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Dapsone hypersensitivity syndrome in an adolescent during treatment during of leprosy.

A 12 y old girl was admitted 24 days after start a WHO multidrug therapy scheme for multibacillary leprosy (dapsone, clofazimine and rifampicin) with intense jaundice, generalized lymphadenopathy, hepatoesplenomegaly, oral erosions, conjunctivitis, morbiliform rash and edema of face, ankles and hands. The main laboratory data on admission included: hemoglobin, 8.4 g/dL; WBC, 15,710 cells/mm3; platelet count, 100,000 cells/mm3; INR = 1.49; increased serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase, alkaline phosphatase, direct and indirect bilirubin. Following, the clinical conditions had deteriorated, developing exfoliative dermatitis, shock, generalized edema, acute renal and hepatic failure, pancytopenia, intestinal bleeding, pneumonia, urinary tract infection and bacteremia, needing adrenergic drugs, replacement of fluids and blood product components, and antibiotics. Ten days after admission she started to improve, and was discharged to home at day 39th, after start new supervised treatment for leprosy with clofazimine and rifampicin, without adverse effects. This presentation fulfils the criteria for the diagnosis of dapsone hypersensitivity syndrome (fever, generalized lymphadenopathy, exfoliative rash, anemia and liver involvement with mixed hepatocellular and cholestatic features). Physicians, mainly in geographical areas with high prevalence rates of leprosy, should be aware to this severe, and probably not so rare, hypersensitivity reaction to dapsone.

Child↗

A double-blind comparative study of hydroxychloroquine and dapsone, alone and in combination, in rheumatoid arthritis.

Eighty patients with active rheumatoid arthritis (RA) entered a double-blind randomized study of 24 weeks duration, to compare the efficacy and toxicity of hydroxychloroquine, dapsone, and a combination of both drugs in treatment of RA. Evaluation of changes in clinical, laboratory and radiologic variables was based on 63 patients completing the trial. There was no clear difference between the three therapy groups in most inflammatory variables after 24 weeks. However, only patients receiving the combination therapy improved significantly in all clinical and laboratory variables. Nine patients in the combination group and four in each single drug group discontinued during the trial, mainly because of toxicity. Four patients taking the combination therapy withdrew because of hemolytic anemia, and none in the dapsone group. These findings suggest that hydroxychloroquine in combination with dapsone is somewhat more effective and less tolerated than single drug treatments.

Adult↗

Acute dapsone intoxication: a case treated with continuous infusion of methylene blue, forced diuresis and plasma exchange.

A case of massive dapsone poisoning (15 g) in a 26 year old man is reported. The patient exhibited high plasma dapsone concentration, marked methemoglobinemia, and signs of hemolysis. He recovered completely after intensive treatment with methylene blue, activated charcoal, forced diuresis, and plasma exchange. In order to avoid overdosage of methylene blue it is concluded that this substance should be given by continuous intravenous infusion in cases with severe methemoglobinemia. This way of administration caused a steady decrease in the methemoglobin concentration compared to intermittent administration. Plasma exchange was of minor benefit, probably due to the large distribution volume of dapsone.

Adult↗

Optical coherence tomographic evaluation of macular infarction following dapsone overdose.

A 16-year-old girl had decrease in vision following dapsone overdose. This case demonstrated optical coherence tomography (OCT) evaluation of macular infarction following dapsone poisoning. OCT showed characteristic serial changes as Stage 1: Cystic macular edema, Stage 2: Resolving cystic change and Stage 3: Foveal atrophy. Hence, OCT could show the progression of foveal atrophy from cystic macular edema following dapsone poisoning.

Adolescent↗

Dapsone chemotherapy of Mycobacterium leprae infection of the neonatally thymectomized Lewis rat.

In order to learn whether the neonatally thymectomized Lewis rat (NTLR) infected with Mycobacterium leprae could serve as a model for chemotherapeutic studies in a situation resembling that found in human lepromatous leprosy, NTLR inoculated with M. leprae either locally or intravenously 9 to 16 months earlier were treated for from 1.5 to 8.5 months with dapsone (4,4'-diaminodiphenylsulfone, DDS) incorporated in the rat chow in the concentration providing the minimal inhibitory concentration of the drug for M. leprae and in the 100-fold larger concentration. NTLR were killed at intervals; the M. leprae were counted and passed to mice. Treatment with the smaller dosage of dapsone neither killed M. leprae nor reduced the number of organisms in the bacterial populations, whereas treatment with the larger dosage both killed M. leprae and reduced their numbers. The rate at which the organisms were killed (i.e., rendered noninfective for mice) was much the same as that in patients treated with dapsone in comparable dosage. The dead organisms were removed from the rat tissues at a faster rate than encountered in patients. The NTLR may indeed be suitable for chemotherapeutic studies relevant to man. In addition, the more rapid disappearance of dead M. leprae from the rat tissues may facilitate the study of treatment regimens designed to eradicate persisting viable organisms.

Animals↗

Dapsone agranulocytosis in a leprosy patient.

Dapsone-induced agranulocytosis is a rare adverse effect. There are various reports of agranulocytosis in patients treated with dapsone for malaria prophylaxis and other dermatological diseases. However, this adverse reaction in leprosy is not often encountered. We describe agranulocytosis in a young patient who was taking dapsone (100 mg) for borderline-tuberculoid leprosy in a rural environment.

Adult↗

Dapsone-trimethoprim for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

All patients with the acquired immunodeficiency syndrome and a first episode of Pneumocystis carinii pneumonia seen at the San Francisco General Hospital between November 1984 and April 1985 were evaluated for oral treatment with dapsone (100 mg/d) plus trimethoprim (20 mg/kg body weight X d). All 15 patients who met the entry criteria improved clinically and radiographically within 3 to 10 days after starting treatment. Repeat pulmonary function tests and gallium lung scans after 3 weeks of therapy also showed improvement. Although side effects occurred in 14 patients, in only 2 were they severe enough to require stopping therapy. Both of these patients had worsening skin rash, and dapsone-trimethoprim therapy was stopped after 10 days. When compared with trimethoprim-sulfamethoxazole or pentamidine used to treat P. carinii pneumonia in similar patients, oral dapsone-trimethoprim is at least as effective, seems to be better tolerated, and may have a lower frequency of serious side effects.

Acquired Immunodeficiency Syndrome↗

Bullous eruption of systemic lupus erythematosus. Dramatic response to dapsone therapy.

Four patients with systemic lupus erythematosus developed a nonpruritic vesiculobullous eruption that was unresponsive to high-dose systemic corticosteroid therapy. In three patients the eruption was not associated with a flare of systemic disease. Biopsy results showed neutrophilic microabscesses at the dermal papillary tips and perivascular lymphohistiocytic infiltrates. Direct immunofluorescence of normal appearing skin not exposed to the sun was positive in all four patients. Due to the unresponsiveness to corticosteroid therapy and the striking histologic resemblance to dermatitis herpetiformis, each of the patients was treated with dapsone. Within 24 hours each patient had prompt cessation of the appearance of new lesions. Improvement of the eruption did not correlate with improvement of the systemic manifestations of their lupus erythematosus. The rapid response to dapsone therapy suggests that dapsone is useful in treating bullous lesions of systemic lupus erythematosus.

Adrenal Cortex Hormones↗

Methemoglobin formation by hydroxylamine metabolites of sulfamethoxazole and dapsone: implications for differences in adverse drug reactions.

Differences in the incidence of adverse drug reactions to trimethoprim-sulfamethoxazole and dapsone may result from differences in the formation, disposition, toxicity, and/or detoxification of their hydroxylamine metabolites. In this study, we examine whether differences in the biochemical processing of sulfamethoxazole hydroxylamine (SMX-NOH) and dapsone hydroxylamine (DDS-NOH) by erythrocytes [red blood cells (RBCs)] contribute to this differential incidence. The methemoglobin (MetHgb)-forming capacity of both metabolites was compared after a 60-min incubation with washed RBCs from four healthy human volunteers. DDS-NOH was significantly more potent (P =.004) but equally efficacious with SMX-NOH in its ability to form MetHgb. The elimination of potential differences in disposition by lysing RBCs did not change the MetHgb-forming potency of either hydroxylamine. At pharmacologically relevant concentrations, greater reduction to the parent amine occurred with DDS-NOH. Maintenance of MetHgb-forming potency was dependent on recycling with glutathione, but no difference in cycling efficiency was observed between DDS-NOH and SMX-NOH. In contrast, the pharmacodynamics of hydroxylamine-induced MetHgb formation were not changed by pretreatment with the glucose 6-phosphate dehydrogenase inhibitor epiandrosterone or by compounds that alter normal antioxidant enzyme activity. Methylene blue, which stimulates NADPH-dependent MetHgb reductase activity, decreased MetHgb levels but did not alter the differential potency of these hydroxylamines. DDS-NOH was also significantly more potent when incubated with purified human hemoglobin A0. Collectively, these data suggest that the inherently greater reactivity of DDS-NOH with hemoglobin, the greater conversion of DDS-NOH to its parent amine, and potential differences in disposition of hydroxylamine metabolites may contribute to the preferential development of dapsone-induced hemotoxicity and sulfamethoxazole-induced hypersensitivity reactions.

Dapsone↗

Dapsone hypersensitivity syndrome with coexisting acute hepatitis E.

A 14-year-old girl presented with fever, generalized lymphadenopathy, skin rash and hepatitis after starting dapsone. All abnormalities reversed with institution of prednisolone therapy after discontinuation of dapsone. The hepatic involvement was of hepatocellular type; it was associated with IgM anti-HEV antibodies, suggesting coexisting acute hepatitis E. We believe a causal link between the hepatotrophic viruses and dapsone hypersensitivity syndrome could exist.

Acute Disease↗

Malaria, leprosy and dapsone.

Although the preventive action of dapsone against P. falciparum malaria was known for many years, there was no report about the incidence of P. falciparum malaria in leprosy patients treated with dapsone, especially from areas of Southeast Asia where both leprosy and malaria are endemic. Therefore, two clinic-based malaria surveys were undertaken at a gap of 12 years, comprising 506 lepromatous leprosy patients and 499 febrile nonleprosy control subjects. Both the surveys showed that the lepromatous patients treated with MDT had only P. vivax malaria (incidence comparable to the febrile nonleprosy controls) with complete freedom from P. falciparum. On the contrary, control sujects not taking any-leprosy drugs and staying with the leprosy patients at the same beggars' home, had both P. vivax and P. falciparum malaria. It is postulated that dapsone provided protection against P. falciparum among leprosy patients.

Adolescent↗

Adverse reactions associated with dapsone therapy in HIV-positive patients: a case presentation and review.

Dapsone is commonly used for the prophylaxis of Pneumocystis jiroveci pneumonia in patients with a diagnosis of HIV infection who have allergies to sulfa-based drugs. Dapsone has several adverse effects in its profile that make it a potentially dangerous second-line agent. We report an adverse effect encountered in an HIV-positive patient receiving dapsone and review the common adverse effects encountered with this alternative treatment option.

AIDS-Related Opportunistic Infections↗

Severe dapsone hypersensitivity syndrome.

Dapsone, a potent antiparasitic and anti-inflammatory compound, is mainly used in the treatment of leprosy and a variety of blistering skin diseases. It may cause a severe adverse drug reaction with multiorgan involvement known as dapsone hypersensitivity syndrome. We report the case of a 21-year-old female patient with dapsone hypersensitivity syndrome. The clinical presentation mimicked a viral exanthema.

Adult↗

Dapsone for thrombocytopenic purpura related to human immunodeficiency virus infection.

PURPOSE: The purpose of this study was to determine the effect of dapsone on platelet count in patients with human immunodeficiency virus (HIV)-related autoimmune thrombocytopenia. PATIENTS AND METHODS: Eleven patients with HIV-related thrombocytopenia received dapsone (50 to 125 mg/day) for 2 to 43 months. Patients with the acquired immunodeficiency syndrome were not enrolled. RESULTS: Of the 11 patients, six developed platelet counts above 50 X 10(9)/L and did not require any other specific therapy. No significant side effects were observed. CONCLUSION: We conclude that dapsone may be effective in some patients with HIV-related thrombocytopenia.

Adult↗

The management of intransigent desquamative gingivitis with Dapsone.

Fifteen patients suffering from intransigent desquamative gingivitis due to lichen planus or benign mucous membrane pemphigoid were treated with dapsone (diphenylsulphapyridine) over a 3-month period. Twelve patients completed the trial. Therapeutic benefit was estimated clinically with the aid of 35mm color transparencies taken at 4-week intervals; and subjectively by the patients estimating their progress as worse, no change, some improvement or complete recovery. Taken as a whole, some 58% of patients had some benefit from therapy. Of the 7 patients with lichen planus, 1 showed complete recovery and 3 showed some improvement. In the 5 patients with desquamative gingivitis due to mucous membrane pemphigoid, 3 showed some improvement and 2 received no benefit. Three patients withdrew from the trial due to side effects of the dapsone such as headaches and nausea. It is concluded that dapsone therapy may be of some use in the management of desquamative gingivitis when traditional treatments have failed. Patients should be warned of the possibility of side effects.

Adult↗

Dapsone neuropathy--report of three cases and pathologic features of a motor nerve.

We report the clinical features, electrophysiologic findings, and dapsone and isoniazid excretion studies in three young people who ingested excessive amounts (2-4 times the prescribed dose) of dapsone for hypopigmented macules and who developed, subacutely, progressive motor neuropathy a few months later. Pathologic studies on a biopsied motor nerve confirmed the electrophysiologic conclusion of distal motor axonopathy. All made a rapid recovery in a few months after dapsone was stopped, although electrical abnormalities persisted. One patient was a rapid acetylator of isoniazid.

Adolescent↗

Suicide with dapsone.

A case of suicide with dapsone is reported in a female medico chemical analysis report confirmed it to be death due to dapsone. Management in case of dapsone poisoning is also discussed.

Dapsone↗

ELISA tests for dapsone and pyrimethamine and their application in a malaria chemoprophylaxis programme.

Enzyme-linked immunosorbent asays (ELISAs) are described for determining levels of dapsone and pyrimethamine in urine. Both assays have a sensitivity of about 20 mug/l and are reproducible, but each produces some false positives. The problem of false positive reactions was partially obviated by requiring positive results in both assays. In a pilot study involving 50 children aged 3 months to 4 years who were given a single dose of Maloprim (pyrimethamine + dapsone), 75% were positive for dapsone 7 days after administration of the drug, while 25% were still positive 15 days after its administration. The corresponding proportions for pyrimethamine were 73% and 30%, respectively. Comparison of the results obtained in a larger chemoprophylaxis trial with those from the pilot study indicated that the assays described could be used to investigate whether antimalarials had been taken.

Child, Preschool↗