CASE
A 60-year-old man presented to the ED at 3:30 am complaining of pain and swelling to his penis which had onset at 6:30 pm the preceding evening. He had three days of sore throat, fatigue, and general malaise with possible fever and had been taking a cold and sinus remedy (ibuprofen/pseudoephedrine). His medications included pravastatin and perindopril. He denied use of any phosphodiesterase inhibitors or other treatments for erectile dysfunction. He denied tobacco, alcohol, street drug use, and herbal remedies.
Initial vital signs were: 36.4 C°, HR 72, RR 23, BP 135/76 and 98% on RA. He appeared severely distressed and was moaning in pain due to a penis that was erect, firm, and markedly tender with no skin changes. Full physical examination revealed a normal oropharynx, and non-tender, reducible left inguinal hernia, and nothing else contributory. Laboratory values: Hb of 133 g/L, WBC 11.6 x 109/L with a neutrophilia of 11.2 x 109/L (2.0-8.0), and platelets 187x109/L (150-400). Sodium was 129 mmol/L (133-145), potassium 4.4 mmol/L (3.3-5.1), chloride 93 mmol/L(98-111), CO2 19 mmol/L (21-31), and creatinine 90 umol/L (50-120).
A diagnosis of ischemic priapism was reached. The preceding sore throat was judged to be irrelevant. A decision to aspirate blood from the corpora cavernosum and inject phenylephrine was made. The patient received sedation by propofol and fentanyl with hemodynamic monitoring. As per European Association of Urology GuidelinesReference Salonia, Eardley and Giuliano 1 , a total of 1,500 mcg of phenylephrine was delivered with aspiration via an 18-G butterfly needle to the right and left corporal bodies during two separate sessions spaced one hour apart. The priapism did not resolve, so the urology service was consulted at 7:30 am. A large hematoma at the injection site on the penile shaft was noted.
Urology noted severe penile pain. The penis was bruised and swollen with a blackened glans, raising the concern for tissue necrosis secondary to phenylephrine. A Marcaine penile block temporarily relieved the pain. Given the lack of a clear etiology, discussion with Interventional Radiology was initiated to consider the role of an angiogram for further diagnosis and treatment. A corporal shunt was also considered.
At 11 am the patient ambulated to the bathroom. He strained to urinate then developed a severe headache. He walked back to his bed where he became diaphoretic, hypoxic, and nauseated. A portable chest x-ray showed no active cardiopulmonary disease. At 12 pm, his blood pressure increased to 218/131 mm Hg, the patient became agitated then unresponsive and apneic. Artificial respirations were initiated immediately and the patient intubated. He then suffered a cardiac arrest and attempted advanced cardiovascular life support (ACLS) resuscitation was unsuccessful.
Autopsy revealed GAS in the blood and lung tissue. Unresolved priapism was noted with septic penile vein thrombosis and infarction. There were septic thromboses (clots containing GAS bacterium) in the blood vessels of the brain, kidneys, heart and lungs, and accelerated post-mortem decomposition.
DISCUSSION
Following the autopsy findings, the presumed pathophysiology is that streptococcal pharyngitis led to invasive GAS (iGAS) disease causing disseminated intravascular coagulation (DIC). Priapism was the predominant presenting feature of DIC. The patient did not clinically appear to have sepsis and remained hemodynamically stable until approximately one hour before his death. He did not manifest the typical ecchymoses, abnormal bleeding, lab work abnormalities, or clinical evidence of other end organ infarction expected in DIC. The absence of typical signs or symptoms of sepsis or DIC in this case is highly unusual, as was the normal platelet count. Coagulation studies and DIC lab work were not ordered because DIC was not suspected clinically. DIC was confirmed by autopsy findings of thromboses in blood vessels of multiple tissues; this is the gold standard for diagnosing DIC. Clinicians are reminded that all DIC laboratory studies have imperfect diagnostic performance.Reference Yu, Nardella and Pechet 2
The possibility that a delayed release of phenylephrine from the penile tissue into the systemic circulation led to the patient’s decompensation, with the onset of headache and hypertension, was considered prior to the autopsy results. One case report of phenylephrine treatment of priapism leading to subarachnoid hemorrhage was found; however, the headache and blood pressure increase in that case was immediate following the phenylephrine injectionReference Davilla, Parker and Webster 3 . In our case, the symptoms and blood pressure did not change for four hours after the final phenylephrine injection. Further, the finding of DIC and GAS sepsis on autopsy make the cause of death abundantly clear. We doubt that phenylephrine contributed in any significant way to our patient’s death.
This is the first reported case of ischemic priapism as the predominant finding of DIC. DIC has been caused by iGAS previously as in a case report from the Lancet in 1988 which reported DIC from GAS that led to two maternal and fetal deaths.Reference Acharya, Lamont and Copper 4 Another report described group A strep cervicitis causing DIC in a female patient.Reference Paraskevaides and Wilson 5 DIC causing priapism is rare but known. In the two prior case reports, we found priapism was part of a constellation of findings of DIC. A 72-year-old male with fever, cough, bronchitis, cirrhosis, and purpura developed priapism after a week of illness which was treated with penile amputation for necrosis.Reference Takamura, Suzuki and Hiei 6 A 61-year-old male developed priapism secondary to cryptococcal infection contracted from pigeon droppings.Reference Wagenhauser, Ertas and Sagban 7 This case of GAS-induced DIC presenting as priapism has never been reported.
The definition of iGAS includes streptococcal toxic shock syndrome (STSS), soft tissue necrosis (e.g., necrotizing fasciitis), meningitis, GAS pneumonia, bacteremia, and other life threatening conditions. 8 This case would fit within the definition of iGAS. The Alberta Health Notifiable Diseases Guidelines on iGAS, last published in June of 2013, 8 list the incidence of severe iGAS as 6.3 cases per 100,000 persons in 2012. An increase in cases during the 1980s and 1990s was related to an increase in prevalence of the M1 and M3 serotypes. 9 iGAS occurs more commonly at the extremes of age and in immunocompromised states. 8 The World Health Organization concludes that 1.78 million new cases of serious GAS occur and are responsible for over 500,000 deaths worldwide annually. 10
Public attention peaks at times of clusters of iGAS disease. The insidious nature of severe cases in healthy hosts can be alarming. Fox stressed the “necessity of early recognition of the varied presentations of these infections” and stated that invasive GAS is “uncommon but fulminant and often lethal.”Reference Fox, Born and Cohen 11 General principles of management of iGAS include early antibiotics, source control, and supportive care. Antibiotics should include a beta-lactam to inhibit bacterial reproduction and clindamycin to inhibit exotoxin synthesis.Reference Fox, Born and Cohen 11 Surgical debridement of any necrotising soft tissue infections is imperative. Pain out of proportion with physical findings is a red flag for necrotising infection. It is unclear in our case the mechanism for the severe pain experienced by our patient—it may have been the severe ischemia from the priapism itself, or septic emboli occluding small penile vessels. Necrotizing fasciitis was not found at autopsy.
Priapism, an erection that persists beyond sexual stimulation or is unrelated to it, is a rare urologic emergency estimated at 0.73 per 100,000 male subjects per year.Reference Roghmann, Becker and Sammon 12 Three types of priapism have been categorized: ischemic, nonischemic, and stuttering. Etiologies are well described in the recent European Association of Urology (EAU) Guideline.Reference Levey, Segal and Bivalacqua 13 In practice, ischemic priapism, also known as low flow priapism, accounts for nearly 95% of all cases.Reference Salonia, Eardley and Giuliano 1 While the EAU guidelines list idiopathic priapism as the most common etiologyReference Salonia, Eardley and Giuliano 1 , our local experience is that iatrogenic causes—especially injection therapy for the treatment of erectile dysfunction and oral trazodone—predominate. EAU guidelines list many other potential causes for ischemic priapism, however, GAS and DIC are absent from this list.
In conclusion, ischemic priapism is a rare urologic emergency. Usual etiologies include injection therapy for erectile dysfunction, oral medications, and idiopathic. Management pathways can be reviewed on online resources such as the EAU guidelines listed in Useful Resources (Figure 1). When confronted with a case where no etiology is apparent, a search for reversible triggers should be undertaken. This is the first report of a case of GAS-induced DIC causing priapism. The reader is reminded that occult DIC should be considered in patients with their first episode of idiopathic priapism and a poor response to cavernosal aspiration and vasoconstrictor injection. A full history of preceding illness, careful physical examination, and DIC lab work should be considered when clinically warranted. Autopsy can be critical to understanding cases of unexpected mortality. Figure 2 summarizes the key findings of this case.
Figure 1 Useful Resources.
Figure 2 Take Home Messages.
Competing Interests: None declared.
