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A 35-year-old man presented to the emergency department with extreme pain in his penis and scrotum. He explained that his symptoms started after he injected cocaine into the dorsal vein of his penis 3 days previously, and the pain has been intensifying. He told clinicians that immediately after injecting the cocaine, he experienced severe pain radiating to the inguinal region and right foot. At the same time, he described observing swelling and blanching on the underside of his penis, accompanied by signs of necrosis and ulceration on the lateral aspect.

Physical examination indicated that the patient had stable vital signs (temperature 37°C, heart rate 86 bpm, and blood pressure 117/63 mm Hg). His mental status was normal, and he was fully aware of his surroundings. He admitted injecting drugs in the past, adding that in the past 2 weeks, he had injected cocaine into the dorsal vein without any ill effects.

Lung auscultation identified bilateral vesicular breathing. On cardiac examination, clinicians noted normal S1 and S2 heart sounds. Abdominal examination showed no sign of enlargement of the liver or spleen. Findings of the neurological examination were unremarkable. On examination of his genitals, clinicians noted ulcers and swelling on the ventral proximal penis and scrotum junction with a discharge of foul-smelling serous fluid. There was no crepitus.

The patient had swollen lymph nodes on both sides of the groin that were tender on palpation and stellate purpura with necrosis of the dorsum of the penis. Laboratory tests revealed a white blood cell count of 11.9 g/dL, erythrocyte sedimentation rate of 43.0 mm/h, and C-reactive protein level of 52.71 mg/L. The patient had normal liver function and electrolytes. His urine drug screen was positive for cannabis, cocaine, and methadone.

A computed tomography (CT) scan of the pelvis with contrast revealed subcutaneous swelling of the penis, with ulceration of the right side of the penile tip. CT findings also included left inguinal adenopathy, with nodes measuring up to 1.7 cm, which was presumably reactive.

Clinicians determined that the symptoms were not due to Fournier gangrene, and began IV treatment that included:

• Piperacillin/tazobactam (Zosyn, 3.375 g every 6 hours)
• Vancomycin (Vancocin, 1.5 g every 12 hours)
• Clindamycin (Cleocin, 300 mg every 8 hours)
• Topical bacitracin/polymyxin (one application every 6 hours)

The patient declined to undergo any surgical debridement. With antibiotic therapy and local wound care, his symptoms gradually improved. A blood culture showed no signs of growth, and clinicians determined he did not have vasculitis or any coexisting sexually transmitted diseases.

After 5 days of treatment, the patient was switched from IV antibiotics to oral trimethoprim/sulfamethoxazole and amoxicillin/clavulanate to complete a total of 10-days of treatment. He improved clinically but was not willing to attempt a drug rehabilitation program. He was subsequently lost to follow-up.

Discussion

Clinicians presenting this cautioned that given cocaine's highly addictive nature, it is vital to elicit a complete history from IV drug users -- especially long-term users -- who might inject sites other than the arms when their usual site becomes unavailable, as in this patient's case.

Case authors described that increase this likelihood, which include: Beginning drug use at an older age (OR 1.039, 95% CI 1.009-1.069), longer time spent as an injection drug user (OR 1.071, 95% CI 1.041-1.102), and higher frequency of injection (OR 1.255, 95% CI 1.072-1.471).

Because cocaine blocks norepinephrine and dopamine presynaptic reuptake, it stimulates central and peripheral adrenergic mechanisms, thus increasing norepinephrine levels, which in turn causes vasoconstriction of the cardiac and peripheral vasculature, authors noted. In addition, the drug results in significant by directly stimulating alpha-adrenergic receptors.

Case authors noted that risks of injecting cocaine include vasculitis, which can result in gangrene. Effects specific to injection in the groin area include Fournier's gangrene, superficial penile necrosis, and scrotal gangrene. Genital skin may be affected by cocaine use, they noted, "regardless of the route of cocaine administration or what type of vascular complication occurs."

These risks may be increased with use of cocaine that has been adulterated with the antihelmintic levamisole, which increases cocaine's profitability and its psychotropic effects, and is found in about 80% of the cocaine seized in the United States, according to the U.S. Drug Enforcement Agency.

Due to its inhibiting effect on monoamine oxidase and catechol-O methyltransferase activity, levamisole increases the level of catecholamine neurotransmitter in nerve synapses, thus potentiating cocaine's effects, case authors stated. The drug has also been implicated in the development of necrotizing vasculitis. "Levamisole-induced vasculitis presents as retiform purpuric lesions that become necrotic, as compared with palpable purpura or Wegener's granulomatosis-like lesions in pure cocaine-induced vasculitis," authors explained.

Levamisole has an immune-stimulating effect that results in production of autoantibodies (antinuclear and antineutrophil antibodies), which are usually positive in patients with levamisole-induced vasculitis. The level of levamisole in blood or urine can be determined with tests administered within 48 hours of last use, authors explained, due to its short half-life of 5.6 hours.

Research has also linked levamisole use with anticardiolipin antibodies and decreased serum complement component 3 levels, case authors noted, adding that their patient tested negative for perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA), cytoplasmic antineutrophil cytoplasmic antibody (C-ANCA), and anticardiolipin antibodies. They explained that it was not possible to determine if this patient's vasculitis was due to levamisole exposure, since he presented more than 48 hours after his last cocaine use.

IV drug users should be counseled to seek help and should be advised to enroll in drug rehabilitation programs, they advised, as cocaine cessation is the only definitive treatment.

As the second most popular illegal drug used in the United States, cocaine use among adults age 25 and 64 has increased by nearly 30% per year since 2013, according to a . Cocaine resulted in 14,666 drug overdose deaths in 2018 alone, which accounts for roughly one in five drug overdose nationwide.

"Intravenous (i.v.) drug use leads to severe injury to the veins, including erythema, thrombophlebitis, vasoconstriction, necrosis, development of venous ulceration, and vein occlusion," case authors wrote.

The group cited a study of in more than 700 persons who injected illicit drugs that found that those who injected in the legs (with or without injection into the arms) were nine times more likely to develop venous ulcers than those who injected in the arms and upper body only, and 35 times more likely compared with those who never injected.

They concluded by urging physicians "to counsel active i.v. drug users regarding possible of injecting drugs in atypical and dangerous injection sites."

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