Generalized granulomatous dermatitis following Mycobacterium w (Mw) immunotherapy in lepromatous leprosy.

Mycobacterium w (Mw) vaccine is a heat-killed suspension derived from a nonpathogenic, cultivable, atypical mycobacterium named Mycobacterium indicus pranii. Mw immunotherapy has been reported to be efficacious as an adjunct to multidrug therapy multibacillary regimen in leprosy patients with high bacillary index. Cutaneous reactions are predominant adverse effects associated with the administration of vaccines. Cutaneous adverse effects ascribed to Mw vaccine are generally limited to the site of injection. We herein describe two cases of lepromatous leprosy who developed an unusual generalized cutaneous reaction following Mw immunotherapy. A high index of suspicion is needed to identify such manifestations in leprosy cases to avoid misdiagnosis of a relapse or a reaction and for appropriate treatment.

[Diagnosis and treatment of leprous neuropathy in practice]. / Diagnostic et traitement de la neuropathie lépreuse en pratique.

Leprosy still affects 240,000 persons every year in the world. It is a particularly common cause of neuropathy and severe disabilities in developing countries. With increasing migration, new cases of leprosy are regularly diagnosed in developed countries, where it still remains rare and so underestimated. Cutaneo-nevritic leprosy is the most frequent form of leprosy. It may be diagnosed by the clinical features and the cutaneous histology and bacteriology. Neuritic leprosy without obvious skin lesions is reported in 5 to 15% of leprosy patients. It must be suspected in persons from areas of endemic disease presenting with nerve thickening and associated nerve deficit. Nerve biopsy is essential for diagnosis. However search for bacilli in cutaneous samples may be of great help and avoid nerve biopsy. Acute and severe neuritis occurs during reactional states, reversal reaction (Type 1) and erythema nodosum leprosum (Type 2). Multidrug therapy is advocated. The treatment of acute neuropathy needs a supplementary medical and sometimes surgical treatment.

The systemic influence of recombinant interleukin 2 on the manifestations of lepromatous leprosy.

14 patients with lepromatous leprosy received twice daily injections of 10 micrograms recombinant interleukin 2 (rIL-2), by the intradermal route, in the skin of the back for 8 d (total dose, 160 micrograms). Lymphokine administration was accomplished without drug toxicity, or the development of acute nerve damage. The majority of patients developed nontender axillary lymphadenopathy during the course of treatment. Local injection sites showed progressively larger zones of induration, peaking at 24 h and persisting for many days. Early 12-h reactions were of a macular, erythematous nature and exhibited an increasingly striking diurnal variation. The morning injection sites were three- to fourfold larger in diameter than those placed in the evening (9 am to 9 pm). Systemic manifestations of intradermal rIL-2 administration were noted. Peripheral blood T cells, including CD4+ and CD8+ phenotypes, increased 2-2.5-fold and NK cells increased sixfold. Elevations in [3H]TdR incorporation into peripheral blood mononuclear cells occurred to a variety of mycobacterial antigens, but not to those of Mycobacterium leprae. Within 2 wk, biopsies at sites far removed from the back showed increased infiltration of mononuclear cells in 12 of 14 patients. Immunocytochemistry revealed the presence of newly emigrated CD4+ T cells, monocytes, and dermal CD1+ Langerhans cells. Endothelial cells of small dermal vessels expressed major histocompatibility complex class II determinants on their surface. Transmission electron microscopy of these specimens revealed markedly enlarged endothelial cells with many surface projections extending into the lumen as well as extravasating lymphoid cells. The numbers of acid-fast M. leprae in the peripheral sites were examined by slit smear and in biopsies of matched leprosy lesions taken before and after IL-2 administration. Within 2 mo, slit smears showed a 0.5 log or greater reduction in 12 of 14 patients, with a mean for all patients tested of 0.5 log units. Biopsy specimens showed a 1 log unit or greater reduction in the bacterial index (B.I.) in 6 of 14 patients. Historical controls in this Nepalese population showed a 0.5 log unit reduction after multidrug therapy over a period of 12 mo. Thus, after 8 d of IL-2 injections, a fivefold reduction in B.I. was observed during the first 2 mo of the study. Antibody levels against M. leprae phenolic glycolipid 1 (PGL-1) and lipoarabinomanan B were markedly elevated after IL-2 injections, while PGL-1 antigen levels were reduced. We conclude that the administration of rIL-2 has had a significant effect in decreasing the total body burden of M. leprae.(ABSTRACT TRUNCATED AT 400 WORDS)

Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients.

10 patients with borderline and lepromatous leprosy were selected for a prolonged trial with recombinant interferon gamma (rIFN-gamma). Patients received 30 micrograms intradermally for six injections over a 9-d period, and then either 100 micrograms intradermally every 1 mo for 10 mo or every 2 wk for 5 mo (total, 1.2 mg). Erythema nodosum leprosum (ENL) was induced in 60% of the patients within 6-7 mo, as compared with an incidence of 15% per year with multiple drug therapy alone. The mean whole-body reduction in bacterial index over the first 6 mo was 0.9 log units. Cutaneous induration at the intradermal injection sites of greater than or equal to 15 mm predicted the development of a subsequent reactional state. Monocytes obtained from patients receiving the lymphokine demonstrated an increased respiratory burst and a 2.5-5.1-fold increase in tumor necrosis factor alpha (TNF-alpha) secretion in response to agonists. Patients in ENL had an even higher release of TNF-alpha from monocytes as well as high levels of TNF-alpha in the plasma (mean, 2,000 pg/ml). Thalidomide therapy was required to treat the systemic manifestations of ENL. Control of toxic symptoms with thalidomide was associated with a 50-80% reduction in agonist-stimulated monocyte TNF-alpha secretion. IFN-gamma enhanced the monocyte release of TNF-alpha by 3-7.5-fold (agonist dependent) when added to patient's cells in vitro, and this could be suppressed by the in vitro addition of 10 micrograms/ml of thalidomide.

Self care groups and ulcer prevention in Okegbala, Nigeria.

OBJECTIVE: To assess the impact of the three self-care Groups on ulcer prevalence and readmission rates in Okegbala hospital. DESIGN: A retrospective, descriptive study. The evaluation combined four data collection methods namely (i) records survey, (ii) semi-structured interviews of individual members of self-care groups, (iii) group discussions and (iv) key informant interviews. RESULTS: Record surveys show that the ulcer prevalence has decreased by almost 75% since the adoption of the self-care group; admissions to hospital for ulcer care have reduced, and the mean interval between admissions has increased by 7 months. Semi structured interviews and group discussions show that all members have a greater sense of control of their ulcers and general health; and that self-care groups have a potential of catalysing community solidarity and development. CONCLUSIONS: This small study shows that self-care groups are valuable for reducing ulcers and giving members a greater sense of control of their ulcers and general health resulting in fewer hospital admissions. We recommend a multi-centre, controlled, prospective study incorporating different settings (e.g. urban, rural, near hospitals, within field leprosy programmes) to test these findings. Such a study has the potential of influencing policy and health-service reorientation of ulcer care in future.

A case of feline leprosy caused by Mycobacterium lepraemurium originating from the island of Kythira (Greece): diagnosis and treatment.

A 2-year-old, 4 kg, healthy, domestic shorthair female cat presented with ulcerated subcutaneous nodules on the commissures of its mouth. The cat was negative for feline leukaemia virus and feline immunodeficiency virus. Skin mycobacteriosis was diagnosed after detection of numerous acid-fast bacilli in Ziehl Neelsen-stained smears from the ulcers. Feline leprosy was suspected following preliminary polymerase chain reaction results: positive for Mycobacterium genus but negative for Mycobacterium tuberculosis and Mycobacterium avium complexes. Mycobacterium lepraemurium was later identified following DNA sequence analysis of the 5' end of the 16S rRNA gene and the 16S-23S internal transcribed spacer region. Microscopic lesions consisted of pyogranulomas containing mainly large foamy macrophages with 10-100 intra-cellular acid-fast bacilli per field. The cat was cured after surgery and a 14-week course of clofazimine (30 mg daily) and clarithromycin (50 mg twice daily).

[Nasal leprosy: impact of multitherapy in the morphology and physiology of the nose]. / Lepra nasal: impacto de la multiterapia en la morfología y la fisiología nasal.

INTRODUCTION: The multi-drug therapy protocol has allowed leprosy patients following this strategy to achieve complete recovery without developing neurotrophic sequelae or deformities. OBJECTIVES: To assess the impact of multi-drug therapy on the development of nasal deformities and nasal airway patency. PATIENTS AND METHOD: In an overall group of 84 patients studied, 38 were treated with a therapy based on a single drug and 22 were treated with multi-drug while 24 subjects formed a control group. Nose morphology was determined by anterior rhinoscopy. Nasal patency and flow resistances were measured by anterior rhinomanometry. The results were compared by using the Anova test for a single variable. RESULTS: The nasal structures in the group with therapy based on a single drug underwent resorption of bone and cartilage in the structures of the nose and increased flow resistance. In the group receiving the multi-drug protocol, there were no significant morphological alterations and nasal patency and flow resistance remained within normal levels. CONCLUSIONS: The multi-drug therapy is effective in preventing the development of nasal deformities and maintains normal nasal airflow.

Lichen scrofulosorum in a patient with lepromatous leprosy after BCG immunotherapy.

Lichen scrofulosorum is a rare form of tuberculid seen in children and young adults. The cutaneous lesions are typically symptomless papular eruptions, associated with a strong Mantoux reaction, tuberculosis of lymph nodes and/or other organs or rarely following BCG vaccination. We describe an unusual case of occurrence of lichen scrofulosorum following BCG immunotherapy in a patient with lepromatous leprosy.

Guillain-Barre syndrome 1N leprosy patients.

Leprosy commonly affects the peripheral and cranial nerves. This involvement often manifests with peripheral neuropathy, occurring as a result of direct invasion of the nerves by lepra bacilli. Immune-mediated neuropathy occurring in leprosy, as part of lepra reaction, has been described earlier. We report here two cases of Guillain-Barre syndrome occurring in patients with leprosy who did not have any obvious evidence of lepra reaction.

Addiction of anti-CD28 antibodies restores PBMC proliferation and IFN-gamma production in lepromatous leprosy patients.

During antigen recognition, T lymphocytes are primed by a physical interaction with antigen-presenting cells (APC). At least two signals are needed to activate T cells. One is provided by T cell receptor (TCR)/CD3 in the context of the mayor histocompatibility complex (MHC), and another signal is mediated by antigen-independent molecules, that is T cell membrane-bound CD28 and its specific ligand B7-1 (CD80) present in APC. Both signals trigger a series of metabolic events initiating right at the cell membrane and ending with activation and proliferation of T cells as well as specific cytokines synthesis. Our main goal was to determine whether deficiency in interferon-gamma (IFN-gamma) production shown by peripheral blood mononuclear cells (PBMC) from lepromatous leprosy (LL) patients, could be overcome by reconstituting in vitro the appropriate signals (by means of addition of anti-CD28 and anti-CD80 monoclonal antibodies). We also determined the stimulation index (SI) in the same PBMC. Our results demonstrated no significant differences in CD80 expression monocytes and B lymphocytes from LL patients when compared with healthy subjects. Nonetheless, CD28 expression significantly decreased in lymphocytes from LL patients (p < 0.01). Regarding IFN-gamma levels and SI, LL-PBMC failure before mitogenic stimuli could be reversed by further incubation with anti-CD28 antibody, but stimulation by specific antigen of Mycobacterium leprae was not changed. Addition of anti-CD80 antibody significantly increased IFN-gamma levels in phytohemagglutinin (PHA)-stimulated PBMC, although proliferation deficiency persisted. Cells stimulated with specific antigen did not modify either their proliferation or IFN-gamma levels.

Cytokine regulation of disease progression in leprosy and tuberculosis.

Studies in our laboratory have focussed on the role of cytokines in the regulation of the cellular immune response and disease progression in two important mycobacterial infection of man, namely leprosy and tuberculosis. Our studies in leprosy have involved the use of key regulatory cytokines such as IFN-gamma in the modulation of the cellular response of infected patients. We have investigated the effect of intradermal administration of low dose IFN-gamma on the lesions of anergic lepromatous patients and have reported an accelerated bacillary clearance from the skin. This was associated with the local accumulation of mononuclear cells and killing of infected macrophages. However, IFN-gamma administration also resulted in the induction of erythema nodosum leprosum, a toxic syndrome associated with excess TNF-alpha production. Both the toxic symptoms and the high levels of TNF-alpha production could be inhibited by thalidomide treatment, a drug we have shown reduces the half life of TNF-alpha mRNA. In preliminary clinical trials in tuberculosis patients we have attempted to use thalidomide to reduce TNF-alpha production and toxicities. These results are discussed.

Sural nerve biopsy findings in leprosy: a qualitative and quantitative light and electron microscope study in 4 treated cases of the lepromatous spectrum.

Reports on biopsy findings in multifascicular nerves in lepromatous leprosy (LL) are rare and detailed morphometrical data are not available. In a case of early LL with normal electrodiagnostic findings in sural nerve, the present study revealed marked segmental de- and remyelination concomitant with the sequelae of considerable Wallerian degeneration of preferentially small myelinated fibers (MF) in spite of a normal number/nerve and density/mm2. Segmental de- and remyelination of several consecutive internodes in teased fibers suggests continuous bacterial spread via Schwann cells. In 2 more advanced LL-cases, nervous parenchyme was severely reduced, in a borderline lepromatous (BL) case obviously in part caused by cell infiltrates and granulomata. Distinct fascicle differences in MF-involvement were demonstrated by coefficients of variation of MF/mm2 and teased fiber preparations in LL, consistent with the hypothesis of initial focal spread of bacteria. Numbers and densities of endoneurial vessels were increased only in the later stages of LL. Enlargement of endoneurial area, due to different factors, was encountered except for the most severe LL-case with extensive endoneurial collagenization. Morphometric results were compared with those of other neuropathies. Intact and degenerating bacteria mostly in phagosomes of Schwann cells associated with unmyelinated axons and in macrophages were seen only in the early LL- and the BL-case. Sparse mononuclear cell infiltrates and small focal necrosis, present even in LL-cases, underline the complex pathogenesis of nerve fiber involvement.

Immunotherapy with Mycobacterium w vaccine decreases the incidence and severity of type 2 (ENL) reactions.

Immunotherapy with Mycobacterium w (M.w) vaccine was given to 45 patients with multibacillary (MB) leprosy; 41 similarly classified patients served as controls. All patients received standard multidrug therapy (MDT). Incidence, severity and frequency of type 2 (ENL) reactional episodes were monitored in both groups in a follow-up extending up to 4 years. Reactions were seen in fewer vaccinated (10/37) BL and LL patients than in the control group (12/34). A total of 20 episodes were recorded in the vaccine group as against 29 in the controls, 75% of reactions were mild in vaccinated and 51.72% were mild in the control group patients, and 3 patients in the control group had more than 3 reactional episodes. None of the vaccinated patients showed this. No additional incidence of neuritis were seen among vaccinated individuals during reactional episodes.

Immunological upgrading with combined immunotherapy and chemotherapy in a lepromatous leprosy patient: a case report.

Immunotherapy with Mycobacterium w was given, in addition to standard multidrug therapy (MDT) to a lepromatous leprosy (LL) patient with a bacteriological index (BI) of 6. After 15 months of treatment this patient attained bacteriological negativity and clinical inactivity. Histopathologically the patient upgraded to borderline-tuberculoid at 12 months, and at 15 months showed features of nonspecific infiltration in the dermis. The rapid immunological upgrading seen in the patient is highlighted in this paper.

Leprosy control in Zimbabwe: from a vertical to a horizontal programme.

In Zimbabwe leprosy control services were re-established in 1983, following the war of independence. Its main objectives were the nation-wide implementation of multiple drug treatment (MDT) and the integration of leprosy control into the general health services. The MDT regimens have led to a rapid reduction of the prevalence of leprosy. At the beginning of 1989 357 patients were on treatment and 1299 under follow-up. Six hundred and twenty-seven new cases have been detected since 1984, which represents an annual case detection rate of 1.6 per 100,000. This seems a fair reflection of the incidence rate, as the new cases are characterized by a minority of patients under the age of 15 (4%) and a lepromatous percentage of 50%. As the budget of the programme has remained unchanged integration of leprosy control into the general health services has become imperative. However, this transition is now hindered by a number of obstacles that were not foreseen at the start of the programme, because they are in measure corollaries of the successful implementation of MDT. Most of the problems that leprosy control is facing in Zimbabwe could have been avoided if instruction in leprosy had been introduced into the curricula of the (para) medical training schools 20 years ago.

Effect of cutaneous cell-mediated immune response to rIFN gamma on Mycobacterium leprae viability in the lesions of lepromatous leprosy.

1. Studies were carried out to determine the effect of intra-dermal injections of recombinant human interferon-gamma (rIFN gamma) on the viability of Mycobacterium leprae. Twenty-three untreated and 4 treated multibacillary patients, 12 with lepromatous leprosy (LL) and 15 with borderline lepromatous leprosy (BL), were selected for intradermal administration of rIFN gamma or PPD. Treated patients (LL and BL) had received multi-drug therapy according to the recommendations of the World Health Organization, i.e., rifampicin (600 mg/month), dapsone (100 mg/day) and clofazimine (50 mg/day and 300 mg/month) for 1-4 months. Three daily doses of 10 or 30 micrograms rIFN gamma induced local induration and mononuclear leucocyte accumulation. Bacteria isolated from a punch biopsy of the site 21 days after lymphokine administration were injected into mouse foot pads and evaluated for viability and growth. 2. The local response to rIFN gamma (specific activity 2 x 10(7) units/mg protein) induced a delay or total inhibition of M. leprae growth in the mouse foot pad, indicating that the cellular response to the antigen reduced local M. leprae viability. The extent of reduction in viability depended on the dose of rIFN gamma injected and the extent of local induration induced by the lymphokine. With a vigorous cell-mediated immune response growth was fully inhibited. 3. A similar but less extensive effect on M. leprae viability was observed in response to the local injection of 5 units in 0.1 ml of purified protein derivative of tuberculin (PPD).

Promoted healing of leprous ulcers by transcutaneous nerve stimulation.

Low-frequency (2 Hz) transcutaneous electrical nerve stimulation (TNS) may produce widespread and prolonged increases in skin temperature in patients with peripheral vascular insufficiency due to improved microcirculation. The method has previously been used successfully to potentiate healing of chronic ulcers of various etiology. The present report describes a similar study, using TNS treatment in attempts to accelerate healing of chronic leprous ulcers that had resisted treatment for several months or years. All other treatment, local and systemic chemotherapy, and daily regime remained as far as possible unaltered. The study was limited to ulceration in the soft tissue of the foot or lower leg. Eleven TNS sessions, each of 30 min duration, were applied per week. In 19 patients (6 out- and 13 in-patients), in whom the TNS treatment was not interrupted, all ulcers healed completely within a mean of 5.2 weeks (range 3-12 weeks). The mean size of the ulcers was 5.2 cu.cm (range 0.2-48.3 cu.cm), and they had persisted for a mean of 15.8 months (range 2-60 months). The 'healing index', i.e. the mean reduction of the ulcer cavity per week, was 1.0 cu.cm/week. The study demonstrates a clear therapeutic effect for low-frequency TNS in patients with leprous ulcers. The mechanisms involved in the accelerated healing are assumed to be increased microcirculation due to sympatho-inhibition and release of endogenous corticosteroids.

Hansen's disease. Practice tips for management.

The author highlights some of the critical features of general practice diagnosis and management of Hansen's disease in First World primary care practice. These features are often not obvious or emphasised in most texts because they are designed for a Third World scenario, where primary care is delivered without the luxury of medically trained practitioners and therefore without the option of emergency steroid therapy.

Lepra Lepromatosa con incio neural puro. A propósito de un caso / No disponible

En la lepra lepromatosa, cuando los troncos nerviosos periféricos son invadidos producen lesiones en la medida en que la enfermedad progresa de manera simétrica y dejan graves secuelas en etapas avanzadas de la enfermedad. Se trata de un paciente masculino, de 56 años de edad, con antecedentes de haber sido tratado por la especialidad de neurología por más de 20 años, debido a que tenía trastornos de la sensibilidad en miembros inferiores, en forma de calcetín que había sido diagnosticado como neuropatía sin causa aparente que acude a consulta de cuerpo de guardia del Hospital Manuel Ascunce de Camagüey, refiriendo que desde hacía unos años presentaba lesiones en forma de manchas por todo el cuerpo, que no le picaban. Al examen dermatológico se constata cuadro cutáneo diseminado constituido por placas infiltradas eritematosas, de bordes mal definidos, en número de más de una veintena, acompañadas de trastornos de la sensibilidad y disminución del vello a ese nivel. Además, con infiltraciones difusas de cara y pabellones auriculares, trastorno de la sensibilidad en miembros inferiores y troncos nerviosos engrosados. La variedad neurítica pura es muy discutida y se cree que los casos que fueron diagnosticados como tales presentaron lesiones cutáneas que pasaron inadvertidas y no dejaron secuelas

In lepromatous leprosy, when the peripheral nervous trunks are invaded they produce lesions to the extent that the disease progresses symmetrically and leave serious sequelae in advanced stages of the disease. This is a 56-year-old male patient with a history of having been treated by the specialty of neurology for more than 20 years, because he had sensory disorders in the lower limbs, in the form of a sock that had been diagnosed as a neuropathy without apparent cause, he went to the on call unit at the Manuel Ascunce Hospital in Camagüey, saying that for some years he had had lesions in the form of spots all over his body that did not itch. The dermatological examination revealed a disseminated cutaneous plaque composed of infiltrated erythematous plaques with poorly defined edges, in a number of more than twenty, accompanied by disorders of sensitivity and hair loss at that level. Also with diffuse infiltration of the face and ears, sensory disturbance in the lower limbs and thickened nerve trunks. The pure neuritic variety is very controversial and it is believed that the cases that were diagnosed as such presented cutaneous lesions that went unnoticed and did not leave sequels