Exanthematous eruption typically appears 4 to 14 days after starting the medication.

Lesions are morbilliform (resembling measles) and are pink, “drug red,” or purple (violaceous) in color (Figs. 26.1 and 26.2).

Lesions begin on the chest (centrally) and spread outward with areas of confluence.

Exanthems tend to be symmetric and occasionally generalized in distribution; they are noted particularly on the trunk, thighs, upper arms, and face.

Typically occur as wheals that may coalesce or take cyclic or gyrate forms (Fig. 26.3).

Lesions usually appear shortly after the start of drug therapy and resolve rapidly when the drug is withdrawn.

Urticaria can be seen anywhere on the body.

Angioedema occurs in a periorbital, labial, and perioral distribution.

This may appear as erythematous (an exaggerated sunburn; Fig. 26.4), eczematous, or lichenoid (resembling lichen planus) eruption.

Lesions generally occur on sun-exposed areas such as the “V” of the neck, upper sternum, extensor forearms, and the face (Fig. 26.5).

Characterized by palpable purpura, sometimes accompanied by fever, myalgias, arthritis, and abdominal pain.

Vasculitis typically begins 7 to 21 days after the onset of drug therapy and may involve other organ systems.

Often idiopathic, palpable purpura can be a reaction to a drug; however, a systemic illness (e.g., systemic lupus erythematosus) may underlie the vasculitis.

Histopathology reveals leukocytoclastic vasculitis.

A comprehensive review of systems and laboratory evaluations to exclude internal involvement is mandatory.

Purpura and vasculitic drug eruptions also tend to occur on the lower extremities.

This is widespread inflammation of the skin (discussed in Chapter 34: Cutaneous Manifestations of Systemic Disease), and it may result from an underlying skin condition, drug eruption, internal malignancy, or immunodeficiency syndrome.

Lymphadenopathy is often noted, and hepatosplenomegaly, leukocytosis, eosinophilia, and anemia may be present.

Stevens-Johnson syndrome (SJS) was traditionally referred to as “erythema multiforme major,” but it is now clear that erythema multiforme (EM) is a distinct cutaneous disorder that is usually triggered by infections (commonly herpes simplex virus), and rarely drugs (see Chapter 27: Diseases of Cutaneous Vasculature).

SJS and toxic epidermal necrolysis (TEN) are variants on a clinical spectrum of drug reactions.

SJS is most often due to drugs, is sometimes idiopathic, but can occasionally be caused by infection with Mycoplasma pneumonia and rarely, immunizations.

SJS is characterized by dusky red macules that may or may not have blistering located on the face and trunk.

Mucous membrane involvement may be severe and is often painful (e.g., erosions, ulcers) (Fig. 26.6).

Constitutional symptoms are often present and can progress to TEN.

By definition, in SJS there is <10% body surface area (BSA) with epidermal detachement (i.e., blistering or sloughing). If there is epidermal detachment of 10% to 30% of the BSA then there is an SJS-TEN overlap and TEN occurs when there is >30% BSA of epidermal detachment.

TEN is a severe, potentially fatal skin reaction that involves a prodrome of painful skin, followed by rapid, widespread (>30% BSA), skin sloughing (Fig. 26.7).

Most cases of TEN are the result of drugs; most commonly implicated agents include sulfonamide antibiotics, antiepileptic drugs, oxicam nonsteroidal anti-inflammatory drugs, allopurinol, nevirapine, abacavir, and lamotrigine.

Symptoms may also include hyperpyrexia, hypotension secondary to hypovolemia, and tachycardia.

Secondary infection and sepsis are major concerns.

Septicemia and multisystem organ failure are the primary causes of death.

Characterized by tender, red, subcutaneous nodules that typically appear on the pretibial areas.

Erythema nodosum is a reactive process often secondary to infection, but it may be caused by medications, especially oral contraceptives and sulfonamides.

Lesions generally appear on the trunk as monomorphic folliculitis-like papules and pustules.

Generalized acneiform eruptions are usually due to systemic steroids (Fig. 26.8).

Rosacea-like lesions may occur on the face secondary to use of topical steroids and are often clinically indistinguishable from ordinary rosacea. A history of long-term, indiscriminate misuse of a potent topical steroid on the face helps confirm the diagnosis (Fig. 26.9).

The condition typically worsens when the topical steroids are discontinued.

Steroid atrophy most often occurs in body folds (axillae and inguinal creases) (Fig. 26.10).

This is a reaction of circular red plaques or blisters that recurs at the same cutaneous site each time the drug is ingested. In other words, a rechallenge of the drug results in an identical eruption at the same site or sites.

Lesions may be round or oval, single, or multiple (Fig. 26.11).

Lesions initially are erythematous; later they become violaceous.

Lesions often blister and erode.

Lesion occurs most often on the hands, feet, and genitalia; multiple lesions may occur on the trunk and extremities. A lesion on the glans penis is not unusual (Fig. 26.12).

The eruption often heals with characteristic postinflammatory hyperpigmentation.