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.