INTRODUCTION
Acne vulgaris (acne) is the most common skin disease, and in many cases a chronic condition constantly changing in its distribution and severity.1 It can result in significant physical and psychological impact lasting for years. It is most common in post-pubescent teens, with boys most frequently affected, particularly with more severe forms of acne. Both prevalence and severity increase with pubertal maturation. The presence of severe acne in childhood (2.8%) is relatively rare, but prevalence steadily increases to reach 12.1% by age 17.2 Adolescents with severe acne have suicidal thoughts more frequently than those with less severe acne.3 A positive family history is associated with higher risk of developing severe acne.4 Acne severity can also be influenced by environmental factors,5 and diet,6 and severe acne is associated with a number of comorbid conditions.2 It persists into adult years in as many as 50% of individuals. Oral antibiotics, such as tetracycline, doxycycline, and minocycline, have been a mainstay of treatment for moderate-to-severe acne. However, their systemic side effects warrant the need to look for alternative treatment options.7-9 In addition, it is recommended their use should be limited to the shortest time possible to minimize the development of bacterial resistance, and that they are used with concomitant topical therapy.10 Although topical treatments alone are not perceived as suited for treatment of the severe papulopustular, non-nodulocystic acne; a topical therapy effective enough to improve severe inflammatory acne alone or in combination without the need for oral isotretinoin (and its associated side effects) or concomitant antibiotic therapy (to reduce microbial resistance) would represent a significant unmet need. A number of fixed combination topical therapies have been studied in moderate-to-severe acne. There are few studies specifically in severe acne patients and many do not include the subpopulation data required to assess utility. Here we review all the available clinical data on the use of topical therapies in severe acne.
Use of Topical Therapy in Combination With Oral Antibiotic in Severe Acne
Studies with topical therapy in severe acne are scarce, and mostly limited to those where they have been used in combination with oral antibiotics. Combining a fixed combination topical with an oral antibiotic provides additional efficacy benefits in severe acne (see Table 1). The efficacy and safety of adapalene 0.1%-benzoyl peroxide 2.5% (0.1% Adap-BP) fixed combination with doxycycline (the most frequently prescribed oral antibiotic for acne in the United States) was assessed in 459 patients with severe acne (Investigators Global Assessment [IGA] score of 4).11 At week 12, the combination was significantly more effective than doxycycline
