masticatory muscle myositis - golden retriever

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I magine what it would be like if your Golden Retriever could not open his mouth to eat and drink. That is often what happens with an autoimmune disorder called masticatory muscle myositis (MMM) that affects the jaw muscles, causing pain and dysfunction. Swollen, painful masticatory (chewing) muscles and an inability to open the mouth (trismus) are clinical signs of the disorder. “These dogs are not able to pick up a ball or eat with- out experiencing severe pain,” says Brian E. Greenfield, D.V.M., who prac- tices at Animal Clinic Northview in North Ridgeville, Ohio. “In the early stages of the disease, the muscles that are used for eating and chewing appear swollen. As the disease progresses, these muscles begin to atrophy, or waste away. Sometimes the eyes appear sunken, or, less commonly, they seem to protrude.” Although MMM can occur in any breed, it occurs more commonly in large breeds, such as Golden Retrievers, Doberman Pinschers, German Shepherd Dogs, and Labrador Retrievers. Young Cavalier King Charles Spaniels may be severely affected and are believed to be genetically predisposed to devel- oping MMM. Although the disorder does not occur on a widespread basis in Golden Retrievers, anecdotal data suggest that the incidence may be increasing. Thus, whenever a Golden is suddenly unable to open his mouth, experts recommend immediate vet- erinary care to determine the cause. The condition occurs in males and females, with an average age of onset of 3 years, though puppies as young as 4 months have been affected. Fortunately, if MMM is diagnosed early, dogs can be treated to increase the likelihood of a full recovery. Research of this disease at the University of California- San Diego led to the development of a blood test in 2004 that detects the presence of 2M antibodies and accu- rately identifies affected dogs. Pathologist Diane Shelton, D.V.M., Ph.D., DACVIM, and her team at the Comparative Neuromuscular Laboratory identified type 2M fibers in the mas- ticatory muscle group and showed that antibodies against type 2M fibers are involved in the pathogenesis of MMM. They found that type 2M muscle fibers are not present in any other muscle group and antibodies against this fiber type are not involved in any other muscle disease. 1 “Masticatory muscle myositis is an inflammatory myopathy,” Shelton explains. “It is a unique myopathy, or muscle disease, in which dogs com- monly have jaw pain and inability to open the jaw. The autoimmune process in this disease involves circulating antibodies that specifically target the masticatory muscles. We still don’t know what causes the autoantibodies to form or why they are directed specifically against the type 2M fibers.” One theory is that antibodies or T-cells generated in response to an infectious agent subsequently cross- react with self-antigens. Antibodies directed against these bacterial anti- gens potentially could cross-react with the 2M fibers. In humans, autoantibodies directed at Streptococcus pyogenes have been shown to attack cardiac and skeletal muscle. Pericarditis and rheumatoid arthritis are examples of diseases in which autoantibodies are directed at specific myofibers. 1 Rhonda Hovan, research facilitator for the GRCA and a member of the club’s Health & Genetics Committee, says, “The genetic components of autoimmune diseases are very complex. Although a great deal of research has been done to identify the causes of human autoimmune diseases, much less research has been done in dogs. Still, the same overall principles of autoimmune disease apply to dogs. Genes play a role in increasing sus- ceptibility to autoimmune diseases, but environmental triggers initiate the onset of clinical signs. “In dogs that are predisposed to autoimmune reactions, suspected triggers include viral and bacterial exposures, possibly vaccinations, hormones, stress, allergens, medica- tions, and environmental toxins. Most of the time, it is impossible to know with certainty what triggers the onset of an autoimmune disease.” Shelton agrees that MMM is not purely a genetic disease. “Hormonal, environmental and other unknown factors come into play,” she says. The genes responsible for a dog’s suscepti- bility to autoimmune diseases are part of the major histocompatibility complex. “Goldens seem susceptible to many autoimmune muscle diseases, including not only MMM but also polymyositis, extra ocular myositis and myasthenia gravis,” says Shelton. “Perhaps the most common autoimmune disease in Goldens and many other breeds is autoimmune thyroiditis, the underlying cause of most canine hypothyroidism.” Determining an Accurate Diagnosis Bill Page of Wildwood, Mo., recalls experiencing MMM with his first Golden Retriever many years ago. “’Buddy’ was diagnosed when he was about 8 years old,” Page says. “It began as soreness when he chewed, so we thought perhaps he had a bad tooth. The veterinarian examined him and diagnosed MMM.” The veterinarian started Buddy right away on prednisone and referred Page to a specialist, who performed a muscle biopsy that confirmed the diagnosis. (Note: This was before the 2M antibody blood test was available.) The pred- nisone was effective. One year later, the signs of MMM recurred, and Buddy again began prednisone therapy, which effectively managed the condition. “The quick diagnosis by our vet- erinarian in the beginning made all the difference in Buddy’s outcome,” Page says. An accurate diagnosis is important in treating dogs with MMM. Early detection and aggressive immunosuppressive Early Diagnosis of Masticatory Muscle Myositis Is Needed for Treatment Success Continued on page 2 Golden Retriever Volume 12 Winter 2014 The 2M Antibody Blood Test M asticatory muscle myositis is an autoimmune disorder in which antibodies attack the 2M fibers in the masticatory (chewing) muscle group. A blood test was developed in 2004 by researchers at the University of California-San Diego to confirm the circulating antibodies that attack 2M fibers. The test is available to veterinari- ans through the Comparative Neuromuscular Laboratory at the University of California at San Diego. For information, visit http://medicine. ucsd.edu/vet_neuromuscular.

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Page 1: Masticatory Muscle Myositis - Golden Retriever

Imagine what it would be like if yourGolden Retriever could not open hismouth to eat and drink. That is often

what happens with an autoimmunedisorder called masticatory musclemyositis (MMM) that affects the jawmuscles, causing pain and dysfunction. Swollen, painful masticatory

(chewing) muscles and an inability toopen the mouth (trismus) are clinicalsigns of the disorder. “These dogs arenot able to pick up a ball or eat with-out experiencing severe pain,” saysBrian E. Greenfield, D.V.M., who prac-tices at Animal Clinic Northview inNorth Ridgeville, Ohio. “In the earlystages of the disease, the muscles thatare used for eating and chewing appearswollen. As the disease progresses,these muscles begin to atrophy, orwaste away. Sometimes the eyesappear sunken, or, less commonly,they seem to protrude.”Although MMM can occur in any

breed, it occurs more commonly inlarge breeds, such as Golden Retrievers,Doberman Pinschers, German ShepherdDogs, and Labrador Retrievers. YoungCavalier King Charles Spaniels may beseverely affected and are believed tobe genetically predisposed to devel-oping MMM. Although the disorderdoes not occur on a widespread basisin Golden Retrievers, anecdotal datasuggest that the incidence may beincreasing. Thus, whenever a Goldenis suddenly unable to open his mouth,experts recommend immediate vet-erinary care to determine the cause. The condition occurs in males and

females, with an average age of onsetof 3 years, though puppies as young as4 months have been affected. Fortunately,if MMM is diagnosed early, dogs canbe treated to increase the likelihoodof a full recovery. Research of thisdisease at the University of California-San Diego led to the development ofa blood test in 2004 that detects thepresence of 2M antibodies and accu-rately identifies affected dogs. Pathologist Diane Shelton, D.V.M.,

Ph.D., DACVIM, and her team at theComparative Neuromuscular Laboratoryidentified type 2M fibers in the mas-ticatory muscle group and showed thatantibodies against type 2M fibers areinvolved in the pathogenesis of MMM.They found that type 2M muscle fibers

are not present in any other musclegroup and antibodies against thisfiber type are not involved in anyother muscle disease.1

“Masticatory muscle myositis isan inflammatory myopathy,” Sheltonexplains. “It is a unique myopathy, ormuscle disease, in which dogs com-monly have jaw pain and inability toopen the jaw. The autoimmune processin this disease involves circulatingantibodies that specifically target the

masticatory muscles. We still don’tknow what causes the autoantibodiesto form or why they are directedspecifically against the type 2M fibers.”One theory is that antibodies or

T-cells generated in response to aninfectious agent subsequently cross-react with self-antigens. Antibodiesdirected against these bacterial anti-gens potentially could cross-react withthe 2M fibers. In humans, autoantibodiesdirected at Streptococcus pyogeneshave been shown to attack cardiacand skeletal muscle. Pericarditis andrheumatoid arthritis are examples ofdiseases in which autoantibodies aredirected at specific myofibers.1

Rhonda Hovan, research facilitatorfor the GRCA and a member of theclub’s Health & Genetics Committee,says, “The genetic components ofautoimmune diseases are very complex.Although a great deal of research hasbeen done to identify the causes ofhuman autoimmune diseases, muchless research has been done in dogs.Still, the same overall principles of

autoimmune disease apply to dogs.Genes play a role in increasing sus-ceptibility to autoimmune diseases,but environmental triggers initiatethe onset of clinical signs. “In dogs that are predisposed to

autoimmune reactions, suspectedtriggers include viral and bacterialexposures, possibly vaccinations,hormones, stress, allergens, medica-tions, and environmental toxins. Mostof the time, it is impossible to knowwith certainty what triggers theonset of an autoimmune disease.”Shelton agrees that MMM is not

purely a genetic disease. “Hormonal,environmental and other unknownfactors come into play,” she says. Thegenes responsible for a dog’s suscepti-bility to autoimmune diseases are partof the major histocompatibility complex. “Goldens seem susceptible to many

autoimmune muscle diseases, includingnot only MMM but also polymyositis,extra ocular myositis and myastheniagravis,” says Shelton. “Perhaps the mostcommon autoimmune disease in Goldensand many other breeds is autoimmunethyroiditis, the underlying cause ofmost canine hypothyroidism.”

Determining an Accurate DiagnosisBill Page of Wildwood, Mo., recalls

experiencing MMM with his first GoldenRetriever many years ago. “’Buddy’was diagnosed when he was about 8 years old,” Page says. “It began assoreness when he chewed, so wethought perhaps he had a bad tooth.The veterinarian examined him anddiagnosed MMM.”The veterinarian started Buddy right

away on prednisone and referred Pageto a specialist, who performed a musclebiopsy that confirmed the diagnosis.(Note: This was before the 2M antibodyblood test was available.) The pred-nisone was effective. One year later,the signs of MMM recurred, and Buddyagain began prednisone therapy, whicheffectively managed the condition.“The quick diagnosis by our vet-

erinarian in the beginning made allthe difference in Buddy’s outcome,”Page says.An accurate diagnosis is important in

treating dogs with MMM. Early detectionand aggressive immunosuppressive

Early Diagnosis of Masticatory Muscle Myositis Is Needed for Treatment Success

Continued on page 2

Golden RetrieverVolume 12 ■ Winter 2014

The 2M Antibody Blood Test

Masticatory muscle myositis isan autoimmune disorder in

which antibodies attack the 2Mfibers in the masticatory (chewing)muscle group. A blood test wasdeveloped in 2004 by researchersat the University of California-SanDiego to confirm the circulatingantibodies that attack 2M fibers.The test is available to veterinari-ans through the ComparativeNeuromuscular Laboratory at theUniversity of California at San Diego.For information, visit http://medicine.ucsd.edu/vet_neuromuscular.

Page 2: Masticatory Muscle Myositis - Golden Retriever

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therapy can help reduce myofiber lossand muscle fibrosis, which can leadto irreversible jaw dysfunction andsevere muscle atrophy.Complete physical and neurological

examinations are necessary to determinethat the clinical signs are restricted tothe jaw muscles. The most definitiveconfirmation of MMM is the 2M anti-body test, which detects the antibodiesthat attack and destroy the 2M musclefibers. A blood chemistry profile deter-mines the creatine kinase (CK) level,which may be mildly elevated duringthe acute phase but becomes normalas the disease progresses. Although ablood test may produce a normal CKlevel, it does not rule out acute MMM.“Clinical signs compatible with MMM

and positive results from a 2M anti-

body test confirm the diagnosis,” saysShelton. “False negatives are possibleif a dog has been given immunosup-pressive dosages of corticosteroids forseven to 10 days before testing or isin the end stage of the disease withsevere loss of myofibers and fibrosis.”A veterinarian also may use radio -

graphs to evaluate the temporoman -dibular (TM) joint and advanced imagingtechniques to help diagnose MMM.A muscle biopsy is useful to demon-strate the inflammation and determinethe severity of muscle fiber loss andthe degree of fibrosis, which may helpto predict a dog’s long-term prognosisand chance for successful therapy.Dogs in the acute phase of MMM

have swollen, painful jaw muscles andtrismus, or the inability to open thejaw. Clinical signs vary in severity andrate of onset. Ocular signs occur in44 percent of dogs and, if severe, canresult in stretching of the optic nerveand subsequent blindness.1 The condi-tion often progresses to the chronicphase, involving muscle atrophy withor without trismus. In some cases,only progressive atrophy of the mas-ticatory muscles is found and anacute phase may not be identified.“Unfortunately, many owners do

not recognize a problem until thechronic phase,” Shelton says. “Dogsgenerally show no other neurologicalor physical abnormalities, which may

help veterinarians differentiate thisdisease from other causes of trismus.” Masticatory muscle myositis is not

the only cause of a dog’s inability toopen the jaw. In MMM, the inabilityto open the jaw under anesthesia isa typical finding. However, this alsocan occur following trauma to the TMjoint or chronic arthritic changes in theTM joints that could restrict movement.Infrequent causes of restricted jawmobility include tetanus, musculardystrophy or other muscle diseases,and even a foreign body in the mouth.In these cases, the 2M antibody testis negative.

Treatment & Breeding RecommendationsAs with Page’s Golden Retriever

Buddy, an accurate diagnosis andprompt treatment are vital to help adog regain the ability to open his mouthwithout pain. Corticosteroids, partic-ularly prednisone, are the cornerstoneof therapy, Shelton says. During theacute phase, corticosteroids help toachieve aggressive immunosuppression.“Immunosuppressive dosages of

prednisone should be continued untila dog has maximum jaw function andhis CK levels are normal,” says Shelton.“At that time, the dosage can betapered to the lowest every-other-daydosage that prevents clinical signs.Once the lowest alternate dosage isreached that keeps the dog free ofclinical signs, the alternate-day therapyshould be continued for at least fourto six months. In most cases, this lowalternate-day dosage should not resultin significant side effects. Many dogsrequire a maintenance dosage through-out their lifetime, though others caneventually discontinue therapy.”Side effects from prednisone include

polyuria, or excessive urination; poly -dipsia, or excessive thirst; and poly -phagia, or excessive appetite. Otherimmunosuppressive drugs, such asazathioprine, can be prescribed if adog cannot tolerate prednisone.Dogs that do not receive proper

treatment are likely to progress tothe chronic phase. “A common prob-lem is dogs receiving an inadequatedosage of corticosteroids for tooshort of time,” Shelton says. “MMMgenerally responds initially to therapy,but relapses occur quickly if treatmentis discontinued prematurely.”“If the disease is diagnosed early

and a dog is treated appropriately,the prognosis is good for dogs withMMM,” Greenfield says. “In thesecases, dogs can usually regain normaljaw mobility and function. If the diseasehas progressed for a longer periodwithout treatment, the amount ofscar tissue formation in the musclescan cause permanent problems.”The prognosis for an individual dog

is determined by the degree of fibro-sis and how well the dog responds tocorticosteroid treatment. Dogs thatreceive aggressive treatment duringthe acute phase generally have a goodoutcome. Because corticosteroids cancause muscle atrophy, progressive

atrophy may not necessarily indicatea worsening disease state. Dogs that relapse may be harder to

treat during the subsequent courseof treatment, Shelton says. Those thatare treated in the chronic phase of thedisease have a more uncertain prognosisthough they can do well if they do notexperience persistent jaw dysfunction.“It is important that owners realize

that though jaw function should improveif treated in the chronic phase, theremay be residual fibrosis and muscleatrophy that could be irreversible,”explains Shelton. Regarding breeding recommendations,

the Golden Retriever Club of Americadoes not consider MMM to be a high-priority disease to target for reduction.“This is due to the genetic and environ-mental complexities, the low incidenceof the disease, the overall good out-come with appropriate therapy, andimportantly, the concern for main-taining as much genetic diversity inthe breed as possible,” Hovan says.“Instead, we suggest that breeders

include MMM along with other auto -immune diseases, such as hypothyroidism,myasthenia gravis and immune-mediatedhemolytic anemia, as one factor whenthey evaluate the overall pros and consof each dog for breeding,” she says. “A dog with a parent, littermate or

offspring that has any autoimmunedisease is at slightly increased risk ofalso having an autoimmune disease— but not necessarily the same disease,”Hovan says. “More important, themajority of dogs with an affectedfirst-degree relative may never beaffected themselves.”A recommended breeding strategy

if a dog has a close relative with anautoimmune disease is to select amate that does not have a first-degreerelative with an autoimmune diseaseand to keep the coefficient of inbreedinglow. “This helps to reduce the likelihoodof both parents having the same MHCgenes, which is important becausediversity within MHC generally reducesthe risk of autoimmune diseases,”Hovan explains. The good news is that breeders

can use these breeding principles tohelp reduce the risk of autoimmunediseases in their puppies withoutunnecessarily reducing genetic diver-sity in the breed. Fortunately, withproper diagnosis and treatment,Golden Retrievers that develop MMMcan live happy, normal lives. ■

1 Melmed C, Shelton GD, Bergman R, Barton C.Masticatory Muscle Myositis: Pathogenesis,Diagnosis and Treatment. Compendium.2004:590-605.

Masticatory Muscle Myositis continued from page 1

Purina appreciates the support of theGolden Retriever Club of Americaand particularly Rhonda Hovan,the GRCA research facilitator, inhelping to identify topics for thePurina Pro Club Golden RetrieverUpdate newsletter.

Recognizing Signs of MMM

Owners who recognize thesesigns of masticatory muscle

myositis (MMM) in their dogs shouldpromptly seek veterinary care. Thesooner a dog is properly diagnosedand begins treatment, the greaterthe chance of recovery. • Inability to open the jaw (trismus)• Jaw pain • Swelling or atrophy of the jawmuscles

• Difficulty eating and drinking • Reluctance to play with toys• Sunken or protruding eyes

Page 3: Masticatory Muscle Myositis - Golden Retriever

AWire Fox Terrier and a Portu -guese Water Dog have beenvying for the top spot in the

Pro Plan Champions Cup Awardstandings all year long. After flip-flopping in the point totals, GCHAfterAll Painting The Sky (“Sky”), a WireFox Terrier, was in the lead throughNov. 30 with 368 points. GCH ClaircreekImpression De Matisse (“Matisse”), aPortuguese Water Dog, was in secondplace with 298 points.

The No. 1 dog in the country, Sky,a 5-year-old female, was bred by A.J.Pertuit Jr. of Central, S.C., and BettySeaton of Scandia, Minn. Sky is co-owned by Victor Malzoni Jr. of SãoPaulo, Brazil, and Torie Steele ofMalibu, Calif., with Mary and ScottOlund of San Rafael, Calif., andDiane Ryan of Laguna Niguel, Calif.Matisse, a 2-year-old male, has

had a whirlwind career, says ownerMilan Lint of New York, who co-ownsthe current No. 2 dog in the countrywith Peggy Helming of Flemington,N.J., and breeder Donna Gottdenkerof Arthur, Ontario, Canada. The win-ningest Portuguese Water Dog of alltime, Matisse has garnered 94 Bestsin Show, 20 Reserve Bests in Showand 140 Working Group Firsts in 2013.The Pro Plan Champions Cup

award program is based on pointstabulated from Bests in Show andGroup placements at more than 200Purina-sponsored all-breed dog showsin 2013. The winner will receive a$10,000 cash prize, an original oil

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to the top-placing dogs as follows:• Second place, $5.000• Third place, $2,500• Fourth place, $1,250To view the point standings and a

list of qualifying dog shows, pleasevisit the Purina Pro Club website atpurinaproclub.com. ■

‘Sky’ Inches Ahead of ‘Matisse’ in Pro Plan Champions Cup Award Standings

Purina-Sponsored Dog Shows* January to March 2014

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* This table lists some, but not all, upcoming Purina-sponsored dog shows.

Coming in January 2014, thePurina Pro Plan SPORT perfor-mance nutrition line is intro-

ducing two nutritional supplementbars to help optimize performancenutrition before and after exercise. TheSPORT PRiME Bar is a pre-exerciseprotein-rich supplement designed to

keep muscles strong during exercise,and the SPORT ReFUEL Bar is a post-exercise supplement that helps replenishmuscle energy stores and promotesmuscle rebuilding. The PRiME andReFUEL Bars are available exclusivelyat pet specialty and farm supply stores.To learn more, visit proplan.com or

call 800-PRO-PLAN (800-776-7526)from 7 a.m. to 7 p.m. Central TimeMonday through Friday to talk witha pet nutrition consultant. ■

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Purina Pro Club Website Gets a New Look & Is Easier to Navigate

“Sky,” a Wire Fox Terrier, is handled by profes-sional handler Gabriel Rangel of Rialto, Calif.

The Portuguese Water Dog “Matisse” is handledby professional handler Michael Scott ofChesapeake City, Md.

New Purina Pro Plan SPORT Bars Help Fuel Active Dogs

3

Page 4: Masticatory Muscle Myositis - Golden Retriever

Purina-Sponsored Sporting Events* January to March 2014

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* This table lists some, but not all, upcoming Purina-sponsored sporting events.

Purina Pro Plan SELECT Grain FreeFormula is the secret to successfor GCH Shadowlands Paws for

Applause at Tristar, says co-owner JulieMatney of Rocklane Kennels in KettleFalls, Wash. The 5-year-old bitch, called“Sydney,” captured Best of Breed forthe second consecutive year in Octoberat the Golden Retriever Club of AmericaNational Specialty in Wichita Falls, Texas.

After her dog struggled with allergiesthat caused skin and ear problems,Matney discovered the alternativesources of carbohydrates in the ProPlan SELECT Grain Free Formula helpedto reduce the dog’s sensitivities. Matney,a professional groomer, was so impressedwith the food that she now recommendsit to others based on her own success. A picky eater, Sydney had turned up

her nose at other grain-free foods, butwhen Matney started feeding Pro PlanSELECT Grain Free in June, the dogreadily ate it, she says. Sydney’s co-owner Sharmin Dominke also feedsPro Plan SELECT Grain Free when thedog is with her in Redmond, Wash.Instead of traditional carbohydrate

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Purina Pro Plan is sold exclusivelyat pet specialty and farm supply stores.For more information, visit proplan.comor to talk with a pet nutrition consul-tant, call 800-PRO-PLAN (800-776-7526) from 7 a.m. to 7 p.m. CentralTime Monday through Friday. ■

Owner Credits Golden Retriever’s Success to Pro Plan SELECT Grain Free Formula

“Sydney” is shown with judge Virginia Lyne,left, and handler Megan Honari.

Want to Reach the Editor?

Have comments about the Purina ProClub Update? Send them to us at:Purina Pro Club Update, c/o Editor,Nestlé Purina PetCare, 2T Checker -board Square, St. Louis, MO 63164or via email at today’[email protected].

PURINAProClubGolden Retriever Update

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PAIDSt. Louis, MOPermitNo. 475

1400 South Highway Dr.Fenton, MO 63026

Scan this QR code on your smartphone to visitpurinaproclub.comfor your Purina Points

Summary and detailed account activity.You alsomay call 1-877-PRO-CLUB (1-877-776-2582).