Background: Recurrent (stuttering) ischemic priapism is a challenging clinical condition. Frequent recurrences result in frequent hospital admissions whereas treatment with a shunting procedure often results in erectile dysfunction. Case presentation: A 22-year-old man with stuttering idiopathic priapism developed erectile dysfunction (IIEF-5 score 12) following a Winter’s shunt; he was given tadalafil, 5 mg/daily, for 6 months. This treatment resulted in progressive restoration of erectile function in the 6 months following the shunt as well as in preventing recurrence of priapic episodes over a 24-month follow-up. Conclusions: This is the first report in literature of chronic treatment of stuttering priapism with a phosphodiesterase-5 inhibitor being able not only to prevent recurrent priapic episodes but also to restore erectile function following a Winter’sshunt. Keywords: Priapism, PDE-5 i, Winter’s shunt, Erectile dysfunction, Tadalafil Background prepriapism erectile function, after 24 h after onset . Recurrent priapism, commonly known as stuttering priap- Herein we describe treating the chronic phase of stuttering ism, is an unusual form of low-flow priapism that usually idiopathic priapism with tadalafil, 5 mg daily, in order to results in cavernous ischemia with consequent damage of preventing recurrences and restoring erectile function fol- erectile function. Sickle cell disease is considered the most lowing Winter’sshunt. common cause or stuttering priapism. Another large number of cases are classified as idiopathic, whereas Case presentation non-erectogenic drugs or neurological disorders are rarely A 22-year-old man presented to our emergency clinic responsible for such condition. with a long-standing (5 h) sustained painful erection. He Primary treatment involves corporal aspiration followed had no history of previous illnesses, trauma, drug intake by intracavernous injection of sympathomimetics ; in or previous similar attacks. He reported having a stable case of failure, a shunting procedure becomes mandatory. heterosexual relationship and that his sustained erection Themostcommonshunting procedureremains theWin- had started outside a sexual encounter. When he was ter’s shunt as it is quick and successful in 50 to 65% of cases asked if this was the first episode, he mentioned that he [2, 3]. Unfortunately, the Winter’s shunt does not prevent had noticed, approximately over the last 18 months, an recurrences [4, 5] and, on the other hand, leads to erectile increase in number and duration of his spontaneous dysfunction (ED) when the procedure is carried out within erections; however, given the absence of significant pain, 24 h of priapism onset , therefore well before ischemia such events were not considered relevant. has led to definite cavernosal damage [7, 8]. Howewer, On examination, the penis was fully erected with a soft satisfactory results have been reported preservation of glans. Intracavernous blood sampling was suggestive for hypoxic, low-flow priapism (Ph 7.06; PCO 14, arterial ref.: * Correspondence: firstname.lastname@example.org 4.5–6.1 kPa; PO 2.6, arterial ref.: 10–13.5 kPa). Moreover, Department of Urology and Renal Transplantation, University of Foggia, penile and perineal duplex ultrasound ruled out an arterio- Foggia, Italy 3 venous fistula. He therefore underwent intracavernous in- Bari-Palese, Italy Full list of author information is available at the end of the article jection (ICI) of etilefrine 5 mg followed by corporeal © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Massenio et al. BMC Urology (2018) 18:54 Page 2 of 3 irrigation/aspiration and again (ICI) of etilefrine 5 mg the other hand, recent studies suggest stuttering priapism followed by corporeal irrigation/aspiration; this procedure, to be related to a defective PDE5 regulatory function in the however, did not lead to penile detumescence. Meanwhile, penis, resulting from altered nitric oxide and cyclic guano- peripheral blood analysis ruled out hematological disorders. sine monophosphate signaling mechanisms which control He was admitted with the diagnosis of low-flow idiopathic erectile function [11–15]. Specifically, altered vascular priapism and scheduled immediate Winter’sshunting. The homeostasis and oxidative stress could cause endothelial procedure was carried out under spinal anesthesia using a damage with reduced production of endothelial NO, which 16-G automatic spring-loaded tru-cut needle and led to leads, by a negative feedback mechanism, to downregula- complete detumescence. tion of PDE-5 expression. Under these conditions, cyclic The following morning, the penis was flaccid but the pa- guanosine monophosphate builds up in the corpora cavern- tient reported having had a spontaneous morning erec- osa and cannot be degraded due to lack of PDE5 function, tion. He was discharged home but, 2 days later, he thus leading to prolonged corporal smooth muscle relax- presented to our emergency clinic with a long-lasting ation/priapism episodes. Moreover, erections may also be (4 h) sustained painful erection outside a sexual encoun- induced by neuronal NOS. Such mechanisms would ex- ter. Again, intracavernous blood sampling was suggestive plain recurrent priapic episodes as well as damage of erect- for hypoxic, low-flow priapism (Ph 7.00, PCO 13, PO ile function in patients with stuttering priapism. 2 2 2.4) and again ICI of etilefrine 5 mg and corporeal irriga- Due to their erectogenic effect, oral PDE5 inhibitors tion/aspiration done twice did not lead to penile detumes- are commonly used as medical treatment for ED; how- cence. Therefore, he was admitted and scheduled for ever, scientific evidence has shown they have a paradox- multiple (two for each corpus cavernosum) Winter’s ical effect in alleviating stuttering priapism [15–20]. shunts resulting in complete detumescence. The urethral Preclinical studies suggest daily administration of catheter, left in place at the end of the procedure, was re- low-dose PDE-5 inhibitors after the acute period of pri- moved on second postoperative day. Persisting complete apism to upregulate PDE-5 gene expression, to stimulate penile detumescence and absence of spontaneous erec- eNOS expression and to reduce the state of dysfunc- tions, the patient was discharged on fourth post-operative tional NO pathway . By doing so, such treatment day with the advice of avoiding sexual encounter. could restore the balance between stimulating and inhi- At one-week follow-up, the penis was fully detumescent biting factors, thus reducing the episodes of priapism but the patient reported a few episodes of spontaneous tu- . In a small case series, Burnett and colleagues  mescence. Therefore, he was allowed to start sexual en- showed that daily PDE5 inhibitor therapy reduced ische- counters. At one-month follow-up, he reported several mic priapism episodes in men with stuttering priapism, episodes of spontaneous tumescence never reaching rigid- either idiopathic or due to sickle-cell disease, without ity and of prolonged (> 3 h) good tumescence but no modifying erectile function. Moreover, there was no ad- penile rigidity during sexual encounters, scoring 12 on verse event and only one patient did not respond to International Index of Erectile Function [IIEF-5] question- treatment. The authors pointed out that such treatment, naire. Following extensive discussion and a written in- which should be started under conditions of complete formed consent, he was given tadalafil, 5 mg daily. At penile flaccidity, was most useful for patients with mild 3-month follow-up, he reported progressive improvement or moderate disease. None of treated patients, however, of his erections, both spontaneous and sexually-induced, had undergone a Winter’s shunt. with an IIEF-5 score of 18. At 6-month follow-up, the To our knowledge, our is the first report of long-term IIEF-5 score had reached 22; daily tadalafil was stopped administration of tadalafil 5 mg/daily for preventing re- and substituted with tadalafil 10 mg on-demand. At current episodes of stuttering priapism as well as for 9-months follow-up, the patient reported having resumed treating ED which had developed after having managed normal spontaneous and sexually-induced erections, with a non-subsiding priapism recurrence by a Winter’s no episodes of prolonged erection nor of tadalafil use; did shunt. As a matter of fact, findings confirmed the ability IIEF-5 score remain at 22. Therefore, he was stopped any of such treatment to preventing recurrent priapic epi- treatment. To date, at 24-month follow-up he has normal sode over the 24 months follow-up period; moreover, it spontaneous and sexually-induced erections without any resulted in progressive restoration of erectile function, drugs; IIEF-5 score remains 22. with IIEF-5 score raising from 12 to 22 in 6 months and remaining stable over the next 18 months. Discussion The pathophysiology of stuttering priapism is unknown. It Conclusion has been speculated that downregulation of adrenorecep- In conclusion, idiopathic priapism is a rare clinical condi- tors in the cavernous smooth musculature or scarring of tion. Acute treatment consists in corporal aspiration, intra- intracavernous venules may trigger recurrences . On cavernous injection of sympathomimetics and, in case of Massenio et al. BMC Urology (2018) 18:54 Page 3 of 3 failure, a shunting procedure. The reported case suggests 15. Champion HC, Bivalacqua TJ, Takimoto E, Kass DA, Burnett AL. Phosphodiesterase- 5A dysregulation in penile erectile tissue is a mechanism of priapism. Proc Natl that prevention of new priapic episodes as well as restor- Acad Sci U S A. 2005;102:1661–6. ation of erectile function following a Winter’s shunt can be 16. Bivalacqua TJ, Musicki B, Hsu LL, Gladwin MT, Burnett AL, et al. achieved by chronic administration of tadalafil, 5 mg/daily. Establishment of a transgenic sickle-cell mouse model to study the pathophysiology of priapism. J Sex Med. 2009;6:2494–504. Such observation could set the basis for more extensive 17. Bialecki ES, Bridges KR. Sildenafil relieves priapism in patients with sickle cell evaluation of such treatment in this unusual condition. disease. Am J Med. 2002;113:252. 18. Burnett AL, Bivalacqua TJ, Champion HC, Musicki B. Feasibility of the use of Abbreviations phosphodiesterase type 5 inhibitors in a pharmacologic prevention ED: Erectile dysfunction; IIEF: International Index of Erectile Function; program for recurrent priapism. J Sex Med. 2006;3:1077–84. NO: Nitric oxide; PDE-5: Phosphodiesterase type 5 inhibitor 19. Bivalacqua TJ, Musicki B, Champion HC, Burnett AL. Phosphodiesterase type 5 inhibitor therapy for priapism. In: Carson IIICC, Kirby RS, Goldstein I, Wyllie MG, editors. Textbook of erectile dysfunction. 2nd ed. New York: Informa Authors’ contributions HealthCare; 2009. p. 428–33. PM: manuscript conception and drafting. ND: data collection. FS: manuscript 20. Burnett AL, Bivalacqua TJ. Priapism: current principles and practice. Urol Clin drafting. GC: clinical supervision. LC: clinical and manuscript supervision. All North Am. 2007;34:631–42. authors read and approved the final manuscript. 21. Champion HC, et al. Phosphodiesterase-5A dysregulation in penile erectile tissue is a mechanism of priapism. Proc Natl Acad Sci U S A. Consent for publication 2005;102(5):1661–6. Written informed consent was obtained from the patient’s next of kin for 22. Anele UA, Burnett AL. Nitrergic mechanisms for management of recurrent publication of this case report and any accompanying images. A copy of the priapism. Sex Med Rev. 2015;3(3):160–8. Epub 2015 Jun 4 written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests. Publisher’sNote Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author details Department of Urology and Renal Transplantation, University of Foggia, Foggia, Italy. Department of Pathology, University of Foggia, Foggia, Italy. Bari-Palese, Italy. Received: 9 January 2017 Accepted: 16 May 2018 References 1. 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Published: May 31, 2018