Primary dapsone-resistant Hansen's disease in California. Experience with over 100 Mycobacterium leprae isolates.

We found that in the years 1978 through 1981 only one of 54 previously untreated patients with Hansen's disease was found to harbor dapsone-resistant Mycobacterium leprae. That single strain was only partially resistant, ie, it was resistant to 0.0001% dapsone in a mouse diet but not to higher concentrations. During the years 1983 through 1988, M leprae from 47 previously untreated patients presenting to clinics in San Francisco, Calif, and Los Angeles, Calif, grew in mice. None of these strains was found to be dapsone resistant. Thus, from 1978 through 1988 only one of 101 M leprae isolates obtained from skin biopsy specimens from patients with leprosy was found to be resistant to dapsone. We have concluded that primary dapsone resistance still does not appear to be a significant problem in California. Owing to the fact that our single resistant case and those reported from international sources are, in general, partially resistant, the potential importance of partial dapsone resistance is discussed.

Low intraocular pressure and postural changes in intraocular pressure in patients with Hansen's disease.

We found intraocular pressures of less than 7 mm Hg in 11 of 72 patients (15%) with early Hansen's disease. Furthermore, significant postural changes in intraocular pressure (greater than 30%) occurred in 43 of 72 patients (60%). This loss of intraocular pressure homeostasis, which results from reduced aqueous humor production or increased uveoscleral outflow with reduced local adrenergic control in the ciliary body-iris-trabecular meshwork region, suggests that early autonomic neuropathy of the eye may occur in Hansen's disease. The only predictive value for significant postural change in intraocular pressure was the presence of immunologically unstable disease.

Effect of dapsone on haemoglobin concentration in patients with leprosy.

Haemolysis and frank anaemia from dapsone therapy of leprosy has been long recognized. However, the frequency and severity of this side-effect have not been well documented. We report herein a retrospective analysis of the effect of daily dapsone (generally 100 mg/day) on the haemoglobin concentration of 100 leprosy patients undergoing initial chemotherapy. The average haemoglobin was found to fall significantly by almost 2 g/dl, from 14.25 +/- 1.27 g/dl to a nadir of 12.31 +/- 1.61 (P less than 0.001). Eighty-three percent of patients had a fall of haemoglobin concentration of 1 g/dl or more, while in 16% of patients the haemoglobin fell greater than or equal to 3 g/dl. Increasing age was found associated with an increased magnitude of dapsone-related haemolysis (P less than or equal to 0.004). Decreasing the daily dose of dapsone was associated with an increased haemoglobin concentration (P less than 0.001%). We have concluded that dapsone commonly results in not only haemolysis but a significant decrease in haemoglobin concentration. This may have serious clinical implications, especially in endemic areas, where, owing to nutrition, malaria, and intestinal parasitism, the haemoglobin concentration is already compromised.

Effective vaccination of mice against Mycobacterium leprae with density-gradient subfractions of soluble M. leprae proteins: clues to effective protein epitopes.

It had previously been discovered that intradermal mouse vaccination with a protein fraction of Mycobacterium leprae (called soluble proteins) in Freund's incomplete adjuvant (FIA) resulted in consistent and long-lived protection against M. leprae multiplication from subsequent viable footpad challenges. In this study certain density-gradient subfractions of this soluble protein, but not others, in FIA afforded vaccine protection. The results of this study suggest which M. leprae proteins may be involved in protective immunity, particularly 1-3 kD, 10 kD, 65 kD, and those of higher molecular weight.

Evaluation of testing modalities for peripheral neuropathy in lepromatous Hansen's disease.

To assess methods for detecting peripheral neuropathy, 28 previously untreated patients with lepromatous Hansen's disease underwent upper extremity manual muscle testing, sensory testing by using monofilaments, and electrophysiological nerve conduction studies (motor and sensory) at their initial examination. All but three patients demonstrated some abnormality identified by at least one of the testing procedures. Sensory testing with monofilaments located the greatest number of abnormalities found in 24 of the 28 patients. Next, electrophysiological testing demonstrated neuropathy in 21 of the 28 patients tested; 20 of these patients had sensory abnormalities and 20 had motor irregularities. The least sensitive method was manual muscle testing, which detected abnormalities in only 12 patients. Furthermore, sensory testing with monofilaments revealed peripheral neuropathy in 5 patients whose electrophysiological studies showed normal sensory patterns, and electrophysiological testing detected abnormalities in 1 patient whose sensory monofilament examination was normal. The results of this study support the usefulness of all three testing modalities.

Lepromatous leprosy: nasal manifestations and treatment with minocycline.

Nasal involvement in lepromatous leprosy is universal and occurs early in the course of the disease. Nasal symptoms include obstruction, crusting, bleeding, and hyposmia. Traditional therapy with dapsone, rifampin, and clofazimine is limited by its cost and toxicity. Minocycline hydrochloride, a tetracycline antibiotic with limited side effects, is promising as a new treatment for leprosy. A case is presented that highlights the clinical presentation, diagnosis, and treatment of lepromatous leprosy.