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Cutaneous adverse effects of anticonvulsants

Introduction

Many drugs can cause cutaneous (skin) side effects. The severity of symptoms can range from mild eruption to life-threatening conditions that cause skin failure and death. Certain groups of drugs are known to cause frequent, specific or severe skin reactions. Anticonvulsants or antiepileptics are one such group of drugs, some of which have notable side effects on the skin.

It is important to recognize side effects involving the skin, as prompt withdrawal of the medication may prevent worsening of symptoms caused by the medication. A decision may need to be made in a patient who has undergone a drug eruption whether to continue an important drug that might have caused the reaction or switch to an alternative drug.

When faced with a new skin rash in a patient, a full drug history is paramount and should include prescription, on the counterand alternative medications that the patient is taking so that the medication rashes can be considered or discarded.

anti-seizure drugs

Anti-seizure medications, also known as anti-epileptic or anti-seizure medications, are a diverse group of medications that are commonly used in the treatment of epilepsy and seizures, and less commonly for other conditions such as trigeminal neuralgia and bipolar disorder. They work by reducing the excessive firing of neurons that happens in a seizure.

Adverse skin reactions

Types of Skin Reactions to Anticonvulsants
Reaction Symptoms
Morbid (similar to measles) drug rash
  • Extended or generalized pink to red maculopapular eruption
  • Itch
  • May progress to exfoliative dermatitis/ /erythroderma
  • Usually resolves quickly on drug withdrawal

Drug induced urticaria (urticaria)
  • Transient cure with pale centers and red edges
  • Migratory pattern, changing shape and location over several hours.
  • Anaphylaxis maybe concurrent or may occur with subsequent administration of the drug
Erythema multiform
  • White lesions (iris)
  • Can imply mucous membranes
  • Self-limiting and usually resolves without complications
Stevens-Johnson syndrome / / toxic epidermal necrolysis (TEN)
  • It usually develops within the first week of taking the medication.
  • Severe and life-threatening skin reaction with sheet-like skin and mucous membrane lost
  • Rare mediated by immune complexes hypersensitivity
Anticonvulsant hypersensitivity syndrome
  • Symptoms usually develop 2 to 6 weeks after starting the medication, but can occur at any time
  • Symptoms include the triad of fever, generalized maculopapular rash, and lymphadenopathy
  • The rash spreads to varying degrees over the trunk and extremities.
  • It can affect internal organs such as the kidneys, liver, central nervous system, and bone marrow.
Cutaneous adverse reaction to anticonvulsants

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morbilliform rash

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Urticaria

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Erythema multiforme

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toxic epidermal necrolysis

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purpuric rash

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gingival hyperplasia

Specific reactions to anticonvulsant drugs.
Drug skin reaction Grades
Carbamazepine
  • Oral ulcers
  • Urticaria
  • Stevens-Johnson / TEN
  • Photosensitivity
  • Cutaneous side effects are the most common side effects causing discontinuation of carbamazepine.
  • There is cross reaction between carbamazepine and amitriptyline.
Phenytoin

  • Erythroderma (reddening of the entire skin).

  • Facial pustules (medicated acne)
  • Hyperpigmentation (darkening of the skin)
  • Hypertrichosis (excess hair growth)
  • Lupus-like symptoms
  • Anticonvulsant hypersensitivity syndrome
  • 5-10% of patients using phenytoin have a skin reaction
  • Hypertrichosis can be irreversible
  • The most common cause of anticonvulsant hypersensitivity syndrome
Fosphenytoin
  • Bullous rash (blisters)
  • Exfoliative dermatitis / erythroderma
  • Pruritus (Itch)
  • Gingival hyperplasia (excessive growth of the gums)
  • Lupus-like symptoms
  • Erythema multiforme

  • Pruritus is present in 49% patients and is dose related.

  • The groin is the most affected
Phenobarbital
  • morbilliform rash
  • Urticaria
  • Erythema multiforme
  • Photosensitivity
  • Skin rash (similar to acne)
  • Purple
Lamotrigine

  • Morbilliform rash (in 10%)

  • Angioedema
  • Pruritus (itching)
  • Stevens-Johnson / TEN
  • Anticonvulsant hypersensitivity syndrome
  • Life-threatening skin reactions occur in 1 in 100 children and 1 in 1,000 adults treated with lamotrigine.
  • Women are at higher risk than men.
Valproic acid
  • Diaphoresis (excessive sweating, hyperhidrosis)
  • Erythema multiforme
  • Transient alopecia (Hair loss)
  • Petechiae
  • Photosensitivity
  • Pruritus
  • It interacts with other anticonvulsants such as lamotrigine, increasing the chance of side effects.

Genetic predisposition to Adverse reactions to anticonvulsants

Some racial groups are especially prone to cutaneous adverse reactions with anticonvulsants. test for an individual allele before starting an anticonvulsant may be helpful in identifying patients at risk.

  • Han Chinese and other Southeast Asian groups who have a particular HLA-B allele, HLA-B*1502 they are significantly more likely to develop serious reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) with anticonvulsants.
  • Japanese, Korean, and white populations in the United States and Europe who carry HLA-A*31:01 They are also prone to developing cutaneous Adverse drug reactions with anticonvulsants