Leprous neuromyositis: A rare clinical entity and review of the literature.

Mycobacterium leprae, the causative agent of leprosy (Hansen's disease), is a slow growing intracellular acid-fast bacillus that affects the skin, peripheral nerves and respiratory tract. In patients with suppressed cell-mediated immunity, the infiltration of the Bacilli can produce disseminated illness such as leprous neuromyositis. We reported a case of 56-year-old gentleman presenting with pyrexia of unknown origin, asymmetric sensory motor axonal polyneuropathy and was on chronic exogenous steroid therapy. On evaluation, his skin, muscle, nerve and bone marrow biopsy showed numerous globi of acid-fast Bacilli suggestive of leprous neuromyositis, a rare form of disseminated Hansen's disease. We reported this case in view of its rarity, atypical manifestation of a relatively rare disease and literature review on poor electrophysiological correlation in the diagnosis of leprous neuromyositis as compared to the histopathological examination.

The disease of CBA and BALB/c mice that follows inoculation of a small number of Mycobacterium lepraemurium into the hind foot pad.

To learn if the lack of an immune response in mice infected with Mycobacterium lepraemurium (MLM) was a consequence of the organisms, we studied the disease that followed inoculation of less than or equal to 5000 organisms into the hind foot pads of CBA and BALB/c mice. The mice of both strains demonstrated a rapid increase of bacterial numbers soon after inoculation, with a slowing of the rate of multiplication once the number of organisms per foot pad passed 3 x 10(7). By 1 year after inoculation, the numbers of organisms had reached levels greater than or equal to 10(11) in the spleen and liver, and greater than or equal to 10(8) in the femoral bone marrow. In mice that had been inoculated with as few as 5 MLM or 50 MLM, the organisms had multiplied to numbers greater than 10(8) in the foot pads and to greater than or equal to 10(9) in the spleens, suggesting that the ID50 of viable MLM may be less than or equal to 5 organisms per foot pad. No protection against superinfection could be demonstrated. On the other hand, initial multiplication of MLM in the foot pads was followed virtually immediately by the death of at least 97% of the organisms.

Bone marrow cyto-morphological changes in multibacillary leprosy.

Seventy-two cases of multibacillary leprosy were investigated for cytomorphological changes and presence of lepra bacilli in bone marrow. These patients were divided in two groups. Group A (28) comprised of new cases and group B (44) of those receiving treatment. Myeloid hyperplasia was mostly seen in patients of group B who had erythema nodosum leprosum. Megaloblastic change in erythroblasts was seen frequently in both the groups. While average number of plasma cells and macrophages was on the higher side of normal range, detection of large number of plasma cells underlined enhanced humoral response and created diagnostic problem with multiple myeloma. Morphological changes in the macrophages, their collections and epithelioid cell granulomas were observed in bone marrow. Their nature and significance is discussed.

Nongranulomatous involvement of the bone marrow in lepromatous leprosy.

Bone marrow involvement in lepromatous leprosy has been characterized histologically by a proliferation of foamy histiocytes containing lepra bacilli, the so-called Virchow cells. The authors have studied three patients with biopsy-proven lepromatous leprosy in whom Fite stain, performed on histologic sections of bone marrow aspirates, demonstrated numerous bacilli lying free in the interstitium in the absence of Virchow cells or focal collections of foamy macrophages. Two of the patients had a recent diagnosis of lepromatous leprosy by skin biopsy; the third patient had a 33-year history of lepromatous leprosy that had been treated. Bone marrow aspirates were performed in all three patients for evaluation of anemia. The findings indicate that the bone marrow may act as a reservoir for viable organisms in the absence of a host response in treated and untreated patients with lepromatous leprosy. The persistence of viable organisms in the bone marrow in patients with lepromatous leprosy may account for the high rate of relapse and/or recrudescence of the disease following cessation of specific therapy. Bone marrow examination with the Fite modification of the acid-fast stain is therefore indicated in such patients to evaluate bone marrow involvement and the efficacy of treatment.

Bacillaemia and bone marrow involvement in leprosy.

Fifty patients (24 new and 26 receiving specific treatment) of leprosy were investigated to study the concentration and morphological index (MI) of the lepra bacilli in skin, peripheral blood and bone marrow. The organisms were detected in 28 cases on skin slit smear examination, in 38 cases on bone marrow examination and in 38 cases on examination of smears made from buffy coat of peripheral blood. Out of 22 cases negative for the bacilli on skin slit smears, 15 had the organisms either in buffy coat or bone marrow or both. Acid fast bacilli in peripheral blood and bone marrow with skin smear negativity were mainly observed in patients with paucibacillary type of the disease and in those who were receiving treatment. Examination of buffy coat and bone marrow for presence of lepra bacilli is suggested to establish the diagnosis in doubtful cases.

Primary visceral virchowian (lepromatous) hanseniasis.

A case of primary visceral virchowian hanseniasis is presented. The onset and symptoms of the disease made one think that it was a lymphoma because of the severe enlargement of the liver, spleen, and lymph nodes. Biopsies of the liver, lymph nodes, and bone marrow revealed virchowian infiltration with acid-fast bacilli and globi. The skin was free of lesions and negative to bacilli, and there were no neural symptoms.

Attempts at cultivation of Mycobacterium leprae in macrophages from susceptible animal hosts.

Macrophages from nude mice, nude rats, and armadillos were cultured in vitro and examined for their ability to support Mycobacterium leprae. No significant growth of this organism were observed after over 200 days of culture. No significant benefit was derived from modifying culture conditions or from variations in the source of macrophages or the source of M. leprae.

In vitro cultivation and characterization of Mycobacterium lepraemurium.

Three different strains of M. lm were regularly grown in vitro from suspensions of mouse organs if at least 10(5) organisms were inoculated on Ogawa egg yolk medium and incubated at 35 degrees C in a humidified, CO2 enriched atmosphere. Growth is slow and requires 2-3 months. Colonies are 1-2 mm in diameter, white to pale yellow. Microscopically the bacteria are acid-alcohol-fast pleomorphic rods with branchings and beaded filamentous forms. Mice inoculated with in vitro grown subcultures develop an infection indistinguishable from the one observed after injection with mouse passage strains of M. lm. The in vitro characteristics of the strains are identical and different from all other known mycobacteria.

Bone-marrow in tuberculoid leprosy.

Twenty-four untreated patients of proved tuberculoid leprosy and five healthy controls were investigated for the involvement of bone-marrow. The cytology was essentially normal and no acid-fast bacilli was seen in the bone-marrow smears.

The role of protein malnutrition in the pathogenesis of ulcerative "Lazarine" leprosy.

1. Clinical and necropsy observations in lepromatous leprosy associated with severe emaciation and accompanying hypoproteinemia suggest that protein deprivation may be of pathogenic significance in the ulcerative phenomenon that is designated "Lazarine leprosy". 2. An experimental utilizing Wiersung rats infected with Mycobacterium lepraemurium and maintained on a protein-free diet was developed for the purpose of studying the effect of protein starvation on the course of chronic mycobacterial disease similar to lepromatous leprosy with respect to pathogen and host inflammatory response. 3. It was possible to maintain the experimental animals on a protein-free diet for up to 18 weeks of concomitant M. lepraemurium infection. This was long enough for the infection to disseminate to a degree that was evident in control animals only several weeks later. 4. The protein-deprived animals showed decreased inflammatory response to the pathogen, presented more rapid dissemination of the infection and harbored more bacilli per macrophage than did animals similarly infected but maintained on a protein adequate diet. This indicates impairment of native cellular immunity by protein deprivation through decrease in ability of macrophages to inhibit bacillary multiplication. 5. There was no evidence of impairment of macrophage ability to phagocytose the pathogens. 6. Morphologically the increased dissemination of pathogens and decrease in inflammatory response was similar to the increase in number and extent of visceral lesions seen in Lazarine leprosy. Decreased ability to dispose of the infecting bacilli was similar in the two models, human and animal. The animal model does not, as does lepromatous leprosy, involve the skin in the infection. Hence comparable ulcerative phenomena were not replicated in the animals. 7. It is suggested that Lazarine leprosy may result from enhanced lepromatous leprous infection occurring as a result of protein malnutrition. The pathogenic mechanism appears to be impairment of cellular immunity probably enhanced by concomitant impairment of humoral antibody immunity resulting also in decreased resistance to pyogenic and other secondary pathogens. The tissue edema attendant on decreased serum osmotic pressure due to lowering of the serum protein fractions enhances the probability of ulceration.

A comparative evaluation of bacteriologic and morphologic indices of Mycobacterium leprae in skin, lymph node, bone marrow, nerve and muscle.

This study elicits the comparative evaluation of the Bacteriologic Index (BI) and Morphologic Index (MI) of the skin, lymph node, bone marrow, nerve and muscle tissues of 15 untreated leprosy patients. The findings of comparable or even higher BI's and MI's in lymph nodes than skin are of considerable interest, especially the presence of a significant percentage of viable bacilli during reaction states when MI of skin and nerve tissue was found to be negative. Evaluation of the BI's and MI's of lymph nodes has been suggested to be of utmost importance for follow-up studies of patients being treated with antileprosy drugs.