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T h e n e w e ng l a n d j o u r na l o f m e dic i n e port-wine stains through greater vessel heating The Authors Reply: With ongoing research in
and deeper vascular injury.2 The improved tech- medicine, investigating the 10-year follow-up re- nology targets the heterogeneity in blood-vessel sults of any medical treatment inevitably leads to sizes that is characteristic of port-wine stains.3 somewhat outdated results at the time of presen- Any study evaluating the response of port-wine tation. This is especially the case in a field that is stains to treatment should include an analysis subject to continuous development, such as pulsed- based on the location of the anatomical malfor- dye–laser treatment of port-wine stains. As Nelson mation and the patient’s age. As compared with and Geronemus point out, the results with newer other areas of the face and neck, port-wine stains pulsed-dye lasers have been reported to be prom- on the center of the face have been shown to re- ising and superior to the results with the laser spond less effectively to treatment and are more used in our study. However, to date no controlled likely to recur.4 An aggressive approach to treat- comparative studies have shown improved clinical ing infants and young children can also allow for efficacy. Whether the new lasers have improved long-term efficacy remains to be reported; in light of our observation of the recurrence of port- wine stains, we certainly hope they do.
Beckman Laser Institute Irvine, CA 92612 No differences or trends in responses to treat- ment related to the anatomical locations of the port-wine stains were observed in either the origi- nal study1,2 or the current follow-up study, possi- New York University Medical Center New York, NY 10016 bly because of the relatively small number of pa- tients. Furthermore, in the original study, age was 1. Huikeshoven M, Koster PHL, de Borgie CAJM, Beek JF, van shown to have no influence on the response to
Gemert MJC, van der Horst CMAM. Redarkening of port-wine stains 10 years after pulsed-dye–laser treatment. N Engl J Med treatment. Therefore, we refrained from perform- ing age-dependent analyses in the current long- 2. Nelson JS, Milner TE, Anvari B, Tanenbaum BS, et al. Dy-
namic epidermal cooling during pulsed laser treatment of port wine stain: a new methodology with preliminary clinical evalu- Menno Huikeshoven, M.D., Ph.D. ation. Arch Dermatol 1995;131:695-700.
Chantal M.A.M. van der Horst, M.D., Ph.D.
3. Barsky SH, Rosen S, Geer DE, Noe JM. The nature and evolu-
tion of port wine stains: a computer-assisted study. J Invest Der- Academic Medical Center 4. Renfro L, Geronemus RG. Anatomical differences of port-
wine stains in response to treatment with the pulsed dye laser. 1. van der Horst CMAM, Koster PHL, de Borgie CAJM, Bossuyt
PMM, van Gemert MJC. Effect of the timing of treatment of port- 5. Geronemus RG, Quintana AT, Lou WW, Kauvar A. High-flu-
wine stains with the flash-lamp–pumped pulsed-dye laser. ence modified pulsed dye laser photocoagulation with dynamic N Engl J Med 1998;338:1028-33.
cooling of port-wine stains in infancy. Arch Dermatol 2000;136: 2. Kauvar AN, Geronemus RG. Treatment of port-wine stains.
Treatment of Kawasaki Disease
To the Editor: In their trial of pulsed cortico- effect, which could therefore be associated with
steroid therapy for primary treatment of Kawa- a secondary increase in inflammation.
saki disease, Newburger et al. (Feb. 15 issue)1 On the basis of nearly 10 years of clinical report that, as compared with placebo, a single experience,2 we designed a regimen involving a pulsed dose of corticosteroid resulted in a shorter short intravenous course of prednisolone and initial period of hospitalization but that the total subsequent oral administration of prednisolone numbers of days of fever and hospitalization, the followed by tapering.3 In a randomized trial per- rates of retreatment, and the coronary-artery out- formed to test the effectiveness of the regimen comes did not differ significantly between the two as an adjunct to intravenous immune globulin, groups. The use of a single-dose regimen without the incidences of retreatment and coronary-artery tapering most likely contributed to their results. abnormalities within 1 month after the start of A single application of a corticosteroid, even at a treatment were less frequent in the corticosteroid high dose, may have a strong but only short-lived group than in the group receiving immune globu- n engl j med 356;26 www.nejm.org june 28, 2007 Downloaded from www.nejm.org at HARVARD UNIVERSITY on July 26, 2007 . Copyright 2007 Massachusetts Medical Society. All rights reserved. lin alone. Our regimen therefore appears to be Andrea Taddio, M.D.
more efficacious than the control regimen. Never- Institute of Child Health theless, the optimal corticosteroid regimen re- 34100 Trieste, Italy mains an issue in the primary therapy of Kawa- Carlos D. Rosé M.D.
Thomas Jefferson University 1. Hashino K, Ishii M, Iemura M, Akagi T, Kato H. Re-treat-
ment for immune globulin-resistant Kawasaki disease: a com- Gunma University Graduate School of Medicine parative study of additional immune globulin and steroid pulse 2. Lang BA, Yeung RS, Oen KG, et al. Corticosteroid treatment
of refractory Kawasaki disease. J Rheumatol 2006;33:803-9.
1. Newburger JW, Sleeper LA, McCrindle BW, et al. Random-
3. Sundel RP, Baker AL, Fulton DR, Newburger JW. Corticoste-
ized trial of pulsed corticosteroid therapy for primary treatment roids in the initial treatment of Kawasaki disease: report of a of Kawasaki disease. N Engl J Med 2007;356:663-75.
randomized trial. J Pediatr 2003;142:611-6.
2. Shinohara M, Sone K, Tomomasa T, Morikawa A. Cortico-
steroids in the treatment of the acute phase of Kawasaki disease. To the Editor: Although the study by Newburger
3. Inoue Y, Okada Y, Shinohara M, et al. A multicenter prospec-
tive randomized trial of corticosteroids in primary therapy for et al. involved assessment of coronary-artery out- Kawasaki disease: clinical course and coronary artery outcome. comes with the use of transthoracic echocardi- ography, we were quite surprised by the inclusion of an example of a coronary aneurysm seen on To the Editor: Newburger et al. studied the ef- multidetector computed tomography (CT) in the
fects of adding intravenous methylprednisolone to accompanying Perspective article by Burns.1 conventional therapy for Kawasaki disease. The We and others2,3 have shown the efficacy of authors found a significantly lower frequency of noninvasive magnetic resonance imaging (MRI) coronary-artery abnormalities in the intravenous- of the heart for both the identification and char- methylprednisolone group than in the placebo acterization of coronary artery disease in patients group within the subgroup of patients who re- with Kawasaki disease (Fig. 1). Patients with quired retreatment with intravenous immune Kawasaki disease require frequent observation over many decades. Given the relatively high doses The identification of predictors of coronary ab- of ionizing radiation associated with multidetector normalities in Kawasaki disease is still problem- atic. Failure of initial treatment with intravenous immune globulin remains the most consistent risk factor for cardiac abnormalities.1 Adminis- tration of intravenous methylprednisolone after the failure of initial treatment with intravenous immune globulin does not seem to be effective in reducing the risk of coronary damage,2 although the current data suggest that this might not be the case for patients who do not have a response to intravenous immune globulin and who have pre- viously received intravenous methylprednisolone.
Since intravenous methylprednisolone admin- istered as a single dose appears to be safe,3 and given our inability to identify a priori the patients who will not have a response to intravenous im- mune globulin, it seems obvious that the concur- rent use of a single dose of intravenous methyl- prednisolone and intravenous immune globulin Figure 1. Three-Dimensional Steady-State Free-Precession
may be our best choice at the moment. It is un- MRI of the Whole Heart in an 8-Year-Old Boy with
Kawasaki Disease and Serial Aneurysms (A) in the
realistic to expect that trials powered to show Right Coronary Artery.
the effectiveness of intravenous methylpredniso- No contrast material was administered.
lone could be accomplished anytime soon.
AUTHOR, PLEASE NOTE:
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Downloaded from www.nejm.org at HARVARD UNIVERSITY on July 26, 2007 . Copyright 2007 Massachusetts Medical Society. All rights reserved. T h e n e w e ng l a n d j o u r na l o f m e dic i n e CT 4 and the heightened potential for radiation- therapy, findings that have been shown to be er- induced fatal cancer in children,5 we believe that, roneous in subsequent prospective trials.2 Chil- if transthoracic echocardiography is inadequate, dren with Kawasaki disease can be characterized these younger patients are best served by the use at the time of presentation with respect to their risk of resistance to intravenous immune globu- lin.3 Until further studies are conducted in high- risk patients, we do not believe that corticosteroid therapy should be used in the primary treatment 1. Burns JC. The riddle of Kawasaki disease. N Engl J Med jane.newburger@cardio.chboston.org
2. Greil GF, Stuber M, Botnar RM, et al. Coronary magnetic
resonance angiography in adolescents and young adults with New England Research Institutes Kawasaki disease. Circulation 2002;105:908-11.
3. Mavrogeni S, Papadopoulos G, Douskou M, et al. Magnetic 1. Pfeffer MA, Jarcho JA. The charisma of subgroups and the
resonance angiography, function and viability evaluation in pa- subgroups of CHARISMA. N Engl J Med 2006;354:1744-6.
tients with Kawasaki disease. J Cardiovasc Magn Reson 2006;8: 2. Rothwell PM. Treating individuals 2: subgroup analysis in
randomised controlled trials: importance, indications, and inter- 4. Coles DR, Smail MA, Negus IS, et al. Comparison of radia-
tion doses from multislice computed tomography coronary angi- 3. Kobayashi T, Inoue Y, Takeuchi K, et al. Prediction of intra-
ography and conventional diagnostic angiography. J Am Coll venous immunoglobulin unresponsiveness in patients with Kawa- saki disease. Circulation 2006;113:2606-12.
5. Brenner D, Elliston C, Hall E, Berdon W. Estimated risks of
radiation-induced fatal cancer from pediatric CT. AJR Am J Dr. Burns Replies: Imaging of the coronary ar-
teries is important in the long-term management The Authors Reply: Inoue and colleagues de- of aneurysms in patients with Kawasaki disease.
scribe the results of their open trial using a pro- Transthoracic echocardiography can be used only longed course of corticosteroids, which we discuss to image the proximal arteries, is dependent on a in our article. We found that clinically significant high level of technical skill, and cannot reliably coronary-artery abnormalities were infrequent in detect stenosis. Advantages of multidetector CT patients in both of our study groups. For this are the assessment of calcification and soft plaque, reason, although the optimal corticosteroid regi- rapid collection of data, and straightforward in- men may be unknown, we believe that cortico- terpretation of images. With proper gating to the steroid regimens requiring a prolonged course of cardiac cycle and lowering of the heart rate with treatment would be difficult to rationalize for the beta-adrenergic blockade, exposures of approxi- primary treatment of all patients with Kawasaki mately 0.67 mSv have been documented for coro- nary-artery studies of children involving multi- Taddio and Rosé highlight an important ques- detector CT (Larkin G, GE Healthcare: personal tion arising from our analyses. Our study was de- communication) (for comparison, one chest radio- signed to test the hypothesis that the addition of graph results in exposure to 0.02 mSv). MRI is safe, intravenous methylprednisolone to conventional but many centers cannot image the coronary ar- primary treatment of Kawasaki disease would im- teries with sufficient precision. All these ap- prove coronary-artery outcomes; the study groups proaches require general anesthesia for young had similar overall coronary outcomes. A post hoc patients, and MRI requires a longer time to cap- subgroup analysis suggested that primary cortico- ture images than does multidetector CT and thus steroid therapy reduced the incidence of coronary- increases the time under anesthesia and associat- artery abnormalities in a high-risk subgroup of ed risks. Clearly, this is an area of medicine that patients in our study who required retreatment is in flux. We look forward to the time when safe, with intravenous immune globulin because of noninvasive imaging methods are widely avail- persistent or recrudescent fever. However, such able at all centers for these children.
subgroup analyses must be interpreted with cau- Jane C. Burns, M.D.
tion1; the literature is replete with subgroup University of California, San Diego analyses suggesting differential responses to La Jolla, CA 92093-0830 n engl j med 356;26 www.nejm.org june 28, 2007 Downloaded from www.nejm.org at HARVARD UNIVERSITY on July 26, 2007 . Copyright 2007 Massachusetts Medical Society. All rights reserved.

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