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Skin Research and Technology 2001; 7: 214–218 Copyright C Munksgaard 2001

Printed in Denmark. All rights reserved


Skin Research and Technology
ISSN 0909-752X

Efficacy of corticosteroids in acute experimental irritant


contact dermatitis?
Cheryl Levin, Hongbo Zhai, Saqib Bashir, Ai-Lean Chew, Angela Anigbogu, Robert Stern and
Howard Maibach
University of California at San Francisco Medical Center, San Francisco, CA, USA

Background/aims: Topical corticoids are used to treat irritant Results: Corticosteroids were found ineffective in treating the
contact dermatitis (ICD) in humans. However, their clinical effi- surfactant-induced irritant dermatitis when compared with the
cacy remains sub judice. This study was designed to assess vehicle and with the untreated control.
the efficacy of low- and medium-potency corticosteroids on irri- Conclusion: The counterintuitive result (in a relatively realistic
tant dermatitis. and robust model) should be interpreted with caution until veri-
Methods: We induced an acute ICD via open application of fied with other irritants of varying physicochemical properties.
sodium lauryl sulphate (SLS) on the hands of subjects. The
dorsal side of hands was irritated with 10% SLS five times in
one day. Once on day 1 and twice daily on days 2–5, 1% Key words: irritant dermatitis – corticosteroid – transepidermal
hydrocortisone, 0.1% betamethasone-17-valerate and vehicle water loss – squamometry – colorimetry
cream (petrolatum) were applied subsequently. Visual grading,
bioengineering techniques and squamometry were used to c Munksgaard, 2001
quantify skin response. Accepted for publication 17 January 2001

I RRITANT contact dermatitis (ICD) is a multifactorial


disease, resulting from acute or cumulative ex-
posure. Traditionally, topical corticoid therapy is
Material and Methods
Subjects
widely utilized, though experimentation in humans Six healthy volunteers, aged 49∫8 (mean∫SD) years,
provides conflicting results (1). In theory, while the provided written informed consent for participation
anti-inflammatory properties of corticoids could im- in a double-blind study (5 men, 1 woman) approved
prove the dermatitis, their anti-proliferative effects by the University of California Committee on Human
might slow recovery of the skin barrier and allow Research. None of the subjects had a history of atopic
further penetration of irritants (2, 3). dermatitis or presented with dermatitis at or near the
Occlusive application of surfactant on human sub- test sites. The studies were performed in April 2000.
jects is a widely employed method of inducing irri-
tant contact dermatitis in vivo. However, the devel- Material and measurements
opment of clinical ICD typically occurs following Ten percent sodium lauryl sulphate (SLS; 99% purity,
open exposure to detergents or other chemical irri- Sigma, St. Louis, MO, USA) dissolved in deionized
tants. Open application of surfactant (rather than water induced ICD. Treatments included 0.1% beta-
patch) mimics a more realistic clinical scenario (4, 5). methasone-17-valerate ointment (Alpharma, Balti-
We induced an acute ICD via open application of so- more, MD, USA) and 1% hydrocortisone ointment
dium lauryl sulphate on the hands of subjects to de- (Pfizer, New York, NY, USA). Petrolatum USP served
fine the efficacy of low- and medium-potency corti- as a vehicle control.
costeroids on irritant dermatitis. Bioengineering tech- Transepidermal water loss (TEWL) was measured
niques and squamometry were used to quantify skin with an evaporimeter (TewameterTM 210, Courage &
response. Khazaka, Cologne, Germany). TEWL is a sensitive

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Efficacy of corticosteroids in ICD

measure of skin water barrier function (6, 7), and pressure. The disk was then removed with forceps in
probes detect changes in the water vapor gradient a uniform direction. This procedure is known as squa-
between the skin surface and the ambient air. A mometry.
colorimeter (Chroma Meter CR 300, Minolta, Osaka, An open application hand washing assay (9) in-
Japan) evaluated the skin color. Colorimetry assesses duced irritation on the dorsal side of the hands. The
the blanching effect of corticosteroids by measuring investigator rubbed 1 ml of 10% SLS solution in her
three space parameters of light (L*a*b*). The L* value hands using tepid tap water (water hardness: 58 mg/l
represents luminance, a* depicts the blend of red and CaCO3). Both of the volunteer’s hands were washed
green and b* measures the blend of yellow and blue. with the same lather 30 times (for approximately 1
The a* parameter was used, as it most closely corre- min) and then rinsed for 15 s. The procedure was re-
lates with erythema (4, 8). Erythema and dryness peated hourly for a total of five hand washes in 1 day.
were assessed separately by a trained investigator SLS was used to model ICD because it is known to
using well-established visual score methods (9). A damage the skin barrier without causing excessive
graded scale of 0–4 was used to describe both the discomfort to the volunteers (12, 13).
erythema and dryness that occurred with the irritat- Immediately after the final washing, three sites
ing agent, with 0 characterizing no redness or no (each with an area of 2.83 cm2) were treated, respec-
erythema and 4 describing a fiery redness or a very tively, with approximately 18 mg/cm2 of betame-
intense dryness. This grading system is described in thasone valerate, hydrocortisone and petrolatum. A
detail in Tables 1 and 2. The outer layer of stratum graded syringe was used to apply the ointments, so
corneum was stripped with a tape disc (D-Squame, that an equal amount of ointment would be adminis-
Cuderm Corporation, Dallas, TX, USA). tered to each site. One site was untreated. Investi-
gators and subjects were blinded to the formulations
tested. The ointments were openly applied once on
Methods the first day and then twice daily at approximately
Upon acclimatization to the room temperature (18– 10:00 a.m. and 4:30 p.m. for four consecutive days.
22 æC, relative humidity 44–61%) for 30 min, two ran- Bioengineering and visual score measurements were
domized sites were chosen on the dorsal side of each taken daily before the second corticoid application.
of the volunteer’s hands for a total of four sites. Base- One stratum corneum stripping was performed on
line measurements of transepidermal water loss, skin each site before the final corticoid application. Squam-
color and visual score were taken at the selected loca- ometry was used to analyze the tape discs. The meth-
tions. On one additional randomized site, a single odology involves staining each tape disc for 30 s with
stratum corneum stripping was performed, based on one drop of toluidine blue and basic fuschin solution
previously described methodology (10, 11). One tape (Polychrome Multiple Stain Delasco, Council Bluff,
disk was applied for 5 s onto the skin using 10 kPa of IA, USA) and then mounting it on a frosted micro-
scope slide (Fisher, Pittsburgh, PA, USA). The slide is
dried on a slide warmer for 10 min. The Chroma C*
value of the stained discs, which roughly correlates
TABLE 1. Visual score of erythema with the amount of stratum corneum stripped (10),
Grade Description was measured (Chroma Meter CR 300, Minolta,
Osaka, Japan). C* is defined as (a2πb2)0.5. A micro-
0 No erythema
1 Slight redness scope magnification of ¿100 was utilized to evaluate
2 Moderate redness intercorneocyte cohesion and the amount and distri-
3 Intense redness bution of dye in cells. Intercorneocyte cohesion was
4 Fiery redness
graded as follows: 0Ωlarge sheet; 1Ωlarge clusters and
few isolated cells; 2Ωsmall clusters and many isolated
cells; 3Ωclusters in disruption, most cells isolated; 4Ω
TABLE 2. Visual score of dryness all cells isolated, many cases of lysis. The amount and
Grade Description distribution of dye in cells was scored according to
the following scale: 0Ωno staining; 1Ωstaining be-
0 No erythema
1 Slight dryness without scaling
tween cells or slight staining in cells; 2Ωmoderate
2 Moderate dryness and scaling staining in cells; 3Ωlarge amount of staining in cells,
3 Intense dryness and scaling but uniform; 4Ωimportant staining in all cells, often
4 Very intense dryness and scaling
with grains.

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Levin et al.

Statistical analysis
The differences in mean TEWL and colorimetric
Discussion
values between the treated, untreated, and vehicle Corticoids may suppress some mildly irritant reac-
control test sites were tested for significance using a tions in humans if given before or concomitant with
repeated-measures ANOVA. The Friedman statistic the insult (14, 15). However, when given subsequent
evaluated visual and microscopic scores. A value of to irritation, corticoid effect remains unclear. The pres-
P⬍0.05 was considered significant. ent study found corticosteroids ineffective in treating
SLS-induced acute irritant contact dermatitis of the
hands. Previous studies by Van der Valk (16) and Le
Results (17) concluded similar results: corticoids were associ-
ated with no or possibly a negative effect in treating
TEWL, chromametry and visual score cumulative ICD. SLS was selected as the irritant in
SLS induced a significant mean increase in TEWL at this study because of its ability to lightly damage the
all test sites (Fig. 1). There was no significant change skin without sensitizing or causing excessive dis-
in TEWL measurements with any of the formulations comfort to the human volunteers (12).
when compared with each other and with untreated We focused on mimicking a clinically realisitic en-
skin. vironment. In contrast to previous studies that used a
SLS induced a decrease in chromametric values in patch to induce ICD (16–19), we chose to irritate the
all test sites. No statistically significant change in skin subclinically via a hand washing assay, since the
chromametric values was observed with any of the development of ICD may occur following open ex-
formulations tested when compared with each other posure to detergents or other chemical irritants (20,
and with untreated skin. The visual score did not dis- 21). Under occlusion, the damaging effect of SLS and
criminate between vehicle, untreated, or corticoid- other detergents may reflect irritation of deeper skin
treated sites. layers. Therefore, open application and patch testing
may investigate different aspects of skin barrier func-
tion (22, 23). We applied corticosteroids twice daily
Squamometry (except for day 1), since this is often the dermatol-
Chroma C* values for vehicle, untreated and corticoid ogist’s recommended dose in the treatment of ICD.
formulations did not significantly differ. Microscopic However, studies comparing repetitive dosing to a
analysis of intercorneocyte cohesion and amount and single dose have failed to reveal increased absorption
distribution of dye in cells did not differentiate be- of corticoids with frequent dosing (24, 25). Since ICD
tween treated or untreated test sites. is often localized to the hands, we chose the hands as
a model for corticosteroid-treated irritant dermatitis.
Ramsing (18) and Berardesca (19) studied the effect
of corticosteroids on acute ICD and found corticoids
to be effective treatments. However, the effect was
small (10% and 7% reduction in TEWL, respectively).
Ramsing only observed an effect on the 7th day of
treatment on the contralateral arm; no significant ef-
fect was observed when comparing treated and un-
treated skin on the same arm or on the first six days
of treatment. While Berardesca found statistical sig-
nificance when comparing corticosteroid-treated and
untreated skin, his study did not compare corticoid
treatment to vehicle control.
Squamometry has previously discriminated be-
tween corticosteroid-treated, vehicular and untreated
skin in the treatment of atopic dermatitis (26) and has
assessed the degree of irritation induced by SLS (9).
Fig. 1. TEWL mean difference from baseline (10% sodium lauryl sul-
In our study, squamometry was non-differentiating.
phate). There was no significant change in TEWL measurements with
any of the formulations when compared with each other or with un- This is consistent with our results using bioengineer-
treated skin. TEWL was significantly increased at all test sites ing equipment, namely TEWL and chromametry.
(P∞0.05). Chromametry values decreased subsequent to SLS-

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Efficacy of corticosteroids in ICD

induced irritation and corticosteroid application. This assay in investigation of subclinical irritant dermatitis in-
duced by sodium lauryl sulphate (SLS) in man: advantage
may have resulted from a 3 æC drop in temperature of squamometry. Skin Res Technol 1998: 4: 244–250.
from day 1 to day 2, causing increased vasodilation of 10. Pierard G, Pierard-Franchimont C, Saint Leger D, et al.
blood vessels (27). The known blanching effect associ- Squamometry: the assessment of xerosis by colorimetry of
ated with corticosteroids may have contributed to the D-Squame adhesive discs. J Soc Cosmet Chem 1992: 47: 297–
305.
decreased a* value as well (28). 11. Ale S, Laugier J-P, Maibach H. Spacial variability of basal
Our study’s findings are significant, but not without skin chromametry on the ventral forearm of healthy volun-
limitation. We tested corticosteroid efficacy in treating teers. Arch Dermatol Res 1996: 288: 774–777.
SLS-induced ICD; inducing ICD with other irritants 12. Wahlberg JE, Maibach HI. Nonanoic acid irritation – a posi-
tive control at routine patch testing? Contact Dermatitis
might be beneficial. Though acute skin challenge with 1980: 6: 128–130.
a surfactant reflects the transient susceptibility of skin 13. Lee CH, Maibach HI. The sodium lauryl sulphate model: an
to the particular irritant, it does not investigate the overview. Contact Dermatitis 1995: 33: 1–7.
skin’s repair mechanisms to cumulative irritation. 14. Kaidbey K, Kligman A. Assay of topical corticosteroids by
suppression of experimental inflammation in humans. J In-
Cumulative dosing of irritant, as performed by Van
vest Dermatol 1974: 63: 292–297.
der Valk (16) and Le (17) would better satisfy this cri- 15. Brunner A, Finkelstein P. A laboratory method for evalu-
terion. Increasing numbers of subjects might discrimi- ation of topical anti-inflammatory agents. Arch Dermatol
nate small differences; yet, the experimental design 1960: 81: 453–457.
16. Van der Valk P, Maibach H. Do topical corticosteroids modu-
(each person acting as their own control) has shown
late skin irritation in human beings? Assessment by trans-
significant discriminatory power in other studies (11). epidermal water loss and visual scoring. J Am Acad Derma-
Other experimental conditions, including the type of tol 1989: 21: 519–522.
chamber used (29), the concentration of surfactant 17. Le TKM, DeMon P, Schalkwijk J, et al. Effect of a topical
corticosteroid, a retinoid and a vitamin D3 derivative on so-
(30), and the temperature of application (31), should
dium dodecyl sulphate induced skin irritation. Contact Der-
not be neglected as they may also affect study results. matitis 1997: 37: 19–26.
Taken together, we’re impressed with the paucity of 18. Ramsing DW, Agner T. Efficacy of topical corticosteroids on
evidence to document the ubiquitous use of topical irritant skin reactions. Contact Dermatitis 1995: 32: 293–297.
19. Berardesca E, Distante F, Vignoli G, et al. Acute irritant der-
corticoids in irritant dermatitis. Thus, we should be
matitis: effect of short-term topical corticoid treatment. In:
motivated to document their relevance in the various Surber C, Elsner P, and Bircher A (eds.) Exogenous derma-
types of irritant dermatitis. We’re aware of the tology. Basel: Karger, 1995: 86–90.
strengths and weaknesses of experimental data; yet, if 20. Tupker R, Vermeulen K, Fidler V, et al. Irritancy testing of
we can show no clear effect in controlled conditions, sodium lauryl sulphate and other anionic detergents using
an open exposure model. Skin Res Technol 1997: 3: 133–136.
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and design on the distribution of erythema induced by so- Address:


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e-mail: himjlm/itsa.ucsf.edu

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