ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS AS A SIDE EFFECT OF QUETIAPINE

Acute generalized exanthematous pustulosis (AGEP), a member of the “neutrophilic dermatoses” was first described by Baker and Ryan in 1968 as exanthematic pustular psoriasis (Baker & Ryan 1968). According to the European Study of Serious Cutaneous Adverse Reactions (EuroSCAR), the incidence ranges from 1 to 5 cases per million per year and the mortality rate approaches 1% to 2%, with the equal age and gender distribution. AGEP erupts suddenly within 1 or 2 days of drug exposure and generally resolves in approximately 2 weeks with sequelae of generalized desquamation. Sidoroff et al. (2001) identified two different temporal patterns of AGEP reaction from the beginning of administration to the onset of a reaction: a first group with a rapid onset (only a few hours to 2-3 days after drug intake, especially antibacterials) and a second group with an interval of 1 to 3 weeks (mean 11 days) for all other drugs. Typical AGEP is a self-limiting disease characterised by an acute cutaneous eruption with non-follicular sterile pustules on an edematous erythema, accompanied by fever above 38°C. In most cases, the skin symptoms begin in the face or in the intertriginous areas, moving to the trunk and the lower limbs in a few hours. On a burning and/or pruritic erythematous background, hundreds of small (pinhead sized < 5 mm), whitish nonfollicular sterile pustules arise, sometimes mimicking a positive Nikolsky’s sign. The mean duration of the pustules is 9.7 days (4-10 days), followed by a characteristic postpustular pin-point desquamation for a few days. About 50% of patients exhibit other skin symptoms like marked edema of the face, purpura lesions (especially on the legs), Stevens-Johnson-syndrome-like “atypical targets”, vesicles and blisters have been described but are not typical. However, clinical diagnosis remains difficult if a monomorphic eruption located on hands and feet is presented. Mild mucous membrane involvement on a single site (mostly a few erosions on the mouth and tongue) may occur in about 20% of cases. High fever usually begins abruptly on the same day (or within 2 to 3 days before or after the eruption) as the pustular eruption and lasts for about 1 week. Lymphadenopathy has been reported in some cases. Histologically, AGEP may demonstrate subcorneal pustules with a background of dermal edema and spongiosis, leukocytoclastic vasculitis, perivascular eosinophils, and focal necrosis of keratinocytes with negative immunofluorescence. According to Speeckaert et al. (2010) AGEP is an uncommon clinical and histopathological reaction pattern, most often described in association with drugs (90% of the cases), acute viral infections (enterovirus (coxsackievirus A9 and B4, echovirus 11 and 30), cytomegalovirus, Epstein-Barr virus, hepatitis B virus, parvovirus B19), Escheria Coli, Chlamydia pneumoniae, Mycoplasma pneumoniae, Echinococcus granulosus, spider bites, heavy metals (mercury), dietary supplements, chemotherapy, radiation and PUVA. Quetiapine is a dibenzothiazepine atypical antipsychotic. It has been proposed that this drug's antipsychotic activity is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5-HT2) antagonisms. It is an antagonist at multiple neurotransmitter receptors in the brain: serotonin 5-HT1A and 5-HT2, dopamine D1 and D2, histamine H1, and adrenergic alpha1and alpha2receptors.