Porth's Essentials of Pathophysiology, 4e

1163

Disorders of Skin Integrity and Function

C h a p t e r 4 6

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