Acute generalized exanthematous pustulosis associated with 2 common medications: Hydroxyzine and benzocaine

To the Editor: Acute generalized exanthematous pustulosis (AGEP) is a significant adverse cutaneous reaction most often induced by drugs or acute infections. In drug-induced AGEP, determining the responsible medication is important, as is identifying cross-reactants, in that early discontinuation and future avoidance of these agents help reduce morbidity.The clinical hallmark of AGEP is the sudden onset of multiple, disseminated, nonfollicular, sterile pustules on an erythematous background, usually with intertriginous accentuation associated with fever (temperature greater than 38°C) and neutrophilia (>7 × 109⁄L). AGEP generally resolves 2 weeks after the causative drug is withdrawn.In our first case, AGEP induced by benzocaine, a 67-year-old man presented with a severe, widespread, pustular eruption with associated fevers, rigors, watery diarrhea, and malaise. Twenty-four hours before the drug eruption, the patient had dental extraction and received a benzocaine spray. Examination demonstrated confluent erythema studded with nonfollicular pustules distributed on the face, trunk, and extremities. Biopsies demonstrated histologic features consistent with AGEP.The patient was treated with oral prednisone and topical corticosteroids. After a 3-day hospitalization, he clinically improved and was discharged home. In follow-up with the Patch Test Clinic, the patient had a 3+ pustular reaction to benzocaine at 96 hours. A biopsy of the benzocaine patch test site was consistent with allergic contact dermatitis.In our second case, AGEP caused by hydroxyzine, a 48-year-old woman with a history of psoriasis presented to a walk-in clinic complaining of generalized pruritus. She was prescribed oral hydroxyzine. Twenty-four hours after hydroxyzine ingestion, a burning erythematous eruption developed on her trunk, extremities, and genitalia. She discontinued the hydroxyzine on day 4. Two days after discontinuing hydroxyzine, fever developed and skin eruption worsened. Skin examination revealed widespread small nonfollicular pustules on an erythematous background. Biopsies showed features of AGEP.The patient was treated with prednisone and betamethasone valerate 0.1% ointment. She was later tested in the Patch Test Clinic and a 3+++ local reaction developed in response to 10% hydroxyzine at 48 and 120 hours. Biopsy of the test site showed a neutrophilic dermatosis favoring AGEP.In each of the aforementioned cases, the eruption started approximately 24 hours after the drug exposure. Each patient remembered at least 1 past exposure to the responsible medication.The sensitivity of patch testing to drugs in AGEP is up to 80%.1Revuz J. Valeyrie-Allanore L. Drug eruptions.in: Bolognia J.L. Jorizzo J.L. Schaffer J.V. Dermatology. 3rd ed. Elsevier Saunders, Philadelphia2012: 335-356Google Scholar Patch testing with the suspected drug can mimic AGEP clinically at the patch test site where it can be biopsied to confirm the diagnosis. The biopsy of the patch site could show classic AGEP or allergic contact dermatitis as in the cases described. Dermatologists can have medications compounded to use for patch testing (Fig 1).To the best of our knowledge, there are no reported cases of AGEP secondary to benzocaine and only 2 previous reports of AGEP caused by hydroxyzine.2Kumar S.L. Rai R. Hydroxyzine-induced acute generalized exanthematous pustulosis: an uncommon side effect of a common drug.Indian J Dermatol. 2011; 56: 447-448Crossref PubMed Scopus (7) Google Scholar, 3Tsai Y.S. Tu M.E. Wu Y.H. Lin Y.C. Hydroxyzine-induced acute generalized exanthematous pustulosis.Br J Dermatol. 2007; 157: 1296-1297Crossref PubMed Scopus (9) Google Scholar It may be that these common medications have caused AGEP in the past that was either unrecognized or not reported. Regardless, it is important that dermatologists be aware of this uncommon yet important adverse event. To the Editor: Acute generalized exanthematous pustulosis (AGEP) is a significant adverse cutaneous reaction most often induced by drugs or acute infections. In drug-induced AGEP, determining the responsible medication is important, as is identifying cross-reactants, in that early discontinuation and future avoidance of these agents help reduce morbidity. The clinical hallmark of AGEP is the sudden onset of multiple, disseminated, nonfollicular, sterile pustules on an erythematous background, usually with intertriginous accentuation associated with fever (temperature greater than 38°C) and neutrophilia (>7 × 109⁄L). AGEP generally resolves 2 weeks after the causative drug is withdrawn. In our first case, AGEP induced by benzocaine, a 67-year-old man presented with a severe, widespread, pustular eruption with associated fevers, rigors, watery diarrhea, and malaise. Twenty-four hours before the drug eruption, the patient had dental extraction and received a benzocaine spray. Examination demonstrated confluent erythema studded with nonfollicular pustules distributed on the face, trunk, and extremities. Biopsies demonstrated histologic features consistent with AGEP. The patient was treated with oral prednisone and topical corticosteroids. After a 3-day hospitalization, he clinically improved and was discharged home. In follow-up with the Patch Test Clinic, the patient had a 3+ pustular reaction to benzocaine at 96 hours. A biopsy of the benzocaine patch test site was consistent with allergic contact dermatitis. In our second case, AGEP caused by hydroxyzine, a 48-year-old woman with a history of psoriasis presented to a walk-in clinic complaining of generalized pruritus. She was prescribed oral hydroxyzine. Twenty-four hours after hydroxyzine ingestion, a burning erythematous eruption developed on her trunk, extremities, and genitalia. She discontinued the hydroxyzine on day 4. Two days after discontinuing hydroxyzine, fever developed and skin eruption worsened. Skin examination revealed widespread small nonfollicular pustules on an erythematous background. Biopsies showed features of AGEP. The patient was treated with prednisone and betamethasone valerate 0.1% ointment. She was later tested in the Patch Test Clinic and a 3+++ local reaction developed in response to 10% hydroxyzine at 48 and 120 hours. Biopsy of the test site showed a neutrophilic dermatosis favoring AGEP. In each of the aforementioned cases, the eruption started approximately 24 hours after the drug exposure. Each patient remembered at least 1 past exposure to the responsible medication. The sensitivity of patch testing to drugs in AGEP is up to 80%.1Revuz J. Valeyrie-Allanore L. Drug eruptions.in: Bolognia J.L. Jorizzo J.L. Schaffer J.V. Dermatology. 3rd ed. Elsevier Saunders, Philadelphia2012: 335-356Google Scholar Patch testing with the suspected drug can mimic AGEP clinically at the patch test site where it can be biopsied to confirm the diagnosis. The biopsy of the patch site could show classic AGEP or allergic contact dermatitis as in the cases described. Dermatologists can have medications compounded to use for patch testing (Fig 1). To the best of our knowledge, there are no reported cases of AGEP secondary to benzocaine and only 2 previous reports of AGEP caused by hydroxyzine.2Kumar S.L. Rai R. Hydroxyzine-induced acute generalized exanthematous pustulosis: an uncommon side effect of a common drug.Indian J Dermatol. 2011; 56: 447-448Crossref PubMed Scopus (7) Google Scholar, 3Tsai Y.S. Tu M.E. Wu Y.H. Lin Y.C. Hydroxyzine-induced acute generalized exanthematous pustulosis.Br J Dermatol. 2007; 157: 1296-1297Crossref PubMed Scopus (9) Google Scholar It may be that these common medications have caused AGEP in the past that was either unrecognized or not reported. Regardless, it is important that dermatologists be aware of this uncommon yet important adverse event.

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