Purple glove syndrome

Overview

Purple glove syndrome (PGS) is a rare but serious complication associated with the intravenous (IV) administration of the anticonvulsant drug phenytoin. It is characterized by the development of painful, purple or dark discoloration of the skin around the IV site, often accompanied by swelling, soft tissue damage, and in severe cases, tissue necrosis. The name "purple glove" refers to the striking appearance of the affected limb, which may resemble a glove due to the uniform discoloration extending over the hand and forearm.

PGS can occur within hours to days after IV phenytoin administration, even when given correctly. It can lead to significant morbidity, including compartment syndrome or the need for surgical intervention. Early recognition and management are crucial to minimize tissue damage and preserve limb function.

Causes

The exact mechanism of purple glove syndrome is not fully understood, but several contributing factors have been identified:

• Extravasation of phenytoin: Leakage of the drug from the vein into surrounding tissues is the primary suspected cause, leading to local irritation and vasospasm

• Alkaline pH of phenytoin solution: Phenytoin’s high pH and propylene glycol content may cause direct endothelial and tissue damage

• Precipitation of the drug: Crystallization in small blood vessels can block circulation, resulting in ischemia and discoloration

• Rapid or high-concentration infusions: Increase the risk of tissue injury and extravasation

• Fragile or small veins: Older adults and pediatric patients are at greater risk due to vein fragility

Symptoms

Symptoms of purple glove syndrome generally develop in the limb where IV phenytoin was administered. They may appear immediately or up to several days later. Clinical features include:

Local Symptoms

• Purplish, blue, or black discoloration of the skin around the IV site

• Swelling and edema of the affected limb

• Coolness to the touch due to impaired circulation

• Pain or tenderness, sometimes severe

• Blistering or skin breakdown in severe cases

Severe Complications

• Compartment syndrome: A surgical emergency due to increased pressure in a muscle compartment, leading to loss of function and tissue death if untreated

• Tissue necrosis: Death of skin and soft tissue requiring debridement or, rarely, amputation

PGS typically involves the hand and forearm but can affect any site where phenytoin was infused.

Diagnosis

Diagnosis of purple glove syndrome is primarily clinical, based on the history of recent IV phenytoin administration and characteristic skin findings. Diagnostic steps may include:

Clinical Evaluation

• Visual inspection of the affected limb

• Assessment of pain, skin color, temperature, and swelling

• Palpation to assess pulses and capillary refill in the extremity

Imaging and Tests

• Doppler ultrasound: May be used to assess blood flow and rule out vascular occlusion

• Compartment pressure measurement: If compartment syndrome is suspected

Differential Diagnosis

• Phlebitis (vein inflammation)

• Cellulitis or localized infection

• Venous thrombosis

• Acrocyanosis or vasospastic disorders

A detailed medication history is essential for diagnosis, especially the route and dosage of phenytoin administration.

Treatment

The primary goal in treating purple glove syndrome is to stop further tissue injury and manage symptoms. Treatment varies depending on severity.

Initial Management

• Immediate discontinuation of phenytoin: Stop the infusion as soon as symptoms are observed

• Elevate the affected limb: Helps reduce swelling and improve circulation

• Apply warm compresses: May promote vasodilation and improve blood flow

• Pain management: NSAIDs or opioids for severe pain

Advanced Interventions

• Surgical consultation: For suspected compartment syndrome or severe tissue damage

• Fasciotomy: May be necessary if compartment syndrome develops

• Wound care: For ulcerated or necrotic skin, including debridement

Alternative Medications

• Consider switching to fosphenytoin, a prodrug of phenytoin with a lower risk of PGS and better infusion tolerance

• Use oral phenytoin when feasible to avoid IV-related complications

Prognosis

The prognosis of purple glove syndrome varies based on the severity of the reaction and the timeliness of intervention. In most mild to moderate cases, symptoms resolve within several days to weeks with conservative management. Skin discoloration and swelling typically subside without long-term consequences.

However, in severe cases, especially those complicated by compartment syndrome or tissue necrosis, patients may experience long-term functional impairment, require surgical intervention, or, in rare instances, face limb loss. Prompt recognition and discontinuation of IV phenytoin are crucial to prevent irreversible damage.

To reduce risk, clinicians should follow best practices for IV phenytoin administration, including using large veins, slow infusion rates, and diluted solutions—or opt for fosphenytoin when available.