Article

Mercury-induced acute generalized exanthematous pustulosis misdiagnosed as a drug-related case.

Department of Dermatology, Fattouma Bourguiba Hospital, Monastir 500, Tunisia.
Contact Dermatitis (Impact Factor: 2.93). 08/2008; 59(1):52-4. DOI: 10.1111/j.1600-0536.2007.01306.x
Source: PubMed
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    ABSTRACT: Acute generalized exanthematous pustulosis (AGEP) is now a well-known clinical entity, characterized by acute onset with associated fever, and numerous non-follicular pin-head sterile pustules on erythematous background. The biopsy evidences subcorneal pustules resembling those of pustular psoriasis. However, polymorphic aspects such as pseudo-erythema multiforme purpuric lesions, and edema are often associated, and with the rapid self-healing course of this impressive pustulosis, allow the differential diagnosis with pustular psoriasis. Most cases of AGEP are drug induced, particularly by antibiotics and mainly beta-lactams. However, a number of other drugs, of which the list is increasing, may be responsible. Few cases are related to other causative factors such as viral infections or ultraviolet radiation.
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    ABSTRACT: Background  Acute generalized exanthematous pustulosis (AGEP) is a rare severe pustular reaction pattern with a typical clinical picture.Objectives  To characterize the histopathological features of AGEP in a large series of cases with a validated diagnosis.Methods  A multinational retrospective histopathological study was conducted. It included 102 hospitalized patients (recruited within the EuroSCAR and RegiSCAR studies) with a validated diagnosis of probable or definite AGEP. A systematic description of the histopathological features in AGEP was done based on a standardized grading system.Results  Sub/intracorneal pustules (41%), intraepidermal pustules (20%) or combinations of them (38%) were observed in 102 cases. The pustules were usually large (> 15 keratinocytes) (82% and 89%, respectively) and regularly contained eosinophils (36% and 32%, respectively). Spongiform features were less prominent in the sub/intracorneal pustules compared with the intraepidermal pustules (44% and 95%, respectively). The main epidermal features were necrotic keratinocytes (67%), including incidental segmental necrosis (7%), and spongiosis (80%) with neutrophil exocytosis (77%). The main dermal features were papillary oedema (88%) and mixed superficial (100%), interstitial (93%), and mid/deep-dermal infiltrates (95%) containing neutrophils (100%) and eosinophils (81%). Follicular pustules were also seen (23%), but vasculitis generally was absent. Classical features of plaque-type psoriasis were infrequent and usually mild. No significant differences were observed between a subgroup of 16 cases with and 86 cases without psoriasis.Conclusions  The present histopathological study concerns a large series of cases with a validated diagnosis of AGEP. It provides diagnostic clues in favour of AGEP in patients with a pustular eruption.
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    ABSTRACT: Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction and is caused by drugs in >90% of cases. It is rare, with an incidence of 1-5 patients per million per year. The clinical manifestations are characterised by fever and the rapid appearance of disseminated sterile pustules 3-5 days after the commencement of treatment. It is accompanied by marked neutrophilia. Mucous membranes are not typically involved. The drugs conferring the highest risk of AGEP according to the EuroSCAR study are aminopenicillins, pristinamycin, hydroxychloroquine, antibacterial sulphonamides, terbinafine and diltiazem. The pathogenesis of AGEP involves the initial influx of CD8 cytotoxic T-cells resulting in the apoptosis of keratinocytes and formation of vesicles. Then CXCL-8-producing and granulocyte macrophage-colony stimulating factor-producing CD4 cells enter the epidermis, resulting in neutrophil mediated inflammation and the formation of pustules. As a result, the histology reveals intraepidermal, usually subcorneal, pustules and an accompanying neutrophilic and lymphocytic infiltrate. Epicutaneous patch testing may also support the diagnosis by causing a localised pustular reaction 48-96 h after the offending drug is applied. The condition usually resolves by 15 days after the causative drug is withdrawn but oral corticosteroid therapy may be necessary in some individuals. The mortality rate is up to 5% and mostly occurs in elderly people who have significant comorbidities.
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