Skip to main content

Streptococcus pneumoniae meningitis in a child with idiopathic nephrotic syndrome: a case report

Abstract

Background

Children with nephrotic syndrome are at increased risk of infections, including bacterial peritonitis, pneumonia, and cellulitis. However, bacterial meningitis, a potentially life-threatening complication, has not been highlighted as an infectious complication of nephrotic syndrome in recent reviews. We report a very subtle and unusual presentation of bacterial meningitis in a child with nephrotic syndrome, which without a high index of suspicion, would have been missed.

Case presentation

A 9-year-old African-American male with a history of steroid-dependent nephrotic syndrome presented to the nephrology clinic for routine follow-up. His medications included mycophenolate mofetil and alternate-day steroids. His only complaint was neck pain and stiffness that the mother attributed to muscle tightness relieved by massage. There was no history of fever, vomiting, headache, photophobia, or altered mental status. On physical examination, he was afebrile (99 °F), but had mild periorbital swelling and edema on lower extremities. He appeared ill and exhibited neck rigidity, and demonstrated reflex knee flexion when the neck was bent. Laboratory evaluation revealed leukocytosis, elevated C-reactive protein, hypoalbuminemia, and proteinuria. Cerebrospinal fluid suggested bacterial meningitis. The patient was treated with ceftriaxone and vancomycin. Both cerebrospinal and blood cultures grew Streptococcus pneumoniae; vancomycin was discontinued. The child completed a 2-week course of ceftriaxone and was discharged home.

Conclusions

A high index of suspicion is necessary in children with nephrotic syndrome treated with corticosteroids, as symptoms may be masked, and thus, a life-threatening disease be missed. Bacterial meningitis should be highlighted as a serious infection complication in children with nephrotic syndrome.

Peer Review reports

Introduction

Infections are leading causes of morbidity in children with nephrotic syndrome (NS). Children with NS are at increased risk of bacterial peritonitis, pneumonia, and cellulitis, as well as sinusitis/tonsillitis, gastroenteritis, and urinary tract infections [1, 2]. Bacterial meningitis, a serious complication of NS, has not been highlighted as a potential infection in NS in recently published reviews, despite the growing number of case reports of this serious complication [3,4,5,6].

Here we present a subtle case of Streptococcus pneumoniae meningitis in a child with NS who presented without fever and with minimal symptoms, and emphasize the need to have a high index of suspicion in children treated with corticosteroids as symptoms may be masked and a life-threatening disease missed.

Case presentation

A 9-year-old African-American male with a history of steroid-dependent NS presented to the nephrology clinic for routine follow-up care in September 2018. He had been diagnosed with NS at 4 years of age, and had multiple relapses and hospitalizations for management of his disease. He was up-to-date with all his immunizations, including vaccination for S. pneumoniae; he had received PCV7 as the initial series and a booster of PCV13. He was receiving mycophenolate mofetil 200 mg twice a day for about 6 months and prednisone 30 mg on alternate days for about 1 month. The child’s only complaint was neck pain and stiffness that had begun 1–2 days prior to presentation. His mother attributed the neck pain to muscle tightness and stated that massages to the area provided some pain relief. There was no history of recent illness, fever, nausea, vomiting, photophobia, headache, seizures, or altered mental status.

On physical examination, he was afebrile and had mild periorbital swelling and edema on lower extremities. He appeared ill, exhibited neck rigidity, and revealed reflex knee flexion on neck flexion. He was transferred to the emergency department (ED) for further evaluation and management. On admission to the ED, his temperature was 99 °F, heart rate 112 beats per minute, respiratory rate 22 breaths per minute, blood pressure 101/72 mmHg, and oxygen saturation 99% on room air. The child persisted with neck stiffness, and roughly 7 hours after presenting to the ED, he developed fever (102 °F). At this time, a lumbar puncture was performed to rule out meningitis. Laboratory evaluation showed mild anemia, leukocytosis with neutrophil predominance, hyponatremia, elevated C-reactive protein (CRP), and an elevated sedimentary rate. Cerebrospinal results demonstrated pleocytosis, with very decreased glucose level. Laboratory findings are summarized in Table 1.

Table 1 Laboratory evaluation

The patient was started on ceftriaxone 100 mg/kg/day and vancomycin 15 mg/kg/day, and was admitted to the pediatric intensive care unit (PICU) for close cardiopulmonary monitoring and further management.

By the second day of hospitalization, both cerebrospinal and blood cultures grew S. pneumoniae,, which was pansensitive, including to ceftriaxone. Vancomycin was discontinued and the child remained on ceftriaxone monotherapy at 100 mg/kg. He was restarted on daily steroid therapy to attain remission of the NS. While in the PICU, the patient developed persistent hypertension and was treated with enalapril 5 mg twice a day. Amlodipine 5 mg once a day was added later as a second antihypertensive to further optimize blood pressure (BP) control. The child was transferred to the inpatient ward where he completed a 2-week course of ceftriaxone with no complications. His overall edema improved, and his BP was controlled on two antihypertensive drugs. He was discharged home on prednisolone, enalapril, and amlodipine, with close follow-up with nephrology as an outpatient.

Discussion

NS is characterized by the presence of proteinuria, hypoalbuminemia, edema, and hyperlipidemia [1, 7]. Minimal change disease and focal segmental glomerulosclerosis are the most common causes of NS in the pediatric population [8]. Regardless of the inciting event or causes, the pathophysiology of the disease remains the same: a dysfunction of the glomerular filtration barrier leading to loss of protein in the urine.

The initial treatment for idiopathic minimal change disease typically involves an 8–12-week course of corticosteroids. About 80% of patient will achieve remission; those who respond are classified as steroid sensitive, and those who do not, are steroid resistant [9]. While the majority will achieve remission, many patients will later develop relapses for various causes, including infections, stress, or environmental factors. Corticosteroids are still the first line of treatment for the relapses, leading to long courses of treatment. Other medications such as mycophenolate mofetil, cyclophosphamide, cyclosporine, or rituximab are utilized in cases of steroid dependence or steroid resistance to decrease the use of steroids or to achieve remission, respectively [7].

Infection remains the leading cause of mortality for children with NS. These children are at increased risk of bacterial peritonitis, pneumonia, and cellulitis; other reported infections include sinusitis/tonsillitis, gastroenteritis, and urinary tract infection [1, 2]. Children with NS have compromised immune systems due to the disease as well as its treatment. In addition to increased loss of urinary albumin, immunoglobulin G (IgG) is lost in the urine of nephrotic children as well [1]. As a result, these children are effectively hypogammaglobulinemic and, thus, have a reduced capacity to fight bacterial infections, especially with encapsulated organisms such as S. pneumoniae, as these encapsulated organisms require IgG for opsonization. In addition to S. pneumoniae, these patients are at increased risk of infection with Neisseria meningitidis and Salmonella species, as well as Enterobacteriaceae. Proteins of the complement system, which play a critical role in the adaptive and innate immune system, may also be excreted in excess in the urine [10]. As stated before, glucocorticoids remain the mainstay of treatment that often require multiple and prolonged courses; steroid therapy increases infection risk [11]. Other immunosuppressive agents, such as mycophenolate mofetil and calcineurin inhibitors (that is cyclosporin and tacrolimus), have also been shown to increase the risk of infection [12].

Bacterial meningitis as a complication of NS has not been highlighted as a potential infection in NS in recent reviews [1, 2]. A recent study that examined pneumococcal sepsis in patients with NS in India over a 14-year period, found only five cases of bacterial meningitis [5]. Typically, bacterial meningitis presents with the sudden onset of fever, headache, and neck stiffness that is usually accompanied by nausea, vomiting, photophobia, and altered mental status. Other reported cases of bacterial meningitis in NS presented with fever, nausea or vomiting, headaches, seizures, or altered mental status, as presenting symptoms [3, 4, 6]. These patients, even without the diagnosis of NS, would have warranted an evaluation for potential meningitis. In contrast, our patient had a subtle clinical presentation without fever, headache, photophobia, or altered mental status. Thus, our case highlights the potential subtle meningitis presentation in patients with NS, which without a detailed evaluation would be missed. The consequences of missing severe bacterial meningitis are very serious, including hearing loss, brain damage, and in rare cases, death.

Previous reported cases of bacterial meningitis in children with NS have occurred in resource-poor countries with incomplete vaccination or with organisms not covered by routine childhood vaccines [3,4,5,6]. In contrast, our patient developed an invasive S. pneumoniae infection even in a country as resource rich as the USA, with universal access to childhood immunizations. It is, therefore, important to alert providers treating children with NS of this severe complication, regardless of country of origin and/or vaccination or socioeconomic status.

The incidence of bacterial meningitis has significantly declined since the 1980s after the introduction of the Haemophilus influenzae type b and S. pneumoniae vaccines [13]. Still, invasive pneumococcal disease remains the most common cause of bacterial meningitis [13, 14]. The first pneumococcal vaccine developed in 1983, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults as well as children older than 2 years of age against invasive disease caused by the capsular serotypes contained in the vaccine. The seven-valent pneumococcal conjugate vaccine (PCV7) was developed in 2000 for use in children younger than 2 years of age. The latest vaccine to be developed in 2010, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7 [15].

According to the most recent Active Bacterial Core surveillance, a core component of the Center for Disease Control and Prevention’s Emerging Infections Programs networks, there were 225 cases of S. pneumoniae-related meningitis in the USA, despite the use of the PCV13 vaccine in 2019. The number has significantly decreased since the institution of the conjugate vaccines, but is still considerable, especially in the immunocompromised population [16]. Unfortunately, there are still considerable number of S. pneumoniae serotypes that are not covered by the current vaccines [17]. Because of the declining incidence rates, physicians must remain vigilant and consider the diagnosis of meningitis, especially in high-risk groups such as NS [18]. The diagnosis still requires a high index of suspicion to obtain the proper diagnostic tests and provide the appropriate treatment to achieve positive outcomes [19].

The mechanism by which the patient developed S. pneumoniae meningitis is not clear. The patient did have a history of spontaneous bacterial peritonitis from S. pneumoniae. The patient may have been colonized leading to bacteremia and then had an hematogenous spread into the cerebrospinal fluid (CSF). The serotype of the pneumococcus for this patient was not identified, limiting our ability to understand the impact of the patient’s vaccination status on his presentation. As mentioned before, the patient completed the pneumococcal vaccine series; however, he still developed pneumococcal meningitis. As noted above, the PCV13 series does not include all serotypes or all invasive serotypes, and our patient had not received the PPSV23. The lack of coverage for various serotypes may explain how a person vaccinated for pneumococcal disease could develop a severe, invasive infection.

Conclusion

This case of meningitis illustrates a very serious complication of NS that not only was very subtle at presentation, but also rarely identified as a risk of NS. Classic symptoms may be masked owing to chronic steroid use. This elusive case of meningitis could have easily been overlooked and missed. The consequences of missing the diagnosis of meningitis are very severe. Thus, we believe that bacterial meningitis should be highlighted as a possible serious complication of NS.

Availability of data and materials

All data generated or analyzed during this study is available on the patient’s medical chart, which is not publicly available.

References

  1. Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. Lancet. 2018;392:61–74. https://doi.org/10.1016/S0140-6736(18)30536-1.

    Article  PubMed  Google Scholar 

  2. Carpenter SL, Goldman J, Sherman AK, et al. Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome. Pediatr Nephrol. 2018. https://doi.org/10.1007/s00467-018-4072-6.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kapoor K, Saha A, Thakkar D, Dubey NK, Vani K. Meningitis and intracranial bleed in a child with steroid-resistant nephrotic syndrome. Saudi J Kidney Dis Transplant. 2015;26:1270–3. https://doi.org/10.4103/1319-2442.168668.

    Article  Google Scholar 

  4. Bunde SVSM, Saxennna A. Bacterial meningitis in a known case of steroid-resistant nephrotic syndrome. Indian J Child Health. 2021;8:338–9.

    Article  Google Scholar 

  5. Mathew G, George AS, Deepthi RV, et al. Epidemiology and outcomes of pneumococcal sepsis in children with nephrotic syndrome in a developing country. Pediatr Nephrol. 2022. https://doi.org/10.1007/s00467-022-05550-0.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Bilici MGF, Ece A. Development of purulent meningitis in a child with nephrotic syndrome while receiving cephtriaxone plus amikacin. Eur J Gen Med. 2006;3:139–41.

    Google Scholar 

  7. Lombel RM, Gipson DS, Hodson EM. Kidney disease: improving global O: treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol. 2013;28:415–26. https://doi.org/10.1007/s00467-012-2310-x.

    Article  PubMed  Google Scholar 

  8. Wang CS, Greenbaum LA. Nephrotic syndrome. Pediatr Clin N Am. 2019;66:73–85. https://doi.org/10.1016/j.pcl.2018.08.006.

    Article  CAS  Google Scholar 

  9. Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2015. https://doi.org/10.1002/14651858.CD001533.pub5.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Skattum L, van Deuren M, van der Poll T, Truedsson L. Complement deficiency states and associated infections. Mol Immunol. 2011;48:1643–55. https://doi.org/10.1016/j.molimm.2011.05.001.

    Article  CAS  PubMed  Google Scholar 

  11. Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. 1989;11:954–63.

    Article  CAS  PubMed  Google Scholar 

  12. Gluck T, Kiefmann B, Grohmann M, Falk W, Straub RH, Scholmerich J. Immune status and risk for infection in patients receiving chronic immunosuppressive therapy. J Rheumatol. 2005;32:1473–80.

    PubMed  Google Scholar 

  13. Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998–2007. N Engl J Med. 2011;364:2016–25. https://doi.org/10.1056/NEJMoa1005384.

    Article  CAS  PubMed  Google Scholar 

  14. Martin NG, Sadarangani M, Pollard AJ, Goldacre MJ. Hospital admission rates for meningitis and septicaemia caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in children in England over five decades: a population-based observational study. Lancet Infect Dis. 2014;14:397–405. https://doi.org/10.1016/S1473-3099(14)70027-1.

    Article  PubMed  Google Scholar 

  15. Daniels CC, Rogers PD, Shelton CM. A review of pneumococcal vaccines: current polysaccharide vaccine recommendations and future protein antigens. J Pediatr Pharmacol Ther. 2016;21:27–35. https://doi.org/10.5863/1551-6776-21.1.27.

    Article  PubMed  PubMed Central  Google Scholar 

  16. CDC. Active bacterial core surveillance report, emerging infections program network, Streptococcus pneumoniae, 2017. 2017.

  17. Balsells E, Guillot L, Nair H, Kyaw MH. Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: a systematic review and meta-analysis. PLoS ONE. 2017;12: e0177113. https://doi.org/10.1371/journal.pone.0177113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Curtis S, Stobart K, Vandermeer B, Simel DL, Klassen T. Clinical features suggestive of meningitis in children: a systematic review of prospective data. Pediatrics. 2010;126:952–60. https://doi.org/10.1542/peds.2010-0277.

    Article  PubMed  Google Scholar 

  19. Mijovic H, Sadarangani M. To LP or not to LP? Identifying the etiology of pediatric meningitis. Pediatr Infect Dis J. 2019;38:S39–42. https://doi.org/10.1097/INF.0000000000002313.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

No source of funding for this study.

Author information

Authors and Affiliations

Authors

Contributions

DG made substantial contribution to acquisition, interpretation, and drafting of the manuscript. AA and RA made substantial contributions to interpretation of data, and substantially revising manuscript. JK made substantial contributions to conception/design, acquisition, interpretation of data, and substantially revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Juan C. Kupferman.

Ethics declarations

Ethics approval and consent to participate

All methods were carried out in accordance with relevant guidelines and regulations under the Declarations section; sub-section Ethical approval and consent to participate.

Consent for publication

Written informed consent was obtained from the patient’s legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guernsey, D., Arun, A., Agha, R. et al. Streptococcus pneumoniae meningitis in a child with idiopathic nephrotic syndrome: a case report. J Med Case Reports 16, 403 (2022). https://doi.org/10.1186/s13256-022-03648-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13256-022-03648-5

Keywords