Center for Dermatology and Laser Surgery, Sacramento, CA, USA
Clinical studies with topical and systemic agents for acne show remarkable improvement over a 3 month period of time, with continued progress in long-term use. However, in clinical practice it is uncommon to see these favorable results. Clinical experience and recent published data suggest that compliance, perhaps better referred to as adherence, is a major obstacle in achieving these outcomes. This article will review this problem and offer a number of suggestions, including dosing considerations and the use of laser/light devices, to better treat the nonadherent patient.
acne, patient compliance, treatment adherence
It is hard to imagine why patients with acne, particularly adolescents who are concerned with their appearance, are noncompliant with effective acne treatments that can significantly improve their condition in a 3 to 4 month period of time. In fact, recent data shows that patients in nonclinical trial settings have an adherence rate of approximately 50%.1 These findings suggest that most of our patients are not adherent. This is accurately reflected in my clinical practice where patients in clinical trials do significantly better than patients who are on routine follow-up at 3 to 4 month intervals. Furthermore, it is a mistake to assume that patients who are distraught with their disease are more compliant than those who are not.2,3
Frequency of Patient–physician Contact
A recent study demonstrated that compliance is enhanced by more frequent office visits at 1 to 2-week intervals even though the effects of the topical acne treatments take 8 weeks to significantly impact the patient’s acne.1 In this investigation, parental reminders were counterproductive, implying that “nagging” elicits opposition, which in turn causes the patient to be less compliant. Therefore, we should not underestimate the effect of a positive therapeutic relationship with positive transference between the patient and health care provider. Hopefully, dermatologists will review these data and consider more frequent visits, especially during the initiation of acne treatments and utilize electronic reminders, such as tweets, to achieve better results.
Fixed-dose Topical Combinations
In this busy world, simplifying an acne program with oncea-day treatment would help with encouraging adherence.4 There are a number of combination products (e.g., benzoyl peroxide with clindamycin, adapalene with benzoyl peroxide, and tretinoin with clindamycin) that utilize multi-agents with complementary modes of action. The concern with the daily use of clindamycin without benzoyl peroxide (BPO) is the welldocumented occurrence of bacterial resistance with clindamycin monotherapy.5 The advent of fixed combination preparations consisting of BPO with a topical antibiotic assures that the patient will not use clindamycin as a single agent. The combination of a topical retinoid with clindamycin is problematic for maintenance therapy where resistance will emerge without the concurrent use of BPO. Ideally in the future, we will have a topical combination product that will include BPO, clindamycin, and a retinoid. These products do simplify the treatment regimen, but the current array of agents are relatively weak and do not well serve our patients with moderate to severe forms of acne. In these patients, adapalene 0.3% gel and tazarotene 0.1% cream are clearly more effective.6 Currently, we utilize these agents in the morning/ evening, or with layering techniques, though I am concerned about adherence and proper use. It would be ideal to have multiagent products with the stronger retinoids in combination with BPO or BPO/clindamycin.
Potential for Devices in Managing Nonadherence
A device administered by a provider to treat acne has a great deal of appeal. This mode of treatment would preclude the development of bacterial resistance with a mechanical, not an antibiotic, mechanism of action. This would be convenient if the therapy could be delivered intermittently with a limited number of treatments. Finally, a machine or mechanical device would almost certainly have a better record of reliability than a teenage patient. Theoretically, it would be ideal if this device produced isotretinoin-like results with permanent or long-lived effects. An intriguing study done by Dr. Rox Anderson’s group at the Wellman Center for Photomedicine with aminolevulinic acid and highdose red light demonstrated dramatic and durable improvement that appeared to be associated with sebaceous gland destruction.7 Unfortunately, the inflammation elicited by the first few treatments was severe, resulting in a vigorous inflammatory response that was likely mediated by the liberation and alteration of the lipids in the sebaceous glands. Others have attempted to reproduce these results by using less light and shorter incubation periods with apparent success, but without the long-lived response that was seen in the original study. Blue light alone has limited utility.8 It activates the porphyrins that are generated in the skin by the host bacteria, which include Propionibacterium acnes, resulting in a mild photodynamic response. Unfortunately, the results are generally modest and require the addition of topical and/or systemic medication to achieve a satisfactory outcome.
Intense pulse light (IPL) devices have an effect on bacterial-derived porphyrins in acne patients.9 There is also a thermal effect on sebaceous glands, epidermal cells in the infrainfundibular region of the follicle, and perhaps the inflammatory cells mediating an inflammatory cascade. From a practical standpoint, the results are modest in my experience. However, when combined with a suction device that removes the material from the follicular canal and the sebaceous gland, there is a significant improvement in efficacy. Numerous studies have documented success in this type of device alone, and our center has worked with the combination pneumatic (vacuum) and broadband light technology, i.e., Isolaze™ and the newer updated Acleara™ instruments.10 The updated version appears to be more comfortable for patients and enhances therapeutic effects. Our experiences have demonstrated that these devices significantly enhance response in the first 5-6 weeks where the topical and systemic agents have virtually no visible effect. The weekly to every-other-week visits also provide an opportunity for encouragement and positive reinforcement.
We and other investigators have studied the utility of the pulse dye laser for the treatment of acne vulgaris.11,12 Yellow light activates the bacterial-derived porphyrins from the skin and diminishes sebaceous gland over-activity. Unfortunately, the penetration of this wave band of light is limited to the depth of sebaceous glands. The results of well-controlled clinical studies have failed to demonstrate a convincing response.11
Non-ablative 1450 nm devices have been used to treat acne with the idea that there is significant absorption by water and sebum.13 Formerly, some have suggested that lasers with this wavelength could destroy or alter sebaceous glands.13 However, the limited depth of penetration of this wavelength permits the lasers to primarily target epidermal cells in the infrainfundibular region of the follicle. Results of clinical studies have shown an encouraging clinical response with limited duration of activity.14
Theoretically, it should be possible to target sebaceous glands by delivering energy that has specificity for lipids. Currently, there is ongoing research with a 1200 nm and 1700 nm laser.15 Unfortunately, there is also significant water absorption around these peaks, which limits the specificity of the absorption to sebaceous glands alone. However, research is ongoing with the hope that there will be devices and methods that allow for specific sebaceous gland destruction.
Gender Differences Associated with Adherence
Some have proposed that adherence or compliance has a great deal to do with the sex of an individual, suggesting that boys by nature are less likely to apply their medication. However, this view is naïve and perhaps sexist since there is absence of data that looks specifically at application adherence with topical agents in males versus females. We have recently completed a study with topical dapsone that showed significantly superior results in females over males.16 While this could be due to compliance, there is also the possibility that females respond differently than males to certain treatments. This could result from hormonal differences, subtle compositional issues with sebum, or other yet to be discovered findings.
Other effective acne therapies are only appropriate for females. Certain oral contraceptives are FDA approved for the treatment of acne vulgaris in women. It might be wise to use these agents on those patients who are considering a form of birth control when treating their acne. In fact, it might be more tolerable and acceptable to consider systemic therapy with an oral contraceptive than with an oral antibiotic in young females with acne.
Patient-specific Dosing Considerations
Understanding the daily activities that an individual usually performs and tying acne treatment to them often ensures better compliance, e.g., applying a topical medication in the period after a daily wash is often convenient. Alternatively, some patients do not wash regularly, but most individuals brush their teeth 1-2 times a day. Attaching the acne treatment to this type of activity often reminds patients to perform their therapeutic regimen. Finally, using topical products with emollients might be difficult for patients who apply makeup after their morning wash.
The noncompliant acne patient is in fact the most common patient in our practices. A strong and positive therapeutic relationship with our patients is extremely important in achieving adequate adherence to a specific treatment protocol. Even though it takes 8-12 weeks to see significant improvement in most acne regimes, an initial 3-5 week visit often can provide an opportunity to encourage our patients and reinforce the importance of the therapeutic agents and their proper use. Alternatively, a device treatment performed weekly to every other week during the first 5-6 weeks can result in more rapid results and positive reinforcement, which will lead to better efficacy. The supportive role of the physician and other providers is critical in achieving success with the noncompliant patient.
- Yentzer BA, Gosnell AL, Clark AR, et al. A randomized controlled pilot study of strategies to increase adherence in teenagers with acne vulgaris. J Am Acad Dermatol 64(4):793-5 (2011 Apr).
- Renzi C, Picardi A, Abeni D, et al. Association of dissatisfaction with care and psychiatric morbidity with poor treatment compliance. Arch Dermatol 138(3):337-42 (2002 Mar).
- Renzi C, Abeni D, Picardi A, et al. Factors associated with patient satisfaction with care among dermatological outpatients. Br J Dermatol 145(4):617-23 (2001 Oct).
- Yentzer BA, Ade RA, Fountain JM, et al. Simplifying regimens promotes greater adherence and outcomes with topical acne medications: a randomized controlled trial. Cutis 86(2):103-8 (2010 Aug).
- Tanghetti E. The impact and importance of resistance. Cutis 80(1 Suppl):5-9 (2007 Jul).
- Tanghetti E, Dhawan S, Green L, et al. Randomized comparison of the safety and efficacy of tazarotene 0.1% cream and adapalene 0.3% gel in the treatment of patients with at least moderate facial acne vulgaris. J Drugs Dermatol 9(5):549-58 (2010 May).
- Hongcharu W, Taylor CR, Chang Y, et al. Topical ALA-photodynamic therapy for the treatment of acne vulgaris. J Invest Dermatol 115(2):183-92 (2000 Aug).
- Marcus SL. A Randomized, evaluator-blinded, parallel group light dose ranging study of photodynamic therapy with Levulan topical solution + blue light versus Levulan topical solution vehicle + blue light on moderate to severe facial acne vulgaris. In: ClinicalTrials.gov NLM Identifier: NCT00706433. Available from: http://clinicaltrials.gov/ct2/show/results/NCT00706433. Accessed: 2011 Oct 12.
- Dierickx CC. Treatment of acne vulgaris with a variable-filtration IPL system. Lasers Surg Med 34(S16):66 (2004).
- Wanitphakdeedecha R, Tanzi EL, Alster TS. Photopneumatic therapy for the treatment of acne. J Drugs Dermatol 8(3):239-41 (2009 Mar).
- Orringer JS, Kang S, Hamilton T, et al. Treatment of acne vulgaris with a pulsed dye laser: a randomized controlled trial. JAMA 291(23):2834-9 (2004 Jun 16).
- Tanghetti EA. Combined extended pulse-duration dye laser/drug therapy for active acne lesions. Lasers Surg Med 32(S15):75 (2003).
- Paithankar DY, Ross EV, Saleh BA, et al. Acne treatment with a 1450nm wavelength laser and cryogen spray cooling. Lasers Surg Med 31(2):106-14 (2002).
- Friedman PM, Jih MH, Kimyai-Asadi A, et al. Treatment of inflammatory facial acne vulgaris with the 1450-nm diode laser: a pilot study. Dermatol Surg 30(2 Pt 1):147-51 (2004 Feb).
- Alexander VV, Ke K, Xu Z, et al. Photothermolysis of sebaceous glands in human skin ex vivo with a 1,708 nm Raman fiber laser and contact cooling. Lasers Surg Med 43(6):470-80 (2011 Aug).
- Harper J, Oefelein M, Tanghetti EA. The efficacy and tolerability of dapsone 5% gel in female versus male patients with facial acne vulgaris: gender as a clinically relevant outcome variable. Poster presented at: 29th Fall Clinical Dermatology Conference 2010. Las Vegas, NV, 8-11 October 2010.