Letters to Dermatology

The association of chloroquine and proguanil is widely used for antimalarial prophylaxis in Plasmodium falciparum – endemic countries with limited to moderate chloroquine resistance [1]. We report the 1st case of acute generalized exanthematous pustulosis (AGEP) due to this drug combination. A 34-year-old woman with a previous history of maculopapular skin rash induced by mefloquine in 1995 was referred to our department in February 1996 because of the rapid onset of a generalized eruption of 2 days’ duration. The eruption began on the face and trunk and subsequently spread to the limbs. It consisted of a diffuse erythema with multiple superficial nonfollicular pustules. A few target lesions were present on the limbs. The rash was highly pruritic. There was no mucosal involvement. She was slightly pyrexial (38°C). She had been taking chloroquine (100 mg/day) and proguanil (200 mg/day) for 10 days as an antimalarial prophylaxis during a travel across Togo (West Africa). She had not been given other medication in the past 3 months and had no history of psoriasis. Laboratory investigations disclosed hyperleukocytosis (22.7× 10/l) with polynucleosis (20×10/l) and eosinophilia (1×10/l). Histopathologic examination of a skin biopsy specimen showed multilocular spongiform subcorneal pustules containing polymorphonuclears and eosinophils. Chloroquine and proguanil were stopped. The eruption resolved after 8 days with no further recurrence. Epicutaneous tests performed 6 months later with chloroquine, proguanil and mefloquine were negative. AGEP is a recently described entity [2] mostly related to drugs, principally antibiotics (beta-lactams and macrolides). Four cases of AGEP due to hydroxychloroquine have been previously reported, the last in 1995 [3] but no case of AGEP induced by chloroquine or proguanil has ever been published. Chloroquine, an amino-4 quinoleine has a few cutaneous side effects apart from pruritus (which may occur in up to 75% of patients) and exacerbation of psoriasis [4, 5]. Proguanil and cycloguanil, two biguanide derivatives, may induce mouth ulcers [6] without any particular skin side effects. They are seldom used alone and mostly given in combination with chloroquine. Finally, mefloquine, an amino-alcohol, can produce life-threatening adverse cutaneous reactions [7] but has no known cross-hypersensitivity with chloroquine. In our case, it was not possible to distinguish between chloroquine and proguanil as the culprit of the AGEP and future antimalarial prophylaxis was further complicated by skin reaction to mefloquine. Reports of severe cutaneous toxicity in patients taking antimalarials and possible cross-reactions are highly warranted.