CLINICAL REVIEW

A systematic review of contact dermatitis

treatment and prevention
Joan Saary, MD, MSc, FRCPC,a,b Roohi Qureshi, MD, MEng, FRCPC,a,b Valerie Palda, MD, MSc, FRCPC,c
Joel DeKoven, MD, MHSc, FRCPC,a,b Melanie Pratt, MD, FRCPC,d,e
Sandy Skotnicki-Grant, MD, FRCPC,a,b and Linn Holness, MD, MHSc, FRCPCa,b
Toronto and Ottawa, Ontario, Canada

Background: Contact dermatitis (CD) is a common occupational disease. There have been no systematic
reviews of CD treatment or prevention.

Methods: Multiple databases were systematically searched. Using independent double review and
published quality review criteria, articles were rated as good, fair, or poor. Treatment benefit data were
tabulated and conclusions were based on the rated strength of published evidence.

Results: In all, 49 studies met inclusion criteria. Barrier creams containing dimethicone or
perfluoropolyethers, cotton liners, and softened fabrics prevent irritant CD. Lipid-rich moisturizers both
prevent and treat irritant CD. Topical skin protectant and quaternium 18 bentonite (organoclay) prevent
rhus dermatitis. Diethylenetriamine pentaacetic acid (chelator) cream prevents nickel, chrome, and copper
dermatitis. Potent or moderately potent steroids effectively treat allergic CD. There were no macrolide
immunomodulator trials that met inclusion criteria. This review did not include studies of children, animals,
or non-English language publications.

Conclusions: A limited number of interventions effectively prevent or treat irritant and allergic CD, but
well-controlled, outcome-blinded studies, particularly in the area of allergic CD prevention are needed.
( J Am Acad Dermatol 2005;53:845-55.)

A significant proportion of occupational disease

is accounted for by occupational contact
dermatitis (OCD)1,2 with incidence rates rang-
ing from 24/100,000 to 170/100,000.3-6 The extent of
Abbreviations used:
ACD:
CD:
ICD:
allergic contact dermatitis
contact dermatitis
irritant contact dermatitis
morbidity is underestimated,7,8 and ameliorating the OCD: occupational contact dermatitis
TEWL: transepidermal water loss
WSIB: Workplace Safety and Insurance Board
From the Gage Occupational and Environmental Health Unit,
Department of Occupational and Environmental Health,
St Michael’s Hospital,a and Departments of Medicine and Public
Health Sciences, University of Torontob; Departments of Med- effects of OCD is an ongoing challenge. The National
icine and Health Policy Management and Evaluation, University Institute of Occupational Safety and Health has
of Torontoc; and Department of Medicine, Ottawa Hospital,d
and Department of Medicine, University of Ottawa.e
identified OCD as a priority research area,9 noting
Funding source: The Workplace Safety and Insurance Board of that ‘‘there has been relatively little occupational
Ontario. research to . . . assist workers who have developed
Conflicts of interest: None identified. skin diseases that commonly afflict them for the rest
This work has been provided to the Workplace Safety and of their lives.’’10
Insurance Board as a technical report and has been orally
presented at the Annual Meeting of the American Contact
Medical management has had little impact on
Dermatitis Society in Washington, DC, on February 5, 2004. clinical outcome in OCD for more than 4 decades
Reprint requests: Joan Saary, MD, MSc, FRCPC, Department of with descriptive and nonexperimental studies (eg,
Occupational and Environmental Health, St Michael’s Hospital, retrospective cohorts) reporting persistent disease in
4th Floor Shuter Wing, 30 Bond St, Toronto, Ontario M5B 1W8, 33% to 81% of the individuals.11-23 Work outcomes
Canada. E-mail: [email protected].
0190-9622/$30.00
have also been poor with between 29% and 72% of
ª 2005 by the American Academy of Dermatology, Inc. OCD-affected individuals reporting skin-related job
doi:10.1016/j.jaad.2005.04.075 changes.1,14,16,18,20,24-26

845
846 Saary et al J AM ACAD DERMATOL
NOVEMBER 2005

The Workplace Safety and Insurance Board addition, studies achieving good or fair ratings were
(WSIB) of Ontario, Canada, has developed a pro- abstracted independently by two authors (R. Q. and
gram of care for OCD. This required that treatment J. S.) for statistically significant differences in clinical,
decisions be evidence-based. Given the significance biophysical, and subjective outcomes (see Appendix
of OCD and the historic lack of ability to modify the C for description of bioengineering outcomes).
clinical outcome, WSIB solicited an independent A summary of the evidence and proposed recom-
review of the literature to aid in the provision of mendations were then generated.
evidence-based recommendations.
RESULTS
METHODS
In 413 initial articles, we found studies examining
A literature search was conducted using the
63 different treatments, and 37 different preventive
MEDLINE, EMBASE, and Cochrane databases from
measures for irritant CD (ICD) and ACD (Table I).
January 1966 to June 2003 to identify relevant
Generally, treatments and preventive measures could
English-language publications. Key search terms
be classified as corticosteroids, nonsteroidal medica-
included: contact dermatitis (CD), contact allergy,
tions such as macrolide immunomodulators, barrier
eczema, controlled study, clinical trial, and treat-
creams, emollients, natural or herbal products, glove-
ment. Complete search strategies are listed in
related interventions, modifications to work process
Appendix A. In addition, references of relevant
or environment, and psychosocial or educational
articles and reviews were manually searched for
interventions. Although other treatments have been
additional sources. Bibliographies of retrieved pub-
proposed (eg, psychiatric intervention, introduction
lications were reviewed to identify sources not
of nurse practitioner) no controlled studies that
obtained in our search. Two authors (R. Q., J. S.)
would meet the inclusion and exclusion criteria
independently reviewed the abstracts to find those
were found.
that met eligibility (inclusion and exclusion) criteria.
After the application of inclusion and exclusion
Any disagreement was resolved by arbitration by a
criteria, only 49 articles that addressed the preven-
third author (V. P.).
tion and treatment of CD met eligibility criteria. In all,
A study was included if it dealt with prevention or
12 met the criteria for good quality,33-44 16 were rated
treatment of CD, either naturally occurring or exper-
as fair,45-60 and 21 were rated as poor and were not
imentally induced, even if not explicitly stated (ie,
further abstracted for results (Table II).61-81 Studies
includes those articles that show correlation be-
are randomized controlled trial unless otherwise
tween modifiable factor and CD), or if the study did
stated. The details of quality evaluations and results
not deal exclusively with treatment for CD, but data
for individual studies are outlined in online supple-
of patients with CD were presented separately, so
mental tables available at www.eblue.org.
that they could be abstracted independently of other
data.
A study was excluded if its subjects were not Prevention of ICD
human or not adult, the language of publication was There is evidence from good-quality studies that
not English, it was not a controlled trial, or there were certain barrier creams, moisturizing creams, and use
less than 10 subjects. Also excluded were studies of softened fabrics are effective in preventing the
dealing with only one contact allergen and its spe- development of ICD. Fair-quality studies indicated
cific treatment, immediate hypersensitivity (type I) that short-term use of certain moisturizers and barrier
reactions, contact urticaria, or atopy. creams and use of cotton glove liners were effective.
The rationale for the decision to exclude the latter Educational interventions were less promising.
was that atopy represents a distinct clinical entity Barrier creams. Two good-quality43,44 and two
from CD, despite the fact that they may occur fair-quality47-52 studies found barrier creams to be
together. The incidence of allergic CD (ACD) super- effective in preventing ICD, and one good-quality
imposed on atopy remains controversial, with some study did not.40 Schliemann-Willers et al43 investi-
studies reporting no greater incidence of ACD gated the ability of pretreatment with different
among those with atopy than healthy participants. concentrations of perfluoropolyether phosphate
Conversely, the atopic response to irritants is in- (Fomblin HC/P2) in different gel bases to prevent
creased compared with control subjects.27-29 experimentally induced ICD to 4 different irritants.
Studies meeting eligibility criteria were then in- Results indicated that 5% HC/P2 was significantly
dependently abstracted by two authors (R. Q. and better than untreated control in preventing irritation
J. S.) using predetermined quality criteria, and (as measured by visual erythema scores, transepi-
were rated as good, fair, or poor (Appendix B). In dermal water loss [TEWL], and chromametry) from
J AM ACAD DERMATOL Saary et al 847
VOLUME 53, NUMBER 5

Table I. Available treatment and prevention methods for contact dermatitis evaluated in controlled trials
ACD ICD
Treatment method or substance
Steroids Bufexamac (Parfenac) 5% cream
Desonide 0.05% cream
Doxepin 5% cream
Short-term parenteral betamethasone sodium
phosphate 4.0 mg/mL
Short-term parenteral dexamethasone sodium
phosphate 4.0 mg/mL
Clobetasone butyrate 0.05% (Eumovate)
Clobetasol propionate 0.05%
Hydorcortisone 1%
Flumethasone pivalate
Mometasone furoate 0.1%
Betamethasone valerate 0.1% (od, bid)
Cutivate with 0.05% micronized fluticasone
propionate (alone of in combination with
Dermalex barrier cream)
Comparisons of different potencies of steroids
Nonsteroidal Cyclosporin (oral and topical) Cyclosporin (oral)
medication Doxepin cream 5% Doxepin cream 5%
Tacrolimus/FK506
Fomblin HC/P2 (perfluoropolyether phosphate)
SDZ ASM 981 (selective cytokine inhibitor)
Azathioprine
Indomethacin 2.5% in skin-base cream
Topical pentoxifylline
Barrier creams Hollister moisture barrier Hydrogel
Mentor shield skin Dimethicone
Hydropel Excipial protect (active ingredient
Uniderm aluminum chlorohydrate 5%)
Dermofilm
Emollients/ Locobase Locobase
lipids Lipid mixtures Locobase repair
Lipid mix and steroid Doublebase
Oil-in-water emulsion with 4% evening Ultrabase
primrose oil Diprobase
Ceridal lipogel
Petrolatum
Decubal
Essex
Oil-in-water emulsion with 4% evening
primrose oil
Cream containing urea 5% and
hydrogenated canola oil 5%
Other Subcutaneous hyposensitization and UVB Lipid mix and steroid
combined
UVB (total body and partial body) Sea water (Pacific Ocean)
Oral hyposensitization NaCl solution
Dietary restriction KCl solution
Organoclay MgCl2 solution
Extract of jewelweed CaCl2 solution
Dermapor semipermeable glove Dermapor semipermeable glove
Cotton glove liners Cotton glove liners
848 Saary et al J AM ACAD DERMATOL
NOVEMBER 2005

Table I. Cont’d
ACD ICD
Prevention method or substance
Barrier cream Dermashield Arretil
Hollister moisture barrier Aluminum chlorohydrate-containing cream
Mentor shield skin Hand sense
Hydropel Stoko emulsion
Uniderm Combinations of barrier and emollient creams
Dermofilm
Emollient/lipid Keri lotion, coconut, soy, sunflower, rape
seed, palm, palm kernel, palm and
rapeseed combination, fish oil, borage
oil, canola, shea butter, fractions of
unsaponifiable lipids from canola oil
and shea butter
Other Low molecular-weight heparin Fabrics treated with fabric softener
Topical pentoxifylline Substituting simple washing for brush washing
Nonlatex gloves Substituting emulsion cleansing for washing with soap
Ginkgo biloba pretreatment Pro-Q aerosol skin protectant
Quaternuim-18 bentonite Temperature of irritant or water
Topical skin protectanteemulsion of Educational interventions
Teflon polymer in perfluoroalkylpolyether Alpha hydroxyacids (glycolic, lactic,
tartaric acids and gluconolactone)

ACD, Allergic contact dermatitis; bid, twice a day; CaCl2, calcium chloride; ICD, irritant contact dermatitis; KCL, potassium chloride;
mg, milligram; MgCl2, magnesium chloride; mL, millilitre; NaCl, sodium chloride; od, once daily; UVB, ultraviolet B.

water-soluble irritants. The lack of efficacy of 2% containing 5% urea and 5% hydrogenated canola oil
HC/P2 against such irritants suggests a dose-re- in preventing experimentally induced ICD and
sponse effect although no interproduct comparisons found this cream to be significantly better than the
were made, only product versus untreated control. untreated control by both clinical and TEWL mea-
Zhai et al44 tested the ability of dimethicone skin sures. Four fair-quality studies also generally found
protectant lotion to prevent experimentally induced moisturizers to be beneficial.48,55,56,60
ICD as measured by visual scoring, TEWL, chroma- Fabric softener. The good-quality study of
metry, and laser Doppler flow. The dimethicone Pierard et al41 evaluated whether fabrics treated
lotion was significantly better than either vehicle- with fabric softener were less irritating than un-
treated or untreated control on 2 of 4 (visual, TEWL) treated fabrics to experimentally irritated and normal
parameters measured. Both of these studies were but sensitive skin. In this study, the intervention
conducted using healthy Caucasian volunteers, involved two repetitions of rubbing a wet towel
which may limit generalizability (ie, external valid- (treated with fabric softener or untreated) on the
ity). Conversely, Perrenoud et al40 demonstrated that forearm, then patting dry 3 times a day for 5 days.
a barrier cream containing aluminum chlorohydrate Results indicated better clinical ratings and improve-
as the active ingredient was ineffective in preventing ment in stratum corneum structure and barrier func-
ICD, and in fact was worse than a vehicle control on tion and hydration in skin exposed to fabrics treated
capacitance measures. with fabric softener (compared with untreated fabrics).
Moisturizers. Two good-quality studies exam- Although the study method may simulate towel use,
ined the role of moisturizers in the prevention of it may not be an adequate model of clothing wear.
ICD. Held and Agner35 examined the ability of both Educational strategies. No studies examining
high- and low-lipid content moisturizers to prevent educational criteria met good-quality criteria. Two
ICD and found that the high-lipid content moistur- fair-quality cohort studies49,50 examined the effec-
izer significantly prevented experimentally induced tiveness of educational interventions in preventing
ICD as measured by TEWL, capacitance, chromame- ICD. Among nursing home workers, participants in
try, and clinical scores, compared with a lower-lipid the intervention group scored higher on a quiz, and
content moisturizer that only showed a preventive showed greater change than the control group on 3
effect with capacitance measures. In 1997, Loden37 of 6 targeted areas for behavioural change. Self-
investigated the application of moisturizing cream reported symptoms were no different between
J AM ACAD DERMATOL Saary et al 849
VOLUME 53, NUMBER 5

Table II. Characteristics of studies abstracted

No. of
No. of articles No. of
titles and selected articles Study design/ Data abstraction Total No. of
abstracts for further meeting quality rating from G- or patients studied
Key question screened review criteria of articles F-quality articles* in G- or F-quality articles
Total treatment 413 131 49 RCT: 39 RCT: 23
search G/F/P:10/13/16 Cohort: 5
Cohort: 10
G/F/P:2/3/5
ICD prevention 16 632
ICD treatment 5 97
ACD prevention 5 291
ACD treatment 5 84

ACD, Allergic contact dermatitis; F, fair; G, good; ICD, irritant contact dermatitis; P, poor; RCT, randomized controlled trial.
*Column sum does not add to total because of some studies addressing either both ACD and ICD or both treatment and prevention.

groups, but clinical examination was significantly dryness by visual examination but no difference
different, although the examination was not blinded from control in either TEWL or erythema.
and was, thus, potentially biased particularly given None of the studies used quality of life or return to
the differing results between the assessors and a work as indicators of outcome.
blinded dermatologist.50 In a different study also
investigating an educational intervention in auxiliary Prevention of ACD
nurses49 no significant difference between interven- There were no studies with a good-quality rating
tion and control groups were found on either clinical that examined the prevention of ACD. Among the
or bioengineering (TEWL) measures). fair-rated studies there was a wide variety of inter-
Gloves. A fair-quality study by Ramsing and ventions tested.45,46,51,58,59 Two studies demon-
Agner54 found that occlusive glove use worsened strated that rhus dermatitis can be reduced in
bioengineering measures of ICD, and that use of a severity or prevented with quaternium-18-bentonite
cotton liner led to better results than a glove alone. (organoclay) lotion,51 and topical skin protectant
(an emulsion with perfluroalkylpolyether, similar to
Treatment of ICD Teflon [DuPont, Wilmington, Del]).58 The chelator
There is evidence from good-36-38 and fair-rated55 diethylenetriamine pentaacetic acid was effective in
studies that lipid-rich moisturizers are effective in the preventing and reducing the severity of patch tests to
short-term treatment of experimentally induced ICD. nickel, and preventing reactions to cobalt and cop-
Loden37 investigated the impact of applying a mois- per, but was ineffective against palladium and
turizing cream containing 5% urea and 5% hydroge- potassium.59 Brehler et al45 found pretreatment
nated canola oil to an experimentally induced ICD with pentoxifylline clinically ineffective in prevent-
site twice daily for 14 days. Barrier function (TEWL), ing nickel allergy reactions.
skin hydration, and clinical evaluations were all
significantly improved compared with an untreated Treatment of ACD
control site. The generalizability of these results is There were 4 good-quality studies that evaluated
limited to acute situations given the end point at 14 treatments for ACD.33,34,39,42 All studies evaluated
days. Loden and Andersson38 evaluated 9 different the effectiveness of various steroids including: fluti-
lipids and concluded that canola oil, its sterol- casone propionate .05% with or without barrier
enriched fraction, and hydrocortisone were the cream, clobetasone butyrate .05%, and clobetasol
only substances affecting the degree of irritation. propionate .05% (Dermoval). In studies by Hachem
Held et al36 also examined a variety of (6 different) et al,33,34 fluticasone propionate .05% was found to
moisturizers and found moisturizers generally effec- improve clinical and nonclinical outcomes com-
tive for both clinical and bioengineering measures, pared with control, and when combined with barrier
with lipid-rich moisturizers such as petrolatum cream, fluticasone improved nonclinical outcomes.
showing greater improvement than less lipid-rich Clinical outcome was improved by barrier cream
moisturizers. alone. Parneix-Spake et al39 found nonclinical out-
One other fair-quality study60 tested a moisturizer comes to be significantly better with clobetasone
applied to dry hands before gloving, and found less butyrate than either 1% hydrocortisone or untreated
850 Saary et al J AM ACAD DERMATOL
NOVEMBER 2005

Table III. Recommendations

Level of evidence Level of evidence
Maneuver Effectiveness for prevention* for treatment* Recommendation*
ICD prevention Barrier creams I-Good40,43,44 There is good-quality
and therapy 5% Perfluoropolyethers evidence to recommend
(Fomblin HC/P2) certain barrier creams for
Dimethicone skin the prevention of ICD,
protectant lotion recognizing some
Hand sense barrier limitations of
cream generalizability.
Excipal protect with I-Fair47,52 There is good evidence to
aluminum chlorohydrate recommend against the
use of aluminum
chlorohydrate-containing
barrier creams
High-lipid content There is good-quality
moisturizers evidence to recommend
Locobase I-Good35,37 the use of moisturizers
5% urea 1 5% hydrogenated I-Good36-38 with high lipid content
canola oil for both prevention and
Petrolatum I-Fair48,55,56,60 treatment of ICD,
Eucerin recognizing some
Palm fats I-Fair55,60 limitations of
Rapeseed in 3/4 measures generalizability
Canola
Stoko emulsion
prevent latex glove-
induced ICD in 3 of 5
measured (P \ .05)]
Fabric softening There is good-quality
Fabrics treated with I-Good41 evidence to recommend
fabric softener less softened fabrics to
irritating untreated prevent ICD, recognizing
fabrics significant limitations of
generalizability
Cotton liners There is fair-quality
Occlusive I-Fair54 evidence to recommend
glove use leads to the use of cotton glove
worse bioengineering liners to prevent ICD,
measures of ICD, recognizing some
and liners under an limitations of
occlusive glove generalizability
mitigate
ACD prevention Quaternium- I-Fair51 There is good-quality
and therapy 18-bentonite prevents evidence to recommend
rhus dermatitis certain allergen-specific
measures for the
prevention of ACD,
recognizing some
limitations of
generalizability
TSP prevents rhus dermatitis I-Fair58
DTPA prevents nickel, I-Fair59
copper, cobalt dermatitis
J AM ACAD DERMATOL Saary et al 851
VOLUME 53, NUMBER 5

Table III. Cont’d

Level of evidence Level of evidence
Maneuver Effectiveness for prevention* for treatment* Recommendation*
Moderate to potent steroids Good33,34,39,42 There is good-quality
- Fluticasone propionate I-Fair57 evidence to
- Clobetasol butyrate recommend the use of
- Clobetasol propionate moderate- to
high-potency steroids to
treat ACD, recognizing
some limitations of
generalizability
QOL and return No studies found The authors conclude there
to work is insufficient evidence to
recommend any
treatment to improve the
outcomes of return to
work and QOL

ACD, Allergic contact dermatitis; DTPA, diethylenetriamine pentaacetic acid; ICD, irritant contact dermatitis; QOL, quality of life; TSP, topical
skin protectant.
*See Appendix B for definitions of quality ratings.

control. Clobetasol propionate proved clinically bentonite can prevent rhus dermatitis and diethyl-
better than 1% hydrocortisone, and 2.5% indometh- enetriamine pentaacetic acid can prevent nickel,
acin and 5.0% bufexamac (Parfenac).42 However, chrome, and copper dermatitis. There is fair evi-
these good-quality studies have limited generaliz- dence that pentoxifylline is not effective in prevent-
ability because the majority of study participants ing nickel allergy.
were Caucasian female volunteers. Treatment of induced ACD. There is good-
Clobetasol propionate .05% was also evaluated in and fair-quality evidence that potent or moderately
one fair-rated study by Vernon and Olsen57 who potent steroids can treat ACD.
found it to be clinically effective in treating rhus
dermatitis compared with white petrolatum. Return to Work and Quality of Life
None of the studies used quality of life or return to No published studies were found examining these
work as indicators of outcome. outcomes, and as such there is insufficient evidence
to recommend that any treatment improves the
SUMMARY AND RECOMMENDATIONS outcomes of return to work and quality of life in CD.
ICD
Prevention. As shown in Table III, there is good- FUTURE RESEARCH
and fair-quality evidence that barrier creams con- Based on the results of this study, and the pro-
taining dimethicone or a high concentration of active cess undertaken to complete it, we recommend the
ingredients such as perfluoropolyethers, short-term following as research priorities in the area of CD
use of high-lipid content moisturizers, use of cotton generally and OCD specifically: (1) studies that
liners if occlusive gloves are worn, and use of assess the effectiveness of preventive measures for
softened fabrics can prevent the development of ACD, particularly generally applicable methods,
ICD. There is good-quality evidence that barrier rather than allergen-specific ways to prevent ACD;
cream containing aluminum chlorohydrate is not (2) studies evaluating treatments for chronic ACD
effective in preventing ICD. More research is re- and ICD; (3) studies designed to evaluate treatments
quired to evaluate educational interventions as pre- and preventive strategies in the real-world setting;
ventive strategies. (4) studies with a focus on return to work as an
Treatment of induced ICD. There is good- and outcome measure; (5) the use of nonsteroid medi-
fair-quality evidence that lipid-rich moisturizers can cations to treat ACD needs closer examination; and
effectively treat ICD. (6) studies of educational interventions.

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19. Lammintausta K, Kalimo K, Aantaa S. Course of hand derma- J. Objective assessment of topical anti-inflammatory drug
titis in hospital workers. Contact Dermatitis 1982;8:327-32. activity on experimentally induced nickel contact dermatitis:
20. Nethercott JR, Holness DL. Disease outcome in workers with comparison between visual scoring, colorimetry, laser Doppler
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1994;30:569-74. 1990;3:248-55.
21. Peter VK. Uber das schicksal der patienten mit gewerbeekzem 43. Schliemann-Willers S, Wigger-Alberti W, Elsner P. Efficacy of a
[The fate of patients with tissue eczema]. Dermatologica new class of perfluoropolyethers in the prevention of irritant
1968;136:236-56. contact dermatitis. Acta Derm Venereol 2001;81:392-4.
22. Rhodes EL, Warner J. Contact eczemaea follow-up study. Br 44. Zhai H, Brachman F, Pelosi A, Anigbogu A, Ramos MB, Torralba
J Dermatol 1966;78:640-4. MC, Maibach HI. A bioengineering study on the efficacy of a
23. Skog E, Tottie M. Occupational eczema causing disablement. skin protectant lotion in prevention SLS-induced dermatitis.
Acta Derm Venereol 1961;41:205-12. Skin Res Technol 2000;6:77-80.
24. Holness DL. Results of a quality of life questionnaire in a patch 45. Brehler R, Maurer O, Grabbe S, Schwarz T. Topically applied
test clinic population. Contact Dermatitis 2001;44:80-4. pentoxifylline has no effect on allergic patch responses. J Am
25. Rosen RH, Freeman S. Prognosis of occupational contact Acad Dermatol 1998;39:1017-21.
dermatitis in New South Wales, Australia. Contact Dermatitis 46. Di Nardo A, Giusti G, Mantovani L, Bianchi B, Seidenari S.
1993;29:88-93. Inhibition of elicitation of contact dermatitis in humans by
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mometasone furoate: evaluation by means of 20-MHz B 67. Drake LA, Millikan LE. The antipruritic effect of 5% doxepin
scanning associated with image analysis. Dermatology 1997; cream in patients with eczematous dermatitis. Arch Dermatol
195:137-41. 1995;131:1403-8.
47. Elsner P, Wigger-Alberti, Pantini G. Perfluoropolyethers in the 68. Epstein WL, Byers VS, Frankart W. Induction of antigen specific
prevention of irritant contact dermatitis. Dermatology hyposensitization to poison oak in sensitized adults. Arch
1998;197:141-5. Dermatol 1982;118:630-3.
48. Held E, Sveinsdottir S, Agner T. Effect of long-term use of 69. Goh CL, Gan SL. Efficacies of a barrier cream and an afterwork
moisturizer on skin hydration, barrier function and suscepti- emollient cream against cutting fluid dermatitis in metal-
bility to irritants. Acta Derm Venereol 1999;79:49-51. workers: a prospective study. Contact Dermatitis 1994;31:176-80.
49. Held E, Wolff C, Gyntelberg F, Agner T. Prevention of work- 70. Granlund H, Erkko P, Eriksson E, Reitamo S. Comparison of
related skin problems in student auxilliary nurses: an inter- cyclosporine and topical betamethasone-17, 21 dipropionate
vention study. Contact Dermatitis 2001;44:297-303. in the treatment of severe chronic hand eczema. Acta Derm
50. Held E, Mygind K, Wolff C, Gyntelberg F, Agner T. Prevention Venereol 1996;76:371-6.
of work related skin problems: an intervention study in wet 71. Grevelink SA, Murrell MA, Olsen EA. Effectiveness of various
work employees. Occup Environ Med 2002;59:556-61. barrier preparations in preventing and/or ameliorating exper-
51. Marks JG, Fowler JF, Sherertz E, Rietschel R. Prevention of imentally produced Toxicodendron dermatitis. J Am Acad
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quaternium-18 bentonite. J Am Acad Dermatol 1995;33:212-6. 72. Halkier-Sorensen L, Thestrup-Pedersen K. The efficacy of a
52. McCormick R, Buchman TL, Maki DG. Double-blind, random- moisturizer (Locobase) among cleaners and kitchen assistants
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containing lotion for protecting the hands of health care Dermatitis 1993;29:266-71.
workers. Am J Infect Control 2000;28:302-10. 73. Ingber A, Trattner A, Cohen I, Mekori Y. Low doses of low
53. Ohlenschlaeger J, Friberg J, Ramsing D, Agner T. Temperature molecular weight heparin in vivo inhibits the elicitation of
dependency of skin susceptibility to water and detergents. contact hypersensitivity. Acta Derm Venereol 1994;74:454-6.
Acta Derm Venereol 1996;76:274-6. 74. Kikuchi-Numagami K, Saishu T, Fukaya M, Kanazawa E, Tagami
54. Ramsing D, Agner T. Effect of glove occlusion on human skin H. Irritancy of scrubbing up for surgery with or without a
(II). Contact Dermatitis 1996;34:258-62. brush. Acta Derm Venereol 1999;79:230-2.
55. Ramsing D, Anger T. Preventive and therapeutic effects of 75. Lauharanta J, Ojajarvi J, Sarna S, Makela P. Prevention of dryness
and eczema of the hands of hospital staff by emulsion cleansing
a moisturizer. Acta Derm Venereol 1997;77:335-7.
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56. Schleimann-Willers S, Grieshaber R, Elsner P. Natural vegetable
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aerosol in treatment of contact dermatitis. Cutis 1978;21:108-10.
Dermatitis 2002;46:6-12.
77. Patterson SE, Williams JV, Marks JG. Prevention of sodium
57. Vernon HJ, Olsen EA. A controlled trial of clobetasol propio-
lauryl sulfate irritant contact dermatitis by Pro-Q aerosol foam
nate ointment 0.05% in the treatment of experimentally
skin protectant. J Am Acad Dermatol 1999;40:783-5.
induced rhus dermatitis. J Am Acad Dermatol 1990;23:829-32.
78. Pigatto PD, Bigardi S, Legori A, Altomare GF, Finzi AF. Are
58. Vidmar DA, Iwane MK. Assessment of the ability of the topical
barrier creams of any use in contact dermatitis? Contact
skin protectant (TSP) to protect against contact dermatitis to
Dermatitis 1992;26:197.
urushiol (Rhus) antigen. Am J Contact Dermatitis 1999;10:190-7.
79. Troost RJJ, Kozel MMA, van Helden-Meeuwsen CG, van Joost
59. Wohrl S, Kriechbaumer N, Hemmer W, Focke M, Brannath W,
T, Mulder PG, Benner R, Prens EP. Hyposensitization in nickel
Gotz M, Jarisch R. A cream containing the chelator DTPA
allergic contact dermatitis: clinical and immunologic monitor-
(diethylenetriaminepenta-acetic acid) can prevent contact
ing. J Am Acad Dermatol 1995;32:576-83.
allergic reactions to metals. Contact Dermatitis 2001;44:224-8. 80. Veien NK, Hattel T, Justesen O, Norholm N. Oral challenge with
60. Zhai H, Schmidt R, Levin C, et al. Prevention and therapeutic balsam of Peru. Contact Dermatitis 1985;12:104-7.
effects of a model emulsion on glove-induced irritation and 81. Wolf-Jurgensen P. Efficacy of bufexamac cream versus beta-
dry skin in man. Occup Environ Med 2002;50:134-8. methasone valerate cream in contact dermatitis: a double-
61. Barsky S. Clinical comparison of desonide cream with fluocin- blind trial. Curr Med Res Opin 1979;5:779-84.
onide cream in steroid-responsive dermatologic disorders.
Cutis 1976;18:826-30.
62. Bauer A, Kelterer D, Bartsch R, Schlegel A, Pearson J, Stadeler Appendix A. Search terms
M, et al. Prevention of hand dermatitis in bakers’ apprentices:
different efficacy of skin protection measures and UVB hard- Search 1: EMBASE \1980 to 2003[
ening. Int Arch Occup Environ Health 2002;75:491-9.
1. Contact dermatitis/dt
63. Berardesca E, Distante F, Vignoli GP, Oresajo C, Green B. Alpha
hydroxyacids modulates stratum corneum barrier function. Br 2. Controlled study/
J Dermatol 1997;137:934-8. 3. Clinical trial/
64. Berardesca E, Barbareschi M, Veraldi S, Pimpinelli N. Evaluation 4. Contact allergy/dt
of efficacy of a skin lipid mixture in patients with irritant contact 5. 1 or 4
dermatitis, allergic contact dermatitis or atopic dermatitis: a
6. 2 or 3
multicenter study. Contact Dermatitis 2001;45:280-5.
65. Berndt U, Wigger-Alberti W, Gabard B, Elsner P. Efficacy of a
7. 5 and 6
barrier cream and its vehicle as protective measures against 8. Limit 7 to (human and English language)
occupational irritant contact dermatitis. Contact Dermatitis
2000;42:77-80. Search 2: EMBASE \1980 to 2003[
66. Dickey R. Parenteral short-term corticosteroid therapy in 1. exp Eczema/
moderate to severe dermatoses. Cutis 1976;17:179-83. 2. Lichen simplex dermatitis.mp.
854 Saary et al J AM ACAD DERMATOL
NOVEMBER 2005

3. Shoe dermatitis.mp. 19. exp Engineering/

4. Latex contact dermatitis.mp. 20. exp Environment, controlled/ or environmental
5. Animal dermatitis.mp. control.mp.
6. Insect dermatitis.mp. 21. exp Protective clothing/ or exp protective de-
7. Chemical dermatitis.mp. vices/
8. Metal dermatitis.mp. 22. 16 or 17 or 18 or 19 or 20 or 21
9. Water dermatitis.mp. 23. 12 and 22
10. Plant dermatitis.mp. 24. Limit 23 to (human and English language and all
11. 3 or 4 or 5 or 7 or 8 or 10 adult \19 plus years[ and [controlled clinical
12. 1 or 11 trial or randomized controlled trial])
13. Treatment.mp. or therapeutics/
Search 5: EBM Reviews—Cochrane Central Register
14. Environmental scan.mp.
of Controlled Trials 2003
15. exp Questionnaires/
1. exp Dermatitis, allergic contact/ or exp dermati-
16. 13 or 14 or 15
tis, contact/
17. Prevention.mp. or exp primary prevention/
2. Limit 1 to randomized controlled trial
18. exp Education/
19. exp Engineering/
20. exp Environment, controlled/ or environmental
Appendix B. Criteria for rating individual studies*
control.mp.
21. exp Protective clothing/ or exp protective de-
GOOD—All the following are met:
vices/
Comparable groups assembled initially and main-
22. 16 or 17 or 18 or 19 or 20 or 21
tained throughout study OR body split-site design
23. 12 and 22
Interventions are clearly described
24. Limit 23 to (human and English language and
Important clinical and nonclinical outcomes are
article and adult \18-64 years[)
25. exp Controlled study/ or exp randomized con- considered
Outcome measurement is well described
trolled trial/
Outcome assessment is blinded
26. 24 and 25
Randomized control trial: intention-to-treat analysis
27. exp Randomized controlled trial/
Cohort: confounders/contaminants noted and cor-
28. 24 and 27
rected for
FAIR—One or more of the following occur, but none
Search 3: MEDLINE \1966 to 2003[
of the flaws listed in ‘‘poor’’ occur: Generally
1. exp Contact dermatitis/
2. Limit 1 to (human and English language and adult comparable groups
Only clinical or only nonclinical outcomes are con-
\19-44 years> and randomized controlled trial)
sidered
Measurement instrument acceptable, but not ideal
Search 4: MEDLINE \1966 to 2003[
(ie, scale not described); and generally applied
1. exp Eczema/
equally
2. Lichen simplex dermatitis.mp.
Randomized controlled trial: no intention-to-treat
3. Shoe dermatitis.mp.
analysis
4. Latex contact dermatitis.mp.
5. Animal dermatitis.mp. Cohort: some important confounders considered
and adjusted for in analysis (see above)
6. Insect dermatitis.mp.
Lack of blinding to outcome assessment or can not
7. Chemical dermatitis.mp.
tell
8. Metal dermatitis.mp.
POOR—One or more of the following fatal flaws
9. Water dermatitis.mp.
exist:
10. Plant dermatitis.mp.
Groups assembled are not comparable either initially
11. 3 or 4 or 5 or 7 or 8 or 10
or throughout the study, or can not tell
12. 1 or 11
13. Treatment.mp. or therapeutics/ Unreliable or invalid measurement methods, or
measures not applied equally, or can not tell
14. Environmental scan.mp.
Key confounders not addressed
15. exp Questionnaires/
Inadequate power to detect equivalency
16. 13 or 14 or 15
17. Prevention.mp. or exp primary prevention/
18. exp Education/ *As described by the US Preventive Services Task Force.30
J AM ACAD DERMATOL Saary et al 855
VOLUME 53, NUMBER 5

Appendix C. Bioengineering outcomes description

Electrical capacitance/corneometry Capacitance (measured on skin surface) is directly proportional to
water content of the horny layer of the skin. A plate capacitor,
which builds up an electrical field at its edges, is used to
measure capacitance.
Chromametry/colorimetry/spectrophotometry Measurement of skin redness/color, which indicates erythema
Echographic evaluation Skin thickness is measured or the difference in extent of area of
inflammation compared with a control
Laser Doppler flow This measures blood flow rate, which is an indicator of dermal
vascularity
Patch test Prevention of positivity or reduction in severity of allergic reaction
Squamometry Corneocytes are sampled using adhesive coated disks. The cells are
stained and then color measurements are made using image
analysis or chromametry (measuring reflected light).31
TEWL TEWL is a good indicator of skin barrier function. An evaporimeter,
consisting of a sensor placed 3 or 6 mm above the surface of the
skin, measures the amount of water loss by evaporation.
Damage to the skin will result in increased water loss.
Water sorption-desorption test This method involves hydrating the skin with water and then
observing the subsequent dehydration activity by means of
serial recording with electrical instruments. It is a useful tool to
measure the dynamic hydration of the skin and the stratum
corneum water-holding properties. Damage to the stratum
corneum reduces its ability to hold water.32
J AM ACAD DERMATOL 845.e1
VOLUME 53, NUMBER 5

Supplemental Table I. Quality assessment of randomized controlled trials in contact dermatitis

Comparable groups assembled initially
Outcome and maintained throughout study or body Important clinical and
assessment split-site design Outcome measurement Interventions are clearly nonclinical outcomes are
Study author(s), year published Quality rating blinded? Initial Maintenance is well described described considered ACD or ICD
Hachem et al, 200233 Good Y SS Y Y Y ACD
Held and Agner, 200135 Good Y SS Y Y Y ICD
Held, Lund, and Agner, 200136 Good Y SS Y Y Y ICD
Perrenoud et al, 200140 Good Y Y Y Y Y Y ICD
Schleimann-Willers, Wigger-Alberti, and Elsner, 200143 Good Y SS Y Y Y ICD
Zhai et al, 200044 Good Y SS Y Y Y ICD
Loden, 199737 Good Y SS Y Y Y ICD
Loden and Andersson, 199638 Good Y SS Y Y Y ICD
Pierard et al, 199441 Good Y SS Y Y Y ICD
Queille-Roussel et al, 199042 Good Y SS Y Y Y ICD
Zhai et al, 200260 Fair N SS Y Y Y ICD
Schliemann-Willers et al, 200256 Fair N SS Y Y Y ICD
Wohrl et al, 200159 Fair Y SS Y Y N ACD
McCormick et al, 200052 Fair Y Y Y Y Y N ICD
Held et al,199948 Fair N SS Y Y N ICD
Brehler et al, 1998445 Fair N SS Y Y N ACD
Elsner et al, 199847 Fair N SS Y Y Y ICD
Di Nardo et al, 199746 Fair N SS Y Y N ACD
Ramsing and Agner, 199755 Fair Y SS Y Y N ICD
Ohlenschlaeger et al, 199653 Fair N SS Y Y Y ICD
Ramsing and Agner, 199654 Fair N SS Y Y N ICD
Marks et al, 199551 Fair Y SS Y Y N ACD
Vernon and Olsen, 199057 Fair Y SS Y Y N ACD
Berardesca et al, 200164 Poor N Y Y Y N N ACD, ICD
Berndt et al, 200065 Poor Y N N Y N Y ICD
Kikuchi-Numagami et al, 199974 Poor N N N Y N ICD
Patterson et al, 199977 Poor N SS N Y N ICD
Berardesca et al, 199763 Poor Y SS Y Y Y ICD
Granlund et al, 199670 Poor Y N N Y Y N ACD
Drake and Millikan, 199567 Poor N N N Y Y Y ICD
Troost et al 199579 Poor N N N Y Y Y ACD
Halkier-Sorensen and Thestrup-Pedersen, 199372 Poor N N N Y Y Y ICD
Grevelink et al, 199271 Poor Y SS Y Y N ACD
Lauharanta et al, 199175 Poor Y Y N Y Y N ICD
Veien et al, 198580 Poor Y Y Y Y Y N ACD
Wolf-Jurgensen, 197981 Poor Y N N N Y N ACD, ICD
Medansky and Handler 197876 Poor Y N N N N N ACD, ICD
Barsky, 197661 Poor Y N N Y Y N ACD
Dickey, 197666 Poor Y Y Y N N N ACD
ACD, Allergic contact dermatitis; ICD, irritant contact dermatitis; N, no; SS, split site; Y, yes.
845.e2 J AM ACAD DERMATOL
NOVEMBER 2005

Supplemental Table II. Quality assessment of cohort studies in contact dermatitis

Comparable groups assembled initially

Outcome and maintained throughout study or Important clinical and
Confounders/Contaminants assessment: body split-site design Outcome measurement Interventions clearly nonclinical outcomes
Study authors, year published Quality rating considered? Blinded? Initial Maintenance well described described considered? ACD or ICD
Hachem et al, 200134 Good Y Y SS Y Y Y ACD
Parneix-Spake et al, 200139 Good Y Y SS Y Y Y ACD
Held et al, 200250 Fair Y N Y Y N Y N ICD
Held et al, 200149 Fair Y N Y Y Y Y Y ICD
Vidmar and Iwane, 199958 Fair Y N SS Y Y N ACD
Bauer et al, 200262 Poor Y N N N Y Y Y ICD
Goh and Gan, 199469 Poor N N N N Y Y Y ICD
Ingber et al, 199473 Poor N N N N Y Y N ACD
Pigatto et al, 199278 Poor Y N SS N Y N ACD
Epstein et al, 198268 Poor N Y N N Y Y N ACD

ACD, Allergic contact dermatitis; ICD, irritant contact dermatitis; N, no; SS, split site; Y, yes.
 J AM ACAD DERMATOL 845.e3
VOLUME 53, NUMBER 5

Supplemental Table III. Summary of results: Effect of preventive interventions on irritant contact dermatitis
Outcomes: All
Study author(s), Quality No. of outcomes
year published rating subjects Population Intervention considered Results* P value Comments: Strengths, weaknesses, EV
Perrenoud et al, Good 21 (5)† Apprentice Barrier cream (Excipal Protect) Clinical score NS Incl: At least 5 shampoos per day done without gloves
200140 hairdressers, applied to hands Tues-Sat × 4 (dryness, redness,
starting their 2nd wk, while subjects exposed to skin breaks): 0-9 Excl: Broken/oozing skin, open wounds, known allergies, use
year of studies; age irritants at work (eg, repeated Subjective NS of potent corticosteroids or any other tx that would interfere
16-30 y (20 female, shampooing, exposure to hair TEWL NS with the study
1 male) care products) Capacitance Higher in control vs treatment <.01
Chromametry NS
Control: Vehicle
Schleimann-Willers, Good 20 Healthy Caucasian Application of 0.05 mL of Clinical exam: Visual C: Lower vs control (LA) d.05 Excl: Skin disease
Wigger-Alberti, and volunteers; age various PFPE phosphate gels to (erythema)
Elsner, 200143 18-33 y (13 women, skin once daily (Mon-Fri week 1, Allowed to shower but prohibited from application of
E: Lower vs control (NaOH, week 1) d.05
7 men) Mon-Thurs week 2) detergents, moisturizers, or emollients, exposure to sun
beds/solar radiation during 12 d of investigation
Gels: F: Lower vs control (NaOH, week 1)
B: Gel base 1 (xanthan gum) as d.05 ICD: Induced by exposure to all of the following
placebo (at different sites):
SLS 5%
C: Gel base 1 + 2% HC/P2 1000 TEWL (g/m2/h) D: Lower vs control (SLS at day 5, 12) d.05 NaOH 0.5%
LA 20%
D: Gel base 1 + 5% HC/P2 1000 E: Lower vs control (SLS, day 5) d.05 TOL 100%

E: Gel base 2 (Carbomer) + 5% EV: Limited

HC/P2 1000 E: Lower vs control (NaOH week 1) d.05
F: Gel base 1 + 5% HC/P2 2000
E: Lower vs control (LA, week 1) d.05
Control:
Untreated
Gel base F: Lower vs control (SLS at day 5) d.05

F: Lower vs control (NaOH, week 1) d.05

Chromametry (a*) C: Lower vs control (LA) d.05

E: Lower vs control (SLS at day 5) d.05
E: Lower vs control (NaOH, week 1) d.05
F: Lower vs control (NaOH, week 1) d.05

Zhai et al, 200044 Good 12 Healthy Caucasian Application of dimethicone skin Clinical: Visual Less in treated vs untreated control <.01 Excl: None stated
volunteers age protectant lotion to test area
43.3 r 7.7 y before irritant exposure Less in treated vs. vehicle control <.05 ICD: Induced by SLS exposure
(7 women; 5 men)
Controls: Magnitude of test effect not stated
Untreated (ie, irritant only) TEWL (g/m2/h) Less in treated vs untreated controls at d.014
Vehicle day 5 EV: Limited
Less in treated vs vehicle control at day 5 <.05

Chromametry (a*) NS

Laser Doppler flow NS

(BFV)
Held and Agner, Good 19 (1)‡ Healthy Caucasian High lipid content moisturizer TEWL A higher vs control (day 8, 12) <.05 Excl: Hx/clinical signs of AD or CD
200135 volunteers; age (Locobase, A) vs moderate/low
24-58 y (15 women, lipid content moisturizer B vs control NS Prohibited: Use of other moisturizers on arms 7 d before or
4 men) (Decubal, B) applied tid × 5 d during study
before exposure to irritant Laser Doppler A vs control NS
ICD: Induced by SLS exposure
Control: Untreated B vs control NS
EV: Limited
Colorimetry (a*) A higher vs control (day 8, 12) <.05
Note: Results indicate that Locobase increases susceptibility
B vs control NS to irritants.
 845.e4 J AM ACAD DERMATOL
NOVEMBER 2005

Outcomes: All
Study author(s), Quality No. of outcomes
year published rating subjects Population Intervention considered Results* P value Comments: Strengths, weaknesses, EV
Clinical erythema A (1.3) vs control (0.8) <.001
(0-3)
B vs control NS

Loden, 199737 Good 13 Healthy subjects; Application of moisturizing TEWL (g/m2/h) Lower at cream-treated skin (12.4) vs <.01 Excl: Visible signs of skin disease; allowed to wash normally
age 24-58 y cream (5% urea and 5% control (19.7) but prohibited from using any other skin care products on
(10 women, hydrogenated canola oil) to arms
3 men) normal skin bid × 14 d; then
induction of irritation with 14% EV: Limited
SLS for 7 h Visual scoring: Sum Lower in cream-treated skin (11.1) than <.05
of 0-3 score for in untreated skin (26.4)
Control: Untreated erythema,
induration, and
vesiculation
expressed as % of
maximum
Pierard et al, 199441 Good 15 Healthy volunteers; Arm washed with wet softened Clinical Smoothness greater at ICD sites treated <.05 Incl: Sensitive skin (confirmed by exam and hx)
age 24-46 y towel for few seconds and then with softened towel (day 8)
patted dry with dry, softened Redness less at ICD sites treated with <.05 Excl: Acute skin disease (on exam), ACD to fabrics/materials
towel (repeated 3 ×/d, 2 ×/arm, softened towel (day 5) used in study
for 10 d) Dryness less at ICD sites treated with <.05
softened towel (day 5-8) ICD: Induced by SLS exposure
Control: Unsoftened towel
Dryness less at normal sites treated with Weakness: Poor model for simulation of wearing clothes
softened towel (day 8) <.05
EV: Limited
TEWL (g/m2/h) Lower at ICD sites treated with softened <.05
towel (day 5, 8)
Capacitance (AU) Higher at ICD sites treated with <.05
softened towel (day 5, 8)
Colorimetry (a*) Lower at ICD sites treated with softened <.05
towel (day 3-5)
Squamametry (c*) Lower at ICD sites treated with softened <.05
towel (day 3, 5, 8, 12)
Schliemann-Willers Fair 20 Healthy Topical application of natural fat Visual score (0-6) Soy B 2.55 d.05 Poorly defined incl/excl criteria: Acute induced ICD (to SLS)
et al, 200256 Caucasians; age bid (× 4 d) Rapeseed B 1.15 <.01
20-38 y Palm/rapeseed 1.10 d.01 Subjects permitted to shower but not bathe
(13 women, 7 men) Control: Untreated Use of detergents, moisturizers, emollients on back not
Palm A 1.30 d.01 permitted
Palm B 1.75 d.01 Exposure to sun beds, solar radiation discouraged
Palm D 1.90 d.01
Eucerin 0.05 d.01 EV: Limited
Petrolatum 0.10 d.01
vs Control 3.80
'TEWL Soy A 31.8 d.01
(g/m2/h)
Soy B 27.6 d.01
Rapeseed B 16.3 d.01
Palm/rapeseed 15.2 d.01
Palm A 14.9 d.01
Palm B 21.0 d.01
Palm C 30.0 d.05
Palm D 24.0 d.01
Eucerin 2.7 d.01
Petrolatum 2.8 d.01
vs Control 40.8

'Chromametry (a*) Rapeseed B 2.60 d.01

 J AM ACAD DERMATOL 845.e5
VOLUME 53, NUMBER 5

Outcomes: All
Study author(s), Quality No. of outcomes
year published rating subjects Population Intervention considered Results* P value Comments: Strengths, weaknesses, EV
Palm/rapeseed 2.34 d.01

Palm A 2.41 d.01

Palm B 3.09 d.01

Palm D 3.48 d.01

Eucerin 0.07 d.01

Petrolatum 0.07 d.01

vs Control 6.77

'Corneometry (AU) Palm A –3 d.05

Eucerin 3 d.01
Petrolatum 2 d.01
vs Control -11

Held et al, 200250 Fair 375|| Employees in elder Formalized educational Skin symptoms NS Excl: None stated
care homes; age program delivered to
19-62 y (342 “participatory team” of 10-20 Power analysis calculated to detect 20% improvement
women, 33 men) workers in each workplace. (clinical evaluation) in intervention group
They were then free to pass
information to other workers as Workplaces randomized to treatment or control
they wished.

Control: Workers at workplaces

where no educational
intervention was given

Clinical exam Greater reduction in symptoms in <.0002

(no, very mild, mild, treated group vs control (after 5 mo)
moderate, severe
symptoms)

Zhai et al, 200260 Fair 15 Healthy Caucasian Application of test emulsion to Dryness (visual) (0-4) NS Poorly defined incl/excl criteria
volunteers; age dorsum of hand before gloving,
|32-64 y (10 men, once daily, × 5 d Erythema (visual) NS EV: Limited
5 women) (0-4)
Control: Untreated Water sorption- Increased water holding capacity in <.05
desorption test treated subjects
TEWL (g/m2/h) Lower TEWL in treated subjects <.05
Capacitance (AU) Increased in treated subjects <.05

Held et al, 200149 Fair 107-13 Student auxiliary 2 × 2-h educational Clinical exam: Extent NS Excl: None stated
dropouts = nurses; age19-55 y interventions using video and of erythema or
94 (96 women, 11 booklets, covering topics of skin irritation (0-74) Good control for confounders
men) physiology, evidence-based Logistic regression
skin care program, plus
 845.e6 J AM ACAD DERMATOL
NOVEMBER 2005

Outcomes: All
Study author(s), Quality No. of outcomes
year published rating subjects Population Intervention considered Results* P value Comments: Strengths, weaknesses, EV
provision of free moisturizer TEWL NS Power analysis calculated on basis of TEWL values

Control: Student auxiliary

nurses who did not receive
educational intervention

Questionnaire: No. of NS
subjects reporting
skin problems
McCormick, Fair 54-2|| Hospital Liberal application of barrier Hand condition –2.1 points (6.5 o2.7) (treated) vs –3.8 .006 Excl: Hypersensitivity dermatitis, eczema, chronic skin
Buchman, and eliminated employees with cream (Hand Sense) to both (scaling, cracking, points (6.8 o 4.7) (control) diseases, work <20 h/wk (*)
Maki, 200052 = 52 long-standing, hands bid (4 wk) pain)
severe hand Confounders: Gloves, number of handwashings, antiseptic vs
irritation Control : Oil containing lotion regular handwash all noted. Lotion provided to all subjects
(Lubriderm) for use, ad libitum; however, amount used was noted. Also,
by end of study, control group washing hands more
Hand flora NS
frequently—any bias from this source should have favored
barrier cream.

Handwashing Control group washing frequency 50% .04 EV: Result generalizable to chronic dermatitis
frequency > treatment group at end of study
Held et al, 199948 Fair 20 Healthy volunteers; Locobase moisturizer to TEWL (g/m2/h) Higher in treated vs control (day 30) <.05 Excl: Hx/signs of dermatological disease, dry/scaly skin
age 21-57 y forearms tid × 27 d
(17 women, 3 men) Permitted to bathe/wash as usual
Control: Untreated
ICD: Induced by exposure to SLS

EV: Limited
Elsner et al, 199847 Fair 10 Healthy volunteers; Application of PFPE before Clinical examination: Lower for all PFPEs vs untreated control <.05 Irritants tested:
mean age 25.5 y exposure to irritant, once daily Erythema (0-5) (SLS, week 1) SLS
(7 male, 3 female) (Mon-Fri week 1, Mon-Thurs Lower for all PFPEs vs untreated control <.05 NaOH
week 2) (NaOH, week 1 and 2) LA
TOL
TEWL (g/m2/h) Lower for all PFPEs vs untreated control <.05
PFPEs tested: (SLS, week 1 and 2)
PFPE 0.5% EV: Limited
Lower for all PFPEs vs untreated control <.05
PFPE 1.0%
(NaOH, week 1 and 2)
PFPE 2.0%
PFPE 4.0%
Lower for PFPEs 4% vs untreated control <.05
(LA, day 12)
Controls:
Untreated Lower for PFPEs 4% vs untreated control <.05
Vehicle (TOL, day 5)
Chromametry (a*) Lower for all PFPEs vs untreated control
(SLS, week 1 and 2)

Lower for all PFPEs vs untreated control <.01

(NaOH, week 1 and 2)
Ramsing and Agner, Fair 12 Healthy volunteers; Application of moisturizer 15 TEWL (g/m2/h) Higher in control vs treated (day 3) .001 Excl: Skin disease
199755 age 25-56 y min before exposure to irritant
(11 women, 1 man) bid × 2d Laser Doppler Higher in control vs treated (day 3) .008 Subjects: Permitted to wash hands normally, ensuring that
flowmetry (BFV) both hands were equally exposed
Control: Some had immersion EC (AU) Lower in control vs treated (day 3) .002
regimen in sterile water at 20°C No other moisturizer permitted 12 h before and during study
period

Amount of moisturizer used (g) noted

Ohlenschlaeger Fair 10 Healthy female Forearm immersion in sterile TEWL (g/m2/h) NS No significant results as no signs of irritation developed
et al, 199653 volunteers; age water at 40°C for 10 min
21-49 y bid × 2 d EC (AU) NS EV: Limited
J AM ACAD DERMATOL 845.e7
VOLUME 53, NUMBER 5

Outcomes: All
Study author(s), Quality No. of outcomes
year published rating subjects Population Intervention considered Results* P value Comments: Strengths, weaknesses, EV
Spectrometry: NS Note: Another part of this study found a significantly higher
Erythema (a*) TEWL with immersion in SLS solution at 40°C compared with
20°C. This study did not meet our inclusion criteria (minimum
10 subjects).

Clinical exam: NS
Erythema, scaling
Ramsing and Agner, Fair 19 (1)|| A: Healthy women; Occlusive glove 6 h/d × 14 d TEWL (g/m2/h) Increased in gloved hand .0007 Excl: Previous hand eczema, anamnesis of AD, sensitized to
199654 age 24-55 y ubiquitous allergens
Control: Bare hand EC (AU) Higher on gloved hand (day 3 and 8) <.0083
but no significant difference day 11-14 Groups comparable with regard to age and gender.
Inflammation/ NS No mention was made of moisturizer use during study
erythema index
(spectrometry) EV: Limited
18 B: Healthy women; Cotton glove worn under TEWL (g/m2/h) Increased in gloved hand (no cotton) d.0077
age 20-48 y occlusive glove 6 h/d × 14 d from day 3 to 14
EC Increased in cotton-gloved hand, but .0066
Control: Gloved hand (no cotton significant only on day 11
glove) Inflammation/erythe NS
ma index
(spectrometry)

a*, balance between red (+ values) and green (– values); AD, Atopic dermatitis; AU, arbitrary unit; b*, the balance between yellow (+ values) and blue (– values); BFV, blood flow volume; bid, twice a day; c*, [(a*)2 + (b*)2]1/2; CD, contact dermatitis; EC, electrical capacitance; EV, external validity,
Excl, exclusions from study being discussed; HC/P2, fomblin HC/P2 (perfluoropolyether phosphate); Hx/hx, history; L*, luminance; LA, lactic acid; NaOH, sodium hydroxide; NS, no statistical significance;
PFPE, perfluoropolyether; SLS, sodium lauryl sulphate; TEWL, transepidermal water loss; tid, 3 times a day; TOL, toluene.
*For example, reduction in relative risk/absolute risk, number of events (treatment vs control).
†Five subjects dropped out for reasons not associated with the study.
‡One subject excluded for noncompliance.
§There were 88 dropouts from the study.
||One subject excluded because of development of dermatitis, day 3.
845.e8 J AM ACAD DERMATOL
NOVEMBER 2005

Supplemental Table IV. Summary of results: Effect of treatments on irritant contact dermatitis
Comments: Induction
Study author(s), Quality No. of Outcomes: All agent/technique, strengths,
year published rating subjects Population Intervention outcomes considered Results P value weaknesses, EV
Held, Lund, and Good 36 Healthy volunteers; age 18-58 y Application of moisturizer tid × 5 d; moisturizers tested: TEWL (g/m2/h) Lower for all moisturizers vs control; rank order (lowest <.05 Excl: Hand eczema, atopic dermatitis
Agner, 200136 (29 women; 7 men) Ceridal Lipogel, petrolatum, Locobase Repair, Locobase, TEWL to highest): petrolatum, Ceridal Lipogel,
Decubal, Essex Locobase, Locobase Repair, Essex, Decubal ICD: Induced by exposure to SLS
EC (AU) Higher for Ceridal Lipogel, petrolatum, Locobase <.05
Repair, and Decubal vs control EV: Limited
Laser Doppler Lower for Ceridal Lipogel, petrolatum, Locobase <.05
flowmetry (BFV) Repair, Locobase, and Decubal, vs control
Erythema index Lower for petrolatum, and Locobase Repair <.05
(spectrometry) (AU)
Clinical: Erythema Lower for Ceridal Lipogel, petrolatum, and Locobase <.05
Repair vs control
Clinical: Scaling Lower for Ceridal Lipogel, petrolatum, Locobase <.05
Repair, Decubal, and Essex vs control
Loden, 199737 Good 13 Healthy subjects; age 24-58 y A: Application of moisturizing cream (5% urea and 5% TEWL (g/m2/h) Lower in treated vs control from graph <.05 Excl: Visible signs of skin disease
(10 women, 3 men) hydrogenated canola oil) to ICD site bid × 14 d
Allowed to wash normally but
Control: Untreated prohibited from using any other skin
care products on arms
Skin hydration Higher in treated vs control (day 4-14) <.05
(corneometry) (AU) ICD: Induced by exposure to SLS
solution

EV: Limited
Clinical: Visual Treated (0) vs control (0) NS
evaluation (0-3) Done in conjunction with a
prevention study

B: Application of moisturizing cream (5% urea and 5% TEWL (g/m2/h) Treated (5.5 r 0.8) vs control (6.37 r 1.4) (day 14 only) <.01
hydrogenated canola oil) to normal skin bid × 14 d

Control: Untreated
Skin hydration Higher in treated vs control (day 1-14) <.05
(corneometry) (AU)

Clinical: Visual Not described N/A

evaluation (0-3)

Loden and Good 21 Healthy subjects; age 22-57 y Irritant-exposed skin treated with various topically applied Visible signs of Hydrocortisone vs control NS Excl: Visible signs of skin disease
Andersson, (14 women, 7 men) lipids × 17 h irritation Petrolatum vs control NS
199638 Fish oil vs control NS ICD: Induced by exposure to SLS
Control: Water
Borage oil vs control NS
Lipids: Hydrocortisone; petrolatum; fish oil; borage oil; EV: Limited
sunflower seed oil; canola oil; shea butter; fractions of Sunflower seed oil vs control NS
unsaponified lipids from canola oil and shea butter Canola oil vs control NS
Canola USF lower vs control <.05
Shea butter vs control NS
Shea USF vs control NS
Laser Doppler (skin Hydrocortisone lower vs control .0031
blood flow) Petrolatum vs control NS
Fish oil vs control NS
Borage oil vs control NS
Sunflower seed oil vs control NS
Canola oil vs control NS
Canola USF lower vs control .0004
Shea butter vs control NS
Shea USF vs control NS
TEWL Hydrocortisone lower vs control .0003
Petrolatum vs control NS
J AM ACAD DERMATOL 845.e9
VOLUME 53, NUMBER 5

Comments: Induction
Study author(s), Quality No. of Outcomes: All agent/technique, strengths,
year published rating subjects Population Intervention outcomes considered Results P value weaknesses, EV
Fish oil vs control NS
Borage oil vs control NS
Sunflower seed oil vs control NS
Canola oil lower vs control .0054
Canola USF lower vs control .0003
Shea butter vs control NS
Shea USF vs control NS
Zhai et al, 200260 Fair 15 Healthy Caucasian volunteers; Application of test emulsion to dorsum of hand before Dryness (visual) (0-4) Less in treated subjects <.05 Poorly defined incl/excl criteria
age 32-64 y with moderately gloving, once daily × 5 d Erythema (visual) NS
dry skin of hands (0-4) EV: Limited
Water sorption- <.05
desorption test (AU)
TEWL (g/m2/h) NS
Capacitance (AU) Not noted
Ramsing and Fair 12 Healthy volunteers; age 21-55 y Application of moisturizer to ICD-affected skin tid × 5 d TEWL (g/m2/h) Higher in control vs treated (day 5 of treatment) .012 Excl: Skin disease
Agner, 199755 (11 women, 1 man)
Laser Doppler NS ICD: Induced by exposure to SLS
flowmetry (BFV)
EC (AU) Lower in control vs treated (day 5 of treatment) .001 Subjects permitted to wash hands
normally, ensuring that both hands
were equally exposed

No other moisturizer permitted 12 h

before and during study period

Amount of moisturizer used (g) noted

AU, arbitrary unit; BFV, blood flow volume; bid, twice a day; EC, electrical capacitance; EV, external validity, Excl, exclusions from study being discussed; ICD, irritant contact dermatitis; incl, inclusion; LA, lactic acid; N/A, not applicable; NS, no statistical significance; SLS, sodium lauryl sulfate; tid, 3 times a day;
TEWL, transepidermal water loss; USF, unsaturated fat.
845.e10 J AM ACAD DERMATOL
NOVEMBER 2005

Supplemental Table V. Summary of results: Effect of preventive interventions on allergic contact dermatitis
Outcomes: All
Study authors, year Quality No. of outcomes
published rating subjects Population Intervention considered Results* P value Comments: Strengths, weaknesses, EV
Wohrl et al, 200159 Fair 45 45 adults with Application of DTPA before Prevention of pos 2.5% NiSO4: 1/28 pos vs 24/28 control <.0001 Well controlled; however, it was not explicitly stated
posi patch tests exposure to allergens (metal) patch test as 5% NiSO4:17/32 pos vs. 30/32 control .0005 that all subjects had Ni allergy.
to Ni, Co, Cu, determined by 1% CoCl2: 6/20 pos vs 19/20 control .001
Pd, r Cr (41 Controls ICDRG criteria 5% CuSO4: 5/14 pos vs 13/14 control .02 Excl: None stated
women, 4 men) Vehicle at patch test site 1% PdCl2: 16/23 pos vs 17/23 control NS
(pos control) KCr: 7/13 pos vs 9/13 control NS EV: Difficult to assess
Vehicle r DTPA Patch test readings at 72 h
Reduction in 2.5% NiSO4 vs pos control <.001 Clinically relevant end point
severity of patch test
reactions (absolute
No. of 3+ reactions)
5.0% NiSO4 vs pos control <.001

Hand flora NS

Handwashing Control group washing frequency 50% .04

frequency > treatment group at end of study
Vidmar and Fair 48 Healthy service Application of TSP before patch Clinical: Patch test 0.37 (treated) vs 2.39 (control) (ie, mean <.001 Excl: Pregnant, HIV+, atopic, significant dermatologic
Iwane,199958 members with testing with urushiol (Rhus reaction severity difference between treated and control condition (determined by investigator), allergic to
self-admitted antigen) (9 point scale from sites = –2.02, 95% CI: 2.18, –1.87) glycols/skin care products, systemic corticosteroids or
hx of poison 0-4, using 0.5 antihistamines within 1 mo, topical steroids on
ivy/oak ACD, Controls increments) arms/forearms within 2 wk, exposed forearms to
92% Caucasian; Pos control (untreated) sunlight to point of erythema within 7 d, sunburn
age 18-44 y Neg control (vehicle) anywhere within 1 mo, NSAID use within 14 d
(34 men, 14
women) Thorough screening process included hx, physical
exam, HIV and pregnancy testing

Patch test evaluation at up to 96 h (powered to

detect t0.2 point difference in score)

EV: Limited
Brehler et al, 199845 Fair 35-2† Volunteers with Pentoxifylline cream applied to Clinical score NS EV: Limited
history of Ni normal skin bid × 8 d (occluded (Rietschel)
contact on day 8) before exposure to Ni
hypersensitivity; patch
age 20-45 y
Control: Cream base

Di Nardo et al, Fair 22 Ni-sensitized MF applied to patch test site 16 Echographic CB vs control 1.38 ± 0.35 vs Not stated Patch test evaluation at 64.5 h
199746 women; age h and 40 h after Ni patch test evaluation (skin 1.68
18-45 y application (occluded) thickness in mm) CP vs control 1.23 ± 0.26 vs Not stated Both outcomes revealed MF to be significantly
1.68 different from all products tested, except CP;
Control: Untreated Ni patch HC acetate vs control NS however, no P values are reported. These data should
be interpreted with caution.
MF vs control 1.35 ± 0.39 vs Not stated EV: Limited
1.68
Image analysis CB vs control 1245 ± 2985 ?
(echo): ' in extent of
area of inflammation
compared with CP vs control 4090 ± 3143 ?
control echo
amplitude on an
arbitrary numerical HC acetate vs control 5275 ± 3052 ?
scale (0-255)
J AM ACAD DERMATOL 845.e11
VOLUME 53, NUMBER 5

Outcomes: All
Study authors, year Quality No. of outcomes
published rating subjects Population Intervention considered Results* P value Comments: Strengths, weaknesses, EV
MF vs control 3617 ± 3154 ?

Marks et al, 199551 Fair 144 Healthy Application of 5% quaternium-18 Clinical: Mean score Lower scores in treated vs control <.0001 Excl: Immunosuppressive disease/meds, topical
volunteers with bentonite lotion before patch on 0-7 scale steroid/other med application to test sites, pregnant,
hx of naturally testing with urushiol (Rhus Clinical: max scores Lower max scores in treated <.0001 nursing, significant cutaneous disorder, absent or
occurring ACD antigen) Clinical: No. with no 98 (68%) treated vs 1 (0.69%) control <.0001 questionable reaction at control site
to poison reaction
oak/ivy with Clinical: Time to Longer time to appearance of reaction <.0001
one episode in appearance of in treated vs control EV: Limited
past 5 y reaction
Control:
Untreated

', Change; CB, clobetasol butyrate; CI, confidence interval; CP, clobetasol propionate; DTPA, diethylenetriamine pentaacetic acid; EV, external validity; Excl, exclusions from study being discussed; HC, hydrocortisone; hx, history; ICDRG, International Contact Dermatitis
Research Group; max, maximum; MF, mometasone furoate; neg, negative; NS, no statistical significance; NSAID, nonsteroidal anti-inflammatory drugs; pos, positive; TSP, topical skin protectant.
*For example, reduction in relative risk/absolute risk, number of events (treatment vs control).
†Two subjects excluded for missing appointments.
845.e12 J AM ACAD DERMATOL
NOVEMBER 2005

Supplemental Table VI. Summary of results: Effect of treatments on ACD

Quality No of Outcomes: All outcomes Comments: Induction agent/technique,
Study authors, year published rating subjects Population Intervention considered Results P value strengths, weaknesses, EV
Hachem et al, 200233 Good 20 White, female volunteers 0.05% Micronized fluticasone TEWL (g/m2/h) Less in treated (day 4, ie, 6 h after treatment <.001 Excl: Active dermatitis, irritant dermatitis,
with Ni contact allergy propionate bid × 4 d (started 48 application) compared with untreated control atopic dermatitis
(confirmed before study); h after Ni patch application) SC hydration (capacitance Improved in vehicle control compared with .007
age 22-42 y [AU]) untreated (day 8), but no significant effect of ACD: Induced using Ni patch
Controls: Saline patch on treatment compared with either vehicle or
normal skin (neg control); untreated control EV: Limited
vehicle applied to Ni patch site Clinical score (sum of Lower in treated (day 7, 8) compared with <.014
(pos control); untreated Ni erythema [0-3], papulation untreated control
patch site (pos control) [0-3], itch [0-3])
Hachem et al, 200134 Good 14 Healthy, white, female Combination therapy A + B: TEWL (g/m2/h) Decreased in A + B vs untreated (day 5, 6, 8) <.009 A: Induced using Ni patch
volunteers with patch- A = 0.05% fluticasone
Decreased in A + B vs A (day 8) .002
confirmed Ni contact propionate, B = Dermalex Excl: Active dermatitis, irritant dermatitis,
allergy; age 24-36 y (barrier cream) applied bid Decreased in A + B vs B (day 5) .022 atopic dermatitis
(day 4-7)
Decreased in A vs B (day 8) .022 EV: Limited
Controls:
Untreated SC capacitance (AU) Increased in A + B vs untreated (day 6, 8) d.035
Only steroid (A)
Increased in A + B vs A (day 7, 8) .035
Only barrier cream (B)
Increased in B vs untreated (day 5-8) d.026
Increased in B vs A (day 6-8) d.019
Clinical score (sum of A + B (2.00) vs B (1.43) (day 7) .041
erythema [0-3], papulation
[0-3], itch [0-3])
B (1.43) vs A (1.86) (day 7) .038

B (1.43, 0.86) vs untreated (2.00, 1.07) (day 7, 8) d.031

Parmeix-Spake, Goustas, Good 18 Healthy female Immediately after patch test Clinical Visual: No significant difference in rate of NS Excl: Skin that would not allow accurate
and Green, 200139 volunteers with hx of Ni (48 h after application) 10 PL of healing evaluation (too dark, too much hair, too
ACD (confirmed by patch Eumovate (CB) 0.05% cream Patient rated pruritus NS many nevi, clinically significant
testing); age 18-45 y applied to test site, then bid for dermatosis), hx of hypersensitivity/allergy
7d to any drug incl study meds or their
TEWL (' from CB) HC 1% cream (–7.1; 95% CI: 11, –3.4) <.001 constituents, treatment with topical or
Controls: (g/m2/h) systemic corticosteroids within previous 4
Untreated Untreated (–8.5, 95% CI: 12, –4.9) <.001 wk, hx of alcoholism/drug abuse
Emollient base
HC 1% cream CB base (–2.8, 95% CI: 6.5, –0.8) NS Prohibited:
Use of concomitant medication
Colorimetry (' from CB) HC 1% cream NS (systemic/topical) during study that may
(AU) have affected outcome
Untreated (-1.5, 95% CI: 2.3, –0.7) <.001 Phototherapy/UV exposure

CB cream base NS A: Induced using Ni patch

Questionable validity of Physician Global

Assessment as outcome measure,
incompatible with blinded assessment

EV: limited
Queille-Roussel et al, 199042 Good 12 Healthy volunteers with Application of anti- Clinical: Visual (0-9) Dermoval showed improvement <.05 Excl: Local/systemic treatment
Ni contact allergy (based inflammatory agents (CP 0.05%, ('day7-day3)
on hx of pos patch test); HC 1%, indomethacin 2.5%, or A: Induced using Ni patch
age 21-38 y (11 women, bufexamac 5.0%) bid × 4.5 d
1 man) Note: Regression model demonstrated
Control: vehicle Colorimetry (a*) Dermoval showed improvement <.05 that the following were predictive of 'VS:
('day7-day3) –6.41 r 0.93 'a*
'L*
'b*
J AM ACAD DERMATOL 845.e13
VOLUME 53, NUMBER 5

Quality No of Outcomes: All outcomes Comments: Induction agent/technique,

Study authors, year published rating subjects Population Intervention considered Results P value strengths, weaknesses, EV
Colorimetry (L*) Dermoval showed improvement <.05 Log (SBF) (day 7)
('day7-day3) 3.16 r 0.75 Log (TEWL) (day 7)
TEWL (g/m2/h) NS Poor/incomplete reporting of results
('day7-day3)
Laser Doppler velocimetry Dermoval showed improvement <.05 EV: Limited
(SBF) –1.17 r 0.20
('day7-day3)

Vernon and Ohlsen, 199057 Fair 20 Subjects with Rhus CP ointment to patch-tested Erythema Less at CP 12 (day 4) v. control <.03 Excl: Pregnant, nursing, dermatitis in study
contact allergy; area (Rhus antigen) bid started area, topical steroids within 2 wk,
age 20-40 y at 12 (CP 12), 24 (CP 24), or 48 h Less at all sites (day 7-10) vs control <.01 immunosuppressed/systemic
(CP 48) after application of corticosteroids within 1 mo, atopic
patch; continued bid for Less at CP12 and CP 24 (day 14) vs control Not dermatitis, asthma, allergic rhinitis,
14 d stated immune disorder, diabetes mellitus
Induration/edema Less at all sites at day 7 vs control <.01
Control: White petrolatum EV: Limited
Less at CP 12 and CP 24 (day 14) Not
stated
Pruritus Less at CP 12 vs/ control (day 2) .05

Vesiculation Less at CP12 (from day 2-14) vs control <.05

Less at CP 24 (from day 4-14) v. control <.05

Less at CP 48 (from day 7-14) vs control <.05

', Change; 'VS, change in visual score; AU, allergenic unit; bid, twice a day; CB, clobetasol butyrate; CI, confidence interval; CP, clobetasol propionate; EV, external validity, Excl, exclusions from study being discussed; HC, hydrocortisone; hx, history; neg, negative; NS, no statistical significance; pos, positive;
SBF, skin blood flow; SC, stratum corneum TEWL, transepidermal water loss.