INTRODUCTION

Rhodococcus equi (previously known asCorynebacterium equi) is an intracellularpathogen that establishes itself inmacrophages by interfering withphagolysosomal fusion (Heitala andArdans 1987). This interference eventuallyresults in the multiplication of thepathogen within the macrophages, whichleads to the formation of granulomas and,eventually, necrosis. The aerobic Gram-positive pleomorphic organisms of R equivary from cocci to rods and are commonlyfound in the faeces of foals and in soil con-taminated by other herbivore faeces. Theorganism has also been isolated from rab-bit and bird droppings, but not from catfaeces (Carman and Hodges 1987).

R equi mainly causes pyogranulomatousbronchopneumonia in foals, with gastroin-testinal involvement in about 50 per centof the cases (Giguere and Prescott 1997). Ithas also been reported to cause ulcerativelymphangitis, cellulitis, subcutaneousabscesses and arthritis in horses (Zink andothers 1986, Perdrizet and Scott 1987). Itis known to cause infections in humanswith defective cell-mediated immuneresponses and those on immunosuppres-sive treatment. About 30 per cent ofinfected human patients have a history ofhaving been in contact with contaminated

herbivore faeces (Prescott 1991). Therehave also been sporadic reports in the liter-ature of Rhodococcus infections in cats asso-ciated with mediastinal and mesentericlymphadenitis (Jang and others 1975) andcellulitis and abscesses, mainly of theextremities (Higgins and Paradis 1980,Elliot and others 1986, Oxenford and others 1987, Fairley and Fairley 1999).

The present report describes a clinicalpresentation in a cat involving the neckand submandibular lymph node, whichresembles ulcerative lymphangitis, celluli-tis and pyogranulomatous disease, as seenin horses. It also describes the cytological,microbiological and histopathologicalfindings and discusses the common pitfallsin the diagnosis of this unusual cause ofpyogranulomatous disease in the species.

CASE HISTORY

A two-year-old neutered female domesticshorthaired cat was presented with a largeulcerated mass on the left side of the neck.According to the owner, a lump hadoccurred on the right side of the neck following a cat fight. Swab specimens, submitted by the referring veterinary surgeon, had identified the presence ofStaphylococcus intermedius and �-haemolytic streptococci on three previousoccasions. On the first two occasions,histopathological examination of biopsyspecimens revealed a pyogranulomatousdermatitis and cellulitis. On the thirdoccasion, intracellular organisms werefound within macrophages. The organismsdid not stain acid-fast with Ziehl-Neelsen(ZN) stain, but they did stain positive withperiodic acid Schiff (PAS) stain.

Despite excisions with wide surgicalmargins and antibacterial therapy with 5mg/kg enrofloxacin (Baytril; Bayer AnimalHealth) followed by 5·5 mg/kg clin-damycin (Antirobe; Pharmacia andUpjohn Animal Health) twice daily, newlesions continued to appear. The cat’s con-dition slowly deteriorated, with the onsetof pyrexia, anorexia and lethargy as the

A. PATEL

Journal of Small Animal Practice (2002)43, 129–132

This report describes a case of Rhodococcus equi infection causing

pyogranulomatous skin disease and cellulitis in a two-year-old

female domestic shorthaired cat. The case differed from previously

reported cases in cats in its clinical presentation and in the

locations of the lesions, which were similar to those seen in horses.

The presence of an intracellular organism was confirmed by cytology

and on histopathology. The aetiological diagnosis was confirmed by

routine biochemical tests specific for R equi on a pure isolate

obtained from a biopsy specimen. The report also reviews the

literature of the documented feline cases and discusses the

common pitfalls in the diagnosis of such infections.

Pyogranulomatous skin disease and cellulitis in a cat caused byRhodococcus equi

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23 Searchwood Road, Warlingham,Surrey CR6 9BB

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disease progressed, at which point the catwas referred.

On referral, a general physical examina-tion revealed the cat to be in poor condi-tion, weighing 2·9 kg, with a temperatureof 39·4°C. On auscultation, the cat wasfound to be tachycardic, with a heart rateof 170 beats per minute. No abnormallung sounds were detected.

The submandibular and the rightprescapular lymph nodes were enlarged.However, the left prescapular lymph nodewas not palpable because the lesion was atthe site of the node. There was a haemo-purulent discharge from a draining sinusover the right parotid gland (Fig 1) and alarge non-painful ulcerated mass of about4 cm diameter, with seropurulent exudate,

on the left prescapular area (Fig 2). Thesurface of the mass had a crater-likeappearance, with exposure of the underly-ing subcutaneous fat and muscle. The sur-rounding skin was alopecic, but surfacelesions were not visible. On palpation, themass was not circumscribed and crepituswas felt under the skin, suggesting deeperinvolvement.

Differential diagnoses at this stageincluded granulomatous dermatitis causedby infectious bacterial, fungal or protozoalorganisms (see Table 1).

Haematological analysis demonstrated aleucocytosis (19·2 �109/litre; referencerange 5 to 18 �109/litre) with a matureneutrophilia (15·1 �109/litre; referencerange 4 to 14 �109/litre). Serum bio-

chemical analysis revealed a raised creatinekinase concentration (132 iu/litre; refer-ence range <120 iu/litre). All other parame-ters were within the normal referenceranges. An ELISA and virus isolation forfeline leukaemia virus antigen andimmunofluorescence for feline immuno-defiency virus antibodies were negative.The antibody titre for feline coronaviruswas 1/10.

Impression smears taken from the sur-face of the ulcerated mass and the drainingtract from the right lymph node werestained with modified Wright’s stain (Diff-Quik; Dade AG) and examined under anoil immersion lens. Numerous neutrophilsand macrophages containing cocci androd-shaped organisms within clear vacuoles

FIG 1. Haemopurulent exudate from a drainingtract (arrow) over the right parotid gland

FIG 2. Appearance of the ulcerated mass on the left lateral neck

Bacteria Non-acid-fast organisms Actinobacillus sp, Arcanobacteriumpyogenes (previously known asActinomyces pyogenes), Rhodococcus equi,Staphylococcus sp, Streptococcus sp,Pseudomonas sp, Proteus sp

Acid-fast organisms Norcardia asteroides, Mycobacteriumlepraemurium, M tuberculosis, M microti,M chelonei, M fortuitum, M phlei, M thermoresistible, M smegmatis

Fungi Subcutaneous mycoses Microsporum canis, Rhizomucor sp,Mortierella sp, Fusarium sp, Paecilomycessp, Alternaria sp, Cladophialiophora sp,Exophiala sp, Moniliella sp, Curvularia sp,Madurella sp, Pythium insidiosum,Sporothrix schenckii

Systemic mycoses Cryptococcus neoformans, Sporothrixschenckii, Histoplasma capsulatum,Blastomyces dermatitidis, Coccidioidesimmitis

Protozoa Leishmania sp

Aetiological agents

Table 1. Infectious agents responsible for granulomatous skin disease in cats

FIG 3. Intracellular organisms within the macrophages (arrows) andsegmented neutrophils found on an impression smear stained withmodified Wright’s stain. �1250

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in the cytoplasm were seen (Fig 3). Several biopsy specimens were obtained

under anaesthesia induced with 80 mg/kgmedetomidine (Domitor; Pfizer AnimalHealth), 0·4 mg/kg butorphanol (Torbu-gesic; Fort Dodge Animal Health) and 5·0mg/kg ketamine (Ketaset; Fort DodgeAnimal Health), injected intramuscularlyfrom one syringe. Biopsy specimens fromthe centre of the ulcerated mass and fromthe surrounding skin were submitted forhistopathological examination and a sample from each site was submitted forbacterial, mycobacterial and mycologicalculture. Thoracic and abdominal radio-graphs did not reveal any abnormalities.....

R equi was recovered from the tissuebiopsy submitted for bacteriological analy-sis. The organism showed in vitro suscepti-bility to enrofloxacin, cefuroxime andoxytetracycline. It was resistant to penicillin,ampicillin, coamoxiclav, cephalexin and co-trimoxazole. Microscopic examinationand culture from biopsies were negative foracid-fast bacteria (Mycobacterial ReferenceLaboratory, Cardiff ) and for fungi (Myco-logical Reference Laboratory, Bristol).

Histopathological examination of thetissue from the ulcerated lesion revealed adiffuse pyogranulomatous reaction (Fig 4)containing foamy macrophages, withinwhich small coccoid organisms were pre-sent. Within the same biopsy there wasevidence of infiltration of mononuclearcells into the muscle tissue. Biopsies fromthe surrounding area showed diffuse der-matitis, with focal aggregates of lymphoidfollicles and deep pyogranulomatous pan-niculitis. The macrophages within thepanniculus also contained numerous intra-cellular organisms.

A diagnosis of cellulitis and subcuta-neous abscess caused by R equi was made.A guarded prognosis was given, because ofthe extent and the chronic nature of the

condition. Doxycycline (Ronaxan; MerialAnimal Health), at 10 mg/kg every 12hours, was administered. Despite support-ive therapy and antibiotic treatment thecat died within two weeks of diagnosis. Apostmortem examination of the thoracicand abdominal organs did not reveal anygross abnormalities. Because of the timelapse between death and necropsy, furthersamples were not submitted for culture......

DISCUSSION

At the time of writing, 11 cases of R equiinfections in cats have been reported andall but three of these involve either the digits or other extremities (Higgins andParadis 1980, Elliot and others 1986, Fairley and Fairley 1999). In the remainingthree cats, internal abcessation and lymphadenitis were diagnosed (Jang and others 1975, Oxenford and others 1987).In two of these three cats, the findings were made at postmortem examination,whereas in the remaining one, infectionwas postulated to have caused pneumonia(Fairley and Fairley 1999).

The present report describes a casewhere cellulitis, abscessation and ulcerativelymphangitis were present in the same cat.In view of the zoonotic potential of someof the organisms causing granulomatousdisease in cats, it is important that thecause of the disease in such cases is pre-cisely identified.

Details of the sampling techniquesused to detect R equi have not beenreported before. In the present case, routine culture techniques using swabsamples failed to identify the organism.Using this technique, several morphologi-cally distinct colonies appeared on theplates and the technician inspecting theplate selected those suspected to be

pathogens for identification. In this case, Staphylococcus intermedius and �-haemolytic streptococci were isolatedfrom swab specimens taken on differentoccasions. It is possible that on these occa-sions the laboratory may have misidenti-fied the colonies of R equi as contaminantsor that they may not have grown at allfrom a swab specimen, since it is an intra-cellular pathogen. Similar difficulties alsoappear to have been encountered inhuman microbiology laboratories (Doigand others 1991).

The biopsy specimens were submittedto specialist laboratories for fungal,mycobacterial and bacterial cultures. Thelaboratory involved in the bacterial culturewas alerted to the possibility that aerobicand anaerobic bacteria, such as R equi,Norcardia asteroides, Arcanobacteriumspecies and Actinobacillus species, could bepresent. The technique of culturing organ-isms from a tissue specimen involvescrushing the material to release the intra-cellular organisms. In this case, the tech-nique produced a pure culture of R equi,which was then easy to identify using rou-tine biochemical tests for the species.

This report emphasises the need to sub-mit biopsy specimens for culture when try-ing to identify intracellular pathogens andalso the importance of alerting the labora-tory to what possible organisms they needto look out for.

PAS, a tissue stain mainly used to iden-tify fungal elements in biopsy specimens,produces a red colour when positive. Itsometimes also stains glycogen, neutralmucopolysaccharides and tissue debris(Scott and others 2001). The presence ofmucopolysaccharides within the bacterialcell wall may account for the positive stain-ing seen in the present case, which couldhave been misleading. However, fungalspores and bacteria can be differentiatedfrom each other by their size on micro-scopic examination.

Of the 11 reported cases of R equi infec-tion in cats, four either died or wereeuthanased. Seven survived, so the progno-sis seems to be reasonably favourable when

FIG 4. Diffuse pyogranulomatousreaction. Haematoxylin & eosin �125

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there is no systemic infection present. Inthe most recent report, five out of six catswith lesions involving distal extremitiesrecovered after antibacterial treatment,whereas one with a suspected infection of the lungs died (Fairley and Fairley1999).

Elliott and others (1986) suggested thatit might be possible to transfer the organ-ism from one animal to another via afomite. Therefore, the various attempts toremove infected tissue by wide marginexcision by the referring veterinary surgeonmay have failed due to the spread of infec-tion during surgery, or because it mayalready have spread via the lymphatic sys-tem. It is postulated that in the present casethe organism probably spread via the latterroute, because following the initial infec-tion on the right side of the neck, the rightsubmandibular lymph node and parotidgland became involved, and because theclinical signs bore close resemblance tothose of ulcerative lymphangitis seen inhorses, pigs and ruminants.

A variety of antibacterial agents havebeen used in the treatment of R equi infection. The isolate in this report wassensitive to enrofloxacin, cefuroxime andoxytetracycline. Based on these results,doxycyline was prescribed. A previousattempt at treatment with enrofloxacinhad shown a poor response. Tetracyclinesact by inhibiting protein synthesisthrough binding to the 30-S ribosomalsubunit, which prevents the transfer RNAfrom binding to its receptor site on theribosome (Papich 1995). Doxycyline is lipid-soluble, which gives it the ability to achieve good intracellular penetration,and it has been advocated as a second-line treatment for other intracellularpathogens, such as opportunistic myco-bacterial infections (Gunn-Moore andShaw 1997). The cat in the present reportmay not have responded to doxycyclinebecause of the extensive spread of theorganism, even though in vitro sensitivityhad been demonstrated.

Naturally occurring infections mostcommonly occur in foals through inhala-

tion of the infectious agent (Giguere andPrescott 1997). In humans, R equi infec-tions have mostly been reported in associa-tion with immunosuppressive diseases ortherapy. It has been most commonlyreported in those which have developedAIDS, those suffering from malignanciesand those undergoing chemotherapy andorgan transplant treatment (Prescott1991).

Using mouse models it has been demonstrated experimentally that immuno-suppression caused by cyclophosphamideand corticosteroids can result in similarinfections to those seen in naturally occur-ring equine cases (Bowles and others 1989).In vitro studies have shown that R equi isable to multiply and persist withinmacrophages (Hondalus and Mosser 1994).In vivo studies in mice have demonstratedthat this ability is correlated with the pres-ence of a virulence-associated plasmid,which allows bacterial multiplication withinthe macrophage and granuloma formation(Hondalus 1997). This virulence-associatedplasmid has been found consistently in R equi isolates from clinically affected foals,but not from clinically affected humans,suggesting that the patient’s immuno-deficiency status allows the less virulentstrains to persist within the macrophages......

ConclusionsAn underlying cause for infection was notidentified in the present case, nor in any ofthe previously reported feline cases. How-ever, bearing in mind that this is an oppor-tunistic organism and with increased use ofimmunosuppressive treatments in bothcancer therapy and, more recently, inorgan transplantation in feline medicine,both clinicians and laboratory techniciansshould not overlook the potential patho-genicity of this organism. Early identifica-tion and appropriate treatment may allowsuccessful treatment.

AcknowledgementsThe author is grateful to Mr M. Ibuoye, of the Department of Pathology and Infec-tious Diseases, Royal Veterinary College,

Hertfordshire, for the bacterial identifica-tion, to Mr R. Gumbrill of Rest Associates,Swaffham Prior, Cambridgeshire, for thehistopathological examination, to Dr I. S.Mason for a critical review of the report, toMr S. Edgill for referring the case and toMs T. Thornicroft for her assistance withthe case.

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