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.

Reversal reaction and Mitsuda conversion in polar lepromatous leprosy: a case report.

A 22-year-old male polar lepromatous leprosy patient who became Mitsuda positive after 36 months of multidrug therapy (MDT) is reported. Lepromatous leprosy (LL) is a state of specific immunosuppression and is invariably irreversible. The finding of Mitsuda positivity in histopathologically proven polar lepromatous leprosy is extremely uncommon, and conversion of lepromin status following MDT has not so far been reported. This case reports confirms the observations made by Waters et al. regarding lepromin conversion in lepromatous patients.

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.

Visible deformity in childhood leprosy--a 10-year study.

Deformity seen in children with leprosy has not often been studied, as the disease itself is less common in children. Deformity, being synonymous with the stigma of leprosy, is a definite social problem in children. In this study we have focused on the burden of deformity in children with leprosy, and various factors responsible for the deformities are discussed. We have observed an incidence of 10.5% of Grade II deformities in children with leprosy, which is very high compared to the community rate of 1.4%. Various factors which contributed significantly to the deformities in our study were: increasing age of children, delay in accessing health care, multiple skin lesions, multibacillary disease, smear positivity, multiple nerve involvement, and reaction at the time of presentation to the hospital. Logistic regression analysis showed that children with thickened nerve trunks had 6.1 times higher risk of developing deformities compared to those who did not have nerve enlargement. Children with the above risk factors should be followed up more frequently so as to detect any deformity as early as possible.

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.

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.

Single lesion borderline lepromatous leprosy.

A patient is reported who presented with a single lesion on the face which, on histopathological examination, was found to be borderline lepromatous leprosy. The importance of doing skin smears as a routine in all patients to differentiate Multibacillary from Paucibacillary disease is emphasized.

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.

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.

Pathology and pathogenesis of leprous neuritis: a preventable and treatable complication

In conclusion, it may be said that many advances have been made in the diagnosis, treatment and prevention of nerve damage. It is now a well accepted fact that the affinity of M. leprae for Schwann cells and the property of M. leprae to grow in cooler sites of the body have made certain segments of nerve trunks vulnerable. Trauma that supervenes the inflammation and swelling severely aggravates the nerve damage. The reactive phase in all forms of leprosy, the etiology of which is not clearly understood, produces intraneural caseous necrosis in tuberculoid disease and microabscesses in lepromatous disease, causing much irreversible damage to nerves. The steroid treatment that is administered during the reactive phase has helped greatly to stop further damage, although the damage already done to nerves is not always reversible. Preventive measures like detecting the disease before nerve trunks are infected and offering prompt and adequate antileprosy therapy as early as possible have helped to reduce the prevalence of deformities. It is hoped that administering steroids along with antileprosy therapy to prevent active inflammation and or fibrosis of the nerve will reduce the prevalence of nerve damage significantly. Measures which provide rest for the infected nerve to prevent trauma should be explored.