Methaemoglobinaemia is an uncommon but potentially serious condition. It can be caused by congenital or acquired cause. Drug-induced methaemoglobinaemia is the commonest cause of acquired methaemoglobinaemia. The clinical signs and symptoms of methaemoglobinaemia include dyspnoea, desaturation, presence of saturation gap, headache, nausea and seizures depending on level of serum methaemoglobinaemia. We illustrate a case of dapsone-induced methaemoglobinaemia and its successful treatment by intravenous methylene blue.
A high-performance liquid chromatographic method was developed to enable dapsone, monoacetyl dapsone and pyrimethamine to be measured simultaneously in plasma samples from volunteers in England and Malaysia who had been dosed with Maloprim. Mean half-lives of 25 and 80 h were calculated for dapsone and pyrimethamine, respectively, but there was wide individual variation. All subjects were found to be classifiable as "slow acetylators".
Dapsone syndrome is a potentially fatal hypersensitivity reaction to sulphone. We report a 12-year-old girl who developed high grade fever associated with intense jaundice, exfoliative skin rash and hepatomegaly after five weeks of starting the multidrug regimen for the treatment of Hansen's disease. Laboratory investigations revealed presence of leucocytosis with eosinophilia, deranged liver enzymes and an abnormal coagulation profile. Immediate cessation of the offending drug and administration of steroid proved successful. A high level of clinical awareness is fundamental for early diagnosis of dapsone syndrome as initiation of a prompt treatment may lead to rapid recovery.
BACKGROUND Leprosy is an infection caused by Mycobacterium leprae. An extensive literature search did not reveal many reports of melioidosis in association with leprosy. CASE REPORT A 22-year-old woman, who was diagnosed with multibacillary leprosy, developed dapsone-induced methemoglobinemia and hemolytic anemia, complicated by melioidosis. Methemoglobinemia was treated with methylene blue and vitamin C. Two weeks of ceftazidime was initiated to treat melioidosis, and the patient was discharged on amoxicillin/clavulanic acid and doxycycline as melioidosis eradication therapy. However, she developed drug-induced hypersensitivity. Trimethoprim/sulfamethoxazole, as an alternative treatment for melioidosis eradication, was commenced and was successfully completed for 12 weeks. During the fifth month of multidrug therapy, the patient developed type II lepra reaction with erythema nodosum leprosum reaction, which was treated with prednisolone. Leprosy treatment continued with clofazimine and ofloxacin, and complete resolution of skin lesions occurred after 12 months of therapy. CONCLUSIONS Our case highlighted the challenges posed in managing a patient with multibacillary leprosy with multiple complications. Clinicians should be aware that dapsone-induced methemoglobinemia and hemolysis might complicate the treatment of leprosy. Our case also highlighted the safety and efficacy of combining ofloxacin and clofazimine as a leprosy treatment regimen in addition to gradual steroid dose titration in the presence of type II lepra reaction.
A controlled clinical trial, using the "double blind " technic, is reported of combined dapsone and ditophal therapy compared with dapsone and placebo in the treatment of pure lepromatous and near lepromatous leprosy. Twenty-five untreated, matched pairs were admitted, and the final analysis was made on 23 pairs and 47 patients studied for one year. Dapsone and ditophal were commenced simultaneously, and over the treatment period 0-1.5 months, a statistically significant (at the 1 per cent level) greater decrease in the percentage of solid-staining bacilli occurred in the smears of pure lepromatous patients treated with ditophal and dapsone than occurred in the smears of patients treated with placebo and dapsone. Therefore, it is evident that combined therapy resulted in a faster rate of killing of leprosy bacilli than did dapsone alone. However, only one method of clinical assessment of the pure lepromatous pairs favored combined therapy; the two other methods of clinical assessment used, and the bacterial index and biopsy index results, all failed to reveal any significant differences between the two treatment groups. In addition, the incidence and severity of erythema nodosum leprosum did not differ in the two groups. Since the more rapid death of bacilli early in treatment had little effect on the rate of improvement of patients after 12 months, the widespread use of ditophal with dapsone does not appear to be justified. Special circumstances are envisaged, however, in which ditophal would be a useful adjunct to treatment. The small number (11) of near-lepromatous patients studied showed a high incidence of lepra reactions, and 4 underwent histologic change during their year in the trial. There was no evidence that the addition of ditophal to dapsone treatment increased the rate of improvement, clinically, histologically or bacteriologically, in this type of leprosy, which, because it is so unstable, appears unsuitable for formal clinical drug trials. Although the majority of the patients included were light-skinned Chinese, no contact dermatitis or other toxic effects of ditophal were observed.
From an extensive search of one of the largest inpatient leprosaria in the world, at Sungei Buloh, Malaysia, nine patients with lepromatous leprosy were discovered who gave prima facie evidence of sulfone resistance. The evidence was based on a failure to show clinical improvement over at least five years despite treatment with sulfones and an absence of a satisfactory fall in the bacteriologic (BI) or the morphologic (MI) index. The selected patients were admitted to our Research Unit for (a) a further six month, rigorously controlled, trial period on DDS (as injectable sulfone, 300 mgm. twice weekly) and (b) DDS sensitivity tests, based on use of the foot pad infection in mice with bacilli obtained from skin biopsies. The response of the nine patients to the six month trial period on DDS was assessed clinically, bacteriologically and histologically, and revealed that only four of the patients failed to respond satisfactorily. Furthermore, the sensitivity tests in the mouse foot pad infection showed that only the strains of M. leprae from the four patients who failed to improve were insensitive to DDS. Thus there was a good correlation between the results of the clinical and experimental studies and for the first time direct proof for the existence of DDS resistant strain s of M. leprae. The MI proved to be the most sensitive of the assessments used to determine the response of the selected patients to a trial period on DDS. The histology of patients with drug resistance is essentially that of relapsing or very acute leprosy. Its features have much in common with those of "histoid" lesions, the latter being distinguished mainly by the absence of cytologic maturation. Classification is complicated by the presence of borderline features in otherwise lepromatous lesions.
An account is given of the first hundred consecutive proven cases of sulphone resistance in leprosy, detected in Malaysia between 1963 and 1974. Proof of resistance was clinical in eighty patients and was obtained by drug-sensitivity testing in mice in ninety-six patients; 76 cases were proved both clinically and experimentally, and there was no discrepancy between the two methods. Sulphone resistance was confined to patients with lepromatous-type leprosy--i.e., patients with a large bacterial population. Clinical evidence of relapse due to drug resistance appeared 5-24 years after the start of sulphone treatment. Low dosage favoured the appearance of resistance; therefore regular treatment of lepromatous leprosy with dapsone in full dosage is recommended. The attainment of "skin smears negative for leprosy bacilli" is no test of cure of lepromatous leprosy.
Proof that a patient is suffering from sulfone-resistant leprosy depends on demonstrating that his bacilli can multiply in the mouse foot pad even when the mice are fed sulfone in the diet. Hitherto the maximal dose of DDS tolerated by the mouse has been used in such tests. This paper concerns a patient whose bacilli multiplied in mice fed lower doses of DDS, but were inhibited when the maximal dose was used . His clinical features are distinctive and probably characteristic of this type of "partial" resistance. It is likely that more cases of this type will be found . Recommendations are made concerning the investigation of possible DDS-resistant leprosy patients and their treatment.
Acne is one of the most common disorders affecting mankind. Although acne does not cause death, it however produces a lot of discomfort, disfigurement and psychological trauma, particularly in teenagers. Acne vulgaris is a chronic condition involving the pilosebaceous unit of the skin. It is characterised by the presence of comedones, inflammatory papules, pustules or cysts, and eventually by scarring. The end result of acne varies from hyperpigmentation, slight pitting, to extremely disfiguring scars that may develop into keloids. Acne fulminans is a rare disorder and is characterised by sudden explosive appearance of highly inflammatory, tender, crusted, ulcerated lesions involving the back, chest and face. It is one of the most scarring acute dermatologic disorders of young people. A case of acne fulminans in a young female who developed haemolysis due to dapsone is reported here.
Matched MeSH terms: Dapsone/adverse effects*; Dapsone/therapeutic use
The proliferative responses of peripheral blood mononuclear cells (PBMC) to Mycobacterium leprae and BCG were studied in two groups of leprosy patients: a group of 8 lepromatous patients who had been on treatment for more than 20 years (TLL) and a group of 8 untreated lepromatous leprosy patients (ULL). The mean response to M. leprae of the TLL group was 6195 cpm with 5 of the 8 patients responding positively. The mean response to M. leprae of the ULL group was 617 cpm, with only 1 patient showing a positive response. The corresponding proliferative responses to BCG were 19,908 cpm in the TLL group and 7908 in the ULL group. Thirteen M. leprae reactive clones were established from 2 TLL patients and 5 M. leprae reactive clones were established from 2 tuberculoid leprosy patients. Seven of these clones, 4 from the TLL patients and 3 from the tuberculoid (TT) patients could be studied further. Three of the TLL clones responded specifically to M. leprae, while one of the clones exhibited a broad cross-reactivity to other mycobacteria. All of these clones were of the CD4+CD8- phenotype. Our findings suggest that responsiveness to M. leprae can be detected in vitro in a proportion of LL patients who have undergone prolonged chemotherapy, and that this response involves M. leprae reactive CD8+CD8- T cells, of which some appear to be specific to M. leprae.
Fifteen patients with pure lepromatous leprosy were treated for 12 months with DDS at 50 mgm. twice weekly. The drug was fully effective in this dose, and the incidence and severity of ENL were not less than on larger doses
In view of the problems caused by the chloroquine-resistance of some strains of Plasmodium falciparum, the authors have investigated the effectiveness of diaphenylsulfone against two such resistant strains, from Malaya and Viet-Nam. They found that diaphenylsulfone given during acute attacks of malaria had a blood schizontocidal activity against the Malayan resistant strain but was not rapidly effective in terminating acute attacks in non-immune persons, and that, when the drug was given prophylactically in relatively small doses, it was substantially effective in preventing patency of mosquito-induced infection with the same strain. The protective effect of diaphenylsulfone is that of a clinical prophylactic or suppressive drug; it does not appear to be a true causal prophylactic. It was also found that the protective effect is vitiated by the concurrent administration of paraaminobenzoic acid.These studies indicate a need for further assessment of the antimalarial value of sulfones and sulfonamides, both alone and in combination with other drugs, for prevention and cure.
Limited data regarding methemoglobinemia in pregnancy, particularly secondary to dapsone is available up to date. We report a case of dapsone-induced methemoglobinemia in a pregnant mother with multibacillary leprosy who presented with fever, productive cough and cyanosis of 2 days duration 2 weeks after multidrug therapy was commenced. On examination, she had central cyanosis with low oxygen saturation (SpO2 = 84-88%). Arterial blood gas analysis showed PO2 of 111 mmHg and SO2 of 98 mmHg. Patient was administered 100% oxygen inhalation, but there was no improvement in cyanosis. Vitamin C (1000 mg/day) was prescribed. Dapsone was replaced by ofloxacin 200 mg twice daily. There was a gradual increase in SpO2 level. She delivered a healthy baby. In conclusion, clinicians should be aware of the side effects of dapsone and know how to promptly manage any undesirable events. Ofloxacin is a safe and feasible alternative in replacement of dapsone in pregnancy.