Invasive Pneumococcal Disease in Older Man, but There's a Worse Problem

A 60-year-old man presented to the hospital after being referred by his general practitioner. He explained on admission that he had been in good health until about 10 weeks earlier, when he began to have episodes of coughing and fever. Clinicians also noted blisters around his mouth extending to his nostrils.

The patient said his first episode of symptoms occurred shortly after he had returned from a cruise in the Baltic Sea. The most recent symptoms had occurred 6 days previously, and had not responded to treatment with clarithromycin.

Assessment on admission showed he had a fever of 40.1°C (about 104.2°F), was tachycardic (109 beats/min), and tachypneic (28 breaths/min), with normal blood pressure of 138/81 mmHg. On auscultation, clinicians noted basal rales over the left lung.

Notable results of his laboratory tests were the following:

• Leukocytosis: 13×10⁹/L (normal range is 3.5×10⁹ L to 10×10⁹ L)

• Elevated C-reactive protein: 303 mg/mL (normal range <10 mg/L)

• Total protein: 97 g/L (normal range 64-83 g/L)

• Low albumin: 26 g/L (normal range 35-52 g/L)

• Hyponatremia: sodium 127 mmol/L (normal range 135-145 mmol/L)

Clinicians ordered a chest x-ray that revealed retrocardiac consolidation of the left lower lobe. The patient was diagnosed with community-acquired pneumonia, and he began empirical treatment with piperacillin/tazobactam and clarithromycin.

Results of blood and sputum cultures on the following day were positive for S. pneumoniae. As a result, clinicians adjusted his therapy to intravenous benzylpenicillin and later to oral amoxicillin. Treatment was continued for a total of 14 days.

The patient was also treated with valaciclovir to address suspected herpes simplex type 1 (HSV-1) infection, a diagnosis that was later confirmed by a polymerase chain reaction test of a swab of one of the blisters around his mouth.

Concerns about the persistent episodes of fever and cough along with evidence of the S. pneumoniae bacteremia and the rampant HSV-1 infection led clinicians to reassess the patient's history in greater detail. On further questioning, the patient reported that in the past month, he had lost 4 kg, and had ongoing night sweats.

Testing for HIV was negative.

Based on the patient's high total protein and low albumin levels, and the pneumococcal infection, clinicians suspected multiple myeloma.

Serum electrophoresis followed by immunofixation identified an IgG kappa monoclonal gammopathy (M-protein 31 g/L, free light-chain kappa 500.2 mg/L, free light-chain lambda 8.8 mg/L, kappa/ lambda ratio 56.84).

A biopsy of bone marrow showed a plasma cell infiltration over 60%. The patient underwent a whole-body low-dose computed tomography scan, which identified four lytic lesions in the pelvis and one in the cervical spine.

These findings established a diagnosis of multiple myeloma IgG kappa, as described in the Revised International Myeloma Working Group diagnostic criteria. When the patient recovered from the bacteremic pneumonia, he was started on standard induction treatment with bortezomib, lenalidomide, and dexamethasone, and scheduled for an autologous hematopoietic stem cell transplantation.

Upon discharge from the hospital, the patient was counseled about the importance of preventing recurrent bacterial infections through treatment with intravenous immunoglobulin, and 1 month later, he received the 13-valent pneumococcal vaccine.

Discussion

Clinicians presenting this rare case of invasive pneumococcal disease (IPD) as the first manifestation of underlying multiple myeloma emphasized the importance of being aware that myeloma could be an underlying disease in patients presenting with IPD.

The authors noted that due to the suppressed humoral and cellular immune responses caused by multiple myeloma, these patients are more susceptible to bacterial and viral infections, with a risk of significant morbidity and premature death. A study of the records of 1,027 Mayo Clinic patients diagnosed with multiple myeloma (median age of 66) found that the median duration of survival was 33 months and did not improve from 1985 through 1998.

Multiple myeloma is a clonal plasma cell proliferation disorder and often involves a premalignant stage, monoclonal gammopathy (MGUS), although the importance of this has not been determined, the case authors noted.

Still, infections that often occur with myeloma and even with MGUS cause early morbidity and mortality. The authors cited a study of 3,107 newly diagnosed patients with multiple myeloma, about 10% of whom died within 60 days, with bacterial infections responsible for 45% of the early deaths. The risk of bacterial infection is increased in myeloma patients with higher disease burden, relapsed disease, and those receiving high-dose chemotherapy, the case author explained.

IPD is defined by the presence of S. pneumoniae in normally sterile sites, such as blood, pleural space, and the cerebrospinal fluid, and is most often associated with bacteremia and pneumonia; about 25% of affected patients have to be admitted to intensive care.

Patients with multiple myeloma are more likely to be severely affected with IPD including bacteremia, the authors said, citing annual rates of approximately 674 cases/100,000 compared with 11 cases/100,000 in the general adult population. A large 12-year retrospective analysis of 479 myeloma patients treated in one hospital before and after the introduction of novel agents found that 65% of patients developed at least one infection, mainly bacterial, and 37% of therapies were associated with at least one infectious episode. The rate of infections remained constant over the 12-year period, and infectious complications did not increase after the routine implementation of novel agents, those researchers stated.

The case authors cited a Mayo Clinic review of diagnosis and treatment of multiple myeloma, which found the most common presenting symptoms to be fatigue and bone pain, with anemia, which contributes to fatigue, noted in approximately 75% of patients. Osteolytic skeletal lesions can be detected in about 80% of patients, and other presenting symptoms include hypercalcemia (15%) and elevated serum creatinine level (2 mg/dL or greater) in 20% of patients.

One reason for the relationship between multiple myeloma and increased risk of infections is reduced secretion of polyclonal immunoglobulin, the case authors said, adding that antibody-dependent humoral immunity is necessary to avoid S. pneumoniae infection.

Thus, preventing infections with S. pneumoniae involves use of pneumococcal vaccines and intravenous immunoglobulin replacement. However, these patients may have impaired responses to vaccination, and the benefit of intravenous immunoglobulin may be confined to patients with stable myeloma and recurrent serious infections or specific antibody deficiencies, the authors noted.

Conclusion

They concluded that the case highlights the importance of a thorough history and interpretation of laboratory tests in the context of IPD. But given the wide range of other predisposing diseases such as lymphoma, HIV, and specific polysaccharide antibody deficiency, screening for myeloma is not justified in all patients without an apparent predisposing factor presenting with IPD.

Still the authors urged vigilance for features of multiple myeloma, such as a history of weight loss, fatigue, and bone pain, when older patients present with IPD. Other warning signs include peripheral neuropathy, unexplained anemia, renal failure, hypercalcemia, and a discrepancy between an elevated total protein and low albumin level.

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