SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgments
  8. REFERENCES
  9. Appendix: A: MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP

Objective

Genetic and environmental factors may contribute to the etiology of the juvenile idiopathic inflammatory myopathies (IIMs), which are systemic autoimmune diseases that are characterized by muscle and skin inflammation. We undertook this study to investigate the association between ultraviolet radiation (UVR) exposure and the clinical and autoantibody expression of juvenile IIM.

Methods

The relationship between UVR exposure in the month before symptom onset and the prevalence of juvenile dermatomyositis (DM), compared to juvenile polymyositis (PM), was assessed in 298 juvenile IIM patients. Among the patients with juvenile DM, the association between UVR exposure and presence of myositis autoantibodies was assessed. Regression models were stratified by sex and race. The association between the regional UV index in US geoclimatic zones and the clinical and autoantibody subgroups was examined by weighted least squares regression analysis.

Results

Among girls in this population, the odds of having juvenile DM, compared to juvenile PM, increased per unit increase in the patients' highest UV index in the month before symptom onset (odds ratio [OR] 1.18, 95% confidence interval 1.00–1.40). Moreover, both the mean and highest UV indices were associated with increasing odds of having anti-p155/140 autoantibodies, with the strongest odds in white males (ORs of 1.30 and 1.23, respectively). No association was observed between the UV index and presence of anti-MJ autoantibodies or lack of any myositis autoantibodies. Across all 9 US geoclimatic regions, the mean UV index was associated with increasing odds of having juvenile DM and anti-p155/140 autoantibodies, but decreasing odds of having anti-MJ autoantibodies.

Conclusion

Short-term UVR exposure prior to illness onset may have a role in the clinical and serologic expression of juvenile myositis. Further research examining the mechanisms of action of UVR in the pathogenesis of juvenile IIM is suggested from these findings.

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of systemic autoimmune diseases with the common feature of chronic muscle inflammation of unknown etiology. In children, dermatomyositis (DM), characterized by skin rashes and photosensitivity, is the most common of the IIMs, and polymyositis (PM), which lacks the characteristic skin rashes, constitutes ∼10% of childhood-onset IIMs. As in adult myositis, juvenile myositis comprises myositis-autoantibody subgroups that define specific phenotypes, each of which is associated with different demographic, clinical, and laboratory features and outcomes ([1]). Some of these autoantibodies are associated with DM, such as anti–Mi-2 and anti-p155/140 (transcription intermediary factor 1γ), and others are associated with PM, such as anti–signal recognition particle ([1]).

Development of the IIMs is thought to be affected by genetic and environmental risk factors. Although HLA, cytokine polymorphisms, and other immunogenetic loci have been identified as genetic risk factors for these diseases ([1]), little is known about their environmental risk factors. Seasonality in birth dates in subgroups of patients suggests that perinatal or neonatal environmental factors, including ultraviolet radiation (UVR), may have a role in the later development of these diseases ([2]). In registry studies, temporal associations with upper respiratory and gastrointestinal infections have been observed. Other exposures have also been observed, including development of symptoms after unusual sun exposure or sunburns ([3]).

In adult IIM, studies in the US and worldwide found a direct relationship between global-surface UVR exposure and the proportion of patients with DM, as compared to the proportion of patients with PM ([4, 5]). Seasonal differences in onset of PM and DM have been reported and are consistent with the role of UVR exposure ([6]). This relationship has not been examined in juvenile IIM populations. We therefore examined whether the prevalence of juvenile DM, as compared to juvenile PM, and the presence of DM-specific autoantibodies are associated with UVR exposure.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgments
  8. REFERENCES
  9. Appendix: A: MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP

Patients

Four hundred thirty-six patients in whom probable or definite juvenile DM or juvenile PM was diagnosed before age 18 years were enrolled in a nationwide registry. Data obtained included the patients' demographic and clinical features on a physician-administered questionnaire, and test results for myositis autoantibodies determined by validated immunoprecipitation methods ([1]). Patients whose first myositis-related symptoms developed before June 1, 1989 (n = 56) and those residing outside the continental US at the time of myositis symptom onset (n = 32) were not included, due to the lack of corresponding surface UVR data. Because the present analysis involved comparison of juvenile DM with juvenile PM and myositis autoantibody subgroups, patients with overlap myositis (n = 37) or those who had not been tested for myositis autoantibodies (n = 13) were excluded; 5 patients were in more than one of the excluded categories. Thus, this study included 271 patients with juvenile DM and 27 with juvenile PM. The distribution of myositis autoantibodies in the patient groups is detailed in Table 1. All participants provided their signed informed consent to participate in the study.

Table 1. Regional and state residential locations of juvenile myositis patients and their mean and highest UV indices within 30 days of myositis symptom onset*
Region, stateUV indexaJuvenile IIM subsetMyositis-specific autoantibodyb
MeanHighestJuvenile DMJuvenile PMAnti-p155/140Anti-MJNoneTotal cases of juvenile IIM
  1. Patients with juvenile idiopathic inflammatory myopathies (IIMs) from 9 US geoclimatic regions (see http://www.ncdc.noaa.gov/temp-and-precip/us-climate-regions.php) were examined. DM = dermatomyositis; PM = polymyositis.

  2. a

    Ultraviolet (UV) indices, which were determined within 30 days of myositis symptom onset, are based on US National Weather Service calculations of the UV index using a computer model that relates the ground-level strength of solar UV radiation to forecasted stratospheric ozone concentration, forecasted cloud cover, and elevation.

  3. b

    Of note, 34 patients with juvenile DM had other myositis autoantibodies that are not shown: 9 patients had antisynthetase autoantibodies, 12 had anti–Mi-2, 6 had anti-Ro, 7 had anti–PM-Scl, 2 had both anti–U1 RNP and anti-Ro, and 1 each had anti–small ubiquitin-like modifier activating enzyme and anti-Th autoantibodies.

Central        
IL4.58.9704017
IN3.89.3200112
KY5.38100101
MO4.210.3512036
OH3.39.317246319
TN2.78.5302013
East north central        
IA5.06.8302013
MI4.110.59241311
MN2.78.2200012
WI3.48.5710418
Northeast        
CT2.19.410021610
DC4.36.8200112
MA4.38.99243211
MD3.011.621576626
ME2.23.2010001
NJ2.48.2815119
NY410.623188624
PA2.57.99332312
Northwest        
ID6.48.3100101
OR2.79701317
WA28.2253861028
South        
KS4.610.4801338
LA4.08.1200022
MS4.911503105
OK4.07.9501105
TX6.812.220145621
Southeast        
FL5.611.812043312
GA7.111.8402014
NC2.24.4202002
SC3.64.7100011
VA3.410.210052310
Southwest        
AZ7.911.9100011
CO7.210.2212003
UT5.78.9503015
West north central        
NE3.18.2311104
West        
CA6.210.420282622
Total27127926378298

Methods

The UV index consists of an integration of the UVR action spectrum–weighted ultraviolet A (UVA) and UVB irradiances over the 290–400-nm range. The US National Weather Service calculates the UV index using a computer model that relates the ground-level strength of solar UVR to forecasted stratospheric ozone concentration, forecasted cloud cover, and elevation (http://www.epa.gov/sunwise/uvicalc.html). Each patient's residential location (city and state) at onset of myositis symptoms was linked to the UV index (Table 1), which was obtained from the National Weather Service UV Index Cities Forecast Archive (ftp://ftp.cpc.ncep.noaa.gov/long/uv/cities). The mean UV index was calculated for each patient by using daily UV index data for 30 days prior to the date of myositis symptom onset, based on the closest city monitored by the National Oceanic and Atmospheric Administration (NOAA). The maximum UV index in the 30 days before symptom onset was also noted. When ≥2 cities monitored by the NOAA were equidistant to the patient's residence, the one closest in latitude was used.

For the 154 patients who were diagnosed between June 1, 1989 and May 31, 1994, UV index data were extrapolated to the 1994 data, due to the lack of available data before 1994. A 30-day interval before symptom onset was selected due to the importance of short-term UVR as a risk factor for other autoimmune diseases, such as lupus ([7]), and known variation of UVR with season, cloud cover, and ozone. We also examined the mean annual UV index from 1995, which was the mean year prior to diagnosis for all patients in the study, to test for associations utilizing methodology similar to that in a prior study of adult IIM ([5]).

Statistical analysis

We modeled the logarithm of odds for the likelihood of having juvenile DM, as compared to juvenile PM, with stratification by sex and race (since sex and race differences have been observed in adult IIM [5]). The UV index was examined as a continuous variable in the regression model, and the odds ratios (ORs) were calculated as the odds of a particular outcome per unit increase in UV index. Separate logistic regression models were also fitted with the following variables: presence of anti-p155/140 autoantibodies, presence of anti-MJ autoantibodies, and no myositis autoantibody; in these analyses, only patients with juvenile DM were used. We also examined the association between regional UV index in 9 US geoclimatic zones (http://www.ncdc.noaa.gov/temp-and-precip/us-climate-regions.php) and the proportion of juvenile IIM patients who had juvenile DM, as well as the proportion of juvenile DM patients who were positive for anti-p155/140 or anti-MJ autoantibodies.

Weighted least squares regression analysis using individual patient data was performed to examine the associations of mean or highest regional UV index for the month before symptom onset with the prevalence of juvenile DM, anti-p155/140 autoantibodies, or anti-MJ autoantibodies in the 9 geoclimatic regions. Weighted least squares regressions were repeated in the subgroup of white patients, and the coefficient of determination was calculated. We assessed the R2 value to determine the fraction of variance explained by the regression model. An R2 value of >0.6 was considered strong, while an R2 value of 0.3–0.6 was considered moderate, and an R2 value of <0.3 was considered weak. SAS software (version 9.1; SAS Institute) was used for all analyses.

RESULTS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgments
  8. REFERENCES
  9. Appendix: A: MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP

Among the patients, 72% were female and the racial distribution was 69.1% white, 15.6% African American, 6.5% Hispanic, and 8.8% of other races. Nonwhites were significantly more likely than whites to have juvenile PM (15.5% versus 6.5%; P = 0.02). White patients were significantly more likely than nonwhite patients to have anti-p155/140 autoantibodies (37.4% versus 14.3%; P = 0.0001). There were no significant sex differences in the clinical or autoantibody groups, and there were no racial differences in the clinical subgroups when stratified by sex. Patients in this analysis resided in a total of 36 states (Table 1) at the time of myositis symptom onset. Most patients resided in the northeast (n = 95), followed by the south (n = 41) and the central region (n = 38).

The mean UV index for the month before symptom onset was highly correlated with the highest daily UV index over the same period (r = 0.98, P < 0.001). The effects of UVR on clinical group and myositis autoantibodies were assessed in the total population of juvenile IIM patients and by sex and race (Table 2). The mean UV index in the month before myositis onset was positively associated with the proportion of juvenile IIM patients who had juvenile DM, but this association was not significant (OR 1.12, P = 0.17). In girls, the odds of having juvenile DM, compared to juvenile PM, increased per unit increase in the patients' highest UV index in the month before symptom onset (OR 1.18, 95% confidence interval [95% CI] 1.00–1.40). Moreover, the patients' mean UV index was associated with increasing odds of the presence of anti-p155/140 autoantibodies (OR 1.10, 95% CI 1.00–1.22) (Table 2).

Table 2. Associations between UV index in the month preceding symptom onset and prevalence of clinical and autoantibody subgroups, by race and sex*
 Juvenile DM/ juvenile PMAnti-p155/140+/ anti-p155/140−Anti-MJ+/ anti-MJ−
  1. Values are the odds ratio (95% confidence interval) for the ultraviolet (UV) index range across the geoclimatic regions in the study. These values represent the odds of an outcome per unit increase in UV index. DM = dermatomyositis; PM = polymyositis.

  2. a

    P = 0.03.

  3. b

    P = 0.05.

All patients   
No. of patients271/2792/17963/208
Mean UV index1.12 (0.95–1.33)1.10 (1.00–1.22)a0.97 (0.87–1.08)
Highest UV index1.09 (0.96–-1.25)1.07 (0.99–-1.17)0.99 (0.90–-1.08)
White   
No. of patients200/1480/12045/155
Mean UV index1.05 (0.84–1.31)1.16 (1.03–1.30)b0.92 (0.81–1.05)
Highest UV index1.04 (0.87–1.26)1.11 (1.01–1.23)a1.04 (0.90–1.22)
Nonwhite   
No. of patients71/1312/5918/53
Mean UV index1.19 (0.93–1.53)0.92 (0.72–1.17)1.08 (0.89–1.30)
Highest UV index1.13 (0.93–1.37)0.94 (0.77–1.14)1.06 (0.93–1.22)
Females   
All   
No. of patients192/1970/12242/150
Mean UV index1.21 (0.98–1.49)0.88 (0.61–1.27)0.99 (0.87–1.13)
Highest UV index1.18 (1.00–1.40)b1.03 (0.93–1.14)1.01 (0.90–1.12)
White   
No. of patients144/1161/8329/155
Mean UV index1.10 (0.85–1.42)0.68 (0.39–1.19)0.99 (0.84–1.16)
Highest UV index1.10 (0.89–1.36)1.07 (0.95–1.20)1.02 (0.89–1.17)
Nonwhite   
No. of patients48/89/3913/35
Mean UV index1.39 (0.95–2.03)1.36 (0.74–2.5)1.00 (0.80–1.25)
Highest UV index1.31 (0.98–1.77)0.92 (0.72–1.16)0.99 (0.82–1.86)
Males   
All   
No. of patients79/822/5721/58
Mean UV index0.95 (0.71–1.28)1.20 (0.98–1.47)0.94 (0.77–1.15)
Highest UV index0.93 (0.73–1.18)1.15 (0.98–1.36)0.96 (0.82–1.12)
White   
No. of patients56/319/3716/40
Mean UV index0.90 (0.55–1.45)1.30 (1.02–1.67)b0.80 (0.62–1.04)
Highest UV index0.89 (0.60–1.34)1.23 (1.00–1.50)b0.86 (0.70–1.05)
Nonwhite   
No. of patients23/53/205/18
Mean UV index0.97 (0.67–1.40)0.94 (0.59–1.49)1.29 (0.88–1.89)
Highest UV index0.93 (0.70–1.24)0.95 (0.66–1.36)1.19 (0.88–1.61)

The association between the mean and highest UV indices in the month before symptom onset and the proportion of juvenile DM patients having anti-p155/140 autoantibodies was stronger in whites (for mean UV index, OR 1.16, 95% CI 1.03–1.30; for highest UV index, OR 1.11, 95% CI 1.01–1.23), with the strongest association seen in white males (for mean UV index, OR 1.30, 95% CI 1.02–1.67; for highest UV index, OR 1.23, 95% CI 1.00–1.50). There was no association between the mean or highest UV index in the month before symptom onset and the proportion of juvenile DM patients having anti-MJ autoantibodies (Table 2), nor was there any association observed in patients who were negative for myositis autoantibodies (results not shown).

Loess regression plots demonstrated that the significant variables in the regression models had linear relationships. There was no significant association between the mean or highest UV index with juvenile DM, as compared to juvenile PM, by racial group in girls or in patients with anti-p155/140 or anti-MJ autoantibodies, as compared to those who were autoantibody negative. There was also no association of the mean UV index in children older than age 7 years, as compared to those age 7 years or younger. We also assessed whether there was any notable association of the UV index data with variables from the year 1995 (the median year before diagnosis for the entire study population), which was similar to the methods utilized by Love et al ([5]), and no significant associations were found.

UV index data were aggregated into 9 regions of the US and displayed graphically in weighted linear regression analyses. There was a moderate association between the mean UV index for the 30 days before myositis symptom onset and the proportion of juvenile IIM patients who had juvenile DM (R2 = 0.42, P = 0.06) (Figure 1A). A similar relationship was seen between the highest UV index in the 30 days before symptom onset and the proportion of juvenile DM cases (R2 = 0.35, P < 0.001).

image

Figure 1. Weighted linear regression analyses of the association between the mean ultraviolet (UV) index in the month before myositis symptom onset in 9 US geoclimatic regions and the proportion of patients in clinical and myositis autoantibody subgroups. The size of the open circle representing each region is proportional to the number of patients residing in that region at the time of myositis onset. A, Mean UV index in relation to the proportion of juvenile idiopathic inflammatory myopathy (JIIM) patients who had juvenile dermatomyositis (JDM), compared to those who had juvenile polymyositis (β coefficient/slope = 0.009, SE = 0.032, R2 = 0.42, P = 0.06). B, Mean UV index in relation to the proportion of patients with juvenile DM positive for anti-p155/140 autoantibodies, compared to those who were anti-p155/140 autoantibody negative (β coefficient/slope = 0.022, SE = 0.011, R2 = 0.15, P = 0.05). C, Mean UV index in relation to the proportion of patients with juvenile DM positive for anti-MJ autoantibodies, compared to those who were anti-MJ autoantibody negative (β coefficient/slope = −0.007, SE = 0.01, R2 = 0.62, P = 0.50).

Download figure to PowerPoint

Among the patients with juvenile DM, the association between the mean or highest UV index and the presence of anti-p155/140 autoantibodies was weak (for mean UV index, R2 = 0.15, P = 0.05; for highest UV index, R2 = 0.08, P = 0.44) (Figure 1B) in the month before symptom onset. We saw moderate-to-strong negative relationships between the mean or highest UV index and the proportion of anti-MJ autoantibody–positive patients (R2 = 0.62 and R2 = 0.59, respectively), but the associations were not significant (P = 0.50 and P = 0.70, respectively) (Figure 1C).

DISCUSSION

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgments
  8. REFERENCES
  9. Appendix: A: MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP

This study examined the variations in juvenile IIM clinical features and serologic expression among certain demographic groups in relation to exposure to surface UVR. As the mean and highest UV indices increased for the month before onset of myositis, white children had higher odds of developing anti-p155/140 autoantibodies, which was particularly true for white boys. For girls, the odds of juvenile DM increased as the highest UV index increased for the month before symptom onset.

When we examined variations across US geographic regions, UVR intensity for the month before symptom onset was moderately associated with the proportion of juvenile IIM patients who had juvenile DM, relative to juvenile PM, and weakly associated with anti-p155/140 autoantibodies. These data showed that certain regions within the US, including the south, southwest, southeast, and west, had a higher prevalence of patients with juvenile DM and anti-p155/140 autoantibodies. In contrast, with regard to positivity for anti-MJ autoantibodies, there was a higher prevalence among patients in northern latitudes, which have lower UVR exposure. These findings suggest that variations in the prevalence of myositis autoantibodies may exist in the US and are related, directly or inversely, to UVR intensity. Similar to the findings in adult myositis in the US ([5]), we found that in patients with juvenile myositis, white race was associated with the effect of UVR in the expression of clinical and autoantibody phenotypes.

Exposure to solar UVR is recognized to have both beneficial and harmful effects on human health. With regard to immune responses, it can suppress immunity and the synthesis of vitamin D, a hormone that alters both innate and adaptive immunity ([8]). The consequences of such UVR-induced changes, in both adults and children, are considerable. The positive outcomes include protection against some T cell–mediated autoimmune diseases, such as multiple sclerosis ([9]), and the negative outcomes include higher risk of skin cancer and less effective control of several infectious diseases ([10]). Overexposure to UVR may suppress proper functioning of the body's immune system and the skin's natural defenses, e.g., by increasing and exacerbating certain autoimmune diseases, such as systemic lupus erythematosus (SLE) ([11]). Geographic variation in exposure to UVR has also been associated with differences in mortality in SLE ([12]).

Our analysis complements the findings in the study by Love et al ([5]), as we looked at whether short-term UVR exposure, as measured by the mean and highest UV indices 30 days before symptom onset, was associated with the proportion of patients with juvenile DM, in particular those with anti-p155/140 or anti-MJ autoantibodies. In our study, we may have used a more relevant window of exposure. For example, risk of SLE has been associated with outdoor work in the year before diagnosis, particularly among those who are prone to sunburn and among persons who had serious sunburns before age 20 years ([7]). Thus, childhood exposure to UVR resulting in sunburn may be important for the later development of some autoimmune diseases.

Studies in adult myositis have examined the influence of UVR on anti–Mi-2 autoantibodies, which are associated with adult DM ([4, 5]). Because those studies showed that few patients with juvenile IIM had anti–Mi-2 autoantibodies, we could not examine the impact of UVR on anti–Mi-2; instead, we looked at the impact on the myositis autoantibodies frequently associated with juvenile DM (anti-p155/140 and anti-MJ autoantibodies). We saw an association between UVR and the frequency of anti-p155/140 autoantibodies that was similar to that found for anti–Mi-2 autoantibodies ([4, 5]). We also saw a negative relationship between UVR exposure and anti-MJ autoantibodies.

Similar to the study by Love et al ([5]), we found evidence of an influence of race and sex on associations with UVR in autoimmune disorders, including an association between UVR exposure and juvenile DM in girls only. In contrast, we found a predominance of boys showing an association of UVR with anti-p155/140 autoantibodies. The reasons for these sex-specific effects on the UVR–juvenile DM relationship remain unclear. Our study may have been underpowered to detect differences in some subgroups in this juvenile IIM population. In the study by Love et al, the findings suggested that UVR exposure has a differential impact on males and females, based on studies in mice ([5]). Previous studies have shown sex and racial differences in vitamin D metabolism ([13]). Of note, skin cancer is more prevalent in men than in women, and men are prone to greater UVR-induced immune suppression ([14]).

In addition, how UVR exposure might result in the development of anti-p155/140 autoantibodies is also unknown. UVR induces a cascade of events involving type I interferons ([5]), which have been associated with DM. The tripartite motif–containing family of proteins, of which the p155/140 autoantigen is a member, are notably up-regulated by interferons ([15]).

Because we could not assess individual exposure to UVR, we used data from the city closest to where the patient lived. We also extrapolated UVR data to 1994 values for those patients whose onset of symptoms was during the 5 years prior to 1994. UVR intensities can vary based on weather and altitude, and that information also was not available. Future studies with individual UVR monitoring would be helpful to confirm the findings of this study.

As expected, our juvenile IIM cohort had a lower prevalence of PM than was found in the adult IIM study, which contributed to a low power to detect effects. Nevertheless, overall, our findings were similar to those in the study by Love et al ([5]), although the effect was smaller. The stronger effect of adult DM, including female susceptibility to UVR exposure, may be related to an interaction of UVR with hormones ([5]), which we were unable to examine. We also did not account for differences in the use of photoprotective measures or in the frequency of sunburns prior to onset of juvenile IIM, which are frequent in teenage children ([16]).

Despite its limitations, this study adds important information about the impact of UVR on autoimmune muscle disease. The observed association of UVR with juvenile DM and with anti-p155/140 autoantibodies has implications for the implementation of photoprotective prevention measures, and suggests that further research regarding the role of UVR in the pathogenesis of myositis in children is needed.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgments
  8. REFERENCES
  9. Appendix: A: MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Rider had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Shah, Rice, Miller, Rider.

Acquisition of data. Shah, Targoff, Rider.

Analysis and interpretation of data. Shah, Rice, Miller, Rider.

Acknowledgments

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgments
  8. REFERENCES
  9. Appendix: A: MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP

We thank Drs. Glinda Cooper and Satoshi Okada for valuable comments after their critical reading of the manuscript. We thank Mona Shah's PhD thesis committee at the George Washington University Department of Epidemiology and Biostatistics, including Dr. Sean Cleary and committee members Drs. Heather Young and Yinglei Lai and examiners Drs. Mark Gourley and Margaret Ulfers, for their valuable feedback on this work.

REFERENCES

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgments
  8. REFERENCES
  9. Appendix: A: MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP

Appendix: A: MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. AUTHOR CONTRIBUTIONS
  7. Acknowledgments
  8. REFERENCES
  9. Appendix: A: MEMBERS OF THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP

Members of the Childhood Myositis Heterogeneity Collaborative Study Group who contributed to this study are as follows: Leslie S. Abramson, Daniel A. Albert, Bita Arabshahi, Alan N. Baer, Imelda M. Balboni, C. April Bingham, William P. Blocker, John F. Bohnsack, Gilles Boire, Gary R. Botstein, Suzanne Bowyer (deceased), Jon M. Burnham, Ruy Carrasco, Victoria W. Cartwright, Gail D. Cawkwell, Chun Peng T. Chao, Randy Q. Cron, Marietta M. DeGuzman, Anne Eberhart, John F. Eggert, Andrew H. Eichenfield, Melissa E. Elder, Terri H. Finkel, Robert C. Fuhlbrigge, Christos A. Gabriel, Vernon F. Garwood, Abraham Gedalia, Stephen W. George, Harry L. Gewanter, Ellen A. Goldmuntz, Donald P. Goldsmith, Gary V. Gordon, Alexia C. Gospodinoff, Beth Gottlieb, Thomas A. Griffin, Brandt P. Groh, Hillary M. Haftel, Michael Henrickson, Gloria C. Higgins, George Ho, Mark F. Hoeltzel, J Roger Hollister, Russel J. Hopp, Lisa Imundo, Jerry C. Jacobs (deceased), Laura James-Newton, Anna Jansen, Rita Jerath, Olcay Y. Jones, Lawrence K. Jung, Thomas V. Kantor, Ildy M. Katona, James D. Katz, Yukiko Kimura, Daniel J. Kingsbury, Steven J. Klein, W. Patrick Knibbe, David K. Kurahara, Andrew Lasky, Julia Lee, Johanan Levine, Carol B. Lindsley, Gulnara Mamyrova, Paul L. McCarthy, John J. Miller III, Stephen R. Mitchell, Hamid Jack Moallem, Chihiro Morishima, Terrance O'Hanlon, Judyann C. Olson, Elif A. Oral, Lauren M. Pachman, Ramesh Pappu, Murray H. Passo, Maria D. Perez, Donald A. Person, Karin S. Peterson, Paul H. Plotz, Marilyn G. Punaro, C. Egla Rabinovich, Charles D. Radis, Ann M. Reed, Robert M. Rennebohm, Peter D. Reuman, Rafael F. Rivas-Chacon, Deborah Rothman, Kenneth N. Schikler, Donald W. Scott, Bracha Shaham, David D. Sherry, Edward Sills, Sara H. Sinal, Robert P. Sundel, Ilona S. Szer, Simeon I. Taylor, Richard K. Vehe, Scott A. Vogelgesang, Larry B. Vogler, Steven Wall, Carol A. Wallace, Jennifer C. Wargula, Patience H. White, M. Jack Wilkenfeld, Andrew P. Wilking, Lan Wu, Christianne M. Yung, and Lawrence S. Zemel.