Midodrine-induced acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is an acute sterile pustular eruption most commonly induced by medications. We present a case of AGEP with erythroderma following use of midodrine in a 58-year-old man. Although antibiotics are most commonly implicated in AGEP, we emphasize that nonantibiotic agents also may cause AGEP, which often manifests after a longer time interval compared to antibiotic-associated AGEP.

[Acute generalized exanthematous pustulosis]. / Akute generalisierte exanthematische Pustulose.

CLINICAL FEATURES: Acute generalized exanthematous pustulosis (AGEP) is a reaction pattern mostly caused by drugs. It is characterized by the rapid occurrence of dozens to thousands pinhead-sized, non-follicular, sterile pustules on a slightly edematous erythematous base, commonly with accentuation in the major flexures and usually accompanied by a facial edema, fever and leukocytosis. Histology reveals spongiform subcorneal and/or intraepidermal pustules, an inflammatory infiltrate consisting of neutrophils and often eosinophils and frequently a marked edema of the papillary dermis. TRIGGERS: Even if in single case reports a large number of drugs has been described as triggers for AGEP, larger studies have revealed a list with an elevated risk to cause the reaction which includes antibacterial agents like ampicillin/amoxicillin, quinolones, pristinamycin, anti-infective sulfonamides, the antimycotic drug terbinafine, (hydroxy)chloroquine, and diltiazem. In some cases infections have been reported as triggers. CLINICAL COURSE, PROGNOSIS AND TREATMENT: AGEP is an acute and--especially in patients with concomitant diseases--sometimes severe reaction. Withdrawal of the causative agent usually leads to a rapid and complete resolution--even without further specific therapy.

A recent update of pharmacogenomics in drug-induced severe skin reactions.

In some adverse drug reactions (ADRs), genetic predisposition plays a significant role in pathogenesis, and the skin is the most frequently reported target. These severe cutaneous ADRs include bullous fixed drug eruptions (FDE), acute generalized exanthematous pustulosis (AGEP), drug-induced hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The putative contribution of individual effector cells in drug hypersensitivity is briefly mentioned. To trigger these drug hypersensitivities, certain class I HLA alleles (e.g., HLA-A and HLA-B alleles) and certain class II HLA alleles (e.g., HLA-DR alleles) have been recently found to be the genetic determinants. One of the best characterized examples mentioned in this article is HLA-B*1502 to determine the incidence of carbamazepine-induced SJS. How drugs are processed and presented by these HLA alleles to activate immune responses has been explained by several hypotheses. Further implication of pharmagenomic findings to prevent drug-induced severe skin reactions can be achieved by pre-screening putative risk HLA alleles before using drugs.