Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2024;14(3):e2024190 1 Tocilizumab-Induced Sweet Syndrome in a Familial Mediterranean Fever Patient: A Case Report Yusuf Can Edek1, Derya Yıldırım2, Melike Urgancı3, Betül Öğüt3, Esra Adışen1 1 Department of Dermatology, Gazi University Faculty of Medicine, Ankara, Turkey 2 Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Ankara, Turkey 3 Department of Pathology, Gazi University Faculty of Medicine, Ankara, Turkey Key words: sweet syndrome, tocilizumab Citation: Edek YC, Yıldırım D, Urgancı M, Öğüt B, Adışen E. Tocilizumab-Induced Sweet Syndrome in a Familial Mediterranean Fever Patient: A Case Report. Dermatol Pract Concept. 2024;14(3):e2024190. DOI: https://doi.org/10.5826/dpc.1403a190 Accepted: March 14, 2024; Published: July 2024 Copyright: © Edek 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, 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 Sweet syndrome is a rare neutrophilic dermatosis charac- terized by painful, edematous, and erythematous papules, plaques, or nodules. The disease can be categorized into three main groups: classical Sweet syndrome, malignancy-related Sweet syndrome, and drug-related Sweet syndrome. Al- though the cause of the disease is not fully known in most cases, infections, malignancies, drugs, and inflammatory dis- eases can be triggering factors. Drug-related Sweet syndrome is a rare subtype of Sweet syndrome and was first described in the literature after the use of trimethoprim/sulfamethox- azole. Over time, drug-related Sweet syndrome cases induced by antibiotics, antivirals, antineoplastics, retinoids, and granulocyte colony-stimulating factor (G-CSF) have been reported. Drug-related Sweet syndrome usually develops within two weeks after initial exposure, and recurrence may be observed with repeated exposure [1]. In this case report, we present a male patient who was followed up with familial Mediterranean fever (FMF) and developed Sweet syndrome secondary to the use of tocilizumab. Case Presentation A 33-year-old male patient presented at our clinic due to painful lesions and fever. His past medical history revealed FMF, renal amyloidosis, and hypertension, and he was taking tocilizumab, anakinra, colchicine, and nifedipine treatments. He described that tocilizumab was started three months prior for FMF. Three days after tocilizumab administration, painful lesions had developed on the legs accompanied by a fever exceeding 38° C, and his complaints recurred with the following drug administrations. On dermatological ex- amination, erythematous papules and nodules on the legs were observed (Figure 1). Laboratory evaluation revealed 2 Research Letter | Dermatol Pract Concept. 2024;14(3):e2024190 Figure 1. (A, B, C) Erythematous papules and nodules on the legs. Figure 2. (A, B, C) Spongiosis, and neutrophil accumulation in the epidermis, perivascular- periadnexal neutrophil-dominated mixed-type inflammation in the dermis (H&E, x40, x100, x100). leukocytosis, neutrophilia, and elevated acute phase reac- tants. Histopathological examination of the punch biopsy from the erythematous nodule showed spongiosis and neutro- phil accumulation in the epidermis, perivascular-periadnexal mixed-type inflammation dominated with neutrophils in the dermis (Figure 2). Based on clinical examination and histo- pathological findings, the patient was diagnosed with Sweet syndrome. Following the discontinuation of tocilizumab and topical steroid treatment, regression of the lesions was observed. When the Naranjo Adverse Reaction Probability Scale calculated for tocilizumab was 7 (5–8: possible), and the patient met all diagnostic criteria for drug-related Sweet syndrome, it was accepted Sweet syndrome had developed secondary to tocilizumab. Conclusion Increased cytokines such as IL-1, IL-6, IL-8, and G-CSF have a role in the pathogenesis of Sweet syndrome, and successful treatment of cases with the inhibition of cytokines supports Research Letter | Dermatol Pract Concept. 2024;14(3):e2024190 3 this role [1-4]. However, in the literature, paradoxically developed Sweet syndrome cases have been reported with treatment agents that inhibit these cytokines [5]. The devel- opment of Sweet syndrome in our patient after the use of tocilizumab, an inhibitor of IL-6, which is involved in the pathogenesis of Sweet syndrome, brings to mind the idea that this may be a paradoxical reaction. Tocilizumab is a recombinant human monoclonal anti- body developed against the IL-6 receptor and is used to treat various diseases such as rheumatoid arthritis, polymyalgia rheumatica, and temporal arteritis. Filippi et al. observed a Sweet syndrome in a polymyalgia rheumatica patient after tocilizumab treatment [6]. Our aim in presenting this case is to raise aware- ness about the cutaneous side effects of tocilizumab and to emphasize the clinical features of drug-related Sweet syndrome. References 1. Shaikh MB, Krunic AL. Drug-Induced Sweet Syndrome. J Allergy Clin Immunol Pract. 2019;7(7):2400-2401. doi:10.1016/j.jaip .2019.07.002 2. Takano Y, Fujino H, Yachie A, Sumimoto SI. Serum cytokine profile in pediatric Sweet’s syndrome: a case report. J Med Case Rep. 2017;11(1):178. Published 2017 Jul 2. doi:10.1186/s13256 -017-1317-0 3. Cook QS, Zdanski CJ, Burkhart CN, Googe PB, Thompson P, Wu EY. Idiopathic, Refractory Sweet’s Syndrome Associated with Common Variable Immunodeficiency: a Case Report and Literature Review.  Curr Allergy Asthma Rep. 2019;19(6):32. Published 2019 May 14. doi:10.1007/s11882-019-0864-4 4. Hwang S, Son H, Moon J, et al. Refractory neuro-Sweet dis- ease successfully treated with tocilizumab and mycophenolate mofetil. Encephalitis. 2021;1(1):20-24. doi:10.47936/encephalitis .2020.00059 5. Haber R, Dib N, El Gemayel M, Makhlouf M. Paradoxical neutrophilic dermatosis induced by biologics and immuno- suppressive drugs: A systematic review.  J Am Acad Dermatol. 2021;85(4):1048-1049. doi:10.1016/j.jaad.2021.02.035 6. Filippi F, Chessa MA, Patrizi A, Baraldi C, Ferrara F, Bardazzi F. Tocilizumab-Induced Sweet Syndrome in a Pa- tient With Polymyalgia Rheumatica.  Dermatol Pract Concept. 2019;10(1):e2020019. Published 2019 Dec 31. doi:10.5826/dpc .1001a19 Table 1. Diagnostic criteria for the diagnosis of drug-related Sweet syndrome Drug Induced Sweet Syndrome Our Case Sudden onset of painful erythematous plaque or nodule + Dense neutrophilic infiltration without signs of leukocytoclastic vasculitis in the histopathological examination + Fever above 38 °C + Temporal relationship between drug intake and clinical findings + Regression of lesions with discontinuation of the drug or systemic steroid treatment +