Abstract Number: 226

Severe ingenol mebutate skin reaction while onmethotrexate: a case series and proposalof pathogenesis

C.Y. Zhao, D.F. Murrell

Meeting: 2015 Dermcoll

Session Information

Date: -

Session Title: Poster Presentations

Session Time: -

Introduction: Ingenol mebutate (Picato) is a new topical
field therapy for actinic keratosis (AK) with a dearth of data
regarding its drug-interactions profile.

Cases series:
1. A 79-year-old female developed erythema, crusty
plaques and periorbital oedema a day after using ingenol
mebutate 0.015% for to her forehead AKs for 2 days. The
erythema persisted for one month. She was on methotrexate
10 mg weekly for her Churg-Strauss syndrome
concomitantly.
2. A 66-year-old female developed erythema, crusty
plaques and vesicles after using ingenol mebutate 0.05%
to her forehead AKs for a day (she was advised to only
use 1 satchet given the stronger strength). She was on
methotrexate 20 mg weekly for her rheumatoid arthritis
concomitantly.

Discussion: From these cases we suspect that severe skin
reactions may be triggered by ingenol mebutate, whilst
patients are on certain systemic medications. Methotrexate
works by depleting the intracellular stores of folate,
with anti-proliferative and anti-inflammatory effects on the
epidermal cell.
Meanwhile, ingenol mebutate works by
rapid necrosis of the dysplastic keratinocytes with immunostimulatory effects.
Differentiating keratinocytes also have
reduced sensitivity to ingenol mebutate.
Therefore, it is likely that the patient was particularly sensitive to ingenol mebutate, as her keratinocytes had reduced differentiation
secondary to the methotrexate use. On literature review,
neither has methotrexate and ingenol mebutate’s drugs
interactions been reported, nor has there been any studies
addressing ingenol’s mebutate drug interactions profile.
Conclusion: These cases highlight the need to evaluate
ingenol mebutate’s drug interactions profile, especially
with anti-proliferative systematic medications such as
methotrexate.