followed by decreased sensation, weakness, and absent reflexes (64,65,69). Disseminated skin
lesions, when present, are similar to EM but smaller and usually multiple in number.
Late disease is characterized by chronic asymmetric oligoarticular arthritis that involves
the large joints (most often the knee). The central nervous system may also be affected,
manifesting as subacute encephalopathy, axonal polyneuropathy, or leukoencephalopathy.
Diagnosis is based on the history and physical exam. Serology is confirmatory but takes
four to six weeks after the onset of symptoms to become positive. CSF should be obtained if
neurological signs are present. Synovial fluid can be evaluated if arthritis is present.
Drug Reactions
Drugs cause adverse skin reactions in 2% to 3% of hospitalized patients (70). Classic drug
reactions include urticaria, angioedema, exanthems, vasculitis, exfoliative dermatitis/eryth-
roderma, erythema multiforme, Stevens–Johnson syndrome, and toxic epidermal necrolysis
(TEN) (70–72). There is no predilection for age, gender, or race (8). Diagnosis of a drug reaction
is based on a patient’s previous reaction to the drug, ruling out alternate etiological causes of the
rash, timing of events, drug levels, evidence of overdose, patient reaction to drug
discontinuation, and patient reaction to rechallenge.
Drug Exanthems
Exanthems are the most common skin reaction to drugs. The rash usually appears within the
first two weeks after the offending drug is started and resolves within days after the drug is
stopped. The rash is often described as morbilliform, macular, and/or a papular eruption.
Pruritus is the most common associated symptom of drug-induced rash. Low-grade fever and
peripheral blood eosinophilia may also occur in association with drug exanthems.
Erythema Multiforme
Erythema multiforme is an acute, self-limited, peripheral eruptive maculopapular rash that is
characterized by a target lesion. Erythema multiforme most often affects persons between 20
and 30 years of age and has a predilection for men. The rash begins as a dull-red macular
eruption that evolves into papules and the characteristic target lesion. Target lesions are often
found on the palms, soles, knees, and elbows. Vesicles and bullae occasionally develop in the
center of the papules (8,72). There are many causes of this disorder (Table 7).
Figure 5 Characteristic rash, erythema migrans, on the arm of a patient with Lyme disease.Source: Courtesy of
the CDC.
30 Engel et al.