Pages 220 - 223 Volume 91, Issue 2
Excess of deaths of leprosy-affected people
Cite this article
C. Ruth Butlin;
Excess of deaths of leprosy-affected people; Leprosy Review; 2020; 91; 2; 220-223; DOI: 10.47276/lr.91.2.220
Leprosy Review
British Leprosy Relief Association
Colchester, UK
‘It must be remembered that leprosy is not one of the killing diseases, because very seldom does a patient finally succumb to it… we should consider the prognosis of leprosy with the greatest of care…’ so wrote Dr Robert Cochrane1 in 1964. Nevertheless, some people do die from leprosy itself and many more die from indirect effects of leprosy. Rogers & Muir in their 1946 textbook2 claimed that ‘while lepromatous leprosy undoubtedly shortens life, the tuberculoid type apparently does not’. In the pre-sulphone era there were several studies of mortality, but most were case series either looking at deaths in hospitals or at deaths in institutions where leprosy-affected people had been confined for many years. Very few authors were able to compare standardised rates with the general population.
A review of 953 deaths of people admitted at Carville (1939-63) showed that there was little difference in the death rate, compared with the general population, except an excess for lepromatous cases during their first year of admission. In particular, there was no excess of lymphomas nor of cancers.3 People admitted to a sanatorium in Argentina4 who died between 1941 and 1960 (630 individuals) had a high proportion of deaths from uraemia, specifically amongst patients who had had leprosy reactions, and from heart disease, in those over 50 years old. The life expectancy was 51 years of age for a lepromatous case compared with 66 years old for members of the general population. The authors concluded that ‘lepromatous leprosy whether quiescent or with reactions, shortens the life of the patient’.4 A community study from The Phillippines5 concluded that, compared with the death rate in the general population (of 17.2/1000 pyar), the death rate was only a little higher for non-lepromatous cases (19.1) but much higher for lepromatous cases (88.9). The difference was greater for younger age groups. In India, from a series of autopsy reports (41 cases who died in hospital between 1941 and 1964), the authors remarked on the fact that most bodies were emaciated and showed signs of neglect. The most common immediate cause of death was tuberculosis, while other causes included ‘severe exacerbation of leprosy’ and tetanus.6 Similar findings came from 150 autopsies at an asylum in Japan: in 54.7% cases, tuberculosis was the cause of death, and second commonest cause was uraemia to which lepromatous cases with reactions were especially susceptible.7
After the introduction of sulphone therapy, apparently the mortality rates amongst leprosy patients fell dramatically8 but in 1972, in India, it was found that the standardised mortality rates amongst lepromatous patients was twice that of non-lepromatous patients and 3.5 times as high as the rate amongst the general population.9 The age of onset of leprosy was shown to be a risk factor for early death amongst lepromatous patients in The Philippines – those with onset before age 18, having a significantly shorter survival than those whose disease began after age 18.8
From China a report on deaths of all people registered as new leprosy cases over a 6 year period found that 221/524 (42%) deaths occurred within 12 months of starting MDT; 143/524 (27%) deaths were attributed to leprosy and of these 37 were within the first 3months of starting MDT (liver impairment, renal insufficiency and dapsone hypersensitivity syndrome were mentioned).10 In Brazil, a review of deaths of 4,907 people who had had leprosy found that in 59.3% cases, leprosy was given as either a contributing or underlying cause of death,11 but unfortunately the mortality rate amongst people diagnosed with leprosy was not compared with the general population mortality rate. Another study from Brazil12 found that leprosy was mentioned on the certification of 0.1% deaths nation-wide, with lepromatous leprosy being the most common form cited. In 38% cases leprosy was said to be the underlying cause of death and in 62% cases it was an associated cause.
What are the possible causes of death directly or indirectly attributable to leprosy? In 1978, Jopling13 stated that in the vast majority of cases, causes of death in leprosy-affected people were the same as for the general population from which they were drawn, with the exception of the following:
renal damage in lepromatous cases; adverse effects of anti-leprosy and anti-reaction drugs; severe leprosy reaction; glottal oedema causing asphyxia; increased incidence of tuberculosis amongst those resident in leprosaria (but not for those living in the community).
He considered it likely that long-term sulphone therapy gave some leprosy patients protection against death from malaria. One might notice that adverse effects of anti-leprosy drugs would include overdose (accidental in children or intentional in adults) which was reduced after the introduction of blister calendar packs. Suicide in response to a diagnosis of leprosy may be less frequent than in the past, but one paper from China reported that the leading cause of death in a cohort of leprosy cases, diagnosed between 2000 and 2005, was suicide.10
Asphyxia from laryngeal involvement in lepromatous leprosy, once a greatly-feared complication, is almost unknown in the modern era since earlier case detection and the use of rifampicin in anti-leprosy chemotherapy regimens has become the norm. However, despite modern anti-reaction therapy, severe ENL reaction is still a life-threatening condition: at a tertiary referral centre out of 99 ENL cases admitted over a 5 year period, 9 died. By comparison there were only 2 deaths amongst 145 cases admitted for reversal reaction.14
Renal impairment as the presumed cause of death was mentioned frequently in early reports4,7 and more recently.10 Autopsy reports suggested it accounted for 11–38% deaths15 and the usual pathology was thought to be either amyloidosis or glomerulonephritis. In renal biopsies the glomerulonephritis of leprosy was shown to be associated with deposition of immune complexes, ENL reaction being proposed as the major source.16,17 Although renal amyloidosis was thought to be less common since the introduction of effective chemotherapy for leprosy and better anti-reaction treatment,15 signs of glomerulonephritis (proteinuria/ hypo-albuminaemia and reduced glomerular filtration rate) were found in a high proportion of patients with ENL even in the modern era.18,19 It is not clear how frequently glomerulonephritis associated with prolonged ENL reaction leads to life-threatening chronic renal disease.
Jopling also stated13 that ‘non-specific impairment of CMI in leprosy is not associated with any predisposition to infections, whether bacterial, viral or protozoal or mycotic, and it is doubtful if there is any predisposition to malignant disease’. This still seems to be true. It remains to be seen whether the covid-19 pandemic will have a greater impact on leprosy-affected communities than on the general population.
Other important (and eminently preventable) causes of death in leprosy-affected people – not listed by Jopling – are the complications of neuropathic damage to limbs, including tetanus or septicaemia secondary to trophic ulceration.8 Although some deaths are clearly an indirect consequence of neural impairment due to leprosy, other surplus deaths may be a non-specific result of unhealthy living conditions associated with disability. Blind leprosy-affected people had a 4.8 times higher death rate than other leprosy-affected people in Korea, even after adjustment for other factors. Those of younger age had a greater relative risk of early death.20 There may also be surplus deaths from other treatable conditions in leprosy-affected people resulting from their difficulty in accessing public medical facilities, in the same way as reduced access to medical care by intellectually-impaired people is associated with reduced life expectancy in UK.21
It is time to consider the mortality rates associated with leprosy in endemic countries in the 21st century, and specifically to ask whether even today those diagnosed with lepromatous leprosy (in particular, young people and those with ENL reactions) have a shortened life expectancy compared with the general population.
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