Histopathological study of ocular erythema nodosum leprosum and post-therapeutic scleral perforation: a case report.

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae , clinically present either as tuberculoid, borderline or lepromatous type. Erythema nodosum leprosum (ENL) is an acute humoral response in the chronic course of lepromatous leprosy. Although very severe ENL reactions are known in systemic leprosy, such severity is rare in ocular tissues. A leprosy uveitis patient suffered from a severe form of post-therapeutic ENL reaction which resulted in perforation of the globe at the site of preexisting subconjunctival leproma. Painful blind eye was enucleated. Histopathological study revealed infiltration of numerous polymorphs and macrophages packed with acid-fast bacilli in the conjunctiva, cornea, ciliary body, ora serrata and sclera. A profuse influx of neutrophils on a background of macrophages packed with M. leprae confirmed the ocular ENL reaction. This case is reported to alert the ophthalmologists to a rare ocular complication of ENL.

Recent histopathological studies in leprosy, with particular reference to early diagnosis and leprous neuropathy.

In histopathological studies in leprosy, two important areas were identified in recently published work. They are early diagnosis and neuropathy. In histopathological examination, finding of M. leprae in tissues and/or granulomatous destruction of nerves are the two important findings to confirm the diagnosis. Immunopathological staining of M. leprae, PCR amplification of M. leprae antigen and S100 staining of Schwaann cells have considerably enhanced the sensitivity of histopathological diagnosis. If the two clinical findings such as hypopigmented patches with impaired sensation and thickened nerves accompanied by loss of sensation are the only ones that are taken into account for diagnosis, then a significant number of early patients will be missed. It is pointed out that biopsy examination of skin and nerves, when necessary, and skin-smear studies are indispensable diagnostic procedures. In the study of leprous neuropathy, there are several studies trying to decipher the entry of M. leprae into Schwann cells. The sharing of antigens between M. leprae and surface membrane of Schwann cells may be an important factor. However, there is much more to be learned in this area. In the control and prevention of neuritis, although corticosteroids administered along with multi-drug therapy was helpful, the benefit was not sustained.

Presence of Mycobacterium leprae in epidermal cells of lepromatous skin and its significance.

A 49-year-old man with lepromatous leprosy treated with dapsone monotherapy for 12 years (1967 to 1979) reported in the hospital in 2003, with relapsed disease. A slit skin smear showed a bacteriological index of 4+. Biopsies from skin lesions before and after anti-leprosy therapy showed features of lepromatous leprosy. Both biopsies showed unusual features of bacillary clumps in epidermal cells demonstrating clearly that dissemination of M. leprae can take place even through unbroken skin. The presence of lepra bacilli in clumps in the epidermis is an indicator that the skin is a potential route of transmission of the disease.

Penile tuberculoid leprosy in a five year old boy.

A 5-year-old contact of a lepromatous leprosy patient with a tuberculoid lesion on the anterior aspect of the shaft of the penis is reported. The child was clinically suspected to have borderline tuberculoid leprosy during a survey of contacts of leprosy patients, which on histopathology revealed features of subpolar tuberculoid leprosy. The father of the child was recently detected as a case of lepromatous leprosy and was started on multibacillary regime of WHO multidrug therapy. The reason for the localization of the lesion to the shaft of the penis is also suggested. Skin as a route of transmission of tuberculoid leprosy is also emphasized.

Light and electron microscopic appearances of peripheral nerves from two lepromatous leprosy patients after 12 months of multidrug therapy and their significance.

Biopsies from radial cutaneous nerves of a lepromatous patient and one borderline lepromatous patient treated with 12 doses of multidrug regimen were studied using light and electronmicroscopes. Histopathologically both showed typical lepromatous neuritis. Electronmicroscopic examination showed demyelination, atrophy and degeneration of myelinated axons and nonmyelinated axons and a marked increase in collagen fibrils. Perineurial cells, Schwann cells and endoneurial macrophages contained numerous persisting M. leprae. Almost all the organisms in macrophages were fragmented and could be considered non-viable. A few M. leprae found in Schwann cells showed structure of viable bacilli. It is possible a few dead or dormant organisms may persist for many years in Schwann cells or in fibrous tissue without producing any ill effects, and may cause relapse only in rare instances. Since 12 months of MDT resulted in the clearance of M. leprae in course of time and the reported relapse rates after years were insignificant, implementation of MDT for a year for all MB patients is justified provided surveillance of these patients is ensured. Administration of uniform MDT for 6 months is worth a trial.

Squamous cell carcinoma of the scalp arising from chronic cutaneous lupus erythematosus: report of two Indian patients.

Squamous cell carcinoma (SCC) usually arises in skin damaged by actinic rays. Exposure to chemicals like coal tar, soot, arsenic and a variety of oils and distillation products is also implicated in its pathogenesis. It occasionally occurs in scars following inflammatory or degenerative processes. It is an end stage complication of a wide array of inflammatory skin conditions. SCC complicating chronic cutaneous lupus erythematosus (CCLE) in Indian patients is rarely reported. Here we report two such Indian patients with long standing CCLE in whom the diagnosis of CCLE and SCC was confirmed by histopathology.

Are viable Mycobacterium leprae present in lepromatous patients after completion of 12 months' and 24 months' multi-drug therapy?

A study was carried out to determine whether or not viable bacilli persist in MB patients treated with 12-month and 24-month multidrug therapy (MDT). In the first group, 60 untreated lepromatous patients who had an initial average bacterial index (BI) of 3+ or more were enrolled. At the completion of 12 months of MDT, skin biopsies were obtained and M. leprae concentrate was inoculated into the footpads of five thymectomized and irradiated (T900r) mice. Rees technique was used for the mouse footpad (MFP) experiment. Harvesting was done it the 6th, 9th and 12th months. Out of the 60 biopsies inoculated into mouse footpads to check the viability of bacilli, 2 skin biopsies (3.3%) showed significant growth and 10 (16%) showed equivocal growth. 27 patients also had nerve biopsies tested for growth in MFP studies. None of the inoculated nerve biopsies showed significant multiplication in the MFP experiments. However, 4 biopsies (14%) showed equivocal growth. In the second group, 20 patients had skin biopsies and 10 had nerve biopsies done at the end of 24 doses of MDT in order to test the viability of bacilli; none of the skin or nerve biopsies from these patients showed any growth. This study showed that M. leprae present in the tissues after 24 doses of MDT are not viable and the drug schedule of 24 doses is adequate to treat leprosy patients, irrespective of their BI. However, a small (3.3%) percentage of the patients with a high BI harbour viable bacteria in the skin after 12 doses of treatment. Since a large majority of the patients (38 patients) who had a high initial BI responded well to the treatment, it is important to find out the reason for the lack of response in two patients. One of the reasons may be the presence of drug-resistant strains. It is important to follow up on these patients for a longer duration to ascertain whether or not they would relapse.

Drug resistant-Mycobacterium leprae--results of mouse footpad studies from a laboratory in south India.

Out of 265 biopsies of leprosy patients received at the Experimental Pathology Laboratory of Schieffelin Leprosy Research and Training Centre from 1987 to 1997 for evaluating resistant strains of M. leprae, using the mouse footpad technique, 49 showed resistant strains of M leprae to varying concentrations of dapsone, rifampicin and clofazimine. 23 (47%) of these were from a control area. With 369 skin-smear positive multibacillary (MB) patients as the risk group (denominator), 23 (6.23%) were resistant to one or more drugs. 18 (4.88%) had dapsone resistance, 5 (1.36%) were resistant to rifampicin and 9 (2.44%) had resistance to low concentrations of clofazimine (0.0001%). Out of the 23 biopsies with drug resistance from the control area, primary dapsone resistance was seen in 7 (30%) biopsies and secondary dapsone resistance in 11 (48%). Primary rifampicin resistance was seen in 4 (17.4%) patients, secondary rifampicin resistance in 1 (4.35%) and primary clofazimine resistance in 7 (30%). 3 (13%) of the strains showed secondary clofazimine resistance. One biopsy had resistant strains to all the three drugs. In a control area where properly supervised effective multidrug therapy (MDT) was regularly administered over the years, the emergence of drug resistance is negligible. It may not be the case if the content, duration and regularity of the drug regimen were not satisfactory. Aware of the possible shortcomings in mass administration of MDT, it is emphasized that mouse footpad studies on drug resistance should be made available at least in endemic areas where the incidence of the disease has not changed despite good MDT coverage in order to monitor the emergence of drug resistance. Research into molecular biological identification of drug resistant-M.leprae should be intensified. These steps would help to institute timely measures to check the spread of any drug-resistant organisms in the community.

Delayed resolution versus treatment failure in paucibacillary leprosy patients under six months fixed duration multidrug therapy.

Thirty paucibacillary (PB) patients were given multidrug therapy (MDT) PB regimen for six months and were examined clinically and histopathologically before therapy, at six months and 12 months after therapy; and in four patients, at 18 to 23 months after MDT. Histopathological activity was present in 50% and 25% of patients after six months and 12 months respectively after MDT. At 18 to 23 months, the four patients continued to have active lesions both clinically and histopathologically. On the basis of this study it is found that fixed duration of MDT is effective in a large majority of patients especially those with indeterminate leprosy. However, there is "delayed resolution" in a significant number of patients which in a few instances may turn out to be "treatment failures". Therefore, a regular follow up of high risk patients for at least two years and if possible, five years, with freedom to intervene with additional anti-inflammatory or antileprosy therapy as desired, is recommended.

Nerve in reversal reaction.

1. Much of the nerve destruction in leprosy takes place during the reactive phase, both during ENL reaction and RR. 2. The high risk patients expected to develop RR are borderline patients with generalized lesions (more than 10 skin lesions) and those presenting with three or more thickened nerve trunks. 3. In RR there is a sudden enhancement of already existing DTH to M. leprae and its antigens resulting in the release of excessive quantities of TNF alpha, INF gamma, and IL-2. The triggering mechanisms of this phenomenon is poorly understood. 4. The already existing granulomas suddenly increase considerably in size due to oedema and rapid influx of lymphocytes, Langhan's and foreign body giant cells. Fragments of M. leprae are also present in the granuloma of some patients. 5. In RR, the acute granulomatous inflammation can produce destruction of nerves even to the extent of causing caseous necrosis of the nerve tissue and irreversible paralysis. The swelling of the nerves due to sudden increase in inflammatory cells and oedema within an unyielding perineurium produce ischaemia and transient paralysis. 6. With prompt administration of anti-inflammatory drugs, paralysis recovers quickly, if it is of ischaemic origin; but will not recover if the Schwann cells and other nerve tissues are destroyed as a result of the immune granuloma. 7. A course of corticosteroids for six months along with anti-leprosy therapy is suggested in high risk patients as a preventive measure. 8. Further the serious problem of continuing nerve damage after clinical cure should be urgently tackled.