100^ International Journal of Leprosy^ 1992

2. KAPLAN, G., MATHUR, N. K., Jon, C. K., NATII, I.and COHN, Z. A. Effect of multiple interferon-gam-ma injections on disposal of Mycobacteriztin leprae.Proc. Natl. Acad. Sci. U.S.A. 86 (1989) 8073-8077.

3. KAPLAN, G., NATHAN, C. F., GANDHI, R., HoRwrrz,M. A., LEVIS, W. R. and COHN, Z. A. Effect ofrecombinant interferon-y on hydrogen peroxide-re-leasing capacity of monocyte-derived macrophagesfrom patients with lepromatous leprosy. J. Immu-nol. 137 (1986) 983-987.

4. KAI'LAN, G., NUSRAT, A., SARNO, E. N., Jon, C. K.,MCELRATII, J., PORTO, J. A., NATHAN, C. F. andCOHN, Z. A. Cellular responses to intradermal in-jection of recombinant human gamma-interferon in

lepromatous leprosy patients. Am. J. Pathol. 128(1987) 345-353.

5. NOGUEIRA, N., KAPLAN, G., LEVY, E., SARNO, E.N., KUSHNER, P., GRANELLI-PIPERNO, A., VIEIRA,

L., COLOMER-GOULD, V., LEVIS, W., STEINMAN, R.,YIP, Y. K. and COHN, Z. A. Defective gamma-interferon production in leprosy; reversal with an-tigen and interleukin-2. J. Exp. Med. 158 (1983)2165-2170.

6. I'TAK, W. and GERSHON, R. K. Immunological ag-nosis: a state that derives from T suppressor cellinhibition of antigen-presenting cells. Proc. Natl.Acad. Sci. U.S.A. 79 (1982) 2645-2648.

Subgroups Among Lepromatous Leprosy—A Viewpoint

To THE EDITOR:In the recent past it has been observed

that all lepromatous leprosy cases do notshow uniformity in the generation of gam-ma-interferon in response to concanavalinA (conA), Mycobacterium leprac, and BCG( 2 ). Similarly, in various vaccine trails near-ly 30%-40% of the patients failed to showlepromin conversion ('). These parameterssuggest that the lepromatous leprosy (LL)cases are immunologically heterogenous,and there is a possibility that there mightbe subgroups among lepromatous leprosycases (4). In our leprosy clinic we have ob-served that some of the LL patients developthe LL form de novo; whereas some acquirethe LL form by gradual downgrading froma higher position in the spectrum of the dis-ease. In the present study an attempt hasbeen made to characterize these two sub-groups on the basis of the a) history of evo-lution of the disease, b) clinical presenta-tion, c) bacteriological status, d) histology,and e) lepromin test.

Fifty-three patients were included in thisstudy, 46 (86.8%) were males and seven(13.2%) females. Their ages ranged from 18to 75 years. The lepromin test was negativein all. From the analysis of our data, twodistinct patterns have emerged. In 29 pa-tients (Group I) none had discrete lesionssuggestive of a higher position in the leprosyspectrum in the past or at the time of ex-amination. All patients showed generalizeddiffuse infiltration; 12 (41.4%) also had nod-

ulation, 20 (69%) had symmetrical periph-eral neuropathy, 19 (65.5%) had edema ofthe hands and feet, eyebrows were intact in13 (44.8%), ichthyotic changes in skin of thelower extremities were seen in 14 (48.3%),evidence of erythema nodosum leprosum(ENL) was seen in 3 (10%), and only 3 (10%)patients had trophic ulcers. In the remaining24 patients (Group II) history of onset ofdisease suggested that the initial lesion in12 patients was an erythematous plaque, 6had maculoanesthetic patch(es), 3 noticedsymptoms of neuropathy, 2 had pain innerve, and 1 observed nodules. On exami-nation, in addition to lesions suggestive oflepromatous leprosy, 17 (70.8%) had a fewskin lesions suggestive of a higher portionof the leprosy spectrum (BT, BB and BL),14 (58.3%) had peripheral neuropathy, 6(25%) had evidence of neuritis, deformitieswere seen in 7 (29.2%), generalized infiltra-tion in 2 (8.3%), nodular lesions were seenin 6 (25%), eyebrows were intact in 10(41.7%), and 6 (25%) had ENL.

The bacterial index (BI) in the slit-skinsmears from four sites was uniformly high(5-6+) in Group I, and there was a goodcorrelation with tissue BI. In Group II, thesmear as well as the tissue BI showed sig-nificant variations from site to site.

To study the nature of the cellular infil-trate, biopsies were taken from three sites.In Group I, since they had generalized dif-fuse infiltration, biopsies were taken froma) one of the extremities, b) the trunk, and

60, 1^ Correspondence^ 101

c) apparently normal-looking skin. In GroupII where there were lesions of a higher partof the leprosy spectrum, biopsies were takenfrom a) a lesion suggestive of lepromatousleprosy, b) a lesion suggestive of a higherpart of the spectrum, and c) normal-lookingskin. In Group I the tissue response in allthree sites was similar and was consistentwith the histology of polar lepromatous lep-rosy (LLp). In Group II (The Table), out of72 biopsies, 38 were from lesions clinicallysuggestive of LL. Of these 38 biopsies, 27showed histology compatible with LLs, 7were LLp, 2 were suggestive of BL, and theremaining 2 had changes of BB. In 13 bi-opsies from lesions having a BL morphol-ogy, histological changes in 9 were of LLs,in 2 were of BL, and in 1 each were of LLpand BB. All six lesions with BB morphologyhad the histology of subpolar lepromatousleprosy (LLs). Out of 4 lesions which wereclinically BT, 2 had the histology of LLsand 1 each had changes of BL and BB. Elev-en biopsies were taken from apparently nor-mal-looking skin, 8 had LLs histology, 1had LLp histology, and 2 showed infiltratesuggestive of indeterminate leprosy ( 4 ).

From the above data it is evident thatpatients in Group I developed the lepro-matous form de novo and should be iden-tified as polar lepromatous (LLp). We be-lieve that LLp cases acquire the immunedefect, the activation of suppressor mech-anisms or the clone deletion, from the be-ginning. However, with the present state ofknowledge it is difficult to comment wheth-er such an immune response is governed bysome genetic factor(s) in the host variationin the strain(s) or organism, or mode of en-try of the organism.

In Group II, history revealed that the ini-tial lesions were usually of a higher part ofthe leprosy spectrum which graduallydowngraded. These patients usually pre-sented with lesions of lepromatous leprosyand, in addition, also showed a few lesionsof a higher part of the spectrum, asymmet-rical neuritis, early onset of deformities,overlapping in histology and clinical diag-nosis of lesions, and variation in smear aswell as in tissue BIs from site to site. Theseobservations suggest that these cases wereable to mount some resistance initially butsubsequently downgraded to acquire lep-

THE TABLE. ClitliCOhiStOiOgiCai Correla-tion in Group II (LLs).

Histological

BT BB BL LLs LLp I

ClinicalNormal (11)^

8^I^2LLs (38)^

27^7^—BL (13)^

2^

9^IBB (6)^

6 — -13T (4)^

1^-

romatous leprosy. We prefer to call such LLpatients subpolar lepromatous (LLs).

It is well known that a percentage of lep-romatous patients show upgrading withtreatment and more frequently on admin-istration of immunotherapy ('). In our ear-lier study, where oral zinc was tried as animmunomodulator, we failed to observehistological upgrading as well as leprominconversion in LLp patients, while a smallpercentage of LLs patients did show the up-grading phenomenon ( 3). These observa-tions indicate that LLs patients are abso-lutely unresponsive.

In conclusion, we would like to stress thatLLp and LLs patients have some basic dif-ference(s) in pathogenesis. These two sub-types can be easily differentiated on the ba-sis of clinical presentation, the BI, and thenature of the infiltrate. The in vitro tests(LLT and LMIT) may not be reliable pa-rameters since they, like lepromin, can beinfluenced by the degree of immuno-suppression and bacterial load. Thissubgrouping of lepromatous leprosy casescan be useful in assessing the extent of ben-efits of various vaccines, immunomodula-tors, interpretations of immunological pa-rameters, and maybe in the understandingof the pathogenesis of leprosy.

—Narendra K. Mathur, M.D.Professor and Head

—Dinesh C. Mathur, M.D.Rajesh D. Mehta, M.D.

Asit Mittal, M.D.Suresh K. Jain, M.D.

Department of DermatologyS.M.S. Medical College and HospitalJaipur 302004, India

102^ International Journal of Leprosy^ 1992

—B. C. Sangal, M.D.Department of PathologyS.D.M. Hospital and Research CenterJaipur 302015, India

Reprint requests to Dr. N. K. Mathur,C-24 Peeyush Path, Bapu Nagar, Jaipur302004, India.

Acknowledgment. The authors wish to acknowledgefinancial grant no. SP/SO/B-30/87 from the Depart-ment of Science and Technology, India, for the supportof the work published here.

2. KAPLAN, G., WEINSTEIN, D. E., STEINMAN, R. M.,LEVIS, W. R., ELVERS, U., PATARROYO, M. E. andCotiN, Z. A. An analysis of in vitro T cell unre-sponsiveness in lepromatous leprosy. J. Exp. Med.162 (1985) 917-929.

3. MATIIUR, N. K., Bum, R. A., MANGAL, H. N. andSHARMA, M. L. Oral zinc as an adjunct to dapsonein lepromatous leprosy. Int. J. Lepr. 52 (1984) 331-338.

4. RIDLEY, D. S. Histological classification and im-munological spectrum of leprosy. Bull. WHO 51(1974) 451-465.

REFERENCESANTIA, N. II. Leprosy vaccine—a reappraisal. (Ed-itorial) Int. J. Lepr. 56 (1988) 310-313.

Immunology of a Burnt-out Lepromatous Leprosy Patient

TO THE EDITOR:

We would like to present a 62-year-oldmale patient born in the province of EntreRios, an endemic region of Argentina, whopresented at our hospital without treatmentand with a leonine facies (Fig. 1) and at-rophy and scars (Fig. 2) consistent withMuir's description of burnt-out cases (S). Thepatient gave a history of having had the skinchanges for 20 years. Repeated skin smearson the skin and nasal mucous membraneswere negative for acid-fast bacilli (AFB). Thepatient underwent a skin biopsy which re-vealed a lepromatous infiltration of the der-mis. Ziehl-Neelsen staining confirmed thelepromatous diagnosis because there wereAFB in the vacuolated cells in the dermis(Fig. 3). Intradermal lepromin testing wasnegative for both the Fernandez and theMitsuda reactions.

Immunologic studies were performed asfollows.

Humoral immunity. A large amount ofantibodies of the IgG type against Myco-bacterium leprae were found in this patientcompared with a pool of treated LL pa-tients' sera. The scrum levels of IgG anti-bodies were tested employing sonicated Al.leprae as antigen in an ELISA. IgG sub-classes of anti-M. leprae antibodies were de-termined using monoclonal antibodies spe-cific for the different IgG isotypes. The

relative proportions of the subtypes were:IgG,, 65%; IgG,, 25%; IgG,, 10%; IgG, notdetectable.

Cellular immunity. T-cell cytotoxicitywas measured against autologous macro-phages with minor modification as de-scribed by Kaleab, et al. (6). Peripheral bloodmononuclear cells (PMBC) were incubatedfor 7 days with or without the addition ofM. leprae or PPD antigens. Target cells wereadherent cells cultured for 6 days withoutantigen and pulsed 24 hr before the assaywith the same antigens. Antigens were em-ployed at the following concentrations:whole Al. leprae, 1.8 x 10 7 bacilli/ml; M.leprae 65-kDa and 18-kDa recombinantproteins, 10 mg/m1; and PPD (Statenserum-institute, Denmark), 20 µg/ml. Cytotoxicitywas measured in a standard 4-hr ''Cr releaseassay. The following results were obtainedat 40:1 effector/target cell ratio:

LL^Normal

.11. lepreze 60% 26% 43%I 8-kDa 65% 27% 26%65-kDa 42% I 0% 41 %PPD 49% 30% 6 7 %

The patient thus shows a high level ofT-cell cytotoxicity against autologous mac-rophages containing M. leprae antigens. Al.leprae antigens were obtained through WHO

Ourpatient