Correspondence Clinical Letter Clinical Letter Severe candidal balanoposthitis on concurrent treatment with secukinumab and the antidiabetic agent empagliflozin (sodium-glucose cotransporter 2 inhibitor – SGLT2-inhibitor) antiseptic and hygienic measures [1]. On this regimen, the infection resolved within one week. Given the clinical course of the condition as well as its persistence, we revised our initial clinical diagnosis of drug-induced angioedema and diagnosed oral and genital candidiasis with severe balanoposthitis. DOI: 10.1111/ddg.13807 Dear Editors, We report on a 59-year-old male patient who was admitted to the hospital with a four-week history of persistent swelling of the lips and tongue, which was suspected to be drug-induced angioedema. He reported that the swelling had first occurred two weeks after starting the angiotensin receptor blocker valsartan (160 mg b.i.d.); he denied shortness of breath, pruritus or urticaria. Treatment with the antihistamine dimetindene (8 mg IV), prednisolone (250 mg IV) as well as discontinuation of valsartan had not resulted in clinical improvement. In addition, he reported to have acutely developed a painful erythematous penile lesion associated with a burning sensation, severe pruritus, pollakiuria and dysuria. The patient had a more than 30-year history of psoriasis and psoriatic arthritis for which he had been on secukinumab (150 mg every 4 weeks) for the past eight weeks. Furthermore, he had type 2 diabetes requiring him to take metformin (1,000 mg b.i.d.), sitagliptin (50 mg b.i.d.) and, for the last three months, also empagliflozin (25 mg daily). Besides moderate lower lip edema and a mildly swollen tongue, clinical examination on admission showed angular cheilitis with erosive/crusted plaques and rhagades (Figure 1). Oral findings included white pseudomembranous patches consistent with erosive candidiasis; only some of the patches could be scraped off. The lesions caused pain and a burning sensation and prevented normal food intake (Figure 2). Genital findings were consistent with balanoposthitis, showing warm, prominent erythema and edema affecting the entire penis from its base up to the phimotic foreskin; in addition, there was a mucopurulent discharge (Figure 3). Blood tests revealed mild leukocytosis (11.6 Gpt/L) and an elevated CRP level (19.6 mg/L). Mycological tests confirmed our suspected clinical diagnosis, showing evidence of Candida albicans both orally and under the foreskin. Both empagliflozin and secukinumab were discontinued. The patient was started on antimycotic treatment with fluconazole (200 mg/day PO for 2 weeks) in accordance with current recommendations. Topical treatment included amphotericin lozenges and clotrimazole 1 % cream applied to the glans and the foreskin; this was supplemented by Figure 1 Angular cheilitis and lower lip edema. Figure 2 Oral candidiasis. Figure 3 Balanoposthitis. © 2019 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2019 1 Correspondence Clinical Letter Initially, we suspected that the condition had been caused by secukinumab, given that interleukin 17A (IL-17A) is physiologically involved in the immune response to cutaneous and mucosal infections caused by Candida spp. [2] and anti-IL-17A antibody treatment is therefore associated with an increased risk of opportunistic Candida infection. However, such severe genital and/or oral candidiasis on secukinumab – requiring treatment discontinuation – is unusual and has previously not been reported [3]. In a systematic review that included roughly 5,000 psoriasis patients treated with secukinumab, the incidence of non-severe candidiasis was found to be 1.7 %. Infections primarily presented with oral involvement and considerably less frequently affected the genitalia. They were readily treatable with antimycotics and usually required no discontinuation of secukinumab therapy [4]. Thus, the severe oral and genital involvement seen in our patient was not easily explained by the use of secukinumab alone. Instead, the oral antidiabetic agent empagliflozin – in conjunction with the preexisting phimosis – was a more plausible cause. While, unlike anti-IL-17A antibodies, oral candidiasis has not been reported in connection with this drug class, genital mycoses have. In a study, the incidence of genital mycosis on empagliflozin was 5 % (over a period of 3.1 years) compared to 1.5 % in the placebo group [5]. This is due to glucosuria caused by selective inhibition of the sodium-glucose cotransporter 2 (SGLT-2) in the renal proximal tubule. Understandably, even mild phimosis can aggravate this effect. While the majority of genital mycoses in the aforementioned study was mild to moderate, such infections may also be severe and require discontinuation of SGLT2 inhibitor treatment [6]. In our patient, empagliflozin was discontinued and consideration was given to subsequent treatment with a glucagon-like peptide (GLP)-1 agonist. In terms of psoriasis treatment, we switched our patient to ustekinumab (anti-IL-12/IL-23 antibody), which is not associated with an increased risk of candidiasis [7]. The class of SGLT2 inhibitors has been experiencing exponential growth in the numbers of prescriptions [8] for diabetes, especially since it was shown that it has an additional benefit in the form of lower cardiovascular mortality [5]. Given the association between psoriasis and the metabolic syndrome, it is safe to assume that there is going to be an increase in the number of patients treated both with an antiIL-17A antibody and an SGLT2 inhibitor. Concurrent use of both drugs likely increases the risk of balanoposthitis in combination with oral candidiasis, as these agents are associated with two independent mechanisms that promote opportunistic Candida infection around the urethral meatus. In such a scenario, phimosis would constitute an additional aggravating factor. 2 Proper selection of patients suitable for combination therapy with SGLT2 inhibitors and anti-IL-17A antibodies should include assessment of the individual risk of developing genital infections. Type 2 diabetes is generally associated with an increased risk of fungal infections [5]. Further predisposing factors include not only the use of immunomodulatory drugs but also the presence of phimosis [9]. The patient was recommended to undergo urological treatment in this regard but has to date declined to do so. When deciding on combination therapy consisting of an anti-IL-17A antibody and an SGLT2 inhibitor, it is important to be particularly vigilant and to observe all preventive measures. In addition, we recommend interdisciplinary management in the event of an infection in order to prevent a psoriasis flare or hyperglycemia. In this respect, our approach involving the switch to a GLP-1 agonist and/or a different biologic is only one of the options available. Conflicts of interest None. I. Moldenhauer 1, R.U. Pliquett2, B. Kreft3, C. Sunderkötter 3 (1) Department of Dermatology and Venereology, University Medical Center, Martin Luther University of Halle-Wittenberg. New address: Department of Internal Medicine I, University Medical Center, Halle (Saale), Germany (2) Department of Internal Medicine II, University Medical Center, Martin Luther University of Halle-Wittenberg. New address: Department of Nephrology and Diabetology, Carl-Thiem Medical Center, Cottbus, Germany (3) Department of Dermatology and Venereology, University Medical Center, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany Correspondence to Dr. rer. nat. Dr. med. Ines Moldenhauer Department of Dermatology and Venereology University Medical Center Martin Luther University of Halle-Wittenberg New address: Department of Internal Medicine I University Medical Center Ernst-Grube-Straße 40 06120 Halle, Germany E-mail: ines.moldenhauer@t-online.de © 2019 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2019 Correspondence Clinical Letter References 1 2 3 4 5 Nenoff P, Krüger C, Paasch U, Ginter-Hanselmayer G. Mycology – an update Part 3: Dermatomycoses: topical and systemic therapy. J Dtsch Dermatol Ges 2015; 13: 387–410. Langley RG, Elewski BE, Lebwohl M et al. 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