Journal of Dermatological Treatment

ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: https://www.tandfonline.com/loi/ijdt20

Effect of pine-tar bath on disease severity in

moderate-to-severe childhood eczema: an
investigator-blinded, crossover, randomized
clinical trial

Wing Gi Gigi Ng, Kam Lun Hon, Jeng Sum Charmaine Kung, Nam Sze Cheng,
Mark Jean-Aan Koh, Huaiqiu Huang, Vivian W. Y. Lee & Ting Fan Leung

To cite this article: Wing Gi Gigi Ng, Kam Lun Hon, Jeng Sum Charmaine Kung, Nam Sze
Cheng, Mark Jean-Aan Koh, Huaiqiu Huang, Vivian W. Y. Lee & Ting Fan Leung (2020): Effect
of pine-tar bath on disease severity in moderate-to-severe childhood eczema: an investigator-
blinded, crossover, randomized clinical trial, Journal of Dermatological Treatment, DOI:
10.1080/09546634.2020.1732284

To link to this article: https://doi.org/10.1080/09546634.2020.1732284

Accepted author version posted online: 18

Feb 2020.
Published online: 16 Apr 2020.

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JOURNAL OF DERMATOLOGICAL TREATMENT
https://doi.org/10.1080/09546634.2020.1732284

ARTICLE

Effect of pine-tar bath on disease severity in moderate-to-severe childhood

eczema: an investigator-blinded, crossover, randomized clinical trial
Wing Gi Gigi Nga, Kam Lun Hona , Jeng Sum Charmaine Kunga, Nam Sze Chenga, Mark Jean-Aan Kohb,
Huaiqiu Huangc, Vivian W. Y. Leed and Ting Fan Leunga
a
Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong; bDepartment of Dermatology, KK Women’s and
Children’s Hospital, Singapore; cDepartment of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University,
Guangzhou, Guangdong, China; dCLEAR - Centre for Learning Enhancement And Research, The Chinese University of Hong Kong, Shatin,
Hong Kong

ABSTRACT ARTICLE HISTORY

Background: Atopic dermatitis (AD) is a chronic inflammatory disease associated with pruritus and Received 14 November 2019
sleep loss. Pine-tar has long been used for various chronic skin conditions in which its polycyclic aro- Accepted 14 February 2020
matic hydrocarbon (PAH) component is anti-inflammatory and its resin acids antiseptic. The null
KEYWORDS
hypothesis of this trial is that there is no difference in clinical efficacy between a pine-tar product and
Pine-tar; atopic dermatitis;
its vehicle for AD. bathing; crossover;
Methods: A 3-month, investigator-blinded, crossover, randomized control trial (RCT) was conducted in randomized clinical trial
which each patient was assigned to bathing with pine-tar bath oil for one month and vehicle bath oil
for another, with a washout period of 1-month in-between. Acceptability and efficacy of the bath
products were measured. Disease severity scores (scoring atopic dermatitis (SCORAD) and patient-ori-
ented eczema measure (POEM), quality of life questionnaires, noninvasive skin biophysiological meas-
urements, blood IgE levels, and Staphylococcus aureus (SA) colonization status were assessed before
and following bathing.
Results: Significant improvements were found in total SCORAD (p ¼ .030), POEM (p ¼ .004), SA colon-
ization status (p ¼ .002), and log-transformed IgE level (p ¼ .009) among patients who bathed with
pine-tar in the overall RCT study using intention-to-treat analysis. For per protocol analysis, significant
improvements were found in total SCORAD (p ¼ .024), objective SCORAD (p ¼ .011), extent (p ¼ .014),
intensity (p ¼ .032), pruritus (p ¼ .047), POEM (p ¼ .044), SA colonization status (p ¼ .035), and log-trans-
formed IgE level (p ¼ .028). Acceptability to both bath-oils was good, and no product-related serious
adverse events were recorded.
Conclusions: Bathing with pine-tar is an efficacious and recommendable adjuvant practice for AD
patients. Disease improvement is associated with reduction of SA and IgE.

Introduction
Eczema or atopic dermatitis (AD) is a common childhood skin dis-
ease associated with impaired quality of life (1,2). Baseline treat-
ment includes regular emollient usage and the proactive usage
of topical corticosteroid and immunomodulating agents during
disease quiescence and flares (1–4). Pine tar is derived from pine
and claimed to contain anti-inflammatory and antibacterial ingre-
dients (5). Pine tar and other tar products had limited popularity
in previous time due to uncertain carcinogenic properties; how-
ever, manufacture process, pine tar is purified to remove toxic
and carcinogenic components in the modern manufacture pro-
cess. It is suggested that the high polycyclic aromatic hydrocar-
bon (PAH) content of tars could be one of the active ingredients
that contribute to anti-inflammatory effects and skin barrier repair
in AD (5–7). In a pilot study, a proprietary bath oil containing
pine tar was efficacious in reducing AD severity (8). It is noted
that parents are very receptive to daily showering and bathing
despite inconsistency with topical treatment. Hence, bathing
could offer an alternative therapy for repairing the skin barrier,
inflammation, and infections associated with AD. The null hypoth-
esis of this randomized trial is that there is no difference in clin-
ical efficacy between a pine tar product and its vehicle for
childhood AD.
Materials and methods
Subject recruitment and study design
This randomized control trial (RCT) study is a 3-month, investiga-
tor-blinded, randomized, crossover, clinical trial. Patients
(4–18 years old) suffering from AD were recruited from the pedi-
atric dermatology clinic at a university-affiliated teaching hos-
pital. Diagnosis of AD was made according to criteria (9). AD
disease severity was assessed using SCORAD (10,11). Patients
with moderate-to-severe disease were recruited. Exclusion crite-
ria included any current or recent use (within past four weeks)
of systemic antibiotic and steroid preparations, patients on
phototherapy or systemic immunosuppressants, and coexisting
skin diseases other than AD. Results from our pilot study

CONTACT Kam Lun Hon ehon@hotmail.com Department of Paediatrics, The Chinese University of Hong Kong, 6/F, Clinical Sciences Building, Prince of
Wales Hospital, Shatin, Hong Kong
ß 2020 Taylor & Francis Group, LLC
2 W. G. G. NG ET AL.
Figure 1. Study design flow chart of randomized crossover trial.
demonstrated that a sample size of 34 was needed for a cross-
over RCT (8). Together with considerations from drop-outs, we
recruited 40 patients for this RCT. Informed written consent was
obtained before recruitment.
Following recruitment, patients were randomly assigned to
treatment first or vehicle first group. Subjects were evaluated
every four weeks at follow-up visit (Figure 1, see study design).
Randomization was carried out by the pharmacy research staff
not involved in this RCT study, using a computerized program. The
study design is a 3-month, investigator blinded, crossover, RCT. For
every patient recruited, he/she would be randomly assigned to
bathing with one of the two study products for four weeks. After a
4-week washout period, the recruited subject would be provided
with the other study product for another four weeks. He/she would
have a follow-up visit every four weeks for clinical evaluations.
Subjects were asked not to use any new medications other
than their usual treatments, including moisturizers, mometasone
furoate 0.1% daily, chlorpheniramine 4 mg or cetirizine 10 mg
daily as topical corticosteroid and oral antihistamine on a prn
basis, respectively. The amount of medication usage was
recorded; disease severity, quality of life, skin biophysiological
parameters, Staphylococcus aureus (SA) colonization status. Blood
markers were only measured for the first two visits phase 1 to
limit the number of blood-taking. Measurement of skin parame-
ters in both study arms was performed after the subjects had
acclimatized in the consultation room for 10–20 min. Patient
acceptability of treatment and adverse events such as allergic
reactions and compliance to treatment were recorded for
both studies.
Studied products
Pine-tar bath oil (Pinetarsol, pine-tar 2.3% w/w, Ego
Pharmaceuticals, Braeside, Australia) and QV bath oil were pro-
vided by Ego Pharmaceuticals (Braeside, Australia) as a vehicle
bath oil for the study. Ingredients of the pine-tar bath oil
included the active ingredient pine-tar (2.3% w/w), and exci-
pients (paraffin-light liquid, laureth-3, isopropyl myristate,
baniaddas 17454(PI) and solvent green 3 CI61656).
Compositions of the vehicle bath oil include paraffinum
liquidum, laureth-3, and isopropyl myristate.

Figure 2. A sample of bath oil repackaged in brown medicinal bottles (210 mL/bottle) by the pharmacy colleagues with measuring cup.
The two bath oils had comparable formulations, except the
active pine-tar ingredients and artificial colorings. Subjects were
provided with adequate amount of bath oil in unrecognizable
packaging (Figure 2). Subjects were instructed to bathe at a
30 mL bath oil þ 100 L warm water concentration, for 15 min
daily for four weeks.
Disease severity scores and quality of life questionnaires
Scoring atopic dermatitis (SCORAD) was used by the investiga-
tor to measure AD severity and served as the primary outcome
measurement of our study (10,12). The Nottingham Eczema
Severity Score (NESS) and patient-oriented eczema measure
(POEM) were long- and short-term disease severity scores,
respectively, while the Children’s Dermatology Life Quality Index
(CDLQI) questionnaire and Pediatric Allergic Disease Quality of
Life Questionnaire (PADQLQ) were dermatological and general
allergy quality of life questionnaires, respectively (9,11,13–15).
These self-reported scores were completed by patients/care-giv-
ers during clinical visits without disclosure to the principal
investigator.
JOURNAL OF DERMATOLOGICAL TREATMENT 3
Skin biophysiological measurements
Skin hydration (SH, in arbitrary unit, a.u.), transepidermal water
loss (TEWL, in g/m2/h) and erythema (a.u.) were measured by
MoistureMeterSC, Vapometer, and SkinColorCatch (Delfin
Technologies Ltd., Kuopio, Finland), respectively (16–18). All of
these noninvasive measurements were taken both at the right
antecubital fossa and the most severe lesional site of the sub-
ject during clinical visits.
Skin swab for S. aureus colonization status
Skin swabs (Copan Innovation, Brescia, Italy) were used to esti-
mate the level of S. aureus growth on skins of recruited subjects
at the right antecubital fossa and the most severe lesional site
and were sent for bacterial culturing. S. aureus growth of the
patients was semi-quantified into four grades, including ‘no
growth’, ‘scanty growth’ (defined as with <104 colony-forming
units per mL), ‘moderate growth’ (104 to 105) and ‘heavy
growth’ (>105) (19,20).
Blood biomarkers measurement
Five milliliters of peripheral blood was drawn from recruited
patients before and after phase 1 treatment. Serum IgE level
4 W. G. G. NG ET AL.

Table 1. Patient demographics of the pine-tar bath RCT study (N ¼ 39). (Table 1). Equal number of patients were allocated to the two
Patient information Mean (SD) Median (IQR) arms. No statistically significant differences were found between
Sex (%) 22 (56.4) male the two groups at baseline by Mann–Whitney’s U test. Thirty-
17 (43.6) female nine subjects successfully completed the 3-month trial.
Age (years) 11.1 ± 4.1 10.9 (7.8–15.0)
SCORAD
Obj. SCORAD 33.9 ± 14.7 32.3 (20.5–43.6) Disease severity changes by SCORAD
Total SCORAD 43.9 ± 16.3 43.8 (29.5–55.1)
Disease extent 37.9 ± 23.6 34.0 (16.0–58.0) After 4-week treatment (phase 1), group 1 patients who used
Disease intensity 7.5 ± 2.9 7.0 (5.0–9.0) pine tar bath oil had a median reduction of objective SCORAD
POEM 16.1 ± 6.8 18.0 (10.0–21.0) by 8.5, reducing from 39.9 (21.5–47.3) to 31.4 (16.6–44.7),
NESS 11.5 ± 2.3 12.0 (10.0–13.0)
CDLQI 8.4 ± 5.1 7.0 (4.0–12.0) p ¼ .03, whereas median score of group 2 patients were 26.8
PADQLQ 27.4 ± 22.4 23.0 (7.0–41.0) (20.4–41.6) at baseline and 26.9 (13.9–48.6) at week 4 (p ¼ .334).
Skin hydration (SH) (a.u.) During phase 2, group 1 patients who were given vehicle bath
At right antecubital fossa 24.5 ± 18.8 18.4 (9.8–30.0) oil in this phase showed an increased median objective
At most severe site 12.1 ± 12.3 6.7 (3.3–13.9)
Transepidermal water loss (TEWL) (g/m2/h)
SCORAD score from 32.3 (16.1–46.8) to 40.5 (15.1–47.1) in
At right antecubital fossa 9.9 ± 6.4 9.0 (6.6–10.8) 4 weeks. Group 2 patients who used pine-tar bath oil showed
At most severe site 14.7 ± 7.9 13.7 (9.0–19.0) only a slight decrease in median objective SCORAD from 24.0
Erythema (a.u.) (19.3–46.5) to 23.7 (17.0–41.0). Changes in both groups did not
At right antecubital fossa 411.2 ± 13.0 410.0 (405.0–421.0)
reach statistical significance in phase 2 (Table 2).
At most severe site 416.9 ± 13.3 414.0 (408.0–427.0)
S.A. colonization status (N ¼ 38) (%) Baseline patient demographics between the two groups
At right antecubital fossa after randomization were statistically insignificant using
No growth 15 (39.5%) Mann–Whitney’s U test (e.g. p ¼ .879 for sex; p ¼ .923 for age).
Scanty growth 18 (47.4%) Overall by intention-to-treat (ITT) approach, patients using
Moderate growth 4 (10.5%)
Heavy growth 1 (2.6%) pine-tar bath oil for four weeks experienced a reduction in
At most severe site mean objective SCORAD from 33.3 ± 15.4 to 30.5 ± 16.1
No growth 17 (44.7%) (p ¼ .057) while using vehicle bath oil for four weeks experi-
Scanty growth 15 (39.5%) enced a reduction in mean objective SCORAD from 32.0 ± 15.5
Moderate growth 6 (15.8%)
Heavy growth 0 (0%)
to 31.1 ± 16.5 (p ¼ .542). Besides, total SCORAD showed a signifi-
Blood markers of atopy cant reduction from 42.8 ± 17.1 to 38.8 ± 18.9 (p ¼ .03) in the
Eosinophil % (N ¼ 36) 8.4 ± 5.5 7.5 (4.0–11.0) pine-tar group but an insignificant change of 40.5 ± 17.6 to
IgE (IU/mL) (N ¼ 37) 4662.0 ± 8795.8 1527.5 (556.3–4978.0) 39.6 ± 18.4 in the vehicle bath group (p ¼ .632). Reduction in
Log [IgE] (N ¼ 37) 3.1 ± 0.9 3.1 (2.7–3.7) pruritus intensity was found in the pine-tar group with a p value
reaching statistical significance (p ¼ .054) while no improvement
was observed in the vehicle group (p ¼ .480) (Table 3).
Per protocol (PP) approach refers to the analyzing of data
was measured by micro-particle immunoassay (IMx analyzer, contributed by subjects with no protocol deviations. A total of
Abbott Laboratories, Chicago, IL) and eosinophil count was per- 18 patients were recorded with protocol deviations. These
formed by the coulter STKS counter (Beckman Coulter, Miami, included: bathed less than four times per week (N ¼ 4), did not
FL) (19,21,22). bath in one whole week (N ¼ 3), stopped bathing (N ¼ 3), used
Traditional Chinese Medicine (TCM) (N ¼ 1), saw doctor in the
Chinese Mainland (N ¼ 1), shower instead of bath (N ¼ 3), missed
Statistical analysis one follow-up (N ¼ 1), used extra anti-septic bathing material
Numerical data were expressed as the mean and standard devi- (N ¼ 1), bathed with basin not large enough (N ¼ 1). Therefore,
ation or median and interquartile range (IQR) Paired t-test or only data from the 21 patients without protocol deviation were
Wilcoxon’s signed-rank test was used to assess pre- and post- used for analysis by PP approach. For pine tar group, median
treatment differences as appropriate and Mann–Whitney’s U test objective SCORAD score decreased from 23.4 (17.3–42.4) to 20.1
was used to compare between group differences. All compari- (14.4–36.4) (p ¼ .011). Total SCORAD score decreased from 35.8
sons were two-tailed, and p values less than .05 were consid- (27.3–52.8) to 25.1 (19.6–43.7) (p ¼ .024). Other components of
ered statistically significant. The statistical analyses were made objective SCORAD (i.e. disease extent and disease intensity) and
with SPSS for Windows 25.0 (IMB Corp., Armonk, NY). Ethical pruritus level were also found to be significantly improving in
approval was obtained from the Joint Chinese University of the pine-tar group (p ¼ .014; p ¼ .032; p ¼ .047, respectively). On
Hong Kong-New Territories East Cluster Clinical Research Ethics the other hand, disease severity was found worsened in all com-
ponents of SCORAD except the level of sleep loss when patients
Committee (ref. CREC: 2017.399, August 24, 2017).
experienced using vehicle bath oil though all these changes did
not reach statistical significance (Table 4). Characteristics of the
Results two treatment groups were the same during analysis using the
Patient demographics ITT or PP analysis approach.

From January 2018 to October 2018, 43 patients were being

Self-reported disease severity score: POEM
assessed for eligibility at the pediatrics outpatient clinic. Forty
patients (22 males, 18 females) with a median age of 10.9 (IQR: Group 1 patients experienced a significant reduction in POEM in
7.8–15.0) were recruited and entered the randomization phase phase 1 with a median score dropping from 18.0 (11.0–20.8) at
Table 2. Clinical characteristics of the two treatment groups in 3 months (median IQR).
Group 1 (pine tar first) (N ¼ 20) Group 2 (vehicle first) (N ¼ 19)
Visit 1 Visit 2 Visit 3 Visit 4 Visit 1 Visit 2 Visit 3 Visit 4
Disease severity
Objective SCORAD 39.9 (21.5–47.3) 31.4 (16.6–44.7) 32.3 (16.1–46.8) 40.5 (15.1–47.1) 26.8 (20.4–41.6) 26.9 (13.9–48.6) 24.0 (19.3–46.5) 23.7 (17.0–41.0)
Total SCORAD 47.7 (33.3–57.1) 39.2 (22.6–52.8) 37.8 (23.2–54.8) 50.0 (21.1–53.6) 37.0 (25.0–46.6) 34.3 (22.7–55.6) 33.4 (27.9–55.5) 31.7 ()23.0–54.5
POEM 18.0 (11.0–20.8) 12.5 (8.0–17.0) 9.5 (6.0–19.0) 15.0 (3.5–12.0) 15.0 (10.0–22.0) 13.0 (8.0–22.0) 15.0 (9.0–19.0) 14.0 (7.0–18.0)
Skin measurements at right anterior fossa
SH 16.8 (7.7–27.9) 19.6 (9.6–31.6) 12.4 (9.8–24.5) 17.5 (11.0–32.0) 21.6 (12.8–40.3) 18.3 (11.6–30.7) 22.2 (13.0–41.0) 21.2 (11.2–28.8)
TEWL 8.3 (6.3–10.5) 7.3 (6.4–12.2) 9.5 (6.1–11.6) 8.9 (7.3–13.9) 9.9 (7.1–12.6) 8.3 (6.0–13.8) 9.1 (6.0–15.2) 9.8 (8.2–13.2)
Erythema 409.5 410.0 411.0 411.0 410.0 404.0 405.5 409.0
(406.5–418.5) (404.0–419.0) (402.0–420.0) (399.3–415.0) (404.0–424.0) (402.0–413.0) (401.3–410.3) (404.0–421.0)
Skin measurements at most severe site
SH 6.5 (3.2–11.6) 8.0 (4.8–21.1) 6.5 (4.8–16.5) 10.5 (4.2–17.4) 10.0 (4.8–26.0) 9.6 (4.8–14.8) 14.1 (4.8–21.7) 9.7 (4.9–21.6)
TEWL 13.6 (9.5–19.7) 12.1 (10.1–15.4) 12.7 (9.8–14.8) 14.3 (11.8–16.6) 13.7 (7.6–18.4) 15.5 (11.4–19.5) 9.1 (6.0–15.2) 15.0 (11.7–20.5)
Erythema 416.5 421.0 415 422.0 413.0 418.0 405.5 417.0
(406.8–418.5) (409.0–426.0) (403.0–427.0) (404.0–432.0) (408.0–427.0) (410.0–428.0) (401.3–410.3) (408.0–430.0)
Blood markers
IgE 2220.0 1640.0 – – 1273.5 966.0 – –
(643.0–6057.0) (651.0–7000.0) (369.0–4239.5) (377.8–4869.8)
Log IgE 3.4 (2.8–3.8) 3.2 (2.8–3.8) – – 3.1 (2.6–3.6) 3.0 (2.6–3.7) – –
Eosinophils 7.0 (4.8–13.5) 5.0 (3.0–11.0) – – 7.5 (3.5–10.3) 6.0 (2.8–10.5) – –
Quality of life
CDLQI 6.5 (4.0–11.0) 6.5 (4.3–10.0) 6.0 (3.3–11.0) 9.0 (3.5–12.0) 8.0 (6.0–14.0) 8.0 (4.0–10.0) 8.0 (4.0–11.0) 7.0 (3.0–10.0)
PADQLQ 27.0 (6.3–47.8) 28.0 (12.3–52.8) 35.0 (16.3–82.5) 16.5 (8.3–46.0) 22.0 (7.0–37.0) 21.0 (14.0–33.0) 47.0 (20.0–63.0) 17.0 (7.0–27.0)
S. aureus colonization status at right antecubital fossa
No growth 8 (40.0%) 14 (70.0%) 12 (60.0%) 12 (60.0%) 7 (36.8%) 13 (68.4%) 10 (52.6%) 14 (73.7%)

JOURNAL OF DERMATOLOGICAL TREATMENT

Scanty growth 9 (45.0%) 6 (30.0%_ 7 (35.0%) 7 (35.0%) 9 (47.4%) 5 (26.3%) 6 (31.6%) 3 (15.8%)
Moderate growth 2 (10.0%) 0 (0.0%) 0 (0.0%) 1 (5.0%) 3 (15.8%) 1 (5.3%) 2 (10.5%) 2 (10.5%)
Heavy growth 1 (5.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)) 0 (0.0%) 0 (0.0%) 1 (5.3%) 0 (0.0%)
S. aureus colonization status at most severe site
No growth 11 (55.0%) 13 (65.0%) 13 (65.0%) 12 (60.0%) 8 (42.1%) 10 (52.6%) 10 (52.6%) 15 (78.9%)
Scanty growth 8 (40.0%) 6 (30.0%) 5 (25.0%) 6 (30.0%) 6 (31.6%) 7 (36.8%) 8 (42.1%) 3 (15.8%)
Moderate growth 1 (5.0%) 0 (0.0%) 1 (5%) 1 (5.0%) 5 (26.3%) 2 (10.5%) 1 (5.3%) 0 (0.0%)
Heavy growth 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (5.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (5.3%)

5
6 W. G. G. NG ET AL.

Table 3. Primary and secondary outcome changes in two groups by intention-to-treat approach (N ¼ 39).
Pine-tar bath oil (N ¼ 39) Vehicle bath oil (N ¼ 39)
Pre Post p Value Pre Post p Value
Physician evaluated disease severity score (SCORAD)
Obj. SCORAD 33.3 ± 15.4 30.5 ± 16.1 .057 32.0 ± 15.5 31.1 ± 16.5 .542
Total SCORAD 42.8 ± 17.1 38.8 ± 18.9 .030 40.5 ± 17.6 39.6 ± 18.4 .632
Extent 37.7 ± 24.8 34.4 ± 24.2 .128 34.2 ± 23.2 34.1 ± 23.9 .957
Intensity 7.4 ± 3.1 6.7 ± 3.3 .088 7.0 ± 3.0 7.0 ± 3.5 .938
Pruritus 6.1 ± 2.4 5.2 ± 2.2 .054 5.4 ± 1.7 5.6 ± 2.2 .480
Sleep loss 3.5 ± 2.8 3.6 ± 3.3 .802 3.2 ± 3.0 3.0 ± 2.9 .728
Patient oriented questionnaires
POEM 15.5 ± 6.7 12.7 ± 6.3 .004 14.3 ± 6.9 14.1 ± 7.5 .811
CDLQI 8.3 ± 4.7 7.0 ± 3.9 .113 8.0 ± 4.6 8.2 ± 5.0 .847
PADQLQ 31.9 ± 21.3 27.5 ± 21.5 .063 27.2 ± 20.2 27.5 ± 24.5 .929
Skin biophysiological parameters (at right antecubital fossa, RAF)
SH 24.1 ± 17.1 22.1 ± 14.2 .476 22.9 ± 16.2 22.2 ± 11.6 .435
TEWL 10.0 ± 5.6 9.9 ± 4.2 .925 10.1 ± 6.3 10.1 ± 4.5 .988
Erythema 409.1 ± 12.6 411.2 ± 12.0 .925 411.1 ± 13.0 408.1 ± 9.4 .140
Skin biophysiological parameters (at most severe site)
SH 12.3 ± 10.2 16.3 ± 16.8 .051 14.4 ± 15.0 13.6 ± 12.2 .675
TEWL 15.0 ± 6.3 14.8 ± 7.5 .898 13.6 ± 7.1 15.2 ± 5.8 .112
Erythema 418.0 ± 14.2 416.2 ± 15.2 .480 416.3 ± 14.0 418.0 ± 12.7 .521
Staphylococcus aureus colonization status (at RAF)
No growth 18 (46.2%) 28 (71.8%) .002 19 (48.7%) 25 (64.1%) .058
Scanty growth 15 (38.5%) 9 (23.1%) 16 (41.0%) 12 (30.8%)
Moderate growth 4 (10.3%) 5.1% 3 (7.7%) 2 (5.1%)
Heavy growth 2 (5.1%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Staphylococcus aureus colonization status (at most severe site)
No growth 21 (53.8%) 28 (71.8%) .109 21 (53.8%) 22 (56.4%) .711
Scanty growth 16 (41.0%) 9 (23.1%) 11 (28.2%) 13 (33.3%)
Moderate growth 2 (5.1%) 0 (0.0%) 6 (15.4%) 3 (7.7%)
Heavy growth 0 (0.0%) 1 (2.6%) 0 (0.0%) 1 (2.6%)
Blood markers
IgE 2220.0 (643.0–6057.0) 1640.0 (651.0–7000.0) .099 1273.5 (369.0–4239.5) 966.0 (377.8–4869.8) .845
Log IgE 3.4 (2.8–3.8) 3.2 (2.8–3.8) .009 3.1 (2.6–3.6) 3.0 (2.6–3.7) .500
Eosinophils 7.0 (4.8–13.5) 5.0 (3.0–11.0) .107 7.5 (3.5–10.3) 6.0 (2.8–10.5) .886

baseline to 12.5 (8.0–17.0) at week 4 (p ¼ .036). On the other
hand, group 2 patients experienced a small reduction from 15
(10.0–22.0) at baseline to 13.0 (8.0–22.0) at week 4 (p ¼ .355).
Further analyzing the seven individual questions in POEM, it
was found that group 1 patients experienced significant
improvements in symptoms of weeping/oozing (p ¼ .031), crack-
ing (p ¼ .020), flaking (p ¼ .010), and dry/roughness (p ¼ .019)
(POEM Q4–7). No statistically significant changes were found in
both groups during washout period and phase 2. Overall ana-
lysis showed significant improvement in POEM when patients
experienced pine-tar bathing but not vehicle oil bathing by
both ITT (p ¼ .004) and PP (p ¼ .044) analysis.
Quality of life questionnaires: CDLQI and PADQLQ
CDLQI scores remain similar for both groups during all clinical
visits. All fluctuations recorded were statistically insignificant in
both groups. For PADQLQ, no statistically significant changes
were found in both groups at phase 1. However, during the
washout period, PADQLQ median score worsened from 28.0
(12.3–52.8) and 21.0 (14.0–33.0) at visit 2 to 35.0 (16.2–82.5) and
47.0 (20.0–63.0) at visit 3 for groups 1 and 2, respectively. Both
changes were significant (p ¼ .022 for group 1; p ¼ .002 for
group 2). In phase 2, median PADQLQ score improved from 35.0
(16.3–82.5) and 47.0 (20.0–63.0) in visit 3 to 16.5 (8.3–46.0) and
17.0 (7.0–27.0) in visit 4 for group 1 and 2, respectively.
PADQLQ changes experienced by the two groups were signifi-
cant (with p<.001 in both groups). Mann–Whitney’s U test was
conducted and found that there were no statistically significant
differences in PADQLQ changes between the two groups during
washout and treatment time in phase 2. There were also no
overall significant changes in CDLQI and PADQLQ recorded by
both ITT and PP analysis between the two groups.
Staphylococcus aureus colonization status
Both group 1 and group 2 patients experienced a reduction (by
at least one grade) in S. aureus colonization status after bathing
for four weeks in phase 1. Reductions in within groups were
statistically significant but between there were no group differ-
ences. No statistically significant changes were observed during
the washout period in both groups. In phase 2, only group 2
patients who switched to using pine-tar bath oil showed an
increased percentage of patients with ‘no growth’ at RAF.
However, such change had not reached statistical significance
(p ¼ .058). Combining data, overall results showed that only
pine-tar treatment provided a statistically significant reduction
in SA colonization (p ¼ .002 by ITT approach, p ¼ .035 by PP
approach), the reduction produced by vehicle bath oil did not
reach statistical significance (p ¼ .058 by ITT approach, p ¼ .705
by PP approach).
Blood markers of atopy (phase 1 only)
IgE level after log-transformation showed a reduction from 3.4
(2.8–3.8) to 3.2 (2.8–3.8) IU/mL (p ¼ .009) in patients who bathed
with pine-tar instead of vehicle.
 JOURNAL OF DERMATOLOGICAL TREATMENT 7

Table 4. SCORAD changes (primary outcome) in two groups by per-protocol analysis (N ¼ 21).
Pine-tar bath oil (N ¼ 21) Vehicle bath oil (N ¼ 21)
Pre Post p Value Pre Post p Value
Physician evaluated disease severity score (SCORAD)
Obj. SCORAD 23.4 (17.3–42.4) 20.1 (14.4–36.4) .011 26.4 (16.6–48.3) 30.5 (13.3–46.6) .181
Total SCORAD 35.8 (27.3–52.8) 25.1 (19.6–43.7) .024 33.4 (23.8–58.3) 45.5 (16.9–53.0) .198
Extent 24.5 (13.3–56.3) 16.0 (11.0–47.5) .014 19.0 (11.0–57.5) 28.0 (8.8–51.0) .154
Intensity 6.0 (4.0–9.0) 5.0 (3.5–7.5) .032 6.0 (4.0–9.5) 7.0 (3.0–10.0) .718
Pruritus 6.0 (5.0–7.0) 5.0 (3.5–6.0) .047 5.0 (4.0–7.5) 5.0 (3.5–7.5) .479
Sleep loss 3.0 (0.5–5.0) 3.0 (0.0–5.0) .697 3.0 (0.0–5.0) 2.0 (0.0–5.5) .969
Patient oriented questionnaires
POEM 15.0 (7.5–20.0) 10.0 (7.0–16.5) .044 15.0 (9.0–20.5) 11.0 (5.5–20.5) .069
CDLQI 6.0 (4.0–11.0) 6.0 (3.5–10.5) .404 7.0 (5.0–12.0) 6.0 (3.0–11.5) .312
PADQLQ 25.0 (11.3–51.5) 21.0 (7.0–55.0) .177 28.5 (16.3–44.8) 19.0 (8.3–47.0) .121
Skin biophysiological parameters (at RAF)
SH 21.5 (12.6–35.4) 21.2 (11.6–29.4) .487 12.8 (9.6–28.2) 15.0 (9.8–31.7) .339
TEWL 8.4 (6.1–10.8) 9.1 (6.8–13.0) .601 9.9 (6.4–13.1) 8.5 (6.9–13.5) .867
Erythema 408.0 (401.5–409.5) 408.0 (404.0–410.0) .204 408.0 (400.5–422.0) 406.0 (399.0–413.5) .958
Skin biophysiological parameters (at most severe site)
SH 8.4 (3.2–16.6) 5.2 (4.5–15.6) .654 6.4 (3.4–11.5) 8.7 (4.9–14.7) .911
TEWL 14.6 (9.8–20.6) 14.1 (10.8–19.2) .835 14.7 (9.7–17.3) 15.1 (11.9–20.9) .118
Erythema 420.0 (407.5–429.0) 420.0 (402.5–424.0) .414 412.0 (402.5–424.5) 418.0 (405.5–430.0) .313
Staphylococcus aureus colonization status (at RAF)
No growth 11 (52.4%) 18 (85.7%) .035 11 (52.4%) 11 (52.4%) .705
Scanty growth 9 (42.9%) 2 (0.1%) 9 (42.9%) 10 (47.6%)
Moderate growth 1 (0.0%) 1 (0.0%) 1 (0.0%) 0 (0.0%)
Heavy growth 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Staphylococcus aureus colonization status (at severe site)
No growth 15 (71.4%) 16 (76.2%) .655 10 (47.6%) 6 (28.6%) .377
Scanty growth 6 (28.6%) 5 (23.8%) 7 (33.3%) 13 (61.9%)
Moderate growth 0 (0.0%) 0 (0.0%) 4 (19.0%) 1 (0.0%)
Heavy growth 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.0%)
Blood markers (N ¼ 13 for pine-tar; N ¼ 8 for vehicle)
IgE 2334.5 (762.3–5353.8) 2084.5 (703.0–4721.5) .060 1281.0 (511.3–2478.8) 1186.0 (531.3–2187.3) .327
Log IgE 3.4 (2.9–3.7) 3.3 (2.8–3.7) .028 3.1 (2.7–3.4) 3.1 (2.7–3.3) .401
Eosinophils 7.0 (5.0–11.8) 4.5 (3.0–10.5) .074 9.0 (4.3–11.5) 7.0 (3.5–13.0) .888

Carryover effects analysis Discussion

Two-way ANOVA analysis by SPSS (IMB Corp., Armonk, NY)
showed that the interaction between treatment sequence and
treatment status (i.e. the product they were provided at that
phase) were insignificant (p ¼ .156). Besides, the objective
SCORAD of both groups after the washout period was insignifi-
cant (p ¼ .879) by Mann–Whitney’s U test, so it may be assumed
a similar baseline again during the start of phase 2, and that
there was no significant carryover effect.
General acceptability of treatment
General acceptability toward both bath oils was positive among all
recruited patients (17,23). Around 70–80% of patients rated good/
very good to both bath oils. It appeared that more patients rated
pine-tar bath oil as ‘very good’ and more patients found vehicle
bath oil ‘poor’. Nonetheless, there were no statistically significant
differences (p ¼ .097) found between these acceptability ratings.
Safety analysis and adverse effects
Adverse events reported were mostly itching (N ¼ 4; N ¼ 1
reported for pine-tar and N ¼ 3 reported for vehicle) and tin-
gling sensations (N ¼ 2, reported for vehicle bath oil). One
patient reported rashes during treatment. No serious adverse
events were reported in this RCT.
Bathing with pine-tar ameliorated eczema severity as evidenced by
a significant reduction in all components of SCORAD during phase
1 trial. Significant improvements in total SCORAD, self-reported
severity questionnaire POEM, SA colonization status and log-trans-
formed IgE level were recorded in the overall analysis using ITT
approach. Reduction in itch level was also recorded in the subject-
ive component of SCORAD with a p value of .054 (trend) using the
ITT approach of analysis. Also, significant improvements were also
found in SA colonization status and IgE level after log-transform-
ation, suggesting that pine-tar may mediate its effects via anti-sep-
tic and anti-inflammatory effects (5,6,24).
During phase 1, there was significant reduction of SA in
both arms of the trial, suggesting bathing per se appear to
reduce SA colonization with or without pine tar (bathing
effect). Our finding concurred with previous observation with
bleach bathing (25). Nevertheless, overall, only pine tar bathing
demonstrated significant reduction of SA, so suggesting the
anti-staphylococcal effect of pine tar, further microbial testing
is warranted (26). IgE serves as a biomarker of atopy in several
clinical trials. Whether pine tar may have systemic and/or cuta-
neous effects on atopy need to be further explored. The
advantage of this trial is the crossover design, using the
patients as their own controls, and needing a smaller sample
size. There are no significant washout effects. We previously
demonstrated that a washout period of 4 weeks is generally
adequate especially for topical treatment (25). Such design is
also good for clinical trials that demonstrate disease alleviation
8 W. G. G. NG ET AL.
rather than cure. In the PP analysis, we note there are a lot of
deviations from protocol. It is believed that more severe
eczema could lead to less adherence to protocol since disease
state of subjects fluctuate more unpredictably. This reflects the
‘real life’ approach to this complementary/adjuvant mode
of therapy.
Our study is limited by being investigator-blinded, as the
pine-tar smell is difficult to mask with placebo. However, the
patients were not prejudiced as to the efficacy of the trial prod-
ucts. Another limitation the intervention was solely dependent
on the subject participation and report. It is true that a sample
size of 39 is comparatively small with regard to large scales
multi-center studies. Nevertheless, it is a reasonable size for a
local RCT study. On top of that, a cross-over approach was
adopted with the aim of increasing the power of study. The
study can be improved in the future by testing other prepara-
tions of pine-tar. There has been no RCT on other pine-tar soap
or lotion products, soap substitutes or soap-less cleansers
to date.
Bathing with pine-tar is an efficacious and recommendable
practice for AD patients alongside their usual disease manage-
ment routine. Disease improvement may be associated with the
reduction of SA and IgE.
Acknowledgements
The research is registered with the Chinese University of Hong
Kong (trial number: CUHK_CCRB00579).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
This project is funded by a Direct Grant for Research, CUHK
[Grant number: 4054365].
ORCID
Kam Lun Hon http://orcid.org/0000-0002-6682-5529
Vivian W. Y. Lee http://orcid.org/0000-0001-5802-8899
Ting Fan Leung http://orcid.org/0000-0002-6469-1926
References
1. Leung AK, Hon KL, Robson WL. Atopic dermatitis. Adv
Pediatr. 2007;54(1):241–273.
2. Leung TN, Hon K. Eczema therapeutics in children: what
do the clinical trials say? Hong Kong Med J. 2015;21:10.
3. van Zuuren EJ, Fedorowicz Z, Christensen R, et al.
Emollients and moisturisers for eczema. Cochrane
Database Syst Rev. 2017;2:CD012119.
4. Hon KL, Kung JSC, Ng WGG, et al. Emollient treatment of
atopic dermatitis: latest evidence and clinical considera-
tions. Drugs Context. 2018;7:1–14.
5. Barnes TM, Greive KA. Topical pine tar: history, properties
and use as a treatment for common skin conditions.
Australas J Dermatol. 2016;58(2):80–85.
6. Schmid MH, Korting HC. Coal tar, pine tar and sulfonated
shale oil preparations: comparative activity, efficacy and
safety. Dermatology. 1996;193(1):1–5.
7. Paghdal KV, Schwartz RA. Topical tar: back to the future.
J Am Acad Dermatol. 2009;61(2):294–302.
8. Hon KL, Ng WGG, Kung JSC, et al. Pilot studies on two
complementary bath products for atopic dermatitis chil-
dren: pine-tar and tea. Medicines (Basel). 2019;6:8.
9. Emerson RM, Charman CR, Williams HC. The Nottingham
Eczema Severity Score: preliminary refinement of the
Rajka and Langeland grading. Brit J Dermatol. 2000;142(2):
288–297.
10. Severity scoring of atopic dermatitis: the SCORAD index.
Consensus report of the European Task Force on Atopic
Dermatitis. Dermatology. 1993;186:23–31.
11. Hon KL, Ng WGG, Kung JSC, et al. Utility of the Pediatric
Allergic Disease Quality of Life Questionnaire for child-
hood eczema. Brit J Dermatol. 2019;181(2):290–295.
12. Kunz B, Oranje AP, Labr
eze L, et al. Clinical validation and
guidelines for the SCORAD index: consensus report of the
European Task Force on Atopic Dermatitis. Dermatology.
1997;195(1):10–19.
13. Hon KL, Lam MC, Leung TF, et al. CDLQI, SCORAD and
NESS: are they correlated? Qual Life Res. 2006;15(10):
1551–1558.
14. Chuh AA. Validation of a Cantonese version of the
Children’s Dermatology Life Quality Index. Pediatr
Dermatol. 2003;20(6):479–481.
15. Gaunt DM, Metcalfe C, Ridd M. The patient-oriented
eczema measure in young children: responsiveness and
minimal clinically important difference. Allergy. 2016;
71(11):1620–1625.
16. Hon KL, Kung J, Ng WG, et al. Are skin equipment for
assessing childhood eczema any good? J Dermatolog
Treat. 2018;1–15.
17. Hon KL, Tsang YC, Pong NH, et al. Patient acceptability,
efficacy, and skin biophysiology of a cream and cleanser
containing lipid complex with shea butter extract versus a
ceramide product for eczema. Hong Kong Med J. 2015;21:
417–425.
18. Hon KL, Wong KY, Leung TF, et al. Comparison of skin
hydration evaluation sites and correlations among skin
hydration, transepidermal water loss, SCORAD index,
Nottingham Eczema Severity Score, and Quality of Life in
patients with atopic dermatitis. Am J Clin Dermatol. 2008;
9(1):45–50.
19. Hon KL, Tsang KY, Kung JSC, et al. Clinical signs,
Staphylococcus and atopic eczema-related seromarkers.
Mol. 2017;22(2):291.
20. Hon KL, Tsang YC, Pong NH, et al. Clinical features and
Staphylococcus aureus colonization/infection in childhood
atopic dermatitis. J Dermatolog Treat. 2015;27:1–6.
21. Hon KL, Tsang YC, Poon TC, et al. Predicting eczema
severity beyond childhood. World J Pediatr. 2016;12(1):
44–48.
22. Hon KL, Leung TF. Seromarkers in childhood atopic
dermatitis. Expert Rev Dermatol. 2010;5(3):299–314.
23. Hon KL, Kung JSC, Tsang KYC, et al. Testing actions of a
multi-action emollient: patient acceptability, efficacy, skin
biophysiology and Staphylococcal isolation. Curr Pediatr
Rev. 2017;13.

24. Reuter J, Wo €lfle U, Korting HC, et al. Which plant for
which skin disease? Part 2: dermatophytes, chronic venous
insufficiency, photoprotection, actinic keratoses, vitiligo,
hair loss, cosmetic indications. J Dtsch Dermatol Ges.
2010;8:866–873.
25. Hon KL, Tsang YC, Lee VW, et al. Efficacy of sodium hypo-
chlorite (bleach) baths to reduce Staphylococcus aureus
JOURNAL OF DERMATOLOGICAL TREATMENT 9
colonization in childhood onset moderate-to-severe
eczema: a randomized, placebo-controlled cross-over trial.
J Dermatolog Treat. 2016;27:156–162.
26. Hon KL, Ip M, Wong CKK, et al. In vitro antimicrobial
effects of a novel pentaherbs concoction for atopic
dermatitis. J Dermatolog Treat. 2017;29:1–3.