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06 January 2021: Articles  Switzerland

More than Meets the Eye: Bacteremic Pneumococcal Pneumonia as the Initial Presentation of Multiple Myeloma

Challenging differential diagnosis

Jonas Jautz1AEF, Eliska Potlukova1E, Franziska Zeeh2E, Michael Osthoff1AEF*

DOI: 10.12659/AJCR.927904

Am J Case Rep 2021; 22:e927904

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Abstract

BACKGROUND: Increased susceptibility to bacterial infections is a hallmark of multiple myeloma (MM). Invasive infections with Streptococcus pneumoniae may be the first manifestation of underlying MM. Clinicians treating patients with invasive S. pneumoniae infections may consider searching for underlying MM in the presence of certain diagnostic findings.

CASE REPORT: A previously healthy 60-year-old man was referred from his general physician because of fever, cough, and chills despite treatment with clarithromycin. The patient had experienced night sweats, weight loss, and recurrent episodes of fever and cough during the last 3 months. Examination was significant for left-sided pulmonary rales. A chest X-ray showed a retrocardiac consolidation of the left lower lobe. The patient was started on empirical antimicrobial therapy for community-acquired pneumonia. Subsequently, blood and sputum cultures were positive for S. pneumoniae. Given the history of night sweats and weight loss, the discrepancy between elevated total protein and low albumin levels, and the diagnosis of pneumococcal bacteremia, multiple myeloma (MM) was suspected and confirmed by immunofixation and bone marrow biopsy.

CONCLUSIONS: This case showed that clinicians should be vigilant for features of MM, which are encountered during history (e.g., weight loss, bone pain) or routine laboratory workup (e.g., unexplained anemia, renal failure, hypercalcemia, or a discrepancy between elevated total protein and low albumin levels) in elderly patients presenting with invasive pneumococcal disease.

Keywords: Herpes Simplex, Multiple Myeloma, Pneumococcal Infections, Pneumonia, Bacterial, Aged, Bacteremia, Middle Aged, Pneumonia, Pneumococcal, Streptococcus pneumoniae

Background

Streptococcus pneumoniae is an important human pathogen responsible for approximately 2 million death per year worldwide [1]. It is included in the list of 12 antibiotic-resistant “priority pathogens” of the World Health Organization that pose the greatest threat to human health. Invasive pneumococcal disease (IPD) is a result of a breach of epithelial or endothelial barriers (tissue invasion) and is defined by an isolation of S. pneumoniae from normally sterile sites (e.g., blood, pleural space, or cerebrospinal fluid) [1,2]. Bacteremia and pneumonia are the most common manifestations of IPD, and they are associated with admission to an Intensive Care Unit in one-fourth of cases [3]. Several risk factors have been recognized, such as age, certain comorbidities, and immunosuppression.

Multiple myeloma (MM) is a clonal plasma cell proliferation disorder that is often preceded by a premalignant stage termed monoclonal gammopathy of undetermined significance (MGUS) [4]. Infections constitute one of the major complications with MM and even with MGUS and cause early morbidity and mortality [5–7]. In the United States, an estimated 32 270 new MM cases and associated 12 830 deaths will occur in 2020 [8]. Augustson et al. [5] analyzed 3107 newly diagnosed MM patients and found that 299 (10%) died within 60 days, with bacterial infections causing 135 (45%) of the early deaths. Higher disease burden, relapsed disease, and high-dose chemotherapy are important factors that determine infection risk [9].

Only a few case reports document IPD as the first manifestation of underlying MM [10]. The aim of the present report is to raise awareness of MM as a possible underlying disease in patients presenting with IPD and highlight features of MM encountered during history or routine laboratory workup.

Case Report

A previously healthy 60-year-old man was referred from his general practitioner due to recurrent episodes of fever and cough during the past 2.5 months. The most recent episode of fever, cough, and chills occurred 6 days before admission and did not response to treatment with clarithromycin. The patient reported that the first episode started shortly after a cruise trip to the Baltic Sea.

On presentation, the patient was febrile (temperature 40.1°C), tachycardic (109 beats/min), normotensive (138/81 mmHg), and tachypneic (28 breaths/min), and basal rales were noted over the left lung on auscultation. Additionally, the patient had perioral grouped blisters extending to the nasal orifices. Laboratory tests were significant for leukocytosis (13×109/L, normal range [3.5–10]×109/L), elevated C-reactive protein (303 mg/mL, normal range <10 mg/L) and total protein (97 g/L, normal range 64–83 g/L), low albumin (26 g/L, normal range 35–52 g/L), and moderate hyponatremia (sodium 127 mmol/L, normal range 135–145 mmol/L). A chest X-ray showed a retrocardiac consolidation of the left lower lobe (Figure 1). The patient was diagnosed with community-acquired pneumonia and started on empirical antimicrobial therapy with piperacillin/tazobactam plus clarithromycin. On the next day, blood and sputum cultures were positive for S. pneumoniae, and the patient was de-escalated to intravenous benzylpenicillin and later to oral amoxicillin and treated for a total duration of 14 days.

Additionally, due to a presumed cutaneous herpes simplex type 1 (HSV-1) infection, the patient was treated with valaciclovir. This diagnosis was later confirmed by a positive HSV-1 polymerase chain reaction result based on a swab taken from a perioral blister.

Given the recurrent episodes of fever and cough, the S. pneumoniae bacteremia, and the extensive HSV-1 infection, a detailed history was again undertaken, which revealed night sweats and a weight loss of 4 kg within the past 4 weeks. An HIV test was negative. Given the discrepancy between the elevated total protein and low albumin levels and the diagnosis of pneumococcal bacteremia, MM was suspected. 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). Bone marrow biopsy revealed a plasma cell infiltration of >60%. Whole-body low-dose computed tomography scan demonstrated 4 lytic lesions in the pelvis and 1 in the cervical spine (Figure 2). Hence, in accordance with the Revised International Myeloma Working Group diagnostic criteria [4], a diagnosis of MM IgG kappa was established. After the patient’s recovery from the bacteremic pneumonia, standard induction treatment with bortezomib, lenalidomide, and dexamethasone was initiated, and the patient was scheduled for an autologous hematopoietic stem cell transplantation.

Treatment with intravenous immunoglobulin to prevent recurrent bacterial infections was discussed, and the patient received the 13-valent pneumococcal vaccination 1 month after discharge.

Discussion

An increased risk of bacterial and viral infections causing substantial morbidity and early mortality secondary to impaired humoral and cellular immune responses is well documented in patients with MM [5,6]. In particular, the burden of IPD including bacteremia is significantly higher (674 cases/100 000 per year vs. 11 cases/100 000 per year in the general adult population) [11]. However, despite this well-documented association, case reports of patients presenting with IPD as the first sign of underlying MM are rare. Kalambokis et al. [10] analyzed data from 17 cases presenting with an acute bacterial infection as the first manifestation of MM. Streptococcus pneumoniae was isolated as the causative pathogen in 65% of the cases (11/17) and was associated with bacteremia, septic arthritis, pneumonia, meningitis, and rarely cellulitis. In a large Swedish population-based study, Blimark et al. [6] showed that patients with MM had an increased risk of pneumonia and septicemia.

Susceptibility to infections is increased in MM patients for several reasons, including a diminished secretion of polyclonal immunoglobulins. In case of S. pneumoniae infection, antibody-dependent humoral immunity is crucial [12]. Strategies to prevent infections with S. pneumoniae therefore include administration of pneumococcal vaccines and intravenous immunoglobulin replacement [13], although vaccine responses may be impaired [14] and the benefit of intravenous immunoglobulin may be confined to patients with stable MM and recurrent serious infections or specific antibody deficiencies [15].

Conclusions

This case report highlights the importance of a thorough history and interpretation of laboratory tests in the context of IPD. Given the low incidence of underlying MM [16] and the variety of other predisposing diseases such as lymphoma, HIV, common variable immunodeficiency [17], or specific polysaccharide antibody deficiency [18], screening for MM is not justified in all patients without an apparent predisposing factor presenting with IPD.

However, clinicians should be vigilant for certain features of MM in elderly patients presenting with IPD that are encountered during history (e.g., weight loss, fatigue, bone pain), physical examination (e.g., peripheral neuropathy), and routine laboratory workup (e.g., unexplained anemia or renal failure, hypercalcemia, and a discrepancy between an elevated total protein and low albumin level) [19].

In conclusion, physicians treating IPD in an elderly patient without a readily identifiable predisposing disease may consider searching for underlying MM to facilitate the diagnosis in an earlier stage.

References:

1.. Weiser JN, Ferreira DM, Paton JC: Nat Rev Microbiol, 2018; 16(6); 355-67

2.. Dockrell DH, Whyte MKB, Mitchell TJ, Pneumococcal pneumonia: Mechanisms of infection and resolution: Chest, 2012; 142(2); 482-91

3.. Marrie TJ, Tyrrell GJ, Majumdar SR, Eurich DT, Invasive pneumococcal disease: Still lots to learn and a need for standardized data collection instruments: Can Respir J, 2017; 2017; 2397429

4.. Rajkumar SV, Dimopoulos MA, Palumbo A, International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma: Lancet Oncol, 2014; 15(12); e538-48

5.. Augustson BM, Begum G, Dunn JA, Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United Kingdom Medical Research Council trials between 1980 and 2002 – Medical Research Council Adult Leukaemia Working Party: J Clin Oncol, 2005; 23(36); 9219-26

6.. Blimark C, Holmberg E, Mellqvist UH, Multiple myeloma and infections: A population-based study on 9253 multiple myeloma patients: Haematologica, 2015; 100(1); 107-13

7.. Kristinsson SY, Tang M, Pfeiffer RM, Monoclonal gammopathy of undetermined significance and risk of infections: A population-based study: Haematologica, 2012; 97(6); 854-58

8.. Siegel RL, Miller KD, Jemal A, Cancer statistics, 2020: Cancer J Clin, 2020; 70(1); 7-30

9.. Brioli A, Klaus M, Sayer H, The risk of infections in multiple myeloma before and after the advent of novel agents: A 12-year survey: Ann Hematol, 2019; 98(3); 713-22

10.. Kalambokis GN, Christou L, Tsianos EV, Multiple myeloma presenting with an acute bacterial infection: Int J Lab Hematol, 2009; 31(4); 375-83

11.. Wong A, Marrie TJ, Garg S, Increased risk of invasive pneumococcal disease in haematological and solid-organ malignancies: Epidemiol Infect, 2010; 138(12); 1804-10

12.. Wilson R, Cohen JM, Reglinski M, Naturally acquired human immunity to pneumococcus is dependent on antibody to protein antigens: PLoS Pathog, 2017; 13(1); e1006137

13.. Terpos E, Kleber M, Engelhardt M, European Myeloma Network guidelines for the management of multiple myeloma-related complications: Haematologica, 2015; 100(10); 1254-66

14.. Renaud L, Schraen S, Fouquet G, Response to pneumococcal vaccination in multiple myeloma: Cancer Med, 2019; 8(8); 3822-30

15.. Chapel HM, Lee M, Hargreaves R, Randomised trial of intravenous immunoglobulin as prophylaxis against infection in plateau-phase multiple myeloma. The UK Group for Immunoglobulin Replacement Therapy in Multiple Myeloma: Lancet, 1994; 343(8905); 1059-63

16.. Gregersen H, Pedersen G, Svendsen N, Multiple myeloma following an episode of community-acquired pneumococcal bacteraemia or meningitis: APMIS, 2001; 109(11); 797-800

17.. Sanges S, Wallet F, Blondiaux N, Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection: Clin Microbiol Infect, 2017; 23(8); 576 e1–e5

18.. Lopez B, Boucher A, Bahuaud M, Specific polysaccharide antibody deficiency revealed by severe bacterial infections in adulthood: A report on 11 cases: Clin Infect Dis, 2017; 65(2); 328-31

19.. Kyle RA, Gertz MA, Witzig TE, Review of 1027 patients with newly diagnosed multiple myeloma: Mayo Clin Proc, 2003; 78(1); 21-33

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923