Administration Of Dapsone Research Articles

Efficacité de la dapsone dans deux cas de lupus miliaire disséminé de la face

Lupus miliaris disseminatum faciei (LMDF) is a rare, chronic and benign facial dermatosis that is regarded as an enigmatic diagnostic and therapeutic entity with spontaneous regression in 2 to 4 years leaving pock-like scars. We present two cases of LMDF: the first concerns a 46-year-old woman who 6 months earlier presented a papular and pustular eruption on her face leaving small pitted scars. The inefficacy of treatment with cyclines, metronidazole and crotamiton as well as the clinical and histological examination results allowed a diagnosis of lupus miliaris disseminatus faciei to be made. The patient was placed on dapsone 100mg per day, which led to a remarkable improvement in the second week, but with depressed scars. The second case concerned an 18-year-old man who for 3 months had been presenting red-brown papules of the face that were resistant to cyclines and to topical retinoids and caused scarring. This clinical aspect, consolidated by the histological result, allowed the diagnosis of LMDF to be made. Administration of dapsone 100mg per day resulted in improvement from the first month, although there were residual cupuliform scars. Dapsone appears to be effective in the management of this disease, as illustrated in our two case reports. However, further studies are needed to confirm these results.

Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury

After spinal cord injury (SCI), a complex cascade of pathophysiological processes increases the primary damage. The inflammatory response plays a key role in this pathology. Recent evidence suggests that myeloperoxidase (MPO), an enzyme produced and released by neutrophils, is of special importance in spreading tissue damage. Dapsone (4,4'-diaminodiphenylsulfone) is an irreversible inhibitor of MPO. Recently, we demonstrated, in a model of brain ischemia/reperfusion, that dapsone has antioxidant, antiinflammatory, and antiapoptotic effects. The effects of dapsone on MPO activity, lipid peroxidation (LP) processes, motor function recovery, and the amount of spared tissue were evaluated in a rat model of SCI. MPO activity had increased 24.5-fold 24 hr after SCI vs. the sham group, and it had diminished by 38% and 19% in the groups treated with dapsone at 3 and 5 hr after SCI, respectively. SCI increased LP by 45%, and this increase was blocked by dapsone. In rats treated with dapsone, a significant motor function recovery (Basso-Beattie-Bresnahan score, BBB) was observed beginning during the first week of evaluation and continuing until the end of the study. Spontaneous recovery 8 weeks after SCI was 9.2 ± 1.12, whereas, in the dapsone-treated groups, it reached 13.6 ± 1.04 and 12.9 ± 1.17. Spared tissue increased by 42% and 33% in the dapsone-treated groups (3 and 5 hr after SCI, respectively) vs. SCI without treatment. Dapsone significantly prevented mortality. The results show that inhibition of MPO by dapsone significantly protected the spinal cord from tissue damage and enhanced motor recovery after SCI.

Drug-Induced Bullous Pemphigoid: Expect the Unexpected

ABSTRACT Several systemic factors are known to contribute oral diseases. At same time, the drugs used for the treatment of such systemic diseases itself might cause spectrum of clinical conditions. The identification of a positive agent becomes difficult when the patient is on multiple drug regimens. Reporting a case of an elderly female patient, who was on regular medication for hypertension over 5 years, developed generalized bullous eruptions in couple of weeks after being treated with Ciprofloxacin and Paracetamol for urinary tract infection. The dermal lesion worsened with administration of Dapsone.

Very late relapse of dapsone-induced methaemoglobinemia

Dapsone, a sulfone active against a wide range of bacteria, is mainly used for Mycobacterium leprae. Moreover, because of its immunosuppressive effect, it is used for many auto-immune diseases [1]. Methaemoglobinemia is an expected adverse drug reaction of dapsone, seldom symptomatic. Long-term administration of dapsone at standard doses (100 mg/day) results in methaemoglobinemia in about 15% of patients [2]. When symptomatic (dyspnea, cyanosis, neurological disorders), methaemoglobinemia is treated with methylene blue (1–2 mg/kg) [3]. Rebounds have been described after dapsone withdrawal, with a maximum delay of 64 h [4]. We report a case of dapsone-induced methaemoglobinemia which relapsed 10 days after drug withdrawal. A 25-year-old woman was diagnosed with systemic lupus erythematosus in January 2009. Organs involved were skin and joints, and hydroxychloroquine alone was prescribed. In October 2009, she developed a bullous dermatitis and dapsone was added to hydroxychloroquine on 26 October 2009. About 1 month later, on 24 November, she was admitted to the hospital for severe dyspnea. Physical examination was normal except for cutaneous cyanosis. Chest computed tomography and electrocardiogram were normal. Arterial blood gas analysis showed pH: 7.63, PaO2: 110 mmHg, PaCO2: 15 mmHg, haemoglobin: 11 g/dL, SaO2: 99.1%; methaemoglobin: 17%. Methylene blue (2 mg/kg) was injected intravenously. Twenty minutes later, the patient was asymptomatic and arterial methaemoglobin was 4%. Dapsone was discontinued and the patient left the hospital on 26 November. Ten days later, she consulted for relapse of dyspnea. Arterial blood gas analysis showed methaemoglobin at 14%. No symptomatic treatment was done and methaemoglobin rate decreased spontaneously to 5% the next day. Hydroxychloroquine was stopped. The compliance of the patient was not doubtful, and no other cause of intoxication causing methaemoglobinemia was found. Methaemoglobinemia in dapsone intoxication is due to the ability of dapsone hydroxylamine, a metabolite of the drug, to react with haemoglobin (Fe) to form methaemoglobin (Fe) [5]. Methaemoglobin is unable to bind dioxygen, which results in functional anaemia. The clinical G. Moulis Service de Medecine Interne, Centre Hospitalier Universitaire de Toulouse, Universite Paul-Sabatier, Toulouse, France e-mail: gmoulis@hotmail.com

The effect of ethyl pyruvate on dapsone-induced methemoglobinemia in rats

Introduction. Dapsone induces methemoglobinemia by oxidant stress; ethyl pyruvate (EP) is an antioxidant and radical oxygen species scavenger. This study was conducted to evaluate the effect of EP on methemoglobinemia induced by dapsone. Methods. Male Sprague–Dawley rats were divided into an EP group and a control group. Rats in the EP group were administered dapsone (40 mg/kg) via the stomach and then EP (40 mg/kg) was injected intraperitoneally. Rats in the control group were administered dapsone followed by Ringer's lactate solution. Methemoglobin concentrations were measured at 90, 180, and 360 min after dapsone administration. Results. Methemoglobin concentrations were not different between time points in the control group. However, in the EP group, the methemoglobin concentrations were significantly lower than those of the control group at 90 and 180 min, but this difference was no longer apparent at 360 min. Conclusion. A single intraperitoneal dose of EP was able to reduce methemoglobinemia induced by dapsone for a short period of time, but this effect was not sustained.

IgG/IgA pemphigus with dyskeratotic acantholysis and intraepidermal neutrophilic microabscesses

Herpetiform vesicles and erythema with erosion developed on the trunk of a 48-year-old Japanese man. Acantholysis was observed in the spinous layer of the lesional epidermis and direct immunofluorescence revealed cell surface deposition of immunoglobulin IgG and C3. Indirect immunofluorescence could not detect circulating anti-cell surface antibodies. Immunoblot analysis detected neither anti-desmoglein (Dsg)1 antibody nor anti-Dsg3 antibody. Enzyme-linked immunosorbent assay could detect IgG and IgA anti-Dsg1 antibodies and IgA anti-Dsg3 antibody, in addition to a gray zone titer of IgG anti-Dsg3 antibody. Intraepidermal neutrophilic infiltration with neutrophilic microabscesses and intense dyskeratotic cells were histopathologically characteristic in this case. Skin lesions improved within 1 month and remission has continued for 9 years under oral administration of dapsone.

Disulone et hépatosidérose

Disulone (dapsone + iron oxalate) is a sulfone used in the treatment of numerous skin diseases. We report two cases of hepatosiderosis secondary to long-term administration of Disulone. Case n degrees 1. A 51-year-old man was treated with Disulone for a neutrophilic skin disease. After 17 years of treatment, elevated serum ferritin and free iron with hemolysis were found. Liver biopsy confirmed hepatosiderosis. A diagnosis of genetic hemochromatosis was ruled out by the absence of C282Y mutation of the HFE gene. Case n degrees 2. A 52-year-old man receiving Disulone for dermatitis herpetiformis for 25 years presented elevated serum ferritin and free iron with hemolysis. Hepatic iron overload was confirmed by liver biopsy. The absence of C282Y mutation (HFE gene) ruled out a diagnosis of genetic hemochromatosis. In our two cases, hepatosiderosis was noted after long-term administration of Disulone. This complication has been reported only rarely. In murine models, a relationship was found between prolonged administration of dapsone and hepatic iron overload as revealed by hemolysis. Although it is difficult to extrapolate this relationship to humans with any certainty, our patients had also chronic hemolysis and iron overload secondary to administration of Disulone. Moreover in France, dapsone is marketed in combination with iron oxalate, with the attendant risk of iron overload. These cases raise the question of the need for serum ferritin analysis during Disulone therapy.

Two cases of eosinophilic pustular folliculitis with atypical clinical features

Eosinophilic pustular folliculitis(EPF) is characterized by recurrent crops of pruritic folliculocentric papulopustules that occur mainly on face, trunk and extremities of young men. The main histologic feature is the infiltration of eosinophils into the follicular epidermis and adjacent dermis. Herein, we report two cases of EPF, one in a 35-year-old female and the other in a 58 year-old man. Histopathologic findings of the skin biopsy taken from 2 patients represented the heavy infiltration of eosinophils around and in the hair follicles, sebaceous glands and blood vessels. We could see beneficial responses by administration of dapsone in both cases.

Brown recluse spider bite to the eyelid

Purpose To present a photographically documented case of a known brown recluse spider bite to the eyelid. Design Interventional case report. Methods The wound was photographed daily during an 11-day hospitalization and at 1 month and 6 months after the injury. Treatment included canthotomy and cantholysis; administration of dapsone, antibiotics, and steroids; and hyperbaric oxygen therapy. Main outcome measures Clinical presentation and course of a known brown recluse spider bite. Results Complete recovery with cicatrization at the site of the bite. Conclusions We present a case of a brown recluse spider bite to the left lower eyelid with a discussion of management and outcome of this rarely reported injury.

Hemolytic drugs aniline and dapsone induce iron release in erythrocytes and increase the free iron pool in spleen and liver

Incubation of rat erythrocytes with the hydroxylated metabolites of aniline and dapsone (4-4′-diaminodiphenylsulfone), phenylhydroxylamine and dapsone hydroxylamine, respectively, induced marked release of iron and methemoglobin formation. On the contrary, no release of iron nor methemoglobin formation was seen when the erythrocytes were incubated with the parent compounds (aniline and dapsone). The acute intoxication of rats with aniline or dapsone induced a marked increase in the erythrocyte content of free iron and methemoglobin, indicating that the xenobiotics are effective only after biotransformation to toxic metabolites in vivo. Prolonged administration of aniline or dapsone to rats produced continuos release of iron from erythrocytes. Marked iron overload was seen in the spleen and in the liver Kupffer cells, as detected histochemically. The spleen weight in these subchronically treated animals was significantly increased. The free iron pool was markedly increased in the spleen and to a lower extent in the liver. The possible relationships between iron release in erythrocytes, oxidative damage seen in senescent cells, hemolysis, overwhelmed capacity of spleen and liver to keep iron in storage forms and subsequent increase in low molecular weight, catalitically active iron is discussed.

Dapsone decreases the cumulative incidence of diabetes in non-obese diabetic female mice.

Dapsone (4,4'-diaminodiphenyl sulfone) has a large clinical experience due to its antimicrobial effects against Mycobacterium leprae, the causative agent of leprosy, and is used clinically where inflammation mediated by neutrophils is perceived to play a role. We administered dapsone in two concentrations (0.001% and 0.0001% w/w of diet) to 30 female non-obese diabetic (NOD) mice to explore the effect of dapsone on the development of IDDM following either a 1-week pulse or 20 weeks of continuous oral dapsone administration. Those mice receiving either the high or low doses of dapsone in the continuous group had a significantly reduced cumulative percentage of onset of IDDM. One of the seven mice given 0.0001% dapsone became diabetic (age 25 weeks), while none of the eight high dose (0.001%) mice developed the disease. Histological examination of pancreatic sections revealed islet infiltration in all groups of animals. The pulse and continuous experiments showed no statistically significant difference in the frequency or severity of lymphocytic infiltration. Dapsone administration did not inhibit growth, and growth rates were greater in those animals receiving the higher dapsone dose compared with the lower dose comparable to controls. We studied whether dapsone influenced murine lymphocyte function in addition to the published effects of the drug on neutrophils. At doses approximating those achieved in vivo (0.4 and 2 micrograms/ml), dapsone was found to inhibit murine splenocyte IL-2 and IL-4 secretion in response to concanavalin A. In view of the wide clinical experience with dapsone, randomized trials of the drug in new onset diabetes may be warranted.

Environmental procarcinogen hypothesis of bladder cancer in humans: Dapsone hydroxylation as a susceptibility risk factor for aggressive bladder cancer

The dapsone recovery ratio (DPRR), which is determined after single oral dose administration of dapsone by measuring the parent drug and hydroxylated metabolite, provides an in vivo measure of the efficiency of the drug metabolizing enzymes responsible for this metabolic route, putatively CYP3A4. This affords the potential to evaluate the hypothesis that this drug metabolizing enzyme system is involved in the pathogenesis of human bladder cancer. The present study is a matched case-control comparison of DPRR in patients with nonaggressive bladder cancer (grades I and II or Ta, T1 and T2, n = 43), patients with aggressive bladder cancer without invasion (grade III or Ta, T1 and T2, n = 32), patients with aggressive bladder cancer and invasion (grade III or T3 and T4, n = 32), and age- and gender-matched subjects with no urologic tumor on cystoscopy from an urban U.K. community (n = 85). Demographic variables associated with aggressive bladder cancer (Gill or T3, T4, Tis) included pack-years of smoking, alcohol intake, and occupational exposure; for nonaggressive bladder cancer variables included smoking and occupational exposure. DPRR exhibited an unimodal distribution in all subjects: activity was significantly reduced in both noninvasive and invasive aggressive bladder cancer, and was a significant risk factor for cancer after adjustment for other significant risk factors. Combining the two aggressive groups, the lowest tertile of DPRR activity was associated with a sixfold increase in risk ( p < 0.02) compared with the upper tertile. We conclude that a low dapsone recovery ratio is an independent risk factor for aggressive bladder cancer irrespective of its stage of invasion and suggest that the enzymes involved in its metabolism are detoxifying enzymes for unknown environmental factors to which an urban community is exposed.

Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data

OBJECTIVES: In this study we evaluated the pharmacokinetics, efficacy and safety of dapsone given 100 mg twice weekly as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with HIV-1 infection. METHODS: This was a prospective open trial, evaluating a total of 55 HIV-1-infected patients with CD4 cell counts below 200/mm3 and without previous episodes of PCP. Plasma concentrations of dapsone were determined with high-performance liquid chromatography (HPLC). After a mean follow-up of 471 days, the PCP rates per year of observation were 6.79%. Discontinuation of treatment as a result of severe side effects was required in four patients (7.5%). At steady state, mean plasma concentrations 24, 72, 96 and 144 h following the administration of dapsone were 1.46plus minus0.8, 0.28plus minus0.20, 0.30plus minus0.21 and 0.37plus minus0.27 mg/L, respectively. Dapsone plasma levels showed a high interpatient variability. The values for the pharmacokinetic parameters were comparable to those described for healthy volunteers. CONCLUSIONS: The administration of 100 mg twice weekly of dapsone seems appropriate to maintain effective plasma concentrations of the drug and to prevent PCP with good safety in patients with HIV-1-related immunodeficiency.

N‐Hydroxylation of dapsone by multiple enzymes of cytochrome P450: implications for inhibition of haemotoxicity.

1. The adverse reactions associated with the administration of dapsone are believed to be caused by metabolism to its hydroxylamine. Previous reports suggest that CYP3A4 is responsible for this biotransformation [1]. 2. Data presented in this paper illustrate the involvement of more than one cytochrome P450 enzyme in dapsone hydroxylamine formation using human liver microsomes. Eadie-Hofstee plots demonstrated bi-phasic kinetics in several livers. No correlation could be established between hydroxylamine formation and CYP3A concentrations in six human livers (r = -0.47; P = 0.34). 3. Studies with low molecular weight inhibitors illustrate the importance of CYP2C9 and CYP3A in dapsone N-hydroxylation. 4. Differential sensitivity of dapsone N-hydroxylation to selective CYP inhibitors indicated that the contribution of individual CYP enzymes varies between livers. Selective inhibition ranged from 6.8 to 44.1% by 5 microM ketoconazole, and from 24.0 to 68.4% by 100 microM sulphaphenazole. The extent of inhibition, by either ketoconazole or sulphaphenazole was dependent on the CYP3A content of the liver. 5. The levels of expression of these cytochrome P450 enzymes may be an important determinant of individual susceptibility to the toxic effects of dapsone, and may influence the ability of an enzyme inhibitor to block dapsone toxicity in vivo. Because of the inability to produce complete inhibition, selective CYP inhibitors are unlikely to offer any clinical advantage over cimetidine in decreasing dapsone hydroxylamine formation in vivo.

Bacillary angiomatosis in an HIV-positive patient. Good response to Dapsone

Object Report the case of a 25 year old HIV patient who developed bacillary angiomatosis.Setting Department of Dermatology, Centenary Hospital, Rosario, Argentina.Objective The patient failed to respond to the standard treatment with erythromycin.Result The patient showed improved by the administration of Dapsone along with Zidovudine.Conclusion This case is reported both because it is a rarely seen disease as well as because a good therapeutic response is obtained.

Bacillary angiomatosis in an HIV‐positive patient. Good response to Dapsone

AbstractObject Report the case of a 25 year old HIV patient who developed bacillary angiomatosis.Setting Department of Dermatology, Centenary Hospital, Rosario, Argentina.Objective The patient tailed to respond to the standard treatment with erythromycin.Result The patient showed improved by the administration of Dapsone along with Zidovudine.Conclusion This case is reported both because it is a rarely seen disease as well as because a good therapeutic response is obtained.

Erythema Gyratum Repens Associated with Hypereosinophilic Syndrome

We report a case of typical erythema gyratum repens lesions observed as a manifestation of idiopathic hypereosinophilic syndrome in a 63-year-old man. While erythema gyratum repens is usually associated with malignancy, an intensive search over a 30-month period failed to reveal any evidence of neoplasm. With administration of dapsone, the typical gyrate lesions disappeared as the subject's hypereosinophilia improved.

Behçet's disease in South African blacks: Report of five cases

Behçet's disease is a multisystemic disorder characterized by oral and genital ulcers. Most commonly seen in the Middle East and Japan, it is rare in black Africans. Behçet's disease in five South African blacks is reported. The patients had a mucocutaneous type of the disease, similar to the form prevailing in Western Europe and the United States. One of the patients had neurologic manifestations, and none had uveitis. In four patients genital and cutaneous lesions responded to administration of dapsone, colchicine, or both.

Adverse Reactions to Dapsone in Persons Infected with Human Immunodeficiency Virus

Dapsone is used in prophylaxis for and treatment of Pneumocystis carinii pneumonia. We present a case of Stevens-Johnson syndrome that was likely induced by administration of dapsone. A review of charts at the HIV Treatment Center of Northwestern University (Chicago) revealed that 40.3% of patients treated with trimethoprim-sulfamethoxazole could not tolerate the medication, while 25.2% of those treated with dapsone were intolerant of the drug. We also found a higher rate of adverse reactions to dapsone among patients with prior intolerance to trimethoprim-sulfamethoxazole than among patients without such a history; however, the difference was not significant.

Emergence of leprosy in a patient with mycosis fungoides

A patient with mycosis fungoides that had progressed to tumor stage responded to chemotherapy and electron beam treatment, but 6 years later a peripheral neuropathy, extensive plaques, erythroderma, and enlarged pinnae containing acid-fast organisms developed while he was being treated with photopheresis. The skin lesions cleared with administration of rifampin and dapsone, but a reversal reaction biopsy specimen showed features of both mycosis fungoides and leprosy. This case raises the question of whether there may be an association between mycosis fungoides and leprosy.