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Palmetun Ekbäck et al. Topical rapamycin tuberous sclerosis clinical practice

to reddish or skin-coloured papules in the centro- graded as no erythema, slight, medium, or severe
[3]
facial area. Patients with these lesions may suffer erythema. Angiofibromas were described as papules
negative emotional impact and stigmatization. In (< 5 mm) or nodules (≥ 5 mm). Both effects on papules,
addition, the angiofibromas can easily bleed after minor nodules and erythema and side effects were evaluated.
[4]
trauma. In 2008, Hofbauer et al. treated a patient The results were compared with the pre-treatment
with oral rapamycin, an mTOR inhibitor, to suppress photos and graded on the scale: no improvement,
graft rejection in one patient with tuberous sclerosis improvement or excellent.
who had received a kidney transplant because of
renal angiomyolipomas. They could report a marked Ethical considerations
[4]
improvement of facial angiofibromas. In 2010, This retrospective study is a clinical follow-up of the
[5]
Haemel et al. succeeded in preparing a topical patients treated with topical rapamycin according to
ointment which had effect on facial angiofibromas. clinical praxis. In Sweden, a formal approval from
[6]
In 2011, Mutizwa et al. reported that an oral solution an Ethics Committee is not needed for a clinical
with rapamycin could be used on the skin with good follow-up. This was also discussed with our Ethical
result. Since then, there are several case reports [7-10] Committee. All patients and/or parents got orally and
and studies [11-14] reporting improvement after topical written information about the treatment and potentially
rapamycin applied once or twice daily. [15-18] side effects and gave their informed consent.

The aim of this retrospective observational study was RESULTS
to describe the outcome in clinical practice treating
angiofibromas in TSC with topical rapamycin. Clinical results
Twenty-three patients (10 males) were included in the
METHODS retrospective observational evalutaion. The mean age
was 19 years (range 2-52 years) [Table 1]. The duration
Patients and methods of treatment was from 3 weeks to 33 months. Six
All patients, who had been treated with topical patients discontinued the treatment. Of these, 2 were
rapamycin between January 2012 through December lost to follow-up; 2 were put on oral everolimus treatment
2014 at the Dermatology Departments Karolinska because of internal hamartomas; and 2 discontinued
University Hospital Stockholm and Örebro University the treatment after 3 weeks because of intractable
Hospital, were followed up in this retrospective side effects, such as skin pain, severe dryness, itching,
observational evaluation. There were in total 23 burning sensations, erythema and swelling [Table 1].
patients. Fifteen of the 23 patients had previously
been treated with CO 2 laser. Sixteen of 23 patients Seventeen patients continued the treatment [Figure 1].
had tuberous-sclerosis-associated neuropsychiatric
disorders (TAND) and 18 had severe epilepsy. All 23 23 patients
patients had been prescribed an oral solution of 0.1%
rapamycin, but told to apply it on all facial lesions once
a day. In case of skin irritation the patients had been
instructed to refrain from treatment for a couple of days
and use a weak topical glucocorticoid cream, and then 2 patients lost before follow-up
resume the rapamycin treatment when the skin irritation
had subsided. In the beginning of the treatment we
instructed the patients/parents to discontinue during the
summer, because of uncertainty regarding interaction 2 patients put on oral
with sunlight. The summer pause was from mid-June to everolimus treatment
mid-August 2012. The patients were initially instructed
to give blood samples for measurement of serum
rapamycin after four weeks of treatment. Treatment 2 patients discontinued
photos were taken. Follow-up was done through visits because of side effects
in person or through e-mailed photos, as some patients
lived far from the clinics. All evaluations were done by
the authors. The authors looked at several photos prior
to the evaluation in order to reach consensus about 17 patients continued
the grading, as there was no standardized grading
system at the time for the evaluation. Erythema was Figure 1: Flow diagram of patient population
Plastic and Aesthetic Research ¦ Volume 3 ¦ October 25, 2016 329