Rash, Drug Eruption

Essentials of Diagnosis

• Usually, abrupt onset of widespread, symmetric erythematous eruption

• May mimic any inflammatory skin condition

• Constitutional symptoms (malaise, arthralgia, headache, and fever) may be present

General Considerations

• Only a minority of cutaneous drug reactions result from allergy

• Penicillin and other β-lactam antibiotics and trimethoprim-sulfamethoxazole are the most common causes of urticarial and maculopapular reactions

• Drug-induced hypersensitivity reaction (also known as drug eruption with eosinophilia and systemic symptoms [DRESS]) is most often caused by

  • Anticonvulsants

  • Allopurinol

  • Sulfonamides

• Stevens-Johnson syndrome/toxic epidermal necrolysis most commonly occur in response to

  • Antibiotics

  • Sulfonamides

  • Anticonvulsants

  • Allopurinol

  • NSAIDs

• Phenolphthalein, pyrazolone derivatives, tetracyclines, NSAIDs, trimethoprim-sulfamethoxazole, and barbiturates are the major causes of fixed drug eruptions

• Calcium channel blockers are a common cause of pruritus and eczemas in the elderly

Demographics

• Rashes are among the most common adverse reactions to drugs and occur in 2–3% of hospitalized patients

Symptoms and Signs

• Drug eruptions are generally classified as "simple" or "complex"

• Simple drug eruptions

  • Involve an exanthem

  • Usually appear in the second week of drug therapy

  • Have no associated constitutional or laboratory findings

  • Antibiotics, including the penicillins and quinolones, are most common causes

• Complex drug eruptions

  • Occur during the third week of treatment on average

  • Have constitutional and laboratory findings, including fevers, chills, hematologic abnormalities (especially eosinophilia), and abnormal liver chemistries or kidney function tests

  • A mnemonic for complex eruptions is "DRESS" (DRug Eruption with Eosinophilia and Systemic Symptoms)

  • Most common causes are the long-acting sulfonamides, allopurinol, and anticonvulsants

  • In patients of certain races, polymorphisms of antigen presenting major histocompatibility (MHC) loci increases risk for the development of severe drug eruptions

  • Coexistent reactivation of Epstein-Barr virus, HHV-6, or cytomegalovirus is often present and may be important in the pathogenesis of these complex drug eruptions

• See Table 6–3

Differential Diagnosis

• Viral exanthem

• Early erythema multiforme

• Other causes of erythema nodosum, eg, infection, sarcoidosis

• Atopic dermatitis (eczema)

• Secondary syphilis

• Systemic lupus erythematosus

• Acute HIV infection

• Scarlet fever

• Toxic shock syndrome

• Lichen planus

Laboratory Tests

• In simple drug eruptions, routinely ordered blood tests should be done to rule out systemic involvement; otherwise, they are of no value

• In complex drug eruptions, complete blood count with differential, liver biochemical tests, and kidney function tests should be monitored

• Serum polymerase chain reaction (PCR) for HHV-6, HHV-7, Epstein-Barr virus, cytomegalovirus, and parvovirus B19 are performed in some centers

Diagnostic Procedures

• Skin biopsies may be helpful

• Observation after discontinuation, which may be a slow process, helps establish the diagnosis

• Rechallenge, though of theoretical value, may pose a danger to the patient and is best avoided

• Systemic manifestations are treated as they arise (eg, anemia, icterus, purpura)

• Antihistamines may be of value in urticarial and angioneurotic reactions

• Epinephrine 1:1000, 0.5–1.0 mL intravenously or subcutaneously, should be used as an emergency measure in anaphylactoid reactions or anaphylaxis

• In drug-induced hypersensitivity syndromes, systemic corticosteroids may be required, most commonly prednisone at a dose of 1 mg/kg/day orally and tapering very slowly

• In the case of allopurinol-induced hypersensitivity reaction,

  • A steroid sparing agent (eg, mycophenolate mofetil) should be started at the time of prednisone initiation

  • Duration of treatment: up to 12 months

Complications

• Some cutaneous drug reactions may be associated with visceral involvement

• The organ systems involved depend on the individual medication or drug class

• Most common is an infectious mononucleosis-like illness and hepatitis associated with administration of anticonvulsants

• Myocarditis may be a serious complication of a drug-induced hypersensitivity syndrome

• Patients may suffer hypothyroidism months after recovering from drug-induced hypersensitivity syndrome

Prognosis

• Drug eruption usually disappears upon withdrawal of the drug and proper treatment

• Drug-induced hypersensitivity syndrome may be associated with autoimmune phenomena, including abnormal thyroid function

When to Refer

• If there is a question about the diagnosis, if recommended therapy is ineffective, or if specialized treatment is necessary

When to Admit

• Stevens-Johnson syndrome/toxic epidermal necrolysis develops in some patients with drug-induced hypersensitivity syndrome, with extensive blistering eruptions resulting in erosions and superficial ulcerations demanding hospitalization and nursing care as for burn patients