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)

Detecting intrinsic muscle weakness of the hallux as an addition to early-stage screening of the feet in patients with diabetes.

AIMS: Present-day screening of the diabetic foot involves the Semmes Weinstein Monofilament Test for evaluating loss of sensibility, while testing for intrinsic muscle weakness is not implied. Just as with the early detection of sensibility loss, early detection of intrinsic muscle weakness might have important implications for the prevention of both ulceration and deformity in patients with diabetes. The purpose of this study is to investigate the prevalence of patients with diabetes presenting intrinsic muscle weakness of the hallux, but with a normal sensibility of the sole of the foot. METHODS: A cross-sectional study design was applied. Intrinsic muscle function of the hallux was measured with the Paper Grip Test, while sensibility of the sole of the foot was measured with the Semmes Weinstein Monofilament Test 5.07/10-g. RESULTS: In a period of three months a total of 266 patients with diabetes (mean age 60, 134 females (50%), 177 type 2 diabetes mellitus (67%)) met the inclusion criteria and were examined for both intrinsic muscle weakness of the hallux and sensibility of the soles of the feet. The results showed that intrinsic muscle weakness was present more frequent in patients with impaired sensibility (P=0.001), also 20% of the population had intrinsic muscle weakness in the presence of normal sensibility. Multivariate regression analysis showed that only age is associated with patients with diabetes presenting normal sensibility but impaired intrinsic muscle function (P=0.017). CONCLUSIONS: The Paper Grip Test could have added value to current physical examination of the feet in patients with diabetes.

The response to chemotherapy of serum Mycobacterium leprae-specific antigen in multibacillary leprosy patients.

We have examined the Mycobacterium leprae phenolic glycolipid-I (PG-I) antigen levels in the sera of 45 multibacillary leprosy patients commencing chemotherapy. The PG-I antigen levels correlated with the bacterial and morphological indices, but not with the serum IgM anti-PG-I antibody levels. Antigen levels were significantly higher in patients with diffuse skin infiltration, but did not vary significantly with other parameters reflecting the duration and extent of untreated disease. The PG-I antigen levels in 27 patients examined serially decreased consistently over the first year of multidrug therapy.

Serological responses in primary neuritic leprosy.

The serological responses to 2 Mycobacterium leprae specific epitopes and one common mycobacterial antigen were examined in 46 untreated patients with primary neuritic (PN) leprosy. M. leprae specific antibodies to the terminal disaccharide of phenolic glycolipid and/or the ML-04 defined epitope on the 35 kDa protein were detected in 41% of PN patients and 47% responded to one of the 3 antigens. This serological response mirrored that observed in paucibacillary leprosy patients. There was a significant increase in the level of antibody response when more nerve trunks were involved. Changes in antibody levels in seropositive PN patients may prove useful in monitoring the response to chemotherapy.

Advantages, indications, and the manufacturing of melted PVC waterpipe splints.

There are several indications when to use splints in the treatment of leprosy. PVC waterpipe is a cheap and easily available material in developing countries. Its advantages, indications, and the manufacturing of splints are described.

Massive deformation of the scrotal wall by idiopathic calcinosis of the scrotum.

Idiopathic calcinosis of the scrotum is a rare disease that may cause massive deformation of the scrotal wall. The first patient we present was also known to have neurofibromatosis. In the second patient we describe, nodules of idiopathic calcinosis of the scrotum were seen with walls that evidenced no epithelial lining, as well as calcification in epithelial cysts. At present, the only possible treatment is excision, and we excised the afflicted skin without problems in primary wound closure.

Cytological needle aspiration of the nerve for the diagnosis of pure neural leprosy.

Pure neural (also called primary neuritic) leprosy manifests itself by involvement of only the nerve in the absence of skin lesions. Therefore, it sometimes can pose a diagnostic problem. Cytological needle aspiration of an affected nerve can be a valuable tool under such circumstances. The method as developed at Anandaban Leprosy Hospital, Nepal, is described and two cases are presented.

Thermographic assessment of perforating arteries. A preoperative screening method for fasciocutaneous and musculocutaneous flaps.

Pre-operative localization of the involved perforating arteries in the planning of musculocutaneous or fasciocutaneous flaps may lead to a higher survival rate of the whole skin island. This in particular will be of importance in donor areas with changed haemodynamics. A noninvasive method is described for the accurate preoperative localization of the perforating arteries of the trunk and extremities; a method which causes minimal discomfort to the patient, but which will help in preparing for a successful operation. We have used this method since 1983 for all high-risk patients, and it has proved to be very useful in our hands.

Cellular immune responses to mycobacterial heat shock proteins in Nepali leprosy patients and controls.

Sixty-three leprosy patients, representing the entire leprosy spectrum from tuberculoid to lepromatous disease, and 17 healthy Nepali subjects were tested for their T-cell responses to the purified p65 and p70 protein antigens of Mycobacterium bovis BCG using a lymphocyte proliferative assay. There was strong correlation between the responses to BCG and M. leprae and the responses to the two antigens. Patients and controls lacking a response to either of the whole cell preparations failed to respond to the purified antigens, while BCG responders at the lepromatous pole of the disease did mount a response to both antigens. Significant differences in the magnitude of the responses to these antigens were obtained between controls and the disease groups. In individual subjects, responses to the two antigens were significantly correlated to each other.

Risk factors for type-1 reactions in borderline leprosy patients.

Type-1 or reversal reactions are the major cause of nerve damage and disability in leprosy. We wished to determine whether there were any clinical or laboratory markers that identified patients with an increased risk of type-1 reaction. 42 (31%) of 136 Nepalese borderline leprosy patients (97 male, 39 female; age range 7-73 years) had a type-1 reaction during the first 2 years of multi-drug therapy. Before therapy, 41 (98%) of the 42 patients were seropositive for antibodies to one of three mycobacterial antigens. Seropositivity for IgM antiphenolic-glycolipid-1 (PGL-1) antibodies, but not IgG anti-lipoarabinomannan or anti-Mycobacterium leprae 35 kDa protein antibodies, was significantly associated with subsequent manifestation of a type-1 reaction (p less than 0.001). The concentration of IgM anti-PGL-1 antibodies in serum was significantly higher in patients in whom a type-1 reaction developed. The risk attributable to anti-PGL-1 seropositivity was independent of leprosy class, skin smear positivity, and the presence of other anti-M leprae antibodies (adjusted odds ratio = 8.7, p less than 0.001). In the 87 patients who had a lepromin test, anti-PGL-1 seropositivity and lepromin reactivity were significant independent risk factors for subsequent reaction. 78% of patients with positive lepromin reactivity and IgM anti-PGL-1 antibodies had type-1 reactions. Patients with these risk factors should be carefully monitored during antimicrobial therapy to permit early initiation of anti-inflammatory treatment thus minimising permanent nerve damage and resultant disability.

Neuritis of the lateral femoral cutaneous nerve in leprosy.

Neuritis of the lateral femoral cutaneous nerve (meralgia paresthetica) is observed more frequently in leprosy than in nonleprosy patients, and its symptoms can easily be confused with those suggesting, e.g., ischialgia. The diagnosis can be confirmed by a diagnostic block with a local anesthetic solution. Analgesics, antiinflammatory drugs, bed rest and, in severe cases, therapeutic blocks were successfully applied in the treatment of the neuritis, and no surgical intervention was needed. Three leprosy patients with severe meralgia paresthetica are presented.

The Kleinert dynamic splint: where it fails and how it can be modified.

After primary tenoraphy of flexor tendons one often finds a hampered function of the DIP-joint. Analysis of the pattern of early mobilization exercised by our patients in the Kleinert splint and analysis of the excursions of the flexor tendons of fresh unembalmed specimens brought us to the conclusion that the Kleinert dynamic splint fails in maintaining a sliding movement of the deep and the superficial flexor tendons along each other because the splint excludes motion at the distal interphalangeal joint. Based on our observations we modified the Kleinert dynamic splint. Our experience with 37 patients shows that this modified splint gives a better function in the DIP-joint.

Contribution of type 1 reactions to sensory and motor function loss in borderline leprosy patients and the efficacy of treatment with prednisone.

The changes in nerve function tests in 297 new leprosy patients over an average period of 30 months were measured. The impact of type 1 reactions (T1R) on sensory and voluntary muscle function was measured by standard tests. Sensory function was improved in patients with single episodes of cutaneous T1R, but not improved in patients with neural T1R or with multiple episodes of either kind of T1R. Patients over 40 years of age improved less than younger patients, and patients admitted for treatment of T1R improved more than those treated as outpatients. These data point to a need to find better regimens for the treatment of nerve damage in T1R.

Serological monitoring of the response to chemotherapy in leprosy patients.

Sixty-five patients initially seropositive for IgM anti-phenolic glycolipid-I (PGL-I) antibodies were tested for antibody levels to PGL-I, lipoarabinomannan (LAM), and the 35-kDa protein of Mycobacterium leprae at regular intervals for up to 30 months following the commencement of multidrug therapy (MDT). There was a steady decline in IgM anti-PGL-I and anti-35-kDa antibody levels to a mean of 17% and 14%, respectively, of the starting level at 24 months. The development of type 1 and type 2 reactions or the presence of drug-resistant organisms in a small number of patients had no significant influence on the changes in antibody level. The rate of decline was similar in different disease categories, but a higher proportion of lepromatous patients remained seropositive at the end of 2 years of treatment than borderline tuberculoid patients. By contrast, the mean IgG anti-LAM antibody levels remained stable or increased. Again the occurrence of type 1 or type 2 reactions had no significant effect on antibody level over 2 years. Falls in the IgM anti-PGL-I antibody levels mirrored the falls in the bacterial index in individual patients and provide an additional parameter for monitoring the response to chemotherapy.

Operational value of serological measurements in multibacillary leprosy patients: clinical and bacteriological correlates of antibody responses.

The antibody responses of 100 previously untreated multibacillary (MB) leprosy patients to one protein and two carbohydrate antigens were examined: 94% of the patients had Mycobacterium leprae-specific antibodies; 89% directed to the species-specific epitope on phenolic glycolipid (PGL-I), 89% against the specific epitope on the 35-kDa protein, and 94% against one or both of the two. By contrast, 67% of the patients had anti-lipoarabinomannan (LAM) antibodies. There were trends for the seropositivity rate and the antibody level to rise with the increasing extent of the disease and as patients moved to the polar lepromatous end of the spectrum. The bacillary load, as measured by the bacterial index, was moderately correlated with the IgM anti-PGL-I and the anti-35-kDa antibody levels and, to a lesser extent, with the IgG antibodies directed at the common mycobacterial carbohydrate LAM. The sensitivity of the IgM anti-PGL-I antibodies for detecting smear-positive MB disease was 91%; that for the anti-35-kDa antibodies was 92%.

Heterogeneity of serological responses in paucibacillary leprosy--differential responses to protein and carbohydrate antigens and correlation with clinical parameters.

We have examined the serological responses of 154 untreated paucibacillary (PB) leprosy patients to two carbohydrate and one protein antigens of Mycobacterium leprae. There was a heterogeneous response with 20% of PB patients having IgM anti-PGL-I antibodies and a similar proportion with IgG anti-LAM antibodies, while 33% had antibodies to the M. leprae-specific epitope on the 35-kDa protein. There was overlap in the responses such that 43% of the patients were seropositive in one of the two M. leprae-specific assays, while 49% were positive in any assay. There was a gradation in seropositivity with increasing extent of disease for each of the clinical parameters measured. Those with established disability at the time of presentation were more likely to be seropositive in each assay.