The observations of a beneficial effect of 5-fluorouracil-induced actinic keratoses (AK) inflammation led to the development of topical fluorouracil, a product registered for the management of AK. A conscientious surveillance of AK inflammation during chemotherapy may conceivably lead to the development of further drugs for treatment of AK. A number of other chemotherapeutics have thus been linked to similar reactions without ensuing development. Here, we describe two further cases linking chemotherapy with carboplatin and paclitaxel to possible anti-AK effects, identifying them as potential treatments. Whether multidrug chemotherapy leads to stronger AK inflammation or cure AK more successfully is currently unknown.

© 2022 The Author(s). Published by S. Karger AG, Basel

A conscientious surveillance of inflammation of manifested and/or subclinical actinic keratoses (AK) during chemotherapy may lead to the development of further drugs for the management of AK. The observations of a beneficial effect of 5-fluorouracil-induced AK inflammation have already contributed to the successful registration of topical fluorouracil in the management of AK [1, 2]. Besides pyrimidine analogs, a number of other chemotherapeutics, classified into chemotherapeutic groups of protein kinase inhibitors, taxanes, folic acid analogs, alkylating agents, platinum compounds, purine analogs, vinca alkaloids, cytotoxic antibiotics, and monoclonal antibodies, have been linked to similar reactions, suggesting potentially meaningful new pharmacodynamics mechanisms for further research [3-12]. Here, we present two interesting new cases of inflammation of AK induced by chemotherapy with carboplatin and paclitaxel to add new evidence for their anti-AK effect. Whether multidrug chemotherapy leads to stronger AK inflammation or cure AK more successfully is currently unknown.

For the case presentation, see Table 1 and Figures 1, 2. The manuscript was prepared according to the CARE Checklist, attached as supplementary material (for all online suppl. material, see www.karger.com/doi/10.1159/000528128).

Close-up photo of the first patient, showing inflamed AK on the extensor part of the right forearm.

Photos of the second patient, showing (a) inflamed AK at the referral and (b) regression of inflammation with few AK left at follow-up several months later.

Our 2 cases of inflamed AK occurred 1 month and 2 days after initiation of chemotherapy. These observations potentially link carboplatin, paclitaxel, and trastuzumab to anti-AK effect.

Selective inflammation of AK during chemotherapy is possibly a consequence of direct cytotoxicity of an active compound on atypical keratinocytes that accumulate ultraviolet-induced damage of deoxyribonucleic acid, but the exact mechanism of how different chemotherapeutics achieve this effect seems to be drug-dependent [13]. Alternative explanations of skin lesions (i.e., subacute lupus erythematosus, actinic lichen planus, cutaneous vasculitis, hypersensitivity drug reactions, drug-induced photosensitivity reactions, and photocontact dermatitis) were in both patients excluded on the basis of a history, typical clinical features of AK, and in the first case with the additional characteristic presence of atypical keratinocytes on histological examination [14-20].

Reports of partially successful curing of AK while undergoing therapy with carboplatin and/or docetaxel, a chemotherapeutic agent belonging together with paclitaxel to the pharmacological group of taxanes, already exist [21-24]. Since a co-occurrence of inflamed AK and treatment with trastuzumab has not been reported before and it targets human epidermal growth factor receptor 2-overexpressed cells, its role in AK inflammation is questionable [25]. This suggests the importance of prioritizing research into potential topical forms of paclitaxel and carboplatin in the management of AK. In conclusion, careful observations of AK inflammation in patients undergoing chemotherapy represent a starting point for the development of new topical products for the management of AK.

Authors would like to thank Luka Čavka, MD, PhD, and Maja Ravnik, MD, for referral of patients to the dermatology department and Jože Pižem, MD, PhD, for the histological examination of the biopsy in the first patient.

Although case reports present only objective data on the patients’ disease and the authors did not test new methods of diagnosis and treatment, ethics approval was not required for the publication of the study according to the rules on the membership, responsibilities, and working methods of the Republic of Slovenia National Medical Ethics Committee (EVA 2019-2711-0059; SOP 2020-01-0342). Written informed consent was obtained from both patients for publication of this case report and any accompanying images.

Gregor Borut Ernst Jemec has received honoraria from AbbVie, Chemocentryx, Coloplast, Incyte, InflaRx, Kymera, Leo Pharma, Moonlake, Novartis, UCB, Union Therapeutics, and Wella for participation on advisory boards and grants from AbbVie, AstraZeneca, CSL, InflaRx, Janssen-Cilag, Leo Pharma, Moonlake, Novartis, Regeneron, and Sanofi for participation as an investigator and received speaker honoraria from AbbVie, Boehringer Ingelheim, Galderma, and Novartis. He has also received unrestricted departmental grants from Leo Pharma and Novartis. Other authors report no conflict of interest.

This work was not supported by any funding.

Špela Šuler Baglama contributed to conception and writing; Anja Trajber Horvat and Irena Peteln contributed to writing; Gregor Borut Ernst Jemec revised the article; all the authors gave final approval of the version of the article to be published.

All data generated or analyzed during this study are included in this article and its online supplementary materials. Further enquiries can be directed to the corresponding author.

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