Cop+Ed+fisse 2006 121Archivio Italiano di Urologia e Andrologia 2022; 94, 1 LETTER TO EDITOR No conflict of interest declared. KEY WORDS: Covid-19; Vaccination; Penile Mondor; Phlebitis. Submitted 9 January 2022; Accepted 16 January 2022 Dear Editor, the pandemic spread of Coronavirus 2 infection (SARS-CoV-2), determining the coronavirus disease 2019 (Covid-19), had devastating consequences globally with several waves affecting social and economic life. The use of masks, physical distancing, testing of exposed or symptomatic persons, contact tracing and isolation have helped limit the transmission where they have been rigorously applied; however, these actions have proved not sufficient to limit the virus spread. The vaccinations are needed to reduce the morbidity and mortality of Covid-19 (1). Two vaccine types have been developed using two different technologies: viral vectors (Vaxzevria; AstraZeneca) and mRNA (Comirnaty-Pfizer and mRNA-1273- Moderna). Aside from transient local and systemic reactions, no safety concerns were identified from vaccination. Nevertheless, there are several concern in the public opinion about the possible consequences on uro-genital system, both in men and women. We know that exist evidence suggesting no embryo and gametes infections by SARS-CoV-2 and no consequences on fertility potential after vaccination (2). Thrombosis is the most severe and nontypical adverse effects of vaccine. Similarly to Covid-19 infection, in which we recognized a predisposition to both venous and arterial throm- boembolism due to excessive vascular and systemic inflammation, endothelial dysfunction, cytokine storm, hypoxia and immobilization, after vaccination there is a growing evidence of thrombotic vaccine-related events (2). During the first wave in 2020, we had already reported an increase in outpatient evaluations of patients complaining of a vascular andro- logical disease, known as penile Mondor disease (PMD) (1). The PMD occurs with palpable subcutaneous cord-like indura- tions beneath the penile skin (Figure 1). Usually, PMD is an under-reported benign, self-limited disease that resolves spontaneously in four to eight weeks. The PMD under reporting may be because the lesion is often non painful and self-resolving. Most patients refrain from seek- ing medical attention, and when they do, sometimes even physicians pay little attention to the lesion. The PMD patho- genesis can be demonstrated by Virchow’s triad. Triggering factors for endothelial damage intersect with underlying risk of blood stasis and hypercoagulability. For example, PMD may occur after frequent, vigorous, prolonged sexual activity, prolonged erection, urogenital infection and sexually transmitted diseases, pelvic surgery, penile trauma, prolonged sit- ting position, hematologic disease or thrombophilia. The intersection between the three Virchow’s factors allows for blood clot formation in PMD typically isolated to the superficial dorsal vein with associated phlebitis (3, 4). Covid-19 infection is also related to PMD, based on several cases report published in the last years (5). Nothing is reported in the literature regarding the possible relationship between vaccination against Covid-19 and PMD. However, in our daily clin- ical practice, in the last three months, we have recorded an increase in outpatient assessments of PMD. We refer to 5 cases whose clinical data are reported in Table 1. COVID-19 vaccination and penile Mondor disease. There is any relationship? Andrea Fabiani 1, Alessandra Filosa 2, Daniele Maglia 1, Emanuele Principi 1, Silvia Stramucci 3 1 Urology Unit, Surgery Department, Macerata Civic Hospital, Area Vasta 3 ASUR Marche, Italy; 2 Pathology Unit, ASUR Marche Area Vasta 5, Ascoli Piceno, Italy; 3 Urologic Clinic, Marche Polytechnic University, Ancona, Italy. DOI: 10.4081/aiua.2022.1.121 Table 1. Clinical data of 5 cases. Patient Age Vaccine type Vaccination month Outpatient evaluation month Coagulation Abnormal sex activity Hystory clinic 1 25 Pfizer July October Normal No Silent 2 37 Moderna September December Normal No Silent 3 21 Moderna August November Normal No Silent 4 24 Pfizer August December Normal No Silent 5 28 Pfizer July October Normal No Silent Archivio Italiano di Urologia e Andrologia 2022; 94, 1 A. Fabiani, A. Filosa, D. Maglia, E. Principi, S. Stramucci 122 Anamnesis and physical examinations were conducted to evaluate any possible cause of PMD. All patients under- went fast abdominal ultrasound and penile ecocolor- Doppler in flaccidity. Laboratory tests with particular interest on coagulation state were performed. Only the symptomatic patients (2/5) were treated with analgesic. Only one case (1/5) received low molecular weight heparin for 15 days. All patient reported complete recov- ery from symptoms and subcutaneous cord-like indura- tions complained at the presentation. PMD usually affect men at 20 to 40 years of age and in our little case series age ranged between 24 and 37 years. All performed vac- cination 4 or 5 months before with mRNA-Comirnaty- Pfizer (3 cases) and mRNA-1273-Moderna (2 cases). No patients declared prolonged or unusual sexual activi- ty. The clinical histories were silent for any possible hypercoagulability status. Vaccinations were the only possible patho- genetic factors linking the 5 young patients. The questions arising from this real-life experience are basically two. Is it therefore possible that there is a pathogenetic link between PMD and vaccination anti Covid-19? Is there any possibility of identifying subjects predisposed to the onset of this vascular disease after vaccination? Although the PMD clinical course is very often self-limiting, in a scenario characterized by an annual anti-Covid vaccination, may be important to always inform young male about the eventuality of developing PMD and alert general practitioners and referral special- ists about the possible increase in the PMD response. From a diagnostic or therapeutic point of view, we don’t identify the need to change the usual attitude. We must continue to reassure the patient and to treat symptomatic cases since PMD can cause significant patient anxiety and embarrassment and may be easily confused with more concerning condi- tions. Our aim is to urge the andrological scientific community to perform a large-scale data collection that allows us to define a correct answer to our questions. REFERENCES 1. Maretti C, Fabiani A, Colombo F, et al. Italian experiences in the management of andrological patients at the time of Coronavirus pandemic. Arch Ital Urol Androl. 2021; 93:111-114. 2. Ruan Y, Hu B, Liu Z, et al. No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: A perspective and urogenital evaluation. Andrology. 2021; 9:99-106. 3. Manimala NJ, Parker J. Evaluation and treatment of penile thrombophlebitis (Mondor's Disease). Curr Urol Rep. 2015; 16:39. 4. Solinas A. Thrombosis of the posterior scrotal vein associated with essential thrombocytemia: Report of a case. Arch Ital Urol Androl. 2020; 92:112-113 5. Lessiani G, Boccatonda A, D'Ardes D, et al. Mondor's Disease in SARS-CoV-2 Infection: A Case of Superficial Vein Thrombosis in the Era of COVID-19. Eur J Case Rep Intern Med. 2020; 7:001803. Figure 1. Clinical appearance (left, thin arrow) and ultrasound feature (right, arrow) of Penile Mondor disease. Correspondence Andrea Fabiani, MD (Corresponding Author) andreadoc1@libero.it Surgery Dpt, Section of Urology, ASUR Marche Area Vasta 3 Macerata Hospital, Via Santa Lucia, 60100, Macerata (Italy) Alessandra Filosa, MD PhD alessandra.filosa@sanita.marche.it Pathology Unit, ASUR MARCHE Area Vasta 5, Ascoli Piceno (Italy) Daniele Maglia, MD emanuele.principi@sanita.marche.it Emanuele Principi, MD emanuele.principi@sanita.marche.it Surgery Dpt, Section of Urology ASUR Marche Area Vasta 3, Macerata Hospital, Macerata (Italy) Stramucci Silvia, MD silvia.stramucci@gmail.com Urologic Clinic, Marche Polytechnic University, Ancona (Italy)