Full Text: Letters

The experience reported by Ujfalussy, et al on the use of intramuscular (im) gold, methotrexate (MTX), and sulfasalazine (SSZ) in psoriatic arthritis (PsA) is very interesting¹. The lack of difference between time on treatment, calculated by survival analysis, with im gold and MTX observed in this study, contrasts with the results obtained in our study and with other reports^2,3.

It is always difficult to explain differences across studies, even more so when treatment is not randomized and the outcome, treatment discontinuation, could be influenced by practice patterns differing across countries. Also, more information about the clinical characteristics of both treatment groups at baseline, about the treatment doses received, and about the results is needed to explore potential reasons for the differences.

I agree with the authors of the letter that non-random allocation of treatment and the fact that some patients having received MTX had failed either im gold or SSZ, are potential explanations for the difference in results observed. If the practice pattern during the study was to reserve MTX for more severe cases or cases refractory to other treatments, this could explain why their results with MTX were less favorable than ours. The authors present information at baseline on age, sex, and disease duration, showing a longer disease duration in the MTX group, but no information regarding disease activity or disease severity. If differences exist at baseline, it would be important to control for them in a multivariate regression analysis, such as a Cox regression analysis, to prevent a confounding effect. To assess whether having used MTX after failure with im gold or SSZ in some of the patients may explain a poorer performance with MTX treatment, one could include order of therapy as a covariate in the Cox regression analysis. Both these analyses were performed in our study and showed that baseline characteristics, other than previous DMARD use, and order of therapy were not significant in our sample. Also, not controlling for repeat observations within patients potentially could dampen a true treatment difference, as patients refractory to all treatments provide multiple observations. The Cox regression method we used allowed the data to be stratified according to first or second treatment course.

It appears that the main difference in the survival results between the 2 studies stems from a shorter survival observed by Ujfalussy, et al for the group receiving MTX [median survival with MTX was 12 months vs more than 5 years in our study (median survival cannot be calculated in our study since less than 50% discontinued treatment, but at 5 years, 54% remained on treatment); whereas median survival with gold was 12 and 14 months, respectively]. Information on the reason for discontinuation may help understand why this difference was observed. Were there more discontinuations for side-effects? If so, it would be interesting to look for differences in practice patterns when dealing with side effects. Or were there more discontinuations for lack of effect? In which case the doses of MTX used in both studies need to be compared. It has been our clinical impression that patients with PsA tend to require higher doses than patients with rheumatoid arthritis.

Finally, the last question to be raised is whether there was a sufficient number of patients taking MTX followed for 2 or more years to have the necessary power to show a difference between the 2 survival curves. Without confidence intervals or number of subjects at risk at different times, it is difficult to assess the certainty of the estimates of survival at 2 years and beyond. The only indication provided is the size of the downward steps on the survival curve, which suggest that the estimates from 2 years onwards are based on relatively small numbers. In our study, although the survival curves appeared different even within the first year, the 95% confidence interval overlapped. The difference between the 2 survival curves became statistically significant only after 1.5 years.

We agree with the conclusion of the authors, that both MTX and im gold are effective treatments, that gold is a good alternative where MTX fails or is contraindicated, and that SSZ, which was not assessed in our study, is another effective treatment, as shown in other controlled studies^4,5.

DIANE LACAILLE, MD, MHSc, FRCPC; HOWARD B. STEIN, MD, FRCPC; JANET RABOUD, PhD; ALICE V. KLINKHOFF, MD, FRCPC, Arthritis Research Centre of Canada; University of British Columbia, Vancouver, Canada.

1. Ujfalussy I, Koo E, Sesztak M. Termination of disease modifying antirheumatic drugs in psoriatic arthritis. J Rheumatol 2001;28: 682-3.

2. Sparado A, Taccari E, Mohtadi B, Riccieri V, Sensi F, Zoppini A. Life-table analysis of cyclosporine A treatment in psoriatic arthritis: comparison with other disease-modifying antirheumatic drugs. Clin Exp Rheumatol 1997;15(6):609-14.

3. Gomez-Vaquero C, Rodriguez-Moreno J, Ros S, Marcos R, Fiter J, Roig Escofet D. Termination of disease-modifying drugs in psoriatic arthritis: study of 109 courses of treatment. Br J Rheumatol 1996;35(6):564-7.

4. Dougados M, Van Der Linden S, Leirisalo-Repo M. Sulfasalazine in the treatment of spondyloarthropathy: a randomized multicentre, double-blind placebo-controlled study. Arthritis Rheum 1995;38: 618-27.

5. Jones G, Crotty M, Brooks P and the Psoriatic Arthritis Meta-analysis Study Group. Psoriatic arthritis: a quantitative overview of therapeutic options. Br J Rheumatol 1997;36:95-9.

Myocarditis Associated with Polymyositis Diagnosed by Gadolinium-DTPA Enhanced Magnetic Resonance Imaging

Cardiac manifestations of polymyositis include congestive heart failure, pericarditis, pulmonary hypertension, mitral valve prolapse, and dissecting aneurysm, and a variety of arrhythmias have been reported^(1.2).

We describe a case of polymyositis manifesting myocardial insult due to myocarditis, suggested by gadolinium diethylenetriaminepentaacetic acid enhanced magnetic resonance imaging (Gd-DTPA MRI) and histologically diagnosed by endomyocardial biopsy.

In November 1998, a 58-year-old man was admitted to hospital due to worsening dyspnea because of congestive heart failure. Symmetric proximal muscle wasting and weakness were found in both upper and lower limbs. Right cardiac catheterization showed moderate pulmonary hypertension. Laboratory examination showed a marked elevation of serum muscle enzymes: 1000-1200 IU/l creatine phosphokinase (CPK)(normal < 150 IU/1), 12.3 IU/1 aldolase (normal 1.7-5.7 IU/1), and 770 ng/ml myoglobin (normal < 60 ng/ml). His condition improved almost one week after drug treatment, and he was discharged.

In January 1999, he was referred to our university hospital for further examination and treatment. On admission, blood pressure was 132/70 mm/Hg and his body temperature was 36.8°C. A chest radiograph showed mild cardiomegaly (cardiothoracic ratio 51.9%). The electrocardiogram showed sinus rhythm (heart rate 77 beats/min), negative T waves in leads I, aVL and V4 through V6, and ST depression in leads V4 through V6. Laboratory studies showed 1827 IU/1 CPK (muscle origin, MM band, normal 36-216 IU/1), 5.0 IU/l aldolase (normal 0.5-3.1), 988 ng/ml myoglobin (normal < 73 ng/ml), 0.18 ng/ml troponin T (normal < 0.25 ng/ml), and 14 ng/ml myosin light chain (normal < 2.5 ng/ml). He was in NYHA class II. Gd-DTPA MRI performed 4 days after admission revealed transmural contrast enhancement in the anterior, lateral, and posterior wall in the left ventrical (Figure 1A, 1B).

Figure 1. A, B: MRI reveal transmural contrast enhancement in the anterior, lateral, and posterior wall in the left ventricle. C. Left deltoid muscle specimen shows hyaline degeneration or severely degenerated single muscle fibers mixed with normal muscle fibers. D. Left ventricular endomyocardial biopsy specimen shows interstitial fibrosis, edema, cellular cluster, and hypertrophy.

Electromyography revealed a characteristic myopathic pattern. Left deltoid muscle biopsy specimens showed hyaline degeneration, or severely degenerated single muscle fibers mixed with normal muscle fibers (Figure 1C). An echocardiogram showed left ventricular dilatation and diffuse hypokinetic wall motion of the left ventricle. There was no valvular disease. Cardiac catheterization was hemodynamically normal. Biplane left ventriculograms revealed generalized hypokinesis in the wall motion. The ejection fraction was 34%. Selective coronary angiograms showed normal epicardial coronary vasospasm. The left ventricular endomyocardial biopsy specimens showed interstitial fibrosis, edema, cellular cluster, and hypertrophy (Figure 1D).

According to the criteria of Bohan and Peter³, the diagnosis was "probable polymyositis" and the case was diagnosed positive based on the criteria of the Japanese Ministry of Health and Welfare⁴.

We diagnosed this patient had cardiac involvement due to polymyositis. Prednisone 60 mg/day was started. On February 15, 1999, because plasma CPK level was still high (688 IU/l), methotrexate 5 mg/week started from the next day. On February 20, 1999, he committed suicide.

Cardiac involvement is one of the most significant clinical factors associated with a poor prognosis for polymyositis. The incidence of cardiac disease in polymyositis was formerly thought to be low, but careful cardiac evaluation has shown it to be much higher. The incidence has been reported as from 37% to 49% in large series^5,6.

Haupt, et al reported that pathological evidence of cardiac involvement in patients with polymyositis included active myocarditis, focal fibrosis, vasculitis, intimal proliferation, and medial sclerosis of vessels⁷. On the other hand, Denbow, et al demonstrated that some patients have histological findings of active myocarditis and others show replacement fibrosis and small vessel disease in the myocardium⁸. In the present case, the pathological findings included interstitial fibrosis, edema, and degeneration of the contractile band. These findings suggested the presence of myocardial inflammatory damage.

Gd-DTPA MRI has been used to detect myocardial damage from active myocardial inflammation⁹. A study using a rodent myocarditis model has shown that accumulation of Gd-DTPA is observable in myocarditis with ongoing replacement fibrosis, in both the active inflammation and the healing stage, but not in scar tissue^10.We have reported that Gd-DTPA is a helpful tool to detect sarcoid heart, eosinophilic myocarditis, ischemic myocardial injury, and subendocardial damage due to aortic valve stenosis^11-13.

Gd-DTPA MRI shows the extent and location of inflammation and fibrosis of the myocardium more clearly than myocardium more clearly than myocardial scintigraphy and echocardiography. We should therefore take the possibility of cardiac involvement into consideration when treating patients with polymyositis. Our case demonstrates that Gd-DTPA MRI may be a helpful and safe tool and is more specific for the evaluation of myocardial damage than conventional noninvasive techniques.

Gd-DTPA MRI may be a useful screening tool for the diagnosis of myocarditis associated with polymyositis, and can be helpful in providing an appropriate treatment.

SHUZO OHATA, MD; TOSHIO SHIMADA, MD; HIROMI SHIMIZU, MD; YO MURAKAMI, MD; Cardiovascular Division, Fourth Department of Internal Medicine, Shimane Medical University, 89-1, Enya-cho, Izumo, Shimane 693-8501; YOSHIO MATSUNO, Division of Cardiology, Matsue City Hospital, 101 Nada-machi, Matsue, Shimane 690-8509, Japan.

1. Askari AD. Inflammatory disorders of muscle: Cardiac abnormalities. Clin Rheum Dis 1984;10:131-49.

2. Yale SH, Adlakha A, Stanton MS. Dermatomyositis with pericardial tamponade and polymyositis with peri cardial effusion. Am Heart J 1993;126:997-9.

3. Bohan A, Peter JB, Bowman RL, Pearson CM. Computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine 1977;56:255-86.

4. Nakano K, Tanimoto K, Kano S, Nishitani H, Saito T. Classification criteria for the diagnosis of dermatomyositis and polymyositis. Tokyo: Japanese Ministry of Health and Welfare, Research Committee for the Autoimmune Diseases; 1992:25-8.

5. Hochberg MC, Feldman D, Stevens MB. Adult onset polymositis/dermatomyositis: and analysis of clinical and laboratory features and survival in 76 patients with a review of the literature. Semin Arthritis Rheum 1986;15:168-71.

6. Henrikkson KG, Standstedt P. Polymyositis-treatment and prognosis: a study of 107patients. Acta Neurol Scand 1982;65:280-300.

7. Haupt HM, Hutchins GM. The heart and cardiac conduction system in polymyositis-dermatomyositis: A clinicopathologic study of 16 autopsied patients. Am J Cardiol 1982;50:998-1006.

8. Denbow CE, Lie JT, Tandcredi RG, Burch TW. Cardiac involvement in polymyositis: A clinicopathologic study of 20 autopsied patients. Arthritis Rheum 1979;27:1088-92.

9. Friedrich MG, Strohm O, Schulz-Menger J, et al. Contrast media enhanced magnetic resonance imaging visualizes myocardial changes in the course of viral myocarditis. Circulation 1998;97:1802-9.

10. Aso H, Takeda K, Ito T, et al. Assessment of myocardial fibrosis in cardiomyopathic hamsters with gadolinium-DTPA enhanced magnetic resonance imaging. Invest Radiol 1998; 33:22-32.

11. Shimada T, Shimada K, Sakane T et al. Diagnosis of cardiac sarcoidosis and evaluation of the effects of steroid therapy by gadolinium-DTPA-enhanced magnetic resonance imaging. Am J Med 2001;110:520-9.

12. Kitamura J, Shimada T, Murakami Y, et al. Gadolinium-DTPA-enhanced magnetic resonance imaging and functional outcome in patients with acute myocardial infarction. Jpn Circ J 1999;63: 453-8.

13. Ochiai K, Ishibashi Y, Shimada T, et al. Subendocardial enhancement in gadolinium-diethylene-triamine-pentaacetic acid-enhanced magnetic resonance imaging in aortic stenosis. Am J Cardiol 1999;83:1443-6.

In an editorial entitled "Ultrasound imaging: A rheumatologist's dream" I speculated on the impact ultrasonography could have in rheumatologic training¹. While on the one hand my dream has recently come true, I have also learned that it was no dream at all but ignorance of what is going on in European rheumatology.

My dream was realized when I attended a workshop organized by Dr. Antonio Reginato from The Cooper Health System and the Division of Rheumatology, UMDNJ/Robert Wood Johnson Medical School at Camden, New Jersey, to honor the late Dr. Joseph L. Hollander. The workshop, "Cutting Edge Diagnostic Techniques and Invasive Rheumatology for the Millennium," took place just before the 2000 American College of Rheumatology Meeting in October in Philadelphia. There were 2 eight-hour sessions devoted to arthroscopy, 2 eight-hour sessions on musculoskeletal ultrasound, plus an eight-hour session on synovial infiltrations, subcutaneous fat aspiration, skin biopsy, salivary gland biopsy, needle muscle biopsy, anterior iliac crest biopsy, and capillaroscopy. Although I did not attend the arthroscopy sessions those who did were delighted with the hands-on approach in realistic plastic models under the authoritative guidance of Drs. Gil A. Reyes and Angel Checa from Havana, Cuba, and Robert W. Ike from Ann Arbor, Michigan. The ultrasound sessions, which I attended, allowed participants to perform a full upper and lower extremity joint ultrasound in healthy persons plus selected joints in patients with inflammatory joint disease. The superb instructors included Drs. Esperanza Naredo and Jacqueline Uson from Madrid, Spain, Antonio Bouffard from Detroit, Michigan, and Walter Grassi from Ancona, Italy. Please note that of the 4 ultrasound instructors one was an American radiologist while the 3 European instructors were rheumatologists with ample experience in musculoskeletal ultrasonography. This session obviously did not make us ultrasonographers, but was enticing enough to send us back trying to figure how to get hold of an ultrasound machine and start exploring the soft tissues. Lecturers in the third session included Drs. Warren R. Heymann, Joseph V. Campelone, Gerald Falasca, and Antonio J. Reginato from Camden, New Jersey, and Drs. Mary-Carmen Amigo and myself from México City, México. Thanks to Dr. Reginato's enterprise this session allowed attendants to practice synovial needle placement using realistic plastic models with an internal sensor that indicated accurate placement, and a hands-on true-cut muscle biopsy session in which attendants tried their hand on a Purdue turkey! Truly, I have never seen a workshop like this, in which the fuzzy fringes of our specialty were probed with vigor and knowhow.

That my ultrasonography dream was only ignorance I learned from our European instructors. At present, to qualify as a rheumatologist in Italy one has to provide evidence of having performed 200 ultrasonic examinations plus 200 capillaroscopic examinations. Ultrasound proficiency is also required in Austria, Germany, and Switzerland. Work is in progress to require ultrasonography proficiency in other European countries.

There is no question that emphasis on biology and experimental medicine, and more recently clinical epidemiology, has built the greatness of rheumatology in the New World. However, to fulfill our duty as specialists in diseases of the musculoskeletal system (which comprise about 30% of our day to day practice) we must become proficient in musculoskeletal medicine. To this end, musculoskeletal ultrasonography provides an unmatched medium. Dr. Reginato's far-seeing, successful workshop should be replicated and expanded by American (in the broad sense) academic rheumatology. The 3 workshop sessions on ultrasonography featured at the San Francisco ACR meeting with a German instructor, Prof. Wolfgang Schmidt, and the musculoskeletal ultrasound study group, represent steps in the right direction.

JUAN J. CANOSO, MD, ABC Hospital, México City, México. E-mail: juan123canoso@prodigy.net.mx

1. Canoso JJ. Ultrasound imaging: A rheumatologist's dream [editorial]. J Rheumatol 2000;27:2063-4.

In the December 2000 issue the report of the Canadian Consensus Conference on hydroxychloroquine, chaired by Dr. John Esdaile, was published. One of the key recommendations was the need to develop up-to-date "patient friendly" information to meet the needs of consumers. In followup to this recommendation, a consumer led workshop was held recently that included representatives of the Canadian Rheumatology Association, Canadian Pharmacists Association, Canadian Ophthalmology Society, Canadian Paediatric Rheumatology Association, Motherisk Canada, Lupus Canada, Canadian Arthritis Patient Alliance, The Arthritis Society, and Health Canada.

In keeping with emerging Therapeutic Products Directorate guidelines, the patient information drafted by this group will be submitted to Health Canada for inclusion in the hydroxychloroquine product monograph that is currently being developed between Health Canada and the manufacturer.

This group process represented an effective prototype for the development of information that will meet the needs of patients and consumers.

CHERYL L. KOEHN, Chair, Workshop Group, Information to the Patient and Physician on Hydroxychloroquine, ACE Planning & Consulting Inc., 4038 West 38th Avenue, Vancouver, BC V6N 2Y9, Canada. E-mail: cherylkoehn@telus.net