Austrian syndrome and multiple myeloma: a fatal combination.

Dear Editor,

The incidence of Streptococcus pneumoniae endocarditis has decreased markedly with the use of antibiotics and stands now at 3% of all cases of endocarditis compared to 10-15% in the pre-antibiotic era.[1] However, the mortality rate remains high ranging from 28% to 60% despite appropriate antibiotic treatment.[2] During the past two decades the numbers of drug-resistant strains of S. pneumoniae have increased worldwide and are now common throughout the United States.[3] We hereby present a case of S. pneumoniae septicemia with evidence of mitral valve endocarditis, meningitis, pneumonia, and endophthalmitis who was also diagnosed with multiple myeloma (MM) at the same time. This may be the first reported case of the Austrian Syndrome associated with MM.

An 84-year-old male with past medical history of hypertension, asthma, and prostate cancer presented with back pain. He was a former smoker, denied alcohol, or intravenous drugs abuse. No prior pneumococcal vaccination was recorded. Heart rate was 91/minute, irregular, blood pressure 156/96 mmHg, temperature 37.4°C, respiration 20/minute. No heart murmur or gallop was heard. He had scattered rhonchi in both lung fields. Laboratory investigations revealed hemoglobin of 11.9 g/dL, white blood cell (WBC) count of 14.2 × 103 / mm3 (neutrophils 94.1%), blood urea nitrogen 10.3 mmol/L, creatinine 124 mmol/L, total protein 66 g/L, and albumin 29 g/L. Corrected serum calcium was 2.27 mmol/L. Urinalysis showed 7-10 WBC per high power field. Blood cultures were obtained and was started on intravenous (IV) levofloxacin 750 mg daily. Chest X-ray showed increased vascular markings in the right lung. Computed Tomography (CT) reported an infiltrate consistent with right lower lobe pneumonia [Figure 1]. On day three, the patient became confused and developed a fever of 38.1°C. A transthoracic echocardiogram did not show any vegetation. Lumbar puncture revealed cloudy spinal fluid with red blood cell count of 50 per mm3, WBC 650 per mm3 (neutrophils 68%, lymphocytes 32%), protein 4.69 g/L, and glucose 0.07 mmol/L. Antibiotic coverage was broadened to IV ceftriaxone 2 gm every 12 hours and vancomycin 1 gm every 12 hours. Blood cultures grew S. pneumoniae, sensitive to ceftriaxone, levofloxacin, and vancomycin. No organisms were identified in the spinal fluid. His WBC count remained between 13 and 17 × 103 / mm3. Magnetic resonance imaging reported unilateral right-sided endophthalmitis. Transesophageal echocardiogram at this time showed a 1.7 × 1.0 cm vegetation on the atrial side of the posterior mitral valve leaflet [Figure 2], fulfilling the modified Duke criteria for endocarditis. CT scan reported multiple lytic lesions within the bodies of the lumbar vertebrae. Serum electrophoresis showed a monoclonal protein spike. Immunofixation confirmed IgG and kappa chains. Bone marrow biopsy revealed increased plasma cells (10-20 %) confirming the diagnosis of MM. Mitral valve replacement was necessary, but his condition deteriorated rapidly. He developed progressive hypotension, hypoxic respiratory failure and died suddenly before surgery could be accomplished.

Figure 1

Computerized tomography scan of chest-right lower lobe pneumonia

Figure 2

Transesophageal echocardiogram-mitral valve vegetation

Robert Austrian described the syndrome that bears his name in 1956 reporting eight patients with S. pneumoniae septicemia and concurrent meningitis, endocarditis, and pneumonia.[4] We identified a total of 22 case reports after a MEDLINE search of all English medical literature since 1956 using ‘Austrian syndrome’ as key word [Table 1]. Fourteen patients (63%) underwent surgical replacement of the affected valves. There were four (18%) deaths. Aronin SI et al. reviewed 197 reported cases of pneumococcal endocarditis from 1966 to 1996, among them 29 had the Austrian Syndrome (14%). The aortic valve was involved in 74% of the patients, mitral 31%, tricuspid 8%, and pulmonary 0.8%. Surgical management decreased the mortality from 62% to 32%.[2] The large vegetation present in the mitral valve made the present case a candidate for surgical intervention since he fitted the American College of Cardiology and the American Heart Association 2006 guidelines for surgical intervention (valve replacement: class IIa and Class IIb).[5] His rapid downhill course precluded valve replacement. In our patient, asthma may have impaired his ability to clear the organism from the respiratory system and MM rendered him immunocompromized. Cheson BD et al. reported that MM serum produces a defect in the activation of the third component of complement.[6] Penicillin-resistant pneumococcal (PRP) strains are reported to be increasing, 24% in the USA, and 58% in some European countries.[1] Empiric treatment for PRP includes ceftriaxone or cefotaxime with vancomycin.[17] If there is resistance to cefotaxime [minimum inhibitory concentration (MIC) ≥2 μg/mL] rifampicin should be added to the vancomycin.[8] Our patient was treated with ceftriaxone and vancomycin. MIC for ceftriaxone was not obtained because the bacterium was penicillin sensitive and therefore the MIC was expected to be ≤2 μg/mL.[9]

Table 1

Cases of Austrian syndrome published in the English literature

In addition to antibiotics, corticosteroids have also been used successfully in the treatment of pneumococcal meningitis and reported to decrease mortality from 34% to 14%.[10] Steroids were not used in our patient.