Erythema multiforme may present with varying degrees of severity (previously
classified as erythema multiforme minor and major) (8). Bullae and systemic symptoms are
absent in less severe erythema multiforme. The rash rarely affects the mucous membranes and
is usually limited to the extensor surfaces of the extremities. This mild form of erythema
multiforme is often associated with herpes simplex virus infection. Conversely, drug reactions
are usually associated with more severe manifestations of erythema multiforme. Mucous
membranes are involved, and the eruptions often become bullous. Fever, cheilosis, stomatitis,
balanitis, vulvitis, and conjunctivitis can also occur (70).
Stevens–Johnson Syndrome
Stevens–Johnson syndrome is a blistering disorder that is usually more severe than erythema
multiforme (73,74). The causes of Stevens–Johnson syndrome are similar to the etiologies of
erythema multiforme (Table 7). Patients with Stevens–Johnson syndrome often present with
pharyngitis, malaise, and fever. The syndrome evolves over a few days with the evolution of
mucous membrane erosions. Small blisters develop on purpuric or atypical target lesions. The
blisters eventually result in skin detachment. Stevens–Johnson syndrome affects less than 10%
of the total body surface (70,74).
TEN
TEN is the most serious cutaneous drug reaction and is defined by blistering of over 30% of the
total body surface area. More than one mucous membrane is involved. It is usually caused by
the same drugs that cause erythema multiforme (Table 7), and its onset is acute. A fever greater
than 39 8 C is often present. Intestinal and pulmonary involvement predict a poor outcome
(70,71).
Table 7 Causes of Erythema Multiforme
Viral infections Anticonvulsants
Herpes simplex 1 and 2 Barbiturates
Epstein–Barr virus Carbamazepine
Hepatitis A, B, C Phenytoin
Varicella zoster Antituberculoids
Parvovirus B19 Rifampin
Bacterial infections Isoniazid
Hemolytic streptococci Pyrazinamide
Pneumococcus Other drugs
Staphylococcusspecies Allopurinol
Proteusspecies Fluconazole
Salmonellaspecies Hydralazine
Mycobacterium tuberculosis NSAIDs
Mycobacterium aviumcomplex Estrogen
Francisella tularensis Physical factors/contact
Vibrio parahaemolyticus Sunlight
Yersiniaspecies Cold
Mycoplasmapneumonia X-ray therapy
Fungal infections Tattooing
Histoplasma capsulatum Poison ivy
Coccidiomycosis Other factors
Parasitic infections Pregnancy
Trichomonasspecies Multiple myeloma
Toxoplasma gondii Leukemia
Antibiotics Collagen diseases
Penicillin Idiopathic (50%)
Tetracyclines
Erythromycin
Sulfa drugs
Vancomycin
Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs.
Source: Adapted from Ref. 72.
Fever and Rash in Critical Care 31