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A Case of primary paucibacillary Dapsone resistance was presented. Its clinical suspicion and diagnosis are stressed. Emergence of dapsone resistance and its implications are shortly reviewed. A short note on its prevention is discussed. Literature is briefly reviewed.
A thirty-one year old male patient was diagnosed and treated for a pure or better primary neuritic case of leprosy with dapsone (100 mg daily for 2 years) and rifampicin (600 mg daily for 6 months). From the very outset, the patient did not show any improvement; on the top of it, he subsequently, developed a cutaneous patch, which on histopathological examination, revealed classical features of BT leprosy. Acid-fast bacilli were absent both in skin slit smear and histologic section. A primary resistance to both dapsone and rifampicin, even in paucibacillary patient, is speculated.
Dapsone and the related sulfapyridine have been valuable therapeutic agents in many inflammatory disease states although the exact mechanism of action remains unclear. In patients with mild CP or the localized (gingival or ocular) variants, dapsone has been shown to be a relatively safe, first drug of choice in therapy before commencing treatment with systemic corticosteroids and/or immunosuppressive agents. In patients with extensive, severe, or rapidly progressive CP, initial therapy with corticosteroids in a dose of 1 to 2 mg/kg/d of prednisone plus immunosuppressive agents such as azathioprine or cyclophosphamide in a dose of 2 to 3 mg/kg/d are recommended.
Dapsone (DDS) in urine of 250 leprosy patients collected on surprise visits were screened by simple paper spot, tile tests and sensitive Enzyme linked immunosorbent assay (ELISA) and Haemagglutination inhibition (HI) tests. The urinary DDS concentration as well as DDS/C ratios were also studied. Simultaneously, 50 microliter of blood was collected from each of these patients and its dapsone content was estimated by HPLC. Urine samples with means of 25 to 30 micrograms/ml DDS and 55-64 micrograms/mg DDS/C ratios were found to give positive tests by any of the above screening procedures, while their mean blood DDS concentration was found to be 0.91 microgram/ml. The corresponding values for those specimens giving negative tests were 3.8 to 5.7 micrograms DDS per ml and 9 to 13 micrograms/mg DDS/C ratio. The blood DDS concentration in this group was ranging from 0.16 to 0.18 micrograms/ml. The findings are discussed in relation to their metabolic significance and their application in a leprosy control programme.
Dapsone (DDS) is a drug of choice in the treatment of leprosy. The DDS and MADDS levels and different pharmacokinetic parameters after a single dose of dapsone and at steady state in leprotic patients have been studied. At steady state, all the patients showed plasma DDS and MADDS levels above 0.5 micrograms/ml throughout the 24-h duration. There was no significant difference in the elimination half-lives of DDS and MADDS after a single dose as compared to at steady state, but AUC0-alpha for both DDS and MADDS were significantly increased at steady state. From these results, it could be concluded that 100 mg daily dose is sufficient to maintain plasma therapeutic concentration in leprotic patients in Indian population.
In 11 patients suffering from polymyalgia rheumatica or Horton's disease, dapsone was associated with corticotherapy because of corticosteroid side effects (11 cases) and/or progression of the disease despite relatively high dose steroid therapy (6 cases). This treatment had to be discontinued in 4 patients because of side effects and in 3 patients because of a recurrence of the disease. Despite these numerous withdrawals, dapsone seems to be of clinical benefit in these patients because of 1) the mildness of the side effects observed in this study, 2) its efficacy evaluated on the improvement of clinical signs of the disease and, overall, on the decrease in the corticosteroid consumption.
The authors report a case of adult rheumatoid purpura with severe gastrointestinal complications which responded extremely well to treatment with Dapsone. Although this drug has been reported to be effective in treating some forms of allergic vasculitis and the cutaneous manifestations of rheumatic purpura, there have not been any previous reports of its beneficial action in the treatment of the gastrointestinal complications of rheumatoid purpura. The mode of action is not fully understood. Dapsone could constitute a valuable therapeutic option together with steroids, parenteral nutrition and plasmapheresis in the treatment of the gastrointestinal complications of rheumatoid purpura.
A preliminary report is presented on the finding in a patient with lepromatous leprosy relapsing after maintaining clinical inactivity and bacterial negativity with dapsone monotherapy for a period of 23 years. Interestingly, Mycobacterium leprae from the fresh skin lesions revealed resistance to both clofazimine and dapsone by standard mouse foot pad testing.
A 31-year-old male patient with lepromatous leprosy developed fever, malaise, nausea, anorexia, lymphadenopathy, hepatitis, exfoliative dermatitis and ainhum like lesions while on multidrug therapy comprised of dapsone, clofazimine and rifampicin. The provocation tests confirmed the dapsone to be cause of this event.
The existence of an association between regularity in dapsone intake and the development of deformity was investigated in 5746 leprosy patients under treatment in South India. The incidence of deformity, year by year over a 5-year period, increased significantly with increasing levels of drug collection. The excess incidence in "more regular" patients was significant at all ages and in both sexes in nonlepromatous (N) cases. The same was true in intermediate (N?L) cases except in patients under 15 years of age. The evidence in lepromatous (L) cases was not so consistent. Independent confirmation of the presence of the association was sought through a matched case-control type of analysis with 140 N, 48 N?L, and 81 L cases, matching being undertaken with respect to sex, age, type of leprosy, year of starting treatment, and observation period. This showed that the mean regularity in cases (deformed patients) before the development of deformity was significantly higher than the mean regularity in the corresponding matched controls, the differences being particularly large among the N and N?L types. These findings raise the possibility of a causal link between regular dapsone intake and the development of deformity.
Guidelines for the assessment of patient compliance to dapsone were developed and evaluated. The urinary dapsone-to-creatinine (D/C) ratio following standardization by dose, ideal body weight, and time since last dose was used for assessment of compliance. Compliance standards were established in 12 patients of known compliance and confirmed prospectively in nine inpatients on 14 occasions. Compliance increased significantly among outpatients (N = 30) attending the University of Illinois Hansen's Disease Clinic from 47% at base line to 73% at 6 months and 80% at 18 months after establishing the monitoring program. In a subgroup of 18 patients, a similar increase in compliance was observed from 50% to 80%. A good therapeutic response was seen in the subgroup patients who were compliant. A poor therapeutic response was seen in the consistently noncompliant patients. These results demonstrate that use of a continual compliance monitoring program can improve patient drug compliance in an outpatient Hansen's disease clinic.
The Urinary DDS/Creatinine ratios in the supervised in-patients and out-patients attending the C.L.T. & R.I., clinic were compared. The subjects of this study were receiving dapsone at the daily dosage of 25, 50 and 100 mg or bi-weekly dosage of 25, 50, 75, 100 and 200 mgs. The mean urinary DDS/Creatinine ratios from out-patients were significantly lower than those of the in-patients in both dosage schedules of treatment and suggest that a certain percentage of out-patients have been irregular in the intake of dapsone in the period immediately prior to the collection of urine specimens. The estimated percentage of gross irregularity of intake is markedly higher in the bi-weekly as compared with the daily dosage schedule. The gross irregularity of intake was particularly marked in the higher dosage groups such as 100 mg daily or bi-weekly and 200 mg bi-weekly. The implications of the findings are discussed.
Previously we observed clinical and histological regression of Kaposi's sarcoma in the skin in a 38-year-old man with AIDS following treatment with Dapsone. This observation initiated the present study where 6 patients with Kaposi's sarcoma in the skin without clinical signs of systemic spreading were treated with Dapsone 100 mg daily for four months. During this treatment clinical and histological regression of Kaposi's sarcoma was found in three patients. In a further patient only clinical regression was found, while no regression was found in the remaining two patients with Kaposi's sarcoma.
A field survey was designed and carried out in parts of Kancheepuram and Tiruvannamalai Leprosy Control Units in Tamilnadu (population 418,000) with the objective of finding out the prevalence of secondary dapsone resistance among 790 lepromatous (LL and BL) cases, who formed the patient population at risk based on certain treatment criteria. Using the mouse footpad experiment, 3 resistant cases were identified in Kancheepuram Unit (prevalence rate of 1.0 per cent) and 11 cases in Tiruvannamalai Unit (prevalence rate of 2.2 per cent). The metabolic status of dapsone was found to be normal in more than 90% of the patients, showing no relationship to occurrence of resistance.
Acetylator phenotype was determined in 54 patients with rheumatoid arthritis (RA) taking dapsone in the course of 2 comparative clinical studies. No significant differences were demonstrated in the assessments, either of efficacy or adverse effects. There appears to be no clinical advantage in assessing acetylator phenotype in patients with RA being treated with dapsone.
A 33-year-old woman had many tender, erythematous and pustular plaques on her face, neck, and extremities. Biopsy findings were consistent with a diagnosis of Sweet's syndrome. A chemotaxis test disclosed increased chemotactic activity of the peripheral blood polymorphonuclear neutrophil leukocytes. The patient was successfully treated with dapsone. To the best of my knowledge, this is the first reported case of Sweet's syndrome in which dapsone therapy was used successfully.
Permeability of Mycobacterium leprae to dapsone in vitro was determined by the ability of the drug to inhibit o-diphenoloxidase of the bacilli. Dapsone showed little effect on the enzyme activity of the intact organisms. When the M. leprae preparations were washed with trypsin, NaOH, or acetone and ether, DDS penetrated the bacillus to inhibit its o-diphenoloxidase. The method might be useful in studying the utilization of added metabolites by purified M. leprae suspensions.
Available reports both from rural and urban leprosy centres prove beyond any doubt that dapsone is not being consumed regularly by all those who show regular clinic attendance. No reports are available from urban field projects where SET programme is being operated. In this study surprise urine samples of 294 patients of all types (smear positive 53%) mainly on dapsone monotherapy attending (1) leprosy treatment centres in slum clinics situated in the field areas adopted for SET work by Bombay Leprosy Project and (2) general hospital clinics situated predominantly outside the project area were analysed for dapsone/creatinine ratio to judge the extent of drug compliance. 201 out of 294 (68%) were regular and 82 out of 294 (28%) were irregular in consuming DDS as judged by urine examination. 67% of smear positive cases were regular. No difference was found in regularity between patients living within the project area (intensive follow up is done in this group to remind about treatment) and outside project area patients (no reminder followup is done). Similarly no difference was observed in regularity amongst the patients attending slum clinics and general hospital clinics. It could be stated that facilities for treatment offered at general hospitals or dispensaries and encouraging voluntary reporting could be quite fruitful and economical for obtaining better drug compliance in urban areas.