DOI: 10.1111/j.1468-3083.2012.04523.

x JEADV

REVIEW ARTICLE

Topical corticosteroids in plaque psoriasis: a systematic

review of risk of adrenal axis suppression and skin
atrophy
E. Castela,*, E. Archier, S. Devaux, A. Gallini, S. Aractingi,** B. Cribier, D. Jullien, F. Aubin,
H. Bachelez, P. Joly,*** M. Le Matre, L. Misery, M.-A. Richard, C. Paul, J.P. Ortonne

Dermatology Department, Nice University, LArchet II Hospital, Nice, France

Aix-Marseille Univ, UMR 911, INSERM CRO2 and Dermatology Department, Timone Hospital, Marseille, France

Dermatology Department, Paul Sabatier University, Toulouse, France

UMR 1027 INSERM, Paul Sabatier University, Toulouse, France

**Dermatology Department, Tenon Hospital, APHP and Paris 6 University, Paris, France

Dermatology Department, University Hospital, Strasbourg, France

Dermatology Department, Edouard Herriot Hospital, Lyon, France

Dermatology Department, Franche Comte University, EA3181, IFR133, University Hospital, Besancon, France

Dermatology Department, Saint-Louis Hospital, Paris, France

***Dermatology Department, Charles Nicolle Hospital, University of Rouen, France

Dermatologist, Caen, France

Dermatology Department, University Hospital, Brest, France

*Correspondence: E. Castela. E-mail: emelinecastela@yahoo.fr

Abstract
Background Topical steroids have been used for more than 50 years in mild-to-moderate plaque psoriasis and
carry a theoretical risk of adverse events.
Objectives The aim of this systematic literature review was to evaluate the risk of hypothalamo-pituitary-adrenal
(HPA) axis suppression and the risk of skin atrophy with topical steroids in the treatment of plaque psoriasis.
Methods A systematic search between 1980 and January 2011 in Medline, Embase and Cochrane databases
(English, French language, adults), using the keywords psoriasis exp mj AND corticosteroid exp mj,
Results Altogether 1269 references were found. Of these 1124 articles were excluded by reading the abstract and
123 by reading the article. A total of 22 randomized trials were selected.
Effects on HPA axis: Thirteen studies, with a sample size varying from 7 to 341 patients, were selected. The effect
on HPA axis was evaluated by the morning cortisol level (11 studies), the 24 h urine steroid levels (five studies)
and or by the Synacthen test (three studies). Reduction of morning cortisol was observed in 025% of patients in
10 short-term studies (two in scalp psoriasis, eight in body psoriasis) and in 48% of patients in the remaining short-
term study (body psoriasis). Only four of these studies with three on body psoriasis evaluated the effect of long-term
treatment defined as 6-month treatment duration or longer and did not identify HPA axis suppression by cortisol
level measurement. The Synacthen test, considered as the gold standard to assess HPA axis, was always normal.
There was no evidence of clinically significant HPA axis suppression due to absorption of topical steroids even when
treating the scalp or in patients with extensive disease.
Risk of skin atrophy: Thirteen studies with topical steroid evaluating treatment durations from 4 weeks to 1 year
were analysed. The frequency of skin atrophy assessed clinically, varied from 0% to 5% of patients.
Conclusions The literature analysis on topical steroids in psoriasis is reassuring although the quality of safety
studies is limited with a majority of short-term studies. Although short-term biological effects of topical steroids on
the HPA axis were observed in several clinical studies, they were not associated with clinical signs. Adequately
designed long-term studies would be necessary to better determine the risk of skin atrophy using modern methods
of evaluation such as dermoscopy and echography.
Received: 10 February 2012; Accepted: 20 February 2012

Funding sources
Abbott France provided financial support for publication but took no further part in the project. The authors have no
financial interest in the subject matter or materials discussed in the manuscript.

2012 The Authors

JEADV 2012, 26 (Suppl. 3), 4751 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
48 Castela et al.

Conflicts of interest
All the authors have been paid consultants of Abbott. In addition C. Paul has been investigator and consultant for
Janssen-Cilag, Leo, Novartis and Wyeth. H. Bachelez has been paid for consulting activities for Centocor, Janssen-Cilag,
Leo Pharma, Novartis, Pfizer and Schering-Plough. B. Cribier has been paid for consulting activities for Pfizer, for
redaction activities by Leo Pharma and Janssen Cilag. and speaker for Pfizer, Leo Pharma and Schering Plough. D Jullien
has been consultant for Merck, Janssen-Cilag, Novartis, Pfizer, and Schering-Plough MSD.. JP Ortonne has been
investigator, speaker and advisor for Schering-Plough MSD, Abbott, Merck Serono, Centocor, Pfizer, Janssen Cilag,
Pierre Fabre, Galderma, Leo Pharma, Meda. L. Misery has been a paid consultant of Novartis, Janssen-Cilag, Leo
Pharma, Pfizer and Pierre Fabre. MA Richard has been investigator and consultant for Janssen-Cilag, Novartis, Pfizer.

pression to prepare for evidence-based recommendations on their

Introduction
Topical steroids are used for more than 50 years for the treatment
of mild-to-moderate adult plaque psoriasis. Their short-term
efficacy varies from 5% to 90% depending upon molecule and
formulation.1
Systemic effects following application of topical steroids are
related to systemic absorption of the product. Exogenous gluco-
corticoids have a suppressive effect on hypothalamic corticotro-
pin-releasing hormone and pituitary adrenocorticotropic
hormone (ACTH). With prolonged use of corticosteroids, sup-
pression of the hypothalamic-pituitary axis (HPA) and adrenal
insufficiency by adrenal glands atrophy may occur, and it can take
months to recover fully after discontinuation of exogenous gluco-
corticoids. The increased level of glucocorticoids in the blood can
also induce clinical signs of hypercorticism (iatrogenic Cushing
syndrome) such as arterial hypertension, diabetes, anxiety or irrita-
bility, facio-troncular obesity, buffalo neck, hirsutism, fragile skin,
pink striae and telangiectasia.
Systemic absorption of topical steroids varies according to age,
skin lesions location and extension of the disease. In addition,
duration of use, potency, formulation and molecule used may
also play a role.2 Moreover, the role of specific skin conditions
needs to be taken into account in the potential for topically
applied steroids to produce side effects. Indeed, diseases associ-
ated with skin barrier damage such as atopic dermatitis or Neth-
erton disease have been associated with increased percutaneous
absorption of topical corticosteroids and HPA axis suppression.
This remains unclear in the context of plaque psoriasis which is
to be considered as a chronic skin disease requiring long-term
therapy in most patients and sometimes large amount of topical
steroids.
Skin atrophy is the most problematic local side effect which
complicating the prolonged use of topical steroids. It is clinically
characterized by thinning of the skin, loss of elasticity, loss of skin
marking, telangiectasia and purpura.
A systematic literature review was carried out on the safety of
topical corticosteroids, especially skin atrophy and HPA axis sup-
use in psoriasis. The methodological approach leading to these
recommendations is described in detail in the same issue of this
journal.3
Materials and methods
A systematic review of all studies investigating topical steroids in
adult psoriasis patients published between 1980 and February
2011 was performed. The Cochrane, Embase and Medline databas-
es were systematically searched. We used a combination of Medi-
cal Subject Headings (Mesh) for our search: psoriasis [Majr] AND
Corticosteroids [Majr]. We used general terms in our search not
to miss safety studies reported as a subpart of efficacy studies. We
limited the literature search to articles on human subjects over
19 years of age, articles in English or French and articles reporting
original data.
Two reviewers (EC, JPO) independently performed parts of the
systematic electronic search and data extraction. Disagreements
were resolved by discussion; reviewers were 100% unanimous in
their final decisions.
Only publications considering skin atrophy and HPA axis sup-
pression as a primary or secondary outcome measures were
retained. We also analysed studies investigating HPA axis suppres-
sion with betamethasone dipropionate-calcipotriene combination.
The following data were extracted for the articles: database, author,
year, study design, inclusion period, number of psoriasis patients,
severity of psoriasis at baseline, frequency of application, amount
of topical steroids applied, body surface area treated, duration of
treatment strategy for maintenance regimen, methods to assess the
effect on HPA axis or skin atrophy, timing of blood and or urine
specimen collection and timing of skin atrophy assessment.
The outcome measures used to assess the suppressive effect of
topical steroids on HPA were as follows: (i) basal plasma cortisol
level (morning fasting cortisol sampled between 7.30 and 8.30 AM)
(ii) 24-h urinary corticosteroids level (free cortisol and
17-hydroxycorticosteroid) (iii) and plasma cortisol level sampled
immediately before and 30 and 60 min following stimulation with
250 lg intravenous injection of Synacthen (cosyntropin or

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JEADV 2012, 26 (Suppl. 3), 4751 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
Topical corticosteroids in plaque psoriasis 49

ACTH) (Synacthen stimulation test), considered as the gold detailed flowchart summarizing the selection process is
standard to assess HPA axis. Depending upon studies, a morning represented in Fig. 1.
fasting plasma cortisol value below 57 lg dL was considered as a
marker of HPA axis suppression. Following stimulation with Hypothalamo-pituitary-axis suppression following topical
cosyntropin a plasma cortisol level below 1820 lg mL was used steroids in psoriasis (Fig. 2)
as lower limit of normal adrenal function. Thirteen studies assessed the effects of topical steroids on HPA axis
The outcome measures considered to assess skin atrophy with during the treatment of plaque psoriasis4,5,79,1417,20,2325: twelve were
topical steroids were clinical examination and echography. parallel-group studies,4,5,7,9,1417,20,2325 one was within-patient studies.8
The proportion of patients with abnormal HPA axis and skin Effect of topical steroids on HPA axis was defined as the primary
atrophy was extracted from the trials. Corresponding 95% bino- outcome measure in six studies4,5,20,2325 and as secondary outcome
mial Confidence Intervals (CI) were calculated from the available in seven studies.79,1417 Treatment duration varied from 7 days4 to
data if not already given in the article [STATA software (StataCorp. 1 year20 with four studies of 6 month to 1 year duration.7,15,20,25
2009. Stata Statistical Software: Release 11. StataCorp LP, College Sample size varied from 7 to 341 patients. Three studies focused
Station, TX, USA)]. on scalp psoriasis.7,9,23 The amount of topical steroids daily applied
or the body surface area treated was reported in only three stud-
Results ies.4,16,24 The amount used, when available ranged from 1.5 to 7 g
Of the 1269 references found, 1124 articles were excluded by read- per day.4,15,16,24 The body surface area treated was not always pre-
ing the abstract and 123 by reading the article. Across the 123 cisely recorded. It ranged from two psoriasis plaques8 to more than
excluded articles, 108 articles were rejected because they exclusively 30% body surface area 25
reported on efficacy. Twenty-two trials were finally selected.425 The Eight short-term studies with duration ranging from 1 to
4 weeks assessed the effects of topical steroids on adrenal axis by
monitoring morning cortisol level.4,5,8,9,16,17,23,24 Five of these studies
also measured 24-h urine steroids level.4,5,15,16,24 Walsh et al.5 com-
Potentially relevant articles published between 1975 and pared the effects on HPA axis of two superpotent topical steroids,
2010 identified by electronic search: N = 1269
Pubmed : n = 629 ; Embase : n = 530 ; Cochrane : n = 110 augmented betamethasone dipropionate and halobetasol propio-
nate (HP) in 40 male patients. The compounds were applied twice
Studies excluded (by reading daily for 2 weeks. The serum and urine cortisol levels were evalu-
of article) N = 123:
Studies excluded (by reading of ated by analysis of covariance model with adjustment for the
title or abstract) N = 1124:
Concerned the same patients: n = 2 observed baseline difference between the two arms. Results were
Children: n = 2
Did not address the question, basic Duplicates: n = 2 expressed as average change from baseline i. e. mean cortisol level
science study, not original study:
Complexity of study design: n = 1 post baseline subtracted from mean cortisol level at baseline. The
n = 1007
Confusion factor: n = 4
Assessed ratio benefits/cost: n = 2 authors demonstrated HPA axis suppression in both treatment
Case report: n = 4
Quality of life studies: n = 2 Studies on topical steroids which do not
Duplicates: n = 113 assess the effects on HPA axis or
group but failed to demonstrated statistical significance between
atrophy: n = 108 treatments. Based on urine cortisol, HP was more likely to sup-
22 articles included press HPA axis especially within the first 5 days of treatment.
Recovery from HPA axis suppression was rapid even upon
Fig 1 Flow-chart of study selection process.

Study Study duration N (arm)

(weeks)

Watson 1990 4 1 7 Halobetasol

23
Andres 2006 1 26
Olsen 1991 9 2 188 Clobetasol
Jegasothy 1985 17 2 57
Weston 1988 24 3 19
Katz 1987 16 2 20
Poulin 2010 7 24 106

Weston 1988 24 3 18 Betamethasone

Katz 1987 16 3 20
Pacifico 2006 8 4 42
Katz 1991 15 24 46
Fluocinonide
Jegasothy 1985 17 2 57
Fig 2 Effects of topical steroids on 0 20 40 60 80
morning cortisol level in the treatment of % of patients with a decrease of morning plasma cortisol level
plaque psoriasis.
Abbreviations: N = number of patients in the topical steroid arm

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JEADV 2012, 26 (Suppl. 3), 4751 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
50
continuation of superpotent topical steroids treatment. Weston
et al. studied the effect of topical steroids on HPA axis at different
time-points.24 They treated 38 male patients with 49 g per week of
either betamethasone dipropionate in an optimized vehicle or
clobetasol propionate ointment applied twice daily for 21 days
and assessed HPA suppression at 4, 7, 14 and 21 days, and 7 days
after end of treatment. Suppression of plasma cortisol levels was
recorded in 53% of patients receiving clobetasol propionate and
17% of patients receiving betamethasone dipropionate
(P = 0.004). The plasma cortisol suppression was most marked
within the first 7 days of treatment and returned to normal 7 days
after stopping treatment.
Considering short-term studies evaluating morning cortisol lev-
els,4,5,8,9,16,17,23,24 the proportion of patients with any reduction in
morning cortisol level was 0% with halobetasol or fluocinonide,
048% with clobetasol propionate and 018% with betamethasone
dipropionate (Fig. 2). There was no evidence of adrenal suppres-
sion of clinical significance. Reduced morning plasma cortisol lev-
els always returned to normal despite continued use 16,17 or within
1 or 2 weeks after stopping treatment.9,16
Two short-term studies used the Synacthen test14,23 to assess
adrenal suppression. Katz et al. conducted a parallel-group trial in
341 patients14 evaluating 0.1% mometasone furoate with or with-
out 5% salicylic acid. At the end of the study no significant
changes in the Synacthen test were noticed in any group. Andres
et al.23 compared clobetasol propionate 0.05% shampoo vs. gel in
scalp psoriasis. No shampoo-treated patient developed HPA axis
suppression vs. 16% of patients treated with the gel.
Four studies assessed the long-term risk of HPA axis suppres-
sion following prolonged use of topical corticosteroids, with three
of them performed in body psoriasis15,20,25 and one in scalp psoria-
sis.7 Treatment duration was 6 months in three studies7,15,25 and
1 year in one study.20 Only one study used the Synacthentest.20
Others monitored the morning plasma cortisol level. In three
studies, no patients showed any HPA axis suppression.7,15,20 In the
last study, Cornell et al.25 found a decrease of morning plasma cor-
tisol in 40% of patients treated by desoximetasone emollient
cream 0.25% twice daily and in 0% of patients treated by beta-
methasone 17-valerate 0.1% cream twice daily. The plasma cortisol
spontaneously returned to normal value in 50% of cases despite
continuation of the use of the medication and within 7 days of
discontinuation of the medication in 50% of cases.
Risk of skin atrophy with topical steroids in plaque
psoriasis
Thirteen studies evaluated the risk of skin atrophy in the treatment
of plaque psoriasis.68,1014,18,19,2123 Of these studies, four were intra-
individual studies6,8,14,22 and nine were parallel-group prospective
studies.7,1013,18,19,21,23 The number of patients varied from 26 to 1421
and the duration of treatment from 4 weeks to 1 year. Only two
long-term studies investigating, respectively, 6 months and 1 year
treatment were available.7,12 Skin atrophy was assessed by clinical
JEADV 2012, 26 (Suppl. 3), 4751 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
Castela et al.
examination in all except one study.23 Katz et al. (1987)16 moni-
tored patients for signs of skin atrophy using a severity scale for
each sign of skin atrophy on target lesions. The proportion of
patients with skin atrophy observed at the end of the treatment
varied from 0 to 5%. In the study by Kragballe et al.,12 634 patients
were randomized double-blind for treatment with 52 weeks of the
calcipotriol betamethasone dipropionate two-compound product
(two-compound group) applied as needed; 52 weeks of alternating
4-week periods of the two-compound product and calcipotriol
(alternating group); or 4 weeks of the two-compound product fol-
lowed by 48 weeks of calcipotriol (calcipotriol group). Treatments
in all groups were applied once a day when required. Skin atrophy
was observed with an incidence of 1.9%. No study specifically
investigated the atrophogenic risk of topical steroids on facial or
intertriginous psoriasis. No study investigated skin atrophy with
dermoscopy. Andres et al.23 used a B scan ultrasound device to
measure skin atrophy in scalp psoriasis patients receiving either
clobetasol dipropionate 0.05% shampoo or clobetasol dipropio-
nate 0.05% gel. Measurements were carried out on different sites
of the forehead. Epidermis plus dermis thickness, expressed in mil-
limetres were monitored using a probe and 20MHz transducer at
baseline and at week 2 and 4. No clinically significant skin atrophy
was observed at any time of the study but after 4 weeks of treat-
ment, a significant decrease of skin thickness was recorded follow-
ing clobetasol dipropionate gel application whereas the short-
contact clobetasol shampoo showed no effect.
Discussion
We show herein that the risk of HPA axis suppression and skin
atrophy with topical steroids in psoriasis is minimal according to
clinical studies. However, it needs to be pointed out that there is a
paucity of data concerning long-term treatment. In addition, the
effect of long-term treatment of large psoriasis surfaces with topi-
cal steroids, which is sometimes advocated in clinical practice, has
not been investigated.
The result of this review concerning the safety of topical steroids
in adult psoriasis is somewhat reassuring. When it comes to sys-
temic side effects, reversible hypothalamic-pituitary-adrenal
(HPA) axis suppression was reported rarely26,27 compared with the
large population of patients treated with topical steroids for psori-
asis worldwide. All cases of prolonged HPA axis suppression are
characterized by misuse of topical steroids: prolonged daily appli-
cation over several years on large surfaces.28 Although transient
reduction of HPA axis function can be observed in up to 48% of
patients,24 this reduction is reversible and not usually associated
with clinical symptoms even during long-term maintenance treat-
ment. In short-term studies, reduction of cortisol plasma levels
was mainly recorded early in the course of the treatment i.e. dur-
ing the first 7 days. Plasma cortisol levels returned to normal
within weeks suggesting that restoration of an epidermal barrier
helped to reduce steroid absorption as healing occurred. Adrenal
suppression is also uncommon and transient with prolonged use
2012 The Authors
Topical corticosteroids in plaque psoriasis
for up to 24 weeks. Clobetasol propionate was shown to be the
most frequently responsible agent for HPA axis suppression even
when treating the scalp with a gel formulation. However, the qual-
ity of HPA axis studies was highly variable and only a minority
met current standards for HPA axis evaluation.
Skin atrophy was only described in 05% of cases according to
the studies. As for the risk of HPA suppression, long-term studies
are rare. Skin atrophy was always clinically assessed with the
exception of a scalp study using echography.23 Skin atrophy might
have been underestimated. This underlines the lack of high quality
studies using state of the art methodology with careful prospective
dermatological evaluation of skin atrophy using dermoscopy and
echography.29
Conclusion
The results of this present review indicate that topical steroids in
the treatment of adult psoriasis are extremely safe if used in accor-
dance with the guidelines.3 The indication of topical steroids for
psoriasis must be restricted to mild or moderate psoriasis with less
than 10% of body surface area affected using a 4-week daily treat-
ment. The efficacy of treatment must be evaluated within
12 months after the initial prescription. This evaluation is essen-
tial to prevent misuse and consequently complications from using
topical steroids.
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