Acute generalized exanthematous pustulosis (AGEP; also known as pustular drug eruption and toxic pustuloderma) is a rare skin reaction that in 90% of cases is related to medication.

[3] Severe cutaneous adverse reaction (SCAR) disorders are regarded as the drug-induced activation of T cells which then initiate innate immune responses that are inappropriately directed against self tissues.

[7] The most frequently reported drugs that have been associated with the development of AGEP include penicillin, aminopenicillins, macrolides, quinolones, sulfonamides, hydroxychloroquine, terbinafine, and diltiazem.

[7][10][15] Herbal medications, spider bites, iopamidol (used for radiocontrast), lacquers, mercury, psoralen (combined with ultraviolet A to treat psoriasis), and xenobiotics have been associated with the development of AGEP in case reports.

[2][7][8] AGEP also differs from the other SCARs disorders in respect to the level of evidence supporting the underlying mechanism by which a drug or its metabolite stimulates CD8+ T or CD4+ T cells.

Studies indicate that the mechanism by which a drug or its metabolites accomplishes this stimulation involves subverting the antigen presentation pathways of the innate immune system.

Those peptides expressing a drug-related, non-self epitope on their HLA-A, HLA-B, HLA-C, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, or HLA-DR proteins may bind to a T-cell receptor to stimulate the receptor-bearing parent T cell to attack self tissues.

[2][17] Variations in ADME, i.e. an individual's efficiency in absorbing, distributing, metabolizing, and excreting a drug) has been found to occur in cases of the DRESS syndrome, SJS, SJS/TEN, and TEN.

[3][19] The presence of this mutation in two seemingly unrelated disorders has led to suggestions that the classification of AGEP as a SCARs or a form of psoriasis requires study.

[19] The diagnosis of AGEP may be forthright in typical cases in which an individual: has taken a drug known to cause the disorder; develops multiple sterile pustules overlying large areas of red swollen skin starting a few days after initial drug intake; and has a histology of biopsied lesions that shows pustules just below the skin's Stratum corneum (outermost layer), apoptotic (i.e. necrotic) keratinocytes, spongiosis of the stratum spinosum, and infiltration of these tissues by neutrophils plus, in many but not all cases, eosinophils.

[20] Other conditions sometimes confused with AGEP include pustular eruptions caused by bacteria, funguses, herpesviridae, and the varicella zoster virus (i.e. causative agent of chicken pox).

SJS, SJS/TEN, and TEN, while initially described as distinct adverse drug-induced cutaneous reactions are now regarded as manifestations of epidermal necrolysis differing only in extent of skin involvement.

Individuals with liver, lung, kidney, and/or severe skin complications may require high dosage systemic corticosteroids and organ-specific interventions.