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PubMedDate not supplied

[Disulone and hepatosiderosis].

BACKGROUND: 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. PATIENTS AND METHODS: 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. DISCUSSION: 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.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Scleritis in relapsing polychondritis. Response to therapy.

The authors reviewed the records of 11 patients with relapsing polychondritis associated with active scleritis and analyzed the immunopathologic characteristics of ocular tissue from three of these. Seven patients (63%) required cytotoxic drugs, alone or in combination with low-dose oral corticosteroids. Only one patient was treated successfully with systemic corticosteroids alone. Two patients were controlled with dapsone and one with an oral nonsteroidal anti-inflammatory drug. Dapsone, which has been reported to be effective in the treatment of relapsing polychondritis, did not control the destructive scleral inflammation in six (75%) of eight patients; two (50%) of four patients with diffuse anterior scleritis were controlled with this drug. Patients with nodular and necrotizing scleritis were controlled with azathioprine and cyclophosphamide, respectively. These data suggest that the ocular manifestations of relapsing polychondritis, especially nodular and necrotizing scleritis, are less amenable to treatment with systemic corticosteroids and/or dapsone and that more potent immunosuppressants (azathioprine and cyclophosphamide) may be required to treat these lesions successfully. Results of histologic and immunofluorescent examination of conjunctival and/or scleral biopsy specimens from three patients confirmed the vasculitic nature of the eye lesions in this disease.

Adrenal Cortex Hormones↗
PubMed1987

Sulfone therapy in the treatment of leukocytoclastic vasculitis. Report of three cases.

Dapsone therapy for leukocytoclastic (necrotizing) vasculitis has been little used, except for the variant forms of erythema elevatum diutinum and urticarial vasculitis. We report three patients with the common (palpable purpura) form of the disease, limited to the skin, and successfully treated with moderate doses of dapsone (100-150 mg daily). Although the natural course of leukocytoclastic vasculitis is highly unpredictable, the prompt disappearance of new lesion formation after initiation of treatment and the rapid recurrence of lesions after therapy is discontinued (both often within 4 to 8 days after the critical dose level is reached) reflect drug efficacy. We believe that dapsone deserves wider evaluation as a therapeutic agent for chronic or recurrent cases of the common form of leukocytoclastic vasculitis.

Adolescent↗
PubMed1998

Oral pemphigoid. Subset of cicatricial pemphigoid?

OBJECTIVE: Cicatricial pemphigoid (CP) is an autoimmune blistering disease characterized by anti-basement membrane zone (BMZ) antibodies with a varied heterogeneous clinical spectrum. We sought to characterize a subset of patients with disease limited to the oral cavity. STUDY DESIGN: Twenty-nine random patients with vesiculobullous disease limited to the oral cavity were studied. We identified patients by clinical criteria, the presence of subepidermal/subepithelial bullae on routine histopathologic study, and deposition of IgG, complement, or both on the BMZ of perilesional tissue by immunopathological studies. Treatment included local and systemic therapies. Patients were monitored for a mean period of 6.7 years (range, 3.5 to 11 years). RESULTS: The female/male ratio was 4.8:1. Patients with limited or minimal disease received local therapy only. In patients with extensive or severe disease, the use of dapsone yielded significant clinical improvement. Long-term follow-up showed that patients with severe disease treated with dapsone followed a clinical course similar to that in patients with minimal disease. CONCLUSIONS: Oral pemphigoid is a distinct clinical subset of CP. Overall it has a relatively benign course compared with that in patients with CP involving the oral cavity and other mucosae and the skin. Patients with minimal disease respond satisfactorily to topical therapy. Patients with severe and extensive disease benefit from dapsone therapy. In most patients the clinical course is prolonged and treatment is required for several months; in our study the mean treatment period was 42 months (range, 24 to 78 months). All the patients in this study went into clinical remission and remained in remission on cessation of therapy. No other mucosae or the skin were involved during the follow-up period.

Adult↗
PubMed2000

Neutrophilic dermatosis of the dorsal hands: pustular vasculitis revisited.

An entity termed "pustular vasculitis of the hands" was recently described. Patients with this condition presented with low-grade fevers and erythematous plaques, pustules, and bullae limited to the dorsal hands and fingers, which were characterized histologically by a dense neutrophilic infiltrate and leukocytoclastic vasculitis. We describe patients with a similar clinical presentation, but who lacked vasculitis on biopsy findings. We describe 3 otherwise asymptomatic patients with hemorrhagic bullae, plaques, and pustules solely on the dorsal hands. Biopsy specimens showed a neutrophilic infiltrate and leukocytoclasis, but no necrotizing vasculitis, and were reminiscent of Sweet's neutrophilic dermatoses. In our patients, corticosteroids or dapsone led to clearing of the lesions, and small maintenance doses of dapsone prevented their recurrence. Our 3 patients had clinical lesions similar to those termed pustular vasculitis of the hands, but which lacked leukocytoclastic vasculitis on biopsy findings. Because of histologic findings and a therapeutic response more characteristic of Sweet's syndrome, we propose the term neutrophilic dermatosis of the dorsal hands. In addition, low-dose dapsone is proposed as a possible first-line therapy in this condition, especially in those with recurrent disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1984

Cancer mortality among patients with Hansen's disease.

For the evaluation of cancer risks associated with immunodeficiencies experienced by patients with Hansen's disease (leprosy) and for the assessment of possible adverse effects of dapsone therapy, a follow-up study was conducted of 1,678 patients admitted to the National Hansen's Disease Center in Carville, La., between 1939 and 1977. Overall, no substantial cancer mortality was observed (standardized mortality ratio = 1.3), nor was there any excess among patients exhibiting defects in cellular immunity by virtue of lepromatous forms of the disease. Notable was the absence of any significant excess of lymphoma (5 observed vs. 2.3 expected), despite the predominance of this tumor in certain other immunodeficiency states. Several cancer sites (oral, bladder, and kidney) occurred excessively, but reasons for the elevations were obscure. Although dapsone has been implicated as a carcinogen in laboratory animals, the use of sulfones, including dapsone, did not appear to affect significantly the risk of any cancers in this population.

Black or African American↗
PubMed1996

Intracellular glutathione in the peripheral blood cells of HIV-infected patients: failure to show a deficiency.

OBJECTIVE: To determine whether HIV-infected patients have a deficiency of intracellular glutathione (GSH) in peripheral blood mononuclear cells (PBMC) and erythrocytes. DESIGN: Initial experiments determining the stability of intracellular GSH preceded the measurement of GSH levels in 33 HIV-positive patients and 40 control subjects within 1 h of isolation of their blood cells. In addition, the susceptibility of erythrocytes to dapsone hydroxylamine-induced methaemoglobinaemia was evaluated. METHODS: GSH levels were determined by an high-performance liquid chromatography method utilizing a fluorescent probe, monobromobimane. The bimane-GSH adduct formed in PBMC was also characterized by mass spectrometry. Methaemoglobin formation on exposure to dapsone hydroxylamine was determined spectrophotometrically. RESULTS: GSH levels remained stable for only 1 h after cell isolation, thereafter showing a decrease of 20 and 60% at 4 and 24H, respectively, There was no difference in the GSH levels in PBMC and erythrocytes of the HIV-positive patients compared with controls. The GSH levels were not related to the disease stage or to CD4+ cell counts. There was no difference in GSH levels in PBMC taken from trimethoprim-sulphamethoxazole-hypersensitive and non-hypersensitive patients. Methaemoglobinaemia on exposure of erythrocytes to dapsone hydroxylamine was concentration-dependent, but there was no significant difference between patients and controls. CONCLUSION: In contrast to previous studies, no deficiency of intracellular GSH in the PBMC and erythrocytes of HIV-infected patients was found. The discrepancy between studies may be methodological reflecting the instability of GSH, which requires prompt sample analysis.

Adult↗
PubMed1993

Cicatricial pemphigoid.

This case of CP is of interest because of its "not-so-benign" course in this patient, its unusual immunofluorescence patterns, and the need for a complex therapeutic regimen to achieve control. This patient had severe ocular; laryngeal, and oropharyngeal involvement leading to visual problems, hoarseness, and marked weight loss and dehydration. He also had anemia thought to be partially related to dapsone use. We believe the side effects of dapsone, combined with fluid retention due to prednisone therapy, contributed to cardiac failure. The diagnosis of CP is usually established by correlation of clinical findings with immunofluorescence studies. However, indirect immunofluorescence may show strong intercellular antibody binding in the epidermis (ie, pemphigus-like antibodies). Treatment alternatives for patients with CP who have adverse reactions to, or no significant benefit from, conventional agents such as dapsone or prednisone may include immunosuppressive agents such as azathioprine or cyclophosphamide. As this case demonstrates, care of patients having CP involves a cooperative effort from a number of different specialties, including dermatology, primary care, ophthalmology, and otolaryngology.

Aged↗
PubMed1997

Meta-analysis of prophylactic treatments against Pneumocystis carinii pneumonia and toxoplasma encephalitis in HIV-infected patients.

In a meta-analysis, we examined the efficacy of aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone or dapsone/pyrimethamine for the prevention of Pneumocystis carinii pneumonia and toxoplasma encephalitis in patients with HIV infection. Of 22 trials, 13 compared trimethoprim-sulfamethoxazole with aerosolized pentamidine, nine compared dapsone alone or in combination with pyrimethamine with aerosolized pentamidine, and eight compared trimethoprim-sulfamethoxazole with dapsone/pyrimethamine. In total, 1484 patients were treated with trimethoprim-sulfamethoxazole, 1548 patients with dapsone/pyrimethamine or dapsone, and 1800 patients with aerosolized pentamidine. For dapsone/pyrimethamine versus aerosolized pentamidine, the risk ratio for P. carinii pneumonia was 0.90 (95% confidence interval [CI], 0.71-1.15), and for toxoplasma encephalitis it was 0.72 (95% CI, 0.54-0.97). For trimethoprim-sulfamethoxazole versus aerosolized pentamidine, the risk ratio of P. carinii pneumonia was 0.59 (95% CI, 0.45-0.76), and for toxoplasma encephalitis it was 0.78 (95% CI, 0.55-1.11). For trimethoprim-sulfamethoxazole versus dapsone/pyrimethamine, the risk ratio of P. carinii pneumonia was 0.49 (95% CI, 0.26-0.92), and for toxoplasma encephalitis it was 1.17 (95% CI, 0.68-2.04). Although current evidence does not allow a definitive recommendation, administration of trimethoprim-sulfamethoxazole for prophylaxis of P. carinii pneumonia and toxoplasmosis in patients with HIV infection is consistent with the available data.

AIDS-Related Opportunistic Infections↗
PubMed1960

Metabolism and excretion of di(p-aminophenyl) sulphoxide in different animal species.

Rabbits, rats and guinea-pigs were treated with di(p-aminophenyl) sulphoxide and their urines examined by an analytical method which permits the simultaneous determination of this compound and of dapsone [di(p-aminophenyl) sulphone] which is a possible product of metabolic oxidation. The method gives for each drug the total of free compound plus acid-labile conjugates. All three species excreted unchanged drug together with dapsone. With rats and guinea-pigs about 33% of the excretion is dapsone, but with rabbits only 6 to 12%. The rate of combined excretion is much greater in rabbits than in the other two species. These results are discussed in relation to the significance of di(p-aminophenyl) sulphoxide as a drug in the treatment of leprosy.

Aniline Compounds↗
PubMed1995

Effect of atovaquone and atovaquone drug combinations on prophylaxis of Pneumocystis carinii pneumonia in SCID mice.

The prophylactic efficacies of atovaquone (ATQ) alone and in combination with azithromycin, clarithromycin, rifabutin, proguanil, PS-15, trimethoprim, co-trimoxazole, or dapsone were investigated in a SCID mouse model of Pneumocystis carinii pneumonia (PCP). ATQ alone was shown to have a significant dose-related effect, and at 200 mg/kg of body weight per day administered orally, the efficacy of ATQ was comparable to that of Septrin (co-trimoxazole). Of the drugs investigated orally in combination with ATQ, only dapsone (25 mg/kg/day) and to a lesser extent PS-15 (5 mg/kg/day) had any noteworthy antipneumocystis activity (at the doses examined) when administered alone. ATQ drug combinations affected the prophylactic efficacy of a subcurative dosage of ATQ (50 mg/kg/day given orally) in the following ways: dapsone (25 mg/kg/day) or co-trimoxazole (25 mg of sulfamethoxazole plus 5 mg of trimethoprim per kg/day) had no significant effect on ATQ, azithromycin (200 mg/kg/day) or clarithromycin (200 mg/kg/day) had a slight additive effect with ATQ, trimethoprim (100 mg/kg/day) or PS-15 (5 mg/kg/day) had an additive effect with ATQ, and proguanil (25 mg/kg/day) or rifabutin (200 mg/kg/day) had a marked synergistic effect on ATQ. The last result was particularly noteworthy as neither proguanil nor rifabutin was effective against PCP when administered alone. None of the drugs examined antagonized the prophylactic activity of ATQ in experimental PCP in SCID mice. The results suggest that clinical trials of ATQ with synergistic drug combinations may now be justified, particularly if such drug combinations improve ATQ's efficacy and broaden its spectrum of activity.

Animals↗
PubMed1999

Subcorneal pustular dermatosis treated with PUVA therapy. A case report and review of the literature.

BACKGROUND: Subcorneal pustular dermatosis (SPD) is a chronic recurrent pustular dermatosis of unknown etiology. Many treatments have been proposed, none of which has been uniformly successful. OBJECTIVE: Our purpose is to report a patient with SPD successfully treated by PUVA and to review the literature concerning phototherapy treatment of SPD. METHODS: A patient suffering from SPD resistant to diaminodiphenylsulphone (dapsone) responded well to a combination therapy consisting of dapsone and PUVA. He received 50 mg/day and 3 PUVA sessions a week. Photographs were taken at baseline and after 15 sessions. RESULTS: The lesions were virtually cleared after 15 sessions. The patient remained free of lesions with a maintenance therapy of dapsone (50 mg/ day) and 1 PUVA session a week. CONCLUSION: The therapeutic value of phototherapy for the treatment of SPD still has to be confirmed and could be a valuable alternative for treatment-resistant patients.

Dapsone↗
PubMed1989

Effects of mutagenic and non-mutagenic aniline derivatives on rat liver drug-metabolizing enzymes.

1. The effect of 4,4'-methylene bis(2-chloroaniline) (MOCA), 4,4'-methylene dianiline (MDA) and 4,4'-sulphonyldianiline (Dapsone) in vivo on xenobiotic biotransformation in male rat liver was studied. 2. Treatment with MOCA or MDA but not Dapsone caused a dose-dependent increase in ethoxyresorufin O-deethylase activity and a concomitant decrease in aldrin epoxidase activity in male rats. 3. Treatment with MOCA or MDA resulted in dose-dependent increases in ethoxycoumarin O-deethylation and epoxide hydrolation, while only MOCA induced cytosolic glutathione S-transferase activity. 4. Treatment with Dapsone resulted in no changes in xenobiotic biotransformation except for the induction of aniline hydroxylation. 5. The results are consistent with the contention that there is a relationship between carcinogenic chemicals and particular alterations in the activities of biotransformation enzymes.

7-Alkoxycoumarin O-Dealkylase↗
PubMedDate not supplied

Management of brown recluse spider bites in primary care.

BACKGROUND: Treatment of brown recluse spider bites remains controversial; there are multiple options but little evidence of their effectiveness. METHODS: Over a 5-year period, family physicians enrolled consecutive patients with suspected brown recluse spider bites. Usual care was provided based on physician preferences. Topical nitroglycerine patches and vitamin C tablets were provided at no cost for those who wished to use them. Baseline data were collected, and patients were followed-up weekly until healing occurred. Outcome measures included time to healing and occurrence of scarring. Regression methods were used to evaluate the impact of the 4 main treatment approaches (corticosteroids, dapsone, topical nitroglycerine, and high-dose vitamin C) after controlling for bite severity and other predictors. RESULTS: Two hundred and sixty-two patients were enrolled; outcomes were available for 189. The median healing time was 17 days. Only 21% had permanent scarring. One hundred seventy-four received a single treatment modality. Among this group, 12 different modalities were used. After controlling for other variables, predictors of more rapid healing included lower severity level, less erythema, and less necrosis at time of presentation, younger age, no diabetes, and earlier medical attention. Systemic corticosteroids and dapsone were associated with slower healing. Predictors of scarring were higher severity, presence of necrosis, and diabetes. Dapsone was associated with an increased probability of scarring. CONCLUSIONS: We found no evidence that commonly used treatment approaches reduced healing time or the likelihood of scarring in suspected brown recluse spider bites.

Administration, Cutaneous↗
PubMed2004

Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance.

Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovecii, in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii. Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone.

Anti-Infective Agents↗
PubMed1975

Rifampin therapy of lepromatous leprosy.

Patients with borderline-lepromatous (BL) or fully lepromatous (LL) leprosy were treated in the sanitarium for approximately 1 year with oral rifampin (600 mg daily) or with oral dapsone (100 mg daily). They were then treated as outpatients with intramuscular acedapsone (225 mg every 12 weeks) or oral dapsone (50 mg daily). They have now been followed for a total of 28 to 34 months. Death of Mycobacterium leprae during the initial 24 weeks was monitored by mouse inoculation with M. leprae from skin punch biopsy specimens. With rifampin therapy, death of M.leprae occurred rapidly, and viable M. leprae were nearly undetectable by the time the first specimen was taken after the start of treatment, at 4 weeks. With dapsone therapy, death of M. leprae was slower, and in some cases the inoculation results were still positive at 12 weeks. The therapeutic response during the period of outpatient treatment has been satisfactory. The number of dead M. leprae, as measured by the bacterial index in skin smears and the number of acid-fast bacteria in skin specimens, has continued to decrease, and clinical progress has been satisfactory. The measured drug-induced death of M. leprae occurred at about the same rate in BL patients as in LL patients. Disappearance of dead M. leprae from the tissues was much more rapid in BL patients than in LL patients.

Acetamides↗
PubMed1980

Intermittent chemotherapy of experimental leprosy in mice.

In this study we assess the degree of prolonged bacteriostasis of Mycobacterium leprae after temporary exposure to ehtionamide or thiacetazone, and relate this to their efficacy when administered intermittently to mice with experimental leprosy infections. The results show that temporary exposure of M. leprae to either of these drugs results in a prolonged bacteriostatic effect, but that efficacy is rapidly lost as the interval between doses is increased. Using the mouse foot pad system, growth of M. leprae is not inhibited by thiacetazone when the frequency of administration is less than three times weekly. When ethionamide is administered once weekly, growth of M. leprae is inhibited but bactericidal activity is lost. When ethionamide is administered in combination with continuous dapsone therapy, either continuously or three times weekly, the bactericidal activity of the drug combination is greater than when either drug is administered alone. However, when ethionamide is administered once weekly in combination with continuous dapsone treatment, the bactericidal effect is identical to that when dapsone is given alone: that is, ethionamide makes no contribution to the combination.

Animals↗
PubMed2004

[Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene].

The relation between diaminodiphenylsulfone (called dapsone)-resistance and point mutations of the dihydropteroate synthase (DHPS) gene was analyzed using dapsone resistant Mycobacterium leprae isolates derived from Japanese leprosy patients. The mutation was found at amino acid residues 53 or 55 of the DHPS. This finding suggests that two specific mutations in the DHPS gene involved in dapsone resistance of M. leprae.

Amino Acid Sequence↗