Letters to the Editor

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2 Gavrovic-Jankulovic M, Cirkovic T, Vuckovic O et al. Isolation and biochemical characterization of a thaumatin-like kiwi allergen. J Allergy Clin Immunol 2002; 110: 805–810. 3 Grozdanovic M, Popovic M, Polovic N et al. Evaluation of IgE reactivity of active and thermally inactivated actinidin, a biomarker of kiwifruit allergy. Food Chem Toxicol 2012; 50: 1013–1018. 4 Palacin A, Quirce S, Sanchez-Monge R et al. Sensitization profiles to purified plant food allergens among pediatric patients with allergy to banana. Pediatr Allergy Immunol 2011; 22: 186–195. 5 Aleksic I, Popovic M, Dimitrijevic R et al. Molecular and immunological characterization of Mus a 5 allergen from banana fruit. Mol Nutr Food Res 2012; 56: 446–453. 6 Nikolic J, Mrkic I, Grozdanovic M et al. Isolation protocol for three important banana allergens. J Chromatogr B Analyt Technol Biomed Life Sci 2014; 962C: 30–36. 7 Clendennen SK, May GD. Differential gene expression in ripening banana fruit. Plant Physiol 1997; 115: 463–469. DOI: 10.1111/jdv.13146

Pyoderma gangrenosum of the penis possibly associated with pazopanib treatment Editor Pyoderma gangrenosum (PG) is an ulcerative, non-infectious and neutrophilic dermatosis that most commonly affects the lower extremities, especially below the knee. PG can involve any cutaneous site, including the scalp, arms, trunk and genitals. Pazopanib is a potent and selective multi-tyrosine kinase inhibitor that blocks tumour growth and inhibits angiogenesis. It has previously been reported that six cases with sunitinib and one case with imatinib induced PG. All seven patients were reported to have ulcers on the lower extremities. Herein, we report the first case of pazopanib-associated PG on the penis with recurrent renal cell carcinoma.

(a)

A 78-year-old Japanese man was referred to our department for skin ulcers on the penis. He had a history of ulcers on the penis during treatment with sunitinib (50 mg daily for 2 weeks followed by a 1 week break) for recurrent multiple bone metastasis from renal cell carcinoma. A previous doctor had diagnosed his erosions as sunitinib-associated PG. He received systemic corticosteroids (50 mg daily) and was tapered off steroids without lesion recurrence. One week prior to his visit at our hospital, he was started on oral pazopanib (800 mg daily) for recurrent multiple bone and lung metastases from renal cell carcinoma. Six days after the initiation of pazopanib, the patient complained of painful ulcers on the glans and penis (Fig. 1a). Topical corticosteroid treatment was not effective and the ulcers expanded. Although pazopanib was discontinued due to adverse events, including general malaise, anorexia and urinary protein 14 days after its initiation, the lesions on the penis expanded gradually. Bacterial cultures of both blood and ulcers were negative. A blood test was negative for rheumatoid factor and antinuclear antibodies. A skin biopsy revealed a neutrophilic infiltrate without evidence of vasculitis or carcinoma (Fig. 1b). Arterial diseases as the cause of the ulceration were excluded by contrastenhanced computer tomography. We diagnosed the ulcers on the penis as PG. The patient was administered systemic corticosteroids (50 mg daily) and the ulcers improved rapidly. He was subsequently tapered off steroids without lesion recurrence. Various multi-tyrosine kinase inhibitors, including pazopanib and sunitinib, are currently available for the treatment of several malignancies. Multi-tyrosine kinase inhibitors predominantly inhibit vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor (c-Kit), which leads to antitumour activity.1–3 Adverse events of multi-tyrosine kinase inhibitors include hypertension, hepatic dysfunction, gastrointestinal dysfunction, thyroid dysfunction and PG.4 The aetiology of PG associated with multi-tyrosine kinase inhibitors was considered in terms of the antiangiogenic effects by VEGFR-

(b)

Figure 1 (a) An irregular, violaceous and undermined border surround the necrolytic cutaneous ulcer. (b) Microscopy of biopsy taken from ulcerative lesion on the penis reveals neutrophilic infiltration of the dermis with abscess formation, dermal oedema and slight spongiosis of the epidermis.

JEADV 2016, 30, 1195–1252

© 2015 European Academy of Dermatology and Venereology

Letters to the Editor

and c-KIT-inhibition, which induced necrosis and the subsequent invasion of neutrophils.5 To the best of our knowledge, this is the first case of PG possibly associated with pazopanib. Although it remains unclear why PG developed on the penis in this case, clinicians should consider the risk of pazopanib inducing PG when the patient has a history of PG associated with another multi-tyrosine kinase inhibitor.

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(a)

S. Usui, A. Otsuka,* Y. Kaku, T. Dainichi, K. Kabashima* Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan *Correspondence: A. Otsuka. E-mail: [email protected]; K. Kabashima. E-mail: [email protected]

(b)

References 1 McCormack PL. Pazopanib: a review of its use in the management of advanced renal cell carcinoma. Drugs 2014; 74: 1111–1125. 2 Miura Y, Imamura CK, Fukunaga K et al. Sunitinib-induced severe toxicities in a Japanese patient with the ABCG2 421 AA genotype. BMC Cancer 2014; 14: 964. 3 Iqbal N, Iqbal N. Imatinib: a breakthrough of targeted therapy in cancer. Chemother Res Pract 2014; 2014: 9. 4 Sodergren SC, White A, Efficace F et al. Systematic review of the side effects associated with tyrosine kinase inhibitors used in the treatment of gastrointestinal stromal tumours on behalf of the EORTC Quality of Life Group. Crit Rev Oncol Hematol 2014; 91: 35–46. 5 Akanay-Diesel S, Hoff NP, K€ urle S et al. Sunitinib induced pyoderma gangrenosum-like ulcerations. Eur J Med Res 2011; 16: 491–494. DOI: 10.1111/jdv.13148

Not just ordinary hand dermatitis: mechanic’s hands revealing dermatomyositis Editor Dermatomyositis, in particular the form associated with antisynthetase or anti-Jo-1 antibodies, can present as ‘mechanic’s hands’, a hyperkeratotic rhagadiform skin eruption mimicking hand eczema. We describe a case that was initially mistaken for hand dermatitis, but in which careful examination of the nailbed offered the clue to the right diagnosis. A woman in her 50s with no known history of atopy was referred to our department because of a therapy-resistant eczematous dermatitis of her hands, which was diagnosed earlier as a hyperkeratotic rhagadiform eczema. She had been treated in the past with topical corticosteroids, methotrexate, isotretinoin and ciclosporin, without success. Interestingly, worsening was also noted after PUVA treatment. Clinical examination showed an accentuation of skin lines, hyperkeratosis and fissuring at the palmar sides and fingertips, along with erythema of the knuckles and a striking ragging of

JEADV 2016, 30, 1195–1252

Figure 1 Clinical presentation. (a) Hand dermatitis with accentuation of skin lines, erythema of the knuckles and periungual erythema with teleangiectasias and splinter haemorrhages. (b) Marked hyperkeratosis on the sides of the fingers.

the cuticles with periungual erythema, teleangiectasias and splinter haemorrhages (Fig. 1a,b). Laboratory tests were notable for an elevated sedimentation rate (33 mm in the first hour) and for the presence of anti-Jo-1 antibodies. Skin biopsy confirmed the acanthosis and hyperkeratosis, and also showed a perivascular lymphohistiocytic infiltrate with subtle signs of interface dermatitis and the presence of Civatte bodies (Fig. 2). Direct immunofluorescence was negative for IgG, IgM, IgA, C3 and fibrinogen. Finally, a capillaroscopy was performed showing giant capillaries, capillary haemorrhages, loss of capillaries and bushy capillaries. The possibility of ‘mechanic’s hands’ or ‘workman’s hands’, a skin manifestation of dermatomyositis,1 was raised. Although differentiation from hand eczema can be challenging,1,2 two clinical elements hinted at the diagnosis in our case: (i) the exacerbation of the skin lesions following PUVA therapy,3 and (ii) the accompanying periungual abnormalities.1 Mechanic’s hands often occur as part of the antisynthetase syndrome, a form of dermatomyositis associated with the presence of anti-Jo-1 antibodies directed against histidyl-tRNA synthetase.4 Apart from mechanic’s hands, this syndrome can accommodate the following constellation of clinical manifestations: fever, polyarthritis, Raynaud’s phenomenon, myositis and interstitial lung disease.4 In our case, pulmonary function tests indeed revealed a decrease

© 2015 European Academy of Dermatology and Venereology

Pyoderma gangrenosum of the penis possibly associated with pazopanib treatment.

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