Anticonvulsant Hypersensitivity Syndrome - Symptoms, Diagnosis, and Treatment

Introduction

Anticonvulsants are primarily used in the treatment of mood disorders and chronic pain. The people taking anticonvulsant medications will experience anticonvulsant hypersensitivity syndrome, AHS. Anticonvulsant hypersensitivity syndrome is a drug-induced skin reaction characterized by fever, skin rash, multiorgan abnormalities, and other types of hepatitis. The exact etiology of anticonvulsant hypersensitivity syndrome, AHS, is unknown. Anticonvulsant hypersensitivity syndrome, AHS is a multiorgan syndrome that sometimes leads to fatal results. AHS is a rare condition, and the diagnosis is made with patch testing and clinical examination. The symptomatic treatment is given for anticonvulsant hypersensitivity syndrome, and avoiding the anticonvulsant medication will improve the symptoms.

What Is Anticonvulsant Hypersensitivity Syndrome?

Anticonvulsant hypersensitivity syndrome, AHS is a drug-induced skin reaction characterized by fever, rash, and swelling of lymph nodes leading to multiorgan failure. The anticonvulsant hypersensitivity syndrome causing anticonvulsants are Carbamazepine, Phenytoin, Lamotrigine, and Phenobarbitone. The symptoms are common in people receiving anticonvulsants for three months and last for two to three weeks. The characteristic feature of anticonvulsant hypersensitivity syndrome is the spiking and high fever. Therefore, early diagnosis and appropriate treatment are necessary to avoid the subsequent recurrence of this syndrome. Sometimes, it causes liver failure and needs hospitalization.

What Are the Symptoms of Anticonvulsant Hypersensitivity Syndrome?

AHS is a rare syndrome causing potentially fatal complications, including liver failure. The symptoms include skin rash, fever, and lymphadenopathy, called the swelling of lymph nodes. The syndrome shows various skin and systemic symptoms. Some of the symptoms of AHS are mentioned below:

• Skin rash.

• High fever and intermittent temperature elevation is the hallmark feature of anticonvulsant hypersensitivity syndrome.

• Lymphadenopathy is the swelling of lymph nodes.

• Erythematous macule.

• Generalized redness or erythema.

• Desquamation.

• Periorbital and facial edema.

• Blisters are present in the edematous site.

• Other skin features include urticaria, purpura, erythema multiforme, and exfoliative dermatitis.

• Toxic epidermal necrolysis, TENS.

• Hepatitis.

• Localized or generalized lymphadenopathy.

• Splenomegaly, enlargement of the spleen.

• Depression.

• Malaise.

• Pharyngitis.

• Hypothyroidism.

• Mood elevations and mood disorders.

• Acute illness.

• Leukocytosis (a disorder characterized by elevated leukocyte counts in the blood).

• Eosinophilia (a greater than normal level of eosinophils).

• Coagulopathy.

What Are the Causes of Anticonvulsant Hypersensitivity Syndrome?

The exact mechanism for anticonvulsant hypersensitivity syndrome is not known. However, it is suggested that AHS is a drug-induced allergic hypersensitivity reaction. Anticonvulsant hypersensitivity syndrome is also a familial case with a similar allergic response due to the inability to detoxify. Detoxification inabilities of arene oxides in anticonvulsants cause AHS. Some of the suggested causes are mentioned below:

• Drug-induced allergic hypersensitivity reaction, the standard drugs causing anticonvulsant hypersensitivity syndrome are Phenytoin, Carbamazepine, Phenobarbitone, and Lamotrigine.

• Inability in arene oxides detoxifications.

• Genetic factor includes human leukocyte antigen allele B*1502.

• Complex immunological changes.

• Chemotoxicity.

• T-cell mediated inflammatory injuries.

• Virus infections.

What Is the Diagnosis of Anticonvulsant Hypersensitivity Syndrome?

The diagnosis of anticonvulsant hypersensitivity syndrome includes drug history and clinical examination. The triad symptoms include fever, rash, and multiorgan involvement. The skin patch test can occasionally be used to identify the medicine that is producing anticonvulsant hypersensitivity syndrome. In addition, blood investigations are done, which show an increase in eosinophil count. The other diagnostic tool for diagnosing anticonvulsant hypersensitivity syndrome is given below:

• History of drug intake.

• Clinical examination of the symptoms, which include fever and skin rash.

• Liver function tests.

• Serum creatine is evaluated.

• Urine analysis is done.

• Liver enzymes such as liver transaminase are evaluated.

• In blood investigations, atypical lymphocytes are present.

• Genetic susceptibility testing.

• Viral serology like hepatitis B, hepatitis C, Ebstein Barr virus, and cytomegalovirus are evaluated.

• Invitro lymphocyte transformation tests.

• In severe cases, electrocardiography, echocardiogram, and chest X-ray are performed.

What Is the Differential Diagnosis of Anticonvulsant Hypersensitivity Syndrome?

The symptoms of anticonvulsant hypersensitivity syndrome are similar to other conditions causing differential diagnoses. Comparing diagnostic features will help in early and correct diagnosis and avoid misdiagnosis. Some of the differential diagnosis of anticonvulsant hypersensitivity syndrome is given below:

• DRESS syndrome (drug-related rash with eosinophilia and systemic symptoms).

• Drug-induced hypersensitivity syndrome.

• Steven Johnson syndrome.

• Toxic epidermal necrolysis.

• Erythema exsudativum multiforme.

• Viral hepatitis.

• Allergic contact dermatitis.

• Erythema multiforme.

• Irritant contact dermatitis.

• Pseudoallergy.

• Urticaria.

• Angioedema.

• Anaphylaxis.

• Serum sickness-like reactions.

What Are the Complications of Anticonvulsant Hypersensitivity Syndrome?

The mild form is not fatal, whereas the moderate to severe form of anticonvulsant hypersensitivity syndrome leads to many complications. Some of the intricacies are given below:

• Acute liver failure.

• Jaundice.

• Multiorgan failure.

• Fulminant myocarditis.

• Hemophagocytosis.

What Is the Treatment for Anticonvulsant Hypersensitivity Syndrome?

The symptomatic treatment is given for anticonvulsant hypersensitivity syndrome. The discontinuation of the implicated drug will improve the symptoms. The safest anticonvulsant drugs, such as Valproate and benzodiazepines, are suggested to avoid the complications of anticonvulsant hypersensitivity syndrome. The general supportive measures are mentioned below:

• Immediate discontinuation of the drugs.

• Topical steroids.

• Cyclosporine administration is effective in drug-induced hypersensitivity reactions.

• Administration of antihistamines.

• Systemic corticosteroids like Prednisone are advised, by which the skin symptoms of the condition are improved.

• Supportive care is given.

• Close monitoring of blood levels is also essential.

• Biochemical levels are also examined.

• Always avoid aromatic anticonvulsant drugs like Phenytoin, Phenobarbitone, Carbamazepine, and Lamotrigine.

• In anticonvulsant hypersensitivity syndrome with familial causes, the family members are informed of the risk of the syndrome.

• Other treatments for skin rash include dressings, emollients, topical steroids, and oral antihistamines.

• Expert nursing care and a warm environment are provided to avoid secondary bacterial infections.

Conclusion

Anticonvulsant hypersensitivity syndrome is a drug-induced hypersensitivity reaction causing cutaneous and systemic symptoms. The hallmark triad symptoms include fever, rash, and multiorgan failure. Generalized redness and edema are also observed in people with anticonvulsant hypersensitivity syndrome. The clinical diagnosis involves the history of drug intake and physical and blood examinations. The exact mechanism is unknown, but in some cases, it is a familial type. Systemic management is given and in case of a severe form of anticonvulsant hypersensitivity syndrome, liver failure results. Therefore, early diagnosis and proper treatment are made, and avoiding the drug-causing hypersensitivity reactions will prevent the subsequent recurrence and complications of the syndrome. In addition, lifestyle modifications, good nursing, and trigger avoidance will improve the condition.