Brain Abscess Caused by Capnocytophaga Species Associated with Anti-Tumor Necrosis Factor-α Therapy

Capnocytophaga spp. are a rare cause of fulminant sepsis in individuals who have been bitten or scratched by a dog. Immunocompromised individuals are at high risk of Capnocytophaga spp. infections [1]. Anti-tumor necrosis factor-α (anti-TNF-α) drugs are a class of drugs that are used worldwide to treat patients with rheumatoid arthritis (RA) and selected other autoimmune inflammatory diseases. Over the past 15 years, an increased rate of serious infections has been reported in patients treated with antiTNF-α drugs [2]. Herein, we report a case of a brain abscess caused Capnocytophaga spp. following anti-TNF-α therapy. To the best of our knowledge, this is the first such case reported in the literature.


Introduction
Capnocytophaga spp. are a rare cause of fulminant sepsis in individuals who have been bitten or scratched by a dog. Immunocompromised individuals are at high risk of Capnocytophaga spp. infections [1]. Anti-tumor necrosis factor-α (anti-TNF-α) drugs are a class of drugs that are used worldwide to treat patients with rheumatoid arthritis (RA) and selected other autoimmune inflammatory diseases. Over the past 15 years, an increased rate of serious infections has been reported in patients treated with anti-TNF-α drugs [2]. Herein, we report a case of a brain abscess caused Capnocytophaga spp. following anti-TNF-α therapy. To the best of our knowledge, this is the first such case reported in the literature.

Case Report
A 71-year-old woman reported that she had vertigo for 10 days. She lived in a suburban district of southern Taiwan with a guard dog outside the house. In the past year, she had taken subcutaneous adalimumab 40 mg twice monthly with oral celecoxib and methotrexate to control her RA. On examination, she had a temperature of 36.7°C, elevated blood pressure of 186/116 mm Hg, heart rate of 93/min, and respiratory rate of 18/min. A physical examination was unremarkable except for an unsteady gait. The peripheral leukocyte count was 16390 cells/µL, and the C-reactive protein level was 0.347 mg/dl. Brain computed tomography scan revealed a hypodense lesion with rim enhancement over the superior vermis and right cerebellum ( Figure 1). Pre-operative brain Magnetic Resonance Imaging (MRI) Diffusion weighted imaging (DWI) showed contrast enhanced lesion over the superior vermis and right cerebellum ( Figure 2). Stereotaxic aspiration of the right cerebellum area was performed with external ventricular drainage. By hospital day 7, Capnocytophaga spp. had been isolated from the brain abscess, and the external ventricular drainage was removed. Thereafter, patient received antibiotic treatment with intravenous amoxicillinclavulanic acid 1.2 gm/day per 12 hours and oral form amoxicillinclavulanic acid 1 gm twice daily sequentially for more than 4 weeks. Two months after her pre-operative brain MRI DWI showed resolution of prior enhanced lesion ( Figure 3). She has uneventfully course after 6 months follow up.
spp. infections were first described presenting as meningitis and sepsis in 1976. The genus Capnocytophaga consists of a variety of commensal species in the oral flora of humans, including Capnocytophaga gingivalis, Capnocytophaga granulosa, Capnocytophaga haemolytica, Capnocytophaga leadbetteri, Capnocytophaga ochracea, Capnocytophaga sputigena and Capnocytophaga genospecies AHN8471. Capnocytophaga canimorsus and Capnocytophaga cynodegmi are part of the oral microbiota of canines and more rarely of cats [1]. A 3-year nationwide survey in the Netherlands reported that the only proven species in Capnocytophaga spp. infections was C. canimorsus [3]. However, identification at the species level remains difficult, and molecular techniques (16S rDNA PCR and sequencing) and mass spectrometry appear to be the most reliable methods to identify the genus [4].
The pathogenesis of Capnocytophaga spp. is not well understood. Most previous studies on Capnocytophaga spp. have focused on C. canimorsus, which exhibits robust growth in mammalian cells, including phagocytes. Surface-localized sialidases can initiate an extensive deglycosylation process of host cell glycoproteins. This mechanism serves as a basis for the growth and persistence of C. canimorsus in vivo [5]. In addition, C. canimorsus has the capacity to deglycosylate human IgGs [6]. However, further studies are needed to elucidate the pathogenesis with regards to anti-TNF-α therapy.
Capnocytophaga spp. can cause infections ranging from selflimited symptoms to fatal sepsis. Classical risk factors include asplenia, immunocompromised status, liver cirrhosis, and heavy alcohol use. A history of a dog bite, contact with dog saliva, cat scratch or contact with cat saliva is found in approximately half of cases. A fulminant course may occur in immunocompromised patients, characterized by sepsis, meningitis, endocarditis, osteomyelitis, purulent arthritis, pneumonia, peritonitis, disseminated intravascular coagulation and fulminant purpura [7]. A brain abscess caused by Capnocytophaga spp. has only been reported in a few studies [8]. Furthermore, only two cases of Capnocytophaga spp. infections following treatment with biological drugs have been reported, however neither of these cases involved a brain abscess, and no cases of a brain abscess caused by Capnocytophaga spp. following anti-TNF-α therapy have been reported. The first of these two cases was a 63-year-old patient with RA who had cellulitis after treatment with etanercept 25 mg twice weekly, and the other was a 20 year-old female with juvenile chronic arthritis who suffered from Capnocytophaga bacteremia after receiving the last course of rituximab 9 months previously [9,10]. Our patient had a history of imitate contact with a dog; however she could not recall any bites or scratches. Although steroids and methotrexate were used in this patient, anti-TNF-α therapy with adalimumab twice monthly was responsible for this opportunistic brain infection. This case should serve to remind physicians of the possibility of central nervous system infections such as Capnocytophaga spp. in pet owners who have been undergoing anti-TNF-α therapy.