Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2024;14(4):e2024243 1 Cutaneous Drug Reaction Due to Bortezomib Characterized by Erythematous Ramified Plaques in a Patient with Multiple Myeloma Emre Güven1, Yusuf Can Edek1, Funda Tamer1, Özlem Erdem2 1 Department of Dermatology, Gazi University Faculty of Medicine, Ankara, Turkey 2 Department of Pathology, Gazi University Faculty of Medicine, Ankara, Turkey Key words: Bortezomib, Drug reaction Citation: Güven E, Edek YC, Tamer F, Erdem Ö. Cutaneous Drug Reaction Due to Bortezomib Characterized by Erythematous Ramified Plaques in a Patient with Multiple Myeloma. Dermatol Pract Concept. 2024;14(4):e2024243. DOI: https://doi.org/10.5826/dpc.1404a243 Accepted: June 5, 2024; Published: October 2024 Copyright: ©2024 Güven et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Yusuf Can Edek. Address: Gazi Universitesi Tip Fakultesi Hastanesi, Emniyet Mahallesi, Mevlana Bulvari, No:29, 06560 Ankara/ Turkey. Telephone Number: +903122026129 / +905062818274 E-mail: yusuf-can-35@hotmail.com. Introduction Herein, we present a patient with multiple myeloma who developed erythematous and ramified skin lesions after the first administration of bortezomib subcutaneously. Case Presentation A 34-year-old male patient was admitted to our Dermatol- ogy Outpatient Clinic with a 4-week history of an asymp- tomatic erythematous rash on the abdomen. The patient was diagnosed with IgG kappa multiple myeloma three months earlier by a bone marrow biopsy and initiated subcutaneous bortezomib 1.5 mg/m2/week, oral lenalidomide 25 mg/day, and intravenous dexamethasone 20 mg/week treatment regimen. The patient stated that the lesion appeared at the bortezomib injection site after the first administration of the drug and flared up after the second administration. He de- nied any allergies, trauma, or infection. Dermatological ex- amination revealed erythematous plaques which showed less erythema in the central parts and ramified extensions of ery- thema forming a spider-like lesion on the right side of the ab- domen (Figure 1A). The histopathological evaluation of the specimen, taken by a punch biopsy from the erythematous plaque, showed mild intercellular edema in the epidermis and perivascular mononuclear inflammation accompanied by eosinophils in the superficial dermis (Figure 2). Thus, the diagnosis of drug reaction was made based on clinical and histopathological findings. The laboratory tests (complete blood count, biochemistry panel, C-reactive protein, eryth- rocyte sedimentation rate, and urine analysis) were all within normal limits. Bortezomib treatment was discontinued, and the lesion regressed after using mometasone furoate 0.1% cream twice daily for two weeks (Figure 1B). 2 Research Letter | Dermatol Pract Concept. 2024;14(4):e2024243 Discussion Bortezomib is a reversible proteasome inhibitor used in the treatment of multiple myeloma and lymphoma. Skin reac- tions have been reported in up to 24% of patients treated with bortezomib, usually after the third or fourth injection, and these reactions have been associated with increased pro- inflammatory cytokine production [1]. Dermatological side effects of bortezomib include injection site reactions, Sweet syndrome, maculopapular eruption, Stevens-Johnson syn- drome, urticaria, cutaneous vasculitis, and neutrophilic der- matosis [1-3]. However, bortezomib-induced skin reactions usually appear as cutaneous nodules, plaques, or morbilli- form erythema. Recently, Han et al. reported a male patient with multiple myeloma who developed bortezomib-related reticular itchy skin rash following the third cycle of the treat- ment [3]. Moreover, a similar case with a spider-like erythem- atous lesion following bortezomib treatment was previously described [4]. Furthermore, Plume et al. reported spider-like injection site reactions in three patients receiving bortezomib and two patients receiving azacitidine for the treatment of multiple myeloma and myelodysplastic syndrome [5]. Conclusion We consider that the ramified spider-like skin eruption devel- oped due to bortezomib since the lesion appeared at the in- jection site following the subcutaneous administration of the drug. Advances in cancer treatment and novel chemotherapy regimens increase the risk of diverse cutaneous side effects, leading dermatologists to take an important role in the man- agement of patients with malignancies. Establishing the cu- taneous side effects of chemotherapy drugs may help to take preventive measures and to initiate appropriate dermatolog- ical treatment as early as possible to prevent cessation or de- lay of the cancer treatment and improve cancer management. Our case will hopefully make a significant contribution to the literature by describing this rare cutaneous side effect of bortezomib and determining its clinical features. References 1. Reyes-Habito CM, Roh EK. Cutaneous reactions to chemo- therapeutic drugs and targeted therapies for cancer: part I. Conventional chemotherapeutic drugs. J Am Acad Dermatol. 2014 Aug;71(2):203.e1-203.e12. doi: 10.1016/j.jaad.2014.04.014. 2. Han J, Owji S, Agarwal A, et al. Bortezomib-Induced Reticu- lar Eruption in Patient with Multiple Myeloma. Dermato- pathology (Basel). 2023 Jul 21;10(3):226-230. doi: 10.3390 /dermatopathology10030031. Figure 1 (A) Erythematous plaques with less erythema in the central parts accom- panied by ramified spider-like extensions on the right abdomen. (B) The lesion healed four weeks after treatment, leaving post-inflammatory hyperpigmentation. Figure 2 (A) Mild intercellular edema in the epidermis and perivas- cular mononuclear inflammation accompanied by eosinophils in the superficial dermis (H&E, ×20). (B) Close view of the eosinophils (H&E, ×400). Research Letter | Dermatol Pract Concept. 2024;14(4):e2024243 3 3. Choi GS, Lee HS, Kim HK. A case of bortezomib (Velcade)- induced Stevens-Johnson syndrome confirmed by patch test. Asia Pac Allergy. 2021 Apr 21;11(2):e17. doi: 10.5415/apallergy .2021.11.e17. 4. Kurtin S, Knop CS, Milliron T. Subcutaneous administration of bortezomib: strategies to reduce injection site reactions. J Adv Pract Oncol. 2012 Nov;3(6):406-10. doi: 10.6004/jadpro .2012.3.6.8. 5. Plume MA, Sibaud V, Bobin A, et al. Spider-like injection site reaction after subcutaneous administration of haematological treatments. J Eur Acad Dermatol Venereol. 2020 Mar;34(3): e142-e144. doi: 10.1111/jdv.16049.