ORIGINAL ARTICLE

1 56
2 A systematic review of safety and 57
3 58
4 efficacy of systemic corticosteroids 59
5 60
6 in atopic dermatitis Q1 61
7 62
8 Sherry Yu, MD,a Aaron M. Drucker, MD, ScM,b Mark Lebwohl, MD,c and Q8 63
9 Jonathan I. Silverberg, MD, PhD, MPHd,e,f 64
10 Boston, Massachusetts; Providence, Rhode Island; New York, New York; and Chicago, Illinois 65
11 66
12 Background: Systemic corticosteroids are often used to treat atopic dermatitis (AD). However, few studies Q4 Q5 67
13 have assessed the safety and efficacy of systemic corticosteroids in AD. 68
14 69
15 Objective: To systematically review the literature on efficacy and safety of systemic corticosteroid use (oral, 70
16 intramuscular, and intravenous) in AD. 71
17 72
Methods: PubMed, Embase, Medline, Scopus, Web of Science, and Cochrane Library were searched. We
18 73
included systematic reviews, guidelines, and treatment reviews of systemic corticosteroid use among
19 74
patients of all ages with a diagnosis of AD (52 reviews and 12 studies).
20 75
21 Results: There was general consensus in the literature to limit the use of systemic steroids to short courses 76
22 as a bridge to steroid-sparing therapies. Systemic side effects include growth suppression in children, 77
23 osteoporosis, osteonecrosis, adrenal insufficiency, Cushing syndrome, hypertension, glucose intolerance, 78
24 diabetes, gastritis, gastroesophageal reflux, peptic ulcer disease, weight gain, emotional lability, behavioral 79
25 changes, opportunistic infections, cataracts, glaucoma, myopathy, myalgia, dysaesthesia, pseudotumor 80
26 cerebri, hyperlipidemia, malignancy, thrombosis, skin atrophy, sleep disturbance, and rebound flaring. 81
27 82
Limitations: Baseline clinical severity, corticosteroid delivery and dose, and treatment response were
28 83
reported incompletely and heterogeneously across studies.
29 84
30 Conclusions: Evidence is not strong enough to determine optimal delivery or duration of systemic Q6 85
31 corticosteroids in AD. ( J Am Acad Dermatol https://doi.org/10.1016/j.jaad.2017.09.074.) 86
32 87
33 Key words: adrenal insufficiency; atopic dermatitis; atopic eczema; corticosteroids; eczema; intramuscular; 88
34 intravenous; oral; rebound flaring; systemic side effects. 89
35 90
36 91
37 Q2 From the Department of Dermatology, Massachusetts General Galderma, GlaxoSmithKline, Kiniksa, Leo, Medimmune, Menlo, 92
Hospital, Bostona; Department of Dermatology, Alpert Medical Pfizer, Realm-1, Regeneron-Sanofi, and Roivant and a speaker
38 School of Brown University, Providenceb; Department of for Regeneron-Sanofi. Dr Yu has no conflicts of interest to
93
39 Dermatology, Icahn School of Medicine at Mount Sinai, New declare. 94
40 Yorkc; Department of Dermatology,d Department of Preventive Dr Silverberg had full access to all the data in the study and takes 95
41 Medicine,e and Department of Medical Social Sciences, responsibility for the integrity of the data and accuracy of the 96
42 Feinberg School of Medicine at Northwestern University, data analysis, as well as for the study concept and design. Drs 97
Chicago.f Yu and Silverberg take responsibility for acquisition of data and
43 Supported by the Agency for Healthcare Research and Quality for drafting of the manuscript. Drs Yu, Drucker, Lebwohl, and
98
44 (grant K12 HS023011) and the Dermatology Foundation Silverberg take responsibility for analysis and interpretation of 99
45 (to Dr Silverberg). the data, as well as for critical revision of the manuscript for 100
46 Disclosure: Dr Drucker is a consultant for Sanofi and RTI Health important intellectual content. 101
47 Solutions, is an investigator for Regeneron and Sanofi, receives Accepted for publication September 28, 2017. 102
research funding from Regeneron and Sanofi, and has received Correspondence to: Jonathan I. Silverberg, MD, PhD, MPH,
48 honoraria (speaker and educational programming honoraria) Northwestern University Feinberg School of Medicine,
103
49 from Astellas Canada, Prime Inc, and Spire Learning. Department of Dermatology, Suite 1600, 676 N St. Clair St, 104
50 Dr Lebwohl is an employee of Mount Sinai, which receives Chicago, IL 60611. E-mail: JonathanISilverberg@Gmail.com. Q3 105
51 research funds from Abbvie, Amgen, Boehringer Ingelheim, Published online ddd. 106
52 Celgene, Eli Lilly, Janssen/Johnson & Johnson, Kadmon, 0190-9622/$36.00 107
Medimmune/Astra Zeneca, Novartis, Pfizer, Regeneron, and Ó 2017 by the American Academy of Dermatology, Inc.
53 ViDac. Dr Silverberg is an employee of Northwestern University https://doi.org/10.1016/j.jaad.2017.09.074
108
54 Feinberg School of Medicine, which receives research funds 109
55 from GlaxoSmithKline; he is a consultant for Abbvie, Eli Lilly, 110

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111 The American Academy of Dermatology design; dosing and route of SCS administration; 166
112 guidelines for treatment of atopic dermatitis (AD) number of patients in the study; and information 167
113 recommend a graded approach, beginning with on efficacy, tolerability, and AEs were collected. 168
114 skin care and trigger avoidance.1 In mild-to- 169
115 moderate AD, topical corticosteroids or calcineurin 170
116
RESULTS 171
inhibitors and antiseptic measures are appropriate.
Literature search
117 Systemic therapy is recommended for persistent, 172
The literature search yielded 2219 nonduplicate
118 moderate-to-severe AD after 173
articles. After title and abstract
119 inadequate response to opti- 174
120 mized topical management. 2 CAPSULE SUMMARY review, 2147 articles were
175
excluded; 52 reviews and
121 A wide range of treatment 176
Systemic corticosteroids are often used 12 studies were included
122 177
d

strategies have been used

to treat atopic dermatitis, but their safety (Supplemental Fig 1; avail-
123 for systemic corticosteroids 178
and efficacy has not been systematically able at http://www.jaad.org).
124 (SCSs) in clinical practice 179
125 reviewed. 180
(eg, different deliveries,
126 dosing, frequencies, and du- dMost data supporting the efficacy of Efficacy 181
127 rations). SCSs are commonly systemic corticosteroids are anecdotal. Oral. There was a general 182
128 used as a first-line systemic dBecause of significant side effects, consensus that SCSs quickly 183
129 treatment of AD,3,4 typically including rebound flaring, use of and effectively decrease clin- 184
130 in short courses to suppress systemic corticosteroids should be ical symptoms of AD, espe- 185
131 AD activity and interrupt limited to short courses as a bridge to cially pruritus (Supplemental 186
132 flares.5 steroid-sparing therapies. Table II; available at http:// 187
133 SCSs may be a useful www.jaad.org).5 Most data 188
134 treatment of AD flares owing supporting use of SCSs were 189
135 to their rapid induction of a clinical response, anecdotal, with little primary 190
136 perceived short-term safety and tolerability, and data. A case series presented 3 patients 191
137 low cost.6 However, few studies have assessed the who achieved good disease control with oral 192
138 efficacy and safety of SCSs in AD. This systematic corticosteroids.8 These authors recommended use 193
139 review sought to summarize the available evidence of long-term SCSs in refractory AD, especially in 194
140 for using SCSs in AD. patients with profound psychosocial consequences. 195
141 A retrospective study showed that 84.2% of patients 196
142 METHODS ranked SCSs as ‘‘very successful’’ treatment of 197
143 Literature search their AD.9 Despite widespread use of SCSs, few 198
144 The following databases were searched through randomized controlled clinical trials (RCTs) were 199
145 December 18, 2016: PubMed (1946- present), Embase conducted. 200
146 (1947-present), MEDLINE, Scopus (1823-present), A double-blind, placebo-controlled, crossover 201
147 Web of Science, and Cochrane Library (1992- RCT was performed; 4 weeks of combined oral and 202
148 present). The search strategy was based on a previous nasal beclomethasone dipropionate (BDP), a 203
149 Cochrane review for AD,7 with inclusion of additional synthetic glucocorticoid, was compared with 204
150 search terms related to steroid use (Supplemental placebo in 26 children with severe AD. BDP resulted 205
151 Table I; available at http://www.jaad.org). in a 22% decrease in mean AD severity using an 206
152 Systematic reviews, guideline statements, and unvalidated outcome, lower parent-assessed overall 207
153 treatment recommendation reviews that were disease activity, and greater treatment preference 208
154 published in English online, available in print, or in toward BDP.10,11 Oral BDP, 600 g 3 times daily for 209
155 press were eligible for inclusion. Manuscripts were 4 weeks followed by 1000 g daily for 6 weeks, 210
156 excluded on the basis of title and/or abstract review improved disease activity in 14 of 15 children with 211
157 if there was no clear indication that either efficacy or severe AD after 4 weeks.12 However, 4 children 212
158 adverse effects (AEs) of SCSs (oral, intramuscular failed to maintain treatment response once the BDP 213
159 [IM], or intravenous) was discussed. Studies cited in was tapered. 214
160 the reviews with primary data on the use and/or AEs Flunisolide, a synthetic steroid analogue, was 215
161 of SCSs in AD were also reviewed. orally administered to 20 children (640 g/d in 216
162 children age \3 years and 1200 g/d in older 217
163 Data extraction children) and resulted in a 49% reduction of clinical 218
164 S.Y. performed title/abstract review and data severity scores versus those with placebo after 219
165 extraction. First author; publication year; study 2 weeks.10,13 After the crossover portion at week 3, 220

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221 AD successfully treated with SCSs found that 276

222 Abbreviations used: 277
they developed acute rebound flares after SCS
223 AD: atopic dermatitis cessation.21 Another study of oral versus IM 278
224 AE: adverse-effect 279
AI: adrenal insufficiency methylprednisolone reported relapse and rebound
225 BDP: beclomethasone dipropionate flares 1 week after steroid discontinuation, with no 280
226 COPD: chronic obstructive pulmonary disease long-lasting improvement in skin disease regardless 281
227 IM: intramuscular 282
RCT: randomized controlled trial of administration.19
228 SCS: systemic corticosteroid AI. A systematic review of adrenal insufficiency 283
229 TAC: triamcinolone acetonide (AI) (cortisol level, #500 nmol/L) after glucocorti- 284
230 coid use identified 74 articles with 3753 participants 285
231 with various medical diagnoses.22 Specific doses 286
232 there was no significant difference in disease severity varied depending on steroid choice (Supplemental 287
233 between groups. Table II). Meta-analysis showed a significant 288
234 One RCT compared prednisolone (0.5-0.8 mg/ increase in absolute risk with medium- (1 month to 289
235 kg/d tapered within 2 weeks) with cyclosporine 1 year) and long-term ([1 year) use, as well as 290
236 (2.7-4 mg/kg/d for 6 weeks) in adults with severe with medium- and high-dose corticosteroids. 291
237 AD.14 Only 1 of 27 patients treated with prednisolone Approximately half of patients had resolution of AI 292
238 achieved sustainable remission, as opposed to 6 of upon retesting at 28 days. Two studies examined the 293
239 17 treated with cyclosporine.5,14,15 risk of AI in AD after use of topical fluocinonide or 294
240 Intravenous. Intravenous methylprednisolone, clobetasol; 1 case of short-term AI was reported; it 295
241 20 mg/kg/d administered for 3 consecutive days, resolved upon retesting. 296
242 resulted in immediate improvement of skin lesions Two RCTs of oral SCSs in childhood AD 297
243 and pruritus in 5 of 7 children.16 Symptom relapse demonstrated no major AEs or relapses after 3 weeks 298
244 occurred after 3 to 18 months.16-18 No other studies of follow-up.10,17 Another study showed that after 299
245 demonstrated the utility of intravenous corticosteroids. 4 weeks of therapy, children receiving oral BDP had 300
246 IM. A double-blind study published in 1963 lower urine-free cortisol levels than their control 301
247 compared the effectiveness of several dosing counterparts, which is suggestive of subclinical 302
248 schedules of oral versus IM steroids in 73 patients adrenal suppression.11 A study of oral BDP in AD 303
249 with eczematous diseases of substantial severity showed that 7 of 10 children taking a maintenance 304
250 (most with AD) over 6 weeks.19 There were no dose had growth impairment after 6 months of 305
251 significant differences between dosage schedules or therapy and numerical reduction in early morning 306
252 method of steroid delivery. Unfortunately, after plasma cortisol level and 24-hour urinary cortisol 307
253 6 weeks of therapy, nearly all patients were lost to excretion.12 An observational study reported that no 308
254 follow-up. patients showed signs or symptoms of AI from IM 309
255 A prospective observational study evaluated IM TAC for various dermatoses.20 Total cortisol level 310
256 triamcinolone acetonide (TAC) in inflammatory decreased significantly at 6 and 12 weeks versus 311
257 disorders (n = 14), including nummular (n = 4), baseline with IM TAC, but mean morning cortisol and 312
258 hand (n = 3), and unspecified dermatitis (n = 1).20 ACTH levels did not differ significantly.20 313
259 Patients received IM TAC in the deltoid muscle, with Tapering of SCSs was deemed unnecessary to 314
260 a second dose at 6-weeks if necessary. There was a minimize the risk of AI with courses lasting less than 315
261 significant decrease in mean Physician Global 1 week.23 However, a 7- to 14-day or 15- to 30-day 316
262 Assessment score at 6 and 12 weeks and in Visual taper until physiologic dose (10 mg/m2/d) was 317
263 Analogue Scale score at 6 weeks compared with recommended for courses of 2 to 3 or 4 or more 318
264 baseline.20 weeks, respectively. 319
265 Other AEs. Significant growth retardation 320
266 occurred in children with severe AD treated with 321
267 Safety and tolerability 4 weeks of oral BDP therapy.12 322
268 SCSs have many AEs limiting their use in AD Corticosteroid allergies should be considered in 323
269 ½T1 (Table I
1-43
). patients with treatment-refractory eczema lesions, 324
270 Rebound AD flares. One study of oral predni- subacute contact dermatitis, systemic contact 325
271 sone for severe AD was terminated early because of dermatitis, or maculopapular exanthems.24 326
272 disease flares in 15 of 38 subjects.14 In all, 81% of Several AEs were observed with IM TAC, including 327
273 patients treated with prednisolone had rebound of increased susceptibility to infection overall and 328
274 their AD compared with 65% of those treated with bacterial superinfection of skin (in particular, exa- 329
275 cyclosporine. A case series of 3 patients with severe cerbation of headache syndromes, perimenopausal 330

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331 Table I. Noted adverse events and excess risk 386

332 387
Adverse event Excess risk in patients with AD
333 388
Rebound flare1-24 10/21 flared while taking prednisolone vs 5/17 while taking
334 389
cyclosporine, requiring early termination2
335 Adrenal suppression1,6,20,25-31 24/26 had lower free urinary cortisol levels at 4 wk, resolved
390
336 by wk 825 391
337 Decreased morning cortisol level and 24-h urine cortisol 392
338 level (not significant on Wilcoxon signed rank test)26 393
339 Significant decrease in morning total cortisol level at 394
340 6 weeks (8.06 6 2.17 g/dL, normal morning level range 395
341 4-23 g/dL, P \ .01) and at 12 weeks (7.8 6 1.69 g/dL, 396
342 P \ .05) compared with baseline (10.54 6 2.77 g/dL) 397
343 without signs or symptoms of adrenal insufficiency28 398
344 AR for adrenal suppression of 487.7 (95% CI: 36.9-60.6)29 399
d Short-term (\4 wk) AR of 1.4 (95% CI 0.3-7.4)
345 d Medium-term (1 mo to 1 y) AR of 11.9 (5.8-23.1)
400
346 d Long-term ([1 y) AR of 27.4 (17.7-39.8)
401
347 d Low-dose AR of 2.4 (0.6-9.3) 402
348 d Medium-dose AR of 8.5 (4.2-16.8) 403
349 d High-dose AR of 21.5 (12.0-35.5) 404
350 HTN1-3,6,7,10,18,19,32-34 3/21 (10%)2 405
351 Nausea/vomiting/GERD/PUD2-4,7,8,18,30,32 3/21 (14%)2 406
352 1/73 (1.4%)4 407
353 Weight gain1,2,10,20,30 2/21 (10%)2 408
354 Opportunistic infections/immunosuppression1,2,4,8,19,25,35,36 1/21 (4%)2 409
355 1/73 (1.4%)4 410
Growth retardation (children)1,3,6,8,10,18,20,21,26,27,30,31,34,37-39 Wilcoxon signed rank test (95% CI 0.3-1.03)26
356 411
Macular-papular exanthema/urticaria7,40 100 case reports in the literature, incidence thought to be
357 \1%40
412
358 Myopathy/myalgia/dysaesthesia2,10,19,30,32 1/21 (5%)2 413
359 Hyperlipidemia2,30,32 4/21 (19%)2 414
360 Elevated liver function test results2 2/21 (10%)2 415
361 Headache2,4,32 2/21 (10%)2 416
362 1/73 (1.4%)4 417
363 Perimenopausal symptoms (hot flashes)4 1/73 (1.4%)4 418
364 419
Other (unspecified risks in patients with AD): Cushing syndrome,8,10,20,34 glucose intolerance/diabetes1,3,6-8,10,18-20,33,34 gastritis,1,34 bowel
365 perforation,30 osteoporosis/osteopenia,1,3,8,18,19,30,34,35,37,41,42 emotional lability/behavioral changes,1,19,20,30 cataracts,1,10,19,20,23,30,31,33,35,37,41
420
366 glaucoma,3,8,10,18,20,31,34 cushingoid body habitus,8,19,30 increased appetite,30 aseptic necrosis/osteonecrosis,10,30 pseudotumor cerebri,30 421
367 acne,30 non-Hodgkin lymphoma,30,32 Kaposi sarcoma,30 squamous cell carcinoma,30,32 other internal malignancy,32 chronic renal disease 422
368 (arteriolopathy and tubular interstitial disease),32 abnormal wound healing,8 thrombosis risk,8 hirsutism/hypertrichosis,8,32 patient 423
369 dependence,32 renal dysfunctio,32 tremor,32 paresthesia/hyperesthesia,32 low quality of life/depression,37,43 gingival hyperplasia,32 424
electrolyte abnormalities (potassium, manganese, uric acid),32 fluid retention,20 skin atrophy,18,34 lymphopenia,21,41 tachyphylaxis,19,31
370 and sleep pattern disturbance.20
425
371 AD, Atopic dermatitis; AR, absolute risk; CI, confidence interval; GERD, gastroesophageal reflux disease; HTN, hypertension; NHL, non-Hodgkin 426
372 lymphoma; PUD, peptic ulcer disease. 427
373 428
374 symptoms, and peptic ulcer disease).19 Another necessary in children, oral corticosteroids should be 429
375 study of IM TAC found no injection site atrophy, given as 1 dose in the morning to minimize growth 430
376 weight gain, hypertension, cushingoid appearance, stunting.25 Finally, a study reported that despite 431
377 hirsutism, pedal edema, easy bruising, irregular treatment success with SCSs, patients rated their 432
378 menses, or mood or appetite changes and decreased health care worse overall and had lower satisfaction 433
379 incidence of rebound exacerbations.20 and poorer quality of life.9 434
380 Intravenous methylprednisolone, 20 mg/kg/d for 435
381 3 days, in severe AD was not associated with DISCUSSION 436
382 observed infections.16 Some authors recommended When systemic treatment is used in moderate-to- 437
383 alternate-day dosing of oral corticosteroids for severe AD and other inflammatory skin diseases, 438
384 children with severe generalized AD to minimize SCSs are among the drugs most widely used. SCSs 439
385 AEs. Others recommended that if daily dosing is provide rapid relief from intractable itch in AD.26,27 440

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441 Yet, significant gaps exist, including optimal dose, 496

Werfel et al, 2014 ; Tanei and Hasegawa, 2016 ; Proudfoot et al, 201344; Borchard and Orchard, 200832; Sonenthal et al,

Lipozenci
c and Wolf, 200746; Ring et al, 201247; Tyler, 201548; Akdis et al, 200641; Turner and Schwartz, 200649; Pua and

Heddle et al, 198425; Aylett et al, 199226; La Rosa et al, 199553; Galli et al, 199436; Ricci et al, 200927; Carbone et al, 20106;

Nankervis et al, 201559; Steinke et al, 201443; Schmitt et al, 200760; Stephens and Cooper, 199961; Broerson et al, 201529;
€tz et al, 201413; Akhavan and Rudikoff, 200810; Saeki
199337; Simon and Bieber, 20143; Stroud et al, 19634; Reddy et al, 201328; Bubmann et al, 20098; Shaw et al, 200930;

Barnetson, 200619; Sidbury and Hanifin, 200035; Correale et al, 199923; Rasmussen, 198950; Rasmussen, 198951; Susac

Basedow et al, 201140; Nesbitt, 199562; Misery, 201114; Roekevisch et al, 201463; Abramovits and Granowski, 201064;
442 frequency, and duration of SCS therapy. With the 497

Vestergaard and Deleuran, 201412; Cookson and Smith, 201245; Bershad, 201115; Katsarou and Armenaka, 201133;

Schmitt et al, 20102; Forte et al, 20055; Lyons et al, 201511; Wolter and Price, 201417; Barnetson and Rogers, 200222
443 limited trials and small cohorts, there is inadequate 498
444 evidence to guide clinical practice on use and dosing 499
445 of SCSs. 500
446 501
447 502

et al, 2009 ; Wang et al, 2016 ; Darsow et al, 2013 ; Gottlieb, 200520; Leung and Barber, 200331
SCS use in AD
448 Recommendations for SCS use in AD are 503
449 ½T2 summarized in Table II.
1-64
Short courses are usually 504
450 safe in treating acute and self-limited dermatoses. 505
451 However, limited data are available for AD 506
452 specifically.28 Some clinicians use SCSs for the initial 507
453 control of severe inflammatory disorders before 508
454 509

David, 198938; Roos et al, 200421; Sarkar and Kanwar, 200254; Verbov, 198955
transitioning or ‘‘bridging’’ to steroid-sparing
455 agents.14,28 Nonsteroidal agents often have delayed 510
456 onset of efficacy and require baseline blood work 511
457 before initiation. Cyclosporine and oral tacrolimus 512

Rubel, 201356; Sidbury et al, 201457; Notaro and Sidbury, 20159; Plo
458 may take 1 to 2 weeks for significant improvement in 513
459 skin disease, whereas mycophenolate mofetil, 514

Study
460 azathioprine, and methotrexate can take 4 to 515
461 516

39
12 weeks to achieve effectiveness. Dupilumab may
462 also take several weeks to achieve clinical efficacy. 517
463 518

Leung and Hon, 201542; Flohr and Irvine, 201318

Anecdotally, SCSs are highly efficacious.
464 519
7

et al, 200724; Landow, 199752; Simon, 201134

However, one of the only head-to-head RCTs done
465 against cyclosporine in 38 adults with severe AD 520
466 found that cyclosporine was more effective at 521
467 achieving stable remission, with less rebound 522
468 flaring.14 Rebound flaring and/or worsening of AD 523

16
469 are common phenomena upon discontinuation of 524
470 SCSs.5,14 525
471 Acute AEs of SCSs include mood disturbances, 526
472 hypothalamic-pituitary-adrenal axis suppression, 527
473 Q7 gastrointestinal upset, myopathies, fluid and sodium 528
1

474 retention, weight gain, immunosuppression, 529

58

475 impaired glucose tolerance, and impaired wound 530

476 healing (Table II 1-64). The most frequently identified 531
Table II. Recommended use of systemic steroids in AD

477 and addressed AEs in AD include rebound flaring 532

478 after discontinuation, hypothalamic-pituitary- 533
479 adrenal axis suppression, and growth retardation in 534
480 children. Long-term AEs are numerous and well 535
481 established.28 536
482 537
Short course for severe AD flare (pediatric)

Suppression of the hypothalamic-pituitary-

Bridge to steroid-sparing systemic therapy

483 adrenal axis can happen by 4 weeks and may be 538

Short course for severe AD flare (adult)

484 subclinical.28 One study demonstrated significant 539

No specific recommendations made

485 reduction in urinary cortisol after 1 month 540

486 of therapy.11,12 AI makes patients particularly 541
487 vulnerable to stress associated with surgery or 542
488 infection. AI may manifest as weakness, fatigue, 543
489 fever, nausea, or anorexia, with hypotension and 544
AD, Atopic dermatitis.
Not recommended

490 shock developing in severe cases.28 Tapering of 545

Recommendation

491 short courses (\1 week) of SCSs is likely 546

492 unnecessary; however, tapering is recommended 547
493 for longer courses to minimize risk for development 548
494 of AI.23 A single morning dose or alternate-day 549
495 dosing of oral corticosteroids may minimize 550

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551 suppression of the hypothalamic-pituitary- an asthma exacerbation.32 Serious AEs were a 606
552 adrenal axis.8,25,28 Alternate-day dosing using an primary outcome, and any AE was a secondary 607
553 intermediate-acting steroid (eg, prednisone) may outcome. No serious AEs were reported in any adult 608
554 allow approximately 12 hours of hypothalamic- studies and 5 pediatric studies. New exacerbations 609
555 pituitary-adrenal axis recovery on the off day.7 during follow-up were reported by 7 studies in 610
556 However, risk for osteoporosis, cataracts, and adults, and 1 study comparing prednisolone with 611
557 growth-retardation is related to cumulative steroid dexamethasone in adults found no differences 612
558 dosing and is not mitigated by this dosing between them. Other AEs were not frequently 613
559 regimen.8,25,28 No studies evaluating the impact of reported. Benefit of one steroid regimen over 614
560 short-term subclinical HPA access suppression were another was not shown. In a single study, short 615
561 identified. One study demonstrated a significant tapers (7 days) were associated with fewer AEs 616
562 decrease in median growth velocity after 4 weeks (including weight gain, edema, acne, and easy 617
563 of oral BDP therapy.12 Study subjects had only bruising) than long taper (7 weeks) was; however, 618
564 short-term follow-up, and the authors did not report the sample size was small. There was no compelling 619
565 whether rebound growth occurred after cessation. evidence of outcome differences between high dose 620
566 Although SCSs are generally thought to be more or longer course versus lower dose or shorter course 621
567 potent than topical corticosteroids, some believe that of prednisolone or dexamethasone. 622
568 higher concentrations in the superficial layers of the A retrospective case-control study of 112 patients 623
569 skin are likely achieved through topical with rheumatoid arthritis who were or were not 624
570 formulations, with fewer AEs.12,29 Topical therapy taking long-term, low-dose (\15 mg/d) prednisone 625
571 is recommended before using SCSs. for more than 1 year found higher rates of AEs in the 626
572 prednisone group.33 AEs included fractures, 627
573 Safety observed with SCSs in other diseases cataracts, serious infections, and gastrointestinal 628
574 In other diseases (eg, chronic obstructive bleeds and/or ulcers. Of note, doses of prednisone 629
575 pulmonary disease [COPD] and asthma), ideal less than 5 mg/d were not associated with 630
576 dosing regimens of SCSs are also scarce. The AEs of significantly increased risk for AEs compared with 631
577 SCSs are better studied in other diseases, which can no prednisone. 632
578 be informative for the AD population, although Finally, a Cochrane review found that regular use 633
579 generalizability to AD is uncertain. of inhaled corticosteroids was associated with 634
580 SCSs may reduce airway inflammation and/or significant growth suppression measured by linear 635
581 decrease airway edema in COPD. However, even growth velocity in children with mild-to-moderate 636
582 short-courses are associated with decreased persistent asthma.34 Growth suppression appeared 637
583 respiratory and peripheral muscle strength.30 Risk to be maximal during the first year of therapy. After 638
584 for AEs rises with increasing frequency and treatment cessation, most trials with follow-up data 639
585 cumulative exposure ([1 g). A Cochrane review showed no significant catch-up growth 2 to 4 months 640
586 compared the efficacy of short- (\7 days) and after treatment cessation. One trial showed 641
587 long-term ([7 days) SCSs in adults with acute accelerated linear growth velocity 1 year after 642
588 COPD exacerbations. Two studies showed no cessation of inhaled corticosteroids; however, a 643
589 difference in the likelihood of hyperglycemia significant height difference remained. 644
590 between the 2 treatment lengths; 1 study noted Our review is limited by the few primary studies 645
591 no difference in the likelihood of developing on SCS use in adults with moderate-to-severe AD. 646
592 hypertension. Other AEs included gastrointestinal There was significant heterogeneity in the quality 647
593 tract bleeding, gastrointestinal reflux disease, sleep and type of data presented from the available 648
594 disturbance, symptoms of congestive heart failure, studies, and all RCT had small sample sizes. 649
595 fractures, and depression. No difference was found In conclusion, the AAD guidelines for systemic 650
596 between durations of treatment with SCSs, therapy in AD discourage use of SCSs because of 651
597 suggesting that such AEs can occur after even limited short- and long-term side effects and an unfavorable 652
598 use. A retrospective cohort study of 1,548,945 adults risk-benefit profile, and they should be limited to 653
599 from a nationwide data set of private insurance acute, severe exacerbations and use as a bridge to 654
600 claims found that short-term use of oral steroid-sparing therapy.5 The literature supports 655
601 corticosteroids for fewer than 30 days for any short-term use of short courses of oral corticosteroids 656
602 indication was associated with increased rates of (\3 weeks) to interrupt acute flares, but rebound 657
603 sepsis, venous thromboembolism, and fracture.31 flaring is commonly observed after discontinuation. 658
604 Another Cochrane review assessed the efficacy If SCSs are used at all, their use should be short-term 659
605 and safety of oral steroids in adults and children with when bridging to other systemic therapies or 660

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661 phototherapy (level II, evidence strength B).5,35-37 20. Gottlieb AB. Therapeutic options in the treatment of psoriasis 716
662 However, the duration of an optimal short course is and atopic dermatitis. J Am Acad Dermatol. 2005;53:S3-S16. 717
21. Roos TC, Geuer S, Roos S, Brost H. Recent advances in
663 not well defined. Use in pediatric AD is not 718
treatment strategies for atopic dermatitis. Drugs. 2004;64:
664 recommended because of growth retardation and 2639-2666. 719
665 other AEs.5 None of the consensus guidelines 22. Barnetson RS, Rogers M. Childhood atopic eczema. BMJ. 720
666 identified in this systematic review addressed 2002;324:1376-1379. 721
667 long-term low-dose steroids (\5 mg/d); however, 23. Correale CE, Walker C, Murphy L, Craig TJ. Atopic dermatitis: a 722
review of diagnosis and treatment. Am Fam Physician. 1999;
668 given the many long-term AEs, longer courses of 723
60:1191-1198.
669 SCSs are not recommended for AD.1 24. Susac A, Babi
c S, Lipozenci
c J. An overview on atopic 724
670 dermatitis in children. Acta Dermatovenerol Croat. 2007;15: 725
671 REFERENCES 158-166. 726
672 1. Werfel T, Schwerk N, Hansen G, Kapp A. The diagnosis and 25. Heddle RJ, Soothill JF, Bulpitt CJ, Atherton DJ. Combined oral 727
graded therapy of atopic dermatitis. Dtsch Arztebl Int. 2014; and nasal beclomethasone diproprionate in children with
673 111:509-520.
728
atopic eczema: a randomized controlled trial. Br Med J (Clin
674 2. Schmitt J, Sch€akel K, F€
olster-Holst R, et al. Prednisolone vs. Res Ed). 1984;289:651-654. 729
675 ciclosporin for severe adult eczema. An investigator-initiated 26. Aylett SE, Atherton DJ, Preece MA. The treatment of difficult 730
676 double-blind placebo-controlled multicentre trial. Br J atopic dermatitis in childhood with oral beclomethasone 731
677 Dermatol. 2010;162:661-668. diproprionate. Acta Derm Venereol (Stockh). 1992;1992: 732
3. Simon D, Bieber T. Systemic therapy for atopic dermatitis. 123-125.
678 Allergy. 2014;69:46-55.
733
27. Ricci G, Dondi A, Patrizi A, Masi M. Systemic therapy of atopic
679 4. Stroud GM, Miller RE, Kozikoski ES. Oral versus intramuscular dermatitis in children. Drugs. 2009;69:297-306. 734
680 methylprednisolone. A double-blind study. Arch Dermatol. 28. Reddy S, Ananthakrishnan S, Garg A. A prospective observa- 735
681 1963;1963:710-714. tional study evaluating hypothalamic-pituitary-adrenal axis 736
682 5. Forte WC, Sumits JM, Rodrigues AG, Liuson D, Tanaka E. alteration and efficacy of intramuscular triamcinolone 737
Rebound phenomenon to systemic corticosteroid in atopic acetonide for steroid-responsive dermatolgoic disease.
683 dermatitis. Allergol Immunnopath. 2005;33:301-311.
738
J Am Acad Dermatol. 2013;69:226-231.
684 6. Carbone A, Siu A, Patel R. Pediatric atopic dermatitis: a review 29. Broersen LH, Pereira AM, Jørgensen JO, Dekkers OM. Adrenal 739
685 of the medical management. Ann Pharmacother. 2010;44: insufficiency in corticosteroid use: systematic review and 740
686 1448-1458. meta-analysis. J Clin Endocrinol Metab. 2015;100:2171-2180. 741
687 7. Tanei R, Hasegawa Y. Atopic dermatitis in older adults: a 30. Shaw MG, Burkhart CN, Morrell DS. Systemic therapies for 742
viewpoint from geriatric dermatology. Geriatr Gerontol Int. pediatric atopic dermatitis: a review for the primary care
688 2016;16:75-85.
743
physician. Pediatr Ann. 2009;38:380-387.
689 8. BuBmann C, Bieber T, Novak N. Systemic therapeutic options 31. Leung AK, Barber KA. Managing childhood atopic dermatitis. 744
690 for severe atopic dermatitis. J Dtsch Dermatol Ges. 2009;7: Adv Ther. 2003;20:129-137. 745
691 205-219. 32. Borchard KL, Orchard D. Systemic therapy of paediatric 746
692 9. Notaro ER, Sidbury R. Systemic agents for severe atopic atopic dermatitis: an update. Australas J Dermatol. 2008;49: 747
dermatitis in children. Paediatr Drugs. 2015;17:449-457. 123-134.
693 10. Akhavan A, Rudikoff D. Atopic dermatitis: systemic
748
33. Katsarou A, Armenaka M. Atopic dermatitis in older patients:
694 immunosuppressive therapy. Semin Cutan Med Surg. 2008; particular points. J Eur Acad Dermatol Venereol. 2011;25:12-18. 749
695 27:151-155. 34. Simon D. Systemic therapy of atopic dermatitis in children 750
696 11. Lyons JJ, Milner JD, Stone KD. Atopic dermatitis in children: and adults. Curr Probl Dermatol. 2011;41:156-164. 751
697 clinical features, pathophysiology and treatment. Immunol 35. Sidbury R, Hanifin JM. Systemic therapy of atopic dermatitis. 752
Allergy Clin North Am. 2015;35:161-183. Clin Exp Dermatol. 2000;25:559-566.
698 12. Vestergaard C, Deleuran M. Advances in the diagnosis and
753
36. Galli E, Chini L, Moschese V, et al. Methylprednisolone bolus:
699 therapeutic management of atopic dermatitis. Drugs. 2014; a novel therapy for severe atopic dermatitis. Acta Paediatr. 754
700 74:757-769. 1994;83:315-317. 755
701 13. Pl€
otz SG, Wiesender M, Todorova A, Ring J. What is new in 37. Sonenthal KR, Grammer LC, Patterson R. Do some patients 756
702 atopic dermatitis/eczema. Expert Opin Emerg Drugs. 2014;19: with atopic dermatitis require long-term oral steroid therapy? 757
441-458. J Allergy Clin Immunol. 1993;91:971-973.
703 14. Misery L. Therapeutic perspectives in atopic dermatitis. Clin
758
38. David TJ. Short stature in children with atopic eczema. Acta
704 Rev Allergy Immunol. 2011;41:267-271. Derm Venereol (Stockh). 1989;1989:41-44. 759
705 15. Bershad SV. In the clinic. Atopic dermatitis (eczema). Ann 39. Darsow U, Wollenberg A, Simon D, et al. Difficult to control 760
706 Intern Med. 2011;155:ITC51-ITC515 [quiz: ICT516]. atopic dermatitis. World Allergy Organ J. 2013;6:6. 761
707 16. Wang IJ, Wang JY, Yeh KW. Childhood atopic dermatitis in 40. Basedow S, Eigelshoven S, Homey B. Immediate and delayed 762
Taiwan. Pediatr Neonatol. 2016;57:89-96. hypersensitivity to corticosteroids. J Dtsch Dermatol Ges.
708 17. Wolter S, Price HN. Atopic dermatitis. Pediatr Clin North Am.
763
2011;9:885-888.
709 2014;61:241-260. 41. Akdis CA, Akdis M, Bieber T, et al. Diagnosis and treatment of 764
710 18. Flohr C, Irvine AD. Systemic therapies for severe atopic atopic dermatitis in children and adults: European Academy 765
711 dermatitis in children and adults. J Allergy Clin Immunol. of Allergology and Clinical Immunology/American Academy 766
712 2013;132:774. of Allergy, Asthma and Immunology/PRACTALL consensus 767
19. Pua VS, Barnetson RS. Recent developments in the treatment report. Allergy. 2006;61:969-987.
713 of adult atopic dermatitis. Australas J Dermatol. 2006;47:
768
42. Leung TN, Hon KL. Eczema therapeutics in children: what do
714 84-89. the clinical trials say? Hong Kong Med J. 2015;21:251-260. 769
715 770

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771 43. Steinke S, Langenbruch A, St€ander S, Franzke N, Augustin M. 54. Sarkar R, Kanwar AJ. Atopic dermatitis. Indian Pediatr. 2002; 826
772 Therapeutic benefits in atopic dermatitis from patients’ 39:922-930. 827
perspective: results of the German national health care study 55. Verbov J. A review of some aspects of the treatment of
773 828
‘Atopic Health’. Dermatology. 2014;228:350-359. severe generalized eczematous dermatoses in children.
774 44. Proudfoot LE, Powell AM, Ayis S, et al. The European J Dermatologal Treat. 1989;1:51-53. 829
775 TREatment of severe Atopic eczema in children Taskforce 56. Rubel D, Thirumoorthy T, Soebaryo RW, et al. Consensus 830
776 (TREAT) survey. Br J Dermatol. 2013;169:901-909. guidelines for the management of atopic dermatitis: an 831
777 45. Cookson H, Smith C. Systemic treatment of adult atopic Asia-Pacific perspective. J Dermatol. 2013;40:160-171. 832
dermatitis. Clin Med (Lond). 2012;12:172-176. 57. Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care
778 833
46. Lipozenci
c J, Wolf R. Atopic dermatitis: an update and review for the management of atopic dermatitis: section 3.
779 of the literature. Dermatol Clin. 2007;25:605-612. Management and treatment wth phototherapy and systemic 834
780 47. Ring J, Alomar A, Bieber T, et al. Guidelines for treatment of agents. J Am Acad Dermatol. 2014;71:327-349. 835
781 atopic eczema (atopic dermatitis) Part II. J Eur Acad Dermatol 58. Saeki H, Furue M, Furukawa F, et al. Guidelines for manage- 836
782 Venereol. 2012;26:1176-1193. ment of atopic dermatitis. J Dermatol. 2009;36:563-577. 837
48. Tyler KH. Dermatologic therapy in pregnancy. Clin Obstet 59. Nankervis H, Pynn EV, Boyle RJ, et al. House dust mite
783 838
Gynecol. 2015;58:112-118. reduction and avoidance measures for treating eczema.
784 49. Turner JD, Schwartz RA. Atopic dermatitis. A clinical Cochrane Database Syst Rev. 2015;(1):CD008426. 839
785 challenge. Acta Dermatovenerol Alp Pannonica Adriat. 2006; 60. Schmitt J, Sch€akel K, Schmitt N, Meurer M. Systemic 840
786 15:59-68. treatment of severe atopic eczema: a systematic review. 841
787 50. Rasmussen JE. Advances in nondietary management of Acta Derm Venereol. 2007;87:100-111. 842
children with atopic dermatitis. Pediatr Dermatol. 1989;6: 61. Stephens RB, Cooper A. The caseload, assessment and
788 843
210-215. treatment of atopic dermatitis: a survey of Australian
789 51. Rasmussen JE. Management of atopic dermatitis. Allergy. dermatologists. Australas J Dermatol. 1999;40:187-189. 844
790 1989;44:108-113. 62. Nesbitt LT Jr. Minimizing complications from systemic 845
791 52. Landow K. Atopic dermatitis. Current concepts support old glucocorticosteroid use. Dermatol Clin. 1995;13:925-939. 846
792 therapies and spur new ones. Postgrad Med. 1997;101: 63. Roekevisch E, Spuls PI, Kuester D, Limpens J, Schmitt J. 847
101-104. Efficacy and safety of systemic treatments of moderate-
793 848
53. La Rosa M, Musarra I, Ranno C, et al. A randomized, to-severe atopic dermatitis: a systematic review. J Allergy Clin
794 double-blind, placebo-controlled, crossover trial of systemic Immunol. 2014;133:429-438. 849
795 flunisolide in the treatment of children with severe atopic 64. Abramovits W, Granowski P. Innovative management of 850
796 dermatitis. Curr Ther Res. 1995;56:720-726. severe hand dermatitis. Dermatol Clin. 2010;28:453-465. 851
797 852
798 853
799 854
800 855
801 856
802 857
803 858
804 859
805 860
806 861
807 862
808 863
809 864
810 865
811 866
812 867
813 868
814 869
815 870
816 871
817 872
818 873
819 874
820 875
821 876
822 877
823 878
824 879
825 880

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881 REFERENCES S20. Ricci G, Dondi A, Patrizi A, Masi M. Systemic therapy of atopic 936
882 S1. Proudfoot LE, Powell AM, Ayis S, et al. The European dermatitis in children. Drugs. 2009;69:297-306. 937
TREatment of severe Atopic eczema in children Taskforce S21. Simon D, Bieber T. Systemic therapy for atopic dermatitis.
883 938
(TREAT) survey. Br J Dermatol. 2013;169:901-909. Allergy. 2014;69:46-55.
884 S2. Sonenthal KR, Grammer LC, Patterson R. Do some patients S22. Broersen LH, Pereira AM, Jørgensen JO, Dekkers OM. Adrenal 939
885 with atopic dermatitis require long-term oral steroid therapy? insufficiency in corticosteroid use: systematic review and 940
886 J Allergy Clin Immunol. 1993;91:971-973. meta-analysis. J Clin Endocrinol Metab. 2015;100:2171-2180. 941
887 S3. Steinke S, Langenbruch A, St€ander S, Franzke N, Augustin M. S23. Carbone A, Siu A, Patel R. Pediatric atopic dermatitis: a review 942
Therapeutic benefits in atopic dermatitis from patients’ of the medical management. Ann Pharmacother. 2010;44:
888 943
perspective: results of the German national health care study 1448-1458.
889 ‘Atopic Health’. Dermatology. 2014;228:350-359. S24. Basedow S, Eigelshoven S, Homey B. Immediate and delayed 944
890 S4. Heddle RJ, Soothill JF, Bulpitt CJ, Atherton DJ. Combined oral hypersensitivity to corticosteroids. J Dtsch Dermatol Ges. 945
891 and nasal beclomethasone diproprionate in children with 2011;9:885-888. 946
892 atopic eczema: a randomized controlled trial. Br Med J (Clin S25. David TJ. Short stature in children with atopic eczema. Acta 947
Res Ed). 1984;289:651-654. Derm Venereol (Stockh). 1989;1989:41-44.
893 948
S5. Aylett SE, Atherton DJ, Preece MA. The treatment of difficult S26. BuBmann C, Bieber T, Novak N. Systemic therapeutic options
894 atopic dermatitis in childhood with oral beclomethasone for severe atopic dermatitis. J Dtsch Dermatol Ges. 2009;7: 949
895 diproprionate. Acta Derm Venereol (Stockh). 1992;1992:123-125. 205-219. 950
896 S6. La Rosa M, Musarra I, Ranno C, et al. A randomized, S27. Notaro ER, Sidbury R. Systemic agents for severe atopic 951
897 double-blind, placebo-controlled, crossover trial of systemic dermatitis in children. Paediatr Drugs. 2015;17:449-457. 952
flunisolide in the treatment of children with severe atopic S28. Nesbitt LT Jr. Minimizing complications from systemic
898 953
dermatitis. Curr Ther Res. 1995;56:720-726. glucocorticosteroid use. Dermatol Clin. 1995;13:925-939.
899 S7. Schmitt J, Sch€akel K, F€olster-Holst R, et al. Prednisolone vs. S29. Lyons JJ, Milner JD, Stone KD. Atopic dermatitis in children: 954
900 ciclosporin for severe adult eczema. An investigator-initiated clinical features, pathophysiology and treatment. Immunol 955
901 double-blind placebo-controlled multicentre trial. Br J Allergy Clin North Am. 2015;35:161-183. 956
902 Dermatol. 2010;162:661-668. S30. Shaw MG, Burkhart CN, Morrell DS. Systemic therapies for 957
S8. Stephens RB, Cooper A. The caseload, assessment and pediatric atopic dermatitis: a review for the primary care
903 958
treatment of atopic dermatitis: a survey of Australian physician. Pediatr Ann. 2009;38:380-387.
904 dermatologists. Australas J Dermatol. 1999;40:187-189. S31. Vestergaard C, Deleuran M. Advances in the diagnosis and 959
905 S9. Galli E, Chini L, Moschese V, et al. Methylprednisolone bolus: therapeutic management of atopic dermatitis. Drugs. 2014; 960
906 a novel therapy for severe atopic dermatitis. Acta Paediatr. 74:757-769. 961
907 1994;83:315-317. S32. Pl€
otz SG, Wiesender M, Todorova A, Ring J. What is new in 962
S10. Stroud GM, Miller RE, Kozikoski ES. Oral versus intramuscular atopic dermatitis/eczema. Expert Opin Emerg Drugs. 2014;19:
908 963
methylprednisolone. A double-blind study. Arch Dermatol. 441-458.
909 1963;1963:710-714. S33. Cookson H, Smith C. Systemic treatment of adult atopic 964
910 S11. Reddy S, Ananthakrishnan S, Garg A. A prospective observa- dermatitis. Clin Med (Lond). 2012;12:172-176. 965
911 tional study evaluating hypothalamic-pituitary-adrenal axis S34. Bershad SV. In the clinic. Atopic dermatitis (eczema). Ann 966
912 alteration and efficacy of intramuscular triamcinolone Intern Med. 2011;155:ITC51-ITC515. 967
acetonide for steroid-responsive dermatolgoic disease. J S35. Katsarou A, Armenaka M. Atopic dermatitis in older patients:
913 968
Am Acad Dermatol. 2013;69:226-231. particular points. J Eur Acad Dermatol Venereol. 2011;25:
914 S12. Forte WC, Sumits JM, Rodrigues AG, Liuson D, Tanaka E. 12-18. 969
915 Rebound phenomenon to systemic corticosteroid in atopic S36. Lipozenci
c J, Wolf R. Atopic dermatitis: an update and review 970
916 dermatitis. Allergol Immunnopath. 2005;33:301-311. of the literature. Dermatol Clin. 2007;25:605-612. 971
917 S13. Werfel T, Schwerk N, Hansen G, Kapp A. The diagnosis and S37. Ring J, Alomar A, Bieber T, et al. Guidelines for treatment of 972
graded therapy of atopic dermatitis. Dtsch Arztebl Int. 2014; atopic eczema (atopic dermatitis) Part II. J Eur Acad Dermatol
918 973
111:509-520. Venereol. 2012;26:1176-1193.
919 S14. Rubel D, Thirumoorthy T, Soebaryo RW, et al. Consensus S38. Tyler KH. Dermatologic therapy in pregnancy. Clin Obstet 974
920 guidelines for the management of atopic dermatitis: an Gynecol. 2015;58:112-118. 975
921 Asia-Pacific perspective. J Dermatol. 2013;40:160-171. S39. Akdis CA, Akdis M, Bieber T, et al. Diagnosis and treatment of 976
922 S15. Tanei R, Hasegawa Y. Atopic dermatitis in older adults: a atopic dermatitis in children and adults: European Academy 977
viewpoint from geriatric dermatology. Geriatr Gerontol Int. of Allergology and Clinical Immunology/American Academy
923 978
2016;16:75-85. of Allergy, Asthma and Immunology/PRACTALL Consensus
924 S16. Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care Report. Allergy. 2006;61:969-987. 979
925 for the management of atopic dermatitis: section 3. S40. Turner JD, Schwartz RA. Atopic dermatitis. A clinical challenge. 980
926 Management and treatment with phototherapy and systemic Acta Dermatovenerol Alp Pannonica Adriat. 2006;15:59-68. 981
927 agents. J Am Acad Dermatol. 2014;71:327-349. S41. Pua VS, Barnetson RS. Recent developments in the treatment 982
S17. Borchard KL, Orchard D. Systemic therapy of paediatric of adult atopic dermatitis. Australas J Dermatol. 2006;47:84-89.
928 983
atopic dermatitis: an update. Australas J Dermatol. 2008;49: S42. Sidbury R, Hanifin JM. Systemic therapy of atopic dermatitis.
929 123-134. Clin Exp Dermatol. 2000;25:559-566. 984
930 S18. Nankervis H, Pynn EV, Boyle RJ, et al. House dust mite S43. Correale CE, Walker C, Murphy L, Craig TJ. Atopic dermatitis: a 985
931 reduction and avoidance measures for treating eczema. review of diagnosis and treatment. Am Fam Physician. 1999; 986
932 Cochrane Database Syst Rev. 2015;1:CD008426. 60:1191-1198. 987
S19. Schmitt J, Sch€akel K, Schmitt N, Meurer M. Systemic S44. Rasmussen JE. Advances in nondietary management of
933 988
treatment of severe atopic eczema: a systematic review. children with atopic dermatitis. Pediatr Dermatol. 1989;6:
934 Acta Derm Venereol. 2007;87:100-111. 210-215. 989
935 990

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991 S45. Rasmussen JE. Management of atopic dermatitis. Allergy. S54. Wang IJ, Wang JY, Yeh KW. Childhood atopic dermatitis in 1046
992 1989;44:108-113. Taiwan. Pediatr Neonatol. 2016;57:89-96. 1047
S46. Susac A, Babi
c S, Lipozenci
c J. An overview on atopic S55. Darsow U, Wollenberg A, Simon D, et al. Difficult to control
993 1048
dermatitis in children. Acta Dermatovenerol Croat. 2007;15: atopic dermatitis. World Allergy Organ J. 2013;6:6.
994 158-166. S56. Gottlieb AB. Therapeutic options in the treatment of 1049
995 S47. Landow K. Atopic dermatitis. Current concepts support old psoriasis and atopic dermatitis. J Am Acad Dermatol. 2005; 1050
996 therapies and spur new ones. Postgrad Med. 1997;101: 53:S3-S16. 1051
997 101-104. S57. Leung AK, Barber KA. Managing childhood atopic dermatitis. 1052
S48. Simon D. Systemic therapy of atopic dermatitis in children Adv Ther. 2003;20:129-137.
998 1053
and adults. Curr Probl Dermatol. 2011;41:156-164. S58. Wolter S, Price HN. Atopic dermatitis. Pediatr Clin North Am.
999 S49. Roos TC, Geuer S, Roos S, Brost H. Recent advances in 2014;61:241-260. 1054
1000 treatment strategies for atopic dermatitis. Drugs. 2004;64: S59. Barnetson RS, Rogers M. Childhood atopic eczema. BMJ. 1055
1001 2639-2666. 2002;324:1376-1379. 1056
1002 S50. Sarkar R, Kanwar AJ. Atopic dermatitis. Indian Pediatr. 2002; S60. Misery L. Therapeutic perspectives in atopic dermatitis. Clin 1057
39:922-930. Rev Allergy Immunol. 2011;41:267-271.
1003 1058
S51. Verbov J. A review of some aspects of the treatment of S61. Roekevisch E, Spuls PI, Kuester D, Limpens J, Schmitt J. Efficacy
1004 severe generalized eczematous dermatoses in children. J and safety of systemic treatments of moderate-to-severe 1059
1005 Dermatolog Treat. 1989;1:51-53. atopic dermatitis: a systematic review. J Allergy Clin Immunol. 1060
1006 S52. Akhavan A, Rudikoff D. Atopic dermatitis: systemic immuno- 2014;133:429-438. 1061
1007 suppressive therapy. Semin Cutan Med Surg. 2008;27:151-155. S62. Abramovits W, Granowski P. Innovative management of 1062
S53. Saeki H, Furue M, Furukawa F, et al. Guidelines for severe hand dermatitis. Dermatol Clin. 2010;28:453-465.
1008 1063
management of atopic dermatitis. J Dermatol. 2009;36: S63. Leung TN, Hon KL. Eczema therapeutics in children: what do
1009 563-577. the clinical trials say? Hong Kong Med J. 2015;21:251-260. 1064
1010 1065
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1103 1158
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1112 1167
1113 1168
1114 1169
1115 1170
1116 1171
1117 1172
1118 1173
1119 1174
1120 1175
1121 1176
1122 1177
1123 Supplemental Fig 1. Preferred Reporting Items for 1178
1124 Systematic Reviews and Meta-Analyses flow diagram. 1179
1125 1180
1126 1181
1127 1182
1128 1183
1129 1184
1130 1185
1131 1186
1132 1187
1133 1188
1134 1189
1135 1190
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1143 1198
1144 1199
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1211 Supplemental Table I. Literature search scheme 1266

1212 for OVID MEDLINE 1267
1213 1268
1. explode DERMATITIS, ATOPIC/
1214 1269
2. atopic dermatitis.mp.
1215 3. dermatitis atopic.mp.
1270
1216 4. explode ECZEMA/or eczema.mp 1271
1217 5. childhood eczema.mp. 1272
1218 6. infantile eczema.mp. 1273
1219 7. neurodermatitis.mp. or exp Neurodermatitis/ 1274
1220 8. Besnier’s prurigo.mp 1275
1221 9. or/1-8 1276
1222 10. adrenal cort* hormone 1277
1223 11. steroid$ 1278
1224 12. glucocorticoid* 1279
1225 13. corticoid* 1280
1226 14. corticosteroid* 1281
1227 15. beclomethasone 1282
16. betamethasone
1228 1283
17. fluticasone
1229 1284
18. cortisone
1230 1285
19. dexamethasone
1231 1286
20. hydrocortisone
1232 21. prednisolone
1287
1233 22. prednisone 1288
1234 23. methylprednisolone 1289
1235 24. methylprednisone 1290
1236 25. triamcinolone 1291
1237 26. or/10-25 1292
1238 27. 9 and 26 1293
1239 1294
1240 1295
1241 1296
1242 1297
1243 1298
1244 1299
1245 1300
1246 1301
1247 1302
1248 1303
1249 1304
1250 1305
1251 1306
1252 1307
1253 1308
1254 1309
1255 1310
1256 1311
1257 1312
1258 1313
1259 1314
1260 1315
1261 1316
1262 1317
1263 1318
1264 1319
1265 1320

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1321 Supplemental Table II. Summary of systemic steroid recommended use in AD 1376
1322 Primary literature
1377
1323 1378
First author, Level of
1324 year published Location evidence Study design Findings 1379
1325 Proudfoot Europe IV Anonymous, online, multiple- - po systemic steroids are used for
1380
1326 et al, 2013S1 response format survey among short-term flare control 1381
1327 members of pediatric dermatology - 30.7% of providers would use 1382
1328 societies and special interest systemic corticosteroids as first-line 1383
1329 groups in 8 European countries to systemic therapy vs 43% of 1384
1330 determine treatment practices in providers who prefer to use 1385
1331 children with severe AD cyclosporine as a first-line agent 1386
1332 Sonenthal United States IV Case reports (n = 3) of patients with - Reserved for severe disease with 1387
1333 et al, 1993S2 severe AD refractory to treatment multiple treatment failures 1388
1334 requiring long-term alternate-day 1389
treatment with po prednisone
1335 1390
(5-15 mg qod)
1336 Steinke Europe III Cross-sectional retrospective cohort - Nearly one-third of patients used
1391
1337 et al, 2014S3 study systemic corticosteroids 1392
1338 Inclusion: adults with AD (n = 1678); - Treatment ranked as successful 1393
1339 mean SCORAD, 42.3 or very successful by 84.2% of 1394
1340 patients but associated with least 1395
1341 satisfaction with health care 1396
1342 Heddle Europe II Double-blind, placebo controlled, - Steroids associated with significant 1397
1343 et al, 1984S4 crossover trial in children (n = 26) improvement in redness, surface 1398
1344 with moderate-to-severe AD damage, and lichenification vs with 1399
1345 Beclomethasone diproprionate, placebo 1400
200 g qid po 1 50 g qid - Significant improvement in daytime
1346 1401
intranasally to each nares for 4 wk itch and antihistamine use vs with
1347 vs placebo placebo
1402
1348 - Parents’ overall assessment of AD 1403
1349 activity lower with steroids vs with 1404
1350 placebo 1405
1351 Aylett Europe II Prospective cohort study of children - 14/15 demonstrated substantial 1406
1352 et al, 1992S5 with severe, diffuse AD benefit 1407
1353 unresponsive to topical therapy - 10/14 reached maintenance dosing 1408
1354 (n = 15) without reflaring 1409
1355 Beclomotheasone diproprionate, 1410
1356 600 g po tid 3 4 wk, then 1411
tapered to maintenance dose
1357 1412
(800-1800 g/d)
1358 La Rosa Europe II Placebo controlled, crossover trial in - 49% reduction in TCS scores vs
1413
1359 et al, 1995S6 children with chronic, severe AD placebo group after 2 wk of therapy 1414
1360 (n = 20) - After the crossover portion at wk 3, 1415
1361 Dosing of flunisolide: no significant difference in disease 1416
1362 - Age \3y: 128 g daily severity between groups 1417
1363 - Age [3 y: 220 g daily 1418
1364 1419
Schmitt Europe II Double-blind RCT of po prednisolone - 10/21 patients treated with
1365 et al, 2010S7 (0.5-0.8 mg/kg, tapered off prednisolone withdrew because
1420
1366 within 2 wk) vs cyclosporine of rebound/exacerbation 1421
1367 (2.7-4.0 mg/kg for 6 wk) - 1/21 treated with prednisolone 1422
1368 Inclusion: severe eczema (SCORAD achieved stable remission vs 6/17 1423
1369 $40) patients treated with cyclosporine 1424
1370 - Study terminated early because of 1425
1371 significant exacerbations 1426
1372 - DLQI lower after treated with 1427
1373 prednisolone vs with cyclosporine 1428
1374 Continued 1429
1375 1430

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1431 Supplemental Table II. Cont’d 1486

1432 1487
Primary literature
1433 1488
First author, Level of
1434 year published Location evidence Study design Findings 1489
1435 Stephens and Australia IV Survey of 149 practicing - 18% of patients classified as having
1490
1436 Cooper, dermatologists in Australian severe AD 1491
1437 1999S8 College of Dermatologists - 17% of patients with severe AD 1492
1438 treated with systemic 1493
1439 corticosteroids 1494
1440 - Low satisfaction with results 1495
1441 Galli et al, Europe IV Pilot study of children with severe AD - 5/7 patients showed improvement 1496
1442 1994S9 unresponsive to conventional in skin lesions 1497
1443 therapy (n = 7) - Dramatic improvement in itching 1498
1444 IV Methylprednisolone immediately after bolus 1499
20 mg/kg/d 3 3 d - Transient decrease in CD41 cell
1445 1500
count
1446 Stroud et al, United States II Double-blind, placebo-controlled - All patients benefited, with no dif-
1501
1447 1963S10 study of IM (40-60 mg weekly) vs ference between dosing schedules 1502
1448 po (6-8 mg daily split into 3 doses) - Relapses occurred in all groups as 1503
1449 methylprednisolone 3 6 wk in early as 1 wk after cessation of 1504
1450 patients with ‘‘eczematous disease corticosteroids, indicating lack of 1505
1451 of substantial severity’’ (n = 73) long-lasting results 1506
1452 Reddy et al, United States IV Prospective observational study with - Mean total cortisol decreased 1507
1453 2013S11 ‘‘steroid-responsive dermatoses’’ significantly 1508
1454 (n = 14) - No patients developed iatrogenic 1509
1455 All patient treated with IM Cushing syndrome or secondary 1510
triamcinolone acetonide, 30 mg adrenal insufficiency
1456 1511
(BMI \30 kg/m) or 60 mg (BMI - Mean Physician and Subject Global
1457 $30 kg/m2) every 6 wk for 12 wk Assessments of Disease Activity
1512
1458 Scale scores were significantly 1513
1459 improved 1514
1460 Forte et al, South America IV Case series - Rebound flare risk during tapering 1515
1461 2005S12 or shortly after discontinuation of 1516
1462 steroids outweighs any benefits 1517
1463 - Authors posit that steroids 1518
1464 may exacerbate IgE-mediated 1519
1465 hypersensitivity 1520
1466 Reviews 1521
1467 First author, Level of 1522
1468 year published Location evidence Study design Recommendations 1523
1469 Werfel et al, 2014S13 Europe III Review article of - Short courses of oral glucocorticos- 1524
1470 graded treatment teroids (3 d-3 wk wk) to interrupt 1525
1471 approach of AD acute flares in severe disease 1526
1472 - Side effects of steroids limit 1527
1473 long-term use 1528
1474 Rubel et al, 2013S14 Australia V Consensus guidelines - Steroids should be reserved 1529
for persistent, widespread,
1475 1530
nonresponsive AD
1476 - Lack of consensus among
1531
1477 committee regarding use 1532
1478 of po corticosteroids 1533
1479 - May be helpful for short courses 1534
1480 (max 6 wk) 1535
1481 - Long-term steroids have little to no 1536
1482 value and should be avoided 1537
1483 Continued 1538
1484 1539
1485 1540

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1541 Supplemental Table II. Cont’d 1596

1542 1597
Reviews
1543 1598
First author, Level of
1544 year published Location evidence Study design Recommendations 1599
1545 Tanei and Hasegawa, Asia III Review of treatment - Moderate-to-severe cases of AD in
1600
1546 2016S15 and prognosis of elderly 1601
1547 AD in the elderly - On the basis of the studies re- 1602
1548 viewed, the mean initial dose of 1603
1549 po prednisolone was 7.7 mg/d, 1604
1550 then tapered 1605
1551 Sidbury et al, 2014S16 United States II Expert opinion, consensus - Steroids should be avoided if 1606
1552 guidelines, and possible 1607
1553 systematic review - Reserved for acute, severe exacer- 1608
1554 bations as short-term bridge to 1609
other systemic steroid-sparing
1555 1610
therapy
1556 - General principle: dosing of 0.5-
1611
1557 1.0 mg/kg with tapering to decrease 1612
1558 risk for adrenal suppression 1613
1559 - Strength of recommendation: B 1614
1560 - Level of evidence: II 1615
1561 Borchard and Orchard, Australia III Review of systemic - Short courses for flare control 1616
1562 2008S17 therapy options (maximum 1-2 times/y), tapered 1617
1563 for pediatric AD over 1-2 wk 1618
1564 - Recommended dosing generally 1619
1565 1 mg/kg/d (po) 1620
- Side effects make repeated courses
1566 1621
of steroids unappealing
1567 Nankervis et al, 2015S18 Europe III Systematic review on - No recommendations made for
1622
1568 avoidance measures systemic steroid use 1623
1569 for treating eczema 1624
1570 Schmitt et al, 2007S19 Europe III Systematic review of - 27 studies included in the review, 2 1625
1571 prospective clinical of which included data on systemic 1626
1572 studies on systemic glucocorticoids (n = 47), both of 1627
1573 therapy in patients which included only pediatric 1628
1574 with severe AD patients 1629
1575 - No data are available for 1630
1576 prednisolone 1631
- Short observation periods after
1577 1632
treatment course limited moni-
1578 toring for relapse
1633
1579 Ricci et al, 2009S20 Europe III Review article on - Steroids are useful to control AD 1634
1580 systemic therapy flares in children 1635
1581 of AD in children - Evidence from trials is insufficient; 1636
1582 no data available for prednisolone 1637
1583 Simon and Bieber, Europe III Review article - Systemic corticosteroids (IV or po) 1638
1584 2014S21 can be used in short courses to treat 1639
1585 severe exacerbation and pruritus 1640
1586 - Not recommended to induce stable 1641
1587 remission or long-term control of 1642
AD
1588 1643
- Controlled clinical trials in children
1589 and adults are lacking
1644
1590 - Recommend 0.75-1.0 mg/kg/ 1645
1591 d tapered in 7-10 d 1646
1592 - One cohort study reported fast and 1647
1593 sustainable results in children after IV 1648
1594 methylprednisolone bolus therapy 1649
1595 Continued 1650

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1651 Supplemental Table II. Cont’d 1706

1652 1707
Reviews
1653 1708
First author, Level of
1654 year published Location evidence Study design Recommendations 1709
1655 Broerson et al, 2015S22 Europe III Systematic review - 12 studies included on patients with
1710
1656 and meta-analysis dermatologic conditions, including 1711
1657 of adrenal insufficiency AD, none of which reported adrenal 1712
1658 in corticosteroid use insufficiency 1713
1659 - Across multiple disease states, high- 1714
1660 dose and long-term steroid treat- 1715
1661 ment both associated with adrenal 1716
1662 insufficiency 1717
1663 - Recommend that all patient with 1718
1664 unexplained symptoms after steroid 1719
withdrawal be tested for possible
1665 1720
adrenal insufficiency
1666 Carbone et al, 2010S23 United States IV Literature review - Steroids should be reserved for se-
1721
1667 vere, recalcitrant cases in children 1722
1668 after multiple treatment failures 1723
1669 - Rebound flares often occur 1724
1670 - Tapering is necessary to prevent 1725
1671 rebound flares if treatment course 1726
1672 [1 wk 1727
1673 Basedow et al, 2011S24 Europe IV Review article - No recommendations for use 1728
1674 - Case reports of immediate hyper- 1729
1675 sensitivity reactions after po, IV, or 1730
intra-articular administration exist
1676 1731
- Incidence of contact allergy to cor-
1677 ticosteroids is $6%, and there is
1732
1678 often a diagnostic delay 1733
1679 David, 1989S25 Europe IV Review article - Limited use in severe, generalized 1734
1680 disease in children 1735
1681 - Attempt qod dosing; if daily, admin- 1736
1682 ister in the morning 1737
1683 Bubmann et al, 2009S26 Europe III Review article - Systemic corticosteroids limited to 1738
1684 exceptional circumstances for pa- 1739
1685 tients with severe AD (SCORAD 1740
1686 $35) 1741
- Treatment may be given as either a
1687 1742
pulse therapy (IV) or over 2-4 wk
1688 (PO) with tapering
1743
1689 - Long-term corticosteroid use is con- 1744
1690 traindicated because of side effects 1745
1691 Notaro and Sidbury, United States III Review article - Systemic steroids can provide acute 1746
1692 2015S27 relief to intractable itch and 1747
1693 dermatitis 1748
1694 - Most children flare immediately af- 1749
1695 ter treatment 1750
1696 - May serve as bridge to other 1751
1697 steroid-sparing therapies in children 1752
Nesbitt, 1995S28 United States III Review article - PO prednisone should be given as a
1698 1753
single, early-morning dose if
1699 necessary to minimize side effects
1754
1700 Lyons et al, 2015S29 United States III Review article on - Systemic corticosteroids should be 1755
1701 pathophysiology avoided even in severe disease un- 1756
1702 and treatment of less required for severe, persistent 1757
1703 AD in children asthma 1758
1704 - Topical corticosteroids likely achieve 1759
1705 higher concentrations at the site of 1760
inflammation
Continued

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1761 Supplemental Table II. Cont’d 1816

1762 1817
Reviews
1763 1818
First author, Level of
1764 year published Location evidence Study design Recommendations 1819
1765 Shaw et al, 2009S30 United States IV Review article - Limit systemic steroid to severe,
1820
1766 persistent disease in children 1821
1767 Vestergaard and Europe III Review article on - Limited data documenting effect of 1822
1768 Deleuran, 2014S31 diagnosis and systemic corticosteroids 1823
1769 management - Anecdotally, steroids are rapidly 1824
1770 of AD effective at controlling symptoms 1825
1771 of a severe flare 1826
1772 - Short course for severe flare of AD 1827
1773 as bridge to steroid-sparing therapy 1828
€tz et al, 2014S32
Plo Europe V Expert opinion - Systemic steroids should be
1774 1829
reserved for severe flares as bridge
1775 1830
to steroid-sparing therapy
1776 Cookson and Smith, Europe III Review article - Use of po prednisone for short
1831
1777 2012S33 courses to treat severe exacerbation 1832
1778 - Use of long-term systemic steroids 1833
1779 is limited by toxicity 1834
1780 Bershad, 2011S34 United States III Review article - Treatment-resistant AD may require 1835
1781 systemic coritcosteroids 1836
1782 - RCTs are lacking and rebound flar- 1837
1783 ing is common 1838
1784 - Long-term systemic corticosteroids 1839
1785 are contraindicated 1840
Katsarou and Armenaka, Europe IV Review article on - For acute flares in elderly patients
1786 1841
2011S35 AD in elderly with AD, consider po prednisolone
1787 patients (20-40 mg/d)
1842
1788 - Monitor closely for hyperglycemia, 1843
1789 hypertension, and ocular side 1844
1790 effects 1845
1791 Lipozenci
c and Wolf, Europe III Review article - Short course of systemic steroids for 1846
1792 2007S36 acute flares 1847
1793 - Avoid long-term use in adults and 1848
1794 children 1849
1795 Ring et al, 2012S37 Europe II Consensus guidelines - Short-term treatment with po glu- 1850
1796 on treatment of AD cocorticosteroids is effective (level 1851
of evidence: D)
1797 1852
- Well-known side effects limit long-
1798 term use
1853
1799 - Systemic steroids have a largely 1854
1800 unfavorable risk-to-benefit ratio 1855
1801 for treatment of AD (Level of evi- 1856
1802 dence: D) 1857
1803 - Systemic steroid use in children 1858
1804 should be even more cautious 1859
1805 than in adults (level of evidence: D) 1860
1806 Tyler, 2015S38 United States IV Review article - Short courses of moderate-dose oral 1861
1807 steroids in pregnancy for acute 1862
flares
1808 1863
Akdis et al, 2006S39 Europe V Consensus guidelines - Short course of systemic steroids for
1809 on diagnosis and management of acute flares
1864
1810 treatment of AD - Long-term use and use in children 1865
1811 in children and adults should be avoided 1866
1812 Turner and Schwartz, United States III Review article - Systemic steroids should be limited 1867
1813 2006S40 to severe, chronic cases and dis- 1868
1814 continued upon symptomatic relief 1869
1815 Continued 1870

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1871 Supplemental Table II. Cont’d 1926

1872 1927
Reviews
1873 1928
First author, Level of
1874 year published Location evidence Study design Recommendations 1929
1875 Pua and Barnetson, Australia III Review article - Systemic corticosteroids achieve
1930
1876 2006S41 control in severe exacerbations but 1931
1877 have many side effects and signifi- 1932
1878 cant risk for rebound 1933
1879 Sidbury and Hanifin, United States III Review article - Systemic steroids (PO, IM) are 1934
1880 2000S42 extremely effective at controlling 1935
1881 symptoms quickly 1936
1882 - Limit to 1-2 treatment courses/y to 1937
1883 avoid side effects 1938
1884 Correale et al, 1999S43 United States III Review article - Systemic steroids reserved for se- 1939
vere, treatment-resistant AD
1885 1940
- Avoid rebound flaring by tapering
1886 and using emollients aggressively
1941
1887 - Children are at increased risk for 1942
1888 side effects 1943
1889 Rasmussen, 1989S44 United States V Expert opinion on - For treatment-resistant AD, consider 1944
1890 pediatric AD short course of po prednisone, 1945
1891 1 mg/kg, for 5-7 d 1946
1892 Rasmussen, 1989S45 United States V Expert opinion - Consider systemic steroids in pa- 1947
1893 tients unresponsive to mild topical 1948
1894 steroids, lubricants, and antihista- 1949
1895 mines, or in patients whose disease 1950
is primarily inflammatory, not
1896 1951
lichenified
1897 Susac et al, 2007S46 Europe IV Review article on - Limit systemic steroids to severe,
1952
1898 AD in children treatment-resistant flares 1953
1899 Landow, 1997S47 United States V Expert opinion - Consider po prednisone, 20 mg/d, 1954
1900 for widespread disease 1955
1901 Simon, 2011S48 Europe IV Review article - Consider methylprednisolone bolus 1956
1902 (IV, 20 mg/d 3 3 d) for severe 1957
1903 exacerbations to stop acute 1958
1904 symptoms 1959
1905 Roos et al, 2004S49 Europe V Review article - Systemic steroids limited to severe 1960
1906 exacerbations and used with 1961
extreme cautious in children
1907 1962
- No evidence-based guidelines
1908 available
1963
1909 Sarkar and Kanwar, India IV Review article - Systemic steroids play a limited role 1964
1910 2002S50 in severe flares in children 1965
1911 Verbov, 1989S51 Europe IV Review article - Short course of systemic steroids for 1966
1912 the rare pediatric patient unre- 1967
1913 sponsive to other treatment 1968
1914 modalities 1969
1915 Akhavan and United States IV Review article - Limited systemic steroid use to 1970
1916 Rudikoff, 2008S52 acute flares to transition to other 1971
1917 steroid-sparing therapies 1972
Saeki et al, 2009S53 Asia IV Expert opinion - Systemic steroids occasionally used
1918 1973
as induction therapy for patients
1919 with severe AD
1974
1920 - Limited, short-term use is 1975
1921 recommended 1976
1922 1977
Continued
1923 1978
1924 1979
1925 1980

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1981 Supplemental Table II. Cont’d 2036

1982 2037
Reviews
1983 2038
First author, Level of
1984 year published Location evidence Study design Recommendations 2039
1985 Wang et al, 2016S54 Taiwan IV Review article - Systemic steroids are not recom-
2040
1986 mended unless required to manage 2041
1987 asthma exacerbations 2042
1988 - May be given as short-term transi- 2043
1989 tion to steroid-sparing therapy 2044
1990 Darsow et al, 2013S55 Europe IV Review article - Systemic corticosteroids are rapidly 2045
1991 effective but should be limited to 2046
1992 severe, acute exacerbations because 2047
1993 of long-term side effects 2048
1994 - Can use systemic steroids as bridge 2049
to other systemic anti-inflammatory
1995 2050
therapy
1996 Gottlieb, 2005S56 United States IV Review article - Systemic corticosteroids are rarely
2051
1997 used as primary treatment of AD 2052
1998 but can be used as a bridge to 2053
1999 steroid-sparing agents 2054
2000 - Severe rebound and significant 2055
2001 toxicity limits utility 2056
2002 - Prolonged use in children is not 2057
2003 recommended 2058
2004 Leung and Barber, Canada IV Review article on - Limited systemic steroids use to 2059
2005 2003S57 managing AD recalcitrant cases or as bridge to 2060
in children other steroid-sparing therapies
2006 2061
Wolter and Price, 2014S58 United States IV Review article - Systemic steroids are rarely indi-
2007 cated in children
2062
2008 Barnetson and Australia IV Review article on - Avoid systemic steroids because of 2063
2009 Rogers, 2002S59 treatment of severe rebound on withdrawal and 2064
2010 AD in children long-term side effects 2065
2011 Misery, 2011S60 Europe IV Review article - No recommendations for use 2066
2012 - Use of glucocorticoids are limited 2067
2013 by side effects 2068
2014 Roekevisch et al, 2014S61 Europe III Systematic review of - 3 RCTs evaluated systemic 2069
2015 all published RCTs glucocoricosteroids 2070
2016 or open-label - 2 small trials evaluated short-term 2071
extension of RCTs efficacy of beclomethasone dipro-
2017 2072
on systemic therapies prionate and flunisolide in children
2018 in patients with on basis of unvalidated outcomes
2073
2019 moderate-to-severe AD - Systemic prednisolone was less effi- 2074
2020 cacious than cyclosporine in adults 2075
2021 with severe AD 2076
2022 - Systemic steroids are not recom- 2077
2023 mended for moderate-to-severe AD 2078
2024 Abramovits and United States IV Review article on - Insufficient evidence to guide clin- 2079
2025 Granowski, 2010S62 management of ical practice of severe hand 2080
2026 severe hand dermatitis dermatitis 2081
2027 Leung and Hon, 2015S63 Asia IV Review article on - Recommendations not possible 2082
treatment of AD because of limited or poor-quality
2028 2083
in children data
2029 2084
2030 AD, Atopic dermatitis; BMI, body mass index; DLQI, Dermatology Life Quality Index; IV, intravenous; po, orally; qid, every 4 days; qod, every 2085
2031 other day; RCT, randomized controlled trial; SCORAD, Scoring Atopic Dermatitis; TCS, total clinical severity; tid, 3 times daily. 2086
2032 2087
2033 2088
2034 2089
2035 2090

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