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Episode #11 – FUO Sighting

11 Cover Art

Summary

You’ll be a true believer after Dr. Rebecca Wallihan pilots us through a case of fever and hepatosplenic lesions

Credits

Host: Sara Dong

Guest: Rebecca Wallihan

Writing/Producing/Editing/Cover Art/Infographics: Sara Dong

Our Guest

Rebecca Wallihan, MD

Dr. Wallihan went to Indiana University for medical school, and then moved to Columbus, Ohio where she completed both her pediatric residency and ID fellowship training.  She is an Associate Professor of Pediatric Infectious Diseases at Nationwide Children’s Hospital and The Ohio State University. She is also the Pediatric Residency Program Director and Vice Chair of Education for the Dept of Pediatrics.

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Culture

Becky likes to listen to true crime and murder mystery podcasts.  Check out her pick: My Favorite Murder

Consult Notes

Consult Q

Fever and hepatosplenic lesions in an otherwise healthy girl

One-liner

7 yo previously healthy female with hepatosplenic bartonellosis (B.henselae)

Key Points

Jump to:

Bartonella – An introduction and some microbiology

  • The genus Bartonella consists of >20 species, but the best known is Bartonella henselae
  • Did you know that B.henselae was not identified as the etiology of cat-scratch disease until 1983?  CSD was first reported in the 1950s!
  • Other Bartonella species to remember:
      • Bartonella quintana: agent of louse-borne trench fever
      • Bartonella bacilliformis: Carrion disease (Oroya fever; verrucaperuana); arthropod vector is sandfly; endemic only in Andes mountains in western South America
      • Other species have been causes of endocarditis as well (B.elizabethae, B.alsatica)
  • Both B.henselae and B.quintana have been identified as causes of bacillary angiomatosis, bacillary peliosis, bacteremia, and endocarditis
  • Fastidious, slow-growing, pleomorphic gram-negative bacilli. Facultatively intracellular

B.henselae – Epidemiology and Transmission

  • Major reservoir: domestic cat
      • Causes an intraerythrocytic bacteremia that can persist for a year or longer in some cats
      • Cat to cat transmission via cat flea (Ctenocephalides felis) with feline infection resulting in asymptomatic bacteremia often weeks to months
        • Fleas acquire the organism when feeding on bacteremic cat, and then shed infectious organisms in their feces
      • Seroprevalence has been reported anywhere from 15-90% in domestic and stray cats in the US
      • Other animals can be infected though (like dogs)
  • Within humans, B.henselae invades endothelial cells causing an acute inflammatory reaction associated with activation of proinflammatory cascade
  • Transmission:
      • Bacteria are transmitted to humans by inoculation thru a scratch, lick, bite from bacteremic cat 
      • Bacteria can also contaminate hands by flea feces, which then touch open wound or eye
      • No convincing evidence of person-to-person transmission or that ticks are competent vector 
      • Most patients have history of recent contact with apparently healthy cats or kittens
      • Kittens are more often bacteremic than older cats
  • Worldwide distribution and a common cause of regional lymphadenopathy/lymphadenitis in children
  • Most cases occur in fall and winter. Seasonality may be related to cat reproductive cycles in combination with flea activity?  (kittens born in midsummer with high flea activity)
  • True incidence of human infection is unknown
  • Cat scratch disease occurs in immunocompetent individuals and infrequently will cause serious illness, but systemic Bartonella infection is described as well.
  • Highest incidence of CSD: 5-9 year olds
  • Incubation period from time of scratch to appearance of cutaneous lesion: 7-12 days
  • Period to appearance of LAD is 5-50d (median 12d)
  • Jackson LA, Perkins BA, Wenger JD. Cat scratch disease in the United States: an analysis of three national databases. Am J Public Health. 1993;83(12):1707-1711. doi:10.2105/ajph.83.12.1707

B.henselae and cat scratch disease (CSD)

  • Cat scratch disease is a local bacterial infection caused by Bartonella henselae
  • The predominant manifestation in an immunocompetent patient is regional lymphadenopathy or lymphadenitis after a scratch or bite from cat
  • Skin papule or pustule at site of inoculation, which then leads to regional lymphadenopathy (where the area drains too) a few weeks later
      • Affected lymph node is enlarged, tender, freely movable
      • Most frequently affects the axillary, epitrochlear, head and neck lymph nodes (where children are often scratched/bitten/licked), but can present with femoral, inguinal, or popliteal LAD
      • 10-25% of affected nodes will suppurate spontaneously
  • Often this infection is self-limited with mild systemic symptoms, and typically lymphadenopathy will resolve spontaneously in about 2-4 months
  • Fever and associated systemic symptoms may be present in about 25-30% of patients

B.henselae and other clinical presentations (systemic or atypical CSD): Bartonella infection can affect many organ systems and remains on many differential diagnoses!  It has a broad spectrum of atypical clinical syndromes, which likely reflect bloodborne disseminated disease.  This episode’s case highlighted hepatosplenic disease and prolonged fever, which can be a fairly common presentation in children.

We quickly touched on a few separate entities that can be caused by Bartonella, largely in immunocompromised hosts:

  • Bacillary angiomatosis
      • Rare disorder with vascular proliferative lesions of skin and subcutaneous tissue
      • Gradual appearance of reddish-brown lesions, which can be verrucous, papular, pedunculated
      • Often erythematous base with vascular appearance, but can also have dry/scaly, hyperkeratotic, or plaque-like appearance
      • Can appear similar to Kaposi sarcoma or pyogenic granuloma
  • Bacillary peliosis
      • Reticuloendothelial lesions in visceral organs, primarily the liver (peliosis hepatitis)
      • Can also involve spleen, abdominal lymph nodes, bone marrow
      • The visceral lesions of bacillary peliosis can be accompanied by cutaneous lesions seen in bacillary angiomatosis
  • These cases are generally diagnosed by biopsy and have characteristic histologic appearance
  • Attempts to culture Bartonella in these cases might be more successful than those specimens from typical cat-scratch disease
  • Lesions and symptoms usually respond rapidly to therapy

Diagnosis of Bartonella henselae infection 

  • As mentioned above, Bartonella is fastidious and isolation in culture is difficult→ so often can’t rely on blood or tissue cultures for diagnosis
  • Serology is the mainstay of diagnosis for Bartonella
      • Indirect immunofluorescent Ab (IFA) assay for serum Ab to antigens of Bartonella spp
          • Any IgM positivity suggests acute or recent infection, but IgM production is brief and could be missed → so low test sensitivity
          • Generally if IFA IgG titer is <1:64, patient does not have acute infection
          • IgG titer >1:256 is considered indicative of acute or recent infection
          • There is a gray zone with IgG titers between 1:64 and 1:256 that may represent past or acute infection → if here, can repeat titers in 2-4 weeks to see if there is a rise
      • Cross-reactivity between B.henselae and B.quintana or other Bartonella species is common 
  • PCR assays are available and can be adjunct diagnostic
      • Would not routinely get blood PCR given poor sensitivity
      • This is mostly helpful on tissue specimens (such as valvular tissue in endocarditis or lymph node biopsy) 
  • Histopathology
      • If tissue is available, bacilli can occasionally be visualized using silver stain (e.g. Warthin-Starry or Steiner stain), however this is not specific for B.henselae
      • Early histologic changes in lymph node specimens: lymphocytic infiltration, epithelioid granuloma formation
      • Later histologic changes: PMN infiltration, necrotizing granulomas
          • May resemble granulomas in patients with tularemia, brucellosis, mycobacterial infections
  • Alattas NH, Patel SN, Richardson SE, Akseer N, Morris SK. Pediatric Bartonella henselae Infection: The Role of Serologic Diagnosis and a Proposed Clinical Approach for Suspected Acute Disease in the Immunocompetent Child. Pediatr Infect Dis J. 2020;39(11):984-989. doi:10.1097/INF.0000000000002852

Treatment of Bartonella

Check out some of the graphics for possible causes of hepatic and/or splenic lesions!  Here are a few references:

We’ve also discussed FUO in prior episodes as well.  You can refresh with the prior graphics in the Episode Art & Infographics section. 

 

A reference for the Parinaud’s oculoglandular graphic: Arjmand P, Yan P, O’Connor MD. Parinaud oculoglandular syndrome 2015: Review of the literature and update on diagnosis and management. J Clin Exp Ophthalmol. 2015;6;443. DOI: 10.4172/2155-9570.1000443

Other miscellaneous mentions and notes:

Episode Art & Infographics

Goal

Listeners will be able to identify Bartonella henselae as the agent in cat scratch disease

Learning Objectives

After listening to this episode, listeners will be able to:

  • Identify different clinical presentations of Bartonella infection
  • Discuss the use and challenges of serology for diagnosis of Bartonella
  • List the available antimicrobials for cat scratch disease

Disclosures

Our guest (Rebecca Wallihan) as well as Febrile podcast and hosts report no relevant financial disclosures

Citation

Wallihan, R., Dong, S. “#11: FUO Sighting”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/d8858088-e6fe-4b1b-a867-6c099b3f1500

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