C h a p t e r 4 6
Disorders of Skin Integrity and Function
1163
and nonimmunologic, can be involved in its pathogen-
esis. The urticarial wheal results from liberation of his-
tamine from mast cells and basophils. Histamine causes
hyperpermeability of the microvessels of the skin and
surrounding tissue, allowing fluid to leak into the tis-
sues, causing edema and wheal formation.
Acute immunologic urticaria is commonly the result
of an IgE-mediated immune reaction that usually occurs
within 1 hour of exposure to an antigen. The most
common causes of acute urticaria are foods or drinks,
medications (most notably penicillin and cephalospo-
rin), insect stings, and exposure to pollens or chemi-
cals. Although nonsteroidal anti-inflammatory drugs,
including aspirin, do not normally cause urticaria, they
may exacerbate the preexisting disease. In rare cases,
urticaria is a manifestation of underlying disease, such
as certain cancers, collagen diseases, and hepatitis. A
hereditary deficiency of a C1 (complement 1) inhibitor
also can cause a condition called
hereditary angioneu-
rotic edema
.
The physical urticarias are a specific form of chronic
urticaria, in which specific physical stimuli reproduc-
ibly elicit wheals.
30,31
Physical urticarias are intermit-
tent, usually last less than 2 hours, are produced by
appropriate stimuli, have distinctive appearances and
locations, and are seen most frequently in young adults.
Dermographism, or skin writing, is one form of physical
urticaria in which wheals appear in response to simple
rubbing of the skin. The wheals follow the pattern of
the scratch or rubbing, appearing within 10 minutes and
dissolving completely within 20 minutes. Other types
of physical urticaria are induced by exercise, sunlight,
water, vibration, cold, and heat. Appropriate challenge
tests (e.g., application of an ice cube to the skin to initi-
ate development of cold urticaria) are used to differenti-
ate physical urticaria from chronic urticaria due to other
causes.
Most types of urticaria are treated with nonsedat-
ing antihistamines that alleviate pruritus and decrease
the incidence of hives without producing drowsiness.
Leukotriene antagonists (zafirlukast and montelukast)
may also be used. Oral corticosteroids may be used in
the treatment of refractory urticaria. Tricyclic antide-
pressant drugs, particularly those with antihistamine
actions, may also be used. Persons who have experi-
enced angioedema of the larynx and pharynx should be
counseled to carry a prescription of epinephrine in an
autoinjectable syringe.
Drug-Induced Skin Eruptions
Most drugs can cause a localized or generalized skin
eruption. Topical drugs are usually responsible for
localized contact dermatitis types of rashes, whereas
systemic drugs cause generalized skin lesions. Although
many drug-induced skin eruptions are exanthematous
or morbiliform (i.e., measleslike), they may mimic most
of the skin disorders described in this chapter. Because
the lesions vary greatly, the diagnosis depends almost
entirely on an accurate patient report, including a full
drug history. Early recognition and discontinuation of
the drug are essential. Management of mild cases is
aimed at eliminating the offending drug while treating
the symptoms. Severe cases require prompt medical
attention.
Some drug reactions result in epidermal cell detach-
ment and bullae (fluid-filled blisters) formation. The
skin detachment seen with bullous skin lesions is dif-
ferent from the desquamation (i.e., peeling) that occurs
with other skin disorders. In the bullous disorders, there
is full-thickness detachment of the entire epidermis from
the dermis. This leaves the person vulnerable to mul-
tiple problems, including loss of body fluids and electro-
lytes, impaired body temperature control, and a greatly
increased risk of infection. Three types of drug reactions
that result in bullous skin lesions are erythema multi-
forme minor, which is usually self-limiting, with a small
amount of skin detachment at the lesion sites; Stevens-
Johnson syndrome, which involves less than 10% of
the body surface area; and toxic epidermal necrolysis,
which involves detachment of more than 30% of the
epidermis.
35
Detachment of 10% to 30% of the epider-
mis is considered an overlap of Stevens-Johnson syn-
drome and toxic epidermal necrolysis.
Etiology and Pathogenesis.
Although the cause of
erythema multiforme minor may be drug induced or
unknown, it frequently occurs after infections, especially
HSV infection. Stevens-Johnson syndrome and toxic epi-
dermal necrolysis are caused by a hypersensitivity reac-
tion to drugs, the most common being sulfonamides,
anticonvulsants, nonsteroidal anti-inflammatory drugs,
antimalarial agents, and allopurinol. The incidences of
Stevens-Johnson syndrome and toxic epidermal necroly-
sis are rare, but mortality rates are high.
36
Recovery is
based on the severity and quick, aggressive treatment.
Manifestations.
The lesions of erythema multiforme
minor and Stevens-Johnson syndrome are similar. The
primary lesion of both is a round, erythematous papule
resembling an insect bite. Within hours to days, these
lesions change into several different patterns. The indi-
vidual lesions may enlarge and coalesce, producing small
plaques, or they may change to concentric zones of color
appearing as “target” or “iris” lesions (Fig. 46-15). The
outermost rings of the target lesions usually are ery-
thematous; the central portion usually is opaque white,
yellow, or gray (dusky). In the center, small blisters may
form on the dusky purpuric macules, giving them their
characteristic targetlike appearance. Although there is
wide distribution of lesions over the body surface area,
there is a propensity for them to occur on the face and
trunk.
Toxic epidermal necrolysis is the most serious type of
drug reaction, with mortality rates of 40%.
35
The person
experiences a prodromal period of malaise, low-grade
fever, and sore throat. Within a few days, widespread
erythema and large, flaccid bullae appear, followed by
the loss of the epidermis, leaving a denuded and pain-
ful dermis. The skin surrounding the large denuded
areas may have the typical target-like lesions seen with
