나(癩)반응에 관한 연구

Abstract

[한글]

Studies on Reactional States of Leprosy

Sung-Hyun Han, M.D.

Department of Microbiology Graduate School, Yonsei, University

(Directed by Professor Joon Lew, M.D., Ph.D.)

The occurrence of reactional states of leprosy in the course of the disease has

long been recognized(Danielssen and Boeck, 1848; Hansen and Looft, 1895).

Reactionla states are defined by Cochrane(1964) as "more or less sudden tissue

responses, resulting from the liberation of bacilli, or their products, into the

tissue, the manifestation of which can either be local or systemic". It is well

known that the reactional states of leprosy are the most distressing complications

of the disease, and that if reactional states intervene and continue to persist it

1) results in suffering of the patient and even death, 2) obstructs the continuance

of antileprosy treatment and 3) tends to induce visceral amyloidosis.

At Madrid Congress 91953 a) the official classification of reactional states of

leprosy into 3 main reactional phases 〔i.e., reactional lepromatous leprosy,

reactional tuberculoid leprosy and reactional (dimorphous) leprosy〕 was made.

Since then various methods of classification of reactional states have been

proposed by workers, and these have resulted in confusing classification of

reactional states. The exact cause (or causes) or the pathogenesis of reactional

states of leprosy is still unknown, but it is generally accepted that the

reactional states of leprosy arise from antigen-antibody reactions, and many

theories and hypotheses have been advocated by leprologists, such as allergy,

disturbance of the immunological equilibrium, autoimmune phenomenon, general

adaptation syndrome of Style and etc.

Though little is known about the pathogenesis of the reactional states of

leprosy, it is generally agreed that a reliable method of prevention or control

would not only simplify and shorten the period of treatment but would also save

much suffering and remove and important cause of deformity in leprosy. Report of

the Panel on Leprosy Reaction (1964) recommended that rational therapy should be

designed primarily to eliminate or interfere with the constant or repeated action

of the determining or 'trigger' causes, and likewise, be conditioned in each case

to the severity of the reactional episodcs. Basic general treatment intended to

central systemic symptoms, and symptomatic treatment designed to act on the acute,

focal or regional manifestations, are general practices in the treatment of

reactional states of leprosy. In addition, specific treatment of leprosy is

maintained, reduced or stopped according to the severity of the reactional states.

At present, the total number of leprosy cases in Korea is estimated to be about

60,000(Kim, 1969), and records indicate that DDS has been brought into therapeutic

use in Korea since 1955. However, no single result of the studies on reactional

states has been reported in Korea.

In this study, a series of study i.e., clinical epidemiology of reactions,

classification, skin bacteriology and leprosy reaction, and treatment, were carried

out in order to define the reactional states of leprosy in Korea, to give some

light on the pathogenesis of reactional states in lepromatous leprosy and to

evaluate overall efficacy of the treatment of leprosy reactions.

Materials and Methods

A. Patients:

1. Out of 1,911 leprosy patients who had registered and had been treated with DDS

at he World Vision Leprosy Research and Treatment Center, 207 cases of leprosy

reaction were included in the study. The type of the disease was classified

according to the method resolved at the Madrid Congress(1953b). As skin tests,

lepromin and tuberculin tests, were conducted.

2. Bacteriological examination of skin smears was made by the skin scraping

method, and the Bacterial Index(B.I.) and the S.F.G. value were calculated by

Ridley's method(1964a, 1964b).

3. Total serum protein was determined by the biuret method, and the serum was

fractionated by paper electrophoresis and the reading was made with Spinco

Analytrol. Mucoprotein was fractionated by paper electrophoresis and total

mucoprotein determination was made.

B. Clinical epidemiology of reactional states of leprosy:

Some important aspects in clinical epidemiology of reactional states of leprosy

were studied in regard to 1) the type of disease and leprosy reactions, 2) duration

between onset of the disease and occurrence of leprosy reaction, 30 duration

between initiation of DDS treatment and occurrence of leprosy reactions and 4)

frequency of occurrence of leprosy reactions and duration of reactional states.

C. Skin bacteriology and leprosy reactions:

Relationships between changes in skin bacteriology and the occurrence of

reactional states in lepromatous leprosy were investigated through 1) Bacterial

Index at registration and leprosy reaction, and 2) changes in B.I. and S.F.G.

values following DDS treatment and leprosy reaction.

D.Treatment of leprosy reactions and its evaluation:

The cases of reactional states were treated with 1) steroids, 2) antipyretics and

analgesics, 3) hypnotics and tranquilizers, 4) antileprosy drugs other than DDS, 5)

miscellaneous drugs and 6) blood transfusion in single of combined medication.

Over-all efficacy of the treatment of leprosy reactions was also evaluated.

Blood transfusions were carried out on 26 patients who were reaction-prone and

resistant to other treatment. As a pilot study to elucidate the mechanism involved

in the treatment of the reactions by blood transfusion, the total serum protein,

serum fractionation and AG ratio were determined before and afer the blood

transfusion.

Results and Summary

1) Based on the clinical epidemiology data of 207 leprosy reaction cases, the

reactional states of leprosy were classified into 5 groups for simplicity and

precticality: (1) erythema nodosum leprosum, (2) acute infiltration and

exacebation, (3) neuritis alone, (4) reactive tuberculoid, and (5) transitional

group.

2) Prior to the occurrence of reactional states, it was observed in lepromatous

leprosy that a drastic change in S.F.G occurred following the initiation of DDS

treatment. However, B.I. did not show a parallel decline and resulted in plateau

formation through the course of antileprosy treatment. With the disappearance of

reactional states in reaction-prone patients, there was observed a concomitant

decline of B.I. which was in plateau state during previous reactional states.

3) Treatment of leprosy reactions which steroids, antipyretics and analgesics,

hypnotics and tranquilizers, antileprosy drugs other than DDS, other miscellaneous

drugs and blood trasnfusion, singly or in combination, resulted in an over-all 80%

relief of reactional states.

4) The efficacy of blood transfusion in the treatment of leprosy reaction was

outstanding as compared to other remedies included in this study. A pilot study to

elucidate the mechanism involved in the efficacy of blood transfusions revealed

that there occurred decreases in total serum protein and gammaglobulin, increases

in albumin, and tendency toward normalization in the A/G ratio and other serum

fractions following blood transfusion.

[영문]

The occurrence of reactional states of leprosy in the course of the disease has long been recognized(Danielssen and Boeck, 1848; Hansen and Looft, 1895).

Reactionla states are defined by Cochrane(1964) as "more or less sudden tissue responses, resulting from the liberation of bacilli, or their products, into the tissue, the manifestation of which can either be local or systemic". It is well known that the reactional states of leprosy are the most distressing complications of the disease, and that if reactional states intervene and continue to persist it 1) results in suffering of the patient and even death, 2) obstructs the continuance

of antileprosy treatment and 3) tends to induce visceral amyloidosis.

At Madrid Congress 91953 a) the official classification of reactional states of leprosy into 3 main reactional phases 〔i.e., reactional lepromatous leprosy, reactional tuberculoid leprosy and reactional (dimorphous) leprosy〕 was made.

Since then various methods of classification of reactional states have been proposed by workers, and these have resulted in confusing classification of reactional states. The exact cause (or causes) or the pathogenesis of reactional states of leprosy is still unknown, but it is generally accepted that the

reactional states of leprosy arise from antigen-antibody reactions, and many theories and hypotheses have been advocated by leprologists, such as allergy, disturbance of the immunological equilibrium, autoimmune phenomenon, general

adaptation syndrome of Style and etc.

Though little is known about the pathogenesis of the reactional states of leprosy, it is generally agreed that a reliable method of prevention or control would not only simplify and shorten the period of treatment but would also save much suffering and remove and important cause of deformity in leprosy. Report of the Panel on Leprosy Reaction (1964) recommended that rational therapy should be designed primarily to eliminate or interfere with the constant or repeated action of the determining or 'trigger' causes, and likewise, be conditioned in each case to the severity of the reactional episodcs. Basic general treatment intended to

central systemic symptoms, and symptomatic treatment designed to act on the acute, focal or regional manifestations, are general practices in the treatment of reactional states of leprosy. In addition, specific treatment of leprosy is maintained, reduced or stopped according to the severity of the reactional states.

At present, the total number of leprosy cases in Korea is estimated to be about 60,000(Kim, 1969), and records indicate that DDS has been brought into therapeutic use in Korea since 1955. However, no single result of the studies on reactional

states has been reported in Korea.

In this study, a series of study i.e., clinical epidemiology of reactions, classification, skin bacteriology and leprosy reaction, and treatment, were carried out in order to define the reactional states of leprosy in Korea, to give some light on the pathogenesis of reactional states in lepromatous leprosy and to

evaluate overall efficacy of the treatment of leprosy reactions.

Materials and Methods

A. Patients:

1. Out of 1,911 leprosy patients who had registered and had been treated with DDS at he World Vision Leprosy Research and Treatment Center, 207 cases of leprosy reaction were included in the study. The type of the disease was classified according to the method resolved at the Madrid Congress(1953b). As skin tests,

lepromin and tuberculin tests, were conducted.

2. Bacteriological examination of skin smears was made by the skin scraping method, and the Bacterial Index(B.I.) and the S.F.G. value were calculated by Ridley's method(1964a, 1964b).

3. Total serum protein was determined by the biuret method, and the serum was fractionated by paper electrophoresis and the reading was made with Spinco Analytrol. Mucoprotein was fractionated by paper electrophoresis and total mucoprotein determination was made.

B. Clinical epidemiology of reactional states of leprosy:

Some important aspects in clinical epidemiology of reactional states of leprosy were studied in regard to 1) the type of disease and leprosy reactions, 2) duration between onset of the disease and occurrence of leprosy reaction, 30 duration

between initiation of DDS treatment and occurrence of leprosy reactions and 4) frequency of occurrence of leprosy reactions and duration of reactional states.

C. Skin bacteriology and leprosy reactions:

Relationships between changes in skin bacteriology and the occurrence of reactional states in lepromatous leprosy were investigated through 1) Bacterial Index at registration and leprosy reaction, and 2) changes in B.I. and S.F.G. values following DDS treatment and leprosy reaction.

D.Treatment of leprosy reactions and its evaluation:

The cases of reactional states were treated with 1) steroids, 2) antipyretics and analgesics, 3) hypnotics and tranquilizers, 4) antileprosy drugs other than DDS, 5) miscellaneous drugs and 6) blood transfusion in single of combined medication.

Over-all efficacy of the treatment of leprosy reactions was also evaluated.

Blood transfusions were carried out on 26 patients who were reaction-prone and resistant to other treatment. As a pilot study to elucidate the mechanism involved in the treatment of the reactions by blood transfusion, the total serum protein,

serum fractionation and AG ratio were determined before and afer the blood transfusion.

Results and Summary

1) Based on the clinical epidemiology data of 207 leprosy reaction cases, the reactional states of leprosy were classified into 5 groups for simplicity and precticality: (1) erythema nodosum leprosum, (2) acute infiltration and exacebation, (3) neuritis alone, (4) reactive tuberculoid, and (5) transitional

group.

2) Prior to the occurrence of reactional states, it was observed in lepromatous leprosy that a drastic change in S.F.G occurred following the initiation of DDS treatment. However, B.I. did not show a parallel decline and resulted in plateau formation through the course of antileprosy treatment. With the disappearance of reactional states in reaction-prone patients, there was observed a concomitant decline of B.I. which was in plateau state during previous reactional states.

3) Treatment of leprosy reactions which steroids, antipyretics and analgesics, hypnotics and tranquilizers, antileprosy drugs other than DDS, other miscellaneous drugs and blood trasnfusion, singly or in combination, resulted in an over-all 80% relief of reactional states.

4) The efficacy of blood transfusion in the treatment of leprosy reaction was outstanding as compared to other remedies included in this study. A pilot study to elucidate the mechanism involved in the efficacy of blood transfusions revealed that there occurred decreases in total serum protein and gammaglobulin, increases in albumin, and tendency toward normalization in the A/G ratio and other serum fractions following blood transfusion.