Trials of daily, long-term minocycline and rifampin or clarithromycin and rifampin in the treatment of borderline lepromatous and lepromatous leprosy

International Journal of Leprosy and Other Mycobacterial Diseases, Jun 2000 by Rea, Thomas H

Unless diabetic nephropathy was present, all blood creatinine levels were normal, indicating no nephrotoxicity from any of the drug combinations used.

No bacteriologic relapses have been found in any of the previously untreated patients enrolled in this study.

DISCUSSION

The long term use of two combination microbiocidal regimens-daily minocycline and rifampin, and daily clarithromycin and rifampin-in the treatment of multibacillary (MB) leprosy has been found to be safe and well tolerated, as judged by comparison with concurrently treated patients receiving daily dapsone and rifampin.

Regarding safety, 48 patients receiving minocycline and rifampin, as well as eight receiving clarithromycin and rifampin, had no serious evidence of bone marrow suppression, hepatic toxicity, or renal toxicity, nor any other serious drug reaction. Again regarding safety, i.e., dangerous drug reactions, leukopenia, and abnormal liver function tests, these patients differed little from 34 concurrently treated individuals receiving dapsone and rifampin. This conclusion must be tempered by the relatively small number of patients treated.

Drug intolerance sufficient to terminate a regimen, as contrasted to drug danger, occurred in response to dapsone, rifampin, and minocycline. It should be emphasized that the attribution of a drug effect was a clinical impression. The inferences of itching and an eruption from rifampin as well as neuropathy from dapsone are challengeable, but in the case of itching, it did recur when rifampin was restarted. Because our clinic has experienced two patients with persistent vomiting in association with clarithromycin use for paucibacillary (PB) leprosy, the absence of intolerance to clarithromycin in this study is most probably due to the small number of patients.

Minocycline-induced hyperpigmentation, first described at sites of cutaneous inflammation (2), has been previously reported in this pattern in a BL patient (3). Also, a diffuse hyperpigmentation has been especially carefully documented in patients treated with acne vulgaris or acne rosacea (1); in these patients the diffuse hyperpigmentation was not seen until 3 years of treatment, but was present in 50% of those treated for 3 years or longer. The pigments involved, as with clofazimine, appear to be multiple, including aggregates of minocycline (13), iron chelated with minocycline (13), and melanin, perhaps induced by activation of tyrosinase, secondary to iron accumulation (3). The pigments are found primarily in macrophages, hence their occurrence in sites of skin inflammation as well as in a generalized distribution in lepromatous leprosy, the clinically normal skin being diffusely infiltrated with macrophages ('S).

Concerning the patterns of minocyclineinduced hyperpigmentation seen in the patients reported here, the patchy blue-black color found at lesion sites was the most common, being particularly apt to appear on the legs and feet. When the hyperpigmentation was diffuse or generalized, it appeared to be melanin or melanin-like, was most pronounced in sun exposed areas, and was seen within 6 months of initiation of treatment. Both patterns were sometimes seen in the same area, usually on the face. The "physiologic" appearance of minocycline-induced diffuse hyperpigmentation may be why it can be better tolerated than that from clofazimine. It is the uniform opinion of the dermatologists attending in this clinic that the hyperpigmentation from minocycline is far more common in leprosy than in acne vulgaris patients, perhaps a consequence of the large number of macrophages in leprosy, whether in or between the lesions, or perhaps a matter of dosage, acne vulgaris patients often receiving 50 mg daily once a remission is produced. As observed by others (1), the diffuse hyperpigmentation is very gradual in onset, hence difficult to perceive by patient and clinician alike. For this reason, and because mild minocycline-induced hyperpigmentation of the legs may be difficult to distinguish from hemosiderin, the exact incidence of minocycline-induced hyperpigmentation is probably under-reported in these patients.