Acute generalized exanthematous pustulosis due to allylisopropylacetylurea: role of IL-17-producing T cells

ARTICLE

Auteur(s) : Takashi UEDA^1,2 ueder@med.kitasato-u.ac.jp, Miho ABE¹, Ryouko OKIYAMA¹, Shuichi OYAMA¹, Kanji SATOH¹, Shinsaku AIBA¹, Satoshi KANEKO¹, Kensei KATSUOKA²

¹ Division of Dermatology, Yokohama Rosai Hospital, 3211 Kozukue, Yokohama-shi, Kanagawa 222-0036, Japan

² Department of Dermatology, Kitasato University Hospital, 1-15-1 Minamiku Kitasato, Sagamihara-shi, Kanagawa 252-0375, Japan

Acute generalized exanthematous pustulosis (AGEP) is an uncommon skin eruption characterized by the acute formation of multiple, small, non-follicular pustules on an erythematous base [1]. We report a case of AGEP due to allylisopropylacetylurea, a weak monoureide sedative, which is usually combined with an antipyretic agent and enhances the analgesic effect.

A 42-year-old woman had taken Children's Bufferin (containing acetylsalicylic acid; Lion Corporation, Tokyo, Japan) in the evening and Eve A (containing ibuprofen, anhydrous caffeine and allylisopropylacetylurea; SSP Co. Ltd, Tokyo, Japan) the following morning for headache and chills. Three days later, she was admitted to our hospital with a fever of 38.5 °C. On physical examination, she had a diffuse, red, pruritic erythema on her face, trunk, and extremities, which was studded with scattered, non-follicular pustules (figure 1A). There was no involvement of the hair-bearing and mucosal regions. Her blood tests showed leukocytosis (17,900 cells/μL) with increased neutrophils (76.0%). A skin biopsy from her jaw showed spongiform changes with subcorneal pustules, and perivascular and diffuse dermal infiltration of lymphocytes and eosinophils. Based on the above findings, a diagnosis of AGEP was made. The drugs were stopped and she was treated with 40 mg/day of prednisolone. After 14 days, the cutaneous eruption had resolved.

Three months after resolution, we performed a 48 hour closed patch test. Both Eve A (1% and 10% petrolatum) and allylisopropylacetylurea (1% and 10% petrolatum) showed a positive reaction (++, International Contact Dermatitis Research Group scale) manifesting as an erythema with numerous vesicles in the patch test area. Patch tests using Children's Bufferin and other components of Eve A were negative. A skin biopsy taken from the positive patch test area at 48 hours showed subcorneal vesicles with lymphocytes (figure 1B). Drug lymphocyte stimulation tests performed four months after resolution showed a positive reaction for both Eve A and allylisopropylacetylurea, with a stimulation index of 3.19 and 2.51, respectively.

Britschgi et al. suggested that the patch test reactions appeared to mirror the acute phase of an AGEP reaction [2]. Furthermore, they analyzed drug-specific T cells generated from three patients with AGEP and their cytokine profiles in vitro [3]. From their study, they proposed that drug-specific CD4+ T cells infiltrate the epidermis and release high amounts of IL-8, a neutrophil-attracting chemokine, resulting in neutrophilic inflammation. In the present case, an erythematous eruption with subcorneal vesicles was seen in the positive patch test area. In addition, the expressions of CD4, CD8 and IL-17 were investigated by immunohistochemistry. Cells in the vesicles were almost all positive for IL-17 and CD4 (figures 1C, D), while most cells were negative for CD8. Considering the possibility that the patch test reaction mirrors the acute stage of AGEP, we speculate that IL-17- and CD4-positive cells appear before the formation of pustules.

Disclosure

Financial support: none. Conflict of interest: none.

References

1 MM Speeckaert, R Speeckaert, J Lambert, L. Brochez Acute generalized exanthematous pustulosis: an overview of the clinical, immunological and diagnostic concepts Eur J Dermatol 2010; 20: 425-433.

2 M Britschgi, UC Steiner, S Schmid et al. T-cell involvement in drug-induced acute generalized exanthematous pustulosis J Clin Invest 2001; 107: 1433-1441.

3 M Britschgi, W.J. Pichler Acute generalized exanthematous pustulosis, a clue to neutrophil-mediated inflammatory processes orchestrated by T cells Curr Opin Allergy Clin Immunol 2002; 2: 325-331.