura; M: Male; F: Female.

Table 2 Summary of non-typhoidal salmonella ca.

Cardiac Manifestation (Cases)	Organisms (Number of cases)	Mortality
Myocarditis (9)	Salmonella typhimurium (5)	77.8% (7/9)
	Salmonella enteritidis (2)
	Salmonella choleraesuis (1)
	Salmonella Heidelberg (1)
Myopericarditis (6)	Salmonella enteritidis (3)	33.3% (2/6)
	Salmonella typhimurium (2)
	Salmonella agona (1)
Pericarditis (27)	Salmonella enteritidis (13)	14.8% (4/27)
	Salmonella typhimurium (6)
	Salmonella arizonae (3)
	Salmonella enterica (3)
	Salmonella Derby (1)
	Salmonella Dublin (1)
Total (42)	Salmonella enteritidis (18)	31% (13/42)
	Salmonella typhimurium (13)
	Salmonella arizonae (3)
	Salmonella enterica (3)
	Salmonella agona (1)
	Salmonella choleraesuis (1)
	Salmonella Derby (1)
	Salmonella Dublin (1)
	Salmonella Heidelberg (1)

The mainstay of therapy in treating the inflammation and pain associated with myopericarditis is non-steroidal anti-inflammatory drugs (NSAIDs)[3]. However when there is a predominant myocarditic component, NSAIDs are often reconsidered, as animal models show increased inflammation and mortality in viral myocarditis[14]. Corticosteroids are also potentially used, but should only be considered in cases of ongoing uncontrolled inflammation, as there is minimal data to recommend its routine use, and there is association with recurrent myocarditis[15]. Anticoagulation can be considered in specific patients, similar to the indications in non-ischaemic dilated cardiomyopathy[16]. These would be if there were new onset AF, clinical or radiographical evidence of arterial or venous thromboembolism, thrombus formation on the echogardiogram, or significant ventricular dysfunction. If treatment was indicated, evidence currently leans towards anticoagulation with warfarin or a Direct Oral Anti-Coagulant, as opposed to single-agent treatment with an antiplatelet[17]. If there are concurrent symptoms of heart failure, routine heart failure treatment should be initiated, including diuretics, angiotensin converting enzyme inhibition, and extended release beta blocker treatment. Invasive treatment is often limited to coronary angiography when differentiating from ACS, as well as pericardiocentesis in the setting of large pericardial effusions with features suggestive of developing or frank cardiac tamponade.

Lastly, it is also important to treat the underlying Salmonella infection, however guidelines vary secondary to local antimicrobial susceptibility patterns. After clinical rehydration, current Australian guidelines[18], recommend treatment with intravenous therapy initially, such as ceftriaxone (2 g IV daily), or ciprofloxacin (400 mg twice-daily), before an oral tail of ciprofloxacin/azithromycin, determined by the severity of the infection.

At this stage, there is very limited high-quality data on long-term prognosis and complications in patients diagnosed with myopericarditis[3]. Nevertheless, it appears that survival rates in idiopathic and infectious myocarditis are overall quite favourable, especially the predominant pericarditis subtype[19]. The main complications are the development or non-resolution of heart failure, cardiomyopathy, arrhythmias, and sudden cardiac death, especially if there is significant myocardial scarring. Routine follow up in the acute phase with echocardiography is recommended, especially if there are clinical or radiological signs of heart failure.

CONCLUSION

The presentation of NTS myopericarditis is varied, however it revolves around two main areas, the symptoms of myocarditis and pericarditis, as well as the infectious symptoms of diarrhoea accompanying Salmonella infection. Definitive diagnosis with biopsy is rarely undertaken, as this is usually a clinical diagnosis from the clinical history and examination, ECG, troponin and echocardiogram, as well as a stool culture for the NTS. There is a lack of consensus regarding the treatment of myopericarditis, however there are well established antibiotic guidelines for NTS. Although NTS is a rare cause of myopericarditis, given the severity of potential sequelae, remains a worthwhile consideration when patients present with symptoms of both infectious diarrhoea and myopericarditis.