Phenytoin Toxicity Clinical Presentation

Establish whether the toxicity is acute or chronic. Important historical elements in acute toxicity are as follows:

• Time of ingestion
• Co-ingestants
• Motivation for ingestion (intentional versus accidental)
• Medications available in the household

Paramedics or family members may be able to provide additional information (eg, medications, past medical history)

In chronic toxicity, important historical elements are as follows:

• Duration of phenytoin use
• Dosing
• Frequency
• Compliance (last dose and missed dose)
• Recent changes in pharmacotherapy

Important elements for patient query are as follows:

• When symptoms began
• Severity of symptoms
• Exacerbating factors
• Associated problems
• Relieving factors

Gingival hyperplasia is the most common adverse effect (20%) seen with chronically elevated serum phenytoin concentrations but is not associated with acute toxicity.

Neurologic findings in phenytoin toxicity may include the following:

• Hyperreflexia or hyporeflexia
• Abnormal gait (bradykinesia, truncal ataxia - Ataxia is very typical with elevated phenytoin levels, and may lead to falls and consequent trauma
• Encephalopathy
• Meningeal irritation with pleocytosis
• Tremor (intention)
• Irritability or agitation
• Confusion
• Hallucinations
• Mental status varies from completely normal to the extremes of stupor and coma, particularly if co-ingestants are present
• Peripheral neuropathy (long-term use)
• Priapism
• Urinary incontinence
• Choreoathetoid movements
• Dysarthria
• Dysphagia
• Seizures (rare)
• Death (rare)

Eye examination may reveal the following:

• Nystagmus (horizontal, vertical)
• Ophthalmoplegia
• Diplopia
• Miosis or mydriasis

Phentyoin has been reported to cause DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), a potentially fatal hypersensitivity reaction. Hypersensitivity reactions, including DRESS syndrome, typically manifest after a delay of 2 - 6 wk after exposure and may include the following:

• Fever, rash, and lymphadenopathy, commonly observed together
• Hepatitis
• Myocarditis
• Systemic lupus erythematosus (SLE)
• Polyarteritis
• Polymyositis
• Eosinophilia
• Megaloblastic anemia
• Pseudolymphoma
• Lymphadenopathy

Cardiovascular findings may include the following:

• Hypotension, bradycardia ^[7] , myocardial depression,  ventricular fibrillation,  asystole, and tissue necrosis ^[8]  all have been associated with the IV formulation.
• Phlebitis, necrosis, even gangrene
• "Purple glove syndrome," comprising distal limb edema, discoloration, and pain after IV administration, usually occurs in elderly patients and after massive/multiple doses

Skin findings may include the following:

• Hirsutism
• Acne
• Rashes, can be mild, morbilliform, scarlatinoid or as severe as Stevens-Johnson syndrome
• Jaundice
• Facial or periorbital edema
• Erythema multiforme (EM)
• Toxic epidermal necrolysis (TEN)

Gastrointestinal/abdomen findings may include the following:

• Right upper quadrant tenderness
• Hepatomegaly
• Splenomegaly
• Nausea
• Vomiting
• Hepatitis

Metabolic findings in patients with chronic phenytoin toxicity include osteomalacia and hypothyroidism.

Fetal hydantoin syndrome

Intrauterine exposure to phenytoin may result in the following physical features:

• Broad nasal bridge
• Wide fontanelle
• Low hairline
• Cleft lip/palate
• Epicanthal folds
• Short neck
• Microcephaly
• Low-set ears
• Small or absent nails
• Hip dislocation
• Hypoplasia of distal phalanges
• Impaired growth
• Congenital heart defects