Ultrasonographic Features of Ulnar Nerve Affected by Hansen's Disease.

Leprosy continues to be a major public health problem in some areas of our country. It predominantly afflicts peripheral nerves and skin and may lead to deformities. Social stigma as a result of deformities further plagues the situation. Prompt and early diagnosis coupled with adequate treatment, concurrent rehabilitative strategies if deformities do occur, and health education help to control the problem. Definitive diagnosis of leprosy has traditionally been based on assessment of slit skin smears (SSS) after AFB-staining and characteristic histopathology after biopsyof the lesion. However, recently, thickening of the peripheral nerves has been demonstrated by ultrasonography and this can be used as a sensitive tool to assess and measure enlargement of peripheral nerves, which are hallmarks for leprosy especially in clinical settings. In this report, the ultrasonographic findings of ulnar nerve enlargement due to leprosy in a fourteen-year-old male patient are described.

Epidermolytic hyperkeratosis with rickets.

A 6-year-old child presented with generalized hyperkeratosis, most marked over the flexures; windswept deformity of the legs; and limping since 3 years. On the basis of the clinical, histopathologic and biochemical findings, he was diagnosed as a case of epidermolytic hyperkeratosis with rickets. He was treated with parenteral vitamin D3 and calcium supplements orally. Nutritional rickets has been reported in children with various types of ichthyosis like lamellar and X-linked types. We report this case of epidermolytic hyperkeratosis with rickets for its rarity.

Delayed clearance of circulating immune complexes in mice following administration of antileprosy drugs.

In this report we describe an animal experiment which showed delayed clearance of preformed 125I-HSA-anti-HSA immune complexes (with five times excess HSA) from the circulation of mice treated with antileprosy drugs (dapsone, clofazimine, and rifampin--multidrug therapy for 7 days) in comparison with normal (untreated) mice. The results also showed delayed retention of the preformed immune complexes in the spleen and kidneys of the antileprosy-drug-treated animals. The exact mechanism of the delayed handling of preformed immune complexes in mice fed antileprosy drugs could not be ascertained. However, in light of the anticomplementary effects of clofazimine and dapsone, as reported earlier, and in light of the large accumulation of clofazimine and rifampin in macrophages, it has been postulated that in the drug-fed animals either the immune complexes could not be phagocytosed by macrophages, through the avenue of their C3b receptors, or the immune complexes could not be downgraded easily within the macrophages overloaded with clofazimine and rifampin. These results might have clinical significance and might throw some light on the prolonged persistence of circulating immune complexes in the vascular bed of lepromatous patients even after clinical remission of erythema nodosum leprosum.

In vivo effects of anti-leprosy drugs on the rat peritoneal macrophages and lymphocyte subpopulations.

The present study describes the in vivo effects of anti-leprosy drugs on rat peritoneal macrophages and T-cell homeostasis. It was observed that BCG-elicited rat peritoneal macrophages produced more H2O2 and expressed more Ia antigen on their cell surfaces compared with resident peritoneal macrophages. Furthermore, elicited macrophages isolated from rats administered multidrug therapy (MDT), consisting of dapsone, clofazimine and rifampicin in high dose (10 x MDT) released more O2-. On the contrary, there was a significant decrease in the Ia antigen expression on these macrophages. Anti-leprosy drug treatment in high dose (10 x MDT) decreased the total number of blood T-helper (W3/25+) cells and increased the total number of blood T-suppressor (OX-8+) cells which resulted in a significant decrease in a W3/25: OX-8 ratio. Electron microscopy of elicited macrophages isolated from 10 x MDT treated rats showed development of many filipodia compared with control macrophages. These data show that 10 x MDT treatment in rats for 1 month alters the homeostasis of blood T-cell subpopulations which perhaps decreases the Ia expression on macrophages. However, the increase in O2- production and the appearance of filipodia on the macrophages is due to a direct effect of drugs on the macrophages. MDT treatment for 1 month in a therapeutic dose has no effect on the above-mentioned parameters.

Anti-leprosy drugs inhibit the complement-mediated solubilization of pre-formed immune complexes in vitro.

Incubation of pre-formed immune complexes (IC) (125I-HSA--anti-HSA) with normal human serum resulted in solubilization of IC. When various anti-leprosy drugs were added to human sera, solubilization of IC was fairly explicit with clofazimine, whereas this effect was marginal with dapsone. Rifampicin hardly displayed this effect. Aspirin, chloroquine, and prednisolone, the drugs used in addition to multi-drug therapy to control reactions in leprosy, were in a position to inhibit the solubilization of 125I HSA--anti-HSA by normal serum only at a very high dose. From the current data of the inhibition of solubilization of pre-formed IC along with our earlier observations on the modulation of complement-mediated haemolysis by these drugs, it may be possible to postulate that clofazimine as well as chloroquine affect early complement components. This may in turn be responsible for preventing the deposition of C3 complement onto IC.

Effect of anti-leprosy drugs on superoxide anion production by rat peritoneal macrophage with special reference to light exposed clofazimine.

The present study describes the in vitro effect of anti-leprosy drugs on superoxide anion (O2-) production by rat resident peritoneal macrophages. Of the three drugs tested i.e. clofazimine, rifampicin and dapsone, the first was most effective in increasing O2- production in a dose dependent manner, while rifampicin had some stimulatory effect and dapsone exhibited minimal action. Furthermore, when clofazimine and dapsone were added together it was observed that the increase of O2- production by macrophages due to clofazimine was not significantly altered by the addition of dapsone. Moreover, it was found that killed Mycobacterium leprae could induce a lesser amount of O2- production in comparison to that of Staphylococcus aureus and the enhancement of O2- release due to clofazimine was stimulus dependent. This increase of O2- release after addition of clofazimine was inhibited by the addition of p-bromophenacyl bromide. Another interesting finding was that the enhancement of O2- production by clofazimine gradually decreased as clofazimine was exposed to light for days. On further investigation it was found that ultraviolet, NMR, infrared and mass spectra of the light unexposed and exposed drug were similar, but the diffusion current of the polarogram of light exposed drug was remarkably more than that observed in light unexposed drug, indicating, thereby, a possible increase in the electron accepting capacity of the light reacted molecule. As far as we know this is the first report describing the effect of light exposed clofazimine on the respiratory burst activity of macrophages.

Interaction of anti-leprosy drugs with the rat serum complement system.

Dapsone, clofazimine and rifampicin, the three most important constituents of multidrug therapy against leprosy, were studied with respect to their effects on the rat serum complement system, in vitro as well as in vivo. Of the three drugs only dapsone and clofazimine exhibited significant in vitro anti-complement activity and only at a very high, non-therapeutic dose of 0.24 mg/ml. On the contrary, rifampicin could not induce significant in vitro complement consumption. Furthermore, dapsone and clofazimine could reduce rat-serum-mediated rabbit erythrocyte haemolysis in the presence of Mg2+-EGTA, indicating that they could also affect the alternative pathway of complement activation. However, the latter pathway of complement consumption by these drugs seems to be insignificant because the factor-B-mediated complement-consumption system is minimal in rat sera. Immunoelectrophoretic study of mixtures of fresh rat sera and anti-leprosy drugs against specific anti-rat-C3 antisera demonstrated that dapsone and clofazimine could not cleave the C3 complement component. In a separate experiment we attempted to reconstitute the haemolytic complement activity consumed by dapsone and clofazimine by adding Crat-EDTA sera (a source of C3, C5, C6, C7, C8 and C9), but at most only 12% reconstitution of haemolytic activity could be achieved. We thus conclude that both dapsone and clofazimine could affect the complement system, predominantly through the earlier complement components and at very high, non-therapeutic doses. On the contrary, in-vivo experiments in rats showed that a combination of these three drugs, when given at a therapeutic dose or at 10 times the therapeutic dose for three months, did not affect the complement system.