Allopurinol hypersensitivity syndrome

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Allopurinol Hypersensitivity Syndrome

Structure of Allopurinol

Allopurinol hypersensitivity syndrome (AHS) is a rare but serious adverse reaction to the medication allopurinol, which is commonly used to treat gout and hyperuricemia. This syndrome is characterized by a combination of severe skin reactions, systemic symptoms, and internal organ involvement.

Clinical Features

AHS typically presents with a constellation of symptoms that may include:

  • Severe skin reactions: These can range from maculopapular rash to more severe forms such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
  • Fever: Patients often experience high fevers as part of the systemic response.
  • Hepatitis: Liver involvement is common, with elevated liver enzymes indicating hepatic inflammation.
  • Renal failure: Acute kidney injury can occur, often necessitating careful monitoring and management.
  • Eosinophilia: An elevated eosinophil count is frequently observed in blood tests.

Pathophysiology

The exact mechanism of AHS is not fully understood, but it is believed to be an immune-mediated hypersensitivity reaction. Genetic factors, such as the presence of the HLA-B*5801 allele, have been associated with an increased risk of developing AHS, particularly in certain ethnic groups.

Diagnosis

Diagnosis of AHS is primarily clinical, based on the presentation of symptoms and a history of recent allopurinol use. Laboratory tests may show elevated liver enzymes, renal impairment, and eosinophilia. Skin biopsy can be performed to confirm severe cutaneous adverse reactions like SJS/TEN.

Management

The cornerstone of management is the immediate discontinuation of allopurinol. Supportive care is critical and may include:

  • Hospitalization: Patients with severe reactions often require intensive care.
  • Corticosteroids: These may be used to reduce inflammation and immune response.
  • Hydration and renal support: Ensuring adequate hydration and monitoring renal function is essential.
  • Treatment of skin lesions: In cases of SJS/TEN, specialized wound care is necessary.

Prevention

Screening for the HLA-B*5801 allele in high-risk populations before starting allopurinol can help prevent AHS. Alternative medications for managing hyperuricemia should be considered in patients with a positive genetic test.

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