10.5826/dpc.1401a34
Introduction: Many topical drugs are used in the treatment of erythematotelangiectatic rosacea (ETR). However, dapsone 5% gel has never been used in ETR to date.
Objectives: To evaluate the efficacy of dapsone 5% gel as a new treatment option for ETR.
Methods: Thirty-five patients with ETR were included in the study. Diagnosis was made with National Rosacea Society criteria. Dapsone 5% gel was used topically twice a day for 12 weeks. Investigator Global Assessment (IGA) 4-point scale ( 0 → Clean, 1 → mild, 2 → moderate, 3 → severe, 4 → very severe), Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI) were used for evaluation (at baseline, 2nd, 6th, and 12th weeks).
Results: IGA scores among baseline (2 → 62.9%, 3 → 34.3%, 4 → 2.9%) and 2nd (1 → 14.3%, 2 → 77,1%, 3 → 8.6%), 6th (1 → 45,7%, 2 → 54.3%) and 12th weeks (1 → 62.9%, 2 → 37.1%) were found to be statistically significant (P &lt; 0.001). Median VAS scores among baseline (median = 7 [5-9]) and 2nd (median=5 [3-8]), 6th (median=5 [3-6]) and 12th weeks (median = 4 [2-6]) were statistically significant (P &lt; 0.001). Median DLQI scores among baseline (median = 8 [6-14]) and 2nd (median = 5 [3-11]), 6th (median = 5 [3-11]) and 12th weeks (median = 4 [2-9]) were statistically significant (p&lt;0.001). Concurrent systemic disease was a risk factor for poor treatment response (P = 0.034). Mild irritation was observed in 3 patients (8.5%) during treatment.
Conclusions: Dapsone 5% gel was effective and well tolerated in ETR treatment.
text/xml
2160-9381
3629
en
Nida  Kaçar
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
erythematotelangiectatic rosacea
Efficacy of Topical Dapsone 5% Gel for the Treatment of Erythematotelangiectatic Rosacea: New Treatment Option with Old Drug
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2024-01-31
2023-06-21
2024-01-31
2024-02-21
e2024034
Dermatol Pract Concept
Introduction: Many topical drugs are used in the treatment of erythematotelangiectatic rosacea (ETR). However, dapsone 5% gel has never been used in ETR to date.
Objectives: To evaluate the efficacy of dapsone 5% gel as a new treatment option for ETR.
Methods: Thirty-five patients with ETR were included in the study. Diagnosis was made with National Rosacea Society criteria. Dapsone 5% gel was used topically twice a day for 12 weeks. Investigator Global Assessment (IGA) 4-point scale ( 0 → Clean, 1 → mild, 2 → moderate, 3 → severe, 4 → very severe), Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI) were used for evaluation (at baseline, 2nd, 6th, and 12th weeks).
Results: IGA scores among baseline (2 → 62.9%, 3 → 34.3%, 4 → 2.9%) and 2nd (1 → 14.3%, 2 → 77,1%, 3 → 8.6%), 6th (1 → 45,7%, 2 → 54.3%) and 12th weeks (1 → 62.9%, 2 → 37.1%) were found to be statistically significant (P &lt; 0.001). Median VAS scores among baseline (median = 7 [5-9]) and 2nd (median=5 [3-8]), 6th (median=5 [3-6]) and 12th weeks (median = 4 [2-6]) were statistically significant (P &lt; 0.001). Median DLQI scores among baseline (median = 8 [6-14]) and 2nd (median = 5 [3-11]), 6th (median = 5 [3-11]) and 12th weeks (median = 4 [2-9]) were statistically significant (p&lt;0.001). Concurrent systemic disease was a risk factor for poor treatment response (P = 0.034). Mild irritation was observed in 3 patients (8.5%) during treatment.
Conclusions: Dapsone 5% gel was effective and well tolerated in ETR treatment.
Nida  Kaçar
2024/01/31
10.5826/dpc.1401a34
e2024034
Pamukkale University Medical Faculty, Dermatology Department, Denizli, Turkey
2160-9381
erythematotelangiectatic rosacea
en
e2024034
Faghihi G, Khosravani P, Nilforoushzadeh MA, et al. Dapsone Gel in the Treatment of Papulopustular Rosacea: A Double-Blind Randomized Clinical Trial. J Drugs Dermatol. 2015;14(6):602-606. PMID: 26091386.
Efficacy of Topical Dapsone 5% Gel for the Treatment of Erythematotelangiectatic Rosacea: New Treatment Option with Old Drug
https://dpcj.org/index.php/dpc/article/download/3629/2430
       Efficacy of Topical Dapsone 5% Gel for the
    Treatment of Erythematotelangiectatic Rosacea:
          New Treatment Option With Old Drug
                                   Şule Gökşin1, Işıl Göğem İmren2, Nida Kaçar1


1 Pamukkale University Medical Faculty, Dermatology Department, Denizli, Turkey
2 Denizli State Hospital, Dermatology Department, Denizli, Turkey



Key words: Dapsone gel, treatment, adverse events, erythematotelangiectatic rosacea.
Citation: Gökşin Ş, Göğem İmre I, Kaçar N. Efficacy of Topical Dapsone 5% Gel for the Treatment of Erythematotelangiectatic
Rosacea: New Treatment Option With Old Drug. Dermatol Pract Concept. 2024;14(1):e2024034. DOI: https://doi.org/10.5826
/dpc.1401a34
Accepted: July 26, 2023; Published: January 2024
Copyright: ©2024 Gökşin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: Şule Gökşin; Design, Concept, Literature search, Analysis and Interpretation, Writing, Critical Review, Işıl İmren Göğem;
Design, Concept, Data Collection and Processing, Literature search, Statistical Analysis, Nida Kaçar; Supervision.
Corresponding Author: Şule Gökşin, Çamlaraltı Mahallesi, Doğan Demircioğlu Caddesi, No:71 Aytuğ Apt. Daire:5, PK:20160,
Kınıklı – Denizli / TURKEY. Tel. Mobil: +90.532.2520634 Fax: +90.258.2966001. E-mail: sule.goksin@hotmail.com




  ABSTRACT             Introduction: Many topical drugs are used in the treatment of erythematotelangiectatic rosacea
                       (ETR). However, dapsone 5% gel has never been used in ETR to date.
                       Objectives: To evaluate the efficacy of dapsone 5% gel as a new treatment option for ETR.
                       Methods: Thirty-five patients with ETR were included in the study. Diagnosis was made with Nation-
                       al Rosacea Society criteria. Dapsone 5% gel was used topically twice a day for 12 weeks. Investigator
                       Global Assessment (IGA) 4-point scale ( 0 → Clean, 1 → mild, 2 → moderate, 3 → severe, 4 → very
                       severe), Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI) were used for eval-
                       uation (at baseline, 2nd, 6th, and 12th weeks).
                       Results: IGA scores among baseline (2 → 62.9%, 3 → 34.3%, 4 → 2.9%) and 2nd (1 → 14.3%, 2 →
                       77, 1%, 3 → 8.6%), 6th (1 → 45, 7%, 2 → 54.3%) and 12th weeks (1 → 62.9%, 2 → 37.1%) were
                       found to be statistically significant (P < 0.001). Median VAS scores among baseline (median = 7 [5-9])
                       and 2nd (median=5 [3-8]), 6th (median=5 [3-6]) and 12th weeks (median = 4 [2-6]) were statistically
                       significant (P < 0.001). Median DLQI scores among baseline (median = 8 [6-14]) and 2nd (median =
                       5 [3-11]), 6th (median = 5 [3-11]) and 12th weeks (median = 4 [2-9]) were statistically significant
                       (p<0.001). Concurrent systemic disease was a risk factor for poor treatment response (P = 0.034).
                       Mild irritation was observed in 3 patients (8.5%) during treatment.
                       Conclusions: Dapsone 5% gel was effective and well tolerated in ETR treatment.




Original Article | Dermatol Pract Concept. 2024;14(1):e2024034                                                                          1
Introduction                                                       Methods
Rosacea is a chronic, recurrent, inflammatory skin dis-            Study Design and Patient Population
ease localized in the centrofacial region, characterized by        This is a single-centre prospective experimental clinical
transient flushing, persistent erythema, telangiectasia, and       study. A total of 35 patients with ETR who applied to the
papulopustular lesions. Rosacea affects 5–10% of the popu-         outpatient clinic between March and November 2022 were
lation and is usually seen after the third decade of life [1,2].   enrolled in the study.
Rosacea can be classified into four subtypes; erythemato-
telangiectatic, papulopustular, phymatous, and ocular rosa-        Diagnosis, Classification, and Staging of the Disease
cea [3]. Erythematotelangiectatic Rosacea (ETR) is the most        Rosacea diagnosis, classification, and staging was done ac-
common and has the most prominent vascular component               cording to the criteria of the National Rosacea Society Ex-
among the other subtypes [4].                                      pert Committee [10].
    An exaggerated innate immune response and neurovas-
cular dysregulation are the two main pathophysiological            Inclusion Criteria of the Patients
factors in the emergence of ETR [5]. Bacterial proteases,
                                                                   Patients over 16 years old diagnosed with ETR by at least
products of Demodex folliculorum and Staphylococcus
                                                                   two dermatologists were included in the study. The diagnosis
epidermidis, heat, stress, irritants, ultraviolet B radiation,
                                                                   of rosacea was made after comprehensive clinical and der-
products of cellular metabolism such as reactive oxygen spe-
                                                                   moscopic evaluation, including histopathologic evaluation
cies (ROS), other known triggers such as spicy food, stren-
                                                                   when needed.
uous exercise activate certain specific receptors and channel
over the skin. All of these triggers lead to the secretion of
                                                                   Exclusion Criteria of the Patients
proinflammatory cytokines, chemokines, proteases, and
                                                                   The exclusion criteria included pregnancy, lactation, immu-
pro-angiogenic factors [1,6]. These factors cause inflamma-
                                                                   nosuppression, glucose 6 phosphate dehydrogenase enzyme
tion in the dermis, which play a major role in the occurrence
                                                                   deficiency, anemia, and methemoglobinemia.
of rosacea [6]. Density of inflammation in the dermis varies
in rosacea between individuals and over time. In the ETR
                                                                   Ethics Committee Approval and Informed Consent
subtype of rosacea, inflammation is seen in both perivascu-
lar and interstitial regions [5]. Cytokines such as vascular       Approval of the Ethics Committee of the Non-Invasive Clin-

endothelial growth factor (VEGF), and proangiogenic fac-           ical Research was taken for this study (Decision number /

tors contribute to angiogenesis by both direct and indirect        year, E-60116787-020-258589 / 2022). Informed consent

mechanisms [7]. Many evidences shows that there is an as-          was taken for all of the patients. This study has been con-

sociation between inflammation and angiogenesis [6]. The           ducted in accordance with the principles of the Declaration

molecular mechanisms underlying the relationship between           of Helsinki.

chronic inflammation and angiogenesis in rosacea have been
clearly demonstrated [6].                                          Treatment Method
    Dapsone is an antibiotic which is a member of the sul-         Only topical dapsone 5% gel was used in the treatment of
fone family [8]. Dapsone has anti-inflammatory activity in         ETR without any topical or systemic agent.
addition to its antibiotic activity. Dapsone also blocks an-
giogenesis by inhibiting some molecular mechanisms such as         Dapson 5% Gel Application
VEGF formation [9]                                                 Dapson 5% gel was applied on the facial lesion (right and
    In the light of this knowledge, we used topical dapsone        left cheeks, forehead, chin and nose) as a thin layer twice a
to treat ETR by targeting chronic inflammation and angio-          day for 12 weeks by sparing the perioral, periorbital regions.
genesis. The absence of a study in the literature investigating
the effectiveness of topical dapsone on ETR makes our study        Determination of Clinical Status
a first.                                                           and Treatment Efficacy
                                                                   Patients underwent 4 visits: a baseline evaluation and visits

Objectives                                                         at weeks 2, 6, and 12. Clinical status of the patients and
                                                                   treatment efficacy were evaluated by Investigator’s Global
In this study, we primarily evaluated the efficacy of dap-         Assessment (IGA), Visual Analogue Scale (VAS), and and
sone 5% gel in treatment of ETR and additionally aimed             Dermatology Life Quality Index (DLQI) scales.
to determine the side effects during treatment in this pa-            The IGA was a grading method used by the physician
tient’s group.                                                     to show the severity of skin disease. Zero to 4 point scale



2                                                                      Original Article | Dermatol Pract Concept. 2024;14(1):e2024034
was used for determining the severity of ETR and clini-                     Table 1. Baseline demographic and clinical
cal status for each patient (Grade; 0 → Clean, 1 → mild,                          characteristics of the patients.
2 → moderate, 3 → severe, 4 → very severe) [11-13].
                                                                                                              N (%) or Median
    To assess subjective disease perception, participants were                      Parameters                   (Min-Max)
asked to mark on a 10-cm continuous VAS how disturbing                    Age                                    38 (19-62)
their rosacea had been during the past 4 weeks. The place of              Gender
every mark on VAS was measured to 1 mm and was scored
                                                                            • Male                               13 (37.1)
from 0 to 10 (0 = not at all disturbing; 10 = maximally
                                                                            • Female                             22 (62.9)
­disturbing) [14].
                                                                          Onset age of rosacea                   34 (16-57)
    The DLQI is planned to evaluate the health-related qual-
                                                                          Disease duration, month                 4 (2-10)
ity of life of adult patients complaining of skin disease. The
                                                                          Rosacea involvement site
DLQI occurs 10 questions regarding patients’ perception
                                                                           • Cheek                               35 (100)
of the effect of skin diseases on different aspects of their
                                                                            • Forehead                           15 (42.9)
health-related quality of life over the last week. Each ques-
                                                                            • Nose                               24 (68.6)
tion is scored on a four-point Likert scale (Very much = 3,
                                                                            • Chin                                8 (22.9)
lot = 2, little = 1, not at all = 0, not relevant = 0, question un-
answered = 0). The DLQI questionnaire (10 questions, max-                 Smoking
imum 30 points) was administered to all patients at baseline                • No                                 24 (68.6)
and at each visit [15].                                                     • Yes                                11 (31.4)
                                                                          Alcohol
Treatment Success                                                           • No                                 19 (54.3)
Treatment success was accepted as an IGA score of 0 or 1, or                • Yes                                16 (45.7)
                                                                                              a
a two-point reduction in score.                                           Triggering factors                     34 (97.1)
                                                                          Skin type
Adverse Events                                                              • Type I                             15 (42.9)
Adverse events were recorded at each visit.                                 • Type II                            19 (54.3)
                                                                            • Type III                            1 (2.9)
Statistical Analysis                                                      Systemic diseaseb
                                                                                                                 11 (31.4)
Analyses were performed with IBM Statistical Package for                  Additional dermatological              19 (54.3)
the Social Sciences (SPSS) for Windows 23.0 (IBM Corp).                   disease
Continuous variables were stated as median, minimum,                      Systemic drug use                       9 (25.7)
maximum, descriptive values, while categorical variables              a
                                                                       Sunlight exposure, psychological stress, warm environment, hot
were stated as number and frequency. In addition to qual-             beverages, spicy food alcohol intake, strenuous exercise, cold
itative statistical methods, the Wilcoxon signed-rank test            weather.
was used to compare the quantitative data. The risk factors           b
                                                                       Cardiovascular disease, diabetes mellitus, hypertension, lung dis-
affecting the efficacy of therapy were established by using           eases, endocrine and metabolic problems… etc. Hypothyroidism is
                                                                      the most common (11.4%).
logistic regression analysis. The statistical significance was
accepted as P < 0.05.

                                                                      the 12th week of treatment (Table 2). The decrease in IGA
Results                                                               score during and at the end of the treatment was statistically
                                                                      significant according to baseline (P < 0.001). Treatment suc-
Patient Data Analysis                                                 cess rate was 62.9% at the end of treatment. The clinical
The mean age of ERT onset was 34. Female patients were                improvement in ERT with dapsone 5% gel treatment in two
more common (female to male ratio:1.7). All patients had              different patients has been shown in Figure 1.
cheek involvement. Almost all patients had a triggering                     VAS score started to decrease after the 2nd week of treat-
cause. Detailed baseline demographic and clinical character-          ment and reached lower values at the end of the treatment
istics of the patients have been shown in Table 1.                    (Table 3). The decrease in VAS score during and at the end of
                                                                      the treatment was statistically significant according to base-
Response to Treatment                                                 line (P < 0.001).
While all patients had an IGA score of 2 or higher at base-                 The increase in DLQI after using topical dapsone 5% gel
line, there was no patient with an IGA score of 3 or 4 at             treatment was statistically significant (P < 0.001) (Table 4).



Original Article | Dermatol Pract Concept. 2024;14(1):e2024034                                                                         3
        Table 2. Investigators Global Assessment score of erythematotelangiectatic rosacea patients
                       in Baseline and Second, Sixth and Twelfth weeks of treatment.
               IGA-ETR scale                          Baseline              2nd week               6th week               12th week
         Clinical Grade             Score              N (%)                  N (%)                 N (%)                      N (%)
 Clean                                 0                 0 (0)                  0 (0)                   0 (0)                   0 (0)
 Mild                                  1                 0 (0)               5 (14,3)              16 (45,7)            22 (62,9)
 Moderate                              2           22 (62,9)               27 (77,1)               19 (54,3)            13 (37,1)
 Severe                                3           12 (34,3)                  3 (8,6)                   0 (0)                   0 (0)
 Very Severe                           4              1 (2,9)                   0 (0)                   0 (0)                   0 (0)
 P                                                        -                  <0,001                 <0,001                <0,001

ETR = erythematotelangiectatic rosacea; IGA = Investigators Global Assessment.




                Figure 1. Clinical improvement in erythematotelangiectatic rosacea with Dapsone 5% gel treatment. Clin-
                ical improvement is seen from grade 3 to 2 in the first patient and from grade 2 to 1 in the second patient.




Adverse Events                                                          Conclusions
Mild adverse events were observed in 3 patients (totally
8.5%, itching in two, burning in one) during treatment.                 The current study demonstrated that dapsone 5% gel
                                                                        was effective in the treatment of ETR. IGA scores and
Risk Factor Analysis                                                    ­patient-assessed VAS scores showed a significant improve-
The absence of systemic disease increased the success rate of           ment and good results during and after dapsone 5% gel
the treatment (P = 0.034) (Table 5).                                    treatment in patients with ETR.



4                                                                            Original Article | Dermatol Pract Concept. 2024;14(1):e2024034
 Table 3. Visual Analog Scale scores of the patients at Baseline and Second, Sixth and Twelfth weeks
                                             of treatment.
                                                  Baseline                   2. week            6. week              12. week
                                                 Median                  Median                 Median               Median
               VAS scores                       (Min-Max)               (Min-Max)              (Min-Max)            (Min-Max)
 VAS                                               7 (5-9)                   5 (3-8)             4 (3-6)               4 (2-6)
 p                                                    -                      <0.001              <0.001               <0.001
 VAS-burning sensation                             5 (2-9)                   3 (1-7)             4 (1-7)               3 (1-6)
 p                                                    -                      <0.001              <0.001               <0.001
 VAS-erythema                                     6 (4-10)                   4 (2-7)             4 (2-6)               3 (2-6)
 p                                                    -                      <0.001              <0.001               <0.001
 VAS-pruritus                                      2 (1-9)                   3 (0-6)             2 (0-5)               2 (0-4)
 p                                                    -                       0.232               0.018                0.005
 VAS-edema                                         2 (1-6)                   2 (0-6)             2 (0-4)               2 (0-5)
 p                                                    -                       0.080               0.005                0.005
VAS = Visual Analog Scale.



     Table 4. Dermatology Life Quality Index (DLQI) score of the patients at Baseline and Second,
                               Sixth and Twelfth weeks of treatment.
                                    Baseline                      2. week                  6. week                 12. week
                                    Median                        Median                   Median                   Median
                                   (Min-Max)                     (Min-Max)                (Min-Max)                (Min-Max)
 DLQI score                          8 (6-14)                     5 (3-11)                 5 (3-11)                  4 (2-9)
 P                                       -                        <0.001                     0.001                   <0.001

DLQI = Dermatology Life Quality Index.


                                                                             Rosacea treatment starts with avoidance of triggers and
             Table 5. Risk factors analysis                            use of mild cleansing and moisturizing agents, as well as
                for treatment efficacy.                                photoprotection [3]. Topical, oral medications, laser or light-
           Variables            Odds ratio (95% CI)           P        based treatments, and injection therapies are used alone or
 Age                              0.96 (0.90-1.02)           0.153     in combination in the treatment of rosacea [3,16,17]. Met-
 Gender                           0.64 (0.15-2.74)           0.550     ronidazole, azelaic acid; sulfacetamide/sülfür, brimonidine,
 Onset age of rosacea             0.96 (0.90-1.02)           0.214     oxymetazoline have been approved by FDA in the treatment
 Disease duration                 0.81 (0.58-1.12)           0.197     of erythema in rosacea [3,18]. Vascular laser and light-based
 Smoking                          0.53 (0.11-2.49)           0.417     therapies (pulsed dye laser, intense pulsed light, Nd: YAG la-
 Alcohol                          0.63 (0.16-2.52)           0.509     ser) can be used for erythema and telangiectasia as a second

 Concomitant systemic             5.25 (1.13-24.42)          0.034     step or combined with topical therapy [3,5,18].
 disease                                                                     Various therapeutic strategies may be needed to achieve
 Additional dermatologic          2.70 (0.64-11.47)          0.178     a better clinical outcome in patients with rosacea because
 diseases                                                              of an overlapping clinical feature of the subtypes [3]. Phy-
 Skin type                        0.49 (0.12-1.98)           0.316     sicians should individualize the treatment according to the
                                                                       subtype and severity of the disease, clinical grade of inflam-
CI = confidence interval.
                                                                       mation and erythema, presence of telangiectasia, triggering
                                                                       factors, and comorbidities. The efficacy of combined treat-
     Furthermore, burning sensation and erythema were sig-             ments in rosacea has been shown to be better than mono-
nificantly reduced after dapsone 5% gel treatment even in              therapy [19-23]. Topical treatments are usually preferred in
the second week compared to baseline. Moreover, the side               ETR [3]. Topical treatments were generally used for an aver-
effects of the drug were subtle, like only mild irritation. This       age of 12-16 weeks in the studies [3,23,24]. We used topical
result showed that the tolerability of dapsone 5% gel was              dapsone 5% gel for 12 weeks. We found that the success rate
also very well.                                                        of treatment was 14.3% at the end of the 2nd week, 45.7%



Original Article | Dermatol Pract Concept. 2024;14(1):e2024034                                                                      5
at the 6th week, and 62.9% at the end of the 12th week.                 To sum up, using dapsone 5% gel was safe, effective,
Overall treatment success rate in rosacea has been reported       and well tolerated in the treatment of ETR. We conclude
to range from 31.9 to 80.3%, similar to our study result with     that dapsone 5% gel treatment in ETR can be acceptable.
a quite acceptable success rate at the 12th week [19-22].         However, we think that further multicentered, randomized,
    In patients who recovered, treatment was discontinued         controlled, large-scale studies with longer follow-up period
at week 12, while in patients who did not improve, the du-        are needed.
ration of treatment was extended for another 4 weeks or
alternative treatment was started. There is no consensus in
                                                                  References
the literature for the duration and certain algorithm of treat-
ment. Furthermore, the expected duration of maintenance            1. Lee HJ, Hong YJ, Kim M. Angiogenesis in Chronic Inflammatory
treatment still remains unclear.                                      Skin Disorders. Int J Mol Sci. 2021;22(21):12035. DOI: 10.3390
                                                                      /ijms222112035. PMID: 34769465. PMCID: PMC8584589.
    Regardless of topical or systemic treatment, adverse
                                                                   2. Dall’Oglio F, Nasca MR, Micali G. Emerging topical drugs for the
events are inevitable. It has been reported that the rates of
                                                                      treatment of rosacea. Expert Opin Emerg Drugs. 2021;26(1):27-
adverse events are observed higher in combined treatments             38. DOI: 10.1080/14728214.2021.1887138. PMID: 33596752.
than topical treatments alone [17,19,23].                          3. Abokwidir M, Feldman SR. Rosacea Management. Skin Ap-
    Brimonidine tartrate gel is the first medication approved         pendage Disord. 2016;2(1-2):26-34. DOI: 10.1159/000446215.
by the FDA for the topical treatment of persistent facial er-         PMID: 27843919. PMCID: PMC5096126.
                                                                   4. Lim HS, Lee SC, Won YH, Lee JB. The efficacy of intense
ythema associated with rosacea, and has been using in the
                                                                      pulsed light for treating erythematotelangiectatic rosacea is re-
first line treatment of ETR for years [5,25]. The rates of ad-
                                                                      lated to severity and age. Ann Dermatol. 2014;26(4):491-495.
verse events have been reported to range from 6 to 14% for              DOI: 10.5021/ad.2014.26.4.491. PMID: 25143679. PMCID:
various concentrations of brimonidine tartrate [17]. When               PMC4135105.
its use is extended, these rates increase to 11-19% [17]. The      5.   Micali G, Gerber PA, Lacarrubba F, Schäfer G. Improving Treat-
most commonly reported side effects are irritation, flushing,           ment of Erythematotelangiectatic Rosacea with Laser and/or
                                                                        Topical Therapy Through Enhanced Discrimination of its Clini-
worsened erythema, burning sensation, and pruritus [17].
                                                                        cal Features. J Clin Aesthet Dermatol. 2016;9(7):30-39. PMID:
Many case reports of contact dermatitis and rebound ery-
                                                                        27672409. PMCID: PMC5023001.
thema have been documented with regard to brimonidine              6.   Buddenkotte J, Steinhoff M. Recent advances in understand-
use [17,26-28].                                                         ing and managing rosacea. F1000Res. 2018;7:F1000 Faculty
    Oxymetazoline side effects are reported as dryness (7%),            Rev-1885. DOI: 10.12688/f1000research.16537.1. PMID:
tingling sensation (3%), and papule formation (3%) [23].                30631431. PMCID: PMC6281021.
                                                                   7.   Brown LF, Detmar M, Claffey K, et al. Vascular permeability
    Metronidazole is generally well tolerated. Side effects
                                                                        factor/vascular endothelial growth factor: a multifunctional an-
such as burning and stinging, dryness, redness, pruritus, and
                                                                        giogenic cytokine. EXS. 1997;79:233-69. DOI: 10.1007/978-3
worsening of erythema were reported to be seen less than                -0348-9006-9_10. PMID: 9002222.
5% of the patients [2].                                            8.   Kwon MJ, Joo HG. Dapsone modulates lipopolysaccharide-
    The common side effects reported during the treat-                  activated bone marrow cells by inducing cell death and
ment of dapsone 5% gel in acne are dryness, erythema,                   down-regulating tumor necrosis factor-α production. J Vet Sci.
                                                                        2018;19(6):744-749. DOI: 10.4142/jvs.2018.19.6.744. PMID:
and burning sensation, along with systemic symptoms such
                                                                        30304888. PMCID: PMC6265590.
as rhinitis, pharyngitis, upper respiratory tract infection,
                                                                   9.   Kanwar B, Khattak A, Kast RE. Dapsone Lowers Neutrophil to
and headache [24]. In our study, adverse events were mild,              Lymphocyte Ratio and Mortality in COVID-19 Patients Admit-
transient, and skin-limited, seen with a lower rate. There              ted to the ICU. Int J Mol Sci. 2022;23(24):15563. DOI: 10.3390
was no worsening of erythema during treatment and no re-                /ijms232415563. PMID: 36555204. PMCID: PMC9779021.
bound erythema was observed after treatment in any of our         10.   Wilkin J, Dahl M, Detmar M, et al. National Rosacea Society
                                                                        Expert Committee. Standard grading system for rosacea: re-
patients.
                                                                        port of the National Rosacea Society Expert Committee on
    Dapsone 5% gel has only been used in the papulopus-
                                                                        the classification and staging of rosacea. J Am Acad Dermatol.
tular subtype of rosacea to date, and its efficacy has been             2004;50(6):907-912. DOI: 10.1016/j.jaad.2004.01.048. PMID:
reported to be as much as metronidazole 0.75% gel [29]. As              15153893.
far as we know, this is the first study in which dapsone 5%       11.   Schaller M, Kemény L, Havlickova B, et al. A randomized phase
gel was used in the treatment of ETR.                                   3b/4 study to evaluate concomitant use of topical ivermectin 1%
                                                                        cream and doxycycline 40-mg modified-release capsules, versus
    The study has also some limitations. It was conducted in
                                                                        topical ivermectin 1% cream and placebo in the treatment of
a single center. The study population was homogenous, lim-
                                                                        severe rosacea. J Am Acad Dermatol. 2020;82(2):336-343. DOI:
iting the external validity of the results. The sample size was         10.1016/j.jaad.2019.05.063. PMID: 31150711.
small, the follow-up period was relatively short, and there       12.   Iskandarli M, Ertam İ, Ünal İ. Impact of intense pulse light on
was no control group.                                                   quality of life in patients with erythematotelangiectatic rosacea.



6                                                                       Original Article | Dermatol Pract Concept. 2024;14(1):e2024034
      Turkderm-Turk Arch Dermatol Venereology 2017;51:46-51.              21. Sanchez J, Somolinos AL, Almodóvar PI, et al. A randomized,
      DOI: 10.4274/turkderm.69008.                                            double-blind, placebo-controlled trial of the combined effect of
13.   Schaller M, Dirschka T, Kemény L, Briantais P, Jacovella J. Supe-       doxycycline hyclate 20-mg tablets and metronidazole 0.75%
      rior Efficacy with Ivermectin 1% Cream Compared to Metroni-             topical lotion in the treatment of rosacea. J Am Acad Dermatol.
      dazole 0.75% Cream Contributes to a Better Quality of Life in           2005;53:791–797.
      Patients with Severe Papulopustular Rosacea: A Subanalysis of       22. Leyden JJ. Randomized, phase 2, dose-ranging study in the treat-
      the Randomized, Investigator-Blinded ATTRACT Study. Derma-              ment of rosacea with encapsulated benzoyl peroxide gel. J Drugs
      tol Ther (Heidelb). 2016;6(3):427-436. DOI: 10.1007/s13555              Dermatol. 2014;13:685–688.
      -016-0133-6. PMID: 27432169. PMCID: PMC4972739.                     23. Sodha P, Suggs A, Munavalli GS, Friedman PM. A Randomized
14.   Abram K, Silm H, Maaroos HI, Oona M. Subjective dis-                    Controlled Pilot Study: Combined 595-nm Pulsed Dye Laser Treat-
      ease perception and symptoms of depression in relation to               ment and Oxymetazoline Hydrochloride Topical Cream Superior
      healthcare-seeking behaviour in patients with rosacea. Acta
      ­                                                                       to Oxymetazoline Hydrochloride Cream for Erythematotelangi-
      Derm Venereol. 2009;89(5):488-491. DOI: 10.2340/00015555-               ectatic Rosacea. Lasers Surg Med. 2021;53(10):1307-1315. DOI:
      0716. PMID: 19734974.                                                   10.1002/lsm.23439. PMID: 34233378. PMCID: PMC9290736.
15.   Dermatology Life Quality Index. Cardiff University, School of       24. Wang X, Wang Z, Sun L, Liu H, Zhang F. Efficacy and safety of
      Medicine. Accessed June 10, 2023. Available from: https://www           dapsone gel for acne: a systematic review and meta-analysis. Ann
      .cardiff.ac.uk/medicine/resources/quality-of-life-questionnaires        Palliat Med. 2022;11(2):611-620. DOI: 10.21037/apm-21-3935.
      /dermatology-life-quality-index.                                        PMID: 35249339.
16.   Zhang H, Tang K, Wang Y, Fang R, Sun Q. Rosacea Treatment:          25. Rainer BM, Kang S, Chien AL. Rosacea: Epidemiology, pathogen-
      Review and Update. Dermatol Ther (Heidelb). 2021;11(1):13-              esis, and treatment. Dermatoendocrinol. 2017;9(1):e1361574.
      24. DOI: 10.1007/s13555-020-00461-0. PMID: 33170491.                    DOI: 10.1080/19381980.2017.1361574. PMID: 29484096.
      PMCID: PMC7858727.                                                      PMCID: PMC5821167.
17.   Anderson MS, Nadkarni A, Cardwell LA, Alinia H, Feldman SR.         26. Lowe E, Lim S. Paradoxical Erythema Reaction of Long-term
    Spotlight on brimonidine topical gel 0.33% for facial erythema            Topical Brimonidine Gel for the Treatment of Facial Erythema
    of rosacea: safety, efficacy, and patient acceptability. P
                                                             ­atient          of Rosacea. J Drugs Dermatol. 2016;15(6):763-765. PMID:
    Prefer Adherence. 2017;11:1143-1150. DOI: 10.2147/PPA.                    27272086.
    S115708. PMID: 28740369. PMCID: PMC5505675.                           27. Cookson H, McFadden J, White J, White IR. Allergic contact
18. Oge’ LK, Muncie HL, Phillips-Savoy AR. Rosacea: Diagnosis                 dermatitis caused by Mirvaso®, brimonidine tartrate gel 0.33%,
    and Treatment. Am Fam Physician. 2015;92(3):187-196. PMID:                a new topical treatment for rosaceal erythema. Contact Der-
    26280139.                                                                 matitis. 2015;73(6):366-377. DOI: 10.1111/cod.12476. PMID:
19. van Zuuren EJ, Arents BWM, van der Linden MMD, Vermeulen                  26768997.
    S, Fedorowicz Z, Tan J. Rosacea: New Concepts in Classification       28. Routt ET, Levitt JO. Rebound erythema and burning sen-
    and Treatment. Am J Clin Dermatol. 2021;22(4):457-465. DOI:               sation from a new topical brimonidine tartrate gel 0.33%.
    10.1007/s40257-021-00595-7. PMID: 33759078. PMCID:                        J Am Acad Dermatol. 2014;70(2):e37-e38. DOI: 10.1016/j
    PMC8200341.                                                               .jaad.2013.10.054. PMID: 24438976.
20. Fowler JF Jr. Combined effect of anti-inflammatory dose doxy-         29. Faghihi G, Khosravani P, Nilforoushzadeh MA, et al. Dapsone
    cycline (40-mg doxycycline, usp monohydrate controlled-release            Gel in the Treatment of Papulopustular Rosacea: A Double-Blind
    capsules) and metronidazole topical gel 1% in the treatment of            Randomized Clinical Trial. J Drugs Dermatol. 2015;14(6):602-
    rosacea. J Drugs Dermatol. 2007;6:641–645.                                606. PMID: 26091386.




Original Article | Dermatol Pract Concept. 2024;14(1):e2024034                                                                              7
