We evaluate and perform histopathology and inoculation in mouse foot pads for all patients who do not have a satisfactory clinical response to WHO-MDT. It was reported that 30% (3/10) of patients diagnosed with Hansen’s disease (HD), classified as borderline-lepromatous (BL) and lepromatous-lepromatous (LL), had a positive innoculation in mouse foot pads (1), and almost all had well-stained (viable) bacilli or bacilli inside endothelial cells (indicating recent bacillaemia) (2). It is known that patients with higher bacillary index (BI) have a high likelihood of relapse (3).
In our experience, the mean interval from end-of-treatment to relapse (indicated by increasing BI) was 8 years for LL patients treated with 12-dose WHO-MDT and 13 years for those treated with 24-dose WHO-MDT. Almost all relapse patients had shown an initial improvement after 12 doses, but most of them had viable bacilli that continued to grow, sometimes with HD reaction (mostly type 2), leading us to conclude that, unfortunately, the patient was not initially cured.
In our referral center, we also deal with the problem of reinfection when household contacts have not been evaluated or followed up. As many as 50% of our patients with relapse are found to have family members with active disease when we contact them by phone calls or reevaluate them clinically at the center. This suggests that relapses are a consequence of both reinfection and ineffective treatment. Indeed, Doull et al (1942) in the Philippines reported a 0.6% per year attack rate for HD among households (4), an early indication that The M. leprae has the ability to remain dormant and viable in family members.
Dr Opromolla, a Brazilian HD specialist, always said that HD endemicity is sustained by LL patients. These cases are very difficult to diagnose, because the majority of recently infected LL patients do not show signs or symptoms of peripheral neuropathy, and most of them have unremarkable signs and symptoms consistent with rheumatism or vascular disease. In my opinion, the expertise required to stain M. leprae in skin slit smear or biopsy slides has been lost over the past 20 years. In my daily practice, I see patients reporting misdiagnosis and with delays in obtaining a correct diagnosis of HD, arising mainly from lack of suspicion and/or mistakes in laboratory tests.
In Brazil, many physicians believe that HD presents as skin patches, like vitiligo. Hansen’s disease is a primary disease of Schwann cells, with or without skin patches, just as syphilis is a primary disease of endothelial cells, with or without skin patches. As there are thousands of Schwann and endothelial cells in skin, both diseases usually have visible skin inflammation, but not always. This compels me to raise the issue of HD classification based upon the number of skin lesions which, from my point of view, is the Apocalypse of Hansen’s disease. If a patient has a single visible (lepromatous) nodule, should they be classified as a paucibacillary (PB) form? Should we consider the LL form only if a patient has six or more visible nodules? Would we consider primary syphilis in those presenting with one skin lesion, secondary syphilis in those with two lesions, and tertiary with three or more skin lesions?
Chaterjee wrote a very good conceptual description of HD as comprising benign and potentially malign groups (5), whilst Ridley stated that only 10% of patients would develop self-limiting disease (6). In the course of my 20-year career as a specialist in Hansen’s disease working actively to care for patients, I saw fewer than ten persons affected by HD classified correctly as the early tuberculoid (TT) or indeterminate (I) forms of the disease. Most TT cases are in fact borderline tuberculoid (BT) who, if treated as TT, typically relapse after 7 years due to inappropriate WHO-MDT treatment for PB HD. Many patients classified and treated as TT and I are macular borderline, developing neuritis during or after MDT and being likely to relapse after 8 years.
In conclusion, the arguments and evidence presented above highlight the importance of improving our understanding of HD and teaching health professionals in endemic countries about the spectral nature of Hansen’s disease.