Interest in dapsone for acne management lies in the contrast between its long pharmacological history and its relatively recent role in topical therapy. The focus of this editorial is the review Safety and effectiveness of topical dapsone in acne treatment: A review, which summarizes data on the efficacy and safety of topical dapsone across different patient groups, considering age, sex, skin phototype, lesion distribution, and comorbidities [1].

Chemical nature and mechanism of action

Dapsone is a sulfone antibiotic with both anti-inflammatory and antimicrobial properties. It has long been used in dermatology for various conditions, most notably leprosy, and has been mentioned in the management of acne vulgaris since 1961.

Its relevance in acne extends beyond its antibacterial effects to its impact on the inflammatory cascade. It is thought to inhibit dihydrofolic acid synthesis, reduce neutrophil myeloperoxidase activity, and modulate chemoattractant signaling involved in neutrophil recruitment. This combination of anti-inflammatory and antimicrobial activity makes dapsone a logical option, particularly for inflammatory acne [2].

From oral therapy to topical formulations

While oral dapsone is effective, its clinical use is limited by the risk of serious adverse events. These include hypersensitivity syndrome developing 2–6 weeks after initiation, as well as rash, fever, hepatitis, and other systemic reactions, which may raise concern even at low doses.

Against this background, the development of topical formulations can be viewed as an attempt to separate local therapeutic effects from systemic toxicity. In clinical practice, dapsone gel 5% (twice daily) and 7.5% (once daily) are used, typically for about 12 weeks, applied in small amounts to affected areas [1, 2].

The transition to topical delivery involved several technological challenges, primarily related to skin permeability. It is not sufficient for the molecule to be included in a formulation; it must penetrate the skin in therapeutically meaningful amounts while maintaining minimal systemic exposure. One proposed solution is the use of mixed micelles as nanocarriers, enhancing both solubility and skin penetration.

As a result, systemic exposure from topical use is substantially reduced: blood concentrations are approximately 1% of those observed after a 100 mg oral dose, and overall systemic levels are 100–145 times lower. Moreover, daily systemic exposure with once-daily 7.5% gel is lower than with twice-daily 5% gel [3–5].

Effectiveness across acne types

Low systemic exposure combined with preserved biological activity expands the potential use of topical dapsone across different patient groups. This is supported by the review, which analyzed PubMed-indexed studies identified using the keywords “topical,” “dapsone,” and “acne” (84 results), along with additional data on rosacea [1].

Studies were included without restrictions on age, sex, or ethnicity, and findings were summarized narratively. This approach provides a broad clinical overview, although direct comparisons between studies should be interpreted with caution.

Overall, topical dapsone demonstrates efficacy across different forms of acne and is generally well tolerated. It reduces both inflammatory and non-inflammatory lesions, although the response is faster in inflammatory acne and more gradual in comedonal acne. This has practical implications: in patients with predominantly comedonal lesions, especially when using the 5% formulation, topical dapsone is better considered as part of combination therapy.

Dependence of response on patient characteristics

Subgroup analyses indicate that treatment response may vary depending on patient characteristics. Greater clinical improvement has been observed in women than in men, and in adults than in adolescents. For example, reductions in total lesion count in women reached 46.6%, with treatment success rates of 48.6%. In another dataset, clinical success (GAAS) in adult women reached 53.5%, exceeding that seen in adolescents.

For the 7.5% gel, age over 18 years and female sex were also predictors of a better response. At the same time, differences across racial groups and skin phototypes were minimal, and tolerability remained consistent [1].

Efficacy is not limited to facial acne. The 7.5% gel has also shown effectiveness in truncal acne, with statistically significant reductions in both inflammatory and non-inflammatory lesions.

Combination therapy

Topical dapsone also adds value to combination regimens. When used alongside systemic isotretinoin, it results in a greater reduction in lesion counts than isotretinoin alone.

In combination with doxycycline hyclate, clinical success was achieved in all patients by week 12, with 82% maintaining results during subsequent topical dapsone monotherapy [1].

Combinations with topical retinoids further enhance outcomes. Adding dapsone approximately doubles treatment success rates compared to retinoid monotherapy. Randomized 12-week studies with adapalene and tazarotene have shown greater reductions in non-inflammatory lesions with good tolerability [1, 4].

Safety and comorbid conditions

From a safety perspective, topical dapsone differs substantially from its oral counterpart. The most common adverse effects are mild local reactions, including dryness, erythema, and burning or stinging sensations, which typically decrease over time. Systemic complaints, such as headaches or upper respiratory tract infections, occur at rates comparable to those in control groups.

Particular attention should be given to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In this population, systemic dapsone is associated with a high risk of hemolytic anemia. However, with topical use, no clinical or laboratory signs of hemolysis were observed over 12 weeks, suggesting its potential for broader use in this group.

It is also important to note that although dapsone is structurally similar to sulfonamides, it is not classified as one, and cross-reactivity is not expected. This is clinically relevant for patients with sulfonamide hypersensitivity.

At the same time, rare but clinically significant adverse events have been reported even with topical use, including methemoglobinemia and hemolytic anemia, most often associated with excessive dosing. Caution is also advised when combining dapsone with trimethoprim–sulfamethoxazole in patients with G6PD deficiency, as both agents may induce oxidative stress in erythrocytes and increase the risk of hemolysis [1].

Summary and clinical perspective

Overall, topical dapsone is effective across various forms of acne and is well-tolerated. It reduces both inflammatory and non-inflammatory lesions, although the onset of action varies depending on lesion type. In comedonal acne, particularly with the 5% formulation, it is best used as part of combination therapy.

The review supports the view that topical dapsone is not merely an alternative option but a practical tool for long-term outpatient acne management, especially when a low systemic burden is desirable. It appears particularly suitable for inflammatory acne, adult patients, and women, although its use is not limited to these groups.

For clinicians, the key takeaway is that topical dapsone does not change the core treatment algorithms for acne but expands them. It offers a safer way to utilize a well-known molecule in situations where systemic dapsone would carry unacceptable risks.

Limitations should also be considered. The review is based on PubMed searches and a narrative synthesis of heterogeneous studies without a unified quantitative analysis. Some conclusions rely on subgroup and post hoc analyses, and treatment response varies depending on acne phenotype and combination regimens. Nevertheless, the overall evidence remains consistent: topical dapsone has a solid evidence base, a favorable safety profile, and a clear role in modern acne management.

In summary, the available data support the use of topical dapsone as an effective anti-inflammatory option with a balanced efficacy–safety profile.

References

1. Alsuwaidan S.N., Qadoumi T.A. Safety and effectiveness of topical dapsone in acne treatment: a review. J Family Med Prim Care 2026; 15(1): 33–38.
2. Searle T., Al-Niaimi F., Ali F.R. Dapsone for acne: Still in use after half a century! J Cosmet Dermatol. 2021; 20: 2036-2039.
3. Rao M.R., Deshpande S., Deshpande P. Dapsone-loaded mixed micellar gel for treatment of acne vulgaris. AAPS PharmSciTech 2023; 24: 109.
4. Draelos Z.D., Carter E., Maloney J.M. et al. Two randomized studies demonstrate the efficacy and safety of 5% dapsone gel for the treatment of acne vulgaris. J Am Acad Dermatol 2007; 56: 439.e1-439.e10.
5. Jarratt M.T., Jones T.M., Chang-Lin J.E. et al. Safety and pharmacokinetics of once-daily dapsone gel, 7.5% in patients with moderate acne vulgaris. J Drugs Dermatol 2016; 15: 1250–1259.