One scientific committee for the project was established, including 8 dermatologists (7 Spanish and 1 Portuguese) focused on facial and truncal acne. The committee, with methodological assistance, defined the objectives, scope, and sections of the document. Four major topic groups were addressed: 1) preferences for topical acne treatment; 2) skin irritation and topical acne treatment with retinoids; 3) recommendations/guidelines to prevent/reduce skin irritation in topical acne treatment with retinoids; and 4) extreme weather conditions and skin irritation and topical acne treatment with retinoids.

A literature review (PUBMED and COCHRANE) on recommendations and strategies to improve the tolerability of topical retinoids in acne treatment was conducted. With the information obtained, the scientific committee created a series of preliminary recommendations.

The scientific committee met twice to review and confirm the objectives, scope, and sections of the document. Subsequently, the results of the literature review and the provisional recommendations were presented and discussed. This led to the definition of 34 final recommendations.

The 34 final recommendations were subjected to consensus using the Delphi method14 to establish the level of agreement on such recommendations.

This was done online through Google Forms and, in addition to the scientific committee, these recommendations were submitted to 125 dermatologists (108 Spanish and 17 Portuguese). Votes were cast on a Likert scale15 from 1 (totally agree) to 5 (totally disagree). Consensus was defined when, at least, 85% of participants voted ≤ 2 (totally agree and agree), and majority when, at least, 70% of participants voted ≤ 2. Recommendations with a level of agreement <85% in the 1st round of voting were voted in a 2nd Delphi round (the cutoff values did not change from the 1st to the 2nd Delphi round). This methodology was selected due to its common and recent use in the field of acne.16,17

When prescribing a topical treatment for facial and truncal acne, what experts value most is its efficacy and tolerability, with a 95.5% and 90.2% level of agreement respectively reached in the 1st round. Simplicity in the routine/dosage achieved a 75.9% level of agreement in the 1st round and majority consensus in the 2nd round with a 82.7% level of agreement.

Recommendation #4. Skin irritation is a barrier to prescribing a topical treatment.

Since only 64.7% of participants agreed with this statement in the 2nd round, it did not reach consensus. That skin irritation is a barrier to prescribing a topical treatment is a debatable and nuanced issue, as experts consider it a limiting factor only if appropriate measures to prevent or treat irritation are not taken, such as prescribing specific non-comedogenic moisturizers or spacing out applications if necessary. With proper precautions, skin irritation should not be an obstacle to prescribing topical retinoids for facial or truncal acne.

Recommendation #5. The waiting time to obtain results is a barrier to prescribing a topical treatment.

This statement received a <50% (47.10%) level of agreement in the 2nd round, and was, therefore, unable to reach consensus. The lack of agreement on this issue created some controversy within the group, as–a priori–the waiting time to see the first results was considered a relevant variable since patients usually prefer quick results. Any retinoid (whether oral or topical) takes time before the first results are noticeable, being a common thing for oral retinoids to cause an initial worsening of acne within the first weeks of treatment.18 One expert recommended starting with topical—before oral—retinoid treatment to avoid the usual initial worsening associated with oral retinoids.

There are patients for whom topical retinoid treatment would be indicated regardless of the time it takes to achieve results, such as patients who do not meet criteria for oral treatment, patients who need combined therapies (oral and topical), and those requiring maintenance with topical retinoids after finishing oral retinoid treatment.

Recommendation #6. Photosensitivity is a barrier to prescribing a topical treatment.

With only 30.10% agreement in the 2nd round, this statement received the lowest level of agreement of all consensus statements. It is well-known that sun exposure should be avoided while on topical retinoids,7 which is why it was particularly notable that there was no agreement on this issue. After analyzing the results, the expert committee explained this lack of agreement by considering that photosensitivity is not a barrier per se since there are easily accessible and applicable tools (photoprotectors) for patients. None of the experts, from the Iberian Peninsula or the Balearic and Canary Islands, would refrain from prescribing a topical treatment due to photosensitivity. Even in some cases with a high risk of photosensitivity, topical retinoid treatment might be preferred over full-dose oral retinoids, which can have more side effects of irritation and photosensitivity than a properly applied topical treatment.

The 6 recommendations voted in this block reached consensus (level of agreement ≥ 85%) in the 1st round, making it the block with the highest level of agreement among all those evaluated.

Recommendation #8. Mild and controllable skin irritation frequently occurs at the beginning of treatment.

Recommendation #10. It is important to tell the patient that temporary irritation is normal and expected and, therefore, treatment should not be discontinued.

These 2 recommendations achieved consensus with a 98.5% level of agreement. Consensus was unanimous regarding irritation being associated with topical retinoid treatment as an expected, mild, and controllable side effect at the beginning of treatment that tends to decrease over time. The entire expert committee agreed on the importance of explaining how retinoids work to avoid treatment discontinuation due to a lack of results within the first few days of treatment or poor tolerability.

Recommendation #7. I consider that irritation is an expected reaction at the start of treatment and not an undesirable side effect.

Recommendation #12. Patients who follow the application recommendations/guidelines properly tend to have fewer skin irritation problems than those who do not.

These 2 issues reached consensus with a 94.7% level of agreement in the 1st round. The experts showed a high level of agreement on the importance of explaining patients that if they apply the guidelines/recommendations properly, they will have fewer tolerability issues, and that they should not discontinue treatment despite initial irritation since it is not an undesirable side effect (except for very sensitive skin).

Recommendation #11. Skin irritation can be prevented and/or reduced by following correct application guidelines/recommendations.

A total of 97% of participants considered that skin irritation treated with topical retinoids can be prevented/reduced if the proper guidelines/recommendations are followed. The expert committee summarized the main recommendations in Figure 2.

Figure 2.

Recommendations from the expert group to prevent/reduce skin irritation in the topical treatment of acne with retinoids.

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In this block, a total of 7 recommendations were evaluated, 4 of which reached consensus in the 1st round. Specifically, recommendation #16, “spacing the applications of topical retinoids helps prevent and/or reduce skin irritation,” with a 99.2% level of agreement, was the recommendation that obtained the highest level of agreement among all the issues on which votes were cast.

Recommendation #13. Applying topical retinoid correctly at night helps prevent and/or reduce skin irritation.

Recommendation #17. Combining treatment with specific non-comedogenic moisturizers and SPF helps prevent and/or reduce skin irritation.

These 2 recommendations achieved broad consensus, with 91% and 94% levels of agreement, respectively in the 1st round as strategies to improve the tolerability of topical retinoid treatment.

Recommendation #14. Washing the face with specific products in the morning to remove retinoid residues helps prevent and/or reduce skin irritation.

Recommendation #15. Drying the skin by patting (without rubbing) helps prevent and/or reduce skin irritation.

These 2 recommendations reached consensus in the 2nd round with a nearly 90% level of agreement in both cases (see detailed results in table 1). The expert committee considers these 2 measures of paramount importance regarding good tolerability associated with topical retinoids: washing the face in the morning to remove the residues of the treatment applied the night before with specific non-comedogenic products and doing so carefully without rubbing the skin when drying.

Recommendation #18. The wash-off technique (applying treatment, waiting 30 to 60minutes, and washing the face with a specific product) is a measure that helps prevent and/or reduce skin irritation.

In the 2nd round, “the wash-off technique (applying treatment, waiting 30 to 60minutes, and washing the face with a specific product) is a measure that helps prevent and/or reduce skin irritation” that obtained a majority level of agreement with 76%. Although this technique can slow down the process of applying treatment, it is an interesting technique for very sensitive skins, especially within the first few days of treatment.

Recommendation #19. I find the following standard administration protocol for initiating topical retinoid treatment for acne to be correct (see figure 2).

A total of 88% of voters found the standard administration protocol for initiating topical retinoid treatment for acne presented in Figure 3 to be correct in the 1st round. Having a validated schedule to start a topical retinoid treatment was a requirement that the expert committee considered necessary when sharing these recommendations with other medical professionals.

Figure 3.

Standard administration protocol for starting topical retinoid treatment for acne. √ indicates the nights when the topical retinoid should be applied.

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With 15 recommendations, this block was the most extensive of the 4 and generally obtained the lowest level of agreement: 8 issues reached consensus (7 in the 1st round and 1 in the 2nd round), 4 issues achieved a majority consensus, and 3 did not reach any levels of agreement.

Recommendation #20. It is preferable to START a topical retinoid treatment for acne when the weather is not extreme.

Recommendation #21. The time of year does not matter when starting a topical retinoid treatment for acne.

Neither of these 2 issues, with 67.7% and 39.8% levels of agreement, respectively, in the 2nd round, reached consensus or a majority consensus either.

Starting topical retinoid treatment during extreme weather conditions, i.e., periods of high sun exposure (summer months in the Iberian Peninsula) or intense cold (winter months in the Iberian Peninsula), were the issues that generated the most controversy within this block. The expert group concluded that, considering that the use of topical retinoids in extreme weather conditions is closely related to irritation (cold) and photosensitization (heat/sun), it seems logical that these issues did not reach consensus (which is consistent with recommendations #4 and #6 from block A, which also did not reach consensus).

Recommendation #26. During extreme weather conditions, I prefer my patients to space out the applications of topical retinoids.

This recommendation received a 59.4% level of agreement in the 2nd round, not reaching a majority consensus or consensus for that matter. The expert committee clarified that the need to space out applications does not depend so much on the time of year but on the tolerability and the phase of the treatment the patient is in. Spacing out applications is a recommended and widely used measure at the beginning of the treatment or when the patient experiences a high level of irritation, regardless of the weather.

Recommendation #32. I avoid topical retinoid treatment in patients with fair skin types during periods of high sun exposure.

A majority disagreement was reached (81.2% in the 2nd round) that, in patients with fair skin phototypes, it is not necessary to avoid topical retinoid treatment during periods of high sun exposure. In fact, although it can occur in any patient, post-inflammatory hyperpigmentation in acne patients is more common in darker skin types.19 The expert committee emphasized that in any patient, the proper application of photoprotection provides protection regardless of the patient's skin type.

Recommendation #33. Irritation due to photosensitization by topical retinoids is a very common issue in my clinical practice.

There was a majority disagreement (80.50% in the 2nd round of voting) that irritation due to photosensitization induced by topical retinoids is a very common issue in the dermatologists’ office. Some experts acknowledged not having seen any patients with photosensitization due to topical retinoids, but some with photosensitization due to oral retinoids.