Tyrosine kinase inhibitors induced scrotal ulcerations: Report of 2 cases

Abhipsa Samal, Nibedita Dixit, Bikash R Kar, Liza Mohapatra
From the Department of Dermatology, IMS and SUM Hospital, Bhubaneswar, Odisha, India

Date of Web Publication27-Apr-2023

Correspondence Address:
Liza Mohapatra
From the Department of Dermatology, IMS and SUM Hospital, Bhubaneswar, Odisha
India
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Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijd.ijd_818_22

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How to cite this article:
Samal A, Dixit N, Kar BR, Mohapatra L. Tyrosine kinase inhibitors induced scrotal ulcerations: Report of 2 cases. Indian J Dermatol 2023;68:235
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Samal A, Dixit N, Kar BR, Mohapatra L. Tyrosine kinase inhibitors induced scrotal ulcerations: Report of 2 cases. Indian J Dermatol [serial online] 2023 [cited 2023 Apr 28];68:235. Available from: https://www.e-ijd.org/text.asp?2023/68/2/235/375213

Sir,

Tyrosine kinase inhibitors (TKIs) have emerged as an important antiangiogenic and antineoplastic therapeutic option for a variety of malignant neoplasms owing to their targeted action. They are known to cause a range of dermatological side effects. These include skin ulceration, rash, hand-foot-skin reaction (HFSR), pigment dilution, alopecia, pruritus, xerosis, scrotal ulceration, subungual splinter haemorrhage and mucositis.[1] Scrotal ulcerations are less commonly seen with these agents. We report two such cases of scrotal ulcerations caused by TKIs. A 65-year-old male with hepatocellular carcinoma presented to the outpatient department with complaints of painful ulcerative lesions over the perineum. The carcinoma was secondary to non-alcoholic steatohepatitis with negative viral serological markers. He had metastasis in the form of a right lung subcentric nodule. The biochemical investigations were normal except for a threefold rise in liver enzymes. The patient was on oral nivolumab (200) initially for 4 months, followed by oral lenvatinib 4 mg twice daily. Within a span of 4 weeks, he developed multiple painful ulcers in the groin, scrotum and perianal region, which did not respond to any conventional therapy [Figure 1]a and [Figure 1]b. The ulcers persisted for five months and were painful enough to limit the patient's daily activities. Therefore, on consultation with the medical oncologist, lenvatinib was stopped. The ulcers healed significantly within 14 days of stopping oral lenvatinib and giving oral antibiotics and local wound care [Figure 2]a and [Fifure 2]b. This confirms the temporal association of scrotal ulceration with the intake of lenvatinib. The second case was a 58-year-old male who presented with similar painful skin ulceration over the right thigh and scrotum [Figure 3]. The patient had a diagnosed case of renal cell carcinoma and had been on oral pazopanib 400 mg once daily for the last 10 months. The patient was then started on oral cabozantinib 60 mg once daily. He developed ulcerations over the thigh and scrotum after 15 days of starting the therapy. There was complete healing of the ulcer in 15 days after withdrawal of cabozantinib [Figure 4].

Figure 1: (a and b) Well defined ulcers and erosions over the groin, perianal area and scrotum following intake of Lenvatinib

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Figure 2: (a and b) Healed ulcers and erosions with post-inflammatory hyperpigmentation

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Figure 3: Two well defined ulcers of size 2 cm × 1 cm on the scrotum following intake of Cabozantinib

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Tyrosine kinases are a family of proteins that play a key role in the cell cycle, proliferation, differentiation, cell death and survival and are crucial in oncogenesis. The scrotal skin and the inguinal area are well vascularised structures and are prone to friction and trauma. It is hypothesised that inhibition of vascular endothelial growth factor and platelet-derived growth factor receptor by the TKIs causes alteration in the repair mechanism. This leads to microvascular structural defects in these areas, resulting in elevated levels of drug in the tissue. Apart from this, hypoxia-inducible factor 1α is speculated to have a role in the development of scrotal ulcers.[2] Dermatological adverse effects in the form of cutaneous ulcerations are uncommon during lenvatinib medication. A thorough literature search revealed hardly three case reports of lenvatinib-induced skin ulceration. Cha et al. reported skin ulceration after treatment with lenvatinib in a hepatocellular carcinoma patient.[3] A cutaneous ulceration in the subclavicular region has also been reported following lenvatinib therapy in a patient with thyroid cancer.[4] The most common cutaneous adverse effect reported with cabozantinib is HFSR, found in approximately 40% of patients.[5] There is no report of scrotal ulceration following cabozantinib in the literature. Drugs can be an important non-venereal cause of scrotal ulceration, out of which chemotherapeutic drugs are the major aetiologies. The scrotal skin, being prone to friction and trauma, is a potential site for ulceration due to TKIs. Recognition of the dermatological toxicities along with appropriate treatment at the right time is essential in order to avoid poor oncological treatment adherence, dose interruption and discontinuation of targeted therapies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

   References Top
1.Stanculeanu DL, Zob D, Toma OC, Georgescu B, Papagheorghe L, Mihaila RI. Cutaneous toxicities of molecular targeted therapies. Maedica (Bucur) 2017;12:48-54.  Back to cited text no. 1
    2.Zuo RC, Apolo AB, DiGiovanna JJ, Parnes HL, Keen CM, Nanda S, et al. Cutaneous adverse effects associated with the tyrosine-kinase inhibitor cabozantinib. JAMA Dermatol 2015;151:170-7.  Back to cited text no. 2
    3.Cha S, Kim DW, Choe JW, Kim TH, Kim SY, Hyun JJ, et al. A case report of a patient presented with skin ulcer after treatment of lenvatinib. J Liver Cancer 2021;21:194-8.  Back to cited text no. 3
    4.Kitamura M, Hayashi T, Suzuki C, Hirano S, Tateya I, Kishimoto Y, et al. Successful recovery from a subclavicular ulcer caused by lenvatinib for thyroid cancer: A case report. World J Surg Oncol 2017;15:24.  Back to cited text no. 4
    5.Cho Y-T, Chan C-C. Cabozantinib-induced hand-foot skin reaction with subungual splinter hemorrhages and hypertension: A possible association with inhibition of the vascular endothelial growth factor signaling pathway. Eur J Dermatol 2013;23:274-5.  Back to cited text no. 5
    
  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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