From the Gut to the Heart: A Rare Case of Pericarditis

Background

Salmonellae are motile gram-negative bacilli that infect a wide range of hosts via fecal-oral transmission. The Centers for Disease Control and Prevention (CDC) estimates in the United States alone, Salmonella causes over 1 million infections and >20 000 hospitalizations [1]. There are over 2500 serotypes of Salmonella, and approximately 50 have been associated with infections in humans [1]. Salmonellosis is classified as typhoid or nontyphoid, but we focus on non-typhoidal salmonellosis in this report [2]. Non-typhoidal Salmonella infections manifest typically as gastroenteritis after the consumption of contaminated food (usually poultry, eggs, and milk products), and are a major cause of diarrhea worldwide. In the United States, nontyphoidal salmonellosis is one of the leading causes of food-borne disease, with Salmonella enteritidis, Salmonella newport, and Salmonella typhimurium being among the serotypes most frequently isolated from these cases [3]. Extra-intestinal manifestations of Salmonella are known to occur, including endocarditis, mycotic aneurysm, visceral abscesses, and osteomyelitis; however, purulent pericarditis associated with cardiac tamponade is rare [4].

Treatment for Salmonella gastroenteritis is mainly supportive with fluids and electrolytes. Extra-intestinal Salmonella infections requires antimicrobial therapy. It is recommended that fluoroquinolones be started empirically for adults with nontyphoidal Salmonella bacteremia due to their excellent intra-cellular penetration and oral bioavailability. However, these should be avoided in children due to data indicating cartilage abnormalities as an adverse effect of fluoroquinolones [5]. Third-generation cephalosporins are a reasonable alternative to fluoroquinolones due to their better adverse effect profile; however, the CDC has reported increasing resistance to cephalosporins, making fluoroquinolones the better choice [6].

Pericarditis is an inflammatory disease of the pericardium, which may have an infectious or a noninfectious cause. It is the most common form of pericardial disease worldwide, with an incidence of 27.7 cases per 100 000 people per year [7]. The classic presentation includes sharp, pleuritic chest pain, pericardial friction rub, widespread ST elevation and PR depression on electrocardiogram, and pericardial effusion seen on echocardiogram [8]. In developing countries with a high prevalence of tuberculosis, tuberculosis accounts for 70% of pericarditis. However, tuberculosis is much less common in developed countries, accounting for <5% of all cases. In developed countries, 80–90% of cases are idiopathic after extensive diagnostic workup and most are presumed to be viral in etiology. The remaining cases with an identified etiology include malignancy (5–10%), systemic inflammatory diseases and pericardial injury (2–7%), tuberculosis (4%), and purulent/bacterial pericarditis (<1%) [7]. Out of the small number of patients presenting with a pericarditis of purulent or bacterial etiology, Salmonella is only responsible for a handful of cases [9].

Treatment for pericarditis includes anti-inflammatory medications. Typical regimens include aspirin (750–1000 mg every 8 hours for 1–2 weeks) or nonsteroidal anti-inflammatory drugs [NSAIDs] such as ibuprofen 600 mg every 8 hours for 1–2 weeks plus colchicine 0.5 mg daily for 3 months along with gastric protection [10]. In addition, patients with bacterial pericarditis require antibiotic therapy sensitive to the identified organism. There are no definitive guidelines for duration of therapy, but a prior case report suggested it is reasonable to consider 2–4 weeks of therapy [11].

As extra-intestinal manifestations of Salmonella are rare, it is important to determine the how the infection seeded extra-intestinally, considering a patient’s risk factors. Here, we present a rare case of Salmonella dublin-associated pericarditis.

Case Report

A 45-year-old White man with a history of hypertension and recent Bell’s palsy presented to the Emergency Department reporting chest pressure and gradually worsening difficulty in breathing along with neck/back pain for 1 week. The chest pressure was described as sharp and relieved by sitting upright. He denied any prior cardiac history and any other associated symptoms, including fevers or recent upper-respiratory symptoms. He had recently traveled to Texas. He denied any cigarette smoking, alcohol intake, marijuana use, or use of illicit substances. He worked as a field engineer and handled automotive chemicals. There was no notable family history of cardiac disease.

On presentation, he was afebrile, tachycardic with heart rate approximately 120 beats per minute, blood pressure was 135/101 mmHg, and respiratory rate was 17 with saturation of 94% on room air. On physical exam, he had known facial droop from prior Bell’s palsy, with no new neurological findings. A cardiac exam was significant for distant heart sounds with S1 and S2 present, no S3 or S4, and no murmurs, rubs, or gallops.

An electrocardiogram revealed diffuse ST elevation throughout most limb leads and precordial leads with ST depression and PR elevation in leads aVR and V1 (Figure 1). Laboratory test results revealed leukocytosis of 19 K/mcL [4–11 K/mcL], acute kidney injury with creatinine 1.4 mg/dL [0.7–1.5 mg/dL], C-reactive protein was elevated at 90 mg/L [1.0–10.0 mg/L], and troponin was <0.02 ng/mL [0.00–0.10 ng/mL]. Chest radiography revealed an enlarged cardiac silhouette. A subsequent computed tomography (CT) scan showed no evidence of aortic dissection or pulmonary embolism, but a moderate-to-large pericardial effusion was noted (Figure 2).

This patient presented with diffuse ST elevations with active chest pain symptoms and had risk factors for coronary artery disease. Although the electrocardiogram was concerning for pericarditis and a CT scan showed pericardial effusion, given the patient’s severity of symptoms and risk factors, he was taken for emergent cardiac catheterization to rule out obstructive coronary artery disease, which revealed patent coronary arteries. Echocardiography showed ejection fraction of 60–65%, with large pericardial effusion with fluid showing a fibrinous appearance. There was no evidence of hemodynamic compromise (Figure 3).

The patient was started on colchicine and ibuprofen for pericarditis and scheduled for pericardial window. He had resolution of leukocytosis and kidney injury the following day. He remained afebrile and hemodynamically stable. Serial echocardiogram showed evidence of tamponade features such as diastolic collapse of right ventricle as well as mitral inflow pattern with significant respiratory variation of 41% (Figures 4, 5).

He underwent a pericardial window via subxiphoid approach the following day with removal of 700 cubic centimeters of light bloody fluid with presence of fibrinous debris in the pericardial cavity. Biopsy from pericardial tissue and lymph node biopsy were performed and a chest tube was placed.

A repeat electrocardiogram showed improving ST elevations (Figure 6). Subsequent laboratory analyses investigating the etiology were negative, including antinuclear antibody (ANA), Lyme IgM and IgG, and HIV.

Pathology from biopsy showed chronic pericarditis, and a lymph node biopsy was negative for malignancy. Pericardial tissue culture grew Salmonella species, and subsequent blood cultures also revealed Salmonella species. He was then started on ceftriaxone. Sensitivities revealed resistance to ceftriaxone, and the antibiotic regimen was switched to ciprofloxacin.

Further history from the patient revealed travel to Illinois 4 months prior to visit a sick relative. He then noticed flu-like symptoms and was diagnosed with Bell’s palsy 1 month later. A COVID-19 test was negative and he was treated with prednisone and valacyclovir. He then traveled to South Carolina and Texas 2 months later. He had a cat and dog at home and denied any new food consumption or recent diarrhea.

The chest tube was removed a few days later, with a post-removal echocardiogram revealing trivial pericardial effusion. Final identification of the organism revealed Salmonella dublin. He was discharged home on colchicine, ibuprofen taper, and ciprofloxacin for 4 weeks. His C-reactive protein down-trended, with a value of 11 mg/L [1.0–10.0 mg/L] 2 weeks after discharge (Figure 7).

Discussion

Salmonella infections are typically self-limited infections contained to the gastrointestinal system. These infections resolve after adequate supportive care with hydration and rest. Fewer than 5% of individuals diagnosed with a Salmonella infection go on to develop bacteremia [4]. Most studies reviewing cases of Salmonella bacteremia are from sub-Saharan Africa, as this region accounts for 79% of all cases globally. In these studies, 65% of cases were in children 5 years of age or younger [12]. When studying the risk factors that predisposed individuals to Salmonella bacteremia in sub-Saharan Africa, HIV patients, infants, and young children with malaria, anemia, and severe malnutrition leading to an immunocompromised state were found to be important risk factors [13]. However, in developed countries, most cases of non-typhoidal bacteremia are associated with gastroenteritis but have no underlying comorbidities or evidence of immunocompromised states. For example, in a series of 144 pediatric cases of non-typhoidal Salmonella bacteremia in Pittsburgh in the United States (median age 10.5 months), 82% of patients were previously healthy [14]. Therefore, it is hard to pinpoint what specific risk factors pre-dispose patients to have extra-intestinal manifestations of Salmonella, but a relatively immunocompromised state can account for multiple comorbid conditions.

Antimicrobial therapy for Salmonella includes fluoroquinolones and third-generation cephalosporins. However, fluoroquinolones are preferred due to increasing resistance of third-generation cephalosporins [6]. This was seen in our patient, whose Salmonella culture results showed resistance to ceftriaxone. Duration of therapy ranges from a 14-day course in otherwise healthy patients with no extra-intestinal focal infections to 4–6 weeks in those who are immunocompromised or have seeding to extra-intestinal sites (eg, grafts, hardware, abscesses, endocarditis, osseous infections) [15].

The interesting part of our case was the serotype identified: Salmonella dublin. Salmonella dublin is a cattle-specific serotype, which typically leads to a diarrheal illness in cattle. Prior research on this serotype showed rare, severe disease in human hosts, often manifesting as bacteremia, osteomyelitis, and meningitis requiring antimicrobial therapy. A recent epidemiologic analysis by the CDC looked at epidemiology of Salmonella dublin from 1968 to 2013. Approximately 4000 cases of Salmonella dublin were isolated from humans. In this analysis, the incidence of infection with Salmonella dublin increased by 7.6 times in 2013 as compared to 1968. During this time, the incidence of other serotypes of Salmonella was steady [1]. The average age of infected individuals was 55 years old [1]. Most often (61% of cases), Salmonella dublin was found in blood cultures [1]. Seventy-five percent of individuals infected with Salmonella dublin were hospitalized as compared to 27% with other serotypes [1]. Approximately 500 cases were attributed to food during that time frame, with 99% of the cases from beef. Another 400 were from live animals, with 99% attributed to cattle [1]. Salmonella dublin has led to outbreaks in the United States, with the most recent outbreak being reported in 2019 from infected cattle, with 13 individuals infected and 1 death [16]. How Salmonella dublin infects humans has been a topic of interest. A 2017 study applied whole-genome sequencing to Salmonella dublin isolates from different countries to assess virulence factors. They found many virulence factors within the genome, but were unable to differentiate invasive from non-invasive and concluded that host immunity plays a major role in invasiveness of Salmonella dublin [17]. There has been an increase in antimicrobial resistance to greater than 7 antibiotic classes, including third-generation cephalosporins [1]. This is theorized to be due to antibiotic treatment of cattle infected with Salmonella dublin.

As mentioned in the introduction, pericarditis is an inflammatory disease of the pericardium. Most cases are presumed idiopathic and are attributed to viral sources after extensive workup reveals no other source. Bacterial or purulent pericarditis accounts for <1% of cases of pericarditis [7]. Infection of the pericardium with a bacterial organism is caused by either direct spread from an intrathoracic focus or as a result of hematogenous spread from another site of infection. The most common organisms associated with bacterial pericarditis are Staphylococci, Streptococci, Haemophilus, and Mycobacterium tuberculosis [18]. Salmonella is only responsible for a handful of cases. Specifically, non-typhoidal Salmonella pericarditis has been linked to less than 40 cases [19–59]. Our literature review found only 1 prior case of Salmonella dublin pericarditis, which was diagnosed in 1990 [20] suggesting that Salmonella pericarditis is a very rare condition. Prior case reports of Salmonella pericarditis also suggest a high mortality rate. One 2020 review performed a comparative analysis of Salmonella pericarditis cases and found a mortality rate of 14.8% [19].

Patients with bacterial pericarditis present similarly as other etiologies of pericarditis, with sharp, pleuritic chest pain, and can have a pericardial friction rub on exam. These patients can present with fevers, but absence of fever does not rule out a bacterial source. As with any other case of suspected pericarditis, all patients should undergo complete history-taking and physical examination, electrocardiography, chest radiography, complete blood count, troponin level, erythrocyte sedimentation rate, C-reactive protein level, and echocardiography [60]. Our patient had this workup performed upon initial evaluation. Depending on additional factors, including immunocompromised status, high fever, signs of sepsis, age, travel history, and exposure to sick contacts, additional testing should be ordered, including blood cultures, viral studies, antinuclear antibody titer, and TB testing [10]. Ultimately, diagnosis is made after obtaining cultures from pericardial fluid if available or from pericardial tissue. The recommended treatment course includes anti-inflammatory medications and antibiotics tailored to the organism identified.

In our case, our patient had additional workup performed, including ANA to assess for an autoimmune etiology for his patient’s pericardial effusion. Lyme IgM and IgG levels were checked to rule out Lyme disease as a cause given the patient had a facial droop along with presence of pericarditis with a pericardial effusion. HIV testing was also performed, which was negative. He then underwent a pericardial window procedure with biopsy of pericardial tissue and lymph node biopsy. The lymph node biopsy was negative for malignancy. When Salmonella was identified in his pericardial tissue culture, we further elicited travel history from our patient. He had a recent travel history but denied consumption of any new foods or any associated diarrheal illness, and it was unclear how he became infected with Salmonella spp. We discussed a potential mechanism of infection after reviewing literature on other Salmonella pericarditis cases. In the prior case of Salmonella dublin pericarditis, the patient was undergoing chemotherapy and therefore was immunocompromised [20]. On review of the other case reports with different serotypes of Salmonella, many of the patients described in those cases were immunocompromised. Those patients either had comorbidities that led to immunocompromised states such as lupus, diabetes mellitus 2, heart failure, end-stage renal disease on hemodialysis, multiple myeloma, or cancer diagnosis, or they were on maintenance doses of steroids, on immunosuppressive therapy, or were recently given steroids or recently received antibiotics [19–59]. After reviewing those case reports, we theorized our patient could have been in a relatively immunocompromised state from prior steroid use for his Bell’s palsy and this predisposed him to a Salmonella infection. He received prednisone for about 1 month. We also theorized that he could have contracted this organism during one of his many travels or through consumption of food, since Salmonella dublin is typically an infection in cattle hosts. We are unsure if he had contact with any infected cattle. As we were not able to definitively find a reason for this patient’s infection, we recommended age-appropriate cancer screening to be performed, such as colonoscopy. He was promptly treated after identification of the Salmonella species. He remained hemodynamically stable until discharge, with subsequent follow-up appointments showing improvement in inflammatory markers and symptoms.

Interestingly, when reviewing the literature, we found that this was the second case of Salmonella-associated pericarditis at our institution; the first case was from Salmonella enteritidis and resulted in ventricular wall rupture [21]. The patient made a remarkable recovery and was eventually discharged to subacute rehabilitation.

Conclusions

It is important to be aware of Salmonella as a rare cause of pericarditis. It is important to take an extensive history when treating these patients, as is investigating why the patient was susceptible to an infection of this rarity, such as if the patient was exposed to medications leading to an immunocompromised state or if age-appropriate cancer screening had been completed. Prompt treatment can help prevent mortality.