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Review
. 2016 Jul 27;17(8):1214.
doi: 10.3390/ijms17081214.

Acute Generalized Exanthematous Pustulosis: Pathogenesis, Genetic Background, Clinical Variants and Therapy

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Free PMC article
Review

Acute Generalized Exanthematous Pustulosis: Pathogenesis, Genetic Background, Clinical Variants and Therapy

Laurence Feldmeyer et al. Int J Mol Sci. .
Free PMC article

Abstract

Acute generalized exanthematous pustulosis (AGEP) is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base and spontaneous resolution usually within two weeks. Systemic involvement occurs in about 20% of cases. The course is mostly benign, and only in rare cases complications lead to life-threatening situations. Recent studies highlight the importance of genetic variations in interleukin-36 receptor antagonist gene (IL-36RN) in the pathogenesis of this disease. The physiopathology of AGEP remains unclear, but an involvement of innate and acquired immune cells together with resident cells (keratinocytes), which recruit and activate neutrophils via production of cytokines/chemokines such as IL-17, IL-36, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα) and chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, has been postulated. Treatment is based on the removal of the causative drug, supportive care, infection prevention and use of potent topical or systemic steroids.

Keywords: acute generalized exanthematous pustulosis; dermatology; drug reaction; skin.

Figures

Figure 1
Figure 1
Putative pathogenic mechanisms in acute generalized exanthematous pustulosis (AGEP). (A) In cases with drug involvement, the initial phase involves stimulation of drug-specific T cells and (B) their migration to the skin; (C) These T cells, possibly together with natural killer T (NKT) cells/natural killer (NK) cells are activated in the skin, where they induce apoptosis of keratinocytes through cytotoxic proteins and Fas/Fas ligand (FasL) interactions resulting in the formation of subcorneal vesicles; (D) Furthermore, these T cells together with subsequently activated bystander and inflammatory cells (keratinocytes, dendritic cells (DC), MC, neutrophils) release various cytokines and chemokines; (E) which predominately lead to neutrophilic inflammation and the formation of pustules.
Figure 1
Figure 1
Putative pathogenic mechanisms in acute generalized exanthematous pustulosis (AGEP). (A) In cases with drug involvement, the initial phase involves stimulation of drug-specific T cells and (B) their migration to the skin; (C) These T cells, possibly together with natural killer T (NKT) cells/natural killer (NK) cells are activated in the skin, where they induce apoptosis of keratinocytes through cytotoxic proteins and Fas/Fas ligand (FasL) interactions resulting in the formation of subcorneal vesicles; (D) Furthermore, these T cells together with subsequently activated bystander and inflammatory cells (keratinocytes, dendritic cells (DC), MC, neutrophils) release various cytokines and chemokines; (E) which predominately lead to neutrophilic inflammation and the formation of pustules.
Figure 2
Figure 2
(A) Widespread rash with numerous pinhead-sized pustules on an erythematous oedematous base; (B) Flexural accentuation with characteristic collarette-shaped desquamation is typically observed in AGEP.
Figure 3
Figure 3
Typical histological features of AGEP are indicated.

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