THE MYOSITIS ASSOCIATION

Treatment IssueWINTER 2004

Two perspectives onmyositis treatment

"The goal of therapy in inflammato-ry myopathies," says Dr. MarinosDalakas, "is to improve musclestrength and activities of daily liv-ing." Dalakas, Chair of TMA'sMedical Advisory Board and Chiefof Neuromuscular Diseases sectionof NINDS, NIH, notes that whenmuscle strength improves, CK lev-els drop; however, the reverse is notalways the case because immuno-suppressants can lower CK levelswithout having a positive effect onmuscle strength. This is sometimesmisinterpreted as an improvement,he says, so doctors will erroneouslyfollow the CK levels instead of themuscle weakness.

Corticosteroids To begin treatment, Dalakas prefershigh-dose prednisone at 60-80mg/day for 3 to 4 weeks followedby a tapering schedule over a 10-week period. His goal is to reach60-80 mg/day on an alternate-dayschedule at the end of the 14 weeks.If prednisone is effective and does-n't produce excessive side effects,he reduces the prednisone by 5-10mg every 3 to 4 weeks until reach-ing the lowest dose possible tomaintain stability. If, however,there are no signs of improvementby the end of the 14-week taper, heconsiders this patient unresponsiveand tapers quickly to beginimmunosuppressive therapy.

Dr. Chester Oddis suggests adivided daily dose at 60 mg/day forPM and DM patients. Once CK

What is myositis? What causes it?How do I know that's what I have?What should I use to treat it?

When you're diagnosed with anyform of myositis, the questions seemendless. At the Annual Conference,Dr. Fred Miller, Senior Investigatorand Chief, EnvironmentalAutoimmunity Group, NIEHS, at theNational Institutes of Health,explained myositis in straightforwardterms and basic concepts for thosejust learning about their conditions.

What is myositis?The general definition of myositisseems basic enough - "myo" meansmuscle and "itis" means inflammationor swelling. But there's much more toit when referring to the chronic form ofmyositis. Myositis is the general termused in dermatomyositis, polymyosi-tis and inclusion-body myositis; butin medical terms, these conditions aremore specifically referred to as idio-pathic inflammatory myopathies (IIMs),or diseases of the muscles with inflam-mation but no known cause. Breakingit down into the specific disease types,polymyositis (PM) means affectingmany muscles; dermatomyositis(DM), involving the skin; inclusion-body myositis (IBM), with inclusions- a kind of cellular hole showing upin the muscles; and juvenile myositis(JM), occurring in childhood, typical-ly at 18 years of age or younger.

Even the more homogeneousgroups of PM, DM, IBM and JMhave a number of factors that causedifferent people to show symptoms in

various ways, and it's important toknow more about each case to plan themost effective course of treatment. Thedilemma lies in the fact that differentpatients are affected in almost uniqueways, says Miller. Some symptomsdevelop slowly, others quickly; peopleexperience different levels of muscleweakness and pain; and about 30 per-cent have joint involvement, he says.Many symptoms are shared by other dis-eases, often leading doctors to other pos-sible diagnoses first.

How do you treat myositis?First, make sure the diagnosis is correct.There aren't clear-cut lines between thedifferent forms of myositis as well asother diseases: "One size doesn't fit allfor myositis," Miller says. This is stillthe art of medicine, not yet the science.Some variables to consider: how muchis disease activity or active inflamma-tion versus disease damage or scarring?What are the risks and benefits of par-ticular drugs used to block the immunesystem? In forming a treatment plan,he recommends a holistic approach,taking into account your own expecta-tions along with possible adverseeffects from treatment. "Your job is tobecome more active in your treatment,"he says.

The primary therapy remains oral orintravenous (IV) corticosteroids - pred-nisone, methylprednisolone, solume-drol. Along with this first-line treat-ment, Miller stresses the importance ofbeginning physical and occupationaltherapy, calcium and Vitamin D supple-

Myositis 101: a beginner’s guide

See Myositis 101, page 21

See Perspectives, page 3 This issue funded in part by unrestricted educational grants fromBristol-Myers Squibb, Genentech, Inc. and IDEC Pharmaceuticals.

2

Published by: TMA, Inc.THE MYOSITIS ASSOCIATION

1233 20th St., NW, Suite 402Washington, DC 20036P: 800-821-7356F: 202-466-8940Email: tma@myositis.orgWeb: www.myositis.org

Executive Director: Bob GoldbergEditors: Theresa Reynolds Curry

Kathryn SpoonerGraphic Design: Jami Latham

BOARD OF DIRECTORS

Richard Bullard III, ChairpersonEdward Grass, Vice ChairpersonEarl Klein, Vice PresidentJanet Schuler, Vice President, SecretaryLynn Chapman, TreasurerJeffrey CampbellJanice GoodellConnie KeelinAndrea MacherFrederick W. Miller, MD, PhDJay ShinnRichard StevensonSeth StopekShari Weber

MEDICAL ADVISORY BOARD

Marinos C. Dalakas, MD, ChairFrederick W. Miller, MD, PhD, Vice ChairWalter Bradley, DM, FRCP, Research ChairLisa G. Rider, MD, Nominating ChairValerie Askanas, MD, PhDRichard Barohn, MDJeffrey P. Callen, MDW. King Engel, MDRobert Griggs, MDJeanne Hicks, MDChester V. Oddis, MDLauren Pachman, MDLawrence H. Phillips II, MDPaul Plotz, MDAnn Marie Reed, MDBarbara Sonies, PhDRichard Sontheimer, MDRup Tandan, MD, FRCPVictoria P. Werth, MD

STAFF

Bob Goldberg, Executive DirectorTheresa Reynolds Curry,

Communications Manager

Jami Latham, Member Services &Operations Coordinator

Beverly Posey, Office AssistantKathryn Spooner, Communications

CoordinatorThe opinions expressed in this newsletter are not necessarily those of The Myositis Association. We do notendorse any product or treatment we report. It is our intent to keep you informed. We ask that you alwayscheck any treatment with your physician. Copyright 2004 by TMA, Inc.

Dear TMA member:

This is the second Annual Special Treatment Issue ofthe OutLook Extra. It is devoted entirely to provid-ing updates on the latest treatment and research newsas well as reports from TMA's Annual Conference,held this year in Las Vegas.

As you read through this issue, you will find a rangeof information - some for those who have recentlybeen diagnosed (Myositis 101: a beginner's guide) to

more technical reports for those better versed in the disease. Likewise, youwill find information from a wide range of researchers - those who havestudied myositis for decades as well as those who are relatively new to thefield and of another generation. The focus of the researchers also variesfrom those nearly exclusively studying only one form of myositis to thosewho are looking at the "big picture" of what environmental factors may becontributing to or causing the full range of inflammatory myopathies.

You will also find questions and comments from people like you - thosewho are living with myositis and have learned firsthand the perplexing andfrustrating aspects of this terrible disease.

TMA is trying, through its publications, online services, support groups andconferences, to provide a forum for all those involved with myositis toshare their experiences and information. We believe that through collabora-tion and information sharing, everyone will benefit - patients, family, physi-cians and researchers.

The Special Treatment Issue is another step along this path.

I hope you find it helpful and informative.

Sincerely,

Bob GoldbergExecutive Director

3

Mycophenolate motefil: up to 2 gdaily. This is a promising, well-toler-ated treatment, though it may take upto three months to notice any clinicalbenefit.

Treatments to considerFor difficult-to-treat cases, both doc-tors introduce intravenousimmunoglobulin at 2 g/kg. Dalakasproposes this over two to five divideddaily doses every five to eight weeks.For DM, Dalakas typically sees anoticeable improvement 15 to 20 daysafter the first treatment. Those withDM may need repeated therapy every6 to 12 weeks to maintain theseresults, he says. In his opinion, IVIgis best reserved as a third-line treat-ment for those who are steroid-resis-tant, though he says it is often a sec-ond-line treatment for children. Hisown experience shows that IVIg iseffective in about half of his PMpatients, but this treatment is noteffective in IBM except for thosewith swallowing problems. Oddispresents several studies on the use ofIVIg in combination with other thera-pies, showing positive results formany refractory or relapsing patients.

Treatments typically aren't asstraightforward as this, though, asthere are a number of symptoms totake into account.Hydroxychloroquine (Plaquenil) at200-400 mg per day, for example,fights the DM rash more aggressively,says Oddis. Also, topical tacrolimus(Protopic) has been shown effectivein studies to combat the skin rash.Lung problems call for stronger thera-pies, and Oddis describes one option:oral corticosteroids at 60-80 mg daily(divided) plus pulse solumedrol at 1gram per day for three consecutivedays, with the addition of an immuno-suppressive early in treatment.

Additional treatmentsAdjuncts to medicinal therapy arekey, says Dalakas. Physical therapyshould be an integral part of the treat-ment plan from the start to address

levels have normalized, usually with-in one to two months, he changes to aonce daily dose and tapers by 20 to25 percent every 3 to 4 weeks toreach 5-10 mg. The patient thenmaintains this dose until he or she hasbeen on corticosteroid therapy for onefull year. This, he says, is for an idealpatient, so there are obviously otherfactors to keep in mind - side effects,lack of response and repeated relapseswhen tapering. In some cases, otheragents are added.

Adding other agentsWhich immunosuppressant your doc-tor chooses, says Dalakas, oftendepends on your doctor's past experi-ence and personal preference. Morecommon immunosuppressive thera-pies are methotrexate, azathioprine,cyclophosphamide, cyclosporine, andmycophenolate motefil. There are nostandard dosages for treating myositis,but Drs. Dalakas and Oddis share themore commonly prescribed regimens.Your own doctors will consider yourmedical histories and symptoms todetermine the right dose for you.

Methotrexate: 7.5 mg per weekorally for three weeks, given at 2.5mg three times at 12-hour intervals,increasing the dose by 2.5 mg perweek to a 25-mg dose. Methotrexateworks faster than azathioprine(below), so it is often considered asthe first addition to first-line therapies.This medicine can be given orally,intravenously or subcutaneously.

Azathioprine: 3 mg/kg orally,though 1.5-2 mg/kg is more common.Azathioprine is well-tolerated buttakes up to six months to showwhether it's effective.

Cyclophosphamide: 0.5-1 mg/m2monthly for those with interstitiallung disease.

Cyclosporine: 150 mg twice dailyor 3-3.5 mg/kg daily, but no morethan 5 mg/kg per day.

Perspectives on treatmentcontinued from cover

muscle weakness, loss of jointmotion, and fatigue, adds Oddis. Forthose with less strength, passiverange-of-motion should begin thetherapy, changing to assisted range-of-motion then a more aggressiveprogram as strength increases.

Nutrition is also an important con-sideration - he recommends a low-carbohydrate, low-salt and high-pro-tein diet; antacids for any gastroin-testinal problems brought on by themedicines; calcium at 1 g per day;Vitamin D at 50,000 units per week;and supplements to protect bone loss.(See extensive osteoporosis section,beginning on page 10). For IBMers,he adds Co-Q10, Vitamin E and crea-tine to his treatment approach.

[Dr. Dalakas' article, "TherapeuticApproaches in Patients withInflammatory Myopathies," and Dr.Oddis' article, "IdiopathicInflammatory Myopathy:Management and Prognosis,"appeared in the December 2003 issueof TMA's electronic full-memberpublication, Update, and are included.Dr. Miller's introduction to myositiswas a 2004 Annual Conference pre-sentation.]

In this issue:Prednisone . . . . . . . . . . . . .4

Prednisone and JM . . . . . .8

Osteoporosis . . . . . . . . . .10

Dysphagia . . . . . . . . . . . .12

Overlap . . . . . . . . . . . . . .14

Anti-inflammatories . . . . .16

Diagnosing IBM . . . . . . . .18

New treatments . . . . . . . .20

Dry Skin . . . . . . . . . . . . . .22

Anti-TNF . . . . . . . . . . . . . .25

Side-effects chart . . . . . . .28

4

It's the drug everyone loves to hate,the pharmaceutical paradox of mod-ern times. Prednisone, in its manyforms, saves lives while it creates amultitude of problems. Once in thebloodstream, prednisone hitches itselfto certain proteins and enters nearlyevery cell in the body indiscriminate-ly. Once there, receptors draw it tothe nucleus where itbinds to genes, causinga variety of effects. Inthe muscle cell, itworks very well todecrease inflammation,ease pain, and restorenormal function. Inthe bone, it decreases the ability ofcells to incorporate calcium, causingosteoporosis; in fat cells, it causes theswollen ("Cushingoid") face and thecharacteristic "buffalo hump" acrossthe back of the neck. The fat cellsalso increase as the brain cells arestimulated by prednisone to thinkyour body requires more and morefood. In your immune system, cellsare slow to respond, increasing thechance of infection of all types.That's because prednisone blocks thespeed that blood travels to the affect-ed cells.

Meanwhile, the brain cells are alsochanged in a way that causes depres-sion, anxiety, or other mood swings.To combat all these effects, physi-cians tinker with the type of pred-nisone, as well as the timing andstrength of the dose, but it's always abalancing act: with less side effects,it's often less effective; the moreeffective dose often has more sideeffects. Prednisone can be inhaled,injected, given orally or intravenous-ly. It can be administered once daily,twice daily, three times daily, as wellas every other day.

Most inclusion-body myositispatients do not benefit from pred-nisone, but because inflammation isalso part of this disease, there may besome initial and continued response.

This is especially true if the patienthas another autoimmune disease.Because of the very slow progress ofIBM, it's difficult to assess the bene-fits of prednisone therapy. Manyclinicians, including Dr. ChesterOddis and Dr. Richard Barohn, willtry prednisone for a short time if thepatient requests, discontinuing it fair-

ly quickly ifthere's noprogress.

Prednisone'sside effects are asinconsistent asthey are trou-bling. In many

cases, they disappear when the drug istapered and discontinued. One of themost troubling side effects, corticos-teroid-induced osteoporosis, is dis-cussed separately in a section devotedexclusively to osteoporosis, beginningon page 10.

Other side effects are caused bythe very properties that make it effec-tive. Since it suppresses the immunesystem, it also increases susceptibilityto infections, especially with long-term use. In turn, infections mayflare the underlying disease, as theyprovide extra stimulation for the sup-pressed immune system. The moon-face or "Cushingoid syndrome" disap-pears rather quickly, and most peopleare able to lose the extra weightcaused by increased hunger and fataccumulation. "Lock the fridge" wasthe advice to those wanting to knowhow to avoid the weight gain almostalways experienced by prednisoneusers. Drs. Oddis and Barohn and Dr.Marinos Dalakas give their pred-nisone patients a low-salt, low-fat,low-sugar diet, and report goodresults if people are able to ignore theprednisone-induced hunger and fol-low the regimen.

Children taking regular prednisonecan experience slower growth andmay be more vulnerable to childhooddiseases. Long-term prednisone users

are at greater risk for vision prob-lems: glaucoma and cataracts as wellas distortion in their vision, especiallywhen tired. At first, prednisone cancause elevated blood pressure, but thebody often adjusts and the blood pres-sure returns to a normal range.Tapering prednisone after the bodyhas made this adjustment may causethe blood pressure to drop below nor-mal. Since the drug is always taperedvery slowly, the body usually adjustsonce again.

Women of childbearing age arevery concerned about the effects ofprednisone on pregnancy and birth. Itdoes not cross the placenta to thebaby during pregnancy, although Dr.Oddis - who has written extensivelyabout myositis and pregnancy - cau-tioned that some other steroids docross over to the baby and can causeharm. In studies, Dr. Oddis and oth-ers found that women who had theirmyositis under control before preg-nancy generally did better than thosewho bore and delivered a child duringa flare. All physicians involved -family practitioner, neurogist,rheumatologist and obstetrician -should consult and treat the pregnan-cy as one with some risks.

The birth of a medical miracle inmid-centuryIn an age where it seems each newday brings another miracle drug, it'shard for us to imagine the scene in1949. The place was the MayoClinic; the drug was "substance X."With extreme secrecy, patients withsevere rheumatoid arthritis were test-ed in trials. The reason for thesecrecy was that preliminaryresults were so amazing thatinvestigators couldn't believetheir eyes. One spring day, theyshared the results of the "sub-stance X" trials with the staffand prepared themselves for theonslaught of publicity and all thehype and hope it was to create.

Prednisone: saves lives, creates havoc

Prednisone's side effectsare as inconsistent asthey are troubling.

5

Wire services around the world toldstories and showed pictures of people- previously barely able to walk -throwing down their crutches, leapingup from their wheelchairs and run-ning upstairs.

"Substance X" was cortisone, adrug that had taken nearly a decade toidentify. The late Dr. Phillip Henchdevoted his life to finding a treatmentfor rheumatoid arthritis, a disease thatwas poorly understood and seemed,even to the most optimistic, to be aheartbreaking diagnosis, often dis-abling and life-threatening.

Like other researchers of his day,Dr. Hench looked for the rare caseswhere the disease under investigationappeared to improve or remit sponta-neously. He and his colleagues notedthat this happened in pregnant womenand patients with jaundice. Theresearchers theorized that thosepatients were producing a substancerelated to their condition that reversedthe disease. Dr. Hench thought it wasprobably a hormone.

By the late 30s, a Mayo Cliniccolleague, Edward Kendall, had iso-lated six hormones from the adrenalglands of cows. He identified theextracts as compounds A, B, C, D, E,and F. Compound E seemed chemi-cally similar to a compound excretedby patients with jaundice, so Dr.Hench thought that might be his "sub-stance X." But it was so difficult to

obtain that it took himyears to accumu-

late enough"compound

E" to treatone

patient.With

excitingresponse in

that onepatient, Hench

had more resources at his com-mand. He gave the drug to several

more Mayo Clinic patients in the daysleading up to that historic spring staffmeeting. He and Kendall traveled toStockholm in 1950 to accept theNobel Prize for Medicine. TheAmerican scientists were joined bySwiss biochemist Tadeus Reichman,whose work with cortisone paralleledtheir own.

The next breakthrough was thedevelopment of synthetic cortisone,or prednisone, and it was usedthroughout the world to fight inflam-mation. As use spread, so did aware-ness of the side effects, and in the lasttwo decades, physicians have used itin combination with other drugs.What scientists are hoping for isanother discovery on the level of Dr.Hench's - a substance that will sup-press targeted reactions of theimmune system without disabling it.

Protection from steroid-inducedosteoporosisCorticosteroids cause bone loss andare the most common cause of drug-related osteoporosis. For many peo-ple who depend on these drugs forsurvival, the loss of bone and conse-quent risk of injury is the most fright-ening side effect of the treatment.Osteoporosis is the major cause ofbone fractures in postmenopausal andelderly women, and prednisone treat-ment adds to the risk. Your bonesdon't remain static as they mayappear, but change constantly, withold bone broken down and replacedby strong new bone. Bone massdeclines in early middle age, andwomen lose more bone mass aftertheir estrogen level drops. Boneswith less mass are more likely tobreak or fracture, even in a minor fall.

Prednisone damages bone byincreasing the bone loss and alsoreducing new bone formation, calci-um absorption and estrogen levels.For those taking prednisone, theamount of bone loss depends on thesize and duration of the dose, andhow strong the bones are when begin-ning the medication. A daily dose of

prednisone higher than 7.5 milligramsover several years results in bone lossand an increased risk of fractures, butshort-term prednisone treatment isless harmful.

The most important step a myosi-tis patient on prednisone therapy cantake is to discuss osteoporosis preven-tion with his physician and get regu-lar bone density tests. If you're underthe age of 35, you can prepare forbone loss in the future and counteractsome of the effects of prednisone byincreasing your calcium intake.Although most people associate calci-um with dairy products, it's importantto know that there are other verygood sources for calcium for peoplewho don't enjoy or don't use milk ormilk products. Green leafy vegeta-bles, shellfish, sardines, oysters,Brazil nuts, tofu, almonds and calci-um-fortified breads and cereals arealso sources of calcium. Most adultsneed 1,000 milligrams of calciumeach day. As you age, you may needmore than 1,500 milligrams each day.Dr. Oddis and other physicians rec-ommend taking calcium in two ormore doses. Doctors are now pre-scribing a number of drugs and com-binations of drugs in the hope ofreducing the risk of osteoporosis inmyositis patients. For new researchon preventing and treating osteoporo-sis, see page 10.

Do you have prednisone-inducedosteoporosis?If you are taking prednisone, or havetaken it for periods of time to treatmyositis, you can find out if you havelost or are losing bone mass by takinga bone density test. Most doctorsbelieve that anyone who is takingsteroids should be tested regularly.Follow-up tests are then made to keeptrack of your progress.

What should you expect from thetest? It's not painful or time-consum-ing. It's done with a bone densitome-ter using a special X-ray. The scancan measure as little as one or two

Continued, next page

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percent loss in bone. CAT scans andultrasound machines may be used inthe future to measure bone density.

Once your bone density is deter-mined, your physician may want tofind out if there are factors other thanyour prednisone use that may con-tribute to osteoporosis. He may orderlab tests, such as a serum calciumtest, a phosphorus test, a protein test,a thyroid hormone test, an alkalinephosphatase test and liver and kidneyfunction tests. He may also prescribecalcium. Some studies claim that cal-cium carbonate supplements containthe highest amount of useful calcium,and the Arthritis Foundation recom-mends calcium in this form. Thisform can be harder for your body toabsorb, so it's recommended that thecalcium be taken with meals.Calcium citrate and calcium glu-conate are easier for some people toabsorb. Another measure you cantake - for overall health as well as tocombat bone loss - is to stop smok-ing. Calcium absorption is reduced insmokers; women who smoke general-ly experience menopause earlier; andsmoking reduces the benefits of estro-gen on calcium absorption.

Another habit that affects boneloss is alcohol consumption. Thiseffect is seen in heavy drinkers, wholose more bone mass and lose it fasterthan those who drink moderately ornot at all. Dr. Oddis also recom-mended weight-bearing exercise toprotect bones. "Weight-bearing"means any physical activity that caus-es your bones to bear weight orincreases the force of gravity againstthem. These are exercises like danc-ing, running, walking, tennis, andcross-country skiing. It is not knownhow long you need to exercise, butaim for 30 minutes most days.Myositis patients, as always, areadvised to check with their doctorsabout exercise. TMA will publish afull discussion of exercise in theMarch issue of The OutLook.

Preventive measures help reduce

the risk of osteoporosis, and the samekinds of measures are recommendedfor those who have already sufferedbone loss because of prednisone ther-apy - exercise, supplements, calciumthrough food. Biphosphonates arecompounds that slow the loss of bonefrom osteoporosis, and restore bonedensity and strength.

In a person with myositis, certainlifestyle changes can also help pre-vent further injury. With bone losscoupled with loss of muscle strength,falls are always a threat. It's impor-tant to do everything possible to pre-vent falls. Our members suggestkeeping living areas well-lit and car-rying flashlights when traveling,installing nightlights, freeing yourhouse of obstacles, installing sturdyhandrails and railings (and usingthem), and designing kitchens that areefficient and safe.

How TMA medical advisors pre-scribe prednisonePrednisone is still the first treatmentfor dermatomyositis and polymyosi-tis. Despite its side effects, it's a life-saver, making death from myositis arare exception. "We all struggle withthis," said Dr. Richard Barohn, "butwe've certainly gotten better at work-ing with the drugs and preventingside effects.”

Oral prednisone is usually givenin a single daily dose of 0.5 to 1.5mg/kg until the strength is normal orthe maximum improvement has beenobtained. Then, prednisone is taperedslowly over a 12-month period.Often after 1 or 2 months on therapy,he switches the patient to every otherday treatment. It's been the experi-ence of many of his patients that thisprocess takes a couple of years.

For more on how different doctorsprescribe prednisone, see "Myositistreatment," cover.

We've learned that early diagnosisand treatment are critical for predict-ing a good outcome. A study of 113patients demonstrated that one-third

of patients with a short delay in diag-nosis responded completely to pred-nisone, compared with much less sat-isfying improvement by all patientswith a long delay. If you see goodresults in blood tests but still havemuscle symptoms, be patient.Someti0mes clinical muscle strengthimprovement lags behind improvinglab tests, and sometimes you feelstronger before the tests confirm animprovement.

Side effects: sometimes morethan you bargained forSome patients respond very well toprednisone and have very minor sideeffects. It's more common, accordingto our members, to respond well inimprovement of strength, but to expe-rience one or more of these sideeffects: weight gain, cataracts, dia-betes, stomach symptoms, osteoporo-sis, and insomnia. When Dr. Barohnprescribes prednisone for his patients,he addresses the side effects from thebeginning. "Each one of our patientson prednisone is given a calorie-restricted diet," he said. It's been hisexperience, and also that of Dr.Marinos Dalakas, that most patientswho adhere to a low-salt, low-fat dietof between 1000-2000 calories, withcomplex carbohydrates and no junkfood or sugar-loaded desserts anddrinks, do avoid the weight gain,bloating, diabetes and "moon-face"associated with prednisone use. "It'sa difficult diet, but it does work," Dr.Barohn said. "It's very similar to thediabetes diet."

He also prescribes supplementalcalcium and Vitamin D for patientswith normal bone density; and thebone density test is repeated everyyear. Those who test below normalare prescribed alendronate sodium aswell as the supplements. Mostpatients don't experience stomachupsets. "If that's the case, I leave wellenough alone," Barohn said.Otherwise, he prescribes Zantac.

See Prednisone, page 21

7

Gardens and yards: good forthe bones

Researchers have linked regular yardwork to the prevention of osteoporo-sis, finding that women aged 50 andolder who gardened at least once aweek showed higher bone densityreadings than those who performedother types of exercise - includingjogging, swimming, walking and aer-obics. By knowing which exercisesprovide the greatest benefit, womencan design a workout regimen thatwill ensure strong bones as they age.Such preventive measures may reducethe number of people who developosteoporosis.

To gain a comprehensive look atthe effects of exercise on olderwomen, researchers looked at theNational Health and NutritionExamination Survey, a dataset collect-ed by the National Center for HealthStatistics, which contains informationon more than 40,000 women.Younger subjects were eliminated,leaving a pool of 3,310 women aged50 and older, and researchers studiedhow often these women performeddifferent activities, including yardwork, calisthenics, bicycling, dancing,aerobics, swimming, jogging, walkingand weight training. Each activitywas related to bone mass, finding thatbicycling, aerobics, dancing, yardwork and weight training were linkedto higher levels of mineral density.

After adjusting for other factors,the results showed only two activitiesto be significant for maintaininghealthy bone mass - yard work andweight training. Researchers certain-ly hadn't expected yard work to besignificant, since it's not consideredan athletic activity. There's a lot ofweight-bearing motion going on inthe garden - digging holes, pullingweeds, pushing a mower. An addi-tional benefit of gardening is the factthat it's performed outdoors, whereexposure to sunlight boosts vitamin Dproduction, which aids the body incalcium absorption. While weight-

bearing activity and vitamin D workdirectly to strengthen women's bones,yard work provides indirect benefitsas well. Of all the activities, yardwork proved the most popular, withnearly half of the subjects - 1,384women - claiming to garden at leastonce a week. Such popularity makesit a highly effective preventive mea-sure.

In the end, the best thing aboutyard work is that so many people arewilling to do it. They don't dread itas exercise, and they'll probably con-tinue to do it as long as they're able.And as long as people stick with anexercise, they can harvest the benefitswell into old age. In addition to exer-cise, women must take other precau-tions, and they must take them asearly in life as possible: at least 1,000milligrams of calcium a day, a healthybody weight, and no smoking orexcessive alcohol consumption.

Stand up straight and callthe "bone phone"

Often the first sign of osteoporosis is afracture or a fall. Now, research showsthat good posture can help people withosteoporosis reduce their risk of bro-ken bones, says University ofALabama registered dietitian BethKitchin, R.D., of the OsteoporosisTreatment and Prevention Clinic. "Forpeople with osteoporosis even move-ment as simple as bending over tounload a dishwasher or wash your facecan lead to a vertebral facture. Learn touse your hips and knees when bending,rather than hunching or rounding yourshoulders forward, to reduce the risk."

The University has become a regionalleader in osteoporosis management,and has also established a hotlineknown as the "bone phone." The UABosteoporosis hotline answers questionsabout osteoporosis. Call toll-free, 1-888-934-BONE.

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ed a liquid antacid called Maalox.Maalox is a mixture of magnesiumhydroxide and aluminum hydroxide,both chemical bases that neutralize theexcess stomach acid produced by the

prednisone. Itook so muchMaalox that thefirst calciumdeposit I gotunder my skincame on the leftthumb I used toopen the lid of

the Maalox bottle. I still have thatcalcium deposit, and it's pretty big.Doctors today recommend calciumcarbonate tablets (Tums) to neutralizestomach acid and provide supplemen-tal calcium. However, antacids don'tstop the damage to the stomachcaused by prednisone, and some per-manent sensitivity remains today, eventhough I have been off prednisone for23 years. The stomach acid issuegoes beyond antacids: it creates anawareness of the acid contents offoods, which most kids don't consider.I had a rapid learning experience todecide what foods to eat and whatfoods to avoid.

A second side effect, which is justas serious, is the loss of calcium fromour bones. After about a year onprednisone, I began to experi-ence short spasms in myback. At that time,there wereno medica-tions toretain calci-um in ourbones, suchas Fosamaxand Actoneltoday. In fact,I took dilutesodium fluoridesolution nominal-ly for this pur-pose, but it had nobenefit. The back

Editor's note: Prednisone is the main-stay of therapy, especially for thosewith juvenile myositis. It typicallyworks quickly and effectively, butalong with the positive impact, itbrings a number of undesirableeffects. Richard Gay, who had JM asa child, explains his personal experi-ence with the side effects of pred-nisone therapy. Fortunately, doctorshave discovered new ways to dealwith adverse effects of prednisone -including introducing steroid-sparingmedicines earlier in treatment - sinceRich was treated for JM 40 years ago.

Getting more than you bargained for

The doctors at the recent TMAConference called juvenile myositis(JM) a "devastating disease." Therealization that juvenile dermato-myositis (JDM) will be with me for along time does not come right awaywhen diagnosed. Even when the doc-tor makes an early and correct diagno-sis, I'm not aware of the serious natureof the illness. The long-term effectsof JDM are not on the front burner.The first thing on my mind is torecover my strength, be able to swal-low food again, and make the itchinggo away.

Thus, the knight on the white horseis prednisone, the most widely usedmedication for JM, and deservedly so.The value of prednisone can be mostreadily appreciated by observing thatin 1964, when I was 13 years old andfirst diagnosed, prednisone was theprimary treatment - in fact, the onlytreatment - for JDM. Now forty yearslater, with amazing progress in medi-cal treatments, prednisone is still theprimary medication. It works, and wehave to give credit where it is due.

Immediate effects - the bad withthe goodBut prednisone has a dark side thatcomes in the form of side effects. In

1964, I knew none of the short- orlong-term side effects of prednisone.I had the immediate reaction of the"moon face," but it was not a majorconcern to me. In today's world ofmake-overs, faddiets, and per-sonal trainers,Madison Avenueis teaching usthat appearanceis the mostimportant thingin our lives.Prednisone makes a rapid and dramat-ic change in appearance. Fortunately,it didn't bother me and my doctor wasable to warn me that it was coming.

In addition, prednisone also causesan increase in acne. As a youngteenager, my acne was difficult tocontrol, and prednisone made itworse. I went to a dermatologistmany times for treatments. I had pim-ples across my back, and my dadwould clean my back when I took abath just to try to control the acne. Asit turned out, time was the only effec-tive remedy for the acne.

Prednisone also makes us suscepti-ble to infections and common illness-es. I remember having many coldsduring high school. It seemed that Iwas always taking Contact - thefavorite cold remedy of the time -while in school. The colds were con-trollable but just didn't seem to goaway. Now I know why: prednisonemakes us susceptible to every oppor-tunistic bug we encounter.

What to watch forThe long-term effects are more subtlebut can be much more serious.Sometimes, you get more than youasked for and there is no easy way tosay, "No, take it back." The first sideeffect I had to deal with was stomachulcers. I took 30 mg/day of pred-nisone for about five years. Within afew months, I noticed trouble with mystomach, and my doctor recommend-

Juvenile myositis and prednisone: battling side effects

Now forty years later, withamazing progress in medicaltreatments, prednisone is stillthe primary medication.

9

Strategies to help along thejourney

By Richard Gay (JM)Given the serious nature of the sideeffects of prednisone, what is a suc-cessful strategy to deal with both theJDM and the side effects?

Recognize that time is our ally inthis endeavor. Surprisingly, my doctorexpected time to be a major factor inbeating the disease. He expected it to"burn out" within a couple of years. Itdid not, but it did become inactiveafter 14 years.

Identify ways to lower the pred-nisone dose while not allowing the ill-ness to get worse. Today we seemany combinations of medicationsused to supplement the prednisoneprecisely with the goal of reducing theamount of prednisone used. In 1970,I was in a trial study using methotrex-ate with prednisone, effectively lower-ing my dose from 30 mg/day to 15mg/day. Within a few months, myback strengthened and I have notworn a back brace since then. Thelong-term decrease in calcium in myback is only slowly recovering.

Use your muscles as much as pos-sible through exercising and stretch-ing. This encourages the healthy partof our body to maintain and build theremaining muscles that aren't dam-aged in the initial illness.

Maintain a healthy emotional andspiritual life. The center of who weare is our own spirit; if we allow it toatrophy, our physical bodies will fol-low. There is a feeling of isolationwith JDM. I was always active invarious organizations at school andchurch, and JDM did not interfere sothe isolation was minimized.

It's a risky balance choosingbetween the illness and the sideeffects of the medication. Medicalscience is making significant progressevery day, and there are some verypromising medicines for JDM andadult dermatomyositis.

Another patient, differentside effects

Joanne has dealt with JM sincechildhood, but she doesn't remem-ber much about the medicine's side

effects. With some help from hermother, here's what she does recall:

As far as I can remember, I was onprednisone, methotrexate, cyclosporinand an aluminum-based liquidmedicine for calcifications, whichmessed around with my stomach. Ihad years of stomach cramping, diar-rhea, and irritable bowel syndrome,even years after I stopped taking it,and it didn't help with the calcium, asI had and still do have a lot.

My parents remember myravenous appetite and how they hadto monitor my diet so I didn't put ontoo much weight, which they saidwas hard because I was always hun-gry. They also watched my sugarintake due to steroid-based diabetes.

Mum said I went through sleep-lessness but didn't know of anythingto help with that. I still have prob-lems sleeping and now take a naturaltablet called Valeria.

For my hair loss, Mum said webasically used sorbalene because theyadvised against anything perfumed -nothing of help for the hair loss.

One thing that we found for ulcerson the skin was EDP powder. Itcomes in a little bottle and is like anantiseptic powder that helps dry outthe ulceration.

Mum said I often had this creepycrawly feeling in my skin, which shethinks may have been my musclesbreaking down. Luckily, I can't actu-ally remember this.

As far as long-term side effects, Ihave diabetes, hypertension, osteo-porosis, and cataracts. I have depres-sion, which has a link to steroids andto diabetes and, as we know, is just aplain old common complaint nowa-days anyway. There are other medi-cal problems, but as I've been told,there has been so little research doneinto the long-term side effects thatthey just can't confirm if they arerelated to the steroids or not.

spasms were the result of the leach-ing of calcium from my back by theprednisone. There was nothing tostop this from happening. The solu-tion was to wear a back brace.Today, many lightweight backbraces made of durable plastic areavailable. In 1965, the brace wasmade of metal that curved aroundthe front of my body to the back,with straps to hold a pad across myback against the metal frame. Itwas uncomfortable and hot; I woreout a number of pads. There was aserious psychological effect becausethere was no expectation that Iwould ever be out of the back brace.

I also noticed that I was notgaining in height or weight, and Iasked my doctor if I would growany more. He told me no. I knownow that prednisone suppresses ourgrowth. I did not have the weightgain that many people ascribe toprednisone, though my appetite wasalways good.

I had the life-giving benefits ofsuppressing the autoimmuneresponse of JDM while experienc-ing the detrimental side effects ofthe medication itself. There areother serious effects that I did notexperience, such as cataracts andmood swings. In fact, I have neverhad to take anti-depressants in the40 years I have had this illness.

By Richard Gay (JM), Co-chairLos Angeles Keep In Touch sup-port group. Edited for space - toreceive a copy of Rich's article inits entirety, emailtma@myositis.org

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Prevention and treatment of osteo-porosis - a serious side effect of pred-nisone therapy and a costly publichealth problem - continues to be ahigh priority for research, and was thesubject of several presentations at theAmerican College of Rheumatology2004 Annual Scientific Meeting.Osteoporosis weakens bones, leavingthem subject to fracture in one out ofevery two women, primarily in thoseover the age of 50. In the U.S. alone,some eight million women and twomillion men run the risk of fractureleading to chronic pain, long-termdisability and even death from thissilent disease. The studies presentedhere are very new: please discussthem with your doctor.

Vitamin D linked with improvedmuscle strength and functionThis research studied patients withknee osteoarthritis, not osteoporosis,but we include it here because it isthe first look at vitamin levels in rela-tion to pain and disability. The 221patients had an average age of 67years and were measured for changesin pain, physical function, musclestrength and blood levels of vitaminD two or more times across a 15- and30-month period. At the beginning,the 48 percent of patients with lowlevels of vitamin D (at or below theamount needed to satisfy the body'srequirements) experienced more painand disability than those with levelsabove the minimum. Researchersalso found that those with low levelsof vitamin D were weaker.

Vitamin D, which comes primarilyfrom exposure to sunlight, promotesthe absorption of calcium and phos-phorus in bone mineralization, growthand repair. Vitamin D also comesfrom dietary sources like oily fish,liver, fortified breakfast cereals anddairy products. The elderly are lessefficient at producing vitamin D fromsunlight and absorbing it from food.To address their higher risk for D

deficiency, the elderly population isoften directed to take a vitamin Dsupplements, of 400-600 InternationalUnits per day. (Exposure to sunshould be limited to five to 15 min-utes on the face, hands or arms, orarms and legs. Dermatomyositispatients should always check withtheir physicians before exposingthemselves to sunlight.)

New oral medication appears toreduce fracturesStrontium ranelate, a new oral medi-cation, may reduce spinal, non-spinal,hip and other fractures in olderwomen with osteoporosis, a largeongoing study suggests. Post-menopausal women were randomlyassigned strontium ranelate or aplacebo, along with calcium and vita-min D supplements for three yearsand testing was broken down into twomulti-national, double-blind con-trolled studies. One focused on thepossible reduction of fractures of thespine in nearly 1,650 women, averageage 69; the other studied non-spinalfractures in more than 5,000 women,average age 76. All women studiedhad low bone density.

In both studies, participants expe-rienced a significant reduction in frac-ture risk. Over the three-year period,36 percent fewer women 74 years ofage or older suffered hip fractures.Concurrently, spinal and non-spinalfractures were reduced by 32 percentand 31 percent, respectively, in thesubgroup of elderly women ages 80and older. Strontium ranelateappeared to both increase bone for-mation and decrease bone density lossin the majority of patients, demon-strating a good bone and general safe-ty response.

"Strontium ranelate is the firstcompound to simultaneously decreasebone resorption and stimulate boneformation," said Jean Yves Reginster,MD, Dept. of Public Health,Epidemiology and Health Economics,

University of Liège,Belgium and World HealthOrganizationCollaborating Center forPublic Health Aspects ofRheumatic Diseases,who was an investigatorin the study. "Given thisand its outstanding safe-ty profile, strontiumranelate could prove to bea first-line treatmentoption for women withlow bone mineral densitywith or without prevalentfractures as well as forelderly women withincreased risk factors of hipfractures."

Osteoporosis cocktail stimulatesnew bone growthThe combination of teriparatide(Forteo®), an injectable parathyroidhormone medication, when adminis-tered with the selective estrogenreceptor modulator, raloxifene (Evista®), improves bone density formation,a new study suggests. Previousresearch had shown that anotherantiresorptive agent, alendronate(Fosamax®), appeared to diminishthe gain in bone density seen withteriparatide alone.

To determine if the benefits ofteriparatide can be enhanced with theaddition of raloxifene, a selectiveestrogen receptor modulator (SERM)which slows bone loss and slightlyincreases normal bone growth,researchers conducted a six-monthrandomized, double-blind study com-paring the use of teriparatide againstthe combination therapy. The 137postmenopausal women participatingin the trial, none of whom had priorosteoporosis treatment, also receivedcalcium and vitamin D supplementsthroughout the course of the study.

Groups on the single and doubleagents showed similar significantincreases in bone formation in months

Osteoporosis - new approaches for crippling disease

11

one, three and six. However, boneresorption was reduced (as measuredby markers of bone turnover foundthrough urine and blood tests) in thegroup taking both medications bymonth three, an effect which persistedto month six. Those taking both teri-paratide and raloxifene had higherbone density at the spine and hip (sig-nificantly higher for the hip site) thanthose on teriparatide alone. "Theresults are encouraging since we arelooking for agents or combination ofagents given together or sequentiallythat will further reduce the rate offracture in high risk patients," saidChad Deal, MD, Cleveland ClinicFoundation, Cleveland, Ohio, and aninvestigator in the study. "The mostimportant question is effect on frac-ture reduction and, although no stud-ies are underway at this time to assessfracture reduction with this combina-tion, the bone density and marker dataare a promising start."

Antibody prevents bone lossA novel treatment administered semi-annually to postmenopausal womenwith low bone density appears torapidly inhibit the bone resorptionprocess, resulting in improvements inbone mineral density at 12 months.Bone is living tissue that is in con-stant regeneration. This means tis-sues that form bone are constantlybeing created and resorbed by thebody. During adolescence and earlyadulthood, bone growth resulting inpeak bone density is due to the signif-icantly greater new bone formation ascompared to bone resorption. Withaging and the loss of estrogen aftermenopause, the balance between boneresorption and new bone formationshifts. More bone is lost than can bereplaced, leaving bones thinner andstructurally weaker. This results inosteoporosis and fragility fractures.

Researchers recently studied anew treatment antibody, AMG 162that binds to a receptor protein on thesurfaces of osteoclasts - the cells thatfunction in the absorption and

removal of bone tissue. AMG 162,which is still in clinical trials, mayprevent bone loss resulting in osteo-porosis and the bone erosions thatlead to rheumatoid arthritis.

To assess AMG 162's effective-ness when administered every sixmonths, researchers conducted a year-long test of different doses of theantibody use in 411 women, averageage 63 years, who are participating inan on-going, randomized study. Eightof the nine treatment groups receiveddouble-blind, subcutaneous injectionsof AMG 162 (six, 14 or 30 milligramsevery three months, or 14, 60, 100 or210 milligrams every six months) or aplacebo. The last group receivedopen-label 70-milligrams of oral alen-dronate once weekly. Urine andblood tests as well as X-rays wereused to evaluate results.

An anti-resorptive response, asmeasured by bone turnover markers(urine and blood tests), was almostimmediately evident in all patientstaking the antibody, and continued toimprove through month four.Depending on AMG 162 dose levels,increases in bone mineral density alsowere observed as early as month one.The most common adverse effect,indigestion, occurred in only a smallportion of all groups. Overall, AMG162 administered once every sixmonths was well tolerated and causeda rapid, dose-dependent increase inbone formation and bone density. "Ifongoing clinical trials demonstratefracture risk reduction, this therapyshould lead to a dramatic improve-ment in patient compliance due to theease of administration compared topresently available osteoporosis treat-ment," said S.B. Cohen, MD, RadiantResearch, Dallas, Texas, and aninvestigator in the study.

Protecting young bonesJuvenile myositis is hard on children'sbones, said Mona Calvo of the Centerfor Food Safety and Applied Nutritionat the Food and Drug Administration.Parents at TMA's Juvenile Myositis

conference were aware that the pred-nisone prescribed for JM, especiallyin large doses, contributes to the lossof children's bones. There are othercontributors, though, Dr. Calvoexplained. The active myositis itselfaffects bone density, as does thereduced activity endured by JMpatients, the decreased sun exposurebecause of the rash, and possibly poorprotein and calorie intake combinedwith poor calcium and vitamin Dintake that can be a side effect of ill-ness and poor appetite. She gave theparents some ideas for preventingbone loss and encouraging good boneformation in children to reduce thechances of future fracture risk. Heradvice for the families was toincrease the amount of calcium, vita-min D and protein intake while alsomaking sure children were exercisingas much as possible under the circum-stances.

Children with myositis need morethan the 800 to 1300 mgs of calciumand the 200 international units ofvitamin D required by healthy chil-dren, Dr. Calvo explained, becausethe prednisone increases the amountof calcium the body loses and inter-feres with the way vitamin D func-tions. Dr. Calvo encouraged parentsto look closely at the "Nutrition Facts"panel on the label of the foods theybuy for their families; to encouragechildren to drink milk and vitamin D-rich beverages; and to avoid the typi-cal US teen's dietary habits, whichhave changed over the years to includehuge amounts of carbonated softdrinks beginning at age 11. Becauseof the higher than usual needs of JMchildren, Dr. Calvo encouraged par-ents to search out calcium and vitaminD fortified foods. Some foodspresently fortified with Vitamin D aremilk, cereal and fruit juices.

Find Quick tips for healthy bones onpage 30, and read how gardeningcan help prevent osteoporosis onpage 7.

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Dysphagia, or trouble swallowing, isa serious side effect of myositis and isoften ignored, says Dr. Todd Levine.This topic is of special interest tohim, both because he is a neurologisttreating people with swallowing prob-lems and because he has personalexperience using a temporary feedingtube following an injury.

Swallowing is one of the mostcomplicated things we do neurologi-cally, he says. Half the brain stem isused to get your food from your lip tothe back of your throat. It's a compli-cated system, as the trachea, whichpasses air to your lungs, and theesophagus, which passes food to yourstomach, are very close together.There are intricate connectionsbetween the brain, nerves and mus-cles. Once something else enters theequation, like muscle disease, the sys-tem breaks down in some way.Michelle Reuther, a speech therapist,notes that a normal swallow occurs inone second. A number of muscles areinvolved in this one second of swal-lowing - the posterior wall and frontmuscles come together, your softpalate moves up, the back of yourtongue stretches and pulls, yourepiglottis closes to cover your airway,and your Adam's apple comes up.When your muscles become weak,she says, the timing slows down.

Signs of dysphagiaThe first complaint for many is fre-quent choking, but Reuther says youmay only feel like you're choking.The food is not blocking the airwaybut instead is stuck in a "pocket"(hypopharynx) at the base of yourtongue near the epiglottis. If thehypopharynx fills up before you'reready to swallow, some of the build-up spills over the epiglottis into yourairway, leading to aspiration.Aspiration pneumonia, which isbrought on by small particles of food in the lungs, is a risk for those with

swallowing difficulties. How do you know if you have

dysphagia? You may realize it's tak-ing much longer to eat meals than itshould - requiring up to 5 to 10 swal-lows to take in a single bite, saysLevine. For him, the easiest diagnos-tic tool is to have his patients drinkwater then say their name. If theirvoice sounds wet, there's a problem.In this situation, the water is sitting inthe top of the esophagus at the tra-chea, where the vocal chords arelocated. His patients end up soundinglike they're talking under water.

Other signs include:Pain when swallowingNo interest in eatingFrequent chokingLow-grade feversCoughing overnight

Signs of dysphagia often happenwhen you're eating out, a time whenyou may not be paying as much atten-tion to your food as you should be,says Reuther. It's important to keepfrom being distracted while you'reeating. If you're already having trou-ble swallowing, she says, you mustconcentrate in order to get the fooddown.

Diagnosing the problemDifferent doctors can diagnose swal-lowing disorders, but speech thera-pists are the most effective. "Andthey can give you techniques to helpyou overcome the problem," saysLevine. Ear, nose and throat doctorsare able to look down your throatwith a scope, and speech therapistscan look into your esophagus whileyou talk or eat to see which musclesare moving and which are not.Doctors are also interested in howyou form a bolus, or the mass ofchewed food - if you don't form aproper bolus, you'll end up with along string of food or liquid to try to

swallow, he says.Reuther encourages everyone to

have a modified barium swallow."With dysphagia," she says, "every-one is different." The barium testshows the therapist exactly when theproblem occurs - before, during orafter the swallow. Knowing thisdetermines what exercises, techniquesor procedures will benefit each indi-vidual. However, swallowing prob-lems don't happen all the time foreveryone. If you notice certain foodscontinuously causing problems, bringthem with you for the test.Otherwise, the test may show a per-fect swallow, she says, even in thepresence of a problem.

Treating dysphagiaThere are many ways to treat dyspha-gia, and their success can be mea-sured. Dr. Levine keeps track ofeveryone's weight in his clinic tomake sure they are receiving adequatenutrition. His experience indicatesthat people with chronic disease domuch better if they maintain a reason-able weight. If you have troubleswallowing, you need to take in morecalories in an easier format, he says.

Though it doesn't seem logical,thinner foods and liquids are not theanswer to dysphagia, as water andother thin liquids are more difficult tocontrol in the swallowing process.Thicker foods are actually easier tocontrol and are therefore easier toswallow. Reuther recommends alter-nating liquids and solids when eatingto prevent any buildup in thehypopharynx. There are also thicken-ers that produce consistencies of nec-tar, honey and pudding. The addi-tives are tasteless, although users maydetect them in water. Thickeningthese thinner liquids slows themdown, providing a better chance toswallow correctly.

Reuther also encourages patientsto be aware when they're eating; dis-traction leads to more problems. Sherecommends that patients keep their

Dysphagia: what you should know

13

chin down to help close off the air-way and bring the muscles closertogether. She gives her clients threeexercises to try - her "holds":

Tongue hold: Stick your tonguebetween your teeth then swallow.This stretches all of your muscles.

Breath hold: Take a deep breath,hold it and swallow. This is difficult,so you have to concentrate to be ableto do this.

Adam's apple hold: Swallow; thenhalfway through the swallow, whenyou feel your Adam's apple going up,leave it there for a second. Then fin-ish your swallow. This is a difficultone to learn.

When techniques and exercises don'twork, different procedures are avail-able. In esophageal dilation, doctorsinsert a dilator into your esophagus tostretch it when the opening is too nar-row. For crycopharyngeal myotomy,a small incision is cut in your muscleto allow food to pass through moreeasily.

If you aren't maintaining yourweight, Levine encourages you toconsider a feeding tube. A feedingtube, also called a G-tube or PEGtube, allows food to bypass the swal-lowing phase of eating by inserting atube directly into your stomach. Thistube then provides your main sourceof nutrition. "People often equatefeeding tubes with ventilators asextraordinary measures," he says."They're two vastly different things."Feeding tubes have many advantages:it's a 30-minute procedure, it's notvisible to others, it's not permanent,and, maybe most importantly to you,you can still eat with a feeding tube.Eating is a sensory pleasure, saysLevine, so with a feeding tube, youcan enjoy a meal with friends andfamily without feeling pressured toeat more quickly. He recommends afeeding tube for anyone who hasrecurring pneumonia, who is losingweight, or for whom eating just isn'tpleasurable anymore. Caregivers get

worn down, too, trying to help some-one who has difficulty swallowing,adds Reuther, and a feeding tube mayalleviate some of their workload andtheir worry.

Resources:

The Dysphagia CookbookThe Dysphagia Cookbook, with aforeword by Dr. Todd Levine, isavailable at TMA's online Marketplaceor by calling 1-800-821-7356.

Written especially for those withswallowing problems, this cookbookoffers tips for preparing and servingfood, information on food consisten-cy, tools and foods to have on hand,and suggestions for eating out.Recipes include vegetable dishes, fishand meats, breakfast foods, salads,sauces, desserts, fruits, and drinks.

Dealing with dysphagia: more helpful hints

Michelle Reuther had a number of suggestions to take home with you.Here are her recommendations, along with general tips from previousTMA publications:

Have a spray bottle with water next to your bed at night, then spray tomoisten your mouth before taking a drink of water. Throughout the day,suck on a Lifesaver or something similar to keep your mouth from becom-ing too dry.

Cut a piece out of a small Styrofoam cup for your nose to fit in whiletaking pills. This allows you to drink water without tipping your headback. You can buy these "nosey cups," but they're just as easy to makeyourself, she says.

Eat less food more often. Eating six smaller meals a day is better thanthree larger ones, especially when eating takes more time. Take in smallamounts of liquid over time to keep the hypopharynx clear.

Take smaller bites of food and smaller sips of liquid, and be sure yourmouth is clear before taking another bite.

Don't eat when you're overly tired. Focus on eating, and avoid distrac-tions like television.

Don't clear your throat when you feel the urge. Instead, swallow. Thisis a smoother action that doesn't irritate the vocal chords and has the sameeffect.

Suck on lozenges, candies or mints when you're coughing a lot. Alsotake in plenty of water and avoid caffeine.

Avoid foods that cause the problem. It's not always easy to determinewhich foods are the culprits, but if you can pinpoint any type - spicy orsweet, thick or thin, hot or cold - stay away from these. On the other hand,some foods may stimulate a swallow. Try mixing flavors or textures to seewhat works for you. Also, avoid foods that are most difficult to control inyour mouth.

Turn your head to the left or right. Decide what position of your headgives you the least problem when swallowing. Sit upright while eatingand 1 to 2 hours afterwards to let gravity help.

Maintain good oral hygiene. Research shows that this prevents aspira-tion pneumonia in individuals with swallowing disorders.

14

Myositis affects such a small percent-age of the population that doctorsdon't often see patient after patientwith the disease. When you haveanother autoimmune disease alongwith myositis, this causes even moreconfusion. It's often hard to sort outthe symptoms of each disease, saysDr. Fred Miller: you typically need tomeet the criteria for all of the diseasesfor them to be considered overlap.

Some more commonoverlapping illnesses arerheumatoid arthritis, lupus,scleroderma and Sjogren's.One research group fromHungary says myositis(mainlypolymyositis)/rheumatoidarthritis overlap affects about 3 to 5%of myositis patients. In terms of thegeneral population, a Romaniangroup states: "The connective tissuediseases comprise a group of syn-dromes of unknown etiology affectingas many as 1 person in 40, often witha predilection for the female sex."Rheumatoid arthritis affects about 1%of the US population, mainly withinflammation of the joints; lupus isless common, afflicting 0.1% of thepopulation with joint, kidney, blood,and skin problems. Even more rare isscleroderma (0.01%), a connectivetissue disease characterized by thick-ening and hardening of fibrous tissue.As with other autoimmune condi-tions, joint stiffness, fatigue, GI andlung involvement, Sjogren's syn-drome (dry mucous membranes), andmuscle aches are common complaintswith scleroderma.

Treating overlapsThere are differences between overlapand non-overlap myositis patients. Inepidemiological studies, Miller notesthat myositis is less severe when thereis an overlapping condition than whena patient has myositis alone. In eithercase, though, doctors are treating thesymptoms of the diseases because

there are no known causes for most ofthem. In reality, doctors treat eachperson's individual problems ratherthan the disease itself.

The treatments used are basicallythe same, as many of the treatmentsused for myositis are applied to thedifferent autoimmune diseases. Thereare similar risk factors for the differ-ent autoimmune diseases as well - forinstance, HLA alleles are found to be

associatedwithmyositis,otherautoim-mune dis-eases, andoverlap

syndromes.As with myositis in general, the

first step is making sure the diagnosisis correct. Is it really myositis, or isanother condition mimicking myosi-tis? Once the diagnosis is accurate,determine if the disease is active or ifit's in the chronic, damaged phase. Inthe latter, physical therapy and reha-bilitation are started to help withexisting muscle function. Finally, it'sessential to keep your own wishesand needs in mind in forming anacceptable, effective treatment plan.

Unfortunately, there are moreunanswered questions than answeredquestions in treating myositis andoverlap syndromes. There are someguides, including certain factors thatcan predict in many cases how you'llrespond to therapy, but these factorsapply to larger groups and not alwaysto individuals. The ultimate goal,says Miller, is prevention.

Which treatment works best?Miller admits that all myositispatients are guinea pigs when theystep into their doctor's offices. Thatsaid, doctors aren't randomly choos-ing medicines but making educatedguesses using information from trialsand other sources. In the end, they're

trying to fix what's bothering you, nottreating each particular overlappingcondition you may have.

More research will lead to moreanswers, and that's where you canhelp: contribute toward the funding ofresearch projects, write your represen-tative in Congress asking for supportfor autoimmune disease legislation,educate others about myositis, andparticipate in clinical trials whenappropriate. There are currentlymany basic research projects, withpromising trials on the horizon.

Questions from you

Is it worth trying alternatives in theabsence of effective conventionalmedicines? If conventional therapiesaren't working for you, alternativetreatments are available. However, besure the risks are low. Alternativesaren't regulated like traditionalmedicines, so doctors don't know allof the possible side effects, saysMiller. There aren't good controlsover these methods.

How long should you stay on a par-ticular medicine to see if it's work-ing? And how do you know themedicine is actually working? Athree-month trial period is adequatefor most medicines, says Miller, butdifferent medicines will have differenttime periods for showing effective-ness. To assess whether it's working,besides simply feeling better, doctorsneed to come up with better measuresof disease improvement and otherfactors. Currently, a group of morethan 100 doctors, called IMACS(International Myositis Assessmentand Clinical Studies Group), is work-ing together to standardize definitionsin order to better compare resultsfrom research trials and clinicalobservations. The group is focusingon definitions for remission, flare,improvement, deterioration, and otherterms. This standardization will leadto clearer answers in the future.

Overlap syndrome: when myositis isn’t your only obstacle

As with myositis in general,the first step is making surethe diagnosis is correct.

15

How do you know you're in remis-sion? Again, says Miller, IMACS isworking on definitions to help withquestions like this. For now, remis-sion means that a person is off allmedicines and has had no evidence ofdisease activity for a period of sixmonths. This is different from a com-plete clinical response, where youhave no evidence of disease activitybut are still taking medication to con-trol the disease. Keep in mind thatdamage may still be there from pastdisease activity, he says, so even inremission, you may not feel quite"normal" even with normal test results.

Why do previously effective drugsbecome ineffective? Doctors don'talways know why the medicinesworked in the first place, says Miller.In cancer studies, it has been docu-mented that patients can develop aresistance to certain medicines, so thismay be the case with myositispatients as well, though there havebeen no studies on this.

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When you're being treated with anumber of medicines for overlap,how do you know what's helping?This depends on a number of factors,he says. It could be related to thesequence in which you started each ofthe medicines, but it remains difficultto determine which medicine is actu-ally working for you. Dr. Millerkeeps his patients in a clinically con-trolled response for three to sixmonths before tapering, then beginsdecreasing the most dangerousmedicine first. He prefers to taperslowly and steadily to avoid flares.

Acupuncture helps inosteoarthritis of the knee

Acupuncture, as a complementarytherapy to drug treatment forosteoarthritis of the knee, is moreeffective than drug treatment alone,find researchers from Spain.

Osteoarthritis of the knee is com-

mon, affecting almost a tenth of thepopulation aged over 55. The role ofacupuncture in osteoarthritis remainscontroversial and few studies compar-ing acupuncture and drug treatmenthave been conducted. A total of 88patients with osteoarthritis of the kneewere randomly divided into twogroups, one receiving acupuncture plusdiclofenac (an anti-inflammatory drug)and the other dummy (placebo)acupuncture plus diclofenac. Treatmentlasted 12 weeks and levels of pain,stiffness, and physical function weremonitored using recognized scales.The acupuncture group had a greaterreduction in pain and stiffness,improved physical functioning andquality of life than the placebo group.Although the 12-week monitoring peri-od may be insufficient to evaluate theeffects of treatment in the medium term,authors say acupuncture as a comp-lementary therapy to drug treatment forosteoarthritis of the knee is more effec-tive than drug treatment alone.

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Drugs like Celebrex and others called"Cox-2s" are generally tolerated verywell by many patients, which is fortu-nate because these drugs are oftenvery helpful for people with pain andinflammation. Most side effects areminor and easily reversible by discon-tinuing the drug. The risk of seriousside effects is small, but a little bit ofunderstanding of the possible side-effects of these drugs can make themsafer to use. If any of the followingguidelines are not clear, or if youthink it does not apply to you, discussthe issue with your physician.

Stop the drug and call your physi-cian immediately if you have anysevere abdominal pain or a black,tarry stool or any blood in your stool,which are signs of internal bleeding.Although the manufacturers say thatthese drugs can be taken on an emptystomach, to help reduce irritation ofthe stomach and prevent an ulcer,take non-steroidal anti-inflammatories(NSAIDs) at the end of a full meal, orwith antacid. Limit alcohol intakesince alcohol can irritate the stomach.

Celecoxib and valdecoxib shouldnot be prescribed for patients withallergy to sulfa-containing drugs (sul-fonamides). Such drugs include theantibiotic trimethoprim-sulfamethoxa-zole (Bactrim, Septra). If you arethinking of taking celecoxib or valde-coxib, make sure that you do not havea history of allergy to such drugs. Ifyou aren't sure if a drug you had abad reaction to fits in this category,ask your physician.

Why Cox-2 agents became sopopular

Cox-2 agents, like Celebrex, Vioxxand Bextra, became immensely popu-lar in a very short time, not becausethey were found to be more effectivethan traditional NSAIDs like aspirin,ibuprofen and naproxen, but becauseof their perceived reduction in sideeffects. A study presented at theAmerican College of Rheumatology

annual meeting said this attribute con-tributed substantially to a dramaticincrease in prescriptions and influ-enced the way physicians prescriberheumatology medication.

Traditional or non-selectiveNSAIDs are effective inhibitors of theenzyme cyclooxygenase (Cox) 1 and2 and so are able to reduce inflamma-tion and musculoskeletal pain. SinceCox-1 enzymes help maintain thebody's internal stability and Cox-2enzymes signal pain and inflamma-tion, the agents that attack both setsof enzymes increase the risk for gas-trointestinal complications like bleed-ing or ulcers in some patients. In1999, the first selective Cox-2inhibitor, celecoxib (Celebrex®),appeared on the market, followed byrofecoxib (Vioxx®), and valdecoxib(Bextra®). These Cox-2 agentsselectively inhibit cyclooxygenase 2,the enzyme responsible for inflamma-tion and pain, but they have noimpact on the beneficial action ofCox-1, thereby reducing the incidenceof GI side effects. This was seen tobe a tremendous benefit to peoplesuffering from chronic inflammatorydiseases, including myositis.

Using source data on prescriptionsales from independent, chain, super-market, mass merchandisers and deepdiscount pharmacies, researchersevaluated the influence of the intro-duction of these Cox-2 inhibitors onthe number of overall NSAID pre-scriptions written between 1998 and2003. Results indicate that NSAIDtherapy prescriptions increased 67.7percent during the five-year periodprimarily because of the availabilityof Cox-2 inhibitors. During the firstyear following their introduction,these Cox-2 agents accounted formore than two-thirds of the increaseseen in NSAID prescriptions.

As might be expected, the newgeneration of inflammation fightershad a huge impact on the anti-inflam-matory market, and they now repre-

sent roughly 44 percent of the totalanti-inflammatory drugs other thansteroids prescribed by doctors, saidBethany Fedutes, a Clinical Specialistin Drug Information at the Universityof Pittsburgh and an investigator inthe study. Of course, traditionalNSAIDs are available over-the-counter in lesser strengths than theprescription forms of these drugs.

Savings on ulcer prevention nevermaterializedBecause of the general expectation ofreduced stomach symptoms inpatients taking Cox-2 therapy,researchers were surprised to find thatphysicians have not decreased thenumber of prescriptions written forulcer prevention medications such asproton pump inhibitors in patientswith rheumatoid arthritis (RA) andosteoarthritis. Patients taking con-ventional NSAIDs for chronic inflam-mation often required additional med-ications to eliminate the potentialstomach distress caused by such aregimen. Because Cox-2 therapiesare thought to be less likely to causeulcers, this was an unexpected find-ing, especially since those promotingthe new class of drugs maintainedthat the additional expense of Cox-2NSAID would be justified because ofthe assumption they would decreasethe number of prescriptions for medi-cations to prevent traditional NSAIDs'side effects.

Researchers conducted a three-year, semi-annual evaluation on10,392 rheumatoid arthritis andosteoarthritis patients and found thatthose taking the drugs that wereassumed to be without stomach com-plications were just as likely to beprescribed ulcer prevention therapy asthose taking the cheaper NSAIDs.

Your own heart and stomach shouldhelp you choose the right drug

The recent announcement that thedrug Vioxx was being pulled from

Confused about anti-inflammatories? Learn the facts

17

pharmacy shelves because of heartand stroke risks left a lot of painpatients stunned, confused and wor-ried. Some are even wondering ifthey should abandon medications thatare in the same family as Vioxx, butdoctors from the University ofMichigan Health System say thereare plenty of options to relieve painand arthritis symptoms, and thatpatients should talk with their owndoctors about what medication orcombination of medications is rightfor them. In light of the effective-ness of traditional NSAIDs likeaspirin and ibuprofen, patients mayhave more choices than they think.

The choice may come down toletting your heart or your gut decide -literally, say the doctors. Patientsshould be treated with medicationsbased in part on their individual risksfor heart disease and stomach prob-lems, says Mark Fendrick, MD, a U-M professor of internal medicine whohas studied the use of the family ofmedicines that includes Vioxx. In2002, he co-created a pain-medica-tion guideline for doctors that waspublished in Pharmacy andTherapeutics and adopted by theMichigan Quality ImprovementCouncil. It took into account earlyevidence that Vioxx and its cousinsmight raise the risk of a heart attack.

"Every patient is different, butthere are clear options even in thewake of the Vioxx situation," saysFendrick. "Patients should work withtheir clinicians to determine the bestcombination for them, and to persistuntil they get relief. No one shouldhave to live with pain and othersymptoms that interfere with theirdaily life." Fendrick's guide fortreating patients' pain can be boileddown to a four-box grid that takesinto account risk for heart diseaseand risk for gastrointestinal problemscaused by NSAIDs. (See back cover.)

It's based on research showingthat Vioxx and similar prescriptiondrugs, traditional NSAIDs, are avail-

able both by prescription and over-the-counter. But either way, they'remuch less expensive than Cox-2inhibitors. The grid also takes intoaccount the fact that many peopletake another NSAID - aspirin - everyday to reduce their risk of a heartattack. Taking aspirin with any otherNSAID, including Cox-2 inhibitors,creates a combined effect thatmarkedly increases the risk of gas-trointestinal complication includingulcers and bleeding.

"Most patients and many clini-cians are unaware of the fact thatadding aspirin to a Cox-2 inhibitortakes away a great deal, if not all, ofthe gastrointestinal safety benefit,"says Fendrick. "In fact, a recentnational study showed that over 50percent of Cox-2 users also takeaspirin, and are therefore puttingthemselves at risk for ulcers and gas-trointestinal bleeding." Add to thatthe added heart risk that Cox-2inhibitors appear to carry, and it turnsout that people who have sufferedheart attacks, chest pains or strokes,or have a high risk for them, proba-bly shouldn't take Cox-2 drugs at all.In fact, a warning to that effect wasplaced on Vioxx years ago. Manypatients who take both kinds ofNSAIDs benefit by adding a stom-ach-protecting drug called an acidblocker, available by prescription(under the names Nexium andPrevacid) or over the counter (sold asPrilosec).

"So, the bottom line is, patientsshould talk with their clinicians abouttheir pain, their heart risk, and theirrisk factors for gastrointestinal com-plication from NSAIDs. Don'tassume that what works for one per-son will work for you, or that risks orside effects are the same for every-one," says Fendrick. "And no matterwhat, be frank with your doctorabout pain that you're feeling,because in the end you should beable to get relief."

Painkillers, antioxidantsfound in tart cherries

The chemicals that give tart cherriestheir red color may relieve pain betterthan aspirin and may provide antioxi-dant protection comparable to com-mercially available supplements likevitamin E, according to MichiganState University researchers. The newfindings "suggest that the consump-tion of cherries may have the poten-tial to reduce cardiovascular or chron-ic diseases in humans (such as arthri-tis and gout)," write the scientists.

The research was published in theJanuary 28, 2004 web edition of thepeer-reviewed Journal of NaturalProducts, published by the AmericanChemical Society, the world's largestscientific society.

While cautioning that studies havenot yet been conducted with humansubjects, lead author Muralee G. Nair,PhD, says their laboratory assayresults suggest that a person eatingabout 20 tart cherries could realizeantioxidant or anti-inflammatory ben-efits. That number of cherries contain12-25 milligrams of the active com-pounds, called anthocyanins, accord-ing to the authors.

In the study, anthocyanins werefound to prevent oxidative damage,caused by oxygen or free radicals,about as well as compounds in com-mercial antioxidants. They also inhib-ited enzymes called cyclooxygenase-1and -2, the targets of anti-inflammato-ry drugs, at doses more than ten timeslower than aspirin. "It is as good asibuprofen and some of the nonsteroidalanti-inflammatory drugs," says Nair.

"Daily consumption of cherrieshas the potential to reduce pain relat-ed to inflammation, arthritis andgout," adds Nair. While reiterating theneed for human studies, he says amarket may one day exist for puttingthe anthocyanins in pill form: "Thenpeople can pop a pill instead of eatinga whole bowl full of sour cherries.That's pretty hard to do."

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Anthony Amato, MD, is Chief of theNeuromuscular Division and Directorof the Clinical NeurophysiologyLaboratory at Brigham and Women'sHospital, Boston. He is alsoAssociate Professor of Neurology atHarvard Medical School.

By now, Dr. Anthony Amato trusts hisclinical instincts when examining anIBM patient: "Here's a man over 50who's weak, who has noticeable atro-phy of his thigh muscles and says he'sbeen getting slowly weaker for yearsbut just thought he was out of shape.Now, you know and I know what hehas. What is it?" The audience replyis unanimous: "IBM."

That's not only the first choice,Amato said, it's likely to be the sec-ond and third choices as well.Addressing the crowd at the AnnualConference, he asked another ques-tion: "How many of you were diag-nosed with another disease - PM orALS or some mixed connective tissuedisease - before the correct diagno-sis?" Seeing almost half of the IBMpatients raise their hands, Amato nod-ded. The clinician's experience is thebest tool for diagnosis, he said: anMRI will only diagnose signalchanges, an EMG might miss it alto-gether. Even with some response tomedicines, said Dr. Amato, he stillquestions the diagnosis. Steroids, forinstance, may slow the progress of thedisease, so there's a modest benefit.However, this improvement doesn'tdissuade him from thinking the dis-ease may be a dystrophy or IBM.Without a major response to treat-ment, he "scratches his head," consid-ering different scenarios to reach theright diagnosis.

Polymyositis is not so easy to pindown, Amato said: "Most often it's acollection of syndromes that do notalways have a lot of features in com-mon." It's a hodge-podge, and if youdon't respond to treatment, chancesare you really have IBM. If it's estab-

lished that you truly have polymyosi-tis, and standard prednisone therapydoesn't help you, it's time to reallywork with your physician, said Dr.Chester Oddis. "This is where it'sessential to find someone who willcommunicate with you, who will tryone treatment and then another andanother until something is effective,"he said. "All of us here get the veryworst cases; and we also consult withother physicians from all over theworld." Oddis said that treating thelung symptoms aggressively isextremely important. "If you havethe JO-1 profile and lung disease,please pursue treatment," he said.There's no magic bullet, just an arse-nal of choices that a skillful cliniciancan offer and monitor. "DM is some-thing you can hang your hat on," headded. "With PM, that's often not thecase." Dr. Fred Miller acknowledgedthat it's frustrating for both the physi-cian and the patient when no exactdiagnosis is possible. "We hope thiswill change," he said, "as we learnmore."

Amato, who has published somewell-received commentary on theconfusion surrounding polymyostis,believes that the disease is very dif-ferent from the classification acceptedby many physicians. "It is not justdermatomyositis without the rash," hesaid. Neither is it one single diseasewith symptoms and syndromes alikein every patient. "What we are reallyseeing is that it is a collection of dis-eases that varies with every patient,"he said. "With PM, I advise people tobe proactive, to understand as muchas possible about their own particulardisease, and to keep working with theteam of doctors they trust."

Even when patients diagnosedwith assumed PM are stabilized usinga combination of treatments like pred-nisone, methotrexate andcyclosporine, Amato still recom-mends retesting for IBM. He'd stillwonder about the diagnosis of PM, he

said. A muscle biopsy doesn't alwaysshow inclusions, so the pattern ofweakness holds clues to the properdiagnosis. If you need three drugs tocontrol your disease but you still expe-rience weakness, this raises questions.

Questions from patients

For the Question-and-Answer sessionat the Annual Conference, Dr. Amatowas joined by Frederick Miller, MD,PhD, the Senior Investigator andChief of the EnvironmentalAutoimmunity Group, NIEHS, at theNational Institutes of Health. Dr.Miller serves on The MyositisAssociation's Board of Directors andas Vice Chair of the MedicalAdvisory Board.

Treatment goalsQ With current treatments, are wetreating the disease or the symptoms?

A "The reality is we don't know thecause of these diseases," said Dr.Miller, "so we are not directly treatingthose diseases with immunosuppres-sants." Since the immune systemseems to be involved at some point inthe disease process, doctors are cur-rently blocking this system to preventsymptoms and further muscle damage.The fact that doctors can't say peopleare cured, he said, points to the factthat doctors are treating the immuneresponse and not the disease itself.

Q I'm willing to take anything thatmight work for IBM. How does thatfit into medical ethics?

A "We as clinicians take an oath tofirst do no harm," said Dr.Amato. Doctors mustcontinually weigh risksand benefits of treatments,and the decision is individu-al to each patient. For somepatients, having a greater riskfor certain side effects orother conditions doesn't mat-

Experience helps when diagnosing IBM

19

ter; for others, this decision is not asstraightforward.

Alzheimer’s treatment for IBM?Q Medicines used to treat myositis atthis point are off-label. Is there anyanecdotal evidence that Aracept, amedicine used for Alzheimer'sDisease, will be effective in treatingmyositis?

A "It's a misunderstanding," said Dr.Amato, "to think of IBM asAlzheimer's of the muscles."Researchers use Alzheimer's as amodel to show that IBM could be adegenerative disease where inflamma-tion is present, he said. InAlzheimer's, however, the problem isextracellular; in IBM, intracellular.Do the amyloids have something todo with the disease (IBM), or are theyjust innocent bystanders? Thatremains to be answered, he said. Inthe meantime, he sees no real reasonto consider Aracept as a possibility intreating myositis, as Aracept targetsthe neurotransmitters of the brain.

Intravenous immunoglobulinQ My husband takes intravenousimmunoglobulin (IVIg) for his IBM,and the doctors feel his disease is sta-bilized because of this. They're afraidto take him off of this treatment. Isthere any proof that IVIg is effectivein treating IBM?

A In large double-blind trials testingIVIg for IBM, the treatment didn'tshow significant benefit in musclestrength, for example. Chances are,

said Dr. Amato,you'll find some

benefit in a par-ticular muscle

group, butit's hardto pin-point

unlessyou're

studyingthat group of

muscles specifically.

It's also difficult to determine if IVIgdoes slow the progression of IBM,even in the absence of dramaticimprovement, as you'd need a rela-tively large number of subjects and alonger period of time for this type ofstudy. In deciding whether or not tocontinue with IVIg, you should weighthe risks versus benefits, consideringtime and cost as well, he said.

Enbrel and ImuranQ I've heard Enbrel loses its effec-tiveness over time, so my doctor isconsidering adding Imuran. Should Ibe concerned about long-term use ofImuran and possible liver damage?

A Enbrel has been shown to be effec-tive in treating rheumatoid arthritisbut not proven for myositis, said Dr.Amato. People do use it to treatmyositis; some with benefit. There isno evidence of long-term liver dam-age. If damage were to occur, hesaid, you would see it early on in thetreatment so that you could stop tak-ing the medicine.

There is a higher risk of malignan-cy with certain medicines, but evenwith the risk being greater than thenormal population, it is still a tinyrisk, he said.

Stem cell researchQ Can you tell us more about stemcell research as it relates to myositis?

A There are some promising leads,said Dr. Miller, but clearer answersare still 5 to 10 years off.Researchers are limited by the Bushadministration's decisions on stemcell research, and it's certainly a topicof much debate.

Oxandrolone for IBMQ How effective is oxandrolone forIBM?

A Dr. Rutkove did one study inBoston looking at oxandrolone, but itdidn't prove to be effective in treatingIBM, said Dr. Amato.

Approval for new treatmentsQ Other countries seem to be lessrigid in their guidelines for approvingand legalizing medicines. Is this thecase?

A This is in fact the case, said Dr.Miller, but the Food and DrugAdministration (FDA) seeks safetyabove all else. There is an increasingtrend toward completing Phase I andII trials in other countries. Thesecountries still follow a set of guide-lines, but they are less rigid thanthose in the U.S. The FDA acceptssome information from these trials,possibly helping to speed up the pro-cess for approving medicines.

It can take from several to 10years to gain FDA approval formedicines. The first phase tests safe-ty and tolerability; the second, effica-cy. Further phases are needed tostudy the treatment in larger groupsand with different conditions beforeapproval is given.

MyostatinQ I've heard myostatin mentioned inthe news recently. Is there any hopein this for those with myositis?

A Myostatin, a protein that occursnaturally in your body, acts to slowmuscle growth. There have beenrecent reports of animals and evenone child without the ability to pro-duce myostatin, resulting in unusuallylarge muscles, said Dr. Amato. Thereare animal models to study the effec-tiveness of medicines aimed atinhibiting myostatin. This seems toimprove muscle strength and to showsome benefit under the microscope,he said.

Studies are currently underway tolook at myostatin and certain muscu-lar dystrophies. This is promising forthose with myositis, he said. He isoptimistic further studies are on thehorizon, focusing on different diseasegroups including myositis.

20

Dr. Todd Levine's fascination withsome rare nerve diseases led him tothe discovery that rituximab - a chem-ical specifically designed to deplete Bcells - would also work for patientssuffering from dermatomyositis.Speaking at the Annual Conference,Levine said that a couple of myositispatients who crossed his path whilehe was using rituximab (marketed asRituxan) for patients with IgM neu-ropathies had such a good responsethat he suggested it for a youngwoman whose dermatomyositis was-n't responding to conventional myosi-tis therapy. The Arizona neurologistwas pleased with the quick, dramaticresults. After her roommate in therehabilitation center requested thedrug and had similar positive results,Levine designed a small trial of hispatients and those referred by TMA.Improvement in the eight patients wasimpressive and the one side effectreported (due to a nursing error) wasquickly resolved. Since one of thepatients was a 12-year-old, Levineexpects rituximab to be a welcomechange from conventional therapy forjuvenile as well as adult myositispatients.

A couple of slides Levine showedthe conference audience demonstratedwhy B cells are considered the culpritin DM. B cells cluster around theportions of slides taken of musclewith obvious damage. B cells arewhat researchers call transient cells:they appear in the cellular transforma-tion from stem cells to plasma cells.The need for a DM treatment that tar-gets these cells is obvious. Levinesaid: conventional treatment withprednisone has the side effects of dia-betes, bone thinning, weight gain andmood swings, sometimes so severethat patients can't continue taking it.(See Prednisone, page 4). That'sbecause prednisone and virtuallyevery other myositis drug targets the

entire immune system. The new tar-geted therapies - those that zero in onthe disease process - are like smartbombs, Levine said. They attack thevery specific cause of the disease,rather than using the shotgunapproach of prednisone, methotrexateand others. Although Levine foundimprovement in all but one of thepatients using rituximab, he can'texplain exactly why. "We don't knowhow it works," Levine told his audi-ence. "That's more common withmedicines than you might think."One patient who had never had anytreatment at all for her myositis didespecially well and didn't require anyother medication, which causesresearchers to speculate that the"smart bombs" might eventually bedesirable as the first choice for DMrather than the last resort.

In conducting his small privatestudy, Levine worked with myositispatients from all over the country. Acouple were not taking prednisone,and some were taking prednisone andother drugs when they enrolled in thestudy. Levine worked with their per-sonal physicians, who graduallytapered the other medication as therituximab took effect. Each patientimproved quickly and sustained theimprovement for several months.They relapsed at different time peri-ods following the last treatment, andLevine found this could be reversedwith sporadic continued treatment.Several continued to augment theirrituximab treatment with small main-tenance doses of prednisone.

Levine pointed out that theinvolvement of B cells is central tothe disease process of dermatomyosi-tis, which targets the blood vesselsaround the muscles rather than themuscles themselves; in polymyositis,the T cells appear to be moreinvolved as they attack the actualmuscles. But new rituximab studies,

led by TMA Medical Advisory Boardmember Dr. Chester Oddis, will beginat several centers, and they willinclude polymyositis as well as der-matomyositis patients, children aswell as adults. The studies will beginin fall, 2005, and TMA will publishtrial enrollment information as soonas it is available.

A patient’s story

Lori Fisher is a long-time member ofThe Myositis Association and recentlyparticipated in a clinical trial study-ing rituximab (Rituxan). She sharesher experience with us:

At the time I heard of Dr. Levine's rit-uximab (Rituxan) study in relcalci-trant and long-term DM patients, myneurologist had just told me to takethe big family vacation toDisneyWorld because there was noth-ing more he could offer me. I'drecently been hospitalized for 14 dayswith a pulmonary embolism follow-ing plasmapheresis, and the neurolo-gist felt I would have to "wait formodern medicine to catch up with mycondition." Fortunately, throughTMA, I'd learned of the Rituxanstudy. When I visited my rheumatol-ogist, Dr. Kathleen Price, I was dou-bly fortunate because her PA hadworked with an oncologist and wasfamiliar with Rituxan.

My first treatment with Rituxanwas a resounding success although itdidn't seem that way at first when twomonths afterwards, I had a DM rash,the beginning of my usual springtimeflare. With the addition of 10 mgs ofprednisone a day, I immediately feltstronger than I had in decades.

Thanks to the Rituxan/decadron (acorticosteroid medicine) infusions fol-lowed by maintenance methotrexateand prednisone, I was soon going hik-ing several times a week on therugged paths of Bull Run Mountain in

Smart bombs vs. shotguns: new medicines attackthe disease, not the whole body

21

Thoroughfare, Virginia. One fineday, I hiked a 6-mile loop trail atManassas Battlefield Park. Thanks toDr. Levine's research, the summer of2003 is one for the memory books.

By December of that year, I need-ed additional treatment, and werepeated the Rituxan. I learned torespect the role B lymphocytes playin fighting infection. I think I usedthe strength from those infusions tofight off several different kinds ofinfections. (See JM and prednisone,page 6.)

I've recently completed my thirdcourse of Rituxan. Amy, Dr. Price'sPA, has told me that everyone in thefield is very excited about Rituxan,especially when it's combined withdaily prednisone. Even though I don'ttake well to prednisone, I've agreed totry 5 mgs a day, to see if it helpsboost me into another remission likethe one in the summer of 2002. Idon't know if I'll ever go back to thetop of Bull Run Mountain, but if Iclose my eyes, I can remember whatit was like to stand there on top of thebig white rocks overlooking thePiedmont at 1,300 feet elevation. Apriceless memory, thanks to Dr. ToddLevine's research!- Lori Fisher

Why a muscle biopsy?

When prednisone was the only toolavailable, it didn't matter so muchwhether the disease being treated wasPM, DM or a collection of syn-dromes, Dr. Levine said. "Since itwas just about all we had and it treat-ed everything, it wasn't so important."Not only is this procedure, whichgives the clinician a picture of theaffected muscle, important for diag-nosis, it's also very important as abeginning marker in the treatmentprocess. Levine expects muscle biop-sies to become routine in myositis astreatment becomes more and moretargeted to very specific diseases.

ments, and, for those with DM, sunprecautions, topical corticosteroidsand hydroxychloroquine (Plaquenil)for the skin involvement. If you haveother factors like lung involvement,intravenous corticosteroids are usedto control the disease more rapidly.Dr. Chester Oddis, a TMA medicaladvisor and professor at theUniversity of Pittsburgh School ofMedicine, suggests IV pulse methyl-prednisolone with the presence oflung problems but notes that immuno-suppressants are often required as well.IV methods are also preferred by manywhen treating children to diminishlong-term adverse effects.

The most common second-linetherapies are methotrexate and aza-thioprine (Imuran). Intravenousimmunoglobulin (IVIg) andcyclosporine also fall into this catego-ry. Often, combinations of medicinesare used for more aggressive treat-ment. There is no standard for whatcombination works most effectively."The reality is we don't know whichpatients will respond best," saysMiller. Tacrolimus (Prograf),mycophenolate motefil (CellCept),cyclophosphamide, and chlorambucilare all considered third-line agents.

Experimental therapies show somepromise, including biologic agentslike infliximab (Remicade). A currentNIH study showed initial positiveresults, with some patients clearlyresponding to Remicade and othersdefinitely not responding. The ques-tion of how many would fall intoeach category remains. In a couple ofyears, results from this trial willexplain this disparity more clearly.

Response to treatmentDoctors can't predict how you'llrespond to any particular therapy,says Miller, but there are some gener-al rules. As with all rules, he pointsout, there are exceptions. Doctorslook at poor prognostic factors - for

example, older patients; those withcardiac, pulmonary or gastrointestinalinvolvement; and patients with alonger delay between disease onsetand the start of treatment - when for-mulating a treatment plan.

With more research, Dr. Miller isoptimistic that answers to the yet-unanswered questions are on the hori-zon. He encourages everyone to helpraise funds for research, writeCongress to increase funding forautoimmune research, and participatein clinical trials as they apply to you.

Myositis 101, continued from cover

Prednisone, continued from page 6Rather than adding another supple-ment, he advises patients to eatbananas for potassium. He recom-mends periodic eye exams to screenfor cataracts.

"Sometimes adjusting the dose ofprednisone will improve insomnia,"he said. "Other times, the patientmakes a natural adjustment after afew days." He has reports frompatients who have been helped bymelatonin, available over the counter.

This material is compiled from lecturesgiven by Dr. Chester Oddis, interviewswith TMA medical advisors, and articlespreviously published by TMA.

Questions about nutri-tion? Use the hotline

Increasingly, research supports thenotion that nutrition may be a keyplayer in preventing illness and pro-moting healing. For instance, tomatosauce is high in lycopene, which mayhelp prevent or slow the progress ofprostate cancer. Many other fruits andvegetables may also have preventivepowers. The Nutrition InformationService maintains the EatRightNutrition Hotline to answer questionsabout good nutrition and health. Callthe hotline at 1-800-231-3438.

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Many myositis patients, young andold, must deal with extremely dry,itchy skin, especially the cracked andscaly hands known as mechanic'shands. With the helpful advice of oth-ers, you can soothe this uncomfortablecondition especially common in dermato-myositis (DM) and polymyositis (PM).

"Even when both skin disease andmuscle disease is present, topicalcream- and ointment-based medica-tions can be applied to the skin rash inorder to minimize the doses of inter-nal medications that are required tocontrol the entire disease," says Dr.Richard Sontheimer, John S. StraussEndowed Chair in Dermatology,Professor and Head, Department ofDermatology, University of IowaCollege of Medicine, and TMAMedical Advisory Board member.

Ointments, oils, creams, and lotions

Moisturizers come in different forms -ointments, oils, creams, and lotions.Ointments most effectively trap themoisture in your skin, says Dr.Sontheimer, but they can also leave agreasy feeling. Use Aquaphor,Vaseline Petroleum Jelly, or anotherointment in a small amount on theaffected area, and rub it in well toavoid excessive greasiness. Oils,including baby and mineral oils, arestill effective without being as greasyas ointments. Creams tend to be morepopular since they disappear whenrubbed in. Dr. Sontheimer citesOriginal Eucerin Cream, Nivea, andNeutrogena Hand Cream/ NorwegianFormula as popular brands that arefrequently recommended by dermatol-ogists. Lotions often contain alcohol,which may cause the skin to dry evenmore if used too often.

Patient-to-patient recommendations

What do patients themselves recom-mend to each other when ordinarylotions don't do the trick? DaleSjogren, a PM sufferer, stumbled uponBadger Balm at his local hardware

store. He coats it on his rough spotsand covers them with a Band-Aidovernight. "It generally heals a crackwithin 12 hours," he says.

Beth, another PM patient andBulletin Board regular, uses No-Crack hand cream she found atwww.restorationhardware.com. "Myfingertips still split and crack attimes," she says. "But not near asmuch when I am using this."

Two more frequent posters on theweb site's Bulletin Board, DorrisNorris and Lea Jaeger, both praiseMSM Cream. Dorris spotted this rem-edy at her health food store; Lea dis-covered a mail order web site, KalaHealth Inc., willing to send it to her inIsrael. "I have IBM and also have fin-gers that split, bleed and get verysore," says Dorris. "[MSM Cream]heals the places quickly."

Other Bulletin Board users volun-teered these helpful products:L'Oreal's Ombrelle 60, a light, non-greasy, and fragrance-free sunscreenthat protects against both UVA andUVB rays; Aquaphor, a fragrance- andpreservative-free lotion that comes inoriginal or healing ointments; andDermaplast, a pain relieving spray thatnumbs and soothes the affected area.You can find most of these products atyour local pharmacies, including CVS(www.cvs.com) and Walgreens(www.walgreens.com); Cheri (DM)came upon L'Oreal's Ombrelle 60online at www.feelbest.com.

Scalp solutions

"Because the hair interferes with theapplication of creams and ointments,the scalp requires a corticosteroidchemical dissolved in other vehiclessuch as solutions, gels, sprays, orfoams," says Dr. Sontheimer. "Apotent corticosteroid solution mas-saged into the still-moist scalp aftershampooing can provide the greatestbenefit from this form of therapy." Inanswer to a fellow Bulletin Boarduser, Jane, a DM patient, recommends

Luxiq (betamethasone valerate), a top-ical corticosteroid, for scalp itch. Thismedicine is available as a prescriptionfoam for scalp rashes. "It actuallyworks like a mousse and gives yourhair fullness while helping yourscalp," she says. She also offers fluo-cinolene acetonide topical solution(also known as Derma-Smoothe/FS)and desonide ointment, both prescrip-tion medications.

Mummy treatment

Sometimes the substances alone arenot enough. For Andrea Clausen,nothing compared to the wet-pack, ormummy treatment prescribed by theMayo Clinic to help her skin moreeffectively absorb her medicatedcreams.

Andrea applies wet dressings ofsoft, white, 100 percent cotton materi-al with lukewarm water (avoid hot orcold), squeezing out the excess waterso the material was damp but not drip-ping. She then applied the prescribedcream to her skin, covering it with thewet dressings. She treated her stub-born rash for thirty minutes twice aday, noticing dramatic results withintwo weeks.

When finished with the treatment,she reapplied the creams or ointments.If mechanic's hands bother you, tryDermpak Gloves to cover the lotion,ointment or cream you choose.Andrea treats her hands when they'reirritated, spreading cream over herhands and wearing the gloves to beduntil her rash improves.

Prevention through sun protectionProtection from the sun's harmful raysguards against drying out your skineven more. Use sunscreen with SunProtection Factor (SPF) 15 or higher,and apply as much as you wouldlotion on dry skin. If you don't use theproper amount of sunscreen, the SPFactually decreases. Be aware that cer-tain medications, including methotrex-ate and tetracycline, increase your

Patients find relief from dry skin, itching, rash

23

sensitivity to the sun, so read thelabels carefully. Using the BulletinBoard to solicit peer advice, Cherisought information on sunscreens withmexoryl to prevent a sun-inducedflare, as recommended by her derma-tologist. Liesl Dutro offeredAnthelios "L" SPF 60 Sun Block asan option, though Chris's responsementioned his recollection of itsstrong scent and greasy feeling.

Sun protection is also available incertain cosmetics, includingDermablend and Covermark. Theseproducts blend physical sunscreenwith cover-up. DermablendCorrective Cosmetics promise natural-looking coverage that won't clog yourpores, are fragrance-free, and resistsmudges. Even more important tothose with skin problems, however, isthe SPF 30. Covermark also offerssun protection, with SPF 20 "FaceMagic" and SPF 16 "Leg Magic" thatwon't rub off or smudge. Covermark'scosmetic camouflage is 100 percentwaterproof and highly pigmented.

The increasing emphasis on sunsafety has spurred companies to createmore stylish, comfortable sunprotec-tive clothes - clothes with the protec-tion woven directly into the fabric.You'll find swimwear, business andpolo shirts, track pants, hats, drivinggloves, canopies, umbrellas, and muchmore. It's important to understand thelabeling, which the Federal TradeCommission monitors carefully. TheUltraviolet Protection Factor, or UPF,measures how much of the sun's radi-ation is absorbed by the fabric. So aUPF of 20 means that 1/20th of theradiation passes through the clothing;or in other words, the fabric reducesyour exposure by 20 times. A UPFvalue of 15-24 is considered goodprotection against UV rays; 25-39,very good; and 40-50, excellent.Some UV protection may be lost if theclothing is overly worn or washed,wet, or stretched out. Enter "sun pro-tective clothing" in your Internetsearch engine to find a list of compa-nies stocking these products.

There are times you may not con-sider sunscreen to be essential, likewhile driving or going for a shortwalk. Windows and car glass do notblock the UVA rays, prompting somecompanies to offer UV light blockingfilm. Fluorescent lights also emitsome UV rays, and you can placeacrylic diffusion shields over the bulbsfor protection. For these protectivefilms and shields, Dr. Sontheimer sug-gests the following companies:Southwall Technologies Inc., NorthSolar Screen, and Llumar. The filmcoatings absorb or reflect from 96 to99 percent of the sun's harmful UVrays. North Solar Screen shades rollup and down so that you can use themaccording to your different needs forday and night, and they offer bulbjackets to provide UV protection fromfluorescent lights.

Direct treatments for JM rashThough prednisone and othermedicines help the rash that comeswith JM, sometimes it's necessary toput ointments directly on the rash tomake it heal. Tacrolimus (Protopic)and pimecrolimus (Elidel) are two ofthe topical creams used to moreaggressively fight the rash.

Julia Becker, now in remissionfrom her JM, participated in aresearch study looking at the effec-tiveness of Protopic on the JM rash.She applied 0.1% topical tacrolimusointment twice a day only on the partsof her skin with a rash. "We didn'treally see any effect at first, but withina few weeks, Julia's rash started get-ting noticeably better," says RalphBecker, Julia's father. "Over the fol-lowing months, she continued to showa gradual improvement in the rash andafter about nine months of use, herrash was gone and we were able todiscontinue using Protopic." Theresearchers concluded that Protopicmay be useful in helping the JM rash,but more studies are needed.

"We had a strong family history ofeczema, so it seemed likely that ourkids would get it," says Shari, a JM

mom. "The most helpful topicalcream we have found is Elidel." Herson Ricky, another JM patient, hasalso found success with nightly appli-cations of Elidel cream.

This information first appeared in the2003 OutLook Extra Treatment Issue.

Dermatologist gives tips forwinter skin care

In the winter, it feels good to wrapyourself up in heavy sweaters andturn up the heat in your house. Buthave you given any thought to what'shappening to your skin as it gets cold-er? That dry itchy skin you get in thewinter can be a direct result of tryingto keep warm. However, winter skincan be prevented with a few simplechanges to your skin care routine.

"The hot air inside your home oroffice can do more damage to yourskin during the winter than the coldair outside," said dermatologistStephen Webster, MD, ClinicalProfessor of Dermatology at theUniversity of Minnesota MedicalSchool. "When the relative humidityinside drops below 60 percent, yourskin begins to lose moisture, causingthat dry, itchy, flaky skin that irritatesso many during the winter months."

The skin is made up of severallayers of cells. The epidermis, the toplayer of the skin, along with the oilglands, produce lipids, and theselipids keep the skin from losing mois-ture and make it soft and supple. Butyour skin is constantly losing mois-ture into the air and every time youwash your skin, you strip away theselipids, letting more moisture evapo-rate and drying the skin. However, inhumid conditions, the skin canreplenish itself by soaking up mois-ture from the air. So, when thehumidity drops, as it does in manyplaces in the winter, your skin losesanother opportunity to moisturizeitself. Couple that with the low

See Skin tips, next page

24

humidity of indoor heating, and hottershowers and baths, and your skin canbecome dry and irritated.

It's these cold weather activities,such as taking hotter showers andturning up the heat that can cause dryskin during the winter. To correctsome of the misconceptions that canlead to dry winter skin, Dr. Websterprovides the following facts:

Myth: The hotter and longer theshower, the warmer I'll feel. Fact: Sure, you'll feel warm, says Dr.Webster, but only for a few minutes.As soon as you step out of the water,your skin begins to lose moisturebecause hot water removes natural oilfrom the skin, making it dry anditchy. Bathe or shower in lukewarm -not hot - water, and limit your show-ers to 5 to 10 minutes.

Myth: Switching your brand of soapcan "confuse" skin, leading to irritation.Fact: All soaps have the potential tocause contact dermatitis, especially ifyou are allergic to certain ingredientsin the soap, says Dr. Webster. It isperfectly fine to use the same brandof soap throughout the year. However,if you find your skin becoming drierin the winter months, look for amilder soap that is fragrance-free. Infact, many soaps today contain mois-turizing ingredients, like oils and vita-mins, which can be beneficial foryour skin all year round.

Myth: Completely dry your skinbefore applying lotions and creams. Fact: Dr. Webster recommendsapplying moisturizers to skin withinthree minutes of stepping out of theshower or bath. Putting on a cream,ointment or lotion helps trap thewater in the upper layers of the skinand decreases dryness and itching.Find a cream or lotion with a lightertexture to avoid greasiness.

Since severely dry skin is lesseffective at providing a barrier against

infection and can split and bleed, cre-ating a greater chance for an infec-tion, Dr. Webster gives these tips for healthier winter skin:

Remember, snow can reflect morethan 80 percent of the sun's damagingrays, so be sure to always wear abroad-spectrum sunscreen with anSPF of 15 or higher. Reapply it everytwo hours for maximum benefit.

Don't forget to protect your lips.Look for a lip balm with an SPF of15 to help prevent chapped lips.

Consider purchasing a humidifierto keep the humidity in your homehigher during the winter.

Dab petroleum jelly on problemareas to seal in moisture and healvery dry skin.

After washing your hands, imme-diately put on hand cream to seal inmoisture.

"The winter months don't have to betorture for your skin," says Dr.Webster. "Remember to place agreater emphasis on moisturizing andvisit your dermatologist if your skinbecomes infected or if you don't seeany improvement in your skin."

Skin tips, continued from page 23

During the medical panel and thequestion-and-answer period, Drs.Oddis, Miller, Amato and Levineanswered questions from the audience.

On CampathWith B cells eliminated in DMpatients, they improve: why not trythis approach to the T cells in IBMand possibly PM? "It's a dangerousthing to wipe out all of your T cells,"says Dr. Levine. That's what's hap-pened to AIDS patients. Campath, atreatment now being studied at NIH,affects the T cells and may have somepromise, Dr. Oddis says. To find outmore about the study, go towww.myositis.org (resources) or callNIH at 301-496-4000.

On cancer and transplant drugsWhy use the "old" drugs taken fromcancer and transplant treatment, whenthese disciplines have moved on tonew drugs? "We're looking for somekind of history," says Levine. "Eventhe old drugs don't have a history withmyositis." He added that it was easyto wipe out the immune system. Thehard part is retaining the helpful immu-nity that everyone needs to survive.

On stem cell therapyIt's political and poorly understood,say Levine, Amato and Miller; and allbelieve it shows promise in myositis,noting that everyone is born with thesame amount of muscle fiber theywill die with. Miller says workingwith the tools available to scientistsunder current Bush administrationpolicy is like having a hand tiedbehind your back.

On the placebo effectScientists must have blind studieswith placebos before truly knowingthe potential of a new drug. Here'swhy: Levine quoted a headache studywhere 40 percent of those getting theplacebo reported improvement. Toget a better sense of the effect,researchers released the 40 percentfrom the trial and tried again. Thepercentage of those receiving theplacebo and reporting improvementremained at 40 percent, indicating thatthe placebo effect is more powerfulthan the researchers had anticipated.

On cancer and dermatomyositisCancer is present in 20 to 30 percentof DM patients over 50 within fiveyears, says Levine. If the cancer istreated and resolved, the DM oftengoes away. If more than 20 yearshave passed between the time ofthe discovery of DM and the dis-covery of cancer, they are not relat-ed, he says. Levine recommends afull body scan for anyone withDM: a procedure that will screenfor the cancers that most common-ly affect DM patients.

Short comments from theconference

25

Etanercept (Enbrel), adalimumab(Humira), and infliximab (Remicade)are self-injectable medications knownas biologic response modifiers thatwork to suppress the tumor necrosisfactor (TNF) proteins associated withinflammation. Suppressing tumornecrosis factor has been an effectivetreatment in the day-to-day lives ofmany patients with rheumatoid arthri-tis, and a number of myositis patientshave found etanercept helpful.

All three TNF agents are knownto be very effective in the treatmentof rheumatoid arthritis (RA) but sincethey are fairly new drugs there is lim-ited information about their long-termeffectiveness and safety. A seven-year study of treatment of patientswith early and long-standing rheuma-toid arthritis with etanercept foundcontinued effectiveness and noincrease in toxicity over time, find-ings that may be useful in predictingtheir effect in myositis patients takingthem over the course of several years.Similarly, a four-year study of adali-mumab plus methotrexate in thetreatment of long-standing moderateto severe rheumatoid arthritis report-ed sustained improvement in arthritiswith no new safety concerns. Bothtreatments allowed patients to takelower doses of corticosteroid medica-tions and methotrexate.

Etanercept was approved in 1998for RA and is prescribed to reducethe signs and symptoms of RA. Itinhibits the progression of structuraldamage, and improves physical func-

tion in patients withmoderate to

severedisease;and it canbe usedalone or

in com-bination

with

methotrexate. Neither etanercept norany other drug has been approved fortreatment of myositis, but there arestudies and informal reports of its usein myositis. Adalimumab wasapproved in 2002 and is prescribedfor reducing signs and symptoms ofRA and inhibiting the progression ofstructural damage in adult patientswith moderately to severely activeRA who have had an inadequateresponse to one or more disease-mod-ifying anti-rheumatic drugs(DMARDs); it can be used alone orin combination with methotrexate orother DMARDs.

"The efficacyand safety of adali-mumab seen in six-month clinical tri-als continues inlong-term follow-up for up to fouryears," saidMichael Schiff,MD, Director, Clinical Research,Denver Arthritis Clinic, and leadinvestigator in the study.

Schiff was encouraged by the con-tinued effectiveness and safety ofetanercept: "We report the longestexperience with etanercept and showthat it continues to be effective withlong-term therapy in patients withactive rheumatoid arthritis and notonly allows for a reduction in back-ground corticosteroid doses but iswell tolerated and serious side effectsare rare," said Michael Weinblatt,MD, Professor of Medicine, Brighamand Women's Hospital and HarvardMedical School, and lead investigatorin the study. Dr. Weinblatt presentedhis study at the annual meeting of theAmerican College of Rheumatology.

Proper management can reducepost-surgical infections in patientstaking etanerceptOne potentially serious side effect ofTNF can be prevented and was dis-

Anti-TNF agents: here for the long term?cussed in a recent study. The sameTNF protein that causes symptoms inautoimmune disease also plays a keyrole in suppressing infections withcertain bacteria in the body.Researchers found that continued useof TNF inhibitors before surgerycould increase the risk of many typesof infections, such as septic arthritis,osteomyelitis or deep wound infec-tion, following surgery.

To assess this post-operative risk,researchers evaluated the outcome of91 rheumatoid arthritis patients, aver-age age 59.5 years, who underwent

bone or jointsurgery betweenJanuary 1, 1999and March 15,2004. Patientswho developeddeep bone or softtissue infectionswithin 30 daysafter surgery

were identified and their medicationswere reviewed.

Of 35 patients receiving treatmentwith a TNF inhibitor at the time ofsurgery, seven developed a post-oper-ative infection. In contrast, only threeof 56 patients not receiving a TNFinhibitor at the time of surgery devel-oped an infection. TNF inhibitor usewas associated with a four-foldincrease in risk for infection.

TNF inhibitors such as etanercept,infliximab and adalimumab can bediscontinued and restarted withoutimpairing the health of patients. Thisstudy concludes that, since each drughas a distinct half-life, patients shouldask their physician for pre-surgeryguidelines.

TMA members using infliximab(Remicade) report careful monitoringby their doctors, who discontinue treat-ment at any sign of infection, thenresume it when the infection is past.

Since they are fairly newdrugs, there is limited infor-mation about their long-termeffectiveness and safety.

27

Recent Changes in Medicare May Affect Where You

Receive Your IVIG Treatments

Effective January, 2005 Medicare has changed the way it pays for IVIG. If you have been receiving IVIG, your treatment will still be covered.

However, you may need to receive your treatment in a different location.

IgG America, a national pharmacy specializing in IVIG, can provide your treatment at home

if you have secondary insurance.

Medicare supplementary coverage, often called "Medigap insurance,"is different from secondary insurance.

Medicare supplementary insurance will not pay for IVIG treatments at home.

To find out if your insurance will cover IVIG services at home,

please call us for a free, confidential analysis.Our toll free number is 877.674.9700.

Home IVIG treatments are safe and convenient. A registered nurse will bepresent throughout your IVIG treatment and all supplies will be provided.

You can receive your treatments during the time you choose, including in the evening or the weekend.

For more information about our company, visit our web sitewww.iggamerica.com

IgG. It’s What We Do. It’s All We Do.

28

Medicines and their side effectsSide effects are an unwanted but often common part of taking certain medicines. Some of these effects

are better known – like weight gain with steroid medicines – while others are less familiar. In some cases,these possible side effects are enough to make you think twice before starting a treatment. Below is a list ofpotential unwanted effects of medicines more commonly used in treating the different types of myositis. Notall effects are listed, and not all that are listed require immediate medical attention.

Be sure to talk to your doctor about what you should expect when taking medicines, and keep a journalof how you feel each day when you start a new treatment. This will help you explain to your doctor how themedicine makes you feel – physically and emotionally.

Generic name Brand name(s)* Possible side effects

Alemtuzumab(IV) Campath

Black stools; chills; cough; diarrhea; dizziness; fever;headache; hives; nausea/vomiting; shortness of breath;sore throat; stomach aches; back pain; tingling;indigestion; decreased appetite.

Azathioprine(Oral, IV) Imuran

Reduced immunity; loss of appetite; nausea/vomiting;skin rash; cough; fever/chills; back pain; painfulurination; unusual fatigue; liver problems; anemia;delayed onset cancers possible.

Corticosteroids(Oral, IV, Topical)[Corticosteroids are a type ofmedicine; this is not the genericname. There are a number ofcommon names for corticosteroids,listed here.]

Prednisone, Prednisolone,Methylprednisolone,Dexamethasone,Betamethasone; Topical:Elocon, Luxiq

Lower resistance to infection (also harder to treatinfections); increased appetite; weight gain;restlessness; rounded, “moon”-like face; stuntedgrowth (in children); acne; nausea; indigestion;moodiness, irritability; decreased appetite; thinningbones; abnormality of fat distribution; diabetes;menstrual irregularities; hypertension; cataracts;insomnia; increased thirst; continual stomach pain;vision changes; headache; irregular heartbeat;increased hair growth. Your body needs time to adjustwhen stopping this treatment. Tapering, or slowlylowering the dose you take, is essential. Report anyside effects to your doctor as you are tapering or whenyou are completely off this medicine.

Cyclophosphamide(Oral, IV) Cytoxan

Darkening of skin, fingernails; loss of appetite; nausea;vomiting; diarrhea; abdominal pain; facial redness;headache; temporary hair loss; cough, hoarseness;fever, chills; pain in low back or side; dizziness;shortness of breath; pulmonary fibrosis; blood in urine(even after treatment stops - check with doctor);secondary malignancies; sterility. Some effects ofcyclophosphamide may not occur for months or yearsafter using this medicine.

Cyclosporine(Oral, IV) Neoral, Sandimmune

High blood pressure; kidney problems; increased hairgrowth; trembling hands; tender or bleeding gums;fever; chills. Doctors may monitor kidney functionwhile on this medicine.

29

Etanercept(IV) Enbrel

Abdominal pain, nausea, vomiting (more in children);throat pain; runny/stuffy nose; diarrhea; loss of energy;chills; cough; fever; skin rash; sneezing; chestcongestion; dizziness; fast heartbeat; frequenturination; headache; joint or muscle pain or stiffness

Hydroxychloroquine(Oral) Plaquenil

Diarrhea; headache; itching; decreased appetite;nausea/vomiting; stomach pain; dizziness; restlessness;change in vision; ringing ears; weakness;drowsiness/headache/excitability signs of possibleoverdose

Infliximab(IV) Remicade

Abdominal pain; cough; dizziness; headache;congestion; nausea; shortness of breath; unusualfatigue; back pain; chest pain; fever/chills; facialflushing; hives; itching

Interferon beta-1a(IV) Avonex Heartburn; indigestion; trouble sleeping; chills;

diarrhea; fever; flu-like symptoms; unusual fatigue

Intravenous immunoglobulin(IVIg)

(Also called immuneglobulin intravenous orIGIV)

Fever/chills; backache; headache; joint pain;nausea/vomiting; leg cramps; rapid heartbeat; skinflushing; troubled breathing; feeling lightheaded;changes in blood pressure; feelings of discomfort

Methotrexate (Oral, IV)[also called amethopterin]

Methotrexate, Rheumatrex

Kidney, stomach or liver problems; temporary hairloss; acne; loss of appetite; nausea/vomiting; diarrhea;stomach pain; malignancies; lungproblems/inflammation; delayed onset cancers

Mycophenolate(Oral, IV) CellCept

Constipation; diarrhea; headache; indigestion;nausea/vomiting; cough; fever/chills; back pain;shortness of breath; mouth sores; white patches in mouth

Pimecrolimus(Topical) Elidel

Burning or itching in hairy areas of skin; skinblemishes; earache; stomach pain; chills; flu-likesymptoms; congestion; fever; loss of appetite; muscleaches; headache; warmth on skin; hives; swelling

Rituximab(IV) Rituxan

Back pain; increased cough; loss of strength; muscleaches; night sweats; pain; rash; sore throat; stomachpain; anxiety; dry mouth; fatigue; headache; increasedhunger and thirst; fever/chills; nausea

Tacrolimus(Oral, IV) Prograf

Kidney problems; reduced ability to fight infections;high potassium in blood; low magnesium in blood;high cholesterol; high blood pressure; abdominal pain;anxiety; chills; diarrhea; fever; flu-like symptoms;decreased appetite; nausea; tingling; difficultysleeping; delayed onset cancers

Tacrolimus(Topical) Protopic

Itching skin (in children); headache; fever; bothersomecough; loss of appetite; hives; chills; flushing;swelling; increased skin sensitivity

* There are a number of brand names for certain medicines. The most common are included here.

30

Stem cells from human bloodhelp repair mouse muscles

Regeneration of damaged hearts usingblood stem cells now appears to beclinically promising, say Texasresearchers who show that in mice,human stem cells use different meth-ods to morph into two kinds of cellsneeded to restore heart function - car-diac muscle cells that contract theheart as well as the endothelial cellsthat line blood vessels found through-out the organ. Using a sophisticatedway of examining the "humanness" ofmouse heart cells, researchers reportin the December 21 issue of the jour-nal Circulation (which was publishedonline December 13) that two monthsafter mice with ailing hearts weretreated with human stem cells, abouttwo percent of cells in their heartshowed evidence of a human geneticmarker.

Furthermore, researchersdescribed, for the first time, howthese human master cells use differentways to become two distinct kinds ofcells needed in the heart. Human stemcells primarily "fuse" onto mouse car-diac cells to produce new muscle(myocyte) cells that have both humanand mouse DNA. But to form newblood vessel cells, they "differentiate"or mature by themselves, presumablyto patch damaged mouse blood ves-sels with human cells.

These findings should help resolvedebate within the field as to whetherstem cell transfer actually creates newtypes of cells that last within a heart,says the study's lead author Edward T.H. Yeh, MD, professor and chair ofThe University of Texas M. D.Anderson's Department ofCardiology.

"We have shown that these stemcells create both types of tissue need-ed to repair areas of damage, that theyuse two different ways to developthem, and that these cells can persistfor up to a year, which is a long timein the life of a mouse," he says."Most of all, this study is important

because it begins to explain why stemcells can help a heart heal," he adds."Clinical trials that use bone marrowstem cells in people with heart dam-age have shown promise, but no oneknows how it works. This starts toprovide an explanation."

Yeh and his research team, whichincludes investigators from the TexasHeart Institute, have been looking fora relatively simple way to help restorethe functioning of hearts damaged bychemotherapy, which can occur in upto 10 percent of cancer patients treat-ed with such drugs, he says."Deriving stem cells from bone mar-row is a complicated matter. It wouldbe much easier for patients if the stemcells were taken from blood. It wouldbe as simple as a blood donation. Cellfusion has been important for musclegrowth, Yeh said. Myocytes fuse toform a muscle and the muscleregrows fused. "This paper shows thatfusion is a predominant event in mus-cle cell generation, and it may workby allowing a cell to enter the cellcycle and divide and produce newprogeny, but all of this is new andneeds to be studied further," Yeh says.

Complementary and alternative medicine usewidespread in pediatric painmanagement programs

The use of alternative medicine hasincreased dramatically in the lastdecade, and complementary and alter-native medicines are now used by 50to 70 percent of children with chronicconditions, yet there was no data oncomplementary and alternativemedicine in university-affiliated pedi-atric pain management programs.

In a study by Yuan-Chi Lin, MD,MPH, visiting associate professor,Department of Anesthesia, Children'sHospital Boston, designed to assessthe availability of complementary andalternative medicine in the United

States and Canada, 52 pediatric painmanagement programs were identi-fied and 43 (83 percent) responded toa telephone survey directed to aphysician or nurse from the pain ser-vice program. The survey revealedthat complementary and alternativemedicines are used in more than 70percent of university-affiliated painmanagement programs. Servicesoffered included biofeedback (at 63percent of the centers); imagery (60percent); relaxation therapy (60 per-cent); massage (49 percent); hypnosis(44 percent); meditation (44 percent);acupuncture (40 percent); art therapy(28 percent); music therapy (23 per-cent); self-help groups (19 percent);therapeutic touch (14 percent); herbalremedies (9 percent); chiropractic (7percent); yoga (5 percent); and Tai-Chi (2 percent).

Of these 43 institutions, 30 (70percent) have pediatric pain clinicsfor chronic pain. According to Lin,who is the director of Pediatric PainManagement Service at LucilePackard Children's Hospital atStanford University and associateprofessor of Anesthesia and Pediatricsat Stanford University School ofMedicine, currently on sabbatical atHarvard, research comparing the clin-ical outcomes and cost effectivenessof complementary and alternativemedicine to conventional therapies isof pressing importance.

Quick tips for healthybones:

Increase calcium by choosingmilk, cereal and fruit juice fortifiedwith vitamin D, leafy greens, cheeseand other calcium-rich foods.

Get plenty of protein.Exercise as much as possible.Avoid the "teen-age" diet of high-

fat, high-sugar junk food and high-sugar soft drinks.

!

31

1233 20th Street, NW, Suite 402Washington, DC 20036

2004 Nobel Prize Winner to participate inTMA IBM Conference

Dr. Aaron Ciechanover, winnerof the 2004 Nobel chemistryprize, will be participating alongwith nearly 30 physicians inTMA's conference on sporadicinclusion-body myositis sched-uled for January 26-28, 2005 inMarina Del Rey, California. Dr.Ciechanover of the IsraelInstitute of Technology was oneof three researchers to share theNobel prize for research in ubiq-uitin and proteasome inhibitionin neurodegenerative disorders.There is growing evidence thatproteasome inhibition plays arole in IBM, and Dr.Ciechanover will present on thistopic as well as coordinate thefinal Conference session, "What

are the most promising aspectsof pathogenesis leading totreatment of IBM?"

The Myositis Association issponsoring this first-ever inter-national scientific conference,"Frontiers of ResearchPotentially Relevant toTreatment." It is by invitationonly and includes the world'sforemost s-IBM physicians andresearchers. TMA MedicalAdvisory Board members Drs.Valerie Askanas and MarinosDalakas are organizing thisevent for invited experts to pre-sent and exchange ideas on s-IBM and to discuss promisingresearch directions for s-IBMsuch as the role that aging

plays, unique aspects of the dis-ease and its symptoms, and theroles of inflammation, beta-amyloids, cholesterol, oxidativestress and protein folding. Thisexciting, historic exchange ofideas in an atmosphere of col-laboration and trust is expectedto both advance the globalunderstanding of IBM and con-clude with a consensus on themost fruitful avenues for futureresearch.

The Muscular DystrophyAssociation is providing fundingto cover the costs of publishingand distributing the s-IBMConference report.

NONPROFITO R G

US POSTAGE

P A I DPermit #129

W aynesboro VA