Liu E1, McKew G1, Lee K2, Ronnachit A1, Cheong E1, Gottlieb T1

1Department of Microbiology & Infectious Diseases and 2 Department of Anatomical Pathology, Concord Repatriation General Hospital, NSW, Australia

Diagnostic dilemmas in assessment of neurological symptoms in a severe case of cat-scratch disease

Cat-scratch disease (CSD) typically manifests

as fever and regional lymphadenopathy

following a cat scratch or bite. Atypical

presentations can include neurological

complications including encephalitis. We report

a case of severe CSD with super-imposed

neurological symptoms, and which posed

multiple diagnostic and management

challenges.

Presentation

A 41-year-old Italian male was referred to Concord ED in

February 2014 by his LMO following 4 weeks of painful right

inguinal lymphadenopathy and crippling myalgias. He had

12 months of intermittent fevers, night sweats and

generalised myalgias, which worsened 2 weeks after a

small dog bite on his left hand in November 2013.

In the 3 months following the canine altercation, he

sustained unintentional weight loss of 20kg, short-term

memory loss, irritability, band-like headaches, insomnia and

blurred vision. Personality and cognitive changes were

corroborated by his wife, who described him as having a

memory “like an elephant” prior to the dog bite. The patient

had not sought any medical attention in the year prior to his

ED presentation.

Zoonotic contacts also included his wife’s pet cat. He had

not travelled to any rural areas but does handle fresh

produce as a fruit-shop owner. He last travelled to Italy 15

years ago. His past medical history is only significant for

fatty liver.

Physical examination revealed right inguinal

lymphadenopathy, with no rash or eschar. Initial pathology

demonstrated mild monocytosis of 1.4 x109/L, reactive

lymphocytes on blood film and a mildly raised CRP at

15mg/L; his baseline pathology including LDH was

otherwise unremarkable.

Discussion

This case is notable and atypical for CSD in several

aspects:

• Severity of disease, prompting a GP referral to an

emergency department

• Predominance of neuropsychiatric symptoms

• Prolonged systemic symptoms

• Regional lymphadenopathy distant from site of putative

inoculation via animal bite

Outside of the well-described neuroretinitis due to

Bartonella infection, Bartonella can also rarely cause a

myriad of neurological presentations. In a review of 15

cases of neurobartonellosis from 2005-2012 by

Breitschwerdt et al, presentations included encephalitis,

meningitis, aphasia, transverse myelitis and psychiatric

presentations [1].

Antibiotics are not routinely recommended for typical CSD

but azithromycin for 5 days can be considered for adult

patients with extensive lymphadenopathy [2]. There is little

evidence to guide treatment of neurobartonellosis at

present; recommendations extrapolated from Bartonella

neuroretinitis suggest doxycycline 100mg b.d. and

rifampicin 300mg b.d. for 4-6 weeks [2]. Azithromycin use

requires close monitoring in prolonged treatment as in vitro

studies have shown development of azithromycin

resistance in Bartonella spp. isolated from cats as early as

the second passage of fortnightly subcultures[3].

The atypical presentation in our patient may also be due to

infection by a non-B. henselae species. Even though the B.

henselae serology was strongly positive, a high rate of

cross-reactivity with other Bartonella species is well-

described (e.g. ≤95% with B. quintana) [4]. The positive

pan-Bartonella PCR and negative B. henselae and B.

quintana specific PCRs also suggests infection with an

alternative Bartonella species.

Conclusion

This case demonstrates an atypical presen-

tation of CSD with prominent neuropsychiatric

manifestations. Because of different treatment

options, it highlights the need to consider and

exclude neurobartonellosis It also highlights

difficulties in establishing a diagnosis of neuro-

bartonellosis.

Fig. 1 (Bottom left) Lymph node showing reactive follicular hyperplasia

and a central necrotic follicle with abundant neutrophils (x4)

Fig. 2 (Bottom right) Higher power field confirming necrotic follicle

replaced by neutrophils and surrounded by histiocytes (x20)

Fig. 3 (Top) Warthin-Starry stain. Numerous gram negative bacilli, some

engulfed by histiocytes.

Diagnosis of Cat Scratch Disease

Excisional lymph node biopsy demonstrated suppurative

changes, with positive Warthin-Starry stain and negative

Period acid-Schiff (PAS), Grocott’s Methenamine Silver

(GMS) and Gram stains. These histological findings were

consistent with CSD.

Bartonella henselae serology by indirect fluorescent

antibody (IFA) testing was strongly reactive (1:512) at time

of presentation and 6 weeks later rose to a titre of 1:1024.

Multiple molecular tests were performed on formalin-fixed

paraffin-embedded tissue section of the right inguinal lymph

node at 3 laboratories:

Lab 1: pan-Bartonella PCR (citrate synthetase target) positive

Lab 2: B. henselae PCR negative

Lab 3: B. henselae & B. quintana PCR negative

Chlamydia trachomatis (LGV) urine PCR was negative.

Toxoplasma, CMV, EBV, rickettsia, syphilis and HIV

serology was negative. Autoimmune screen was negative

Assessment of neurobartonellosis

A 3 week course of azithromycin 500mg daily was

prescribed. The patient defervesced, however there was no

improvement in his neurological symptoms. Rifampicin

300mg bd and doxycycline 100mg bd were then given

empirically for an additional 6 weeks, to ensure adequate

treatment of neurobartonellosis and to cover the possibility

of azithromycin resistance.

However further investigations were not suggestive of

neurobartonellosis. He had no signs of neuroretinitis on

ophthalmic examination, normal EEG and only minimal

frontal microvascular disease on brain MRI. CSF analysis

showed no pleocytosis, protein of 0.47g/L, normal glucose

and negative Bartonella henselae PCR.

Neuropsychiatric testing also suggested our patient had

pseudo-dementia (psychogenic cognitive impairment) due

to anxiety over pending litigation, chronic sleep deprivation

and escalating work pressures.

He was somewhat relieved by this diagnosis and has

improved on amitriptyline.

FEB 2014

ED presentation

NOV 2013

Dog bite

Fever, night sweats, generalised myalgias

Weight loss of 20kgs

Short term memory loss & personality change

FEB 2013

inguinal lymphadenoapthy

JAN 2014

TIMELINE OF ILLNESS

References

[1] Breitschwerdt E, Sontakke S, Hopkins S. Neurological Manifestations of Bartonellosis in Immunocompetent Patients: a composite of reports from 2005-2012. J Neuroparasitol 2012; 3:15.

[2] Rolain J, Brouqui P, Koehler J, Maguina C, Dolan M, Raoult D. Recommendations for treatment of human infections caused by Bartonella species. AAC 2004; 48:1921–1933.

[3] Biswas S, Maggi RG, Papich MG, Keil D, Breitschwerdt EB. Comparative activity of pradofloxacin, enrofloxacin and azithromycin against B. henselae isolates collected from cats and a human. JCM 2010; 48:617–618.

[4] Sander A, Berner R, Ruess M. Serodiagnosis of cat scratch disease: response to Bartonella henselae in children and a review of diagnostic methods. Eu Journal of Clin Micro & Inf Dis 2001; 20:392–401.

Acknowledgements

Prof. Ed Breitschwerdt, Intracellular Pathogens Research Laboratory, North Carolina State University, College of Veterinary Medicine, North Carolina, USA

Dr Richard Malik, Valentine Charlton Specialist, Centre for Veterinary Education, University of Sydney, NSW, Australia

Dr Jenny Robson, Clinical Microbiologist, Sullivan-Nicolaides Pathology, Queensland, Australia

Dr Briony Hazelton, Microbiology Registrar, Pathology West, Westmead Hospital, NSW, Australia.