Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2024;14(1):e2024012 1 Penile Granulomas Induced by Isotretinoin Antonios Kanelleas1,2, Georgia Pappa1, Eleni Routsi1, Vassilis Milionis1,3, Evangelia Bozi1, Alexandros Katoulis1 1 2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens, Medical School, “Attikon” General University Hospital, Athens, Greece 2 Dermathens Private Practice, Athens, Greece 3 Istomedica Private Anatomic Pathology Lab, Athens, Greece Key words: isotretinoin, acne, adverse event, pyogenic granuloma Citation: Kanelleas A, Pappa G, Routsi E, Milionis V, Bozi E, Katoulis A. Penile Granulomas Induced by Isotretinoin. Dermatol Pract Concept. 2024;14(1):e2024012. DOI: https://doi.org/10.5826/dpc.1401a12 Accepted: May 15, 2023; Published: January 2024 Copyright: ©2024 Kanelleas 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: Prof. Alexandros Katoulis, “Attikon” General University Hospital, 2nd Dept. of Dermatology-Venereology, Athens, Greece. E-mail: alexanderkatoulis@yahoo.co.uk Introduction Pyogenic granuloma (PG) is a common, acquired, benign vascular tumor arising on skin and mucous membranes [1]. Isotretinoin, a retinoid used in the treatment of moderate to severe acne, is associated with several adverse events, includ- ing PG development [2]. We report a case who developed two penile PGs following treatment with oral isotretinoin for acne. Case Presentation A 29-year-old male patient presented to our outpatient dermatology clinic with a 3-month history of two smooth, erythematous, exophytic lesions on the penis; the first on the glans (Figure 1A), and the second near the frenulum of the penis (Figure 1B). The patient reported that the lesions were asymptomatic, except for some occasional bleeding, and had gradually increased in size over the past few months. He denied trauma or prior contact with chemicals or allergens before the lesion development. The patient had a history of moderate to severe acne and had completed a 6-month course of oral isotretinoin treatment approximately 3 months prior to the lesions onset. During treatment with isotretinoin, he noticed the abrupt onset of a hemorrhagic nodule on the lat- eral nail fold of the right big toe, initially considered to be an ingrown nail. However, after surgical excision of the lesion, it was histologically confirmed to be a PG. Clinical examination of total skin and mucous membranes was otherwise unremarkable. Serologic testing for hepatitis B, C, HIV and VDRL/TPHA were negative. Swab cultures from lesional skin for aerobic and anaerobic bacteria were also negative. Shave biopsies of both lesions were obtained. Differential diagnoses included genital warts, amelanotic melanoma, and squamous cell carcinoma. Histopathological examination revealed a lobular proliferation of congested capillary vessels. There was a superficial mucosal erosion, while the underlying stroma was edematous with a mixed 2 Research Letter | Dermatol Pract Concept. 2024;14(1):e2024012 Figure 1. A. Erythematous, glistening, well-demarcated, infiltrated plaque on the glans of the penis in a 29-year-old pa- tient previously treated with oral isotretinoin. B. A second red, fleshy nodule with a broad base near the frenulum of the penis in the same patient. Figure 2. A, B. Shave biopsy showing lobular configuration of proliferating congested capillary vessels (H&E, x40 and x100 respective ly). perivascular inflammatory infiltrate (Figure 2, A and  B). These findings were consistent with PG. The lesions were surgically excised, and histologic examination confirmed the original diagnosis of PG. No recurrence was observed on 6-month follow-up. Conclusions One plausible explanation for the occurrence of post- isotretinoin PG in our case could be the epidermal barrier impairment caused by isotretinoin, further potentiated by Research Letter | Dermatol Pract Concept. 2024;14(1):e2024012 3 localized trauma and infection, predisposed by sexual prac- tices or poor hygiene of the area, leading to granulation tis- sue production [3,4]. In the literature, there are very few cases of isotretinoin- induced PGs. Most of them were periungual (lateral and distal nail folds), but there were also cases arising on the head, trunk, or upon prior acneic lesions [2,3]. There is only one report of multiple anogenital PGs in a young female that appeared during isotretinoin treatment, requiring dose modification [5]. However, in our case, the development of PGs occurred three months after the completion of isotretinoin treatment. The present case highlights the need to consider PG in our differential diagnostic approach of vascular lesions of the skin and mucous membranes, including the genitals, in patients treated with isotretinoin. More studies are needed for a better understanding of the pathophysiology of PG oc- currence after treatment with isotretinoin. References 1. Sarwal P, Lapumnuaypol K. Pyogenic Granuloma. 2022 Oct 23. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publish- ing; 2023 Jan–. PMID: 32310537. 2. Benedetto C, Crasto D, Ettefagh L, Nami N. Development of periungual pyogenic granuloma with associated paronychia fol- lowing isotretinoin therapy: a case report and a review of the literature. J Clin Aesthet Dermatol. 2019;12(4):32-36. PMID: 31119008. PMCID: PMC6508482. 3. Puig L, Moreno A, Llistosella E, Noguera X, de Moragas JM. Granulation tissue proliferation during isotretinoin treatment. Int J Dermatol. 1986;25(3):191-193. DOI: 10.1111/j.1365 -4362.1986.tb02218.x. PMID: 2939033. 4. Del Rosso JQ. Clinical relevance of skin barrier changes asso- ciated with the use of oral isotretinoin: the importance of bar- rier repair therapy in patient management. J Drugs Dermatol. 2013;12(6):626-631. PMID: 23839177. 5. Cuenca-Barrales C, Ródenas-Herranz T, Linares-Gonzalez L, Ruiz-Villaverde R. Pyogenic Granuloma in an Atypical Location Following Isotretinoin Treatment. Sultan Qaboos Univ Med J. 2018;18(3):e409-e410. DOI: 10.18295/squmj.2018.18.03.028. PMID: 30607291. PMCID: PMC6307634.