DISCUSSION
Acne is a common skin condition usually characterized by a prolonged course, a recurring pattern of flare-ups and remissions, with a psychologic and social impact, that affects the individual’s quality of life.1-7,9 Thus, proper treatment is imperative for these patients.
A central role of antibiotics and retinoids as systemic therapies for acne is well established despite a challenged safety profile, that for many lead to significant adverse effects often resulting in ceased treatment.14,20,46,69 Therefore, low-dose regimens of oral retinoids or antibiotics combined with corticosteroids or other anti-inflammatory therapies represent an interesting alternative approach.14,21-26 Furthermore, other viable and more recent options to overcome the limitations associated with standard established acne therapies,20,46 are light-based therapy such as FLE with previous clinical evaluation reporting improvement of at least one IGA grade by week 12 for 88,8% of patients treated for moderate to severe acne.15 Acne is a highly complex and multifactorial skin condition, which challenge treatment. It is unknown why some patients respond less pronounced to FLE treatment or tetracycline alone or why only some patients experience severe adverse effect of standard dose isotretinoin therapy. However, combination therapies are often advantageous for complex skin diseases such as acne and rosacea,12,70 leading to our hypothesis that targeting several acne infliction factors by combining FLE with low-dose isotretinoin or tetracycline treatment is highly advantageous. Our objective was therefore to describe the efficacy and safety of the combination of FLE with low-dose systemic drugs, isotretinoin or tetracycline in treatment of moderate to severe acne.
Efficacy evaluation was performed by IGA grading severity and improvements at week 6, 12, 33 and 52. We found that at the first assessment, 6 weeks after treatment was initiated, all patients showed improvements of at least 1 IGA grade in their clinical skin conditions, while 50% showed 2 IGA grades improvement. This fast response can sometimes be obtained in patients treated with standard dose of tetracycline,71 but is unlikely to be explained by the low-dose regimen of tetracycline or isotretinoin used in this trial, suggesting a positive additive effect of FLE. Moreover, efficacy evaluation at week 12 revealed that as much as 75% of the treated cases dropped to an IGA grade of 1, which could likely not be ascribed to low-dose systemic treatment alone, further substantiating the positive effect of the tested FLE-combination therapy. All patients treated with isotretinoin reached and maintained an IGA grade of 0 at weeks 33 and 52. The three cases treated with tetracycline; however, obtained not more than a drop in IGA grade to 1 at weeks 33 and 52. This further corroborates the efficacy of combining low-dose systemic treatment with FLE therapy, although seemingly more efficient when combined with isotretinoin compared with tetracycline. Although, more cases are needed to further assess these considerations, they are in line with or recent and imminent observations.65
Symptoms of acne is known to fluctuate and worsening in beginning of treatment is a common side-effect, often requiring long-term systemic therapy to obtain and maintain clearance.11 This has many disadvantageous, for standard dose isotretinoin this associates with continuous risk of adverse affects such as increased CPK levels and xerosis, whereas tetracycline risk development of antibiotic resistance.72 Interestingly, we found that remarkable improvements of the disease was obtained fast and persisted throughout the evaluation period with only one course of antibiotic treatment necessary, besides follow-up FLE sessions at week 33 and 52. The clinical, cellular and molecular pathways targeted and modulated by FLE is currently under investigation. Results so far indicate that FLE modulate activity and function of several skin cells as well as directly target bacterial viability,17-19,49,62 suggesting that FLE improve acne symptoms by targeting several aspects of the disease. We speculate that the combined treatment of moderate-severe acne by FLE, targeting inflammation and likely other aspects of this complex condition in combination with initial isotretinoin that lower sebum production or tetracycline directly killing C. acnes bacteria lay the basis for consistent normalization of the skin.
Finally, all 12 enrolled patients completed the therapy and were satisfied with the outcome, treatment was well-tolerated overall, and no severe adverse effects were reported. In general, patients experienced fast (within few weeks) improvement of their inflammatory acne skin conditions with redness reduction, edema decreasing and a general improvement of skin appearance. Low-dose isotretinoin treatment was maintained for some patients, evaluated individually according to obtaining the desired clearance, but no intolerable adverse effects were reported in relation to this. Our results support the combination of FLE treatment with tetracyclines or low-dose isotretinoin in moderate to severe acne. Although both isotretinoin and tetracycline are potential photosensitizing drugs,11,72 their use according to our study protocol, did not negatively interfere with FLE treatment, but seemingly enhance its efficacy in a safe and long-term manner.