Lori E. Shapiro

Lamotrighe-Induced Severe Cutaneous Adverse Reactions

Summary: Purpose: We systematically reviewed and analyzed published and unpublished cases of Stevens‐Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN) associated with lamotrigine (LTG) therapy to identify characteristics of these reactions.

Cytochrome P-450 3A: Interactions with dermatologic therapies

Recent case reports and studies suggest that interactions involving the cytochrome P-450 mixed function oxidase system are important causes of medication toxicity and decreased efficacy during combination drug therapy. The cytochrome P-450 3A3/4 isoenzyme is involved in many significant drug interactions. New and familiar drugs continue to be implicated as having potentially serious interactions with this group of enzymes. An understanding of the basic principles of these interactions may have a major impact on patient outcome.

Mechanisms of drug reactions: the metabolic track.

Hypersensitivity syndrome (HSR) describes a drug-induced symptom complex consisting of fever, rash, and internal organ involvement. Although these reactions are rare, they are very important because of their severity and unpredictability. The metabolic conversion of drugs to chemically-reactive products is now established as a prerequisite for many idiosyncratic drug reactions. In the setting of HSR, an imbalance in the rates of formation of reactive metabolites and of enzymatic detoxification can lead to accumulation of these byproducts. Reactive metabolites could act as haptens eliciting an immune response, covalently bind target proteins causing cell death, or interact with nucleic acids leading to mutations. The lymphocyte toxicity assay (LTA) provides an in vitro assessment of host susceptibility to reactive metabolites of a given drug. It has validated the clinical finding of increased risk of HSR in first degree relatives of patients. It is hoped that the LTA will be used to predict host susceptibility before drug exposure. Ultimately it is hoped that the genetic defects that lead to drug reactions will be identified. This would improve drug development safety and allow primary prevention of serious reactions.

Dapsone in prevention of recurrent neutrophilic eccrine hidradenitis

Neutrophilic eccrine hidradenitis has been described in patients with acute myelogenous leukemia and other malignant diseases, usually during chemotherapy. We describe a 46-year-old man with Hodgkins disease in whom neutrophilic eccrine hidradenitis developed after each of the first two treatments with lomustine. Dapsone, 100 mg daily, was initiated 48 hours before the patients third treatment with lomustine and was continued for 14 days. This regimen was successful in suppressing the reaction during the first course and three subsequent courses of lomustine.

Serious dermatologic reactions in children.

Although serious reactions comprise only a small percentage of total adverse drug reactions, they are important in terms of morbidity and potential mortality. An update on serious dermatologic reactions in children is presented including serum sickness-like reactions due to cefaclor, hypersensitivity syndrome reactions (HSRs), and drug-induced pseudoporphyria. More detailed information on minocycline-induced reactions including drug-induced lupus and HSRs and lamotrigine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome will be discussed.