Liu E 1 , McKew G 1 , Lee K 2 , Ronnachit A 1 , Cheong E 1 , Gottlieb T 1 1 Department 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 x10 9 /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.