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neck&#44; and hands&#46; The cutaneous eruption had started from the dorsal parts of both hands with a burning&#44; prickling&#44; and itching sensation one month ago&#46; Within a week&#44; the erythematous cutaneous eruption spread to the face and neck with no involvement of the sun-protected areas&#46; He was diagnosed with MTC 5-years ago&#46; Subsequently&#44; he had bilateral total thyroidectomy along with central and right neck dissection&#46; Positron Emission Tomography&#47;Computed Tomography &#40;PET&#47;CT&#41; revealed findings consistent with lytic bone metastases&#46; He was then treated with 2 cycles of radioactive lutetium Lu-177 dotatate therapy along with zoledronic acid monthly for seven months&#46; Since he showed partial response to radioactive therapy&#44; oral vandetanib 300&#8239;mg per day was started for metastatic MTC treatment&#46; No other recently administered systemic or topical photosensitizer was noted&#46; Two months after the start of oral vandetanib&#44; he developed erythematous&#44; photodistributed papules and plaques involving both dorsal hands&#47;feet&#44; neck&#44; and face &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; with the permission of the patient&#41;&#46; Pre-diagnoses of phototoxic or photoallergic drug eruption associated with vandetanib were considered&#46; A 4&#8239;mm punch biopsy was taken from the dorsal hand&#46; Prominent vacuolar degeneration and hyperpigmentation were observed in the epidermis&#59; extravasated erythrocytes&#44; coat-sleeve-like perivascular lymphocytic infiltration&#44; and solar elastosis were present in the dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The findings were compatible with interface dermatitis and since necrotic keratinocytes were dominant&#59; phototoxic dermatitis was the favored diagnosis&#46; He was started topical mometasone furoate treatment resulting in some improvement&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Vandetanib is an oral chemotherapeutic agent that shows its effect by inhibiting several kinases and thereby interfering with tumor growth and angiogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Although vandetanib is reported to have systemic side effects such as myalgia&#44; fatigue&#44; hypertension&#44; and transaminitis&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> dermatologic manifestations such as pruritus&#44; xerosis and acneiform cutaneous eruption are also associated with vandetanib&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Photosensitive drug eruptions can be classified into phototoxic and photoallergic forms&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Increased oxidative stress and inflammation due to UV exposure and EGFR inhibition are held responsible for the development of photosensitive drug reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Photosensitizer drugs become activated after UV absorption leading to cytotoxic cell injury and increased oxidization which causes phototoxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Incriminated phototoxic agents are furocoumarins&#44; tetracyclines&#44; fluoroquinolones&#44; antifungals&#44; antimalarials&#44; non-steroidal anti-inflammatory drugs&#44; and chemotherapeutic agents&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Yin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> reported a case of phototoxic drug eruption on the face and neck developing in a patient under vandetanib treatment for MTC&#46; Other than phototoxicity&#44; vandetanib is also shown to be associated with photoallergic dermatitis&#44; photoonycholysis&#44; cutaneous brown&#47;blue-gray pigmentation&#44; folliculitis&#44; hypertrichosis&#44; periorbital edema&#44; perifollicular dark blue&#47;gray macules&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Topical corticosteroids&#44; sun avoidance&#44; and sunscreen are usually effective for mild to moderate photosensitive reactions&#46; As new targeted therapy agents for various malignancies are developed&#44; plentiful dermatologic side effects will likely be encountered&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0020" class="elsevierStylePara elsevierViewall">None declared&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Informed consent for publication of medical images was taken from the patient&#46; The patient authorized the use of his pictures in the article&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0030" class="elsevierStylePara elsevierViewall">Ecem Bostan&#58; Conceptualization&#59; visualization&#59; writing the original draft&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Duygu Gulseren&#58; Conceptualization&#44; supervision&#44; and editing</p><p id="par0040" class="elsevierStylePara elsevierViewall">Ozay Gokoz&#58; Conceptualization&#44; supervision&#44; and editing&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Case Letter
Phototoxic drug eruption induced by vandetanib used for the treatment of metastatic medullary thyroid cancer
Ecem Bostana,
Corresponding author
bostanecem@gmail.com

Corresponding author.
, Duygu Gulserena, Ozay Gokozb
a Department of Dermatology and Venereology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
b Department of Pathology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
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neck&#44; and hands&#46; The cutaneous eruption had started from the dorsal parts of both hands with a burning&#44; prickling&#44; and itching sensation one month ago&#46; Within a week&#44; the erythematous cutaneous eruption spread to the face and neck with no involvement of the sun-protected areas&#46; He was diagnosed with MTC 5-years ago&#46; Subsequently&#44; he had bilateral total thyroidectomy along with central and right neck dissection&#46; Positron Emission Tomography&#47;Computed Tomography &#40;PET&#47;CT&#41; revealed findings consistent with lytic bone metastases&#46; He was then treated with 2 cycles of radioactive lutetium Lu-177 dotatate therapy along with zoledronic acid monthly for seven months&#46; Since he showed partial response to radioactive therapy&#44; oral vandetanib 300&#8239;mg per day was started for metastatic MTC treatment&#46; No other recently administered systemic or topical photosensitizer was noted&#46; Two months after the start of oral vandetanib&#44; he developed erythematous&#44; photodistributed papules and plaques involving both dorsal hands&#47;feet&#44; neck&#44; and face &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; with the permission of the patient&#41;&#46; Pre-diagnoses of phototoxic or photoallergic drug eruption associated with vandetanib were considered&#46; A 4&#8239;mm punch biopsy was taken from the dorsal hand&#46; Prominent vacuolar degeneration and hyperpigmentation were observed in the epidermis&#59; extravasated erythrocytes&#44; coat-sleeve-like perivascular lymphocytic infiltration&#44; and solar elastosis were present in the dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The findings were compatible with interface dermatitis and since necrotic keratinocytes were dominant&#59; phototoxic dermatitis was the favored diagnosis&#46; He was started topical mometasone furoate treatment resulting in some improvement&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Vandetanib is an oral chemotherapeutic agent that shows its effect by inhibiting several kinases and thereby interfering with tumor growth and angiogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Although vandetanib is reported to have systemic side effects such as myalgia&#44; fatigue&#44; hypertension&#44; and transaminitis&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> dermatologic manifestations such as pruritus&#44; xerosis and acneiform cutaneous eruption are also associated with vandetanib&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Photosensitive drug eruptions can be classified into phototoxic and photoallergic forms&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Increased oxidative stress and inflammation due to UV exposure and EGFR inhibition are held responsible for the development of photosensitive drug reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Photosensitizer drugs become activated after UV absorption leading to cytotoxic cell injury and increased oxidization which causes phototoxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Incriminated phototoxic agents are furocoumarins&#44; tetracyclines&#44; fluoroquinolones&#44; antifungals&#44; antimalarials&#44; non-steroidal anti-inflammatory drugs&#44; and chemotherapeutic agents&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Yin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> reported a case of phototoxic drug eruption on the face and neck developing in a patient under vandetanib treatment for MTC&#46; Other than phototoxicity&#44; vandetanib is also shown to be associated with photoallergic dermatitis&#44; photoonycholysis&#44; cutaneous brown&#47;blue-gray pigmentation&#44; folliculitis&#44; hypertrichosis&#44; periorbital edema&#44; perifollicular dark blue&#47;gray macules&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Topical corticosteroids&#44; sun avoidance&#44; and sunscreen are usually effective for mild to moderate photosensitive reactions&#46; As new targeted therapy agents for various malignancies are developed&#44; plentiful dermatologic side effects will likely be encountered&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0020" class="elsevierStylePara elsevierViewall">None declared&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Informed consent for publication of medical images was taken from the patient&#46; The patient authorized the use of his pictures in the article&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0030" class="elsevierStylePara elsevierViewall">Ecem Bostan&#58; Conceptualization&#59; visualization&#59; writing the original draft&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Duygu Gulseren&#58; Conceptualization&#44; supervision&#44; and editing</p><p id="par0040" class="elsevierStylePara elsevierViewall">Ozay Gokoz&#58; Conceptualization&#44; supervision&#44; and editing&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Article information
ISSN: 03650596
Original language: English
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