Attention is drawn to a number of recently described skin conditions and a number of new treatments which, in the opinion of the writer, warrant more extensive publicity
In a survey of over 1,000 patients with leprosy, 47 cases ( 4.4 per cent) were found to have glucose-6-phosphate dehydrogenase deficiency. A controlled clinical study suggests that such a deficiency does not modify the overall response to therapy but may predispose to a greater tendency to leprosy reactions. All patients were receiving 600 to 800 mgm. of sulphone per week and none had a frank haemolytic anaemia.
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
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.
The first three patients with proven DDS-resistant leprosy infections were treated for one year with the riminophenazine
derivative B.663 (300 mgm. daily for six days a week). All of them showed satisfactory clinical, bacteriologic and histologic
improvement, which at the time of writing has been maintained for a total period of 28 months. The results show that
active leprosy resulting from resistance to one drug can still respond satisfactorily to a different type of drug, as is the case with drug resistance in other bacterial infections. In this limited study B.663 showed no toxicity, but the degree of skin discoloration was disconcerting to Chinese patients.
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.
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.
Kveim tests using a validated material have been undertaken in Malaysia on 39 patients (32 Chinese; 4 Malay and 3 Aboriginal) with lepromatous or tuberculoid leprosy. All the patients had been treated for leprosy, most for two or more years. The tests were read microscopically. Of the 21 lepromatous patients one gave a weak positive and two an equivocal Kveim test whereas four of the nine tuberculoid patients gave equivocal or weak Kveim positivity. Only the tuberculoid form elicits a higher proportion of granulomas than might be expected in a comparable normal population. Of nine patients (8 lepromatous; 1 tuberculoid ) who failed to sensitize well to tuberculin
following two BCG vaccinations, two gave equivocal Kveim tests similar in appearance to those in the other groups.