30 December 2021: Articles
Unknown etiologyAbdullah Mousa Alzahrani 1ABEF*, Jumanah H. Basalelah1AE, Mishal S. Alarifi1E, Shaheed S. Alsuhaibani1A
Am J Case Rep 2021; 22:e935716
BACKGROUND: Having painful intermittent penile erections that last less than 4 h is known as stuttering priapism. Sickle cell disease is a well-known risk for stuttering priapism; although, other causes could be related to this disorder. To date, no study has examined the relationship between stuttering priapism and electronic cigarettes (e-cigarettes).
CASE REPORT: We present a case of a 31-year-old man who came to our clinic with recurrent stuttering priapism. He had no chronic medical illnesses. He had smoked half a pack of cigarettes per day for the past 6 years but had shifted to vaping e-cigarettes for which he used several e-fluids and brands. His stuttering priapism started approximately 1 week after he began vaping. A detailed history and physical examination were unremarkable. Laboratory results showed a normal complete blood count and metabolic panel along with a normal testosterone level and negative sickle cell screening test. The chest X-ray and abdominal and pelvic ultrasound were normal. Initially, we reassured the patient; however, his condition persisted with no significant changes in his general health or lifestyle. We asked him to stop using e-cigarettes, and after he stopped, his stuttering priapism surprisingly completely resolved. He has not experienced a single episode of stuttering priapism in the 3 months since the cessation of e-cigarettes use.
CONCLUSIONS: The relationship between stuttering priapism and e-cigarettes remains largely unexplored in the literature. Whether e-cigarettes and e-fluids represent a risk factor for priapism in novice e-cigarette smokers warrants further investigation.
Keywords: E-Cigarette Vapor, Priapism, Smoking Devices, Vaping
Stuttering priapism is defined as the recurrence of painful unwanted erection that occurs intermittently, usually for a shorter duration than full ischemic priapism. It can, however, increase in frequency and duration and develop into a full episode of ischemic priapism . Historically, stuttering priapism has been predominantly associated with sickle cell disease. Yet, idiopathic priapism still encompasses a meaningful proportion of cases, which is roughly estimated to be more than half of all priapism cases .
The exact mechanisms underlying stuttering priapism are not well known, which is suggestive of a multi-factorial disease etiology, including aberrant nitric oxide (NO) bioavailability, blood viscosity, and vascular reactivity. Disease management is currently focused on preventing the development of a full episode of ischemic priapism and dealing with possible consequences of erectile dysfunction .
Data on the association between electronic cigarettes (e-cigarettes) and stuttering priapism are lacking. Here, we present the first case of 1 possible adverse effect of e-cigarettes in a young male patient. We link the patient’s presentation to e-cigarettes after ruling out well-known causes. Moreover, the presentation was only during a very specific period of time that coincided with when he started using e-cigarettes, with no other potential explanations. Most importantly, his symptoms completely resolved with no recurrence after the complete cessation of e-cigarette use.
A 31-year-old healthy man presented to our clinic with a complaint of intermittent prolonged painful erections that had started 3 weeks prior. He described the erections as rigid, painful, and lasting for 2 to 4 h about 5 to 7 times per week with no sexual stimulation at all. He took nonsteroidal analgesics for pain and could not think of the reason behind his condition. He had no history of trauma to his penis or any erectogenic or psychotropic medications. He also had no history of pelvic trauma or surgery. He had a 3-pack-year smoking history; however, he switched to e-cigarettes about 1 month prior to presentation. He used 3 different juices in his e-cigarettes with a 1: 1 ratio of propylene glycol to vegetable glycerol; however, although he was unaware of the desired strength, he was using e-cigarettes 3 to 4 times per day. He did not consume alcohol or abuse drugs. He has no family history of hematological diseases or cancers. He was single and worked as a health educator. He had not traveled anywhere recently nor had he come into contact with any patients with tuberculosis. His systemic review was unremarkable. A thorough physical examination revealed normal chest and cardiovascular systems. His abdominal examinations showed no hepatosplenomegaly or other palpable masses. The genitalia examination revealed a normal phallus and meatus and palpable testes with no masses or varicocele. His lower limb and neurological examinations were also completely normal. A complete blood count showed red blood cell count of 5.2×106/µL, hemoglobin level of 14.6 g/dL, hematocrit of 44.1%, platelet count of 322×103/µL, and a testosterone level of 295 ng/dL. Additionally, the sickle cell screening test was negative. We did an abdominal ultrasound, which revealed a normal liver and spleen, and no urinary system abnormality; his pelvic ultra-sound was unremarkable as well. Initially, we diagnosed his condition as idiopathic stuttering priapism. We did not offer him any medications, only reassurance and close follow-up. He came to the follow-up after 2 weeks from his initial visit with the same issue, with no worsening or progression. We discussed any recent lifestyle changes, and he confirmed that e-cigarette use was the only recent change and that he was still unable to adjust the proper e-juice dose. Therefore, we asked him to stop smoking e-cigarettes completely. He came back weeks later to report the complete resolution of his condition. Three months later, he still had not had a single episode after completely stopping his use of e-cigarettes and returning to his usual tobacco cigarettes. The patient provided his written informed consent to publish his report under the condition of confidentiality.
Priapism is a prolonged undesirable erection that continues hours beyond or even without sexual arousal. The characteristics of priapism divide this condition into 3 usual types: ischemic (low flow), non-ischemic (high flow), and stuttering. Painful persistent erections that last more than 4 h are the defining characteristic of ischemic priapism. If this type of painful erection occurs often and for less than 4 h irrespective of sexual motivation, it is referred to as a stuttering, intermittent, or recurrent priapism . As such, stuttering is a subtype of ischemic priapism, and some patients might progress from stuttering to ischemic episodes, which is a medical emergency that requires urgent intervention to prevent serious complications from this condition, such as corporal fibrosis and subsequent erectile dysfunction .
The incidence of stuttering priapism is not well studied in the literature, potentially because the nature of spontaneous detumescence leads to the rare presentation of patients with stuttering priapism in emergency departments or specialized clinics. However, because stuttering priapism is a subtype of ischemic priapism, its incidence might reflect, to some extent, the magnitude of such a rare entity. Kulmala et al reported an incidence of ischemic priapism as 0.5 per 100 000 person-years in Finland. However, another European study found a higher incidence of ischemic priapism of 1.5 per 100 000 person-years. That study included all patients who presented to general practitioners, which could explain the higher incidence compared to the Finish study [4,5]. A study in the United States measured the incidence of priapism through nationwide emergency department visits between 2006 and 2009 and found an incidence of 5.34 per 100 000 person-years . Unfortunately, none of the aforementioned studies mentioned the incidence of stuttering priapism in patients who had developed ischemic priapism, regardless of the cause.
Stuttering priapism shares, to some extent, the same causes that can lead to ischemic priapism, which are uncountable . Sickle cell disease is a common well-known cause of ischemic priapism. A study reported the lifetime incidence of priapism in sickle cell disease to be as high as 42%, of which stuttering priapism proceeded the episodes of ischemic priapism 75% of the time . On the other hand, Earle et al reported that more than two-thirds of their cohort of priapism cases were caused by vasoactive intracavernosal injections, while the remaining cases were due to antipsychotics, anticoagulants, drug abuse, and idiopathic causes . Several other studies have reported causative factors such as benign and malignant hemato-logical disorders, genitourinary neoplastic metastasis, toxins, neurologic conditions, metabolic diseases, and vasoactive and non-vasoactive medications [7,10–12]. A study conducted on 42 rats investigating oral tobacco dust found that rats exposed to more than 4 g of tobacco developed ischemic priapism, compared with the control group in which not a single case of priapism was found. However, no human study reports the effect of smoking on stuttering priapism, and, therefore, no study has identified e-cigarettes as a possible trigger of stuttering priapism.
E-cigarettes are battery-powered nicotine delivery devices with several models and brands and a myriad of flavors that produce aerosols denoted as vapor generated from heating the e-liquid, which is composed of propylene glycol/vegetable glycerol mix with or without nicotine . Their usage is growing rapidly among young adults worldwide. The US Food and Drug Administration recommends considering e-cigarettes as a tobacco product . The safety of e-cigarettes is questionable, and the World Health Organization has proposed that e-cigarettes represent a significant health risk. Despite claims of fewer toxins in e-cigarettes than traditional in tobacco products, the evidence is lacking . E-cigarettes have serious pulmonary side effects, reflected by the condition named e-cigarette (or vaping) product use-associated lung injury after fatal acute lipid pneumonia, which is registered in the United States . Several studies have emphasized the adverse effects of e-cigarettes on other systems, including the gastrointestinal tract (eg, dry mouth, sore throat, and gum bleeding), and the neurological, immune, nephrological, and cardiovascular systems . Moreover, explosive injuries and serious burns from e-cigarettes are likely complications .
The mechanisms underlying stuttering priapism have molecular and biological elements. Expanding the medical therapies to look at the origins of such a condition and the relationship to e-cigarettes is warranted . A penile erection physiologically depends on many molecular, hormonal mediators that require a complex network of connections between the vascular, neurological, and endocrine systems. Molecular erec-tile and anti-erectile facilitators and mediators include neuronal NOS, endothelial NOS, cyclic guanosine monophosphate (cGMP), and phosphodiesterase type-5 (PDE-5). Several other mediators are involved in penile tumescence and detumescence processes that can contribute directly or indirectly to stuttering priapism, such as the Rho A/Rho-kinase pathway, adenosine, opiorphins, and other gaseous molecules (eg, carbon monoxide and hydrogen sulfide) . Oxidative stress also plays a crucial role in triggering stuttering priapism through a direct impact on the NO/cGMP system locally in the penile corpora by reducing the bioavailability of NO. In this regard, increased oxidative stress on the corpora of mice exposed to e-cigarette fluid was described by Nguyen et al as more endothelial damage than that of the control group . Kuntic et al reported that the effect of e-cigarettes on the endothelial malfunction of the cardiovascular system is indicative of oxidative stress along with other markers, including lipid peroxidation and inflammation. Moreover, the same study found that the increased oxidative stress on the endothelium was dependent on reactive oxygen species (ROS) and other mediators linked to e-cigarettes . Endothelial smooth muscle in a state of stuttering or ischemic priapism generates more ROS, which could be exacerbated in some e-cigarettes smokers, leading to more endothelial damage and distribution of NO synthesis causing an episode of priapism . Lee et al studied the effects of flavored liquid of e-cigarettes on endothelial cells and came to similar conclusions as the aforementioned studies: that the flavors increase ROS and disrupt NO synthesis and that eventually more endothelial damage could be a trigger of priapism or erectile dysfunction in a population of smokers with unspecified characteristics . Consequently, e-cigarettes might incur stuttering or ischemic priapism according to these molecular theories. Our patient’s active e-cigarette smoking when he experienced stuttering priapism and the complete resolution of his condition upon cessation is in line with the clinical presentation and the literature that describes the pathophysiology of stuttering priapism.
The hallmark of stuttering priapism management focuses on the prevention of such an event; this can be accomplished by stopping the triggering substance or treating the primary cause if known. Clinical therapies include medications aimed at either adjusting hormones or increasing the smooth muscle tone of the corpus cavernosum. Hormonal adjustment aims to decrease testosterone levels and minimize the androgenic effect on penile erections by administering gonadotropin-releasing hormone agonists, antiandrogens, diethylstilbestrol, and ketoconazole . PDE-5 inhibitors are usually used to prolong penile erections by reducing cGMP breakdown; however, long-term use causes a paradoxical effect and marked stuttering priapism relief in patients with sickle cell disease and other causes of this condition .
Surgical intervention can be considered for patients with prolonged stuttering priapism that advances to the ischemic type. Corporal aspiration with phenylephrine injection, proximal or distal shunting, and penile prosthesis insertion are the surgical options available to these patients .
Stuttering priapism has various causes, of which many remain unknown. E-cigarettes could be one such reason in a genuine tobacco smoker who switched to vaping. The type of smoking needs to be documented in detail in a patient’s medical history, particularly for those patients who could fill the cognizance gap in the relationship between e-cigarettes and priapism.
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