Lenvatinib-induced severe generalized erythematous rash in a patient with hepatocellular carcinoma

概要

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Lenvatinib-induced severe generalized
erythematous rash in a patient with
hepatocellular carcinoma

Matsumoto, Yukari
Fukumoto, Takeshi
Takahashi, Wakako
Nishigori, Chikako
(Citation)
Dermatology Reports,15(2):9617

(Issue Date)
2023

(Resource Type)
journal article

(Version)
Version of Record

(Rights)
©Copyright: the Author(s), 2023
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0
International License (CC BY-NC 4.0).

(URL)
https://hdl.handle.net/20.500.14094/0100482715

Dermatology Reports 2023; volume 15:9617

Lenvatinib-induced severe generalized erythematous rash in a patient
with hepatocellular carcinoma
Yukari Matsumoto, Takeshi Fukumoto, Wakako Takahashi, Chikako Nishigori

Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan

Conflict of interest: the authors declare no potential conflict of interest.

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Funding: none.

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Ethical approval and consent to participate: written informed consent was obtained from the patient.

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Availability of data and material: data and materials are available by
the authors.

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Received for publication: 29 October 2022.
Accepted for publication: 11 November 2022
Early view: 29 December 2022.

This work is licensed under a Creative Commons AttributionNonCommercial 4.0 International License (CC BY-NC 4.0).

©Copyright: the Author(s), 2023
Licensee PAGEPress, Italy
Dermatology Reports 2023; 15:9617
doi:10.4081/dr.2023.9617

Publisher's note: all claims expressed in this article are solely those
of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article or claim
that may be made by its manufacturer is not guaranteed or endorsed
by the publisher.

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Contributions: YM, TF and CN designed the study and wrote the
manuscript. YM, TF, WT and CN contributed to data collection and
interpretation of the results. MY, TF, and TW and CN approved the
final manuscript.

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Key words: lenvatinib, rash, hepatocellular cancer, multikinase
inhibitor, ichthyosis.

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Correspondence: Takeshi Fukumoto, Division of Dermatology,
Department of Internal Related, Kobe University Graduate School
of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Tel.: +81.78382613 - Fax: +81.783826149.
E-mail address: fuku@med.kobe-u.ac.jp

(E7080) versus sorafenib in first-line treatment of subjects with
unresectable hepatocellular carcinoma] trial showed that lenvatinib is non-inferior to sorafenib in terms of overall survival of
patients with unresectable hepatocellular carcinoma (HCC); thus,
the FDA approved lenvatinib as a first-line drug for the treatment
of unresectable HCC.1,3,4 According to REFLECT and SELECT,
common adverse events (AEs) for lenvatinib include hypertension
and diarrhea.2,3 To our knowledge, no detailed cases of lenvatinibinduced generalized erythematous rash (GER) have led to its discontinuation.1-4 Herein, we present the first such case reported in
detail.
A 72-year-old man and a history of ichthyosis and no history
of allergies underwent partial liver resection (hepatic segment
VIII) for the treatment of HCC. Six months after surgery, computed tomography revealed unresectable HCC lung metastases for
which he received lenvatinib.
Two weeks after the administration of lenvatinib, erythematous scales covered his entire body (Figure 1 a-c). He had been
diagnosed with dermatomycosis of the skin of whole body and
treated by terbinafine tablets and luliconazole cream at another
hospital; nevertheless, his symptoms worsened. Two weeks after
commencing dermatomycosis treatment, he presented with GER
and was admitted to our hospital. We discontinued all oral drugs
and applied urea 10% cream. The eruptions improved within two
weeks.
Two weeks after discharge, lenvatinib was re-administered
because the patient’s metastatic lung tumor enlarged, which led to
a recurrence of erythema with pruritus on the upper part of
patient’s body. Laboratory examination showed an increased
blood eosinophil count (1449/μL). Histopathological examination
of a specimen of the erythematous lesion of his thigh revealing
acanthosis, slight liquefaction degeneration, slight reduction of
granular cell layer, and lympholic infiltration around the blood
vessels of the dermis (Figure 1 d-f). Lenvatinib was again discontinued; difluprednate ointment and urea 10% cream were prescribed. Within two weeks, the eruption improved. We performed
a patch test of Lenvatinib after the informed consent, similar to a
previous report of sorafenib showing positive results of patch
test,5 which was positive per the standards set by the International
Contact Dermatitis Research Group. Based on that result, we diagnosed the patient with lenvatinib-induced GER.
Palmer-plantar erythrodysesthesia syndrome,2 a known cutaneous AE of Lenvatinib, is also the most common AE for the multikinase inhibitor sorafenib.3 In contrast, there have been no
detailed case reports of lenvatinib-induced GER. Although our
patient’s history of ichthyosis and mycosis complicated his diagnosis of GER, the results of patch test by using lenvatinib confirmed the diagnosis. One limitation is that it is unclear how much
his congenital ichthyosis affected on the present condition. As
lenvatinib is a standard drug in cancer therapy, physicians should
be aware of this potentially serious AE.

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To the Editor:
Lenvatinib, an oral multikinase inhibitor, was approved by the
United States Food and Drug Administration (FDA) for the treatment of radiation-refractory differentiated thyroid cancer in
2015.1,2 In 2017, the phase 3 study of lenvatinib (E7080) in differentiated cancer of the thyroid (SELECT) demonstrated that lenvatinib prolongs progression-free survival in such patients.1,2
Thereafter, the REFLECT [multicenter, randomized, open-label,
phase 3 trial to compare the efficacy and safety of lenvatinib

[Dermatology Reports 2023; 15:9617]

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Letter

References

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Figure 1. Patient’s clinical and histopathological features. a-c) A few days after hospitalization, erythema covered the body;
d-f) histopathological examination of a specimen of the erythematous lesion of his thigh revealing acanthosis, slight liquefaction degeneration, slight reduction of granular cell layer, and lymphocytic infiltration around the blood vessels of the dermis (H&E staining, original
magnification; d) ×40, scale bar =200 µm; e) ×100, scale bar =100 µm (f)×200, scale bar = 50 µm) .

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first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial.
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Cancers (Basel) 2020;12.
5. Ikeda M, Fujita T, Mii S, et al. Erythema multiforme induced
by sorafenib for metastatic renal cell carcinoma. Jpn J Clin
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