RESULTS
Therapy combinations were tailored according to the individual patient´s response to previous treatments, health condition, and current wishes. In half of the cases, patients were not eligible to standard doses of isotretinoin due to previous discontinued therapy caused by severe adverse effects, including dryness of skin, elevated levels of creatine phosphokinase (CPK) or transaminase, worsening of symptoms, or preceding disease history (Figure 1A-D). Furthermore, most patients had previously been treated with tetracycline and topical therapeutics without effect. These patients were in this trial treated with FLE in combination with low-dose isotretinoin alone or for some female cases together with contraceptives. Substantial improvements in acne symptoms were observed in all six patients already at week 6 after treatment was initiated with further gradual clearance throughout the trial and complete clearance at week 52 (Figure 1A-D).
A group of non-responders to tetracycline and topical treatments was treated with FLE in combination with low-dose isotretinoin (Figure 2 and 3A). In these patients a similar gradual clearance was seen throughout the treatment and observation time. Especially a marked progressive reduction in inflammation was observed (Figure 2 and 3A).
Finally, three patients with moderate acne symptoms were treated with FLE combined with tetracycline. For these patients previous treatment using topical or standard dose tetracycline or isotretinoin regimes failed. Although substantial improvements were observed for all three patients, few papules and comedones remained and complete clearance was not obtained (Figure 3B-D).
Taken together, all patients showed substantial improvements in the clinical appearance of the skin already at week 6 after treatment was initiated (Figure 4A). In 50% of the cases, patients showed a marked enhancement quantified by a 2-grade improvement according to the IGA scale, whereas the remaining 50% presented with a 1-grade decrease according to the IGA score (Table III). At the week 12 evaluation, 75% of patients showed a reduction in clinical severity to IGA 1. The remaining 25%, showed improvements corresponding to 1- to 2-grade IGA reduction although maintaining IGA scores of 2-3. Interestingly, at the evaluation at week 33 and 52 patients treated with FLE in combination with isotretinoin reached and maintained an IGA score of 0 at week 33 and 52, whereas the three patients treated with FLE combined with tetracycline presented an IGA score of 1 (Table III).
At the final evaluation at week 52, patients evaluated satisfaction with the clinical outcome and the treatment as a whole. All patients reported high satisfaction rates with the treatment results. Overall, 75% of subjects were very satisfied and 25% satisfied with the treatment outcome (Figure 4B). Thus, we found a substantial association between IGA-rated improvement and patient satisfaction.
Adverse effects related to the treatments were assessed after each FLE session by the patients evaluating and reporting. Overall, no severe or intolerable adverse effects were reported (Figure 4C) and no patients discontinued the study. In line with previous clinical studies,15,16 a few patients reported that FLE treatment induced transient erythema (lasting no more than 36 hours), temporary skin hyperpigmentation or a slight sensation of burning during the session (Figure 4C). The most reported side-effects related to the systemic therapy, including dryness of skin and mucosae in patients taking isotretinoin and transient abdominal swelling (lasting a few days) in patients on tetracycline (Figure 4C).