Acute Generalized Exanthematous Pustulosis Induced by Fexofenadine.

Acute generalized exanthematous pustulosis (AGEP) is a skin eruption, frequently drug induced and characterized by the acute development of multiple sterile minute pustules on an erythematous base. There is no case of fexofenadine-induced AGEP in literature (PubMed search). A 40-year-old female presented to us with fever and sudden onset development of multiple discrete to coalescent 1-2 mm nonfollicular pustules on an erythematous base present mainly on her trunk and upper extremities for past 2 days. She had a history of use of fexofenadine 180 mg OD for rhinitis for 2 days. Gram's stain showed no organism and pus culture showed no growth. Histopathological examination revealed subcorneal pustules with epidermal spongiosis. Scattered neutrophils and eosinophils were noted in the dermis. During this period, she took fexofenadine 180 mg unknowingly once following which she developed similar episode within 24-48 h. After withdrawal of the drug, the lesions subsided with scaling in 8-10 days. To the best of our knowledge, this is the first reported case of AGEP induced by fexofenadine. Recognition of such a rare entity is important given the frequent usage of fexofenadine for allergic disorders.

What was known?

Acute generalized exanthematous pustulosis is an acute skin eruption frequently drug induced.

Introduction

Acute generalized exanthematous pustulosis (AGEP) was first described by Baker and Ryan in 1968 as exanthematic pustular psoriasis in 5 patients with no history of psoriasis and was drug-induced.[1] The term AGEP was first used by Beylot et al in 1980.[2] It is a self-limiting disease characterized by acute onset of lesions after intake of the drug with disappearance of lesions within 15 days after discontinuation of the drug; the presence of numerous nonfollicular sterile pustules, <5 mm on an erythematous background, fever >38°C, and peripheral blood leukocytosis (neutrophilia) and a histopathological finding of subcorneal pustules, epidermal spongiosis, and dermal collection of neutrophils and eosinophils ± vasculitis and focal keratinocyte necrosis.[3]

Ninety percent cases of AGEP are attributed to drugs (mainly antibiotics, such as amino-penicillin and macrolides). There are reports of AGEP caused by various drugs in literature; however, this is the first reported case of fexofenadine-induced AGEP.

Case Report

A 40-year-old female presented to our outpatient department with fever >38°C and sudden onset development of multiple discrete to coalescent 1–2 mm nonfollicular pustules on an erythematous base present mainly on her trunk and upper extremities for the past 2 days [Figure 1]. She gave a history of intake of fexofenadine 180 mg OD for rhinitis. She developed the lesions after 2 days of the start of treatment. There were no systemic complaints and no family history. Mucosa and nails were uninvolved.

Figure 1

1–2 mm nonfollicular pustules on an erythematous background on the trunk

On investigating the patient, hemogram revealed leukocytosis with neutrophilia. Gram's stain showed no organism and pus culture showed no growth. The histopathology report revealed subcorneal pustules with epidermal spongiosis along with scattered neutrophils and eosinophils in the dermis [Figure 2]. During this period, she took fexofenadine 180 mg once unknowingly following which she developed similar episode within 24–48 h. After withdrawal of the drug, the lesions subsided with scaling in 8–10 days. A diagnosis of AGEP caused by fexofenadine was made on the basis of clinical features, histopathology, and an accidental oral provocation test. The score on Naranjo adverse drug reaction probability scale was 9.

Figure 2

H and E section of the biopsy specimen showing subcorneal pustules with neutrophils and epidermal spongiosis (×400)

Discussion

Drugs known to cause AGEP are β-lactam antibiotics, macrolides, doxycycline, terbinafine, nifedipine, carbamazepine, and others.[3]

Fexofenadine is an active metabolite of terfenadine and is a second generation antihistamine derived from piperidines. The most common adverse reactions related to fexofenadine have been a headache, dizziness, daytime drowsiness, nausea, and it has been very rarely reported to cause hypersensitivity.[4] AGEP developing as a side-effect of antihistamines such as cetirizine[5] and hydroxyzine[6] has been reported in the past but not to fexofenadine.

The exact mechanism of fexofenadine-induced AGEP in our patient could not be elucidated.

There are four case reports of fexofenadine-induced urticaria in literature.[789] One of the possible mechanisms of urticaria is it being a Type IV hypersensitivity reaction.[10] AGEP is also a Type IV delayed hypersensitivity response,[10] thus, fexofenadine might have induced AGEP by the same mechanism as in the case of urticaria.

Our patient demonstrated clear clinical and histopathological findings of AGEP induced by fexofenadine. The condition resolved quickly and completely after discontinuation of the drug.

We are reporting this case as, to the best of our knowledge, there is no case of fexofenadine- induced AGEP in literature until date. Knowledge of such a rare adverse effect is important as fexofenadine is a commonly prescribed drug by dermatologists, otorhinolaryngologists, and general practitioners for various indications.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Acute generalized exanthematous pustulosis induced by fexofenadine is an unknown entity, not reported so far.