Cases of leprosy due to immune reconstitution inflammatory syndrome (IRIS) in individuals starting anti-HIV therapy are rare, unlikely to pose a risk of infection to other HIV-positive patients or members of the wider community, and not life-threatening, an editorial in the February 3rd edition of the British Medical Journal stresses. The authors also write that occasional cases of non-fatal leprosy due to IRIS in antiretroviral-treated patients need to be seen within the context of the hundreds of thousands of lives saved per year in resource-limited settings due to expanding use of anti-HIV therapy.
In October 2006 the New York Times reported a “startling and worrisome link” between antiretroviral therapy and leprosy. The article noted that a small number of individuals who started anti-HIV treatment in countries where leprosy is endemic developed an unusually florid type of the disease soon after commencing treatment with anti-HIV drugs.
But the authors of the BMJ editorial go to lengths to explain that although HIV and leprosy are feared and stigmatised illnesses, IRIS is a well-known complication of anti-HIV therapy, and anti-HIV therapy is not causing new cases of leprosy. They also stress that the type of leprosy that develops due to IRIS is not a public health risk.
Leprosy and IRIS
HIV has had little effect on either the epidemiology or the clinical manifestations of leprosy. However, the authors note that IRIS is a “new and unexpected clinical interaction between these diseases in patients who have just started treatment.” The first published case of leprosy-associated IRIS was in 2003 and involved a Ugandan patient in London. More cases have since been reported, many in South America.
In most of the reported cases, IRIS triggered the first manifestation of leprosy symptoms. Some of the cases have been severe, involving skin ulceration, long lasting inflammation, and neuropathy.
IRIS associated with common AIDS-defining illness has been frequently observed in resource-rich settings such as the UK. As antiretroviral access improves in resource-limited settings, IRIS involving opportunistic infections endemic in these areas have occurred, for example the parasitic infections leishmaniasis, strongyloidiasis, and schistosomiasis. The authors write, “leprosy has joined this growing list of tropical infections associated with immune reconstitution disease.”
Indeed, as access to HIV therapy is expanding in countries where leprosy is endemic, it should not be surprising that reports of leprosy-associated IRIS are increasing. For example India, which has a rapidly growing HIV epidemic, had over 160,000 new cases of leprosy in 2005.
What is IRIS?
IRIS involves the emergence of symptoms associated with a pre-existing infection that was not causing illness, or the deterioration of an infection that had been responding to treatment. This is because anti-HIV therapy causes a rapid recovery of immune responses, triggering a response to infections. IRIS usually occurs during the first four months of anti-HIV treatment - the period of most rapid immune recovery.
The need for perspective
The authors emphasise that leprosy-associated IRIS is not a public health worry. “Leprosy presenting as immune reconstitution disease represents the manifestation of previously subclinical disease and not the development of new infections”, they write. New cases of leprosy due to IRIS do not, therefore, represent a deterioration of leprosy control measures. Furthermore, the type of leprosy that develops in IRIS cases is usually non-infectious, meaning “these cases are unlikely to pose a risk of infection to people in antiretroviral treatment clinics or in the community.” In addition, although IRIS associated with tuberculosis can prove fatal, this is not the case with leprosy due to immune reconstitution.
The authors conclude with a plea for perspective, writing, “antiretroviral treatment will continue to save hundreds of thousands of lives each year, but unusual manifestations of immune recovery, including leprosy, will inevitably occur.”
Two stigmatised illnesses
The authors stress the importance of viewing a leprosy IRIS from the patient’s perspective. “HIV infection and leprosy are both highly stigmatised diseases”, they write, “and having both is understandably distressing.” This distress is likely to be increased if the patient incorrectly concludes that anti-HIV therapy caused their leprosy. “Frequent cases of this disease could make patients less enthusiastic about antiretroviral treatment programmes”, suggest the authors.
Medical staff providing anti-HIV therapy in countries where leprosy is endemic need to be aware that the disease may present as IRIS. This is vitally important as delayed diagnosis of the disease could result in permanent disability. Staff should therefore be suspicious of any red swellings on the skin or neuropathy during the early months of antiretroviral therapy.
Studies are needed to determine the manifestations and frequency of leprosy-associated IRIS, and the authors note that there are still some questions regarding its optimum management.
Lawn SD et al. Leprosy after starting antiretroviral treatment: an increasingly reported clinical problem but not a serious public health risk. BMJ 334: 217 - 218, 2007.