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Urticarial vasculitis syndrome effectively treated with dapsone and pentoxifylline.

Urticarial vasculitis is difficult to treat. We report here on a 40-year-old woman with a 16-year history of idiopathic hypocomplementemic urticarial vasculitis syndrome. Her disease had been resistant to treatment with H1- and H2-blockers, indomethacin, dapsone and interferon alpha but responded to > 25 mg/day prednisolone. Monotherapy with pentoxifylline was also of only minor benefit. Using a combination of dapsone (100 mg/day) and pentoxifylline (1,200 mg/day), we observed a gradual improvement resulting in a complete remission within 8 weeks. Complete control of symptoms could be maintained for 18 months without any serious side-effects. This type of treatment may be of benefit in other therapy-resistant cases of hypocomplementemic urticarial vasculitis syndrome, particularly in view of its excellent tolerance.

Adult↗

Use of dapsone in the treatment of Pneumocystis carinii pneumonia in a foal.

A 6-month-old male Quarter Horse was evaluated for chronic respiratory tract disease. Diagnostic investigations revealed pulmonary inflammation; Pneumocystis carinii was detected within macrophages. Lymphocyte subpopulation phenotyping and immunoglobulin concentration analysis were performed and results suggested immune suppression. Trimethoprim-sulfamethoxazole administration was initiated; the colt was discharged but was reexamined 8 days later because of profuse diarrhea and endotoxemia. Bacterial culture of feces recovered Salmonella spp resistant to trimethoprim-sulfamethoxazole, and a diagnosis of antimicrobial-associated colitis was made. Bilateral fibrinous hypopyon developed and was treated with topical medication and intracameral injections of human recombinant tissue plasminogen activator. Dapsone (3 mg/kg [1.4 mg/lb], PO, q 24 h; dose extrapolated from human data) was administered for treatment of P carinii pneumonia (56-day treatment period). The colt recovered from the pneumonia and diarrhea. Dapsone may be a useful adjunct to traditional treatment for P carinii pneumonia in horses or as a sole medication for horses that cannot tolerate other treatments.

Animals↗

Acute dapsone intoxication: a case with prolonged symptoms.

A 45-year-old man ate about 10 gm of dapsone (DDS). After initial vomiting marked methemoglobinemia with cyanosis, headache, and confusion developed. Methemoglobinemia subsided 7 days after ingestion when the concentrations of DDS and monoacetyldapsone (MADDS) were at the therapeutic level. Signs of hemolysis appeared on the third day after DDS ingestion, the hemolysis being maximal more than one week after ingestion. The initial disappearance of DDS and MADDS was slow, the apparent half-lives being 88 and 67 hr, respectively. Peroral activated charcoal seemed to shorten the half-lives of DDS and MADDS markedly. This result supports the concept of the enterohepatic cycle of dapsone and recommends the use of activated charcoal for several days in acute poisonings caused by DDS.

Acetylation↗

Repetitive doses of activated charcoal in Dapsone poisoning in a child.

A case of Dapsone poisoning, treated by repetitive dosing with activated charcoal, is reported. This 18-month-old child showed remarkably rapid resolution of his symptoms with this mode of therapy, becoming symptom free in 64 h. This rapid improvement is attributed to interruption by activated charcoal of the enterohepatic circulation of Dapsone. This mode of therapy may be indicated for other compounds having an enterohepatic circulation.

Charcoal↗

A case of methemoglobinemia after ingestion of an aphrodisiac, later proven as dapsone.

Methemoglobin (MetHb) is an oxidation product of hemoglobin in which the sixth coordination position of ferric iron is bound to a water molecule or to a hydroxyl group. The most common cause of acquired MetHb-emia is accidental poisoning which usually is the result of ingestion of water containing nitrates or food containing nitrite, and sometimes the inhalation or ingestion of butyl or amyl nitrite used as an aphrodisiac. We herein report a case of MetHb-emia after ingestion of an aphrodisiac, later identified as dapsone by gas chromatograph/mass selective detector (GC/MSD). A 24-year old male was admitted due to cyanosis after ingestion of a drug purchased as an aphrodisiac. On arterial blood gas analysis, pH was 7.32, PaCO2 26.8 mmHg, PaO2 75.6 mmHg, and bicarbonate 13.9 mmol/L. Initial pulse oxymetry was 89%. With 3 liter of nasal oxygen supplement, oxygen saturation was increased to 90-92%, but cyanosis did not disappear. Despite continuous supplement of oxygen, cyanosis was not improved. On the fifth hospital day, MetHb was 24.9%. Methylene blue was administered (2 mg/kg intravenously) and the patient rapidly improved. We proved the composition of aphrodisiac as dapsone by the method of GC/MSD.

Administration, Oral↗

Dapsone-induced erythroderma with Beau's lines.

A 35-year-old female with borderline lepromatous (BL) leprosy who suffered from dapsone-induced erythroderma is reported. Sudden onset of erythroderma gave rise to a temporary arrest of the function of nail matrix with the resultant Beau's lines. She rapidly recovered with omission of dapsone and therapy with systemic corticosteroids and a topical emollient. In view of the potentially fatal hypersensitivity reaction, we suggest that any patient on multidrug therapy for leprosy needs an urgent referral to a dermatologist if the patient develops a skin rash during the first two months of treatment.

Adult↗

Longitudinal study on relapses of leprosy in Polynesian multibacillary patients on dapsone monotherapy between 1946 and 1970.

Between 1946 and 1970, 295 new leprosy patients were detected in French Polynesia, of whom 145 were multibacillary. Of these 145, put on dapsone monotherapy, 131 reached bacteriological negativity in a period of time ranging from 2 to 12 years (average 4.72 years) and were followed-up for a period of time ranging from 19 to 43 years (median follow-up period after bacteriological negativity; 18 years). Among the 131 patients, 36 relapses were detected, the first one 4 years after bacteriological negativity and the last one 26 years after. The crude relapse rate was 27.5%, the risk of relapse was 1.39 per 100 patient years and the cumulative relapse probability, calculated using the lifetable method, reached 0.38 +/- 11 by year 31 of the study. From these findings one may assume that, at least in French Polynesia, one-third to one-half of multibacillary patients put on dapsone monotherapy would relapse if still present 36 years after bacteriological negativity. Such results re-emphasize the need for leprosy patients to be treated with multidrug therapy as recommended by WHO.

Dapsone↗

Increase in the incidence of dapsone hypersensitivity syndrome--an appraisal.

There has been an increase in the reports of dapsone hypersensitivity syndrome (DHS) in the past few years, coinciding with the introduction of multidrug therapy (MDT) for leprosy world-wide. The exact cause of this phenomenon is not clear. We report four cases of DHS observed among 252 leprosy patients on MDT and one case of DHS in a patient taking dapsone for nodulocystic acne in the Dermatology Department of the Osmania General Hospital, Hyderabad, India, between June 1997 and January 1999 with few unusual features. In two of these five patients maculopapular rash was severe and progressed to erythroderma. Introduction of MDT in 1982 has not only decreased the prevalence of leprosy but also brought about a positive change in the attitude of people which increased the voluntary reporting of leprosy patients. This, coupled with improvements in organization of leprosy control and awareness among medical personnel of DHS, are probably the most important reasons for the increased reporting of DHS in recent years.

Adolescent↗

Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group.

OBJECTIVE: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia. DESIGN: A randomized, double-blind study. SETTING: 24 U.S. academic medical centers. PATIENTS: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less. INTERVENTION: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone. MEASUREMENTS: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions. RESULTS: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P=0.2), therapeutic failure (P>0.2), or a complete course of therapy (P>0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P>.02). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P=0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P=0.01). CONCLUSIONS: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

AIDS-Related Opportunistic Infections↗

Dapsone-induced methhaemoglobinaemia: a source of diagnostic confusion.

Arterial desaturation as measured using pulse oximetry may not reflect cardiorespiratory disease; other possible causes, including certain drugs, should be sought. Within the literature, examples exist of dapsone-induced methaemoglobinaemia causing diagnostic confusion, particularly where respiratory disease is a feature. Few cases have been reported that demonstrate the potential of relatively low levels of methaemoglobinaemia to upset pulse oximetry readings. We describe three examples of dapsone-induced methaemoglobinaemia emphasising the potential for low-grade methaemoglobinaemia to cause diagnostic confusion. Widespread use of the pulse oximeter indicates this problem may occur more regularly, hence there is a need for increased awareness.

Adolescent↗

Erythema elevatum diutinum: skin and systemic manifestations, immunologic studies, and successful treatment with dapsone.

Erythema elevatum diutinum is a disease characterized by red, pink, purple and yellow cutaneous papules, nodules, and plaques distributed mainly over extensor surfaces. Histologically, there is leukocytoclastic vasculitis with fibrinoid necrosis of the upper and mid dermal vessel walls. Two of the five patients presented had moderately severe arthralgias and, unlike previously reported cases, three of them had a long history of bacterial infections and one had a coincident IgA monoclonal gammopathy. Each of the four patients treated with dapsone responded dramatically with rapid resolution of existing lesions and marked diminution of systemic symptoms. Skin lesions and systemic complaints recurred within 12 to 48 hours after discontinuing dapsone. Four of the patients had Arthus-like reactions to SKSD skin tests prior to therapy, with a marked decrease in the response after institution of therapy. Neutrophil chemotactic responsiveness of two patients was impaired. The sera of three patients had significant C1q binding activity suggesting that they might have circulating immune complexes.

Adolescent↗

[Dapsone in skin diseases].

This article reviews mechanism of action, adverse effects, drug interactions of dapsone and its application in dermatology. Dapsone belongs to sulfones group and is mainly recommended in skin diseases where gathering of neutrophiles or eosinophiles are found.

Anti-Infective Agents↗

Dapsone-induced peripheral neuropathy.

Peripheral neuropathy occurred in a 32-year-old man who was receiving dapsone (Aviosulfon) for dermatitis herpetiformis. Neurological examination showed polyneuropathy that involved the median and ulnar nerves, with a lesser involvement of other peripheral nerves. After treatment with dapsone was discontinued, the neuropathy reversed itself, with practically complete return of function of all nerves involved.

Adult↗

[The treatment of cutaneous loxoscelism with dapsone].

Previous treatment of dermic lesions caused by brown recluse spider bite has given disappointing results. Cold, steroids and surgical measures are usually ineffective. Following encouraging results reported with the use of dapsone (4-4 diamine diphenyl sulphone) we treated 2 patients with severe dermic lesions. Both recovered satisfactorily. Thus, dapsone is an effective therapy for dermic lesions caused by brown recluse spider bite. The potential toxic effects of this sulphone derivative suggest that it should be used only in severe cases of the disease.

Adult↗

In vitro and in vivo experiments with the new inhibitor of mycobacterium leprae brodimoprim alone and in combination with dapsone.

The antibacterial effect of brodimoprim alone and in combination with dapsone has been studied in vitro in cell-free systems and in whole mycobacterial cells as well as in vivo in mice and humans. The obtained inhibitory effects in vitro and in vivo against model mycobacterial strains and M. leprae, the pharmacokinetic properties in human and its synergistic effect with the most used drug in the chemotherapy of leprosy, dapsone, make brodimoprim a promising candidate in the therapy of leprosy.

Adenosine Triphosphate↗

Primary dapsone resistance as assessed by uptake of labelled thymidine by the macrophage resident Mycobacterium leprae.

12 untreated lepromatous leprosy patients were screened for primary dapsone resistance by the uptake of labelled thymidine by macrophage resident M. leprae. There were found to harbour primary dapsone resistant strains of M. leprae and another three partially resistant strains to the drug. This rapid, simple and reliable method should be used routinely to screen leprosy patients, for drug resistance.

Cells, Cultured↗