Acute generalized exanthematous pustulosis induced by hydroxychloroquine

ARTICLE

Auteur(s) : A. MARTINS, L.C. LOPES, M.J. PAIVA LOPES, J.C. RODRIGUES

Department of Dermatology. Hospital do Desterro, Rua Nova do Desterro, 1169-100, Lisbon. Portugal.
<andreagomesmartins@hotmail.com>

Acute Generalized Exanthematous Pustulosis (AGEP) is a severe eruption, usually drug related. It is characterized by high fever and numerous small, primarily nonfollicular sterile pustules, arising within large areas of edematous erythema. The lesions appear on the intertriginous areas or on the face. Patients report pruritus or local burning sensations [1]. Use of hydroxychloroquine has been reported as a rare cause of AGEP, with 14 cases described in the literature [2, 3]. Other antimalarial agents have rarely have been associated with AGEP [2].
We report a case of hydroxychloroquine-induced AGEP in a 51-year-old white woman, without personal or familiar history of psoriasis, who presented with generalized pustules and erythematous plaques. She had started Deflazacort 60 mg daily two months before and hydroxychloroquine 400 mg daily 2 weeks before for rheumatoid arthritis under investigation.
The eruption was predominantly on the trunk and proximal limbs, accompanied by pruritus, without fever. The mucous membranes were not involved. Skin examination revealed numerous nonfollicular, < 5 mm pustules over the trunk and limbs (figure 1), coalescing in erythematous plaques on the face, neck, trunk and limbs. Some pustules developed erythematous collarettes. The lesions evolved with superficial desquamation.
Marked leukocytosis with an elevated neutrophil count and an elevated erythrocyte sedimentation rate was seen. Electrolyte levels and results of urinalysis, renal and liver function tests were normal. Skin biopsy revealed subcorneal spongiform pustules, edema of the papillary dermis and a mixed inflamatory infiltrate with exocytosis of neutrophils.
Hydroxychloroquine was discontinued at the initial presentation and she was treated with systemic corticosteroids. The lesions were cleared 3 weeks later.
A review of the literature shows 3 case reports of AGEP induced by hydroxychloroquine very similar to our case [2, 4], except for one of them which was also associated with puvatherapy [4].There are reports of positive patch tests to drugs in patients with AGEP, suggesting the involvement of T cells [5]. AEP seems to be a clinical and pathological entity distinct from acute pustular psoriasis and the main differences between them are the drug history and the acuteness of the disease in AGEP [1]. Its incidence has been understimated, as many cases may have been confused with pustular psoriasis [6]. Other diseases can also be confused with AGEP, for example, some exanthematous drug eruptions, Toxic Epidermal Necrolysis (TEN) and Drug reactions with Eosinophilia and Systemic Symptoms (DRESS) [1].
In an important 16 year review of 207 cases of severe pustular eruptions notified to the French Pharmacovigilance Centre, hydroxychloroquine was the third medication associated to AGEP and death ocurred in 4 cases (2%). Only recently has this important side effect been reported in the «adverse events» section of the summary of product characteristics of hydroxychloroquine. Because it is essential to discontinue the causative drug as soon as possible if a pustular eruption occurs, the notification of side effects by physicians to pharmacovigilance centres is important to public health dissemination of warnings [3].
Diagnosis of AGEP can be difficult because hydroxychloroquine has been reported to exacerbate psoriasis, which can appear clinically similar to AGEP.Given the common use of hydroxychloroquine for numerous dermatological conditions, it is important to remember this rare, but severe, side effect. n

1. Bolognia JL, Jorizzo JL, Rapin RP. Dermatology, Mosby edition 2003; volume 1: 341.

2. Evans CC, Bergstresser PR. Acute Generalized Exanthematous Pustulosis precipitated by Hydroxychloroquine. J Am Acad Dermatol 2004; 50(4): 650-1.

3. Saissi EH, Beau-Salinas F, Jonville-Béra AP, Lorette G, Autret-Leca E. Médicaments Associés à La Survenue d’Une Pustulose Exanthématique Aigue Généralisée. Ann Dermatol Venereol 2003; 130: 612-8.

4. Bonnetblanc JM, Combeau A, Dang PM. Pustulose Exanthématique Aigue Généralisée Photodéclenchée par L’Association Hydroxychloroquine-Puvathérapie. Ann Dermatol Venereol 1995; 122: 604-5.

5. Taberner R, Puig L, Gilaberte M, Alomar A. Acute Generalized Exanthematous Pustulosis Induced By Terbinafine. Eur J Dermatol 2003; 13: 313-4.

6. Roujeau JC, Bioulac-Sage P,Bourseau C, Guillaume JC, Bernard P, Lok C, et al. Acute Generalized Exanthematous Pustulosis: analysis of 63 cases. Arch Dermatol 1991; 127: 1333-8.