What is purple glove syndrome?

From the Guidelines

Purple glove syndrome is a rare but serious complication associated with intravenous phenytoin administration, characterized by purple discoloration of the skin, edema, pain, and potential skin necrosis, as noted in the context of its adverse effects 1. The condition typically presents within 24-48 hours after phenytoin infusion and can progress to compartment syndrome in severe cases, potentially requiring surgical intervention. Key aspects of purple glove syndrome include:

• Its association with the high alkalinity and poor solubility of phenytoin, leading to extravasation, vascular irritation, and local tissue damage.
• Risk factors such as peripheral IV administration, especially in small veins, rapid infusion rates exceeding the recommended 50 mg/minute, and high drug concentrations.
• Management strategies that include immediate discontinuation of phenytoin, elevation of the affected limb, monitoring for vascular compromise, and supportive care.
• Prevention strategies involving the use of fosphenytoin, which has better solubility, administering phenytoin through central lines when possible, ensuring proper dilution, maintaining slow infusion rates, and promptly flushing the IV line after administration, as these methods can mitigate the risk of purple glove syndrome, as implied by the comparison of phenytoin's adverse effects with those of other drugs like fosphenytoin 1.

From the FDA Drug Label

Edema, discoloration and pain distal to the site of injection (described as “purple glove syndrome”) have also been reported following peripheral intravenous phenytoin injection Local toxicity (Including Purple Glove Syndrome) [see Warnings and Precautions- 5 (5. 8)] 5. 8 Local Toxicity (Including Purple Glove Syndrome) Soft tissue irritation and inflammation has occurred at the site of injection with and without extravasation of intravenous phenytoin.

Purple Glove Syndrome is a condition characterized by edema, discoloration, and pain distal to the site of injection, often occurring after peripheral intravenous phenytoin injection. It is a form of local toxicity that can range from slight tenderness to extensive necrosis and sloughing. The syndrome may not develop for several days after injection, and resolution of symptoms may be spontaneous, but skin necrosis and limb ischemia have occurred, requiring interventions such as fasciotomies, skin grafting, and, in rare cases, amputation 2.

From the Research

Definition and Characteristics of Purple Glove Syndrome

• Purple glove syndrome (PGS) is a devastating complication of intravenous (IV) phenytoin administration, characterized by pain, edema, and purple-blue discoloration of the limb distal to the site of injection 3, 4.
• It is an uncommon but serious adverse drug reaction that can progress to necrosis if not promptly addressed 5.
• The pathophysiology of PGS remains uncertain, but multiple mechanisms have been reported, including extravasation and microvascular thrombosis 6, 7.

Clinical Presentation and Diagnosis

• Initial presentation of PGS is characterized by pain, skin discoloration, and edema, which can progress to gangrene if left untreated 3, 4.
• The condition can be diagnosed based on clinical presentation, and imaging studies such as Doppler ultrasound and conventional angiography may be used to identify arterial or venous thrombosis 7.
• PGS can be associated with significant vascular thrombosis and potentially limb-threatening ischemia, and prompt recognition and management are crucial to prevent long-term sequelae 7.

Treatment and Prevention

• Treatment of PGS includes supportive care such as limb elevation and heat or cold application, utilization of systemic antibiotics, anticoagulants, or vasodilators, and local infiltration of hyaluronidase, heparin, or other compounds 7.
• Invasive interventions such as regional anesthesia, thrombectomy, fasciotomy, and debridement may be necessary in severe cases 7.
• To decrease the morbidity of IV phenytoin or fosphenytoin use, avoidance of small hand veins, adherence to recommended IV administration guidelines, and monitoring of the infusion site for reactions are recommended 7.
• Alternative anticonvulsant drugs should be considered in patients at risk for PGS when possible 7.