By: Sharon Janak, PharmD Candidate c/o 2013

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How can we distinguish between vascular injury and Purple Glove Syndrome (an adverse effect of phenytoin)?  What are the warning signs and symptoms?

Phenytoin is an anticonvulsant used to treat generalized tonic-clonic and partial seizures. It stabilizes neuronal cell membranes of the motor cortex by facilitating the efflux or inhibiting the influx of sodium ions when an electrical impulse is initiated. When phenytoin is injected into smaller veins in the hands, it can lead to Purple Glove Syndrome (PGS), a delayed soft tissue injury.^2,3,4 Although PGS is often overlooked, the true prevalence of PGS may be as high as 5.9%.⁴

It is important to distinguish between PGS and other possible complications, such as extravasation and cellulitis. Several signs and symptoms can be used to differentiate between PGS and extravasation. If the patient is experiencing PGS, the symptoms such as skin discoloration, pain, and edema will continue to worsen despite discontinuing the phenytoin infusion and removing the catheter. The pattern and change of color are also distinct—the skin will turn from red to purple. During the progression stageof PGS, the discoloration spreads around the sides of the fingers, the hand, and the forearm.  Petechiae, i.e. pinpoint, round, red spots, also occur due to intradermal hemorrhage. It is distinguished from cellulitis by its quicker onset, distinct discoloration, and lack of infectious discharge and fever.³

Patients experience edema, purple-blue discoloration, and pain in the hand and surrounding areas adjacent to the site of phenytoin administration. PGS progression has three stages: appearance, progression, and resolution. In the appearance stage, there is a bluish purple discoloration around the intravenous insertion site.  However, it is important to note that the discoloration can start out as mild redness. This usually occurs 2 to 12 hours after phenytoin is administered. In the progression stage, edema, discoloration, and pain worsen as more tissue is damaged. The effects depend upon the dose and the frequency of phenytoin administration. Patients may also experience fluid-filled blisters and sloughing of the skin.^2,3,4  Upon closer inspection, petechiae on the finger pads and palms can be observed.³ During the resolution stage, the lesions, edema, and discoloration attenuate.^2,3,4  Healing begins from the outer edges of the discolored area and gradually moves inward toward the site of venipuncture.^2,3 The resolution stage generally takes about 2 to 4 weeks, but the pain may continue for weeks to months.³ 

There are several suggested mechanisms for the pathophysiology of PGS. One such mechanism is that the basicity of the intravenous phenytoin solution injures blood vessels. The high pH may lead to vasoconstriction, decrease blood flow, disrupt the endothelium, and leak phenytoin into the surrounding tissues. Since phenytoin is highly protein bound, oncotic pressure is increased outside the blood vessels, causing edema. Another possible mechanism is that the blood vessels are damaged by the insertion of an intravenous catheter. The small tears that occur help phenytoin leak into tissues. Other investigators have suggested that phenytoin solution mixes with precipitates from blood in the intravenous cannula, causing backflow and entry into the tissue. The final proposed mechanism is vasculitis, or inflammation of the blood vessels, which facilitates the formation of thrombi (blood clots impeding blood flow).^2,4

PGS can be prevented or recognized earlier in the course of progression. Risk factors for PGS include pre-existing vascular disease, unconsciousness (rendering the patient unable to report pain), female gender, age over 60 years, and age below 7 years.^2,3,4  These populations should be assessed more frequently to prevent any complications. To prevent vessel injury, Snelson and Dieckman recommend a maximum infusion rate of 40 mg/min for most patients. Cardiac patients should receive phenytoin at a rate no greater than 25 mg/min, preferably between 5 and 10 mg/min. A large vein in the forearm should be used, as opposed to a smaller one on the dorsal side of the hand.³ A catheter larger than 20 gauge⁷ and a 0.22-micron filter should also be used.³  The area around the site of infusion should be carefully and regularly examined. If any abnormalities develop, the intravenous catheter should be removed.³

To treat PGS, the phenytoin infusion should be discontinued, and the patient should be given supportive care. Examples of such care include frequently assessing the affected area, applying dry heat and a compression glove or splint, and elevating the limb. This will help mitigate symptoms and aid in healing.^2,3,4 Many cases have been managed successfully with complete resolution of symptoms after one month.^5,6,7 In rare cases, PGS can be severe enough to warrant surgery or amputation.⁵

Purple Glove Syndrome is a relatively rare and often overlooked adverse effect of phenytoin administration. The serious risks associated with the syndrome warrant more proactive care such as monitoring higher-risk patients. By successfully identifying PGS early, and not confusing it with other problems such as extravasation and cellulitis, patients can be treated sooner and faster, saving them from months of painful reactions.

SOURCES:

1. Phenytoin.  Lexi-Comp Online.  Hudson, OH.  Available at: http://online.lexi.com/crlonline
2. Bhattacharjee P, Glusac E.  Early histopathologic changes in purple glove syndrome.  Journal of Cutaneous Pathology.  2004: 31: 513–515.
3. Snelson C, Dieckman B.  Recognizing and Managing Purple Glove Syndrome.  Critical Care Nurse.  2000: 20:3; 54 – 61.
4. Chokshi R, Openshaw J, Mehta NN, Mohler E.  Purple glove syndrome following intravenous phenytoin administration.  Vascular Medicine.  2007; 12: 29–31.
5. O’Brien TJ, Cascino GD, So E, Hanna DR.  Incidence and clinical consequences of the purple glove syndrome in patients receiving intravenous phenytoin.  Neurology. 1998; 51:1034-1039.
6. Sonohata M, Asami A, Tsunodal K, Hotokebuchi T.  Purple glove syndrome associated with intravenous phenytoin administration in a patient with severe mental and motor retardation.  Journal of Orthopaedic Science.  2006. 11:409–411.
7. Santoshi JA, Justin AS, Jacob JI, Pallapati SC, Thomas BP.  Purple glove syndrome: a case report: Hand surgeons and physicians be aware.  Journal of Plastic, Reconstructive & Aesthetic Surgery. 2010. 63: e340-2.

Published by Rho Chi Post