Original Article

Efficacy of Topical Dapsone 5% Gel for the Treatment of Erythematotelangiectatic Rosacea: New Treatment Option with Old Drug

Author Affiliation(s)


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 < 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.

Keywords : dapsone gel, treatment, adverse events, erythematotelangiectatic rosacea


Rosacea is a chronic, recurrent, inflammatory skin disease localized in the centrofacial region, characterized by transient flushing, persistent erythema, telangiectasia, and papulopustular lesions. Rosacea affects 5–10% of the population and is usually seen after the third decade of life [ 1 , 2 ] . Rosacea can be classified into four subtypes; erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea [ 3 ] . Erythematotelangiectatic Rosacea (ETR) is the most common and has the most prominent vascular component among the other subtypes [ 4 ] .

An exaggerated innate immune response and neurovascular dysregulation are the two main pathophysiological factors in the emergence of ETR [ 5 ] . Bacterial proteases, products of Demodex folliculorum and Staphylococcus epidermidis , heat, stress, irritants, ultraviolet B radiation, products of cellular metabolism such as reactive oxygen species (ROS), other known triggers such as spicy food, strenuous exercise activate certain specific receptors and channel over the skin. All of these triggers lead to the secretion of proinflammatory cytokines, chemokines, proteases, and pro-angiogenic factors [ 1 , 6 ] . These factors cause inflammation in the dermis, which play a major role in the occurrence of rosacea [ 6 ] . Density of inflammation in the dermis varies in rosacea between individuals and over time. In the ETR subtype of rosacea, inflammation is seen in both perivascular and interstitial regions [ 5 ] . Cytokines such as vascular endothelial growth factor (VEGF), and proangiogenic factors contribute to angiogenesis by both direct and indirect mechanisms [ 7 ] . Many evidences shows that there is an association between inflammation and angiogenesis [ 6 ] . The molecular mechanisms underlying the relationship between chronic inflammation and angiogenesis in rosacea have been clearly demonstrated [ 6 ] .

Dapsone is an antibiotic which is a member of the sulfone family [ 8 ] . Dapsone has anti-inflammatory activity in addition to its antibiotic activity. Dapsone also blocks angiogenesis by inhibiting some molecular mechanisms such as VEGF formation [ 9 ]

In the light of this knowledge, we used topical dapsone to treat ETR by targeting chronic inflammation and angiogenesis. The absence of a study in the literature investigating the effectiveness of topical dapsone on ETR makes our study a first.


In this study, we primarily evaluated the efficacy of dapsone 5% gel in treatment of ETR and additionally aimed to determine the side effects during treatment in this patient’s group.


Study Design and Patient Population

This is a single-centre prospective experimental clinical study. A total of 35 patients with ETR who applied to the outpatient clinic between March and November 2022 were enrolled in the study.

Diagnosis, Classification, and Staging of the Disease

Rosacea diagnosis, classification, and staging was done according to the criteria of the National Rosacea Society Expert Committee [ 10 ] .

Inclusion Criteria of the Patients

Patients over 16 years old diagnosed with ETR by at least two dermatologists were included in the study. The diagnosis of rosacea was made after comprehensive clinical and dermoscopic evaluation, including histopathologic evaluation when needed.

Exclusion Criteria of the Patients

The exclusion criteria included pregnancy, lactation, immunosuppression, glucose 6 phosphate dehydrogenase enzyme deficiency, anemia, and methemoglobinemia.

Ethics Committee Approval and Informed Consent

Approval of the Ethics Committee of the Non-Invasive Clinical Research was taken for this study (Decision number / year, E-60116787-020-258589 / 2022). Informed consent was taken for all of the patients. This study has been conducted in accordance with the principles of the Declaration of Helsinki.

Treatment Method

Only topical dapsone 5% gel was used in the treatment of ETR without any topical or systemic agent.

Dapson 5% Gel Application

Dapson 5% gel was applied on the facial lesion (right and left cheeks, forehead, chin and nose) as a thin layer twice a day for 12 weeks by sparing the perioral, periorbital regions.

Determination of Clinical Status and Treatment Efficacy

Patients underwent 4 visits: a baseline evaluation and visits at weeks 2, 6, and 12. Clinical status of the patients and treatment efficacy were evaluated by Investigator’s Global Assessment (IGA), Visual Analogue Scale (VAS), and and Dermatology Life Quality Index (DLQI) scales.

The IGA was a grading method used by the physician to show the severity of skin disease. Zero to 4 point scale was used for determining the severity of ETR and clinical status for each patient (Grade; 0 → Clean, 1 → mild, 2 → moderate, 3 → severe, 4 → very severe) [ 11 13 ] .

To assess subjective disease perception, participants were asked to mark on a 10-cm continuous VAS how disturbing their rosacea had been during the past 4 weeks. The place of every mark on VAS was measured to 1 mm and was scored from 0 to 10 (0 = not at all disturbing; 10 = maximally disturbing) [ 14 ] .

The DLQI is planned to evaluate the health-related quality of life of adult patients complaining of skin disease. The DLQI occurs 10 questions regarding patients’ perception of the effect of skin diseases on different aspects of their health-related quality of life over the last week. Each question is scored on a four-point Likert scale (Very much = 3, lot = 2, little = 1, not at all = 0, not relevant = 0, question unanswered = 0). The DLQI questionnaire (10 questions, maximum 30 points) was administered to all patients at baseline and at each visit [ 15 ] .

Treatment Success

Treatment success was accepted as an IGA score of 0 or 1, or a two-point reduction in score.

Adverse Events

Adverse events were recorded at each visit.

Statistical Analysis

Analyses were performed with IBM Statistical Package for the Social Sciences (SPSS) for Windows 23.0 (IBM Corp). Continuous variables were stated as median, minimum, maximum, descriptive values, while categorical variables were stated as number and frequency. In addition to qualitative statistical methods, the Wilcoxon signed-rank test was used to compare the quantitative data. The risk factors affecting the efficacy of therapy were established by using logistic regression analysis. The statistical significance was accepted as P < 0.05.


Patient Data Analysis

The mean age of ERT onset was 34. Female patients were more common (female to male ratio:1.7). All patients had cheek involvement. Almost all patients had a triggering cause. Detailed baseline demographic and clinical characteristics of the patients have been shown in Table 1 .

Response to Treatment

While all patients had an IGA score of 2 or higher at baseline, there was no patient with an IGA score of 3 or 4 at the 12th week of treatment ( Table 2 ). The decrease in IGA score during and at the end of the treatment was statistically significant according to baseline (P < 0.001). Treatment success rate was 62.9% at the end of treatment. The clinical improvement in ERT with dapsone 5% gel treatment in two different patients has been shown in Figure 1 .

VAS score started to decrease after the 2nd week of treatment and reached lower values at the end of the treatment ( Table 3 ). The decrease in VAS score during and at the end of the treatment was statistically significant according to baseline (P < 0.001).

The increase in DLQI after using topical dapsone 5% gel treatment was statistically significant (P < 0.001) ( Table 4 ).

Adverse Events

Mild adverse events were observed in 3 patients (totally 8.5%, itching in two, burning in one) during treatment.

Risk Factor Analysis

The absence of systemic disease increased the success rate of the treatment (P = 0.034) ( Table 5 ).


The current study demonstrated that dapsone 5% gel was effective in the treatment of ETR. IGA scores and patient-assessed VAS scores showed a significant improvement and good results during and after dapsone 5% gel treatment in patients with ETR.

Furthermore, burning sensation and erythema were significantly reduced after dapsone 5% gel treatment even in the second week compared to baseline. Moreover, the side effects of the drug were subtle, like only mild irritation. This result showed that the tolerability of dapsone 5% gel was also very well.

Rosacea treatment starts with avoidance of triggers and use of mild cleansing and moisturizing agents, as well as photoprotection [ 3 ] . Topical, oral medications, laser or light-based treatments, and injection therapies are used alone or in combination in the treatment of rosacea [ 3 , 16 , 17 ] . Metronidazole, azelaic acid; sulfacetamide/sülfür, brimonidine, oxymetazoline have been approved by FDA in the treatment of erythema in rosacea [ 3 , 18 ] . Vascular laser and light-based therapies (pulsed dye laser, intense pulsed light, Nd: YAG laser) can be used for erythema and telangiectasia as a second step or combined with topical therapy [ 3 , 5 , 18 ] .

Various therapeutic strategies may be needed to achieve a better clinical outcome in patients with rosacea because of an overlapping clinical feature of the subtypes [ 3 ] . Physicians should individualize the treatment according to the subtype and severity of the disease, clinical grade of inflammation and erythema, presence of telangiectasia, triggering factors, and comorbidities. The efficacy of combined treatments in rosacea has been shown to be better than monotherapy [ 19 23 ] . Topical treatments are usually preferred in ETR [ 3 ] . Topical treatments were generally used for an average of 12–16 weeks in the studies [ 3 , 23 , 24 ] . We used topical dapsone 5% gel for 12 weeks. We found that the success rate of treatment was 14.3% at the end of the 2nd week, 45.7% at the 6th week, and 62.9% at the end of the 12th week. Overall treatment success rate in rosacea has been reported to range from 31.9 to 80.3%, similar to our study result with a quite acceptable success rate at the 12th week [ 19 22 ] .

In patients who recovered, treatment was discontinued at week 12, while in patients who did not improve, the duration of treatment was extended for another 4 weeks or alternative treatment was started. There is no consensus in the literature for the duration and certain algorithm of treatment. Furthermore, the expected duration of maintenance treatment still remains unclear.

Regardless of topical or systemic treatment, adverse events are inevitable. It has been reported that the rates of adverse events are observed higher in combined treatments than topical treatments alone [ 17 , 19 , 23 ] .

Brimonidine tartrate gel is the first medication approved by the FDA for the topical treatment of persistent facial erythema associated with rosacea, and has been using in the first line treatment of ETR for years [ 5 , 25 ] . The rates of adverse events have been reported to range from 6 to 14% for various concentrations of brimonidine tartrate [ 17 ] . When its use is extended, these rates increase to 11–19% [ 17 ] . The most commonly reported side effects are irritation, flushing, worsened erythema, burning sensation, and pruritus [ 17 ] . Many case reports of contact dermatitis and rebound erythema have been documented with regard to brimonidine use [ 17 , 26 28 ] .

Oxymetazoline side effects are reported as dryness (7%), tingling sensation (3%), and papule formation (3%) [ 23 ] .

Metronidazole is generally well tolerated. Side effects such as burning and stinging, dryness, redness, pruritus, and worsening of erythema were reported to be seen less than 5% of the patients [ 2 ] .

The common side effects reported during the treatment of dapsone 5% gel in acne are dryness, erythema, and burning sensation, along with systemic symptoms such as rhinitis, pharyngitis, upper respiratory tract infection, and headache [ 24 ] . In our study, adverse events were mild, transient, and skin-limited, seen with a lower rate. There was no worsening of erythema during treatment and no rebound erythema was observed after treatment in any of our patients.

Dapsone 5% gel has only been used in the papulopustular subtype of rosacea to date, and its efficacy has been reported to be as much as metronidazole 0.75% gel [ 29 ] . As far as we know, this is the first study in which dapsone 5% gel was used in the treatment of ETR.

The study has also some limitations. It was conducted in a single center. The study population was homogenous, limiting the external validity of the results. The sample size was small, the follow-up period was relatively short, and there was no control group.

To sum up, using dapsone 5% gel was safe, effective, and well tolerated in the treatment of ETR. We conclude that dapsone 5% gel treatment in ETR can be acceptable. However, we think that further multicentered, randomized, controlled, large-scale studies with longer follow-up period are needed.


  1. Angiogenesis in Chronic Inflammatory Skin Disorders Lee HJ, Hong YJ, Kim M. Int J Mol Sci.2021;22(21):12035. CrossRef PubMed
  2. Emerging topical drugs for the treatment of rosacea Dall’Oglio F, Nasca MR, Micali G. Expert Opin Emerg Drugs.2021;26(1):27-38. CrossRef PubMed
  3. Rosacea Management Abokwidir M, Feldman SR. Skin Appendage Disord.2016;2(1–2):26-34. CrossRef PubMed
  4. The efficacy of intense pulsed light for treating erythematotelangiectatic rosacea is related to severity and age Lim HS, Lee SC, Won YH, Lee JB. Ann Dermatol.2014;26(4):491-495. CrossRef PubMed
  5. Improving Treatment of Erythematotelangiectatic Rosacea with Laser and/or Topical Therapy Through Enhanced Discrimination of its Clinical Features Micali G, Gerber PA, Lacarrubba F, Schäfer G. J Clin Aesthet Dermatol.2016;9(7):30-39.
  6. Recent advances in understanding and managing rosacea Buddenkotte J, Steinhoff M. F1000Res.2018;7. CrossRef PubMed
  7. Vascular permeability factor/vascular endothelial growth factor: a multifunctional angiogenic cytokine Brown LF, Detmar M, Claffey K, et al. EXS.1997;79:233-69. CrossRef PubMed
  8. Dapsone modulates lipopolysaccharide-activated bone marrow cells by inducing cell death and down-regulating tumor necrosis factor-α production Kwon MJ, Joo HG. J Vet Sci.2018;19(6):744-749. CrossRef PubMed
  9. Dapsone Lowers Neutrophil to Lymphocyte Ratio and Mortality in COVID-19 Patients Admitted to the ICU Kanwar B, Khattak A, Kast RE. Int J Mol Sci.2022;23(24):15563. CrossRef PubMed
  10. Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea Wilkin J, Dahl M, Detmar M, et al. J Am Acad Dermatol.2004;50(6):907-912. CrossRef PubMed
  11. A randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40-mg modified-release capsules, versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea Schaller M, Kemény L, Havlickova B, et al. J Am Acad Dermatol.2020;82(2):336-343. CrossRef PubMed
  12. Impact of intense pulse light on quality of life in patients with erythematotelangiectatic rosacea Iskandarli M, Ertam İ, Ünal İ. Turkderm-Turk Arch Dermatol Venereology.2017;51:46-51. CrossRef
  13. Superior Efficacy with Ivermectin 1% Cream Compared to Metronidazole 0.75% Cream Contributes to a Better Quality of Life in Patients with Severe Papulopustular Rosacea: A Subanalysis of the Randomized, Investigator-Blinded ATTRACT Study Schaller M, Dirschka T, Kemény L, Briantais P, Jacovella J. Dermatol Ther (Heidelb).2016;6(3):427-436. CrossRef PubMed
  14. Subjective disease perception and symptoms of depression in relation to healthcare-seeking behaviour in patients with rosacea Abram K, Silm H, Maaroos HI, Oona M. Acta Derm Venereol.2009;89(5):488-491. CrossRef PubMed
  15. Dermatology Life Quality Index Cardiff University, School of Medicine .
  16. Rosacea Treatment: Review and Update Zhang H, Tang K, Wang Y, Fang R, Sun Q. Dermatol Ther (Heidelb).2021;11(1):13-24. CrossRef PubMed
  17. Spotlight on brimonidine topical gel 0.33% for facial erythema of rosacea: safety, efficacy, and patient acceptability Anderson MS, Nadkarni A, Cardwell LA, Alinia H, Feldman SR. Patient Prefer Adherence.2017;11:1143-1150. CrossRef PubMed
  18. Rosacea: Diagnosis and Treatment Oge’ LK, Muncie HL, Phillips-Savoy AR. Am Fam Physician.2015;92(3):187-196.
  19. Rosacea: New Concepts in Classification and Treatment van Zuuren EJ, Arents BWM, van der Linden MMD, Vermeulen S, Fedorowicz Z, Tan J. Am J Clin Dermatol.2021;22(4):457-465. CrossRef PubMed
  20. Combined effect of anti-inflammatory dose doxycycline (40-mg doxycycline, usp monohydrate controlled-release capsules) and metronidazole topical gel 1% in the treatment of rosacea Fowler JF. J Drugs Dermatol.2007;6:641-645.
  21. A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea Sanchez J, Somolinos AL, Almodóvar PI, et al. J Am Acad Dermatol.2005;53:791-797.
  22. Randomized, phase 2, dose-ranging study in the treatment of rosacea with encapsulated benzoyl peroxide gel Leyden JJ. J Drugs Dermatol.2014;13:685-688.
  23. A Randomized Controlled Pilot Study: Combined 595-nm Pulsed Dye Laser Treatment and Oxymetazoline Hydrochloride Topical Cream Superior to Oxymetazoline Hydrochloride Cream for Erythematotelangiectatic Rosacea Sodha P, Suggs A, Munavalli GS, Friedman PM. Lasers Surg Med.2021;53(10):1307-1315. CrossRef PubMed
  24. Efficacy and safety of dapsone gel for acne: a systematic review and meta-analysis Wang X, Wang Z, Sun L, Liu H, Zhang F. Ann Palliat Med.2022;11(2):611-620. CrossRef PubMed
  25. Rosacea: Epidemiology, pathogenesis, and treatment Rainer BM, Kang S, Chien AL. Dermatoendocrinol.2017;9(1):e1361574. CrossRef PubMed
  26. Paradoxical Erythema Reaction of Long-term Topical Brimonidine Gel for the Treatment of Facial Erythema of Rosacea Lowe E, Lim S. J Drugs Dermatol.2016;15(6):763-765.
  27. Allergic contact dermatitis caused by Mirvaso®, brimonidine tartrate gel 0.33%, a new topical treatment for rosaceal erythema Cookson H, McFadden J, White J, White IR. Contact Dermatitis.2015;73(6):366-377. CrossRef PubMed
  28. Rebound erythema and burning sensation from a new topical brimonidine tartrate gel 0.33% Routt ET, Levitt JO. J Am Acad Dermatol.2014;70(2):e37-e38. CrossRef PubMed
  29. Dapsone Gel in the Treatment of Papulopustular Rosacea: A Double-Blind Randomized Clinical Trial Faghihi G, Khosravani P, Nilforoushzadeh MA, et al. J Drugs Dermatol.2015;14(6):602-606.

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