Review Question - QID 219834

The presentation of this patient’s erythematous and edematous hand in the setting of recent IV phenytoin therapy, along with a positive response to conservative management, suggests he sustained a phenytoin extravasation injury and has developed Purple Glove Syndrome, a rare but serious adverse effect of phenytoin administration. Chemical extravasation injuries occur when therapeutic agents escape the vasculature and cause various soft tissue injuries, depending on the offending agent.

Chemical extravasation injuries represent an uncommon but potentially severe complication that may occur after the administration of a variety of therapeutic agents. Agents responsible for these injuries may be generally classified into one of two subgroups: (1) irritants, which may cause local inflammatory reactions but are not considered to be directly toxic to tissue, and (2) vesicants, which possess a capacity for direct tissue toxicity, and therefore may lead to more severe cutaneous reactions consisting of sloughing, deep tissue damage, and blistering. Neonatal, elderly, and obtunded patients are of particular risk, secondary to factors such as smaller caliber or structurally weaker vessels, and a relative inability to verbalize their pain. The clinical presentation of these injuries is dependent on the offending agent, and prompt diagnosis and institution of early treatment measures are paramount to preventing severe sequelae, such as full-thickness skin ulceration, compartment syndrome, or necrosis, which may necessitate surgical reconstruction or, in rare cases, amputation. Management of extravasation injury includes first stopping the intravenous infusion and marking the border of the involved region if possible, followed by elevation, immobilization, and application of heat or ice, depending on the agent. Further management comprises local or injectable antidotes, subcutaneous irrigation techniques, surgical debridement, and possibly fasciotomies.

Hannon and Lee provided a broad overview of the diagnosis and management of chemical extravasation injuries, highlighting multiple commonly implicated agents such as phenytoin, total parenteral nutrition (TPN), vasopressors, arginine, chemotherapeutic agents, and radiographic contrast medium. They note that injury secondary to these agents is a function of four factors: the infusion pressure, the osmolarity of the extravasate, its inherent cytotoxicity, and its possible vasoconstrictive properties. They concluded that the exact pathophysiology of the phenytoin extravasation reaction has not yet been determined but is likely related to the precipitation of the drug out of solution. Proposed mechanisms include blocking intravenous flow, disrupting venous integrity secondary to high solution alkalinity (pH ≈ 12), and phenytoin binding to local proteins in the subcutaneous tissue, leading to elevations of oncotic pressure and edema. Ultimately, this may manifest as “Purple Glove Syndrome,” characterized by edema, dark red or violet skin discoloration, and extreme pain.

Hahn and Shafritz reviewed extravasation injuries with a focus on chemotherapeutic agents. They note that extravasation injury is considerably more common in the chemotherapy patient and pediatric population, which calls for particular attention to this topic as these patients are particularly vulnerable to both the local and possible systemic consequences of cutaneous injuries. They highlight a variety of reported cutaneous reactions secondary to the extravasation of various chemotherapeutic agents, concluding that treatment should be tailored to the specific offending agent identified with a variety of antidote agents available for use.

Figure 1 is a clinical photograph of a patient with “Purple Glove Syndrome” 72 hours following phenytoin administration. Note the generalized hand edema and the characteristic dark red or violet skin discoloration.

Incorrect Answers:
Answer 1: Acute thrombus formation within the axillary vein describes an upper extremity deep venous thrombosis (DVT). This typically presents as diffuse extremity swelling distal to the thrombosis site and would be less likely to resolve without the use of anticoagulation, thrombolysis, or thrombectomy.

Answer 3: Polymicrobial bacterial infection extending to local myofascial tissue describes necrotizing fasciitis (Type 1). Although the patient in this question does have an elevation of their CRP, this is not uncommon following traumatic brain injury and is typically more significantly elevated in the setting of necrotizing fasciitis. Additionally, although skin changes may be similar to those pictured, surgical debridement is ultimately required to resolve the infection.

Answer 4: Immune-mediated inflammatory myopathies are a family of autoimmune disorders, including dermatomyositis. Skin lesions consist of the characteristic heliotrope rash on the face and more diffuse cutaneous lesions affecting the elbows, knees, and knuckles (Gottron Papules). Given the proximity of recent phenytoin infusion and isolated single extremity involvement, this clinical presentation is more consistent with extravasation injury.

Answer 5: Staphylococcus aureus infection involving the digital flexor tendon sheaths describes pyogenic flexor tenosynovitis, of which S. aureus is the most common cause. Although this disease process may spread throughout the deep spaces of the hand and cause diffuse skin changes such as those pictured, extensive multi-digit involvement would not be expected to improve without administering antibiotics——ultimately, irrigation and debridement are often required.