Minoxidil is a direct-acting peripheral
vasodilator for the treatment of symptomatic
hypertension, or refractory
hypertension associated with target organ damage, that is not manageable with a
diuretic and two other
antihypertensive drugs. The most frequent adverse events associated with
minoxidil include
hypertrichosis and cardiovascular events related to its powerful
antihypertensive effect, and less frequently, rashes, bullous eruptions, and
Stevens-Johnson syndrome (SJS). Evidence suggests that SJS and
toxic epidermal necrolysis (TEN) are variants of a single disease with common causes and mechanisms, but differing severities. Epidermal detachment is mild in SJS, moderate in overlap SJS-TEN, and severe (> 30% of body surface area) in TEN. We describe a case of
minoxidil-associated SJS that evolved into fatal TEN. A 69-year-old African-American woman with a history of
chronic kidney disease was admitted to the hospital for a
cerebrovascular accident and uncontrolled
hypertension. On hospital day 12, oral
minoxidil was added to her
drug regimen. On day 23, she developed a maculopapular
rash on her face that gradually diffused to her chest and back. Vesicles and papular lesions extended to her extremities and mucosal membranes; results of a skin biopsy revealed SJS. A positive Nikolsky's sign (
blisters spread on application of pressure) was detected. On days 27-31, diffuse
bullae developed with
rash exacerbation. Skin detachment exceeded 30% and was consistent with TEN. The patient died on day 39. An evaluation of the causality and time course suggested that
minoxidil was the most likely culpable
drug, with a Naranjo
adverse drug reaction probability scale score indicating that the likelihood of the association was possible (score of 3). The mechanism of this reaction has not been well elucidated. It may be related to an impaired clearance of the
minoxidil metabolite, or an immune stimulation resulting in apoptosis and epidermis destruction. To our knowledge, this is the first case report of fatal TEN associated with
minoxidil. This case report emphasizes the importance of monitoring for serious dermatologic reactions in patients receiving
minoxidil therapy.