Combination therapy for solar lentigines

Journal of Drugs in Dermatology, Sept-Oct, 2004 by Patricia K. Farris

Abstract

Solar lentigines are benign, hyperpigmented lesions that present a significant cosmetic nuisance for many middle-aged and elderly patients with chronic accumulated sun exposure. While previous monotherapies designed to lighten these lesions offer relatively modest improvement, there are several new treatment options. Combination topical therapy using 2% mequinol/0.01% tretinoin [Solage[R] Topical Solution] has been shown to markedly reduce lesion darkness with few side effects. Chemical peels can give good results either alone or in combination with topical therapy. Cryotherapy is an effective and inexpensive way of treating solar lentigines while IPL and lasers are more costly treatment options. For patients desiring treatment, optimal cosmetic improvement can be achieved using a combination of topical and procedural therapies.

**********

Introduction

Solar lentigines, also termed senile lentigines, are extremely common hyperpigmented macular lesions, ranging from pale yellow to dark brown, that appear on sun-exposed areas of the body (Figure 1). Solar lentigines are most common on the dorsa of the hands, the forearms, and the face. They are characterized by increased numbers of active melanocytes and increased melanin production resulting from years of cumulative sun exposure (1). They are virtually ubiquitous in elderly Caucasians and appear in 90% of light-skinned individuals over the age of 60 (2).

[ILLUSTRATION OMITTED]

Although benign, solar lentigines pose a significant cosmetic problem for many patients. Not only do they detract from the appearance when they are present in large numbers, but many people associate them with aging. The lay terms for these lesions are "age spots" or "liver spots." Due to their benign nature, many dermatologists and family physicians downplay them to patients. However, it is important to understand the level of psychosocial stress that may attend solar lentigines and to offer treatment to those patients who are distressed by these lesions. The ideal therapy for lentigines would be inexpensive, achieve results rapidly, involve no down-time and have no risk of complications. No perfect therapy exists, however, there are numerous treatment options. Their selection depends upon patient factors including budget, ability to comply with therapy and time constraints.

[FIGURE 1 OMITTED]

Topical Therapies

A variety of topical monotherapies have been used to treat solar lentigines including hydroquinone, topical retinoids, and kojic acid. However, a long latency is required before their results become visible and many patients become discouraged before significant improvement occurs. Hydroquinone monotherapy is minimally effective for lentigines and may cause irritation.

Combination topical therapy offers a significant advantage over monotherapy. It is an inexpensive option for patients who may not be able to make frequent office visits. It requires a relatively long treatment period, and diligent compliance with therapy is essential for their success.

A dual-combination topical solution of 2% 4-hydroxyanisole (mequinol) and 0.01% tretinoin [Solage[R] Topical Solution] has been introduced for the treatment of lentigines and other hyper-pigmented lesions. Mequinol has been shown to be less irritating than hydroquinone in animal studies and has no known cytotoxicity to human melanocytes (3). The efficacy and safety of the combination mequinol/tretinoin product in the treatment of solar lentigines was studied in two phase III randomized, controlled double-blind trials (4). The first trial consisted of a 24-week treatment phase followed by a 24-week no-treatment regression phase to study the duration of effect. The study enrolled 595 subjects whose mean age was 62.6 ([ or -]9.51 SD) years. The patients were randomized to receive either mequinol/tretinoin (n=217), tretinoin alone (n=217), mequinol alone (n=106), or vehicle (n=55).

The second Phase III trial included a 24-week treatment phase followed by a 4-week no-treatment phase. It enrolled 580 subjects whose mean age was 63.9 ([ or -]9.14 years). There were 212 subjects in the mequinol/tretinoin group, 210 in the tretinoin group, 105 in the mequinol group and 53 in the vehicle group. Lightening of the treated lesions occurred gradually over 24 weeks.

In both trials, the mequinol/tretinoin combination was clinically superior to monotherapy with either of its components and vehicle on the forearm and face (P[less than or equal to].03). In Trial 1, 52% and 56% of the mequinol/tretinoin group achieved moderate or better clinical success, by physician's global assessment, on the face and forearms compared with 35% and 43% in the tretinoin group, 24% and 33% for the mequinol group and 17% and 19% for vehicle. The combination formulation continued to demonstrate statistically significant superiority (P[less than or equal to].003) to each of its active ingredients alone and to vehicle. It was also superior to each of its active components and vehicle for "target lesion pigmentation" and "physician's assessment of overall cosmetic effect" for forearms and face. In Trial 2, the mequinol/tretinoin combination demonstrated significant superiority in the physician's global assessment over each of its active ingredients and vehicle on the forearm at the end of treatment. For the face, the combination formulation achieved significant superiority over mequinol and vehicle (P=.0001) and was directionally superior to tretinoin in achieving moderate or greater improvement. However, the difference (57% vs 48%) was not statistically significant (P=.2).