Original Article

Submitted: 5.6.2015 DOI: 10.1111/ddg.12889

Accepted: 19.10.2015
Conflict of interest
The present study was
conducted with financial
support from Bayer Austria
Azelaic acid 20 % cream: effects on
LLC. The interpretations and
conclusions contained in this
quality of life and disease severity in
manuscript are solely those of
the authors listed.
adult female acne patients

Julius Thomas Kainz1, Gabriele Summary

Berghammer2, Piet Auer- Background: Data on the efficacy of acne treatments and their impact on quality of
Grumbach3, Verena Lackner4, life (QoL) in adult patients is sketchy.
Sylvia Perl-Convalexius5, Objective: Assessment of the efficacy of azelaic acid 20 % cream (Skinoren®) on acne
Rodica Popa6, Barbara severity and disease-related QoL.
Wolfesberger 7 Patients and methods: Noninterventional study in adult female patients with mild to
moderate acne. Efficacy variables included DLQI and acne severity on the face, chest,
(1) Dermatology Practice, 8430, and back using the Investigator's Global Assessment (IGA) scale (grade 1 = nearly clear
Leibnitz, Austria skin; 2 = mild acne; 3 = moderate acne). Visits were scheduled at baseline, at 4–8
(2) Medical Writer, 1090, Wien, Austria weeks, and at twelve weeks.
(3) Dermatology Practice, 8200, Results: Of the 251 women enrolled, 59 % had grade 1 acne at baseline; 31 %, grade
Gleisdorf, Austria 2; and 10 %, grade 3; the most commonly affected area of the body was the face (IGA
(4) Dermatology Practice, 4020, Linz, grades 2 or 3: 79 %). After twelve weeks, there was significant improvement of acne on
Austria the face (IGA grades 0 or 1: 82 %), chest, and back. Median DLQI decreased from nine
(5) Dermatology Practice, 1200, at baseline to five after twelve weeks. Ninety percent of physicians and patients rated
Vienna, Austria the tolerability of the treatment as very good or good.
(6) Dermatology Practice, 8490, Bad Conclusions: Treatment with azelaic acid 20 % cream significantly improves acne
Radkersburg, Austria severity and disease-related QoL in adult women.
(7) Dermatology Practice, 9020,
Klagenfurt, Austria

While physical symptoms such as pain and ecchymosis

Introduction
come to the fore in patients with severe acne, mild to mo-
Although generally considered a disease of adolescence, there derate acne is primarily associated with psychosocial im-
is increasing epidemiological data suggesting that acne also pairment [16]. Acne can have profound effects on patients’
affects a considerable number of adults [1–15]. According to self-esteem, and may lead to anxiety, withdrawal, decreased
a UK population study, 54 % of women over 25 years of age ability to concentrate at work, depression, and interpersonal
have facial acne [9]. A French survey among women 24–40 conflicts, thus resulting in sustained impairment in quality of
years of age showed an acne prevalence of 41 % [7], while life [5, 10, 15, 17–19]. The psychological and social impact of
a US survey revealed that 51 % of women 20–29 years old adult acne can therefore be just as severe as in patients with
had acne, with 35 % of 30–39-year-olds; 26 % of 40–49- psoriasis [11], chronic asthma, epilepsy, diabetes, lower back
year-olds; and 15 % of 50–59-year-olds [6]. Some of these pain, or arthritis [20].
studies concluded that women are more frequently affected Despite the high prevalence of adult acne and the associ-
by adult acne than men [6, 7, 9]. ated psychological burden, there have only been few studies

© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2016
1
 Original Article Azelaic acid 20 % cream in adult female acne patients

on the effects of adequate treatment on the quality of life in most common ADRs associated with azelaic acid (according
this age group. Azelaic acid (Skinoren® 20 % Cream, Bayer) is to the SPC) – burning, pruritus, and erythema at the applica-
recommended as first-line monotherapy in women with both tion site – were explicitly mentioned on the case report form
inflammatory and noninflammatory adult acne [2]. Its effi- (CRF), and documented by checking the appropriate box.
cacy is comparable to that of other topical agents used in the Other ADRs reported by the patients were recorded as free
treatment of mild to moderate acne [21, 22]. A dicarboxylic text. At baseline and at follow-up visit 2, the patient's skin
acid that naturally occurs in the human body, azelaic acid has type (seborrheic, dry, atopic, mixed) was assessed. Any rea-
antiinflammatory, antibacterial, antikeratinizing, antioxi- sons for early withdrawal from the study were also recorded.
dant, and tyrosinase-inhibiting effects, and thus tackles mul- Patient data was recorded using CRFs, which were avai-
tiple pathogenic causes of acne at the same time [21, 23–29]. lable both in paper form and in an identical electronic version
The objective of the present noninterventional study was to on the Internet. Entry of data documented on paper CRFs
assess the correlation between acne and quality of life in adult was done manually in a single session by experienced person-
female patients 20 years and older, based on data collected in nel. Plausibility and consistency checks were carried out for
routine clinical practice. In addition to the efficacy and safety data validation.
of azelaic acid cream, we, for the first time, collected data on its
impact on quality of life as a function of disease severity. Statistical analysis

Raw data were analyzed by descriptive statistical analysis

Patients and Methods
using the observed cases method, and exploratory comparisons
Study design between the initial and follow-up visits. Missing data were
not imputed. No confirmatory hypothesis testing was done.
Herein, we report on a prospective, noninterventional mul- Continuous quantitative data are presented as specific values,
ticenter study in adult female patients with mild to moderate means, medians, standard deviations (SDs), minimums, and
acne. The study was approved by the competent ethics com- maximums. Ordinal data are expressed as absolute and relative
mittee. Office-based dermatologists were asked to recruit percentages, means, SDs, minimums, and maximums. Catego-
female patients 20 years and older who met the following rical data are described by absolute and relative frequencies. A
inclusion criteria: 1) history of acne of at least three months, two-tailed nominal p-value of < 0.05 was used. Depending on
2) eligibility for treatment with azelaic acid 20% cream (Ski- the scale of measurement, the McNemar test, paired Wilcoxon-
noren®) according to the summary of product characteri- Mann-Whitney U test, or paired t-test was used (categorical
stics (SPC), and 3) willingness to give their informed consent data, ordinal data, quantitative data) for intraindividual com-
for participation in the study. Patients with a legal guardi- parisons. Independent samples were analyzed using appro-
an, those requiring systemic acne treatment at the time of priate tests. Correlation analyses were conducted using the
enrollment, as well as individuals who had been taking an least-squares method. Statistical analysis was carried out using
oral contraceptive with anti-acne effects for less than six IBM APL2 (version 2, service level 20) for Windows.
months were excluded from participating in the study.
Study participants were instructed to apply the cream Results
twice a day. The most important efficacy parameters were qua-
lity of life, as determined using the validated German transla- Between August 2011 and January 2012, 257 patients were
tion of the Dermatology Life Quality Index (DLQI) [30], and enrolled in this noninterventional study by a total of 37 office-
acne severity, as rated by the treating physician, based on the based dermatologists. Of these, 251 women met the inclusion
Investigator's Global Assessment (IGA) scale [31]. By definiti- criteria and were included in the final analysis. One hundred
on, mild to moderate acne included IGA grades 1 to 3. and ninety-five patients attended follow up visit 1; 154 pati-
Visits were scheduled at baseline, at 4–8 weeks (follow-up ents, follow-up visit 2. Patient demographics are summarized
visit 1), and at twelve weeks (follow-up visit 2). At each visit, in Table 1.
the DLQI score, data on the prescribed acne therapy (azelaic
acid alone or in combination with other topical and/or cos- Pretreatment
metic agents), and disease severity (IGA grade) on the face,
neck, and back were documented. Follow-up visits 1 and 2 Data on pretreatment within the six months prior to study
included the assessment of efficacy and safety, from the per- enrollment was available for 241 women. Ninety individuals
spective of both the physician and the patient, as well as the (37 %) had already received treatment for the current acne
frequency and duration (in minutes) of adverse events (AEs) flare-up. Forty-two women (47 %) had exclusively received
or drug-related AEs (adverse drug reactions, or ADRs). The topical treatment; 22 (24 %), topical and systemic therapy;

2 © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2016
Original Article Azelaic acid 20 % cream in adult female acne patients

Table 1 Demographic patient characteristics (n = 251)

Parameter Mean (SD) Median (min.–max.)

Age [years] n = 232 30.4 (9) 27.1 (18.1–64.1)
Height [cm], n = 246 165.9 (5.6) 166 (150–181)
Body weight [kg], n = 246 62 (9.4) 60 (45–90)
Age at the time of initial diagnosis [years], n = 231 19 (8.3) 16 (0–64)
Time since initial diagnosis [years], n = 231 10.1 (8.7) 9 (0–39.4)
N %
IGA grade,* n = 250
 0, clear skin 0 0
 1, nearly clear skin 147 59 %
 2, mild acne 78 31 %
 3, moderate acne 24 9.6 %
 4, severe acne** 1 0.4 %
DLQI score, n = 244
 0–1, no impact on the patient's life 5 2%
 2–5, mild impact on the patient's life 29 12 %
 6–10, moderate impact on the patient's life 115 47 %
 11–20, severe impact on the patient's life 80 33 %
 21–30, extreme impact on the patient's life 15 6%
Skin type, n = 239
 Seborrheic 83 35 %
 Dry 24 10 %
 Atopic 8 3%
 Mixed 124 52 %
Type of adult acne, n = 231
 Persistent acne 194 84 %
 Late-onset acne 37 16 %
Ethnic background, n = 216
 European 214 99 %
 Asian 1 0.5 %
 African American 1 0.5 %
*Grade 0, clear skin without any inflammatory or noninflammatory lesions;
Grade 1, nearly clear skin with isolated noninflammatory lesions, and, at most, one small inflammatory lesion;
Grade 2, mild acne with multiple noninflammatory lesions, and, at most, few isolated inflammatory lesions (exclusively
­papules or pustules, no nodular lesions);
Grade 3, moderate acne with numerous noninflammatory lesions as well as few isolated inflammatory lesions, but no more
than one small nodular lesion;
Grade 4, severe acne with numerous noninflammatory and inflammatory lesions, but no more than a few nodular lesions; [31]
**One patient with IGA grade 4 disease was enrolled in the study despite the fact that she did not meet the inclusion criteria.
While she was not excluded from the final analysis, she did drop out after the initial visit so that any effects on the study's
results may be considered negligible.

© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2016
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 Original Article Azelaic acid 20 % cream in adult female acne patients

and 15 (17 %), exclusively systemic acne treatment. The 10 % to 19 %. The percentage of women with atopic skin
most frequently prescribed topical agents were erythromy- remained constant at 3 % (Table 1).
cin (n = 35), benzoyl peroxide (n = 34), clindamycin (n = 21),
and adapalene (n = 16). The most common systemic drugs Effect of treatment on quality of life
included minocycline (n = 20), doxycycline (n = 11), and iso-
tretinoin (n = 11). The mean DLQI score decreased from 10.2 at baseline to 7.8
at follow-up visit 1 and 5.8 at follow-up visit 2 (Table 2). The
Overall IGA scores at baseline median DLQI decreased from 9 at baseline to 7 at follow-up
visit 1 and 5 at follow-up visit 2, with the maximum DLQI
At baseline, 59 % of patients had nearly clear skin (IGA dropping from 28 to 19.
grade 1); 31 %, mild acne (IGA grade 2); and 10 %, moderate The percentages of the various DLQI impairment cate-
acne (IGA grade > 2) (Table 1). gories – from none to extreme impact on quality of life – over
the course of the study are shown in Figure 1. At the time of
Acne treatment regimens study enrollment, 47 % of patients experienced the impact
of acne on their quality of life as moderate; 33 %, as severe;
At baseline, 146 women (58 %) were prescribed azelaic acid 6 %, as extreme. Among patients with extreme impairment
monotherapy; 58 (23 %), combination therapy with another of quality of life, ten patients had an IGA grade of 1; three,
topical agent; 28 (11 %), azelaic acid in combination with cos- IGA grade of 2; and only one, an IGA grade of 3. After twelve
metic treatment; and seven (3 %), azelaic acid in combinati- weeks of treatment, the percentage of patients who experien-
on with another topical agent as well as cosmetic treatment. ced no or only minor impact on the quality of life had increa-
Topical agents prescribed in addition to azelaic acid included sed from 14 % at baseline to 59 %. Over the same period, the
benzoyl peroxide, alpha hydroxyl acid (AHA) peeling agents, percentage of patients with severely impaired quality of life
adapalene, salicylic acid, clindamycin, erythromycin, isotreti- had dropped from 33 % to 9 %; those with extreme impair-
noin, nicotinamide 4%/antibacterial adhesive substance 1 % ment, from 6 % to 0 %.
(Papulex Gel®, Sinclair Pharma), and Effaclar® products (La
Roche-Posay). While the percentage of patients who were Effect of therapy on acne severity
given azelaic acid (as monotherapy or in combination with
another topical agent) remained unchanged over the course of Figure 2 shows the percentages of patients by IGA grades
the study, the percentage of those who received azelaic acid in over the course of the study. The area of the body most com-
combination with cosmetic treatment rose from 14 % at base- monly affected was the face, with 53 % of patients having
line to 20 % at follow-up visit 2. Overall, 89 patients received mild and 26 % having moderate acne. After twelve weeks of
azelaic acid monotherapy over the entire course of the study. treatment, these figures had dropped to 15 % and 2 %, res-
pectively. There was also a significant clinical improvement
Concomitant systemic medication on the chest and back.
Of the 154 patients who attended both follow-up visits,
At the time of enrollment, 46 women were on contraceptives, 30 (19 %) exhibited IGA grade 0 on the face, chest, and back
nine of whom were using preparations with anti-acne effects at end of study, and thus were completely free of symptoms.
that they had been taking for more than six months prior to Ninety-two (60 %) of the 154 patients showed either IGA
the commencement of the study. Other concomitant syste- grade 0 or 1 on the face, neck and back. The median DLQI
mic therapies taken by one patient each included cyproterone score for these 92 patients decreased from 9 at baseline (ran-
acetate (Andro-Diane®) for the treatment of ovarian cysts, ge: 0–21) to 4 (range: 0–16) at follow-up visit 2.
metformin (Glucophage®) for the treatment of polycystic
ovary syndrome, and antihormone therapy for the treatment Correlation between DLQI and IGA
of endometriosis. One other patient was treated with methot-
rexate (Ebetrexat ®), dexibuprofen (Seractil®), and levothyro- At baseline, the mean DLQI score in patients with an overall
xine (Euthyrox ®). IGA grade of 1 was 10.3 (SD = 5.1; median = 9; range = 0–25),
while it was 9.4 (SD = 5.3; median = 8; range = 1–28) in
Skin type over the course of the study patients with an overall IGA grade of 2, and 11 (SD = 4.2;
median = 10; range = 6–21) in those with an overall IGA gra-
After twelve weeks of azelaic acid treatment, the percentage of de of 3. Forty percent of patients with IGA grade 1 at baseline
patients with seborrheic skin decreased from 35 % to 22 %, experienced severe or extreme impairment in quality of life;
while the percentage of patients with dry skin increased from the corresponding figures for patients with IGA grade 2 or

4 © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2016
Original Article Azelaic acid 20 % cream in adult female acne patients

Table 2 DLQI scores overall as well as by age group and treatment regimen, mean (SD)

Age groups Baseline (n = 251) Follow-up visit 1 (n = 195) Follow-up visit 2 (n = 154)
All patients 10.2 (5.2)** 7.8 (4.9)** 5.8 (3.2)**
Subgroup analysis by age at baseline
 < 20 years (n = 175)* 10.1 (5.2) 8.1 (5) 5.9 (3.4)
 21 to 30 years (n = 34)* 9.4 (4.8) 7.7 (5.6) 5.1 (2.6)
 31 to 40 years (n = 9)* 8.9 (3.6) 5.6 (1.4) 5.7 (1.9)
 > 40 years (n = 10)* 10.2 (5.1) 7 (4.2) 5.1 (2)
Subgroup analysis by age at initial diagnosis
 ≤ 25 years (persistent acne, n = 192)* 10 (5.1) 8.1 (5.1) 5.9 (3.3)
 > 25 years (late-onset, n = 36)* 9.8 (4.6) 6.4 (3.2) 5.1 (2.1)
Subgroup analysis by treatment regimen
 Azelaic acid monotherapy (n = 89)* 9.6 (4.4) 7.2 (4.1) 5.5 (2.8)
 Combination therapy (n = 155)* 10.5 (5.4) 8.4 (5.4) 6.3 (3.6)
*n = Number of patients with pertinent data at baseline.
**Statistical tests with respect to random fluctuations of changes over time using the nonparametric sign test (Dixon-Mood)
showed statistical significance (p < 0.001) for the following comparisons: baseline vs. follow-up visit 1, baseline vs. follow-up
visit 2, and follow-up visit 1 vs. follow-up visit 2.

3 at baseline were 29 % and 46 %, respectively. Although Safety and tolerability

the quality of life at baseline decreased with increasing acne
severity, there was only a weak correlation (r = 0.21) between Over the entire study period, no serious AEs were reported.
DLQI scores and IGA grades. It is the principal investigators’ opinion that all non-serious
Correlations between DLQI scores and IGA grades by AEs were related to the use of azelaic acid cream. At fol-
skin area over the course of the study were similarly weak. At low-up visit 1, 88 (45 %) of the 195 patients still participating
baseline and follow-up visits 1 and 2, the respective correla- in the study at this point reported no ADRs on azelaic acid.
tion coefficients were r = 0.29, 0.47, and 0.39 for facial acne; Considering the group of 154 patients who completed both
r = 0.29, 0.31, and 0.37 for chest acne; and r = 0.27, 0.31, and follow-up visits, 69 (45 %) patients at follow-up visit 1 and
0.35 for acne on the back. 99 (64 %) patients at follow-up visit 2 exhibited no adverse
effects, which indicates that the frequency of ADRs decreases
Efficacy assessment by physician and patient with increasing treatment duration.
Of the ADRs explicitly described on the CRFs, burning
Sixty-five percent of physicians rated the therapeutic efficacy was the most frequently reported adverse effect, followed by
as very good or good at follow-up visit 1. By follow-up visit 2, pruritus and erythema (Table 3). By follow-up visit 2, the fre-
that percentage had risen to 85 %. Among patients, the cor- quency of all three ADRs had dropped by more than half. The
responding figures were 51 % and 75 %, respectively. median duration of burning was 10 minutes (range = 1–288)

21–30 Extreme impact on the patient’s life

11–20 Severe impact on the patient’s life
6–10 Moderate impact on the patient’s life
2–5 Minor impact on the patient’s life
0–1 No impact on the patient’s life Figure 1 Percentage of patients by
Baseline Follow-up visit 1 Follow-up visit 2 degree of quality of life impairment
(n = 244) (n =185) (n =140) (DLQI) over time.

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 Original Article Azelaic acid 20 % cream in adult female acne patients

Face

IGA grade 4 (severe acne)

IGA grade 3 (moderate acne)
IGA grade 2 (mild acne)
IGA grade 1 (nearly clear skin)
IGA grade 0 (clear skin)

Baseline Follow-up Follow-up

(n = 234) visit 1 visit 2
(n =170) (n =145)

Chest

IGA grade 4 (severe acne)

IGA grade 3 (moderate acne)
IGA grade 2 (mild acne)
IGA grade 1 (nearly clear skin)
IGA grade 0 (clear skin)
Baseline Follow-up Follow-up
(n = 210) visit 1 visit 2
(n =155) (n =129)

Back

IGA grade 4 (severe acne)

IGA grade 3 (moderate acne)
IGA grade 2 (mild acne)
IGA grade 1 (nearly clear skin)
IGA grade 0 (clear skin) Figure 2 Percentage of patients by
Baseline Follow-up Follow-up IGA grade on the face, chest, and back
(n = 199) visit 1 visit 2 over time.
(n =148) (n =118)

at follow-up visit 1, and 5 minutes (range = 2–504) at fol- (range = 1–61) at follow-up visit 2. The median duration of
low-up visit 2. The median duration of pruritus was 5 mi- erythema was 10 minutes (range = 1–504) at follow-up vi-
nutes (range = 1–504) at follow-up visit 1, and 2–3 minutes sit 1, and 10 minutes (range = 5–20) at follow-up visit 2.

Table 3 Adverse drug reactions (ADRs) reported at follow-up visits 1 and 2

Follow-up visit 1 (n = 195) Follow-up visit 2 (n = 154)

Number of patients Number of ADRs (%) Number of patients Number of ADRs (%)
Burning at the application site 205* 83 (40.5 %) 152 27 (17.8 %)
Pruritus at the application site 204* 62 (30.4 %) 152 19 (12.5 %)
Erythema at the application site 205* 43 (21 %) 151 12 (7.9 %)
*Includes patients with documented ADRs on the CRF who did, however, not attend follow-up visit 1.

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Original Article Azelaic acid 20 % cream in adult female acne patients

In addition, six patients reported ADRs that were not Subgroup analyses by age
explicitly documented on the CRFs: skin dryness (n = 1), skin
dryness and flaking (n = 1), as well as inflammatory, pain- The correlation between patient age and selected study para-
ful, and pruritic pustules on the chin, forehead, and cheeks meters was examined in two subgroup analyses. One of these
(n = 1); there was no specific information on the nature of the analyzed the correlation between age at baseline and quality
ADRs in the remaining three patients. of life and/or acne severity. Of the 228 patients whose age was
available, 175 were ≤ 20 years old at baseline; 34, 21–30; nine,
Assessment of tolerance by physicians and patients 31–40; and ten, older than 40. With respect to DLQI scores,
there were no statistically significant differences between age
At follow-up visits 1 and 2, 90 % and 96 % of physicians, groups (Table 2, Figure 3). While there were significant age
respectively, rated the tolerability of azelaic acid as very good effects with regard to IGA grades, especially at baseline, these
or good. Among patients, the corresponding figures were effects disappeared over the course of the study.
85 % and 94 %. Given that adult acne can be classified – according to its
course – in persistent and late-onset acne, we also conducted
Reasons for withdrawal from the study a subgroup analysis according to age at the time of initial on-
set. In keeping with a commonly used definition [2, 32, 33],
With respect to DLQI scores and IGA grades, there were no we made a distinction between patients whose acne had al-
significant differences between patients who dropped out ready been present in adolescence and then persisted into
of the study after the initial examination (n = 56) or after adulthood (persistent acne, n = 194) and those in whom
follow-up visit 1 (n = 41), and those who participated th- acne had first occurred after the age of 25 (late-onset acne,
roughout the entire study. As regards the 56 patients who n = 37). Neither at baseline nor at follow-up visits 1 or 2 were
withdrew from the study after the initial examination, no there statistically significant differences (p > 0.05) between
information was provided as to the reason for withdrawal. these two groups with respect to DLQI scores or IGA grades
Among the 41 patients who withdrew after follow-up visit 1, on the face or back. While there were significant differences
reasons were stated in 26 cases. Five of these 26 patients as regards IGA grades on the chest at follow-up visits 1 and 2
terminated treatment with azelaic acid as a result of clinical (Figure 4), these appear to have little clinical relevance.
improvement, which, in their eyes, rendered any further tre-
atment unnecessary. Twelve patients discontinued treatment Subgroup analysis by monotherapy vs.
due to lack of a therapeutic response; four, due to lack of
combination therapy
response and ADRs; two, due to ADRs; and one patient each,
due to atopic dermatitis, pregnancy, or lack of response due Compared to patients who had received combination the-
to polycystic ovary syndrome. rapy (including azelaic acid) (n = 161), subgroup analysis of

DLQI IGA (face)

by age at baseline by age at baseline

Baseline Follow-up Follow-up Baseline Follow-up Follow-up

visit 1 visit 2 visit 1* visit 2
IGA (chest) IGA (back)
by age at baseline by age at baseline

≤ 22 years
21‒30 years
31‒40 years
> 40 years

Baseline** Follow-up Follow-up Baseline* Follow-up Follow-up

visit 1 visit 2 visit 1 visit 2
Figure 3 DLQI scores and IGA grades
*p < 0.05
**p < 0.01 by age at baseline.

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7
 Original Article Azelaic acid 20 % cream in adult female acne patients

DLQI IGA (face)

by age at baseline by age at initial diagnosis

Baseline Follow-up Follow-up Baseline Follow-up Follow-up

visit 1 visit 2 visit 1* visit 2
IGA (chest) IGA (back)
by at initial diagnosis by at initial diagnosis

≤ 25 years
> 26 years

Baseline** Follow-up Follow-up Baseline* Follow-up Follow-up

visit 1 visit 2 visit 1 visit 2 Figure 4 DLQI scores and IGA grades
*p < 0.05 by age at initial diagnosis.

patients (n = 89) who had received azelaic acid as monothe- depression and suicidal thoughts [46–48] are well docu-
rapy over the entire course of the study revealed (Table 2) mented [2, 10, 18, 49]. Given that acne is generally typically
no statistically significant differences (p > 0.05) – neither at considered a disease of adolescence, studies on its psycho-
baseline nor at follow-up visits 1 or 2 – with respect to DLQI logical ramifications have primarily focused on this age
scores or IGA grades on the face, chest, or back, either. This group. The results of the present study confirm that adults
is also true for the assessment of therapeutic efficacy and to- may be just as affected. At baseline, 86 % of women re-
lerability by physicians and patients. ported either moderate, severe, or extreme impairment of
Remarkably, the final assessment revealed that ‘failure their quality of life. This is consistent with recent results
to follow-up with their physician’ as reason for treatment obtained by Tanghetti et al. [10] who reported that 83 %
discontinuation was documented in none of the patients on of women between the age of 25 and 45 felt burdened by
azelaic acid monotherapy, however, in 57 % of individuals on their facial acne. The present study and theirs also observed
combination therapy (p < 0.001. similar figures with respect to the degree of impairment,
While 6 % of patients on azelaic acid monotherapy with 6 % respectively 10 % of women rating it as extreme;
showed an inadequate therapeutic response, that figure was 33 % respectively 29 %, as severe; 47 % respectively 35 %,
35 % in those receiving combination therapy (p < 0.005). as moderate; 12 % respectively 9 %, as low; and 2 % res-
Tolerability issues were documented in 6 % of patients on pectively 1 %, as irrelevant.
azelaic acid monotherapy, and in 22 % of individuals on Although the quality of life decreased with increasing
combination therapy (p < 0.05). acne severity, especially at baseline, there were only weak
correlations. This was highlighted by the fact that, although
at baseline 90 % of patients had nearly clear skin or mild
Discussion
acne according to the overall IGA grade, at the same time
The present study is the first to assess the effects of topical 86 % experienced moderate, severe, or extreme impairment
azelaic acid on the severity of mild to moderate acne and di- of their quality of life. Moreover, the percentage of patients
sease-related quality of life in adult female patients. Not only who experienced severe or extreme acne-related impairment
does it show that acne can have a sustained impact on the in quality of life was nearly the same in individuals with
quality of life of adult women, but also that treatment with IGA grade 1 or 3 disease. This observation is consistent with
azelaic acid 20 % cream can significantly improve both cli- previous findings that found no or only a weak correlation
nical disease severity as well as quality of life. An interesting between acne severity and quality of life [10, 11, 16, 35–37,
additional finding is the weak correlation between disease 39, 41, 50], suggesting that even mild acne – likely in combi-
severity and the extent of impairment in quality of life. nation with other factors such as emotional or work-related
The correlation between acne and impaired quality of problems or low self-esteem – can be associated with tre-
life [11, 18, 34–40], low self-esteem [16, 41, 42], as well mendous psychosocial stress [51]. There was an increase in
as psychological morbidity [15–17, 19, 43–45] including the degree of correlation between acne severity and quality

8 © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2016
Original Article Azelaic acid 20 % cream in adult female acne patients

of life over the course of the study. This observation corro- – broaden the scope of existing clinical data with results in
borates results by Jones-Caballero et al. [35], and indicates adult women between the age of 18 and 64.
that the dissociation between psychological stress and acne The pathogenesis of adult acne does not seem to subs-
severity weakens once the patient receives medical attention. tantially differ from that of acne in adolescence; nevertheless,
The weak correlation between disease severity and quality the adult form exhibits some morphological peculiarities, in
of life also emphasizes that instruments used to assess qua- particular a greater tendency for inflammation, hyperpig-
lity of life may be able useful in complementing disease as- mentation, and scarring [2, 10, 32]. It appears remarkable
sessment [22]. that, in the present study, women above the age of 40 al-
Treatment with azelaic acid 20 % cream for a period of most exclusively had facial acne; in this context, however, it
twelve weeks resulted in statistically significant improvement is important to note that the number of respective cases was
of acne severity and quality of life. As already reported for relatively small. Goulden et al. [32] suggested that the high
younger patient populations [19, 35, 52–54], this shows that percentage of women in their study who did not respond to
effective treatment is able to alleviate the physical and psy- multiple cycles of antibiotic treatment could have been due
chological stress associated with adult acne. Both the DLQI to antibiotic resistance of P. acnes. One advantage of azelaic
scores and IGA grades already showed marked improvement acid is that it does not induce bacterial resistance. Besides,
at 4–8 weeks post treatment initiation, which became even azelaic acid has no phototoxic or photoallergic potential [55];
more pronounced between follow-up visits 1 and 2. After it does not cause systemic adverse effects; it does not ble-
twelve weeks of treatment, 75 % of patients and 85 % of phy- ach clothes; it is useful in the treatment of postinflammatory
sicians rated the therapeutic efficacy as very good or good. hyperpigmentation [24]; and it is not teratogenic [21], thus
In this regard, there was no significant difference between making it a particularly ideal therapeutic option for women
patients with persistent acne and those with late-onset acne of childbearing age.
(age range 26–64 years in our study). The results presented herein corroborate that even mild
As with most topical agents, azelaic acid, too, can cau- to moderate forms of acne can greatly impair the quality of
se local adverse effects and has been shown to occur in one- life in those affected. Due to the frequently missing corre-
third of patients in clinical trials [21] – a percentage that is lation between clinical disease severity and its impact on
consistent with the results of the present study. The most the patient's psyche, the use of a questionnaire to assess the
common local reactions include sensory symptoms such as extent of disease-related psychological burden can be bene-
burning and pruritus; these are attributed to the acidic pro- ficial. In our cohort of adult acne patients, treatment with
perties of azelaic acid, which cause irritation of free nerve azelaic acid 20% cream over a period of twelve weeks led to
endings in the skin [21]. However, both the incidence as a significant improvement in clinical disease severity as well
well as the duration of local reactions are highest in the as in disease-related quality of life.
first 4–8 weeks of treatment, and decrease with increasing
treatment duration [21]. Although 18 % of patients still re- Acknowledgments
ported local reactions at follow-up visit 2, more than 90 %
of patients and physicians rated the tolerability of azelaic The authors wish to thank all dermatologists for their
acid cream as good or very good, suggesting that the bene- participation in the study and DI Kurt Neumann for statistical
fit-side effect ratio of the preparation was perceived to be advice as well as statistical design and data analysis.
favorable.
Confirmed by our study, topical therapies are generally
Correspondence to
considered sufficient for successful treatment of mild adult
acne [2]. Azelaic acid – originally a by-product discovered in Dr. med. Julius Thomas Kainz
the context of research on pigmentary disorders – has three Dechant-Thaller-Straße 34
pharmacologically active effects relevant to acne treatment:
it normalizes keratinization, and it has antibacterial (against 8430 Leibnitz, Austria
intrafollicular Propionibacterium (P.) acnes) as well as an- E-mail: [email protected]
tiinflammatory effects [21, 23–29]. Comparative studies
with comedonal acne and papulopustular acne have shown
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