Early histopathologic changes in purple glove syndrome

Abstract

An 86-year-old African-American man presented with tonic-clonic seizures. Intravenous phenytoin was urgently administered into the dorsum of the right hand. The patient developed a raised purple area of discoloration around the intravenous insertion site within 2 h and edema and vesiculobullous lesions of the distal forearm, hands, and fingers within 8 h. Microscopic sections from a biopsy at 12 h revealed epidermal necrosis, superficial ulceration, and a mild superficial and deep perivascular lymphoid infiltrate, associated with numerous thrombi of small vessels throughout the dermis. The findings were judged to be consistent with soft-tissue injury associated with intravenous administration of phenytoin, also termed purple glove syndrome. Purple glove syndrome, named for its distinctive purple discoloration and swelling of the hands in the distribution of a glove, is an uncommon complication of intravenous phenytoin administration through small dorsal veins of the hands. It is comprised by pain, discoloration, and edema in the vicinity of intravenous infusion of phenytoin through dorsal veins of the hand. The histopathologic features of fully developed lesions have been reported; however, early-stage findings have not been previously described, and the histogenesis of this lesion is controversial. The presence of thrombi in this early-stage lesion suggests that thrombosis plays a role in the initial pathogenesis of this condition.

Purple Glove Syndrome after Phenytoin or Fosphenytoin Administration: Review of Reported Cases and Recommendations for Prevention

“…In terms of site, PGS is most commonly associated with upper extremities; however, it has been also reported in lower extremities and referred to as purple sock syndrome [13][14][15][16]. Bhattacharjee et al summarized the disease course into three temporal stages of injury: initial painful blue-purple discoloration and edema around the IV catheter site, subsequent worsening of pain, edema, and discoloration with development of epidermal sloughing, ulceration, or bullae formation, and neuromuscular symptoms such as paresthesias or weakness, and eventually resolution of edema and discoloration starting from the periphery of the injury and moving toward the site of catheter insertion [17]. Timing of these stages appears quite variable, with initial discoloration occurring from minutes to days after phenytoin administration and tissue recovery spanning days to months [18,19].…”

“…There are also a subset of more severe cases in which the second stage of expanding edema and superficial tissue damage is followed by dermal and subcutaneous tissue necrosis and ischemia leading to permanent injury, surgical debridement, or amputation. Tissue samples obtained both early and late in the course of symptoms have shown the common presence of epidermal necrosis, subcutaneous edema, perivascular lymphoid infiltration, and local vascular thrombosis [17,20,21].…”

“…The observation that multiple cases of PGS have been reported without IV catheter extravasation suggests the presence of an additional underlying pathophysiology [4, 5, 13, 15-17, 19, 21, 23, 27-42]. The repeated finding of microvascular thrombosis on histopathology and the association between documented large vessel thromboses in the most severe cases of PGS suggests that an unidentified procoagulant mechanism may be responsible for the extent of tissue destruction [17,20].…”

“…On follow-up evaluation documented in 79 of 82 cases, fiftyfour (68.4 %) subjects demonstrated full recovery of function and appearance of the affected extremity. Of those reports that specified duration, resolution of symptoms occurred after a median of 14 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) days. Sixteen (20.3 %) cases noted permanent skin changes without functional motor or sensory deficits.…”

“…Pain is also likely to be present, but its presence may often be obscured by pathologic or iatrogenic-induced alteration in consciousness after a seizure. Alterations in appearance including blistering, erythema, or necrosis are more common than deficits in function, such as paralysis or sensory changes, potentially allowing for a more rapid diagnosis [1,6,12,17]. Time to onset of symptoms was generally rapid, consistent with a potentially ischemic pathology, though cases were reported up to 5 days after the last dose of phenytoin [52].…”