Infective endocarditis initially manifesting as pseudogout

Abstract

Infective endocarditis is a commonly encountered disease in which diagnosis is often challenging due to the variety of clinical manifestations. Early identification is key due to risk of mortality without treatment. In this case, a 31-year-old man presented with pseudogout of the right ankle and COVID-19 infection. Further workup showed blood cultures growing Staphylococcus aureus, and the diagnosis of infective endocarditis was confirmed by echocardiography. Independently, pseudogout and infective endocarditis result in activation of the innate immune system and can manifest with joint inflammation. Their co-occurrence likely resulted in an augmented inflammatory response due to overlap in their pathophysiologic pathways.

Infective endocarditis (IE) is a bacterial infection of the endocardium that often affects the heart valves. Risk factors for IE include preexisting valvular disease, a recent dental procedure, and intravenous drug use. The most commonly isolated bacteria is Staphylococcus aureus. In 2009, there were over 40,000 hospital admissions for IE, with admissions increasing in each of the five prior decades.¹ Prompt diagnosis and treatment are paramount due to the mortality rate; estimated in-hospital mortality alone was 19.7% in the 2000s.² Common symptoms include fever, chills, fatigue, arthralgias, myalgias, cardiac manifestations, and extracardiac manifestations that are attributed to embolic disease and immune complexes. Our case describes what appears to be an extremely rare occurrence of IE manifesting initially with pseudogout of the ankle. IE commonly manifests with musculoskeletal symptoms and can mimic other diseases. However, an association between IE and pseudogout has not been illustrated.

CASE PRESENTATION

A 31-year-old man presented to the emergency department with a 1-week history of pain in the right ankle and shoulders associated with progressive weakness and fatigue. Before the onset of joint pain, he had fevers and chills. He also had a 7-month history of intravenous fentanyl use, with the last use being 3 days prior to admission. He was afebrile with normal vital signs. Physical examination revealed a small effusion in the right ankle and tenderness to palpation. Range of motion in the ankle was limited by pain. No cardiac murmurs were present. Laboratory studies were significant for an elevated creatinine of 5.4 mg/dL, white blood cell count of 14.9 × 10³/µL, erythrocyte sedimentation rate of 123 mm/h, and C-reactive protein of 35.1 mg/dL. An x-ray of the right ankle showed no abnormalities. Joint aspiration of the right ankle yielded yellow, cloudy fluid with 16,000 white blood cells. Gram stain of the synovial fluid was negative for bacteria but showed polymorphonuclear cells. Bacterial and fungal cultures showed no growth. However, positively birefringent rhomboid-shaped calcium pyrophosphate (CPP) crystals were identified. He was treated with intravenous fluids for his acute kidney injury and prednisone for pseudogout. Secondary causes of pseudogout, such as primary hyperparathyroidism, hypomagnesemia, hemochromatosis, and gout, were evaluated with serum blood tests and ruled out.

The following day, blood cultures from admission grew methicillin-sensitive S. aureus, and his COVID-19 polymerase chain reaction test was also positive. A transthoracic echocardiogram showed a large 1.5 × 1.9 cm vegetation attached to the septal leaflet of the tricuspid valve. The patient was started on intravenous nafcillin for IE and supportive care for COVID-19 infection. He improved clinically but ultimately left against medical advice after just 3 weeks of treatment.

DISCUSSION

Typical features of IE include fever, general malaise, weakness, immunologic phenomena (e.g., Osler’s nodes, Roth spots), and vascular phenomena (e.g., septic emboli, Janeway lesions). Musculoskeletal manifestations are relatively common, occurring in 19% to 44% of patients.³ Myalgias with arthralgia/arthritis are the most common musculoskeletal complaint and may be the only musculoskeletal manifestation.^4,5 These initial musculoskeletal manifestations distract from the underlying diagnosis, which may delay time to appropriate treatment and increase mortality. A literature review using PubMed, Cochrane, and MEDLINE between 2000 and 2020 uncovered a case of IE manifesting with septic arthritis and pseudogout but no other cases that manifested with pseudogout in the absence of a septic joint.

It is now widely accepted that the musculoskeletal features of IE are due to circulating immune complexes. Although the mechanism is not fully elucidated, it is believed to be the result of immune complex deposition and complement activation in the target tissues.⁶ CPP crystal deposition occurs in the joint space and most commonly in the knee. The presence of these crystals results in activation of the innate immune system and the inflammatory-mediated damage seen in acute CPP crystal arthritis (formerly known as pseudogout).⁷ The pathogenesis involves the activation of the NLRP3 inflammasome, resulting in release of the cytokine interleukin-1β, which is proinflammatory.⁸ Subsequent macrophage-mediated release of interleukin-1β and tumor necrosis factor alpha, both of which attract neutrophils to the joint, further propagates the inflammatory response.⁹ The above inflammatory response was likely amplified by the presence of circulating immune complexes due to the concurrent IE, which would also result in chemotaxis of neutrophils and macrophages, thereby augmenting the inflammation.

Some well-established risk factors for pseudogout include hyperparathyroidism, hypomagnesemia, hemochromatosis, and joint trauma, none of which were present in this patient.^7,10,11 Furthermore, the prevalence increases with advancing age and presentation is uncommon in patients under the age of 60.^11,12 Finally, this patient was also diagnosed with COVID-19, which commonly manifests with arthralgias and may have contributed to some of his joint pain.^13,14

In summary, we report a case of a 31-year-old man with IE who was initially diagnosed and treated for a case of pseudogout. Physicians need to be aware of the wide array of clinical manifestations of IE and the fact that musculoskeletal complaints are relatively common.