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Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch

Year: 2012

Successfull medical treatment of Erysipelothrix rhusiopathiae-induced lumbosacral discospondylitis in a dog

Golini, L ; Morgan, Joe P ; Glaus, Toni M ; Steffen, Frank

DOI: https://doi.org/10.1136/vr.100657

Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-62130 Journal Article Accepted Version

Originally published at: Golini, L; Morgan, Joe P; Glaus, Toni M; Steffen, Frank (2012). Successfull medical treatment of Erysipelothrix rhusiopathiae-induced lumbosacral discospondylitis in a dog. Veterinary Record, 170(21):543b. DOI: https://doi.org/10.1136/vr.100657 Veterinary Record

Confidential: For Review Only

Successful medical treatment of Erysipelothrix rhusiopathiae-induced lumbosacral discospondylitis in a dog

Journal: Veterinary Record

Manuscript ID: vetrec-2012-100657.R2

Article Type: Short communication

Date Submitted by the 17-Feb-2012 Author:

Complete List of Authors: Golini, Lorenzo; VetSuisse Faculty, University of Zurich, Department of Small Animal, Neurology Service Morgan, Joe; Vetsuisse Faculty University of Zurich, Department of Small Animals, Section of Diagnostic Imaging Glaus, Tony; University of Zurich, Steffen, Frank; VetSuisse Faculty - University of Zurich, Department of Small Animals, Neurology Service

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1 2 3 4 1 Successful medical treatment of Erysipelothrix rhusiopathiae-induced lumbosacral 5 6 2 discospondylitis in a dog 7 8 3 9 Confidential: For Review Only 10 1 2 11 4 Golini, L. DVM MSc(Behavior) , Morgan, J.P. Prof. Dr. Med.Vet. DACVR , Glaus, 12 13 5 T Jr. Prof. Dr Med Vet DACVIM (Internal Medicine) DECVIM (Cardiology)3, 14 15 6 Steffen F PD Dr Med Vet DECVN1, 16 17 18 7 1. Neurology Service, Department of Small Animals, VetSuisse Faculty, University of 19 20 8 Zurich, Winterthurerstrasse 260, 8050 Zurich, Switzerland 21 22 23 9 2. Section of Diagnostic Imaging, VetSuisse Faculty, University of Zurich, 24 25 10 Winterthurerstrasse 260, 8050 Zurich, Switzerland. 26 27 11 3. Cardiology Service, Clinic for Small Animal Internal Medicine, VetSuisse Faculty, 28 29 30 12 University of Zurich, Winterthurerstrasse 260, 8050 Zurich, Switzerland 31 32 13 33 34 14 35 36 37 15 38 39 16 40 41 17 42 43 44 18 45 46 19 47 48 49 20 50 51 21 52 53 22 54 55 56 23 57 58 24 Address correspondence to: Dr. L. Golini ([email protected]) 59 60

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1 2 3 4 25 The lumbosacral disk is a common site for the settlement of local or systemic 5 6 26 bacterial infections, leading to lumbosacral discospondylitis (Burkert and others 2005; 7 8 27 Gilmore 1987). More commonly isolated organisms include Staphylococcus spp., 9 10 Confidential: For Review Only 11 28 Brucella canis, Streptococcus spp. and Escherichia coli, additional less common 12 13 29 organisms include Pasteurella multocida, Actinomyces viscosus, Nocardia spp., 14 15 30 Mycobacterium avium, Proteus spp. and Corynebacterium spp. (Betbeze and 16 17 18 31 McLaughlin 2002; Burkert and others 2005). In human medicine, pyogenic vertebral 19 20 32 osteomyelitis is mainly due to Streptococcus aureus, followed by E. coli, Coagulase- 21 22 Propionibacterium acnes Erysipelothrix 23 33 negative staphylococci and (Zimmerli 2010). 24 25 34 rhusiopathiae is rarely recognized as zoonotic agent of osteomyelitis in 26 27 35 immunodeficient patients but it is easily treatable. Whereas this organism is a very 28 29 30 36 important pathogen in pigs, where acute disease is characterized by sudden death or 31 32 37 general signs of septicaemia, the sub acute form is characterized by classical 33 34 38 diamond-skin light pink to reddish lesions or a chronic form could result with signs of 35 36 37 39 local arthritis or proliferative pathological changes in the heart (Wang and others 38 39 40 2010). To the authors’ knowledge, E. rhusiopathiae has only been described in 3 fatal 40 41 41 canine cases, of which 2 dogs had discospondylitis as part of the disease (Burkert and 42 43 44 42 others 2005; Houlton and Jefferies 1989; Seelig and others 2010). The present case 45 46 43 report illustrates the clinical and radiological features; diagnostic procedure, clinical 47 48 49 44 cure and long term clinical follow up of a dog diagnosed with Erysipelothrix 50 51 45 rhusiopathiae-induced lumbosacral diskospondylitis. 52 53 46 The dog, a 13year old male Labrador retriever, was presented to the Neurology 54 55 56 47 Service of the Veterinary Teaching Hospital Faculty of Veterinary Medicine 57 58 48 University of Zurich for a second opinion about a long term problem in failure to 59 60 49 jump and walk normally. The dog had been living in Ibiza, Spain, since it was born

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1 2 3 4 50 where it was regularly vaccinated, yearly de-wormed and during the warm season was 5 6 51 wearing a deltametrine based collar to reduce the risk of phlebotomus bites. Since two 7 8 52 months before presentation the dog had shown apathetic behaviour, progressive 9 10 Confidential: For Review Only 11 53 worsening of difficulties to walk normally and jump into the car, with occasional 12 13 54 tenesmus and uncontrollable pain during petting the lumbosacral area. At clinical 14 15 55 examination, the dog was apathetic, febrile (40,3°C) and panting, the mucous 16 17 18 56 membranes were mildly reddish and the heart rate was 150 beats per minutes. The 19 20 57 heart auscultation was mildly arrhythmic without murmurs. The dog had no 21 22 23 58 neurological deficits, however, he showed pain on palpation of the caudal abdomen 24 25 59 and in the lumbosacral area as well as pain upon extension of the hips (lordosis test) 26 27 60 and trans-rectal palpation of the ventral aspect of the sacrum. On rectal palpation, the 28 29 30 61 prostate was moderately enlarged but not painful. Lumbosacral disease was clinically 31 32 62 suspected and an infectious cause was presumed; degenerative, neuropathic or 33 34 63 neoplastic disease involving the cauda equina or the bone and joints structures of this 35 36 37 64 anatomical area were considered less likely. 38 39 65 Radiographs of thorax, caudal abdomen, lumbosacral area and hips of the dog were 40 41 66 performed under sedation (should this be anaesthesia from what follows below?). 42 43 44 67 Thorax, abdomen and hips were unremarkable and the vertebrae between C6 and L6 45 46 68 showed no obvious pathological changes. A heavy pattern of spondylosis deformans 47 48 49 69 was present around L6-7 and L7-S1 ventrally and laterally. The endplates of the 50 51 70 vertebrae L7-S1 were sclerotic with associated intervertebral disc space collapse. 52 53 71 Lytic/destructive lesions in the mid portion of the endplates were also observed (Fig.1 54 55 56 72 and Fig.2). The radiological diagnosis supported the clinical suspicion of 57 58 73 discospondylitis at the lumbosacral joint superimposed to chronic spondylosis 59 60 74 deformans.

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1 2 3 4 75 With the dog still under anaesthesia, a fluoroscopically guided fine needle aspiration 5 6 76 of the L7-S1 disk was performed. A 20G 90 mm long spinal needle was aseptically 7 8 77 inserted perpendicularly through the surgically prepared skin into the disk (Fig. 1), 9 10 Confidential: For Review Only 11 78 and gentle aspiration was performed with a sterile 10 cc syringe. The aspirated 12 13 79 material was gently deposited on a sterile transport swab, suitable for both aerobes 14 15 80 and anaerobes (COPAN Innovation, Brescia, Italy). A second sample was obtained by 16 17 18 81 inserting the needle on a different path from the first one and flushing the disk with 1 19 20 82 ml of sterile and pyrogen – free irrigation solution (NaCl 0.9%, B. Braun Melsungen 21 22 23 83 AG, Germany). The re-aspirated fluid was transported to the laboratory by means of 24 25 84 anothersterile transport swab similar to previous one. Finally, ultrasound examination 26 27 85 of the heart was performed and did not reveal any abnormalities, specifically, all 28 29 30 86 cardiac valves were free of any suspicion of endocarditis. 31 32 87 Routine haematological examination showed severe leukocytosis (65.000 WBC/ul; 33 34 88 reference range: 4.700 – 11.300 cells/ul) with a left shift (6000/ul bands; reference 35 36 37 89 range: 0-800 cells/ul) and monocytosis (1500/ul; reference range: 200 – 920 cells/ul). 38 39 90 Urine analysis obtained by cystocentesis did not reveal pyuria or bacteria, but urine 40 41 91 was cultured nevertheless. Ultrasound evaluation of the prostate gland and of the 42 43 44 92 testicles did not reveal any abnormalities other than expected with older age, and a 45 46 93 fine needle aspiration of the prostatic tissue was cytologically unremarkable. Blood 47 48 49 94 cultures for aerobic and anaerobic bacteria were taken, sampling 10 ml of whole 50 51 95 blood hourly three times and putting the blood into a commercially available 52 53 96 transportation/culture medium (BC0102M, Oxoid SIGNAL blood culture system 54 55 56 97 medium; Oxoid Limited, Basingstoke, UK). 57 58 98 Recovery from anaesthesia was uneventful and the dog was administered first 59 60 99 generation intravenous cefazolin (Kefzol, TEVA Pharma AG, Basel, Switzerland) at

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1 2 3 4 100 22 mg/Kg/TID. General physical condition, gait abnormalities and pain improved 5 6 101 significantly by the following day. After 24 hours of intravenous antibiotic treatment, 7 8 102 the dog was discharged with long-term oral antibiotic treatment at the same dosage 9 10 Confidential: For Review Only 11 103 (Cefaseptin forte, Vétoquinol AG, Switzerland), to be modified based on 12 13 104 microbiological culture and sensitivity results. 14 15 105 No etiological agent growth was obtained from either urine culture or blood cultures 16 17 18 106 while from the disk material a small Gram-positive bacillus was cultured from both 19 20 107 the FNA of the disk and the disk wash. An amplification of 1600 base pairs with 21 22 23 108 conventional PCR for the 16S rDNA of the bacterium was performed, according to 24 25 109 the protocol developed by Medlin et coll (Medlin and others 1988), and using as 26 27 110 forward primer the sequence 5‘-CAG AGT TTG ATC CTG GCT CAG-3‘ and as 28 29 30 111 reverse primer 5‘-TAC GG(CT) TAC CTT GTT ACG ACT T-3’. Afterwards, the 31 32 112 amplified gene was sequenced and compared with an online gene bank 33 34 113 (http://blast.ncbi.nlm.nih.gov; accessed on March 2010). The sequenced gene showed 35 36 37 114 a perfect homology with the available sequences of Erysipelothrix rhusiopathiae. The 38 39 115 same procedure was subsequently performed on the blood sampled previously for 40 41 116 culture, leading again to the identification of DNA of Erysipelothrix rhusiopathiae. 42 43 44 117 The antibiogram showed that it was sensitive to cefazolin and therefore this treatment 45 46 118 was continued for 3 months. Regular telephone follow-up confirmed the resolution of 47 48 49 119 all clinical signs at 20 days after discharge, and after 6 weeks the dog was jumping 50 51 120 and running normally. After 3 months, the referring veterinarian stopped the treatment 52 53 121 and at the time of writing, 9 months after diagnosis, the dog has not been showing any 54 55 56 122 recurring clinical signs. 57 58 123 Discospondylitis is an infection of the intervertebral disc that spreads through both 59 60 124 endplates and proceeds slowly into the two contiguous vertebrae (Gilmore 1987).

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1 2 3 4 125 Although any intervertebral disk space may be affected, the lower cervical, the 5 6 126 midthoracic, the thoracolumbar and the lumbosacral disks are more often involved in 7 8 127 dogs (Burkert and others 2005; Gilmore 1987; Kinzel and others 2005; Kornegay and 9 10 Confidential: For Review Only 11 128 Barber 1980). Clinical signs range widely from pain alone to non-ambulatory para- or 12 13 129 tetraparesis, either flaccid or spastic, depending upon the localization of the 14 15 130 inflammatory and compressive process (Betbeze and McLaughlin 2002; Burkert and 16 17 18 131 others 2005; Kornegay and Barber 1980). Male dogs are twice as likely to be affected 19 20 132 as females and the risk increases with age (Burkert and others 2005). Additional 21 22 23 133 predisposing factors are previous surgery, treatment with immunosuppressive drugs, 24 25 134 or systemic or local infections, most commonly located in the lower urinary tract 26 27 135 (Burkert and others 2005). In intact male dogs, a common infectious route to affect 28 29 30 136 the lumbosacral disc is through the lymphatic vessels that drain the prostate gland 31 32 137 with subsequent arterial spread. Primary hematogenous spread is also a recognized 33 34 138 route of infection (Betbeze and McLaughlin 2002; Burkert and others 2005; Gilmore 35 36 37 139 1987) Rarely, penetrating wounds, migrating foreign bodies, like foxtail or other plant 38 39 140 thorns, or even more seldom sterile procedures, as epidural punctures, can convey 40 41 141 bacteria into the affected site (Betbeze and McLaughlin 2002; Corlazzoli and 42 43 44 142 Pizzirani 1998; MacFarlane and Iff 2011). 45 46 143 For the aforementioned reason urine culture should be performed systematically in all 47 48 49 144 dogs with lumbosacral discospondylitis even in absence of pyuria, even though urine 50 51 145 culture are negative in up to 40% of the cases (Burkert and others 2005; Gilmore 52 53 146 1987; Kornegay and Barber 1980). The combination of urine and blood cultures yield 54 55 56 147 a successful etiological diagnosis in more than 70% of the cases (Betbeze and 57 58 148 McLaughlin 2002; Burkert and others 2005; Gilmore 1987; Kinzel and others 2005). 59 60 149 Pre-treatment of affected animals with antibiotics could lead to false negative culture

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1 2 3 4 150 results. Finally, as also performed in the case reported here, a direct biopsy of the 5 6 151 inflamed tissue either by fluoroscopic guidance or computer tomography and by 7 8 152 direct surgical sampling in order to isolate and identify the responsible bacteria is an 9 10 Confidential: For Review Only 11 153 accurate diagnostic procedure in 76% to 100% of the cases (Gilmore 1987; Kinzel 12 13 154 and others 2005; Kornegay and Barber 1980; Vignoli and others 2004; Zimmerli 14 15 155 2010). 16 17 18 156 A multitude of bacteria are commonly isolated from dogs with discospondilyitis, 19 20 157 however, Erysipelothrix rhusiopathiae has only been described in two clinical reports 21 22 23 158 with discospondylitis in which dogs showed widespread joint inflammation, 24 25 159 endocarditis and discospondylitis at multiple sites (Burkert and others 2005; Houlton 26 27 160 and Jefferies 1989; Seelig and others 2010). Furthermore, besides polyarthritis and 28 29 30 161 aortic valve endocarditis, discospondylitis was also found in 8 of 9 Beagle dogs 31 32 162 experimentally infected with Erysipelothrix rhusiopathiae (Houlton and Jefferies 33 34 163 1989; Schütt and others 1978). 35 36 37 164 E. rhusiopathiae is a facultative, non-spore-forming, non-acid-fast, small, Gram- 38 39 165 positive bacillus. Its distribution is worldwide and it can survive for long periods in 40 41 166 the soil as well as in marine environment(Wang and others 2010). Interestingly, E. 42 43 44 167 rhusiopathiae is known to be a natural host of the slim of some fishes without causing 45 46 168 any apparent disease (Wang and others 2010). As for other cases, the route of 47 48 49 169 infection in our patient was not determined. 50 51 170 To the author’s knowledge, this is the first clinical report describing the successful 52 53 171 treatment of lumbosacral discospondylitis due to E. rhusiopathiae. The initial 54 55 56 172 antibiotic choice was a first generation cephalosporin, which is suggested by several 57 58 173 authors as drug of choice when the causing organism is unknown, and which then was 59 60 174 proven to be effective in our case based on the sensitivity results and clinical course

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1 2 3 4 175 (Burkert and others 2005; Gilmore 1987; Kornegay and Barber 1980). The duration of 5 6 176 antibiotic treatment in discospondylitis does not have a fixed rule and has ranged from 7 8 177 2 to 130 weeks in various reports (Betbeze and McLaughlin 2002; Burkert and others 9 10 Confidential: For Review Only 11 178 2005; Gilmore 1987). It is mainly guided by radiological evidence of bone healing or, 12 13 179 if repeated radiographs can not be taken, it should last at least two weeks beyond the 14 15 180 cessation of clinical signs (Gilmore 1987). In our patient in the absence of control 16 17 18 181 radiographs we advised for a 12 weeks long treatment regimen. 19 20 182 In conclusion, although rarely encountered in the clinical practice Erysipelothrix 21 22 rhusiopathiae 23 183 may cause discospondylitis in dogs. The prognosis seems to be 24 25 184 favourable in the absence of mulitfocal infection like polyarthritis and endocarditis. 26 27 185 28 29 30 186 Bibliography 31 32 187 BETBEZE, C. & MCLAUGHLIN, R. (2002) Canine diskospondylitis: Its etiology, 33 34 188 diagnosis, and treatment. Veterinary Medicine 97, 673-681 35 36 37 189 BURKERT, B. A., KERWIN, S. C., HOSGOOD, G. L., PECHMAN, R. D. & 38 39 190 FONTENELLE, J. P. (2005) Signalment and clinical features of diskospondylitis in 40 41 191 dogs: 513 cases (1980-2001). Journal Of The American Veterinary Medical 42 43 44 192 Association 227, 268-275 45 46 193 CORLAZZOLI, D. & PIZZIRANI, S. (1998) Discospondylitis in the dog. Waltham 47 48 49 194 Focus 8, 2 - 11 50 51 195 GILMORE, D. R. (1987) Lumbosacral discospondylitis in 21 dogs. Journal of the 52 53 196 American Animal Hospital Association 23, 57–61 54 55 56 197 HOULTON, J. & JEFFERIES, A. (1989) Infective polyarthritis and multiple 57 58 198 discospondylitis in a dog due to Erysipelothrix rhusiopathiae. Journal Small Animal 59 60 199 Practice 30, 35-38

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1 2 3 4 200 KINZEL, S., KOCH, J., BUECKER, A., KROMBACH, G., STOPINSKI, T., AFIFY, 5 6 201 M. & KUPPER, W. (2005) Treatment of 10 dogs with discospondylitis by 7 8 202 fluoroscopy-guided percutaneous discectomy. The Veterinary record 156, 78-81 9 10 Confidential: For Review Only 11 203 KORNEGAY, J. N. & BARBER, D. L. (1980) Diskospondylitis in dogs. Journal Of 12 13 204 The American Veterinary Medical Association 177, 337-341 14 15 205 MACFARLANE, P. D. & IFF, I. (2011) Discospondylitis in a dog after attempted 16 17 18 206 extradural injection. Veterinary Anaesthesia and Analgesia 38, 272-273 19 20 207 MEDLIN, L., ELWOOD, H. J., STICKEL, S. & SOGIN, M. L. (1988) The 21 22 23 208 characterization of enzymatically amplified eukaryotic 16S-like rRNA-coding 24 25 209 regions. Gene 71, 491-499 26 27 210 SCHÜTT, I., BRASS, W., WEIS, R., TRAUTWEIN, G. & KERSTEN, U. (1978) 28 29 30 211 Experimentelle Infektion von Hunden mit Erysipelothrix rhusiopathie. Klinische, 31 32 212 röntgenologische, bakteriologische, serologische und pathologisch-anatomische 33 34 213 Befunde. Kleintierpraxis 23, 149-212 35 36 37 214 SEELIG, U., KLOPFLEISCH, R., WEINGART, C., WALTHER, B., LUEBKE- 38 39 215 BECKER, A. & BRUNNBERG, L. (2010) Septic polyarthritis caused by 40 41 216 Erysipelothrix rhusiopathiae in a dog. Veterinary Comparative Orthopaedics and 42 43 44 217 Traumatology 23, 71-73 45 46 218 VIGNOLI, M., OHLERTH, S., ROSSI, F., POZZI, L., TERRAGNI, R., 47 48 49 219 CORLAZZOLI, D. & KASER-HOTZ, B. (2004) Computed tomography-guided fine- 50 51 220 needle aspiration and tissue-core biopsy of bone lesions in small animals. Veterinary 52 53 221 Radiology and Ultrasound 45, 125-130 54 55 56 222 WANG, Q., CHANG, B. J. & RILEY, T. V. (2010) Erysipelothrix rhusiopathiae. 57 58 223 Veterinary Microbiology 140, 405-417 59 60

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1 2 3 4 224 ZIMMERLI, W. (2010) Clinical practice. Vertebral osteomyelitis. New England 5 6 225 Journal of Medicine 362, 1022-1029 7 8 226 9 10 Confidential: For Review Only 11 227 Legend of the Figures 12 13 228 14 15 229 Figure 1: Laterolateral radiograph of the lumbosacral region during the FNA 16 17 18 230 aspiration. Laterolateral radiograph of the lumbosacral joint with a heavy pattern of 19 20 231 spondylosis deformans at L6-7 and L7-S1. A collapsed LS disk space is evident plus 21 22 23 232 endplate sclerosis at this disk space. The centrally located end plate lysis is difficult to 24 25 233 visualize because of the laterally positioned superimposed spondylosis. The tip of the 26 27 234 needle is within the center of the intervertebral disk. 28 29 30 235 Figure 2: Ventrodorsal radiograph of the lumbosacral joint. The same features seen 31 32 236 on Fig.1 are also evident as well as the bony response of the spondylosis deformans 33 34 237 that bridges the L7 – S1 disk space laterally. The bone lysis within the endplates is 35 36 37 238 clearly identified on this view. 38 39 239 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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