FIXED DRUG
ERUPTION
Fixed
drug eruptions are responsible for up to 20% of all cutaneous drug eruptions.
They can occur anywhere on the body and have been reported to occur in reaction
to a long list of medications. There are a few medicines in particular that
have been associated with fixed drug eruptions. One of the most frequent causes
in the past was phenolphthalein contained in over-the-counter laxatives. After
the numerous side effects from this medication were revealed, it was withdrawn
from the market and is now of only historical significance. Fixed drug
eruptions are unique in many ways, both clinically and histologically. The
exact pathogenesis is unknown.
Clinical Findings: Clinically,
fixed drug eruptions appear as oval to round, dusky red to purple macules with
minimal surface change. Some cases have shown bullous-type reactions. The fixed
drug eruption is unique in that it recurs in the same location time and time
again as the patient is reexposed to the offending agent. Sometimes months may
pass between exposures, and yet the reaction recurs in the same location. The
glans penis, the oral mucosa, and the hands are the most commonly involved
areas, although any area of the skin may be involved. Most cases show one area
of reaction, but some have more than one. It is unusual to have more than five
areas of involvement, but case reports of widespread involvement have been
reported. In these cases, the differential diagnosis includes erythema
multiforme. Another characteristic feature is the postinflammatory
hyperpigmentation that occurs after resolution. This is caused by the vast
amount of pigment incontinence that results from disruption of the
dermalepidermal junction. This hyperpigmentation can take months
to years to resolve.
The list of medications that can
cause fixed drug eruptions continues to grow. The most frequently reported
culprits are the sulfa-based antibiotics, nonsteroidal antiinflammatory
medications, and tetracycline-based antibiotics. Common over-the-counter
medications have also been reported to cause fixed drug eruptions, including
acetaminophen and herbal supplements. For this reason, a thorough history that
includes both prescription and other medications is required.
Histology: Fixed drug eruptions are categorized in the
lichenoid pattern of histological skin disease. These drug reactions show a
prominent lichenoid infiltrate with lymphocytes. The infiltrate is associated
with very noticeable vacuolar change of the basilar layer of the epidermis and
prominent formation of necrotic keratinocytes (Civatte bodies). There is
melanin incontinence within the dermis in all cases, and this can be used to
differentiate fixed drug eruption from other lichenoid reactions. The bullae
form within the subepidermal space in the bullous variant of fixed drug
eruption. Rare variants of fixed drug eruption have been described that have included
evidence of vasculitis. This form is exceedingly rare.
Pathogenesis: The etiology is unknown. Research has indicated
that CD8+ T cells are the primary cell type within the inflammatory
infiltrate. This abnormal immune response is responsible for the tissue damage.
The precise interaction and mechanism by which certain medications react with
the immune system of susceptible individuals to cause fixed drug eruptions has
not been elucidated.
Treatment: The main point in therapy is making the correct
diagnosis and removing the offending agent. Once this is done, the lesions heal
within a month. Medium to potent topical corticosteroids can be used to help
relieve pruritus and potentially speed healing. Fixed drug eruptions often
leave an area of postinflammatory hyperpigmentation or hypopigmentation after
the initial reaction has resolved. This pigmentary abnormality can last for
months to years.
