Pneumococcus beyond an Austrian syndrome – A case report

Abstract

Austrian syndrome is a rare entity characterized by Osler’s triad: endocarditis, pneumonia and meningitis, caused by Streptococcus pneumoniae (Austrian, 1957 [1]). This aggressive syndrome is associated with high morbidity and mortality, often due to the involvement of the heart valves and their destruction (Nogué et al., 2019 [2], Araji et al., 2008 [3]).

We present a case of Austrian syndrome in a splenectomised elderly patient with an unusual presentation: septic arthritis complicated by endocarditis, septic cerebral emboli, meningitis and pneumonia. Despite appropriate therapy, the prognosis remained poor and the patient died at day 7.

Introduction

Streptococcus pneumoniae are gram-positive bacteria that commonly colonize the mucosal surfaces of the human upper respiratory tract [4]. In susceptible people however, they can lead to the development of disease through a wide range of infections, including blood and sterile sites - invasive pneumococcal disease (IPD) [5] Local spread, aspiration or seeding to the bloodstream appear to be the main mechanisms in which invasive diseases develops, but other factors including age, lifestyle traits, comorbidities and even the implied strain have their role [4].

A rare but catastrophic manifestation, a triad of pneumonia, endocarditis and meningitis, was described in 1881 by Sir William Osler. In 1957, Robert Austrian reported 8 cases of Osler’s triad in which 6 patients died, mainly due to aortic valve rupture [1].

Although the incidence IPD has decreased initially due to the introduction of beta-lactam therapy and posteriorly due to universal vaccination [3], it remains a major cause of mortality and morbidity in Europe, especially in immunocompromised patients or with multimorbidity [5].

Case description

We reported a case of an 84 year-old female, partially dependent in daily-life activities for the last 6 months, after a severe SARS-CoV-2 infection.

She had a past medical history of splenectomy due to Immune thrombocytopenic purpura, Rheumatoid Arthritis medicated with methotrexate and corticosteroids and total knee prosthesis bilateral, last revision 8 years ago. Medical records about pneumococcal immunization were not available.

She resorted to an orthopedic surgeon, following a 4-days history of disabling knee pain, fever and anorexia. Upon initial observation, inflammatory signs and ROM limitation were noted. A clinical diagnosis of septic arthritis was made and the patient was referred to the Emergency Room (ER). Blood test on ER admission revealed leukocytosis (WBC 16.6 × 10⁹/L) with neutrophilia (81.2%) and a raised C-reactive protein. She was taken to the Operating Room (OR) and knee arthrotomy, debridement and lavage was performed. Synovial and capsular biopsy, pus samples and blood cultures were collected.

She was admitted to intensive care (ICU) after surgery, with a septic shock diagnosis. Vancomycin and Ceftriaxone were promptly started. As part of the ICU initial screening, a pneumococcal urine antigen test was performed and came back positive. On day 1 of ICU, a preliminary blood culture result reported a gram-positive cocci. Based on this finding, an echocardiogram was performed to rule out endocarditis. However, it demonstrated several mitral vegetations resulting on a partial posterior leaflet destruction, compatible with the diagnosis of endocarditis. Surgical intervention was discussed with a cardiothoracic surgeon, but due to the patient’s age and comorbilities, she was not eligible for surgical treatment at that time.

On day 2, vasopressor support was suspended. While gradually reducing sedation, focal neurologic deficits were observed: left hemiparesis, left conjugate eye deviation and severe aphasia. Cranial CT scan showed multiple ischemic lesions, compatible with an embolic etiology, suggesting septic cerebral emboli. Lumbar puncture was performed: CSF showed a glucose concentration of 42 mg/dL, a WBC of 453 cells/uL, a positive pneumococcal CSF antigen test and a diagnostic of meningitis was made. On day 3, biopsy and blood cultures came back positive for S. pneumoniae. Antibiotic therapy was de-escalated according to antibiogram to Cefotaxime. Despite effective antibiotic therapy, the patient worsens with a decreasing GCS score (14–11) and recurrent fever. The patient had an unfavorable clinical course, with progressive mental status deterioration and respiratory failure. On day 4 of hospitalization, a new infiltrate on plain chest radiograph developed, suggesting pneumonia, thus completing the diagnosis of Austrian syndrome associated with septic arthritis and embolic stroke.

Given the poor prognosis, the CNS involvement and associated comorbidities, therapeutic measures were not sufficient and patients comfort was optimized. She died on day 7.

Discussion

The clinical spectrum of S. pneumoniae infection is wide and include several entities that are uncommon these days but were frequent in the pre-antibiotic era. It remains however a common cause of otitis media, sinusitis, conjunctivitis and the main cause of community-acquired pneumonia and bacterial meningitis in adults [5].

Pneumococcal Septic Arthritis is usually described as “rarely encountered” but it can account up to 6% of all bacterial arthritis in some series [3]. It usually arises from hematogenous seeding of a joint with a primary focus being identified only in 52% of the patients and without any extra-articular disease up to 16% [6]. According to Ross, Saltzman, Carling and Shapiro (2013) major risk factors for adult pneumococcal arthritis include rheumatoid arthritis (22%), alcoholism (20%), osteoarthritis (14%), prosthetic joints (14%), coronary disease (10%) and corticosteroid use (9%). Classic risk factors associated with Austrian Syndrome also include alcoholism, immunosuppression (e.g. asplenia, corticosteroids users, transplant recipients) and other comorbidities including diabetes mellitus [2].

In this patient, the primary cause of septic arthritis was not identified. No signs of other local infections were reported during primary examination. She was admitted to the ICU under deep sedation and mechanical ventilation, so clinical history was not directly obtained from the patient. Even though the articular source was surgically controlled and the patient was under adequate antibiotic therapy, the infection spread to multiple sites including lungs, heart and central nervous system.

S. pneumoniae is currently an infrequent cause of severe infectious endocarditis (IE), however, a preliminary result of Streptococcus bacteraemia, a genus of bacteria that include S. viridans group and S. bovis, forced us to rule out endocarditis [7]. Once endocardial infection is established, the course is typically aggressive: the presentation is generally acute, there’s a rapid valvular destruction and extracardiac sequels, including hemodynamic instability and systemic embolization, as reported in our case, are common [3].

Regarding central nervous system involvement, acute ischemic stroke is the most common neurologic complication of IE. The pattern seen on CT, with multifocal infarction, suggested a cardioembolic origin. Management in the setting of IE differs, and anticoagulation |antiplatelet agents are contraindicated [8]. Meningitis is a relatively rare complication of IE and the reverse may also occur. However, after bloodstream invasion, the release of inflammatory mediators caused by infection facilitates pneumococcal crossing of the blood-brain barrier and the development of meningitis [9].

Despite aggressive therapeutic management, Austrian syndrome remains associated in literature with high morbidity and mortality. The difficulty of early recognition of heart involvement (lack of stigmas and symptoms already explained by lung and CNS involvement) contribute to the prognosis. Much of the literature on Austrian syndrome emphasizes the need for early surgical intervention, quoting a reduction in death rate from 60% to 32% when early surgical approach is adopted [10].

In our case, due to all the comorbidities, the patient was not eligible for surgical treatment. The damage made by IPD lead us to reduce the therapeutic effort, and the patient died at day 7.

The patient had a previous history of splenectomy and no records of pneumococcal vaccination were available. The spleen is a lymphoid organ with a crucial role in eliminating encapsulated bacteria. Infections are the most frequent complication and severe infections may occur. A rapidly progressive fulminant infection, known as OPSI, overwhelming post-splenectomy infection, has been linked to the increased risk of spontaneous bacteraemia that these patients present, with S. pneumoniae as the main culprit in over 50% of cases. Incidence of OPSI has been reported to be 5% over the long-term and mortality can reach up to 50%. The presentation is non-specific, there is often no obvious portal of infection and it may rapidly progress to death within 24–48 h [11], [12]. Prevention of infection relies on immunization, prophylactic antibiotics and patient education, since most patients are not properly informed about the risks and preventive measures [11].

Routine immunization has been available since the late 80s and has changed profoundly the incidence IPD and pneumonia. There are currently two principal types of pneumococcal vaccines in use: pneumococcal polysaccharide vaccine (PPV) which is not recommended in children less than 2 yo, may require re-vaccination and promote a less robust immune response compared with pneumococcal conjugate vaccines (PCV), which are highly immunogenic but are effective against a smaller subset of serotypes [13].

CRediT authorship contribution statement

Each author contributed to the writing of this paper.

Sources of funding

No funding required.

Ethical approval

Yes.

Consent

Report approved by the ethics committee. No close relatives for sign consent.

Conflicts of interest

No conflicts to declare.