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