Hypersensitivity syndrome is an idiosyncratic adverse drug reaction that begins acutely in the first 2 months after initiation of drug and is characterized by fever, severe disease with characteristic infiltrated papules and facial edema or an exfoliative dermatitis, lymphadenopathy, hematologic abnormalities (eosinophilia, atypical lymphocytes), and organ involvement (hepatitis, carditis, interstitial nephritis, or interstitial pneumonitis). The mortality rate is 10% if unrecognized and untreated. Lesional biopsy specimens show a lymphocytic infiltrate, at times mimicking a cutaneous lymphoma.
Causes of Drug Hypersensitivity Syndrome
Some patients have a genetically determined inability to detoxify the toxic arene oxide metabolic products of anticonvulsant agents. Slow N-acetylation of sulfonamide and increased susceptibility of leukocytes to toxic hydroxylamine metabolites are associated with higher risk of hypersensitivity syndrome.
Symptoms of Drug Hypersensitivity Syndrome
A high fever is usual noticed first. This is quickly followed by a widespread skin rash made up of redness, little bumps (papules) and pustules. The rash can last many weeks and may progresses to erythroderma or exfoliative dermatitis, where all the skin peels off. The severity of the rash does not necessarily correlate with the extent of internal organ involvement. Later symptoms depend on the internal organs affected.
Diagnosis
Proposed Diagnostic Criteria
- Cutaneous drug eruption.
- Hematologic abnormalities (eosinophilia ≥ 1500/ µL or presence of atypical lymphocytes).
- Systemic involvement (adenopathies ≥2 cm in diameter or hepatitis (SGOT ≥2N) or interstitial nephritis or interstitial pneumonitis or carditis). Diagnosis is confirmed if three criteria are present.
Treatment
Identify and discontinue the offending drug.
Symptomatic Treatment Oral antihistamine to alleviate pruritus.
Glucocorticoids Topical High-potency topical glucocorticoids applied bid are usually helpful in relieving cutaneous symptoms of pruritus but do not alter systemic hypersensitivity.
Systemic Prednisone (.5 mg/kg per day) usually results in rapid improvement of symptoms and laboratory parameters.
Future Drug Therapy Cross-sensitivity between various aromatic antiepileptic drugs occurs, making it difficult to select alternative anticonvulsant therapy.
Prevention
The individual must be aware of his or her specific drug hypersensitivity and that other drugs of the same class can cross-react. These drugs must never be readministered. Patient should wear a medical alert bracelet.
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