Inflammatory myopathies are a heterogeneous group of

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1 J Vet Iter Med 00;: Cie Iflmmtory Myopthies: A Cliicopthologic Review of 00 Cses Jso Evs, Dold Levesque, d G. Die Shelto A retrospective study ws performed o 00 rdomly selected cses of iflmmtory myopthy i dogs from digostic muscle biopsies received t the Comprtive Neuromusculr Lbortory, Uiversity of Clifori, S Diego. The most commo cliicl sigs i dogs digosed with iflmmtory myopthy were geerlized wekess, stilted git, dysphgi, mstictory or geerlized muscle trophy, ibility to ope the jw, megesophgus, d dysphoi. Mylgi ws rrely described. Age of oset rged from to yers. Geders were eqully represeted. Breed distributio pproximted the 00 Americ Keel Club registrtio sttistics (r.) with the otble exceptio of Boxers d Newfoudlds. From the results of muscle biopsies, cliicl sigs, d presece or bsece of tibodies gist type M fibers, dogs were clssified s geerlized iflmmtory myopthy (gim) icludig immue-medited polymyositis; ifectious d preeoplstic myositis; d, rrely, dermtomyositislike or overlp sydromes or uclssified myositis or focl iflmmtory myopthy (fim) icludig mstictory muscle d extroculr myositis. Averge cretie kise (CK) d sprtte miotrsferse (AST) cocetrtios i gims were sigifictly higher th those with fims (P.0). Neoplsi developed i of 00 dogs withi moths of digosis of polymyositis, with lymphom digosed i of Boxers. Iflmmtory myopthy ws ssocited with tibody titers gist ifectious diseses i dogs. Neospor cium d Heptozoo mericum cysts were foud i tissues of dogs ot serologiclly tested. Atibodies gist uidetified srcolemml tige were foud i of Newfoudlds with polymyositis. The spectrum of cie iflmmtory myopthies c be brod, with ifectious etiologies reltively commo, d c iclude preeoplstic d uchrcterized sydromes. Key words: Dermtomyositis, Extroculr myositis, Mstictory muscle, Polymyositis. Iflmmtory myopthies re heterogeeous group of disorders chrcterized by osuppurtive cellulr ifiltrtio of skeletl muscle. The term polymyositis hs bee used i both hum d veteriry medicie to describe geerlized iflmmtory myopthies regrdless of etiology. I hum medicie, the term specificlly is reserved for myositis of presumed immue-medited etiology. For cosistecy, the term geerlized iflmmtory myopthy (gim) is used i this report s geerl descriptio for diffuse iflmmtory myopthies, icludig ifectious d preeoplstic sydromes, d the term focl iflmmtory myopthy (fim) is used for the loclized sydromes. Dermtomyositislike, uclssified, d overlp sydromes will be chrcterized seprtely. Both geerlized d focl forms of iflmmtory myopthies hve bee reported i the dog. Geerlized iflmmtory myopthies iclude polymyositis (PM), immue-medited disorder with digostic criteri, icludig cliicl sigs of muscle wekess, stilted git, d muscle trophy; bormlly high serum cretie kise (CK) cocetrtios; borml electromyogrphy (EMG); egtive serologic tests for ifectious disese; d histologic cofirmtio of lymphocytic ifiltrtes i skeletl muscle. gims lso hve bee ssocited with ifectious gets, icludig protozo, s well s rickettsi,, spirochetes, d other bcteri., Recet evidece hs co- From the Veteriry Neurologicl Ceter, Ls Vegs, NV 0 (Evs, Levesque); d the Deprtmet of Pthology, Uiversity of Clifori, S Diego, L Joll, CA (Shelto). Portios of this study preseted t the 00 ACVIM Forum i Chrlotte, NC. Reprit requests: Dr Jso Evs, Veteriry Neurologicl Ceter, N Ribow Boulevrd, Ls Vegs, NV 0; e-mil: DrJsoDVM@ol.com. Submitted Februry, 00; Revised Mrch, 00; Accepted April, 00. Copyright 00 by the Americ College of Veteriry Iterl Medicie 0-0/0/0-00/$.00/0 firmed ssocitio betwee mligcy d iflmmtory myopthies i hums. I dogs, few reports lso hve ssocited iflmmtory myopthies with eoplsi, icludig brochogeic crciom, myeloid leukemi, tosillr crciom, d other mligcies., Focl iflmmtory myopthies iclude mstictory muscle myositis (MMM),0 d extroculr myositis (EOM), with cellulr ifiltrtes restricted to these prticulr muscle groups. The most commo cliicl sigs ssocited with MMM re ibility to ope the jw, jw pi, d mstictory muscle trophy. Cellulr ifiltrtes i MMM selectively ffect the muscles iervted by the mdibulr brch of the trigemil erve, icludig the msseter, temporlis, pterygoids, tesor tympi, d tesor veli pltii muscles. Mstictory muscles coti uique muscle fiber type, type M, tht differs both histochemiclly d biochemiclly from fiber types preset i limb muscles. A recet study suggested tht immuologiclly distict microeviromet lso might be preset i mstictory muscles compred with limb muscles. I PM, CD cells were preset i greter umbers th CD cells, T cells used predomitly the T-cell receptor, d o B cells were foud. I MMM, CD cells were preset i greter umbers th CD cells, T lymphocytes utilized both d receptors, d multifocl clusters of B lymphocytes were preset. Atibodies gist mstictory muscle type M fibers lso hve bee cosistetly ssocited with MMM. 0 Extroculr myositis is fim with cliicl sigs restricted to the extroculr muscles with sprig of the mstictory d limb muscles. The immue respose might be directed gist uique tiges ssocited with this muscle group. Bilterl exophthlmos from swellig of the extroculr muscles is the oly cliicl sig i EOM. Exophthlmos lso c be foud i MMM but, whe preset, is result of swellig of the pterygoid muscle d ot the extroculr muscles., Serum tibody titers for tibod-

2 0 Evs et l ies gist mstictory muscle type M fibers re egtive i EOM. Dermtomyositis, first described i Collies, is ucommo immue-medited geerlized iflmmtory disorder ffectig the ski, skeletl muscle, d vsculture. 0 Dermtomyositis most commoly occurs i Collies d Shetld Sheepdogs,, but spordic cses hve bee described i other breeds. Although ot yet documeted i dogs, dermtomyositis ssocited with mligcy frequetly hs bee reported i hums., The purpose of this study ws to further clssify cie iflmmtory myopthies d determie the reltive frequecies d breed predispositios of the vrious sydromes, etiologies, d log-term outcomes o the bsis of the summry fidigs of siglmet, cliicl sigs, histopthologic descriptios, cliicopthologic fidigs, d serologic tests. Dt ws compiled d lyzed from 00 dogs previously digosed with iflmmtory myopthy o the bsis of muscle biopsy evlutio. Methods d Mterils Histopthology d Histochemistry Biopsy specimes from dogs with cliicl sigs cosistet with muscle disese were collected by prcticig veteriris throughout the Uited Sttes through ope surgicl biopsy procedure. The most commoly submitted muscles for histopthologic evlutio icluded the temporlis d msseter muscles for suspected MMM; the lterl rectus muscle for suspected EOM; d the triceps brchii, vstus lterlis, cril tibil, biceps femoris, d gstrocemius muscles for geerlized disorders. Ifrequetly submitted muscles icluded the suprspitus, lrygel muscle, deltoideus, biceps brchii, semimembrosis, ifrspitus, d extesor crpi rdilis. After shipmet of cold tissue to the Comprtive Neuromusculr Lbortory t the Uiversity of Clifori, S Diego, muscle specimes were sp froze i isopete, precooled i liquid itroge, d stored t 0 C util evlutio. All muscles submitted to the lbortory were evluted with stdrd pel of histochemicl stis d rectios s described by Dubowitz. Routie histopthology ws performed o froze muscle sectios with the hemtoxyli d eosi d modified Gomori trichrome stis. Mcrophges were idetified withi cellulr ifiltrtes with the use of the cid phosphtse sti, d eosiophils were idetified by the peroxidse rectio. Cse Selectio Two hudred rdomly selected dogs from the tissue rchives of the Comprtive Neuromusculr Lbortory, previously digosed with iflmmtory myopthy o the bsis of evlutio of muscle biopsy specimes betwee d 00, were retrospectively lyzed. Iformtio icludig siglmet, ptiet history, presetig cliicl sigs, results of eurologic exmitios, cliicopthologic d serologic fidigs, electrodigostic evlutio, idividul medicl tretmet, d ptiet follow-up ws obtied from the smple submissio forms, d follow-up questioires were completed by the submittig veteriris. Cliicopthologic Evlutio Miimum dtbses, icludig CBC, biochemicl lyses, d routie serologic tests, were performed t vrious commercil digostic lbortories by stdrd procedures. Dt regrdig white blood cell cout, serum CK, sprtte miotrsferse (AST) d lie miotrsferse (ALT) ctivities, totl thyroxie cocetrtios, tiucler tibody titer, d Coombs d rheumtoid fctor tests were obtied from the submissio form or questioire. Atibody titers gist mstictory muscle type M fibers d cetylcholie receptors b were performed t the Comprtive Neuromusculr Lbortory by methods described previously., Results of serologic testig for Toxoplsm godii, Neospor cium, Borreli burgdorferi, Ehrlichi ci, d Rickettsi rickettsii specificlly were requested o the questioire. Although referece vlues for the respective tests for ifectious orgisms vried mog differet commercil or istitutiol lbortories, tibody titers were cosidered positive if the titer ws higher th the lowest positive result expected by previous exposure or vccitio s described i published reports. Myositis ws clssified s ssocited with ifectious get if serum from ffected dog ws positive for circultig tibodies to the get d cliicl sigs respoded to pproprite timicrobil medictio or if orgism ws idetified o muscle biopsy specimes or t postmortem exmitio. Electrodigostic Testig Electrophysiologic testig ws performed by stdrd procedures 0 t severl sites. Results of EMG d motor erve coductio velocity (NCV) studies performed durig the digostic workup of dogs with suspected iflmmtory myopthy were obtied from the submissio form d questioire. Cliicl Outcome Recovery ws defied s the time from digosis to whe dogs hd show cliicl improvemet but still were o medicl therpy for cliicl sigs of iflmmtory myopthy. Norml ws defied s the time to resolutio of cliicl sigs d the discotiutio of medictios for tretmet of the iflmmtory myopthy. The time from oset of cliicl sigs to digosis (ie, muscle biopsy), the time to recovery or to orml, or the time to deth ws determied from the submissio form d follow-up questioire. Sttisticl Alysis All sttisticl comprisos betwee groups were mde by Studet s t-test. The level of sigificce chose ws P.0. Correltio lysis ws pplied to sctterplot to mesure the correltio coefficiet (r) of the reltioship betwee the percet popultio distributio of breeds i the study compred with the percet popultio distributio of breeds of the geerl popultio s reported by 00 Americ Keel Club (AKC) registrtios. Results Clssifictio of Cie Iflmmtory Myopthies Clssifictio ws bsed o combitio of histopthologic cofirmtio of the iflmmtory myopthy, geerlized or focl cliicl sigs, results of serologic testig for ifectious diseses, d results of the M tibody test. gim (0/00, 0%; Fig A) d MMM (/00,.%; Fig B) were most frequetly digosed. Smll umbers of dogs hd overlp sydrome i which cellulr ifiltrtio ws preset i both mstictory muscle d limb muscle biopsies, d tibodies were detected gist type M fibers (/00,.%). gims were further clssified to iclude () immue-medited PM i of 0 (%) dogs, () ifectious etiology i 0 of 0 (.%) dogs, d () preeoplstic sydrome i of 0 (.%) dogs. For the dogs with preeoplstic sydrome, tumor cells were ot idetified i the origil biopsies but were detected i repet muscle specimes up to moths fter the origil digosis. Other ifrequet digoses icluded dermto-

3 Cie Iflmmtory Myopthies Fig. Muscle biopsies re show from dogs with vrious iflmmtory myopthies, icludig immue-medited polymyositis (A), mstictory muscle myositis (B), d uchrcterized myositides ssocited with ecrotizig vsculitis (C) (str idictes ecrotic vessel wll, the lume is occluded), d mcrophgic myositis with ocsetig gruloms (D). Hemtoxyli-eosi. Br 0 m for ll prts. myositislike sydrome (/00,.%), EOM (/00, %), or uclssified myositis (/00,.%). Dogs with cliicl sigs d histopthologic fidigs i muscle biopsies ot typicl of the trditiol clssifictios of iflmmtory myopthy were digosed with uclssified myositis. All dogs i this ctegory hd egtive serology results for ifectious diseses s well s egtive M tibody titers. Uclssified myopthies icluded those ssocited with ecrotizig vsculitis (Fig C) or grulomtous myositis (Fig D). Siglmet A summry of ge, geder, d time from oset of cliicl sigs to digosis d recovery for 00 dogs with iflmmtory myopthy is show i Tble ; the commo gim clssifictios re show i Tble. A geder predilectio for iflmmtory myopthy ws ot evidet. The overll me ge for ll dogs ws.. yers. Sigifict differeces (P.0) were foud for dogs with overlp sydrome (. 0. yers), dermtomyositislike sydrome (.. yers), d ifectio with N cium (.. yers). The me time to digosis (ie, biopsy) fter the oset of cliicl sigs for dogs with gim (.. weeks) d overlp sydrome (. weeks) ws sigifictly differet from dogs with MMM (.. weeks), dermtomyositislike sydrome (. weeks), EOM ( 0.0 week), d uclssified myopthy (.. weeks) compred with other groups (P.0). This fidig might reflect more distiguishble cliicl sigs i the ltter groups, resultig i erlier digostic testig. The 0 breeds represeted i this study d the me ge for ech breed re listed i Tble. The distributio of listed breeds correlted with the distributio of the geerl popultio s reported by 00 AKC registrtios (r.) with the exceptio of Boxers ( ) d Newfoudlds ( ), which were overrepreseted (Fig ). I dditio, the Airedle ( 0.0 yers), Akit ( 0.0 yers), Brird ( 0.0 yers), Britty Spiel ( 0.0 yers), Chihuhu ( 0.0 yers), Eglish Bulldog (.. yers), Fox Terrier (.0 yers), Mlmute ( 0.0 yers), Mstiff (. 0. yers), Newfoudld (..

4 Evs et l Tble. Age, sex, d cliicl outcome for 00 dogs with iflmmtory myopthy. gim MMM OS DM EOM UN Totl Number i study 0 00 Age (yers) Rge Geder MN FS M F Oset (weeks) Rge Recovery (weeks) Rge Norml (weeks) Rge Died (weeks) Rge Euthized (weeks) Rge Lost to follow-up gim, geerlized iflmmtory myopthy; MMM, mstictory myositis; OS, overlp sydrome (combied polymyositis d MMM); DM, dermtomyositislike sydrome; EOM, extroculr myositis; UN, uclssified myositis; M, mle; MN, cstrted mle; F, femle; FS, spyed femle. Recovery ws defied s the time from digosis to whe dogs hd show cliicl improvemet but were still o medicl therpy for cliicl sigs of iflmmtory myopthy t the time of the report. Norml ws defied s the time to resolutio of cliicl sigs d the discotiutio of medictios for tretmet of the iflmmtory myopthy. Me SD. yers), Pit Bull ( 0.0 yers), d Weimrer (.0 yers) breeds were ffected t sigifictly youger ges (P.0) th other breeds i this study, d more Newfoudlds were uder yer of ge (/,.%) th y other group. Cliicl Sigs Cliicl sigs i dogs with geerlized d focl forms of iflmmtory myopthies re summrized i Tble. The most commo cliicl sigs i gims icluded wekess, stiff git, dysphgi, geerlized muscle trophy, d megesophgus. Decresed or bset spil reflexes (ie, geerlized lower motor sigs) lso were observed i of (.%) dogs with geerlized wekess. Surprisigly, mylgi ws described i oly dogs: dogs were digosed with uclssified myositis becuse of grulomtous or srcoidlike myositis, d dog ws digosed with T godii ifectio. I Newfoudld dogs, predomit cliicl sigs geerlly were ssocited with lrygel, phrygel, d esophgel dysfuctio. Te dogs with geerlized muscle trophy becuse of PM were reported to hve either proouced mstictory muscle trophy or mstictory muscle trophy s the iitil cliicl sig. Dogs with fims showed cliicl sigs referble to the ivolved muscle group, icludig ibility to ope the jw, trophy of the mstictory muscles, or exophthlmos. Mstictory muscle trophy loe ws described i dogs (.%), ibility to ope the jw loe i dogs (0%), d combied ibility to ope the jw d mstictory muscle trophy i dogs with MMM (.%). A ibility to ope the jw lso ws reported s oe of the cliicl fidigs i dogs with gim (%) d i dog with overlp sydrome (%). Both dogs with EOM oly demostrted bilterl exophthlmos (00%). Three dogs with MMM (.%) d dog with overlp sydrome (%) lso demostrted bilterl exophthlmos s prt of the cliicl presettio. Geerlized lower motor euro wekess ws more commo i dogs with ifectious myositis compred with dogs with other forms of gim. Two dogs with N cium relted myositis demostrted the chrcteristic pelvic limb rthrogryposis. Te dogs with iflmmtory myopthy were febrile o cliicl exmitio. Six febrile dogs were digosed with PM, with ifectio by Heptozoo mericum, with eosporosis, with MMM, d the other with uclssified myositis. Cliicopthologic Fidigs The results of cliicopthologic testig from dogs i the differet ctegories of iflmmtory myopthy re sum-

5 Cie Iflmmtory Myopthies Tble. Age d cliicl outcome for dogs with geerlized iflmmtory myopthy: immue-medited polymyositis d ifectious d preeoplstic myositis. Immue-medited Rge Number Age (yers) Oset (weeks) Recovery (weeks) Died/euthized (weeks).. 0 Ifectious Toxoplsm godii Rge Neospor cium Rge Borreli burgdorferi Rge Rickettsi rickettsii Rge Ehrlichi cis Rge Heptozoo mericum Preeoplstic Rge LTF, lost to follow-up. Vlues for recovery d orml, s previously defied, were combied i this tble. Me SD N/A.. 0 LTF mrized i Tble. There were o sigifict differeces i me white blood cell cout mog groups (P.0). The me CK ctivity i dogs with gim d overlp sydrome ws sigifictly higher (P.0) th i dogs with MMM, dermtomyositislike sydrome, d uclssified myopthy. CK ctivities were ot mesured i the dogs with EOM. Me AST ctivity i dogs with gim d overlp sydrome lso ws sigifictly higher (P.0) th i dogs with MMM d dermtomyositislike sydrome. AST ctivities were ot reported i dogs with EOM or uclssified myositis. Me ALT ctivity ws sigifictly lower (P.0) i dogs with MMM d sigifictly higher (P.0) i dogs with uclssified myositis compred with other groups. ALT ctivities were ot reported i dogs with EOM d overlp sydrome. No sigifict differeces were observed i totl thyroxie cocetrtios mog the differet groups (P.0). Atibodies gist mstictory muscle type M fibers were detected i dogs with MMM (%) d i ll dogs with overlp sydrome (00%). Acetylcholie receptor tibody titers ( ) d tiucler tibody ( ), Coombs ( ), d rheumtoid fctor ( ) test results were ll egtive. Atibodies gist uidetified srcolemml tige were foud o histopthologic lysis i of Newfoudlds with PM (Fig ). Respose to edrophoium c ws egtive i ll dogs tested ( ). Electrophysiologic Alysis Electromyogrphy d motor NCV fidigs i dogs with iflmmtory myopthies re summrized i Tble. EMG ws performed o (.%) dogs, d motor NCV studies were evluted o (%) dogs. Fibrilltio potetils d positive shrp wves were idetified i 0 (%) dogs with gim, icludig those with myopthy secodry to T godii (), N cium (), d B burgdorferi (), d i dogs with preeoplstic myositis. Similr chges lso were foud i the mstictory muscles of dogs with MMM () d i limb muscles of dogs with dermtomyositislike sydrome (), uclssified myositis (), d overlp sydrome (). Complex repetitive dischrges were foud i dogs with immue-medited PM d i dogs with uclssified myopthy. EMG ws orml i of (.%) dogs with gim, icludig with toxoplsmosis, with eosporosis, d with preeoplstic myositis. Mild decreses i motor NCV were foud i dogs with gim d were orml i dogs with gim d dogs with dermtomyositislike sydrome. Of the dogs with decresed motor NCV, were digosed with eosporosis d with toxoplsmosis. A dditiol dog with decresed motor NCV hd iflmmtory spil fluid lysis but ws ot serologiclly tested for either T godii or N cium. Oe dog with decresed motor NCV ws ot serologiclly tested for either T godii or N cium but showed cliicl im-

6 Evs et l Tble. Breed distributio of the 00 dogs with iflmmtory myopthy compred with ssumed distributio of the geerl popultio bsed o the 00 AKC registrtios. Breed gim MMM OS DM EOM UN Totl Study % AKC % Age (yers) Airedle Akit Austrli Cttle Dog Berese Mouti Dog Border Collie Boxer Brird Britty Spiel Chihuhu Chespeke By Retriever Cocker Spiel Collie Welsh Corgi (Pembroke) Dlmti Doberm Pischer Dchshud Eglish Bulldog Fox Terrier Golde Retriever Germ Shepherd Germ Shorthired Poiter Greyhoud Jck Russell Terrier Keeshode Lbrdor Retriever Lhs Apso Mlmute Mstiff Miiture Pischer Miiture Schuzer Mixed breed Newfoudld Old Eglish Sheepdog Pekigese Pit Bull Pomeri Poodle (Stdrd) Pug Rottweiler Smoyed Shrpei Siberi Husky Schipperke Eglish Spriger Spiel Sit Berrd Stffordshire Terrier Terrier cross Weimrer West Highld White gim, geerlized iflmmtory myopthy; MMM, mstictory myositis; OS, overlp sydrome; DM, dermtomyositislike sydrome; EOM, extroculr myositis; UN, uclssified myositis; AKC, Americ Keel Club. provemet with clidmyci loe. A fil dog with preeoplstic myositis secodry to lymphosrcom lso hd decresed motor NCV. Histopthologic Chrcteriztio Histopthologic fidigs of muscle biopsies from dogs i the differet ctegories of the iflmmtory myopthies re summrized i Tble. The most commo ptters of cellulr ifiltrtes were vrious combitios of lymphocytes, histiocytes, d mcrophges, with or without eosiophils. Neutrophils rrely were foud. Eosiophils were most commo i dogs with iflmmtory myopthy resultig from ifectious get or i MMM. Twelve dogs with iflmmtory myopthy becuse of T godii (%) d dogs

7 Cie Iflmmtory Myopthies Fig. Sctterplot digrm comprig the percet breed popultio distributio of the dogs i this ivestigtio with ssumed breed distributio of the geerl popultio s reported by 00 Americ Keel Club (AKC) registrtios. The str d petgo represet the Newfoudld d Boxer breeds, respectively. Tble. Presetig cliicl sigs i 00 dogs with iflmmtory myopthy. gim MMM OS DM EOM UN Totl Number i study 0 00 Geerlized cliicl sigs Geerlized wekess Stiff git Dysphgi Megesophgus Geerlized muscle trophy Geerlized LMN sigs Dysphoi Fever Ibility to ope jw Exophthlmos 0 0 Focl cliicl sigs Ibility to ope jw oly Mstictory muscle trophy oly Mstictory muscle trophy d ibility to ope jw Exophthlmos oly gim, geerlized iflmmtory myopthy; MMM, mstictory myositis; OS, overlp sydrome; DM, dermtomyositislike sydrome; EOM, extroculr myositis; UN, uclssified myositis; LMN, lower motor euro. Dogs with the geerlized cliicl sigs hd or more of the listed cliicl sigs. Some dogs hd oly or very focl cliicl sigs s listed bove.

8 Evs et l Tble. Summry of the cliicopthologic fidigs of 00 dogs with iflmmtory myopthy. gim MMM OS DM EOM UN Totl Number i study 0 00 CK (IU/L) Rge AST (IU/L) Rge ALT (IU/L) Rge WBC ( 0 ) Rge TT Rge,.,.,0 0.., , ,0.,. 0,. 0. 0,. 0,00. NP NP,,. 0,0 NP NP.. 0 NP...,.,,0.., NP NP NP NP.0. M Ab ND ND Positive Negtive AChR Ab (egtive) ND ND gim, geerlized iflmmtory myopthy; MMM, mstictory myositis; OS, overlp sydrome; DM, dermtomyositislike sydrome; EOM, extroculr myositis; UN, uclssified myositis; CK, cretie kise; AST, sprtte miotrsferse; ALT, lie miotrsferse; WBC, white blood cell cout; TT, totl thyroxie cocetrtio (RIA); M Ab, M tibody titer; AChR Ab, cetylcholie receptor tibody (mysthei grvis); NP, iformtio ot provided; ND, test ot doe. Me SD. Fig. Fresh froze biopsy from the deltoid muscle of -yer-old femle spyed Newfoudld dog with -moth history of dysphgi, excessive droolig, exercise itolerce, d geerlized muscle trophy. Distict lbelig of the srcolemm (rrow) ws foud fter icubtio with the immuoreget Stphylococcl protei A horserdish peroxidse idictive of boud tibodies. Br 0 m.

9 Cie Iflmmtory Myopthies Tble. Electromyogrphic (EMG) d motor erve coductio velocity (MNCV) studies i dogs with iflmmtory myopthy. gim MMM OS DM EOM UN Totl Number i study 0 00 EMG Norml FP/PS CRD MNCV Norml Slight decrese 0 gim, geerlized iflmmtory myopthy; MMM, mstictory myositis; OS, overlp sydrome; DM, dermtomyositislike sydrome; EOM, extroculr myositis; UN, uclssified myositis; FP, fibrilltio potetils; PS, positive shrp potetils; CRD, complex repetitive dischrges. with iflmmtory myopthy from N cium (.%) hd eosiophils i muscle biopsy specimes. Oly 0 of (.%) dogs with egtive serologic titers for either T godii or N cium hd eosiophils i muscle biopsy specimes. Eosiophils were foud i of (0%) muscle biopsy specimes from dogs tht hd ot bee tested for either T godii or N cium. Distributio of cellulr ifiltrtes usully ws multifocl d most commoly edomysil with ivsio of oecrotic fibers or edomysil d perivsculr. Perimysil d perifsciculr distributios were lso foud. A edomysil distributio of cellulr ifiltrtes ws most commo i dogs with PM, wheres perivsculr distributio ws most commo i dogs with MMM. Atrophic fibers most typiclly hd roud shpe d ivolved both muscle fiber types. Occsiolly, ecrotic fibers or bsophilic regeertig fibers were foud. Muscle fiber trophy ws most commoly moderte or severe. Perifsciculr trophy ws typicl oly of dogs with dermtomyositislike sydrome. A bsece of fiber trophy ws foud i dogs with gim, i dogs with MMM, d i dogs with uclssified myositis. Fibrosis ws preset i vryig degrees, hvig edomysil or perimysil distributio. Edomysil fibrosis ws most commo i dogs with gim, wheres both edomysil d perimysil fibroses were commo i dogs with MMM. Complete loss of muscle fibers with replcemet by coective tissue (ed-stge fibrosis) ws foud i dogs, d bsece of fibrosis ws foud i dogs. Perifsciculr fibrosis ws foud i ll dogs with dermtomyositislike sydrome. Serology for Ifectious Diseses Results of serologic testig for vrious ifectious diseses re summrized i Tble. Of the dogs tested for serologic evidece of exposure (reciprocl titers ) to T godii (/00,.%), (.%) were positive. Reciprocl titers gist T godii tiges rged from to,0. Serologic evidece of exposure to N cium, with reciprocl titers rgig from to,00, ws foud i Tble. Histopthologic chges i muscle biopsy specimes of 00 dogs with iflmmtory myopthy. gim MMM OS DM EOM UN Totl Number i study 0 00 Cells L, M L, M, E M Histio PC PMN Distributio EN EN, PV PE EN, PE PF MF Atrophy Noe Mild Moderte Severe Fibrosis Noe EN PE EN, PE PF Ed stge (PF) 0 gim, geerlized iflmmtory myopthy; MMM, mstictory myositis; OS, overlp sydrome; DM, dermtomyositislike sydrome; EOM, extroculr myositis; UN, uclssified myositis; L, lymphocytes; M, mcrophges; E, eosiophils; PC, plsm cells; PMN, polymorphoucler cells (eutrophils); EN, edomysil; PV, perivsculr; PE, perimysil; PF, perifsciculr; MF, multifocl. of dogs tested (.%). N cium cysts were foud i muscle biopsy specimes from dogs (.%) with serologic evidece of exposure to N cium. Oe dog ws ot tested serologiclly for N cium, but N cium cysts were idetified o muscle biopsy specime evlutio. Thirty-four d dogs tested egtive for serologic evidece of exposure to T godii d N cium, respectively. Forty-eight dogs with ssumed PM were ot tested for serologic evidece of either T godii or N cium ifectio. Serologic evidece of exposure lso ws foud to B burgdorferi (/,.%), Ehrlichi cis (/,.%), d R rickettsii (/,.%). Reciprocl titers gist tiges to B burgdorferi rged from to. Both reciprocl titers gist tiges to E cis were 0, d reciprocl titers gist tiges to R rickettsii rged from 0 to. H mericum cysts were foud i the muscle biopsy specime of dog. Oe dog lso ws positive for circultig tibodies to Dirofilri immitis o routie serologic testig. Negtive serologic tests for ifectious gets icluded those for Brucell cis, Bbesi cis, Leptospir cicol, Leptospir ictohemorrhgic, Coccid-

10 Evs et l Tble. Serologicl testig for ifectious etiologies i 00 dogs with iflmmtory myopthy. Prmeter gim MMM OS DM EOM UN Totl Number i study 0 00 Toxoplsm godii Negtive Positive Neospor cium Negtive Positive Borreli burgdorferi Negtive Positive Ehrlichi cis Negtive Positive Rickettsi rickettsii Negtive Positive Heptozoo cis (positive) Dirofilri immitis (positive) Brucell cis (egtive) Bbesi cis (egtive) Leptospirosis c (egtive) Other d (egtive) 0 b gim, geerlized iflmmtory myopthy; MMM, mstictory myositis; OS, overlp sydrome; DM, dermtomyositislike sydrome; EOM, extroculr myositis; UN, uclssified myositis. Eleve dogs hd serologic evidece of exposure to N cium. Aother dog hd N cium cysts idetified o muscle biopsy evlutio but ws ot serologiclly tested for tibodies to N cium. b H mericum cysts were foud o muscle biopsy evlutio. c Serologic testig for exposure to leptospirl orgisms ws directed gist both Leptospir cicol d Leptospir ictohemorrhgic. d Other serologic tests for evidece of ifectious diseses icluded Coccidiodes immitis (), Cryptococcus eoforms (), Blstomyces dermtiditis (), d Histoplsm cpsultum (). ioides immitis, Cryptococcus eoforms, Blstomycoses dermtididis, d Histoplsm cpsultum. Specific Therpies The most commo therpies used for the tretmet of iflmmtory myopthy were either predisoe d loe (), combitio of predisoe d tibiotic (0), or tibiotic loe (). The tibiotics used loe to tret iflmmtory myopthy icluded clidmyci e (), cephlexi f (), doxycyclie g (), d erofloxci h (). Three dogs were treted with combitio of clidmyci d doxycyclie, d other dog ws treted with combitio of getmici i d cephlexi. Oe dog ws treted with combitio of trimethoprim-sulfdizie, j clidmyci, pyrimethmie, k d decolute. l Combied predisoe d clidmyci ws dmiistered to dogs, d predisoe d zthioprie m were used together i dogs. Two dogs lso were treted with coezyme Q0 d L- critie o i dditio to predisoe d zthioprie. Other ifrequetly used drugs icluded pyridostigmie p loe, L- thyroxie q loe, or L-thyroxie i dditio to specific therpies for iflmmtory myopthy. The ower of dog declied trditiol medicl tretmet i fvor of differet homeopthic therpies. Oe dog died d dog ws euthized immeditely fter the muscle biopsy. The medicl therpy employed ws ot reported i dogs (%). Outcome Summry iformtio regrdig the outcomes of dogs with vrious forms of iflmmtory myopthy is show i Tble. Noe of the dogs with MMM died or were euthized. All recovered, lthough my required log-term medictio to prevet relpse. Of dogs with PM, died or were euthized, were improved but still required medictio, d 0 were reportedly orml d off medictio. Of dogs with ifectious myositis, dogs digosed with T godii d dog ech with N cium, E cis, d B burgdorferi were reported orml t the completio of medicl therpy. Six dogs with N cium; dogs with T godii; d dog ech with H mericum, R rickettsii, d B burgdorferi were reported improved but still o medictio. Oe dog with B burgdorferi d dog with T godii died, d dog ech with N cium, E cis, R rickettsii, d B burgdorferi were euthized. Seve dogs with T godii, dogs with N cium, d dogs with B burgdorferi were lost to follow-up. Of the dogs digosed with gim by T godii or N cium, d dogs, respectively, were reported improved to orml fter course of cli-

11 Cie Iflmmtory Myopthies Iflmmtory Myopthy gim Immue-medited Ifectious Preeoplstic MMM OS DM EOM UN Outcome of 00 dogs with iflmmtory my- Tble. opthy. Recovered Norml b 0 Died Euthized LTF Totl Totl gim, geerlized iflmmtory myopthy; MMM, mstictory myositis; OS, overlp sydrome; DM, dermtomyositislike sydrome; EOM, extroculr myositis; UN, uclssified myositis; LTF, lost to follow-up. Recovery ws defied whe dogs hd show cliicl improvemet but were still o medicl therpy for cliicl sigs of iflmmtory myopthy t the time of the report. b Norml ws defied s resolutio of cliicl sigs with the dog off medictios for tretmet of the iflmmtory myopthy. dmyci loe. Oe dog with borreliosis ws reported improved fter tretmet with doxycyclie loe. All dogs digosed with preeoplstic PM either died or were euthized. Of the dogs with dermtomyositislike sydrome, ws reported recovered d off medictios, ws reported stble while still o medictios, d ws lost to follow-up. Of the dogs with EOM, ws reported stble while still o medictios d ws lost to follow-up. Of the dogs with uclssified myopthy, were reported recovered d off medictios, ws reported stble while still o medictios, were euthized, d were lost to follow-up. Discussio Results of this study suggest broder spectrum of cie iflmmtory myopthies th previously described. Although severl breeds of dogs were ffected, Boxers d Newfoudlds were overrepreseted. Of Boxers iitilly digosed with gim, were digosed with lymphom severl moths lter. A plstic roud cell tumor d plsmcytom lso were lter digosed i other Boxers fter the oset of gim. At the time of digosis of the iflmmtory myopthy, o evidece of eoplstic cells ws foud i the biopsy sectios, wheres t the time of digosis of eoplsi, eoplstic cells were observed i the muscle biopsies. This fidig suggests tht iflmmtory myopthy might be preeoplstic sydrome i this breed. Neoplsi lso developed withi moths of iitil digosis i other breeds of dogs. Breed-ssocited PM ws idetified i the Newfoudld dogs. Ulike the other breeds, these dogs hd circultig utotibodies gist uidetified srcolemml tige supportig humorl immue compoet. With the exceptio of few spordic cses of iflmmtory myopthy i other breeds, Newfoudlds with PM teded to be ffected t youger ge compred with other breeds. Megesophgus d dysphgi lso were more commo i Newfoudlds compred with other dogs with iflmmtory myopthy. I geerl, the cliicl sigs of focl or geerlized forms of iflmmtory myopthies i the dogs of this study were cosistet with previous descriptios. Iterestigly, lthough muscle pi ws reported previously i dogs with iflmmtory myopthy, mylgi ws rrely reported i this lrge group of dogs. It is possible tht mylgi ws preset but ot detected, but the bsece of mylgi is cosistet fidig i hums with PM., gims lso were preset i greter umber th MMM. This fidig might ot be ccurte reflectio of the frequecy of these disorders becuse the serologic test for mstictory myositis ow is vilble for the digosis of MMM d some cliicis prefer to do this test loe without muscle biopsy. A previously urecogized overlp sydrome ws idetified i dogs, i which cliicl sigs of both MMM d PM were preset. All dogs hd utotibodies gist mstictory muscle type M fibers. I hums, overlp sydrome is defied s severe geerlized form of iflmmtory myopthy i which more th immue-medited sydrome is preset. This disorder is chrcterized by the presece of PM or dermtomyositis cocurret with other disorders of coective tissue such s scleroderm, systemic lupus erythemtosus, d Sjögre s sydrome. For the purpose of this report, overlp sydrome is defied s the combied digosis of PM d MMM. Dogs with overlp sydrome hd cellulr ifiltrtio i both limb d mstictory muscles chrcteristic of PM d were positive for circultig tibodies gist mstictory muscle type M fibers chrcteristic of MMM. Of the dogs with overlp sydrome, died, ws euthized, d ws lost to follow-up. These fidigs suggest more severe, geerlized immue-medited disorder i dogs with overlp sydrome, s described i hums. Recetly, overlp sydrome of MMM d mysthei grvis hs bee idetified (Shelto, upublished observtios). O the bsis of cliicl d electrophysiologic exmitio loe, it would be difficult to differetite the vrious iflmmtory myopthies. Combitios of digostic tests described i this study could be useful i rechig digosis. Cliiclly, mstictory muscle trophy d ibility to ope the jw were most commo i MMM but lso were foud i severl cses of gim with subcliicl limb muscle ivolvemet. Mstictory muscle trophy might be sequel of chroic corticosteroid therpy regrdless of the uderlyig disese process. Muscle biopsy d serum tibody titers gist mstictory muscle type M fibers should differetite MMM d PM, but these tibodies c be preset i overlp sydrome. Similrly, etiology for the iflmmtory myopthies would be difficult to determie from histopthology loe. A edomysil d perivsculr distributio of cellulr ifiltrtes d edomysil d perimysil fibrosis were most commo i dogs with MMM, wheres edomysil distributio of cellulr ifiltrtes d edomysil fibrosis were most commo to gim sydromes. Although lymphocytes d mcrophges were commo to ll of the iflmmtory myopthies, the presece of eosiophils suggested ifectious myositis. Eosiophils lso were foud i pproxi-

12 0 Evs et l mtely 0% of mstictory muscle biopsies from dogs with MMM. Prsitic cysts i muscle biopsies lso would support ifectious disorder. I recet immuohistochemicl study evlutig pheotypes of cellulr ifiltrtes i dogs with iflmmtory myopthy, it ws similrly difficult to clssify the gims o the bsis of histopthology loe. I tht study, popultios of dedritic cells i dogs with ifectious myositis were mrkedly icresed over T cells compred with tht observed i dogs with PM, but iflmmtory myopthies resultig from immue-medited d preeoplstic disorders could ot be differetited. Both MMM d EOM c preset cliiclly with exophthlmos from iflmmtio of the temporlis d pterygoid muscles i MMM d the extroculr muscles i EOM., The M tibody titer should differetite these disorders. Typicl ski lesios i dogs with dermtomyositis should differetite this disorder from other gims. I dditio, the distributio of the cellulr ifiltrtio, muscle fiber trophy, d fibrosis i dogs with dermtomyositislike sydrome ws perifsciculr. The presece of circultig tibodies to ifectious gets such s T godii or N cium is suggestive of ifectious myositis, but defiitive digosis c oly be mde by idetifictio of orgisms i muscle biopsy specimes. Although icresed mcrophge or histiocytic cell popultio might be idictive of ifectious etiology, miiml histologic differeces c be idetified i dogs with PM d i those with cocurret tibodies gist ifectious gets; cosequetly, pproprite timicrobil therpy is wrrted. The cliicl respose of some of these dogs to timicrobil therpy loe supports this recommedtio. If the ssocitio betwee eosiophils i the muscle biopsy specimes d ifectious disorders is ccurte, ifectious myositis, especilly from T godii d N cium, could be more commo th previously believed. Further ivestigtio of this ssocitio is wrrted, d we recommed serologiclly testig ll dogs digosed with gim for both T godii d N cium s prt of the miimum dtbse. The pthologic chges i dogs did ot fll ito the specific clssifictio groups. Dogs i this ctegory hd geerlized cliicl sigs d were egtive for M tibodies d for tibodies gist ifectious gets. The histologic chrcteriztio ws tht of collge vsculr disorders, grulomtous myositis, d srcoidlike myopthy, s described i hums. Further ivestigtios re eeded to more ccurtely clssify these disorders. Over the log term, with pproprite therpy, dogs with MMM teded to improve, s did dogs with gim, lthough residul muscle trophy, prticulrly i the mstictory muscles, or reduced muscle fuctio remied i some dogs. Dogs with iflmmtory myopthy becuse of presumed ifectious etiology lso improved, provided ccurte digosis ws mde d pproprite timicrobil therpy employed. Although follow-up ws ot vilble o lrge umber of dogs, preeoplstic myositis geerlly crried poor progosis. O the bsis of the results of this study, more th digostic modlity is required to cofirm etiology for iflmmtory myopthy. Muscle biopsy is criticl for the idetifictio of iflmmtory myopthies i geerl d c determie etiology i some cses. A combitio of cliicl sigs, serologic testig for utotibodies d ifectious gets, d immuopheotypig of cellulr ifiltrtes i muscle biopsy specimes might be required to determie specific etiology. With the exceptio of the preeoplstic sydromes, most iflmmtory myopthies re tretble if digosed erly d treted ppropritely. Foototes M tibody titer, Comprtive Neuromusculr Lbortory, Uiversity of Clifori, S Diego, L Joll, CA b Acetylcholie receptor tibody titer, Comprtive Neuromusculr Lbortory, Uiversity of Clifori, S Diego, L Joll, CA c Edrophoium, Tesilo, Aquest, Liberty Corer, NJ d Predisoe, Deltsoe, Upjoh Compy, Klmzoo, MI e Clidmyci, Atirobe, Upjoh Compy, Klmzoo, MI f Cephlexi, Keflex, Dist, Idipolis, IN g Doxycyclie, Vibrmyci, Pfizer, Ic, New York, NY h Erofloxci, Bytril, Miles, Ic, Shwee, KS i Getmici, Getoci, Scherig-Plough Aiml Helth, Keilworth, NJ j Trimethoprim/Sulfdizie, Tribrisse, Mllickrodt Veteriry, Ic, Mudelei, IL k Pyrimethmie, Drprim, Burroughs Wellcome, Reserch Trigle Prk, NC l Decoquite, Deccox, Alphrm Ic, Fort Lee, NJ m Azthiprie, Imur, Burroughs Wellcome, Reserch Trigle Prk, NC Coezyme Q0, CoMl Q0, Nutrmx Lbortories, Edgewood, MD o Levocrtie, Critor, Sigm Tu Phrmceuticls, Ic, Githersburg, MD p Pyridostigmie, Mestio, Roche Merieux, Ic, Athes, GA q Levothyroxie, Soloxie, Diels Phrmceuticls, Ic, St. Petersburg, FL Ackowledgmets The uthors thk Norm Prdes for excellet techicl ssistce. Fudig for this study ws provided by grt from the Musculr Dystrophy Associtio (GDS) Refereces. Egel A, Hohfeld R, Bker BQ. The polymyositis d dermtomyositis sydromes. I: Egel A, Frzii-Armstrog C, eds. Myology, d ed. New York, NY: McGrw-Hill; :.. Koregy J, Gorgcz E, Dwe D, et l. Polymyositis i dogs. J Am Vet Med Assoc 0;:.. Podell M. Iflmmtory myopthies. I: Shelto GD, ed. Neuromusculr Diseses. Veteriry Cliics of North Americ. Smll Aiml Prctice. Phildelphi, PA: WB Suders; 00:.. Brber JS, Trees AJ. Cliicl spects of cses of eosporosis i dogs. Vet Rec ;:.. Berger SL, Plmer RH, Hodges CC, Hodges DG. Neurologic mifesttios of tryposomisis i dog. J Vet Med Assoc ; :.. Brud KG, Blgbum B, Toivio-Kiuc M, et l. Toxoplsm polymyositis polyeuropthy A ew cliicl vrit i mture dogs. J Am Aim Hosp Assoc ;:.. Crig TM, Joes L, Nordgre R. Digosis of Heptozoo cis by muscle biopsy. J Am Aim Hosp Assoc ;0:0 0.

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