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CASE REPORT
Year : 2022  |  Volume : 49  |  Issue : 2  |  Page : 207-209

Bacterial meningitis as the first presentation of multiple myeloma


1 Department of Critical Care, Datta Meghe Institute of Medical Sciences (Deemed to be University), Jawaharlal Nehru Medical College, Wardha, Maharashtra, India
2 Department of Pathology, Datta Meghe Institute of Medical Sciences (Deemed to be University), Jawaharlal Nehru Medical College, Wardha, Maharashtra, India
3 Department of Medicine, Datta Meghe Institute of Medical Sciences (Deemed to be University), Jawaharlal Nehru Medical College, Wardha, Maharashtra, India
4 Department of Nephrology, Datta Meghe Institute of Medical Sciences (Deemed to be University), Jawaharlal Nehru Medical College, Wardha, Maharashtra, India

Date of Submission18-Feb-2022
Date of Acceptance28-Jun-2022
Date of Web Publication23-Aug-2022

Correspondence Address:
Samarth Shukla
Department of Pathology, Datta Meghe Institute of Medical Sciences (Deemed to be University), Jawaharlal Nehru Medical College, Sawangi, Meghe, Wardha - 442 004, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.jss_34_22

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  Abstract 


Multiple myeloma (MM) is a monoclonal gammopathy. Patients with MM are vulnerable to infections, especially by encapsulated bacteria. These infections have been associated with severe morbidity and mortality in MM. A key underlying cause of the immune system's decline in MM is insufficient production of polyclonal immunoglobulin, which manifests as severe hypogammaglobulinemia. An acute bacterial infection is rarely the first sign of the disease. We present a case of a 65-year-old male who presented to us with fever and disorientation. Clinical examination revealed signs of meningeal irritation. Cerebrospinal fluid study confirmed bacterial meningitis. Associated features such as renal failure, high erythrocyte sedimentation rate, hyperglobulinemia, and anemia lead to suspicion of MM which was later confirmed by serum electrophoresis.

Keywords: Bacterial infections, meningitis, multiple myeloma


How to cite this article:
Zutushi S, Shukla S, Acharya S, Bhawane A, Mishra P, Singh S. Bacterial meningitis as the first presentation of multiple myeloma. J Sci Soc 2022;49:207-9

How to cite this URL:
Zutushi S, Shukla S, Acharya S, Bhawane A, Mishra P, Singh S. Bacterial meningitis as the first presentation of multiple myeloma. J Sci Soc [serial online] 2022 [cited 2022 Oct 3];49:207-9. Available from: https://www.jscisociety.com/text.asp?2022/49/2/207/354269




  Introduction Top


In multiple myeloma (MM), there is uncontrolled proliferation of plasma cells resulting in the formation of a monoclonal immunoglobulin, which proliferates and overwhelms the bone marrow. Infections usually occur within 3 months of diagnosis and/or at initiation of chemotherapy.[1],[2] Several evidences suggest that the poor prognostic indicators of MM are male sex, age more than 75 years, declining performance status of the patient, hypercalcemia, raised lactate dehydrogenase, hypoalbuminemia, low body mass index, and early infections.[2],[3] The mortality in MM cases because of infections can be up to 65%.[4],[5]


  Case Report Top


A 65-year-old male presented to the emergency department (ED) of this hospital with chief complaints of back pain for 15 days, as well as altered mental status with fever for 4 days. The patient was relatively alright 15 days back when he developed low back pain which was continuous, dull aching type and was aggravated especially at night. There was no radicular pain, bladder and bowel incontinence, and weakness in the lower limb. The patient visited a private hospital for the back pain and was treated with pain killers. The back pain continued at home, and 4 days before the admission, he developed fever and altered mentation as history given by relatives. There was no history of vomiting, convulsions, cough, and dyspnea.

On examination in the ED, the patient was febrile (temperature -38.3°C) and tachycardic (heart rate -131 bpm). Blood pressure was 80 mmHg systolic. Central nervous system (CNS) examination revealed a Glasgow coma scale of 7 (E-2, M-3, V-2), with positive neck stiffness and Kernig's sign. He was then admitted to the medical intensive care unit.

Laboratory investigations revealed anemia (Hgb 7.9 g/dL), total leukocyte count - 14,500/mm3 with 90% neutrophilia, blood urea -102 mg/dL, serum creatinine -5.4 mg/dL, total protein -10 g/dL, albumin -2.8 g/dL, and globulin -7.2 g/dL. Erythrocyte sedimentation rate (ESR) was 112 in the 1st h. Cerebrospinal fluid (CSF) analysis revealed increased total protein (615 mg/dL), increased white blood cell (WBC) (146 cells/mm3) with neutrophils (80%), and decreased glucose (24 mg/dL). The adenosine deaminase level in the CSF was 8 U/L (normal <40 U/L). Gram stain of CSF was negative, and CSF culture revealed Gram-positive diplococci. A diagnosis of bacterial meningitis was kept, and the patient was started on intravenous (IV) fluids: ceftriaxone 2 g IV 12 hourly, injection (inj.) vancomycin 1 g IV 12 hourly, inj. ampicillin 2 g IV 4 hourly, and dexamethasone 10 mg IV 6 hourly, starting 20 min before the antibiotics were started, along with vasopressor and other medications.

MM was suspected due to infection, elevated ESR, hyperglobulinemia, anemia, and renal failure. Urine for Bence Jone's protein was negative. Serum protein electrophoresis revealed the presence of a distinct M-band (3.5 g/dL) in the beta 2-region [Figure 1]. In immunofixation and immunoglobulin quantitative assays, the patient's alpha 1 and 2-microglobulin levels were both abnormally high, at 5.6 and 55.4 μg/L, respectively. A skeletal survey revealed no osseous lytic lesions. A bone marrow biopsy revealed features of MM [Figure 2].
Figure 1: Serum protein electrophoresis showing M-band in beta 2 region. Ref. = Reference, Conc. = Concentration, A/G ratio = Albumin to Globulin

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Figure 2: Bone marrow smears obtained with Leishman's stain showing plasmacytosis. Plasma cells population is composed of both mature and immature plasma cells. Mature cells have abundant deeply basophilic cytoplasm with perinuclear hof, eccentric nuclei (with coarse cart wheel chromatin). Immature plasma cells showing binucleation and mild pleomorphism (a, high power view, ×40 and b, oil immersion view, ×100)

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Chemotherapy was postponed due to the current infection. The patient was managed with empirical antibiotics, IV fluids, two sessions of hemodialysis, ventilatory and vasopressor support, and steroids. After 9 days, the patient succumbed to his illness.


  Discussion Top


MM is characterized by the multiplication of plasma cells that produce enormous amounts of monoclonal antibodies. The sentinel episode of infection is usually more common in the first 3 months after a diagnosis of MM, according to Chapel and Lee.[6] The next vulnerable period for acquiring infections is within first 3 months of chemotherapy in 75% of cases. The bulk of these bacterial infections are of respiratory or urinary tract.[6]

In MM, T cells are prevented from entering an inflammatory pathway, which stops cytokine secretion.[7],[8] In both stable and advancing MM, transforming growth factor-β or interleukin (IL)-10, or both, has been shown to diminish T cells expressed by dendritic cells (DCs).[9] DCs then produce a lot of IL-10 and relatively little IL-12, lowering their effectivity.[10]

In MM, the signaling molecules such as T-helper 17 cells which inhibit bacterial penetration into the mucosal cells are dysfunctional.[11],[12] B-cells inhibition causes polyclonal hypoglobulinemia, which is common in MM.[13],[14]

Patients with MM are at a higher risk of infection, particularly from encapsulated bacteria such as Streptococcus pneumoniae. Meningitis and pneumonia are the most dangerous forms of infections in MM.[15],[16],[17],[18],[19]

Patel and Nikcevich[20] described a case of pneumococcal meningitis as the first presentation of MM. They hypothesized an underlying immunodeficiency because a stained CSF smear revealed numerous extracellular Gram-positive diplococci, indicating a lack of complement activation. Despite high CSF bacterial concentrations, WBCs (0–20/mm3) have been associated with a bad outcome.[21]


  Conclusion Top


MM is a monoclonal gammopathy where there is a clonal proliferation of a single immunoglobulin by malignant plasma cells. It usually occurs in elderly males and presents with bone pains, renal failure, and anemia. Infections are commonly associated with MM because of immune dysfunction. Most common sites are respiratory and genitourinary, but rarely, CNS infections can be the primary manifestation. Any elderly male presenting with serious systemic infections and other associated features such as renal failure and skeletal symptoms should alert the treating physician to rule out MM by appropriate investigations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Terebelo H, Srinivasan S, Narang M, Abonour R, Gasparetto C, Toomey K, et al. Recognition of early mortality in multiple myeloma by a prediction matrix. Am J Hematol 2017;92:915-23.  Back to cited text no. 1
    
2.
Karlsson J, Andréasson B, Kondori N, Erman E, Riesbeck K, Hogevik H, et al. Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance. Clin Vaccine Immunol 2011;18:969-77.  Back to cited text no. 2
    
3.
Tete SM, Bijl M, Sahota SS, Bos NA. Immune defects in the risk of infection and response to vaccination in monoclonal gammopathy of undetermined significance and multiple myeloma. Front Immunol 2014;5:257.  Back to cited text no. 3
    
4.
Augustson BM, Begum G, Dunn JA, Barth NJ, Davies F, Morgan G, et al. 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;23:9219-26.  Back to cited text no. 4
    
5.
Hsu P, Lin TW, Gau JP, Yu YB, Hsiao LT, Tzeng CH, et al. Risk of early mortality in patients with newly diagnosed multiple myeloma. Medicine (Baltimore) 2015;94:e2305.  Back to cited text no. 5
    
6.
Chapel HM, Lee M. The use of intravenous immune globulin in multiple myeloma. Clin Exp Immunol 1994;97 Suppl 1:21-4.  Back to cited text no. 6
    
7.
CDC C. Fungal diseases. Retrieved online at: http://www. cdc. gov/ncezid/dfwed/mycotics 2018;2.  Back to cited text no. 7
    
8.
Cook G, Campbell JD, Carr CE, Boyd KS, Franklin IM. Transforming growth factor beta from multiple myeloma cells inhibits proliferation and IL-2 responsiveness in T lymphocytes. J Leukoc Biol 1999;66:981-8.  Back to cited text no. 8
    
9.
Brown GD. Phagocytes play a significant role in innate antifungal immunity. Annu Rev Immunol 2011;29:1-21.  Back to cited text no. 9
    
10.
Brown RD, Pope B. Dendritic cells from myeloma patients are numerically normal but functionally deficient because they fail to up-regulate CD80 (B7-1) expression after huCD40LT activation due to transforming growth factor-1 and interleukin-10 suppression. Blood 2001;98:2992-8.  Back to cited text no. 10
    
11.
Ogawara H, Handa H, Yamazaki T, Toda T, Yoshida K, Nishimoto N, et al. High Th1/Th2 ratio in patients with multiple myeloma. Leuk Res 2005;29:135-40.  Back to cited text no. 11
    
12.
Mozaffari F, Hansson L. Signaling molecules and cytokine production in T cells of multiple myeloma patients showed an increase in aberrations as the disease progressed. Br J Haematol 2004;124:315-24.  Back to cited text no. 12
    
13.
Paris C, Scott GB, Cook G. Th17 cells are increased in the bone marrow but not the peripheral blood in multiple myeloma and demonstrate defective functionality and aberrant phenotypes. Blood 2014;124:3420.  Back to cited text no. 13
    
14.
Rawstron AC, Davies FE, Owen RG. In multiple myeloma, B-lymphocyte suppression is a reversible condition that affects only normal B-cell progenitors and plasma cell precurso. Br J Haematol 1998;100:176-83.  Back to cited text no. 14
    
15.
Naderi HR, Sheybani F, Khodashahi R. Multiple Myeloma with a high grade fever and loss of consciousness is an unusual presentation. Int J Med Pharm Case Rep 2016;6:1-7.  Back to cited text no. 15
    
16.
Kalambokis GN, Christou L, Tsianos EV. Multiple myeloma presenting with an acute bacterial infection. Int J Lab Hematol 2009;31:375-83.  Back to cited text no. 16
    
17.
Gregersen H, Pedersen G, Svendsen N. Multiple myeloma following an episode of community-acquired pneumococcal bacteraemia or meningitis. APMIS 2001;109:797-800.  Back to cited text no. 17
    
18.
Pasa S, Altintas A, Cil T, Ustun C, Bayan K, Danis R, et al. Two cases of bacterial meningitis accompanied by thalidomide therapy in patients with multiple myeloma: Is thalidomide associated with bacterial meningitis? Int J Infect Dis 2009;13:e19-22.  Back to cited text no. 18
    
19.
Rodríguez-Créixems M, Muñoz P, Miranda E, Peláez T, Alonso R, Bouza E. Recurrent pneumococcal bacteremia. A warning of immunodeficiency. Arch Intern Med 1996;156:1429-34.  Back to cited text no. 19
    
20.
Patel MR, Nikcevich DA. The value of looking. Multiple myeloma discovered by an unusual finding in Gram-stained spinal fluid. N C Med J 2002;63:129-30.  Back to cited text no. 20
    
21.
Tunkel AR. Hartman BJ. Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39:1267-84.  Back to cited text no. 21
    


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  [Figure 1], [Figure 2]



 

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