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PubMed2004

Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial.

BACKGROUND: Increasing resistance to sulfadoxine-pyrimethamine is leading to a decline in its effectiveness. We aimed to assess the safety profile of chlorproguanil-dapsone (CD), and to compare the safety and efficacy of this drug with that of sulfadoxine-pyrimethamine (SP) as treatment for uncomplicated falciparum malaria. METHODS: We undertook a double-blind, randomised trial in 1850 consecutively recruited children with uncomplicated falciparum malaria, pooling data from five African countries. Analyses were based on all randomised patients with available data. FINDINGS: CD was significantly more efficacious than SP (odds ratio 3.1 [95% CI 2.0-4.8]); 1313 patients (96%) given CD and 306 (89%) given SP achieved acceptable clinical and parasitological response by day 14. Adverse events were reported in 46% and 50% of patients randomised to CD and SP, respectively (treatment difference -4.4%, [95% CI -10.1 to 1.3]). Haemoglobin in the CD group was significantly lower than in the SP group at day 7, a difference of -4 g/L (95% CI -6 to -2). Mean day 14 haemoglobin (measured only for the small number of patients whose day 7 data caused concern) was 94 g/L (92-96) and 97 g/L (92-102) after CD and SP, respectively. Glucose-6-phosphate dehydrogenase deficient patients on CD had greater odds than those on SP of having a fall of 20 g/dL or more in haemoglobin when baseline temperature was high. Methaemoglobinaemia was seen in the CD group (n=320, mean 0.4% [95% CI 0.4-0.4]) before treatment, 4.2% (95% CI 3.8-4.6) (n=301) at day 3, and 0.6% (0.6-0.7) (n=300) at day 7). INTERPRETATION: CD had greater efficacy than SP in Africa and was well tolerated. Haematological adverse effects were more common with CD than with SP and were reversible. CD is a useful alternative where SP is failing due to resistance.

Africa↗
PubMed1996

Dapsone in prevention of recurrent neutrophilic eccrine hidradenitis.

Neutrophilic eccrine hidradenitis has been described in patients with acute myelogenous leukemia and other malignant diseases, usually during chemotherapy. We describe a 46-year-old man with Hodgkin's disease in whom neutrophilic eccrine hidradenitis developed after each of the first two treatments with lomustine. Dapsone, 100 mg daily, was initiated 48 hours before the patient's third treatment with lomustine and was continued for 14 days. This regimen was successful in suppressing the reaction during the first course and three subsequent courses of lomustine.

Antineoplastic Agents↗
PubMed1996

Widespread pruritic plaques in a patient with subacute cutaneous lupus erythematosus and hypocomplementemia: response to dapsone therapy.

We describe a patient with subacute cutaneous lupus erythematosus, widespread pruritic papulosquamous plaques, and hypocomplementemia. Skin biopsy specimens revealed liquefaction degeneration and colloid bodies and dyskeratotic cells in basal and suprabasal layers. An immunofluorescence study revealed deposits of IgG, IgM, and C3 at the dermalepidermal junction in a bandlike pattern, and particulate IgG deposition in the basal and suprabasal layers. Treatment with prednisolone (15 mg/day), chloroquine phosphate (200 mg/ day), cyclosporine (5 mg/kg daily), and gold (10 mg/day) failed to reduce pruritic plaque formation, and pulse methylprednisolone therapy led to only a transient remission. Clinical exacerbations correlated with a decrease in complement levels. The disease was successfully controlled with dapsone (75 mg/day) and prednisolone (25 mg/day).

Adult↗
PubMed1998

Folliculitis spinulosa decalvans: successful therapy with dapsone.

A 27-year-old male patient presented with scaly erythema and crusts on the scalp. Since birth, he suffered from dry skin and inflammation of the eyelids. Scarring alopecia was noticed in some regions of his scalp. Folliculitis spinulosa decalvans was diagnosed. Therapy with isotretinoin and topical corticosteroids was without effect. In contrast, 100 mg of Dapsone per day led to resolution of the inflammatory signs. This enabled him to cover the disfiguring scarring alopecia with a permanent hairpiece. His condition has been stable after 18 months without the enlargement of the scarred alopecic areas.

Adrenal Cortex Hormones↗
PubMed2001

A spectrophotometric method for the determination of metoclopramide HCl and dapsone.

A rapid, sensitive and selective spectrophotometric method has been developed for the quantitative determination of metoclopramide hydrochloride (MCP) and dapsone (DAP) in both pure and dosage forms. The method is based on the diazo coupling reaction of the drugs with a new coupling agent, dibenzoyl methane in an alkaline medium. The resulting coloured azo dyes exhibit maximum absorption at 440 nm for MCP and at 470 nm for DAP with a molar absorptivity of 2.85x10(4) and 1.71x10(4) l mol(-1) cm(-1) for MCP and DAP, respectively. All variables have been optimized. No interferences were observed from excipients and the validity of the method was tested against reference method.

Anti-Infective Agents↗
PubMed2001

Immunohematotoxicity studies with combinations of dapsone and zidovudine.

We investigated the immunohematoxicities of the antiparasitic drug dapsone (DDS) and the antiretroviral drug zidovudine (ZDV, AZT) given alone or in combination in BALB/c mice. DDS is used for prophylaxis and treatment of Pneumocystis carinii infection in AIDS patients. We examined the impact of concurrent administration of these drugs on the immune and hematopoietic systems because DDS causes hematotoxicity and ZDV therapy results in bone marrow toxicity. Daily oral administration of DDS at 25 and 50 mg/kg for 28 days caused a slight anemia, marked methemoglobinemia, reticulocytosis, and a moderate leukopenia (P < 0.01 for all parameters) but had no discernible effect on platelet count. In DDS-treated mice, the proliferative response of splenic T cells to concanavalin A was > or = 35% higher than that manifested by splenocytes from vehicle-treated control mice. ZDV at 240 and 480 mg/kg was not immunosuppressive but caused low-grade macrocytic anemia, thrombocytosis, and neutropenia; these effects were drug dose-dependent and statistically significant (P < 0.01). Concurrent administration of DDS and ZDV augmented the severity of ZDV-mediated macrocytic anemia, and 7 of 12 (58%) mice did not survive treatment with the high doses of DDS and ZDV (50 and 480 mg/kg, respectively). On the other hand, co-administration of ZDV mitigated DDS-induced methemoglobinemia and the DDS-associated elevation in lymphoproliferative response. These data suggest interaction between DDS and ZDV in mice and indicate a need for caution in using DDS as long-term therapy in AIDS patients receiving ZDV.

AIDS-Related Opportunistic Infections↗
PubMed1989

Design and in vitro evaluation of dapsone-loaded micropellets of ethyl cellulose.

A controlled-release dosage form was manufactured by dispersing ethyl cellulose sol in acetone into a medium of mineral oil. Dapsone was used as the model drug. The powdered drug was dispersed in the ethyl cellulose sol, and the formulation variables affecting the production of the discrete and spherical micropellets and their size distribution were investigated. The percentage of SPAN 80 in the formulation affected the yield and physical properties of the micropellets. The in vitro drug release followed first-order diffusion-controlled dissolution. More than 85% of the drug was released over 5 hr for all formulation batches, with delayed release over the drug dissolution profile.

Capsules↗
PubMed1996

Recurrent annular erythema with purpura: a new variant of leucocytoclastic vasculitis responsive to dapsone.

Annular lesions are rarely reported in the clinical spectrum of leucocytoclastic vasculitis, except in the acute haemorrhagic oedema of the skin. We report three patients who suffered from an extraordinary recurrent annular dermatitis, for 4 years in one case and for decades in the other two. The eruption was characterized by purpuric lesions that had a centrifugal evolution, creating target- or polycyclic patches disseminated on the limbs and trunk. The patients' general condition remained excellent during the attacks. All lesions spontaneously disappeared within 2 weeks, but recurred monthly. In all three cases, the histological changes were consistent with leucocytoclastic vasculitis. One patient had ulcerative colitis and another had a benign immunoglobulin A (IgA) monoclonal gammopathy. These two patients showed a good response to dapsone therapy. This dermatosis probably represents a new and rare variant of leucocytoclastic vasculitis.

Dapsone↗
PubMed1997

Acne fulminans and erythema nodosum during isotretinoin therapy responding to dapsone.

Acne vulgaris is very common, 85% of teenagers being affected at any one time. In most cases, the disease is mild and patients do not present to the dermatologist. Most are instead treated with over-the-counter products and conventional treatment such as peeling agents or topical and systemic antibiotics. Isotretinoin has revolutionized the treatment of severe acne unresponsive to oral antibiotics. Explosive and very severe acne such as pyoderma faciale, acne conglobata and acne fulminans are rare, the features that distinguish acne fulminans from the other conditions being systemic upset with fever, joint pain, malaise and leucocytosis, while there have been two reports of the condition associated with erythema nodosum. The recommended treatment for acne fulminans is a combination of oral steroids and systemic antibiotics, isotretinoin probably not being the treatment of choice. We now report a patient who developed acne fulminans and erythema nodosum within 3 weeks of starting isotretinoin and then responded to dapsone without oral steroids.

Acne Vulgaris↗
PubMed2001

Dapsone in rosacea fulminans.

Rosacea fulminans is a rare disease with female predominance characterized by abrupt onset of pustules, papules, and confluent nodules on the face. The conventional treatment consists of systemic glucocorticoids and isotretinoin. We present the case of a 56-year-old woman with a marked facial papulopustular eruption that had followed an initial period of severe seborrhoea. Conventional treatment produced no clear improvement. Dapsone treatment achieved complete healing in 5 weeks.

Administration, Oral↗
PubMedDate not supplied

Childhood pemphigus vulgaris treated with dapsone: a case report.

A 5-year-old boy developed hemorrhagic mucocutaneous blisters on various parts of the body leading to fetor, dysphagia, dysuria, anal pruritus, pain on defecation, and weight loss. The histopathology showed the classic features of pemphigus vulgaris, and direct immunofluorescence showed intercellular deposition of IgG and C3 in the epidermis. Circulating pemphigus antibodies were also detected. He was treated with a combination of systemic prednisone and dapsone which induced a rapid remission and controlled the disease well. He has been in remission for 1 year and 7 months with no immunosuppressive therapy except for the use of topical agents for the oral lesions. An adjuvant to corticosteroids has been used only once before in children with pemphigus vulgaris under the age of 12 years. This is the third and the youngest child in the literature treated in this fashion.

Child, Preschool↗
PubMed1977

Experimental studies of the potentiation of proguanil and pyrimethamine by dapsone using Plasmodium berghei in white mice.

An accurate system with stringent criteria has been established to test antimalarial drugs and drug combinations against Plasmodium berghei in mice. Minimum effective doses for a number of antimalarial drugs have been determined when used in this system. Considerable potentiation of the activity of pyrimethamine and to a somewhat less extent of proguanil by dapsone has been demonstrated. The need to extend studies of these combinations to the parasites of human malaria is discussed in terms of establishing a safe chemoprophylactic regime in the presence of drug-resistant strains of parasites.

Animals↗
PubMed2006

Pemphigus foliaceus induced by radiotherapy and responsive to dapsone.

Pemphigus foliaceus induced by ionizing radiation therapy is a rare condition. We describe the case of a 70-year-old female who developed pemphigus foliaceus after X-ray treatment for an adenocarcinoma of the left breast. The eruption started at the portal of irradiation and only subsequently spread to other cutaneous areas. Mucosal membranes were not affected. Skin lesions were completely responsive to dapsone therapy.

Adenocarcinoma↗
PubMed1996

In-vitro activity of macrolides alone and in combination with artemisin, atovaquone, dapsone, minocycline or pyrimethamine against Cryptosporidium parvum.

The anticryptosporidial activity of four macrolides alone and in combination with other antimicrobial agents was investigated against ten clinical isolates of Cryptosporidium parvum recovered from stools of AIDS patients. The susceptibility tests were performed by inoculation of the protozoa on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of azithromycin, clarithromycin, roxithromycin, spiramycin, alone or in combination with artemisin, atovaquone, dapsone, minocycline or pyrimethamine. Most of the agents had an inhibitory effect on parasite growth, but only at high concentrations. No agent was able to inhibit parasite growth completely, even at the highest concentrations used. The more effective agents, azithromycin, clarithromycin, roxithromycin, minocycline and pyrimethamine, produced no more than a 13.1-27.8% reduction in oocyst count and no more than a 15.1-35.7% in schizont count. Positive interaction was clearly demonstrated when macrolides were tested in combination with minocycline or pyrimethamine.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

A case of acute dapsone poisoning: toxicological data and review of the literature.

A case of nonfatal, acute poisoning following the ingestion of an undetermined amount of dapsone (DDS) in a 49-year-old woman is presented. The clinical features were dyspnea and deep cyanosis. Methemoglobinemia was 39.0% on admission. DDS was identified and quantitated in blood samples taken on the third day (sample A) and fifth day (sample B) in the hospital using a high-performance liquid chromatographic technique with diode-array detection. DDS concentrations were 26.99 and 8.40 micrograms/mL in samples A and B, respectively. Results are discussed in the light of an extensive review of the literature (1950-1993) available on DDS poisonings.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

A rapid, specific, and sensitive method for the determination of acetylation phenotype using dapsone.

An original, simple, specific, and rapid high-performance liquid chromatography assay for the determination of dapsone and monoacetyldapsone in human plasma is presented. The procedure consists of extracting the drugs and the internal standard (phenacetin) from 1 mL plasma with ethyl ether at alkaline pH. A liquid chromatograph equipped with a reversed-phase 5-microm C8 analytical column was used. The drugs were eluted with a mixture of water and methanol (70:30, v/v). Flow rate and wavelength were set at 1 mL/min and 286 nm, respectively. The precision, linearity, and limit of quantitation of the method were within acceptable limits. The method was considered adequate and has been used for the determination of the acetylator phenotype in population studies.

Acetylation↗
PubMed1997

Skin involvement with Pneumocystis despite dapsone prophylaxis: a rare cause of skin nodules in a patient with AIDS.

Pneumocystis carinii pneumonia is among the most common life-threatening opportunistic infections that occurs in those with HIV infection and a depleted absolute CD4+ T-lymphocyte count. Fortunately, with the advent of effective prophylaxis, this AIDS-defining complication is diminishing. Rarely, Pneumocystis carinii (P carinii) occurs outside the lungs, typically in the setting of prophylaxis with aerosolized pentamidine or no prophylaxis at all. This is the case of a man with advanced AIDS and bilateral hyperpigmented axillary nodules secondary to cutaneous pneumocystosis. Unlike most other examples of extrapulmonary P carinii, dissemination occurred without documented pulmonary infection and despite prophylaxis with high-dose dapsone. A biopsy should be performed on unusual cutaneous lesions in the setting of advanced AIDS because unexpected findings may have important therapeutic implications.

AIDS-Related Opportunistic Infections↗