My patient with acute onset headache, photophobia, and neck stiffness does not have CSF pleocytosis. Could she still have meningitis?

Although the clinical diagnosis of meningitis is often supported by the presence of abnormal number of WBCs in the CSF (AKA pleocytosis), meningitis may be present despite its absence.

Among viral causes of meningitis in adults, enteroviruses are associated with lower CSF WBC count compared to herpes simplex and varicella zoster, with some patients (~10%) having 0-2 WBC’s/mm31,2.  Of interest, among children, parechovirus (formerly echovirus 22 and 23) meningitis is characterized by normal CSF findings3.

Though uncommon, bacterial meningitis without CSF pleocytosis has been reported among non-neutropenic adults,  including Neisseria meningitidis, Streptococcus pneumoniae, Hemophilus influenzae, Listeria monocytogenes, E. coli, and Proteus mirabilis4A European study also reported normal CSF WBC in nearly 10% of patients with Lyme neuroborreliosis (including meningitis) caused primarily by Borrelia garinii5.

Cryptococcal meninigitis may also be associated with normal CSF profile in 25% of patients with HIV infection6.

 

References

  1. Ihekwaba UK, Kudesia G, McKendrick MW. Clinical features of viral meningitis in adult:significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections. Clin Infect Dis 2008;47:783-9. https://www.ncbi.nlm.nih.gov/pubmed/18680414
  2. Dawood N, Desjobert E, Lumley J et al. Confirmed viral meningitis with normal CSF findings. BMJ Case Rep 2014. Doi:10.1136/bcr-2014-203733. http://casereports.bmj.com/content/2014/bcr-2014-203733.abstract
  3. Wolthers KC, Benschop KSM, Schinkel J, et al. Human parechovirus as an important viral cause of sepsis like illness and meningitis in young children. Clin Infect Dis 2008;47:358-63. https://www.ncbi.nlm.nih.gov/pubmed/18558876
  4. Hase R, Hosokawa N, Yaegashi M, et al. Bacterial meningitis in the absence of cerebrospinal fluid pleocytosis: A case report and review of the literature. Can J Infect Dis Med Microbiol 2014;25:249:51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211346/pdf/idmm-25-249.pdf
  5. Ogrinc K, Lotric-Furlan S, Maraspin  V, et al. Suspected early Lyme neuroborreliosis in patients with erythema migrans. Clin Infect Dis 2013; 57:501-9. https://www.ncbi.nlm.nih.gov/pubmed?term=23667259
  6. Darras-Joly C, Chevret S, Wolff M, et al. Cryptococcus neoformans infection in France: epidemiologic features of and early prognostic parameters for 76 patients who were infected with human immunodeficiency virus. Clin Infect Dis 1996;23:369-76. https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/23/2/10.1093/clinids/23.2.369/2/23-2-369.pdf?Expires=1501035620&Signature=FhHMHUHAMmT3rz4ld8QAMet-weu-BWgm5YR6nA4jjSGVGIeaVlMNPgeOkW2fniiel54HQhIs1Kkp3PpzT1glxhJeZvQiGXQCSOoF-jS1SK7S~kBb-oHs4qsIJzN0OJxNAXfoJi4bl7OeKaLTyIE3P8~slwH0BBi7RncSYVgVR4NkOnFpYgn27~wY7pDSUNWvzGFKoSeYGeM0TsAqna-QmXzodITB5bgr1mO6Q6OGUxCsqRwhr6xNb~4G93oqRcsO19gyUluCE0xYt0KbKWuQxJeh8AbtJkNrS08~XInMR50bQZOUb80j0~dtg9jRTGzXQaDllVByoX2Alr48hlhogw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q
My patient with acute onset headache, photophobia, and neck stiffness does not have CSF pleocytosis. Could she still have meningitis?

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?

Howell-Jolly bodies (HJBs, Figure) are often indicative of asplenia (either post-splenectomy or congenital absence) or hyposplenism associated with a variety of conditions, including  sickle cell disease, autoimmune disorders, celiac disease, inflammatory bowel disease (particularly ulcerative colitis), HIV, cirrhosis, primary pulmonary hypertension, splenic irradiation, amyloidosis, sarcoidosis, bone marrow transplantation, and high-dose corticosteroid therapy1-4.

Patients with pneumonia and HJBs on peripheral smear may be hyposplenic and at risk of potentially serious infections, predominantly caused by encapsulated bacteria eg, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis3.  Such patients should be immunized against these organisms, including sequential receipt of both conjugated and polysaccharide pneumococcal vaccines3,5.

HJBs are nuclear remnants in circulating mature red blood cells which are usually pitted by the spleen under normal physiological conditions. 

Final Fun Pearl:  Did you know that  HJBs were named after Henry Howell, an American physiologist who pioneered the use of heparin as an anti-coagulant and Justin Jolly, a French hematologist who was among the first to film mitotic activity in cells?

howelljollymgh

Figure. Howell-Jolly body in an RBC. Photo courtesy of Michael S. Abers, MD

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References

  1. Di Sabatino, A, Carsetti R, Corazza G. Post-splenectomy and hyposplenic states. Lancet 2011;378:86–97. https://www.ncbi.nlm.nih.gov/pubmed/21474172
  2. Brousse, V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol 2014;166: 165–176. https://www.ncbi.nlm.nih.gov/pubmed/24862308
  3. Mathew H, Dittus C, Malek A, Negroiu A. Howell-Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock. Clin Case Rep 2015;3:714-717. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551333
  4. Ryan FP, Smart RC, Holdsworth CD, et al. Hyposplenism in inflammatory bowel disease 1978;19:50-55. https://www.ncbi.nlm.nih.gov/pubmed/624506
  5. Kuchar E, Miśkiewicz K , Karlikowska M. A review of guidance on immunization in persons with defective or deficient splenic function. Br J Haematol 2015; 171:683-94.  http://onlinelibrary.wiley.com/doi/10.1111/bjh.13660/full

Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny, Poland

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?