Comparative study of efficacy and safety of hydroxychloroquine and chloroquine in polymorphic light eruption: a randomized, double-blind, multicentric study.

BACKGROUND: Polymorphic light eruption is the most common photodermatosis characterized by nonscarring, pruritic, erythematous papules and plaques. AIM: To evaluate the efficacy and safety of hydroxychloroquine in comparison with chloroquine in patients suffering from polymorphic light eruption. METHODS: This was a randomized, double-blind, comparative, multicentric study conducted at two centers. This study enrolled 68 (58.1%) males, 49 (41.8%) females whose ages ranged from 18-73 years and average weight was 57.89 +/- 8.27 kg. A total of 117 patients were enrolled in the study. Out of 117 patients, 63 patients were randomized to receive hydroxychloroquine tablets 200 mg twice daily for the first month and 200 mg once daily for the next month. Similarly, 54 patients were randomized to receive chloroquine tablets 250 mg twice daily for the first month and 250 mg once daily for the next month. The total duration of therapy for both the study arms was two months. The severity and frequency of burning, itching, erythema and scaling were evaluated at predetermined intervals (at baseline, after four, eight and 12 weeks of therapy). RESULTS: A significant reduction in severity scores for burning, itching and erythema was observed in patients treated with hydroxychloroquine than with chloroquine (P P = 0.229). The good to excellent response was reported by 68.9% of the patients who received hydroxychloroquine and by 63% of the patients who received chloroquine. The adverse events reported were mild to moderate and none of the patients reported any serious adverse events or ocular toxicity in this study. CONCLUSION: Hydroxychloroquine was found to be significantly more effective than chloroquine in the treatment of polymorphic light eruption and can be used safely in the dosage studied in such patients with little risk of ocular toxicity.

Dapsone therapy for malaria during pregnancy: maternal and fetal outcomes.

The need to consider using dapsone in pregnant women for its antimalarial activity is becoming greater in areas where Plasmodium falciparum resistance to chloroquine and pyrimethamine-sulfadoxine is rapidly increasing. Dapsone in combination with other antimalarials might provide a valuable alternative for both treatment and prophylaxis. This review assesses the clinical pharmacology of dapsone and its adverse drug reactions in relation to haemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency, blood dyscrasias and methaemoglobinaemia. Studies are summarised reporting its use in leprosy, dermatological and other conditions, and malaria, in relation to maternal and infant outcomes. A total of 924 pregnancies were identified during which dapsone therapy was taken. Only limited data are available and this precludes a meaningful quantitative benefit-risk analysis. Mild degrees of haemolysis consistently occur with continued therapy, although adverse effects may be less likely with intermittent treatment, as most reported adverse effects have occurred with long-term use of dapsone. There are a number of gaps in knowledge where more data are needed. These include no data on pharmacokinetics in pregnancy and whether these are altered with co-administration of chlorproguanil. Potential complications in women with severe anaemia are unknown and there is no information on haemolytic effects in women or the fetus with G6PD deficiency. The use of dapsone in HIV-infected women in malarious areas could carry increased risks because of the immunosuppressive actions of the drug. Trials of dapsone therapy in pregnancy should be considered in malarious areas where there is good reason for its deployment. Controlled trials have provided data on maternal tolerance, and dapsone in combination with other antimalarial drugs can offer clear benefit in terms of improved birthweight. The use of dapsone combinations should be considered when no good alternative is available and the threat of malaria is the greater risk.

Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention.

Agranulocytosis is a rare, severe and unpredictable idiosyncratic reaction associated with drug therapy that can lead to life-threatening illness. Typically, the patient presents with a fever and evidence of infection 1-3 months after initiation of drug administration with a neutrophil count below 0.5x10(9) l. Of the drugs linked with this disease, aminopyrine, dipyrone, clozapine, anti-thyroid agents, sulphonamides and dapsone are the best documented. Generally, agranulocytosis is associated with older individuals (>60 years) and those of non-Caucasian descent. The incidence of agranulocytosis in subjects taking oral dapsone in combination with maloprim for malaria is 1 -- 10-20,000 while leprosy patients treated with dapsone exhibit virtually zero risk of agranulocytosis. However, dapsone is unusual in that during the rare but severe inflammatory disease, dermatitis herpetiformis (DH), the risk of agranulocytosis is multiplied between 25 and 33 fold compared with normal patients. It is conceivable that dapsone might exhibit a similar risk in coeliac disease, a condition related to DH. As dapsone plasma levels in DH subjects can be high (2-10 microg/ml) the increased risk of agranulocytosis could be related to drug dosage, or increased immune responsiveness. The high risks in DH patients probably necessitate monitoring of neutrophil cell population in the first 3 months of therapy, while topical usage of the drug in acne treatment in otherwise healthy patients predominantly below the age of 25 is at the opposite end of the risk scale, probably as low as 1 in 10-20,000 patients.

Adverse effects of chemotherapeutic agents used in tropical medicine.

Traditionally, many of the chemotherapeutic agents used in tropical medicine have possessed limited efficacy and serious adverse effects. This scenario has been revolutionised by the introduction into clinical parasitology of the benzimidazole compounds, praziquantel (and other schistosomicidal agents) and ivermectin for helminthiases, and the 5-nitroimidazoles for protozoan infections. An effective armamentarium against Plasmodium spp. infections, especially P. falciparum, is receding as widespread multiple drug resistance becomes commonplace. Although management of several more exotic parasitic infections, including trypanosomiasis, leishmaniasis and onchocerciasis remains unsatisfactory, several newer and relatively non-toxic preparations (including eflornithine and ivermectin) are now available, and offer optimism. However, there remains a very long way to go before a single preparation is available to combat all major protozoan and/or helminthic infections; such an agent would also need to be 100% effective when given as a single dose, safe not only in the healthy adult but also during pregnancy and lactation, stable at high ambient temperature and relatively low in cost.