Accepted Manuscript

Dermatomyositis Part 2: Diagnosis and Treatment

Reid Waldman, M.D., Madeline E. DeWane, B.A., Jun Lu, M.D.

PII: S0190-9622(19)32308-4
DOI: https://doi.org/10.1016/j.jaad.2019.05.105
Reference: YMJD 13599

To appear in: Journal of the American Academy of Dermatology

Received Date: 20 March 2019

Revised Date: 9 May 2019
Accepted Date: 11 May 2019

Please cite this article as: Waldman R, DeWane ME, Lu J, Dermatomyositis Part 2: Diagnosis and
Treatment, Journal of the American Academy of Dermatology (2019), doi: https://doi.org/10.1016/
j.jaad.2019.05.105.

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 ACCEPTED MANUSCRIPT
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1 Dermatomyositis Part 2: Diagnosis and Treatment

2 Reid Waldman, M.D.1 Madeline E. DeWane, B.A.2 Jun Lu, M.D.1
1
3 University of Connecticut Department of Dermatology, Farmington, CT 06032
2
4 University of Connecticut School of Medicine

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5 Corresponding Author:
6 Jun Lu, M.D.
7 21 South Road

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8 Farmington, CT 06032
9 jlu@uchc.edu

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10 Tel: 860-679-4600
11 Word Count: Manuscript – 2997, Abstract – 134

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12 Figures: 5
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13 Tables: 3
14 References: 88
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15 Funding: This article has no funding source.

16 Conflicts of Interest: None of the authors have relevant conflicts of interest.
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17 Key Words: Dermatomyositis, Juvenile Dermatomyositis, cancer associated

18 dermatomyositis, anti-MDA5 dermatomyositis
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19 Statement on Prior Presentation: This work has not been previously published or presented.
20 Reprint Requests:
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21 Jun Lu, M.D.

22 21 South Road
23 Farmington, CT 06032
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24 jlu@uchc.edu
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25 Tel: 860-679-4600
26

27
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28 Abstract

29 Part II of this CME Series reviews the initial evaluation of patients with suspected

30 dermatomyositis (DM), the relevant work-up for malignancy and interstitial lung disease once a

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31 diagnosis of DM is made, and treatment recommendations for patients with DM based on disease

32 severity, presence of systemic symptoms, and myositis specific antibody profiles. This review

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33 emphasizes the emerging role of myositis specific antibodies (MSAs) in the diagnosis of DM and

34 highlights how MSAs can be used to guide the appropriate work-up for malignancy and

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35 interstitial lung disease. The treatment approach proposed by this CME discusses both

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36 established and novel therapies for DM and highlights the importance of considering lesion type,
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37 degree of muscle involvement, presence of systemic symptoms, presence of MSAs, and patient

38 age when determining the best treat approach for a patient with DM.
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40 Introduction

41 The evaluation and management of patients with suspected dermatomyositis (DM) is

42 evolving. Part II of this CME Series will review the initial evaluation of patients with suspected

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43 DM as well as the relevant work-up for systemic manifestations once a diagnosis is made.

44 Recommendations for treatment based on disease severity, the presence of systemic symptoms,

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45 the presence of myositis specific antibodies (MSAs), and patient age will be given. The

46 integration of MSAs into the management of DM patients will be emphasized. Treatment

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47 recommendations will include a discussion of emerging therapies.

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48 The Initial Approach: Diagnosing Dermatomyositis
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49 The initial evaluation of patients with suspected DM must include a total body skin

50 examination, objective muscle strength examination, and a laboratory work-up.1 In equivocal

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51 cases, skin biopsy, muscle biopsy, or muscle imaging may clarify the diagnosis.2 Historically, a
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52 diagnosis of DM was made based on criteria proposed by Bohan and Peter in 1975.3 Many new
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53 classification systems have subsequently been proposed (Table 2). Most recently, the European

54 League Against Rheumatism/American College of Rheumatology (EULAR/ACR) developed the

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55 first validated classification criteria with a reported sensitivity of 87% and specificity of 82% for

56 a diagnosis of DM. However, the sensitivity of these guidelines is poor for diagnosing
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57 amyopathic DM because only limited types of cutaneous lesions are included in their scoring
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58 system.4,5 Additionally, the only MSA included in the EULAR/ACR criteria is Anti-Jo-1, as

59 other antibodies were not widely available at the time the guidelines were formed.1

60 The authors have modified the EULAR/ACR diagnostic approach to incorporate the use

61 of multiple newly available MSAs (Table 1, Figure 1). Incorporation of MSAs into diagnostic
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62 criteria of DM is beneficial for several reasons: 1) it facilitates diagnosis of DM, especially in

63 cases of CADM; 2) it separates patients with DM into clinically relevant subsets (which helps

64 tailor the additional work-up for systemic manifestations based on an individual’s MSA profile);

65 and, 3) it obfuscates the need for muscle biopsy in many cases. A 2018 study in JAMA

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66 Neurology supports the use of MSAs in diagnosis; in this study, patients with idiopathic

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67 inflammatory myopathies (IIMs) were appropriately classified as having DM, inclusion body

68 myositis(IBM), immune-mediated necrotizing myositis (IMNM), or anti-synthetase syndrome

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69 (ASS) based solely on MSA profile and clinical manifestations.6

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70 Evaluation for Systemic Manifestations AN
71 Once a diagnosis of DM has been confirmed, patients must undergo additional work-up

72 to identify systemic manifestations. This work up should be directed by the patient’s MSA
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73 profile. An in-depth review of the clinical manifestations associated with each MSA is provided
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74 in Part I of this CME Series. Dermatologists using MSAs as part of their clinical decision

75 making must ensure that they are ordering a testing assay that reliably detects and discriminates
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76 between relevant MSAs, as some assays perform less reliably than others.7,8
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77 Malignancy Work-Up

78 The estimated prevalence of malignancy in adult DM patients is 20%. The risk of

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79 developing malignancy is highest within a year of diagnosis and remains elevated for up to 5
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80 years.9 Malignancy risk is also increased for males and those over 45 at the time of diagnosis.10,9

81 In juvenile dermatomyositis (JDM), malignancy is extremely uncommon with no cases of

82 malignancy-associated JDM identified in the EuroMyositis registry.11 As highlighted in Part I,

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83 malignancy-associated DM primarily occurs in adults who are either anti-TIF1 or anti-NXP2

84 positive.11,12

85 Patients with JDM do not require any work-up for malignancy.11 A suggested algorithm

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86 for appropriate malignancy screening in newly diagnosed adult DM patients is detailed in Figure

87 2. Adult DM patients who are both anti-TIF-1 and anti-NXP2 negative (i.e. low-risk of

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88 malignancy associated-DM) require history, physical examination, “age-appropriate” cancer

89 screening, and symptom-targeted cancer screening alone as there is not strong evidence to

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90 suggest that individuals without these antibodies are at an appreciably elevated risk for

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91 malignancy compared to the general population.12 Aggressive work-up for malignancy in these
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92 patients is likely to be costly and invasive, and available evidence suggests that it is unlikely to

93 improve outcomes. Possible exceptions to this recommendation are: 1) anti-SAE positive

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94 individuals, as some studies have demonstrated a risk for malignancy in these patients, although

95 this finding has not been uniformly reproducible and 2) MSA-negative patients, as a recent large,
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96 retrospective study suggested that these patients have a three-times elevated risk of developing
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97 malignancy over matched controls.12

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98 Given the paucity of data about cancer risk in these two sub-populations, it may be

99 reasonable to further stratify cancer risk with serum biomarkers, although such an approach has
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100 never been studied or suggested for this “intermediate-risk” population specifically. Annual
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101 soluble Programmed Death Ligand-1 (sPDL-1) measurements can be considered, as extremely

102 elevated levels of sPDL-1 have been associated with malignancy in DM patients.13,14 Use of

103 cancer serum biomarkers (e.g. CEA, CA 19-9) other than prostate specific antigen, a potential

104 component of “age-appropriate” screening, has not been demonstrated to be effective for

105 detecting malignancy in DM patients.15

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106 In addition to “age-appropriate” and “symptom-targeted” malignancy screening,

107 individuals who are anti-TIF1 or anti-NXP2 positive (i.e. high-risk for malignancy-associated

108 DM) should undergo whole body imaging with either CT, MRI, or PET-CT.13,16 These

109 modalities have been proven to detect DM-associated malignancies that would be missed by

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110 “age-appropriate” and “symptom-targeted” screening.17 No study has compared superiority of

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111 one imaging modality over the others. Studies that have failed to demonstrate benefit with the

112 use of whole-body imaging have not sub-selected for high-risk patients.18

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113 The appropriate re-imaging interval in high-risk individuals who had an initially negative

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114 work-up for malignancy has not been studied. As an increased malignancy risk is present for up
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115 to five years after DM onset, some authorities recommend annual imaging until that time point is

116 reached.13 Finally, high-risk individuals who would not receive upper and lower endoscopy as
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117 part of their “age-appropriate” screening and who do not have malignancy identified on other

118 work-ups should consider undergoing this testing.13

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119 Interstitial Lung Disease Work-Up

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120 Evaluation for interstitial lung disease (ILD) in patients with a new diagnosis of DM
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121 involves identifying whether a patient has ILD, and if so, whether a patient has a poor prognosis

122 subset of ILD termed rapidly progressive ILD (RPILD). The early identification of RPILD is
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123 essential as it is fatal within six months in 50% of cases and the prognosis can be improved if
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124 treatment is initiated prior to the development of abnormalities on High-Resolution Computed

125 Tomography (HRCT).19,20

126 Figure 3 provides an algorithm for evaluating DM patients for ILD. All patients require

127 pulmonary function testing (PFTs) and DLCO (diffusion capacity of the lung for carbon
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128 monoxide) at the time of diagnosis.21 In asymptomatic patients with restrictive physiology

129 present on PFTs and decreased DLCO, or in patients with symptoms suggestive of ILD, HRCT is

130 indicated.21 If ILD is not present on an initial work-up, patients can be monitored clinically with

131 a plan to repeat HRCT if new or worsening pulmonary symptoms develop.21 All patients with

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132 evidence of ILD require urgent pulmonology evaluation.

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133 Anti-MDA5 antibodies are present in at least half of all cases of DM-associated ILD and

134 more than 80% of cases of DM-associated RPILD.20,22,23 In JDM, anti-MDA5 positivity is also

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135 predictive of ILD and RPILD with an estimated sensitivity of ~70% for ILD.24 Because RPILD

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136 can evade imaging during its early stages, testing serum biomarkers that correlate with the
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137 presence of ILD and that are elevated prior to imaging changes should be considered.25,26

138 Elevated levels of serum ferritin, Interleukin 18, Krebs von den Lungen-6 (KL-6) and anti-
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139 MDA5 antibodies themselves have been associated with the presence of ILD, and laboratory

140 testing for these biomarkers should be considered in all patients with anti-MDA5
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141 dermatomyositis.27–31
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142 Other Systemic Work-Up

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143 Part I of this CME series discusses the many other potential systemic manifestations of

144 DM and JDM. Given their relative infrequency, screening for these manifestations with a
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145 targeted review of symptoms is reasonable.

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146 General Treatment Approach

147 Management of DM is nuanced; dermatologists frequently diagnose the disease and have

148 primary responsibility for the cutaneous manifestations of the disease, but myopathy and other
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149 systemic manifestations often drive therapy. The appropriate treatment approach is determined

150 by consideration of five factors:

151 1) Lesion type – Is the lesion nonvasculopathic (e.g. shawl sign, heliotrope rash),

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152 vasculopathic (digital pulp ulcers, inverse gottron’s papules), or calcinotic?

153 2) Degree of muscle involvement – Is the patient amyopathic/hypomyopathic? Does the

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154 patient have persistent cutaneous symptoms despite having controlled myopathy? Is the

155 patient post-myopathic (i.e. have the patient’s muscle symptoms resolved despite being

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156 off treatment but residual cutaneous disease is still present)?

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157 3) Presence of systemic symptoms – Are other organ systems involved? Is there an
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158 associated malignancy?

159 4) Presence of MSAs – What clinical subset does the patient have as suggested by the
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160 presence of MSAs?

161 5) Patient age – Does the patient have adult or juvenile dermatomyositis?
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162 This section will discuss each of these factors with an emphasis on the use of a multidisciplinary
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163 approach in settings where muscle involvement or systemic symptoms are present.
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164 Considering Lesion Type

165 Nonvasculopathic Cutaneous Disease

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166 Three layers of therapy should be used for all patients with nonvasculopathic disease: sun

167 protection, topical therapy with corticosteroids and/or calcineurin inhibitors, and systemic

168 therapy.32,33 This section will focus on systemic therapies. A treatment algorithm for adult DM

169 is presented in Figure 4.

170 Systemic Corticosteroids

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171 Systemic corticosteroids are the gold standard initial treatment for DM-related myopathy.

172 However, they should not be used in CADM and should not be used as a monotherapy as this

173 approach is frequently ineffective and associated with the development of unacceptable long-

174 term adverse effects.34–36 Similarly, in cases where a patient’s myopathy is controlled with

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175 corticosteroids but cutaneous symptoms persist, a dose increase in corticosteroids alone is not

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176 recommended. A combination of systemic corticosteroids with oral immunosuppressants or

177 biologics should be used at disease onset in patients with myopathy or other systemic symptoms,

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178 similar to how combination therapy is employed in bullous disorders to limit systemic

179 corticosteroid use.34,37

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180 Antimalarials

181 Traditional treatment algorithms have emphasized hydroxychloroquine as the first-line

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182 systemic agent for cutaneous DM. However, recent evidence suggests that patients treated with
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183 hydroxychloroquine are more likely to flare their cutaneous disease than they are to achieve

184 satisfactory disease control from hydroxychloroquine monotherapy.35,36,38,39Patient MSA profiles

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185 may predict risk of cutaneous flare after hydroxychloroquine initiation with anti-SAE positive
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186 patients at the highest risk and anti-MDA5 patients without demonstrable risk. 40 Furthermore,

187 unlike other systemic therapies, none of the antimalarials have an effect on the non-cutaneous
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188 manifestations of DM (e.g. myopathy, ILD).41,42 Given the favorable side effect profile of
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189 antimalarials they can be considered as adjuvants when disease control is inadequate with other

190 systemic agents.35,36,42,43

191 Mycophenolate Mofetil (MMF) and Methotrexate (MTX)

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192 In the absence of vasculopathic or calcinotic lesions the first line systemic therapies for

193 nonvasculopathic DM are mycophenolate mofetil (MMF) and methotrexate (MTX).38,44–48 Both

194 of these medications often require high dosing, with many adults requiring 3 grams of MMF

195 daily or 25 mg of MTX weekly. These medications should be started in conjunction with

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196 systemic corticosteroids when myopathy is present. However, systemic corticosteroids do not

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197 need to be used in conjunction with these medications when treating CADM or post-myopathic

198 cutaneous disease.

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199 There are no head-to-head studies comparing MMF and MTX, but several considerations

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200 may favor the use of one agent over the other; MTX often has faster onset (~ 4 weeks) and has
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201 clinical trial data supporting its use as a steroid-sparing agent. Additionally, MMF is effective for

202 treating ILD .37,49,50 Treatment failure with one agent is not predictive of treatment failure with
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203 the other.

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204 Rituximab
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205 In cases where a combination of systemic corticosteroids and an oral immunosuppressant

206 fail, rituximab is the appropriate next step in therapy.51–53 In individuals with vasculopathic
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207 and/or calcinotic lesions, adults with anti-MDA5 positivity, or children with NXP-2 positivity,

208 rituximab plus systemic corticosteroids can be considered as a first-line treatment.54–56 Support
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209 for the use of rituximab comes from the largest clinical trial ever conducted for IIMs, the
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210 Rituximab in Myositis (RIM) trial.51 This trial demonstrated that 83% of children and adults with

211 DM who previously failed systemic corticosteroids and at least one immunosuppressant

212 improved with rituximab and were tapered off systemic steroids more quickly.51 MSA-positive

213 individuals had a greater chance of responding favorably to rituximab than MSA-negative

214 individuals.51
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215 Additionally, several recent findings suggest rituximab may have disease modifying

216 properties. Rituximab is the only treatment associated with improvement in nail fold capillary

217 abnormalities which may represent prevention of pathogenic vessel damage. In cases where

218 MSAs are presumed to be pathogenic, (e.g. anti-MDA5 DM) rituximab likely works through a

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219 similar mechanism as in pemphigus (a condition in which it has been shown to be disease

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220 modifying).51,57 The two major limitations to the use of rituximab are that it has a slow onset and

221 a risk of serious infection greater than 6%.51,56

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222 The frequency with which individuals receiving rituximab should undergo an additional

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223 round of treatment is unknown. In the RIM trial, CD19+ numbers rebounded above 5 cells/uL at
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224 weeks 32-36 on average.51 Based on the pemphigus literature, it may be reasonable to trend

225 peripheral B cell concentrations to guide therapy.58

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226 Intravenous Immunoglobulin (IVIG)

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227 A reasonable treatment option in patients who have failed or who are intolerant of
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228 rituximab is intravenous immunoglobulin (IVIG).43,59,60 It is also recommended for patients with

229 controlled myopathy but persistent cutaneous disease.61 In cases with severe disease that is
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230 refractory to IVIG, subcutaneous immunoglobulin administration can be considered if

231 available.62
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232 Calcineurin Inhibitors

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233 Calcineurin inhibitors (typically cyclosporine and less frequently tacrolimus) are

234 reasonable third-line options or are useful in cases in which myopathy is controlled but other

235 immunosuppressants are not controlling cutaneous disease.48 Although cyclosporine is as

236 effective as MTX based on the Pediatric Rheumatology International Trials Organization
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237 (PRINTO) data, MTX and MMF are preferred because the PRINTO trial demonstrated that

238 cyclosporine use was associated with a greater risk of serious adverse effects.37 Calcineurin

239 inhibitors are also a reasonable choice in patients with co-morbid interstitial lung disease.63,64

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240 Other Traditional Therapies

241 Other therapies that can be considered include infliximab, azathioprine, and

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242 cyclophosphamide. However, these should be reserved for refractory cases given the plethora of

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243 superior options listed above.65–67

244 Vasculopathic Cutaneous Disease

245
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Vasculopathic skin lesions include ulceration, inverse Gottron’s papules, and nailfold
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246 capillary abnormalities. These lesions are notoriously refractory to immunosuppressive therapy
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247 and confer significant morbidity even in the absence of other cutaneous disease. The only

248 systemic agent with robust data supporting its use for vasculopathic lesions is rituximab.
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249 However, rituximab alone is often ineffective for treating ulceration.56,68 Intralesional
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250 corticosteroids are frequently used for treating ulcerations and inverse Gottron’s papules and

251 may be effective, but recent evidence supports using vasodilatory agents. Case studies suggest
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252 that nifedipine, sildenafil, intravenous prostaglandins, and bosentan should be added as early

253 adjuncts given the otherwise refractory nature of these lesions.69

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254 Calcinosis Cutis

255 Like vasculopathic lesions, calcinotic lesions are typically refractory to

256 immunosuppressive therapy. Patients with JDM and calcinosis should be preferentially treated

257 with IVIG as it has the best data supporting its use for calcinosis specifically.59,70,71 For a detailed
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258 discussion of calcinosis cutis-directed therapies, the authors encourage readers to review the

259 JAAD CME Series on calcinosis cutis.72

260 Considering Degree of Muscle Involvement

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261 Patients with myopathy should be managed in conjunction with a rheumatologist or

262 neurologist. Controlled cutaneous disease is not predictive of controlled myopathy and vice

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263 versa. Unlike in patients with CADM (for whom monotherapy with oral immunosuppressants is

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264 a reasonable first-line therapy), first line therapy for management of the myopathy component of

265 DM is the simultaneous initiation of corticosteroids and a steroid-sparing immunosuppressant

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266 (e.g. MMF, MTX).37 Subsequent treatment choices in individuals with recalcitrant myopathy are
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267 similar to those highlighted above for the treatment of refractory cutaneous disease.

268 The appropriate treatment for persistent cutaneous involvement in patients with
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269 controlled myopathy depends on the treatment the patient is currently receiving and the degree of
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270 severity of the cutaneous involvement.73 Dose escalations of an oral immunosuppressant,

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271 initiation of hydroxychloroquine, initiation of IVIG, or initiation of rituximab can all be

272 reasonable next steps depending on the clinical scenario.61Post-myopathic cutaneous disease can
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273 be managed similarly to CADM.

274 Considering Systemic Symptoms

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275 Treatment of the systemic symptoms associated with DM is beyond the scope of this

276 CME series and should be addressed as part of a multidisciplinary approach.

277 Considering MSAs

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278 MSAs will undoubtedly be used to personalize treatment decisions for patients with DM

279 in the future. However, at this time there is a paucity of data supporting such an approach.

280 Several anecdotally supported treatment considerations have been mentioned above.

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281 Considering Age

282 Only two clinical trials have specifically evaluated patients with JDM (the PRINTO and

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283 RIM trials), but consensus opinions are also available from the Childhood Arthritis and

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284 Rheumatology Research Alliance (CARRA) and Single Hub and Access point for pediatric

285 Rheumatology in Europe (SHARE) registries.37,51,56,74,75 Review of these pivotal studies

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286 supports the approach to JDM proposed in Figure 5. All patients should at least be started on a
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287 combination of systemic corticosteroids with either MTX or IVIG to decrease long-term steroid

288 burden.37,75 In patients that fail first-line treatment, have severe disease with ulceration,
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289 calcinosis, or lipodystrophy at the time of presentation, or have poor prognosis NXP-2 disease,

rituximab plus systemic corticosteroids can be considered.56 Other biologics, cyclophosphamide,

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291 and JAK inhibitors can be considered in patients with refractory disease.65,67,76
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292 Emerging Treatments

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293 Several novel approaches to DM have recently garnered significant interest. JAK

294 inhibitors (JKIs) will be discussed here as they have the most robust evidence for the treatment
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295 of cutaneous DM. Other emerging treatments are listed in Table 4.

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296 Jak Kinase Inhibitors

297 DM is driven by type I interferons. Both in vivo and in vitro data has shown that JKIs

298 decrease levels of type I interferons in individuals with DM.77 Case series have shown that

299 several JKIs are effective for treating refractory cutaneous disease.78 One series has also shown
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300 that JKIs may be an effective add-on therapy in patients with RP-ILD.79 There is an ongoing

301 clinical trial assessing the efficacy of tofacitinib in refractory DM that is assessing both skin and

302 muscle outcomes.

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303 Conclusion

304 A thorough initial assessment of patients with suspected DM is essential to making a

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305 diagnosis with as little delay and morbidity as possible. The management of DM is nuanced and

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306 requires a constant assessment for the development of systemic symptoms. A multi-disciplinary

307 approach is recommended.

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309 Figure 1. Diagnostic algorithm for adult and juvenile DM.

310 *As indicated in Part I Table I.
311 **Pts < age 18 at time of symptom onset are considered to have JDM.
312 ***ADM pts should be monitored regularly for development of muscle involvement.

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313

314 Figure 2. Malignancy work-up for newly diagnosed DM patients.

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316 Figure 3. Interstitial lung disease work-up for newly diagnosed DM patients.

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317
318 Figure 4. Adult DM treatment algorithm
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320 Figure 5. JDM treatment algorithm
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- Total body skin exam

Exam History & physical examination - Manual strength testing
of bilateral extremities
and neck flexors
- CK
Baseline laboratory testing Muscle enzymes - LDH
- AST

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- Aldolase
- Mi2
- TIF1

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DM-specific autoantibodies - MDA5
- NXP2
- SAE

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- Jo-1
Anti-synthetase syndrome - PL-7
Auto-antibody testing autoantibodies - PL-12
- EJ

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- OJ
IMNM autoantibodies - SRP
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(if indicated clinically) - HMGCR

- ANA
Other connective tissue disease- - Ro/La
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related autoantibodies - dsDNA

(if indicated clinically) - Anti-Sm
- Scl-70
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If the above testing is equivocal - T2 weighted MRI of area

of weakness
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Further testing If diagnosis remains uncertain - Muscle biopsy of

affected area identified
on MRI
337 Table I. Initial workup for suspected DM based on EULAR/ACR criteria
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Classification Criteria Included Entities Defined Benefits & Limitations

system
Bohan and Clinical -Definite DM -High sensitivity but low
Peter (1975) -Skin rash (heliotrope rash or -Probable DM specificity82
80,81
Gottron sign) -Possible DM - Outdated
-Symmetric proximal muscle -Definite PM conceptualization of DM
weakness -Probable PM and PM as related entities

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-Possible PM on a spectrum of
Laboratory inflammatory myopathy83
-Elevation of skeletal muscle -Does not specify how to

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enzymes exclude other forms of
myopathy82
Other
-EMG findings

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-Muscle biopsy findings

Tanimoto Clinical

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(1995)84 -Skin rash (heliotrope rash or -PM specificity82
Gottron’s sign or linear extensor
erythema)
-Proximal muscle weakness
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-Muscle pain on grasping or

spontaneous pain
-Nondestructive arthritis or
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arthralgia
-Fever
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Laboratory
-Elevated CK or aldolase
-Elevated CRP or ESR
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-Positive anti-Jo-1 antibodies

Other
-Abnormal EMG findings
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-Abnormal muscle biopsy

Targoff Clinical -Definite IIM -Sensitivity 93%, specificity
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(1997)85 -Skin rash (heliotrope rash or -Probable IIM 89% using EULAR/ACR
Gottron sign) -Possible IIM dataset82
-Symmetric proximal muscle -Subclassifies
weakness DM, IBM, JDM,
amyopathic DC
Laboratory (ADM)
-Elevation of skeletal muscle
enzymes
-Presence of any MSA
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Other
-EMG findings
-Muscle biopsy findings

Dalakas and Clinical -Definite PM -High specificity but low

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Hohlfield -Skin rash (or calcinosis) -Probable PM sensitivity using
(2003)86 -Myopathic muscle weakness -Definite DM EULAR/ACR dataset82
-Probable DM

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Laboratory -Definite ADM
-Elevated muscle enzymes

Other

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-Muscle biopsy findings
-EMG findings
ENMC (2003)87 Clinical -Definite DM -High specificity but low

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-Age -Probable DM sensitivity using
-Muscle weakness (specifies time -ADM EULAR/ACR dataset82
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course and pattern) -DM sine
-Skin rash (heliotrope, periorbital dermatitis
edema, Gottron’s papules/sign, V -Definite PM
sign, shawl sign, holster sign) -Probable PM
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-Non-specific
Laboratory myositis
-Elevated CK -Immune-
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-Detection of MSAs mediated

necrotizing
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Other myopathy
-EMG findings (IMNM)
-MRI findings
-Muscle biopsy findings
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EULAR/ACR Clinical -Algorithm -Large dataset

(2017)82 -Age determines IIM -Sensitivity 93%, specificity
-Muscle weakness probibility 88% (with muscle biopsy
-Skin rash (heliotrope rash, -Subclassifies data)
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Gottron’s papules, Gottron’s sign) PM, IBM, DM, -Sensitivity 87%, specificity
ADM, JDM 82% (without muscle
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Laboratory biopsy data)

-Positive anti-Jo-1 antibody -Subclassification limited by
-Elevated CK, LDH, AST, ALT small sample size for some
entities
Other -Requires additional
-Muscle biopsy findings validation in Asian and
African populations
-Can diagnose DM without
muscle biopsy when typical
skin findings are present
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Mariampillai -47 variables used in multiple -DM

(2018)88 correspondence analysis -IBM
-Included sociodemographic -IMNM
variables, skin lesions, biological -ASS
variables (including CK levels and
MSAs), histological variables,
clinical muscular variables, and

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347 Table II. Classification systems for IIMs.

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Administration
Tocilizumab IV IL-6 Inhibitor Y
Aletuzumab IV Anti-CD52 N
Abatacept IV Co-stimulatory Modulator Y
Infliximab IV TNF inhibitor Y
Anakinra SubQ IL-1 Inhibitor N
Eculizumab IV C5-blocking agent N

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Apremilast PO PDE4 Inhibitor Y
370 Table III. Emerging treatments for DM

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391 Abbreviations
392 Myositis specific antibodies (MSAs)
393 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR)
394 Idiopathic Inflammatory Myopathy (IIM)

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395 Juvenile dermatomyositis (JDM)
396 Inclusion body myositis (IBM)
397 Immune mediated necrotizing myositis (IMNM)

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398 Anti-synthetase syndrome (ASS)
399 Soluble Programmed Death Ligand-1 (sPDL-1)

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400 Interstitial lung disease (ILD)
401 Rapidly progressive ILD (RPILD)

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402 High-Resolution Computed Tomography (HRCT)
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403 Pulmonary function testing (PFTs)
404 DLCO (diffusion capacity of the lung for carbon monoxide)
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405 Krebs von den Lungen-6 (KL-6)

406 Mycophenolate mofetil (MMF)
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407 Methotrexate (MTX)

408 Rituximab in Myositis (RIM)
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409 Intravenous Immunoglobulin (IVIG)

410 Pediatric Rheumatology International Trials Organization (PRINTO)
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411 Childhood Arthritis and Rheumatology Research Alliance (CARRA)

412 Single Hub and Access point for pediatric Rheumatology in Europe (SHARE)
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413 JAK Inhibitors (JKIs)

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421 References
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