Histopathological activity in paucibacillary leprosy patients after ROM therapy

International Journal of Leprosy and Other Mycobacterial Diseases, Dec 1999 by Ebenezer, Gigi J, Job, Charles K

Histopathological Activity in Paucibacillary Leprosy Patients after ROM Therapy1

Almost two decades after the introduction of multidrug therapy (MDT) the treatment of leprosy and an intensive drive on the part of the World Health Organization (WHO) and the national leprosy programs to eliminate leprosy as a public health problem, there have been several reports of patients being detected at an early stage, presenting with just a single skin lesion (4,11). In 1995 WHO passed a recommendation that patients with five skin lesions or less and/or only one nerve trunk involvement should be considered as paucibacillary (PB) leprosy patients (15). These patients were to be treated with fixed-duration MDT composed of dapsone 100 mg daily and rifampin 600 mg once a month for 6 months. During this time various clinical trials to check the efficacy of other antimicrobial drugs against leprosy had been undertaken (1,5). These trials have confirmed that minocycline is highly effective both clinically and microbiologically in mouse foot pad models inoculated with Mycobacterium leprae (2,3,6). It is known that a single dose of rifampin (600 mg) exerts a strong bactericidal effect on M. leprae (7,10) and together with ofloxacin (400 mg) and minocycline (100 mg) would form an effective drug combination (ROM) to treat any early PB leprosy lesion in which the bacterial population is expected to be well below I million (11). To our knowledge no histological studies have been conducted to find out the effectiveness of ROM to clear inflammatory granulomatous response in early skin lesions in leprosy patients.

MATERIALS AND METHODS

Serial skin biopsies from 13 PB leprosy patients who had been clinically diagnosed and classified according to the RidleyJopling classification as borderline tuberculoid (BT) patients attending the outpatient department of The Leprosy Mission Hospital, Naini, Utter Pradesh, India, were sent to us for histopathological examination. Each patient had a comprehensive clinical examination and the morphology and the site of skin lesions were recorded. Skin-smear examination for acid-fast bacilli (AFB) was done from routine and selective sites.

A single dose of rifampin 600 mg, ofloxacin 400 mg, and minocycline 100 mg (ROM) was given. Before giving these drugs an elliptical piece of skin was biopsied from an active patch using local anesthesia. The skin biopsies were fixed in 10% formalin and processed for paraffin sections. Serial sections of 5(mu)m thickness were cut and stained with hematoxylin and eosin (H&E) for routine study and a modified Fite-Faraco stain for AFB (8). Patients were grouped histopathologically in accordance with the Ridley and Jopling classification (12) . At 6 and 12 months after ROM therapy, skin biopsies were taken from the same lesions.

All skin biopsies were assessed for type of granuloma, granuloma fraction, nerve inflammation and the presence or absence of AFB. The histological findings were graded as "active" when there were dermal infiltration by epithelioid granulomas and the granuloma fraction was more than 10% in the dermal tissue. It was graded as "resolving" when epithelioid granuloma was absent and the lymphohistiocytic infiltrate was less than 10% and "inactive" when the lymphohistiocytic infiltrate was less than 5%.

RESULTS

Of the 13 patients 8 were males and 5 were females. The age of the patients ranged from 4 to 38 years with a mean of 26 years. Four patients presented with three patches, seven patients presented with two patches, one patient had a single lesion and another patient presented with one skin patch and an enlarged left radial cutaneous nerve. Skin smears were negative in all of them.

Initial histopathological examination showed that 11 belonged to the BT type of the disease (The Table, Fig. 1). Seven of these 11 patients showed AFB only in the dermal nerves with a Bacillary Index of the Granuloma (BIG) of 1 . One patient showed AFB in nerves, granulomas and dermal smooth muscles with a BIG of 2 . Two were classified as indeterminate and neither of them showed AFB. The second histopathological examination, done 6 months after ROM therapy, showed that of the 11 histologically diagnosed BT cases, three continued to show granulomatous inflammation. Only lymphocytic collections occupying about 10% of the dermis were seen in seven (Fig. 2) and one was inactive (Fig. 3). AFB persisted within the nerves of these patients. Both indeterminate cases were found to be inactive.

Histological examination undertaken 12 months after ROM therapy showed that epithelioid granulomas were present only in 2 cases, collections of lymphocytes persisted in 3 cases and 8 patients were inactive. AFB were absent in all of them. It is interesting to note that of the two patients with unresolved granulomas one had three skin lesions and the other had two. Of the three biopsies with persisting granulomas one patient had three skin lesions and the others had two. All three biopsies with persisting lymphocytic collections were from patients with three lesions. The granuloma fractions in the skin of these leprosy patients before and 6 and 12 months after ROM therapy is contrasted in Figure 4.