Correspondence

Correction

Intravenous Immune Globulin for Dermatomyositis

N Engl J Med 1994; 330:1392-1393May 12, 1994

Article

To the Editor:

The recent report by Dalakas et al. (Dec. 30 issue)1 on the treatment of dermatomyositis with intravenous immune globulin states, “In five patients who had a major improvement after the third infusion, we performed another open-muscle biopsy.” Yet the description of the study design indicates that “the code was not broken until all the patients completed the study and a second muscle biopsy was performed.” Where are the results of the other biopsies?

This information is critical if the reader is to judge whether the conclusion that treatment with immune globulin leads to “marked improvement or resolution of the histologic and immunopathological findings on the repeated muscle biopsies” is correct. If the biopsies were not done, then the study protocol was not adhered to.

Second, quantitative improvement was noted in the paired muscle-biopsy specimens. My calculation of the mean ratio of muscle fibers to capillaries, using the data provided in the text, showed a decrease in the ratio from 2.42 to 1.38 -- a much less impressive change than that indicated in the article (from 3.4 to 1.5).

Third, Figure 2 is said to illustrate “marked improvement” of the chronic rash after treatment. One cannot arrive at this conclusion from looking at the figure. The different appearance of the hands could easily be explained by the differences in magnification, the background color of the skin, and the contrast between the lesions given the naturally colored nails in one photograph and the bright red nail polish in the other. All three factors enhance the apparent severity of the lesions in Panel A (the untreated rash) and decrease it in Panel B (after treatment).

A. Keith W. Brownell, M.D.
University of Calgary, Calgary, AB T2N 4N1, Canada

1 References

1. 1

   Dalakas MC, Illa I, Dambrosia JM, et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1993-2000
   Full Text | Web of Science | Medline

Author/Editor Response

Dr. Dalakas replies:

To the Editor: Regarding Dr. Brownell's first question: the code was broken only after all patients had completed the study and quantitative immunocytochemical studies of the second muscle-biopsy specimens had been performed. Our protocol called for repeated biopsies in patients whose muscle strength had markedly improved, regardless of the type of treatment they received. It would have made no sense to perform repeated biopsies in patients who did not improve clinically. As we stated, when the code was broken, it became clear that all the repeated biopsies had been performed in patients who had received intravenous immune globulin and not placebo. The purpose of the repeated biopsies was not to establish the drug's efficacy but to determine the immunopathological correlates of the improvement. As we have stated elsewhere,1,2 improvement in a patient with myopathic weakness is defined as an increase in muscle strength sufficient to affect the activities of daily living, and not solely as a morphologic change in the muscle.

Dr. Brownell's second point is mathematically correct, although it is of no consequence for our conclusion. The mean number of muscle fibers was inadvertently reported as 34 ±2 instead of 34 ±20, which accounts for the discrepancy in the ratio. The difference in the ratio of muscle fibers to capillaries was impressive because, as we stated in our report, it became normal in three patients.

Dr. Brownell's third point, in which he questions the details of the photographs, is surprising, because we explicitly stated that the photographic conditions were the same before and after therapy. Although marked improvement of the active violaceous rash on the face, hands, and chest was unequivocally documented by all observers early in the course of treatment, we elected to show the improvement in the chronic, scaly eruptions on the knuckles, which was unexpected. The bright red nail polish does not distract from the evident improvement in the scaly rash on the more proximal knuckles. On the contrary, clearing of the thickened, cracked, and distorted cuticles allowed the patient to use nail polish for the first time in years.

The improvement in patients with active dermatomyositis treated with intravenous immune globulin is impressive. Since the study reported in our article,3 we have documented the efficacy of intravenous immune globulin administered in an open-label manner. A patient we recently treated used a cane before therapy but was able to exercise on parallel bars after two courses of intravenous immune globulin. Her scores on a test of maximal voluntary isometric contractions, the most objective way of assessing muscle strength,4,5 increased from 202 to 358.

Marino C. Dalakas, M.D.
National Institutes of Health, Bethesda, MD 20892

5 References

1. 1

   Dalakas MC. Polymyositis, dermatomyositis, and inclusion-body myositis. N Engl J Med 1991;325:1487-1498
   Full Text | Web of Science | Medline

2. 2

   Dalakas MC. Clinical, immunopathologic, and therapeutic considerations of inflammatory myopathies. Clin Neuropharmacol 1992;15:327-351
   CrossRef | Web of Science | Medline

3. 3

   Dalakas MC, Illa I, Dambrosia JM, et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1993-2000
   Full Text | Web of Science | Medline

4. 4

   Andres PL, Hedlund W, Finison L, Conlon T, Felmus M, Munsat TL. Quantitative motor assessment in amyotrophic lateral sclerosis. Neurology 1985;36:937-941
   Web of Science

5. 5

   Dalakas MC, Stein DP, Otero C, et al. Effect of high dose intravenous immunoglobulin on amytrophic lateral sclerosis and multifocal motor neuropathy. Arch Neurol (in press).
   

Citing Articles (4)

Citing Articles

1. 1

   Peter D. Donofrio, Alan Berger, Thomas H. Brannagan, Mark B. Bromberg, James F. Howard, Normal Latov, Adam Quick, Rup Tandan. (2009) Consensus statement: The use of intravenous immunoglobulin in the treatment of neuromuscular conditions report of the aanem AD HOC committee. Muscle & Nerve 40:5, 890-900
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2. 2

   Eizo Saito, Takao Koike, Hiroshi Hashimoto, Nobuyuki Miyasaka, Yasuo Ikeda, Masako Hara, Hidehiro Yamada, Tadashi Yoshida, Masayoshi Harigai, Yoichi Ichikawa, . (2008) Efficacy of high-dose intravenous immunoglobulin therapy in Japanese patients with steroid-resistant polymyositis and dermatomyositis. Modern Rheumatology 18:1, 34-44
   CrossRef

3. 3

   Marinos C. Dalakas. (2006) The role of high-dose immune globulin intravenous in the treatment of dermatomyositis. International Immunopharmacology 6:4, 550-556
   CrossRef

4. 4

   P. Cherin, S. Pelletier, A. Teixeira, P. Laforet, T. Genereau, A. Simon, T. Maisonobe, B. Eymard, S. Herson. (2002) Results and long-term followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: An open study with thirty-five adult patients. Arthritis & Rheumatism 46:2, 467-474
   CrossRef