A Systematic Literature Review of the Burden of Ischemic Priapism in Patients with Sickle Cell Disease

INTRODUCTION: Ischemic or low-flow priapism is a serious condition characterized by a persistent, painful erection that lasts at least 4 hours or is unrelated to sexual stimulation. Both stuttering (repeated short episodes) and fulminant (long-lasting) priapism are prevalent in men and boys with sickle cell disease (SCD). Approximately 40% of patients with SCD will experience priapism during their lifetime. The objective of this study was to conduct a systematic literature review (SLR) to identify published studies reporting the burden associated with priapism in patients with SCD.

METHODS: MEDLINE, Embase, Cochrane CENTRAL/CDSR and 14 congresses were searched from May 9-16, 2019. Results were screened against predefined criteria by two independent researchers. Studies assessing the clinical, humanistic, or economic burden of human patients with SCD and priapism (N≥15) were included. Outcomes of interest included priapism-related symptoms, treatment-related complications, quality of life (QoL), and economic burden.

RESULTS: The literature search identified 1236 articles; 62 full-text studies were reviewed in detail and 34 studies were included in the analysis. Most studies were retrospective observational (21), others were prospective (7 observational, 6 interventional). Study size varied widely (range: 15-10,788 patients). Of 27 studies that reported mean or median patient age, the age statistic for patients with SCD and priapism ranged from 10 to 32.

Overall, 19 studies reported at least one aspect of clinical burden. Thirteen reported the rate of erectile dysfunction or impotence, ranging from 0% to 56%. Eight reported treatment-related complications, including perceived penile scarring/deformity (19.4%) and small intrapenile hematoma (13.3%).

Nineteen studies reported QoL outcomes. Eight reported physical outcomes, including a negative impact of SCD-related priapism on sleep quality and worse scores on periodic limb movement and apnea hypopnea indices. Seven reported measures of sexual function, including low rates of satisfactory sexual intercourse. One study reported a diminished Sexual Health Inventory for Men score in patients with active priapism, and another found a statistically significant relationship between stuttering priapism and premature ejaculation. Three studies reported measures of mental function, one of which outlined increased cognitive fatigue and impaired emotional functioning among children with priapism and another reported that 36% of patients had substantial to very extreme worry regarding episodes of priapism. Use of validated measures for QoL were limited: 3 studies assessed patients with the International Index of Erectile Function (IIEF) and 1 with the Priapism Impact Profile (PIP). No studies measuring the burden to caregivers of pediatric patients with priapism were identified.

Eight studies reported the economic burden of priapism in patients with SCD, including rates of emergency department visits (4 studies: 56.5% sought hospital treatment - 26/46; 49.8% admission to the hospital out of emergency department visits - 5371/10,788; 50.4% admitted at the emergency department - 930/1844; 26% vs. 11% readmission vs no readmission - p <0.001) and hospital length of stay (4 studies: mean 3.38 days; mean 3.8 days; median 2 days; median 5 days in patients who received an exchange transfusion as a treatment for priapism.). Three studies reported direct treatment costs, ranging from a mean of $4496 (2015 USD) for patients who did not undergo penile operations to a mean of $19,670 (2013 USD) total adjusted hospital costs for patients receiving both transfusions and urologic procedures.

CONCLUSIONS: This SLR identified 34 studies reporting the burden of priapism in patients with SCD. No RCTs were identified. The use of comprehensive or validated measures of humanistic burden was limited. Manifestations of priapism are wide-ranging, including painful treatment-related complications, impaired sleep, and diminished physical, mental and sexual function. Patients with priapism and SCD are more likely to visit the emergency department and experience longer hospital stays compared to SCD patients without priapism. Together, the evidence identified in this SLR indicates that priapism not only can result in erectile dysfunction, but can impair multiple dimensions of a patient's physical and mental health.