V'olunlc 67. Numher 3('rinted in the USA.

(ISSN 0148916X)

INTERNAFIONAl. JOIRNAI. Ur LEMOS)"

Risk Factors for Erythema Nodosum Leprosum'Rakesh Manandhar, Joseph W. LeMaster, and Paul W. Roche'

Erythema nodosum leprosum (ENL) isan acute inflammatory condition afl'ectinglepromatous leprosy paticnts. The conditionis charactcrized by the appcarancc of multi-ple, tender, red, skin noduies accompaniedto a variable extent by fever, edema, vas-culitis, neuritis and iritis. Thc frcquency ofENL appears to be lower in patients onmultidrug therapy (MDT) compareci withpaticnts on dapsone monotherapy (l). Thismay bc due to the antiinllammatory proper-ties of clofazimine, which is particularlywell absorbed into the skin, although it mayalso be that carlier treatment has reducedthe proportion of highly smear-positive pa-tients, and this may explain a decline inENL prevalence.

ENL is an important clinicai complica-tion in leprosy which must bc promptly andeffectively treatcd. To recognize which pa-tients are at high risk of developing thiscondition, we have used the pre-treatmentclinicai and laboratory data from more than500 new patients to identify factors con-tributing to a high risk of ENL. Using theseresults, it is possible to set simple criteria atdiagnosis for those paticnts who need to bemonitored for ENL during and after theirleprosy chemotherapy.

MATERIALS AND METHODSWe examined the hospital records of ali

649 previously untreated borderline lepro-matous (BL) and lepromatous (LL) casesregistered as regular MDT patients between1989 and 1997. Only paticnts who wereregular attendees at the Anandaban LeprosyHospital clinics were included.

' Received for publication on 28 December 1998.Accepted for publication in revised form on 20 May1999.

R. Manandhar, B.Sc. (Hons.); J. W. LeMaster,M.D., P. W. Roche, Ph.D., Mycobacterial ResearchLaboratory, Anandaban Leprosy Hospital, P.O. Box151, Kathmandu, Nepal.

Reprint requests to Paul Roche, Ph.D. at the aboveaddress or FAX: 977-1-290-538; e-mail:roche @ umn.mos.com.np

Ali data werc collected at the patients'first consultation. This included age, sexand clinicai classification based on the Rid-iey-Jopling classification ( 7 ). Confirmationof clinicai classification by histopathologywas available in only a minority of cases.The number of years since thc appcaranccof thc first symptoms as rcported by the pa-ticnts was recorded as a measure of theiength of the untreated disease. The cumu-lativc disability index (DI) of each paticntaccording to the World Health Organization(WHO) classification system (I") was alsorecorded. In addition, the number of bodyarcas (BA) with disease were noted basedon thc numbcr of BA with cithcr skinpatches or enlarged nerves. This was basedon a scalc with a maximum of 9, consistingof 4 for the trunk divided sagitally anteriorand posterior, 4 for the limbs, and 1 for thehead (' `). The total number of patches, en-larged nerves, presence of skin infiltrationand nodules were also recorded. The meanhacterial indcx (BI) was calculatcd fromslit-skin smears taken from a minimum offour sitos, including a clinicai lesion. Themorphological indcx (MI) was calculatcd asthe percentage of solid-staining bacilli seenin 200 acid-fast bacilli (AFB). IgM anti-phenolic glycolipid-I (PGL-I) antibodieswere measured as described previously (`').

Erythema nodosum leprosum (ENL) wasdef►ned clinically as the appcarancc of mul-tiple tender or painful erythematous nod-ules in the skin accompanied by fever andmalaise.

Statistics. The differences in the rangeof quantitative variables between differentpaticnt groups werc tested by means of theMann-Whitney U Test.

Chi-squared contingency tables wereused to calculate the unadjusted odds ratios(OR) and the 95% confidence intervals(95% CI) for differences in the prevalenceof ENL between patients with and thosewithout individual clinicai or laboratory pa-rameters. The unadjusted OR and 95% CIfor the differences in the prevalence of mul-

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67, 3^Manandhar, et ai.: Risk Factors for ENL^271

At presentation^1 to 6 mo 7to122mo^13to18mo^19to24^24 mo

Months of MDT

FIG. 1. Time of occurrence of ENL in 108 patients under MDT treatment.

tiple episodes of ENL hctween patientswith and without individual clinicai or lab-oratory parameters were also calculated.

Adjusted OR and 95% CI were calcu-lated by logistic regression to assess the sig-nificance of individual factors. Only riskfactors with unadjusted OR signifìcantlymore or less than 1.0 (except for age andsex) were included.

RESULTSOf the 649 patients, 86 were excluded

for reasons of defaulting, transfer to anothercenter, or incorrect diagnosis or classifica-tion. The records of the remaining 563 pa-tients were examined for baseline (i.e., atdiagnosis) clinicai, bacteriological andserological data as well as a history of ENL.

The 563 patients consisted of 422 (75%)inale and 141 (25%) female patients withan age range of 3 to 85 years. There were351 (62%) borderline lepromatous (BL)and 212 (38%) lepromatous (LL) patients.Ali the patients received WHO/MDT multi-bacillary (MB) treatment.

The patient group had an average ofseven body arcas with disease (range 1-9);among these were 273 (48%) patients whohad disease in ali nine body arcas. The pa-

tient group had an average of four nervesenlarged (range 0-12); 535 (95%) patientshad at least one enlarged nerve. Skin nod-ules and infiltration were present in 98(17%) and 366 (65%) of the patients, re-spectively. Of patients with a disabilitygrading at presentation, 305 (66%) had es-tablished disability (that is, a disability in-dex greater than 0). Three-hundred-twenty-eight (58%) patients presented more than ayear after the appearance of the clinicaisymptoms. Skin smears (BI) were positivein 470 (83%) patients, negativo in 85(15%), and not done in cight. Thc MI waspositive in 89, negative in 168, and notdone in 306 patients. PGL-I antibodieswere positive in 320 (70%), negative in 135(30%), and not done in 108 patients.

Among the 563 patients, 108 (19%) hadan ENL reaction during the study period.Patients were self-referring outpatients andwere generally admitted for treatment of thereaction. About 20% of ENL cases had neu-ritis and 5% had iritis. The severity of theENL reaction varied and treatment was var-ied appropriately, with milder cases (aboutone-third) trcated with nonsteroidal antiin-flammatory drugs and those with more se-vere ENL or neuritis treated with steroids

272^ International Journal of Leprosy^ 1999

TABU, 1.^Mediar rabies and ranges for patieiils it'ith and without ENL and for pa-tients with a single episode and multiple episodes of ENL.

VariablesNon-ENI.(N = 455)

(range)

ENL(N = 108)

(range)

Single episode(N = 51)(range)

Multiple episodes(N = 55)(range)

Age (yrs.) 40 35' 35 31.5(3-85) (12-68) (13-68) (12-60)

Bacterial index 2.7 4 ' 4 4(RI) (0-6) (0-6) (0-6) (1-5.75)

No body arcas 8 9 9 7with disease (0-9) (2-9) (2-9) (2-9)

No. enlargednerves

4(0-12)

6' ,(0-12)

5.5(0-12)

6(0-10)

Years untreated 2'' 2 3disease (1-33) (1-14) (1-13) (1-14)

Disability 1index (0-3) (0-2) (0-2) (0-2)

Anti-PGL-1 0.4 0.605 0.65antibody levei (0-3.4) (0-3.2) (0.017-3.03) (0-3.22 )

Morphological O 0 O oindex (0-40) (0-70) (0-25) (0-40)

Statistically significant difference; Mann-Whitney U test, p <0.001.Statistically significam difference; Mann-Whitney U test, p <0.01.

and/or thalidomide. There was an averageof two episodes of ENL per patient: 49(45%) patients had a single episode, 27(25%) two, 13 (12%) three, 6 (5%) four, 2(2%) five and 5 (5%) had more than 5episodes of ENL.

Thirty-five (34%) of the ENL cases hadno previous antileprosy treatment at thetime of reaction; 34 (32%) had ENL reac-tion in the first 6 inonths of MDT, 14 (13%)between 7 and 12 months after the begin-ning of MDT, 8 (7%) between 13 and 18months of treatment, 3 (3%) betweèn 19and 24 months, and 10 (9%) after 2 years ofMDT (Fig. 1).

Table 1 shows median values of vari-ables in patients with and without ENL andin patients who had single and multipleepisodes of ENL. Patients who had ENLwere significantly younger, had a higher BI,a higher levei of anti-PGL-I antibodies,more enlarged nerves, longer periods of un-treated disease and less established disabil-ity than did patients without ENL. Therewere no significant differences in the me-dian values between patients with singleepisodes of ENL and those with multipleepisodes of ENL. However, those who hadmultiple episodes of ENL were younger,had more enlarged nerves, and had a higherlevei of anti-PGL-I antibodies than did thosewho had only a single episode of ENL.

The differences in the prevalence ofENL according to the presence or absenceof individual clinicai or laboratory parame-ters were assessed (Table 2). LL patientshad a significantly higher prevalence ofENL (33%) than did BL patients (11%, p<0.001).

Patients with a BI of >4+ had a signifi-cantly higher prevalence of ENL (32%)than did patients with a BI of <4+ (14%, p<0.001). Patients with more than five en-larged nerves had a significantly higherprevalence of ENL (27%) than did thosewith the number of enlarged nerves 55(14%, p <0.001). Patients with skin nodules(21%) had a significantly higher prevalenceof ENL than did those without nodules(13%, p <0.05). Patients with diffuse skininfiltration had a higher prevalence of ENL(26%) than did those without (6%, p<0.001). Patients who were IgM anti-PGL-I antibody positive (21 %) were morelikely to develop ENL than were those whowere antibody negative (13%).

The prevalence of ENL was not signifi-cantly different between male and femalepatients, between patients older than 40,and those <_40, between patients who haduntreated disease for more than 1 year, andthose who reported less than 1 year of un-treated disease. It was also not significantlydifferent between patients with established

67, 3^Manandhar, et al.: Risk Factors for ENL^273

TABLE 2. Relationship between clinicai and laboratorv parameters and the prevalenceo/ ENL (N = 563).

VariablesNo. with

ENL/totalpositive (%)

No. withENL/total

negative (%)Unadjusted odds ratio

(95% CI)Adjusted odds ratio'

(95% CI)

Male 81/422 (19) 26/140 (19) 1.003 (0.61-1.62) 0.89 (0.48-1.64)Age >40 39/246 (16) 69/317 (22) 0.677 (0.43-1.04) 0.69' (0.5-0.94)LL 70/212 (33) 38/351 (11) 4.06' (2.56-6.43) 2.88'1 (1.59-5.2)Sulcar >4+ 51/160 (32) 56/395 (14) 2.83` (1.8-4.4) 1.39' (1.11-1.76)Body arcas with

disease = 9 54/273 (20) 54/290 (19) 1.07 (0.7-1.64) ND'No. enlarged

nerves >5 61/227 (27) 44/308 (14) 2.2° (1.4-3.4) 1.17 (0.68-2.0)Nodules 26/122 (21) 58/441 (13) 1.68' (1.0-2.8) 0.77 (0.4-1.46)Infiltration 95/366 (26) 13/197 (7) 4.96` (2.65-9.29) 2.71' (1.14-6.41)More than 1 year

untreated disease 73/328 (22) 30/200 (15) 1.62^ (1.0-2.59) NDDisahility

(Dl >0) 47/305 (15) 36/158 (23) 0.6' (0.05-1.14) NDPGL-I Ah

positive 68/320 (21) 18/135 (13) 1.75' (0.99-3.09) 0.86 (0.45-1.65)Morphological

index positive 15/89 (17) 42/168 (25) 0.67 (0.08-1.25) ND

Includes ali confounders and age and BI as categories.Statistically significant, p <0.05.Statistically significant, p <0.01.

''Statistically significam, p <0.001.ND = Not done.

disability and those with a positive MI andthose with a negative MI, nor betweenthose with disease in ali body arcas andthose with less diffuse disease.

A clear association was found betweenthe incrcasing BI and the prevalence ofENL (p <0.001) (Fig. 2). Likewise, therewas a trend for the prevalence of ENL todecrease in older patients (Fig. 3), but thisdid not reach statistical significance.

Logistic regression analysis. The unad-justed OR suggested a significant effect ofeight factors on the prevalence of ENL: a)an LL classification, b) a smear >4+, c)more than five enlarged nerves, d) the pres-ence of nodules or e) infiltration, f) morethan 1 year of untreated disease, g) the ab-sence of disability, and h) seropositivity foranti-PGL-I antibodies (Table 2). Logisticregression was used to estimate the adjustedeffect of each factor controlling for the sig-nificant confounding effects which wefound to be present. Age greater than 40, anLL classification, a smear >4+, more thantive enlarged nerves, the presence of nod-ules or infiltration, and anti-PGL-I antibodyseropositivity were found to be significantconfounders of each other and so were in-

cluded in the logistic regression analysis.Other factors (body arcas, length of un-treated disease, disability and positive MI)which had nonsignificant unadjusted ORwere excluded.

After adjustment, a significant increasein the risk of ENL is found for only thrcefactors: LL classification (OR = 2.88), skininfiltration (OR = 2.71) and smear >4+ (OR= 1.39). Age greater than 40 was signifi-cantly associated with a decreased risk ofENL (OR = 0.69). The risk of ENL de-creased linearly in the model as age in-creased. The risk of ENL increased linearlyas the BI increased.

An analysis of risk factors for multipleepisodes of ENL was also performed (Table3). Unadjusted OR identified five factorsassociated with an increased risk of multi-ple episodes of ENL: a) an LL classifica-tion, b) a smear >4+, c) more than fivenerves enlarged, d) the presence of skinnodules or e) infiltration. Age more than 40was associated with a significantly de-creased risk of ENL. When the same logis-tic regression model was applied to the out-come of multiple episodes of ENL, only anLL classification (OR = 4.6) and smear >4+

274^ International Journal o/'LeprosV^ 1999

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Neg^Less than 1- >1-, to <=2-^>2+ to <=3+^>3+ to <=4+^>4+

Bacterial índex

FIG. 2. Relationships between the bacterial index and the prevalence of ENL.

(OR = 1.42) were associated with increasedrisk of multiple episodes of ENL, whileolder patients were at significantly lowerrisk (OR = 0.55). When factors in patients

with multiple episodes of ENL were com-pared with those of patients with singleepisodes of ENL in logistic regressionanalysis, only the LL classification was as-

TABLE 3. Relationship between clinicai and laboratorV pcn n neters and the prevalenceof multiple episodes of ENL compareci with no ENL.

VariablesNo. with

ENL/totalpositive (%)

No. withENL/total

negative (%)Unadjusted odds ratio

(95%/o C1)Adjusted odds ratio'

(95% C1)

Male 39/422 (9) 16/140 (11) 0.72 (0.39-1.32) 0.72 (0.33-1.53)Age >40 15/246 (6) 40/317 (12.6) 0.45^ (0.24-0.83) 0.55` (0.36-0.85)LL classitication 41/212 (19) 14/351 (4) 5.77' (2.99-11.11) 4.6' (1.98-10.7)Smear >4+ 26/160 (16) 29/395 (7) 2.54° (1.43-4.52) 1.42' (1.0-2.0)Body arcas

with disease = 9 23/273 (8) 32/290 (11) 0.75 (0.42-1.33) ND'No. enlarged

nervos >5 34/277 (I5) 21/308 (6.8) 2.68` (1.47-4.86) 1.08 (0.54-2.18)Nodules 15/122 (12) 40/441 (9) 1.92' (1.01-3.65) 0.82 (0.37-1.8)Inliltration 50/366 (13) 5/197 (2.5) 6.07' (2.34-15.75) 2.93 (0.77-11.1)More than 1 year

untreated disease 37/328 (II) 16/200 (8) 1.46 (0.79-2.7) NDDisability

(Dl >0) 28/305 (9) 19/158 (11) 0.73 (0.39-1.36) NDPGL-1 Ab

positive 38/320 (12) 17/135 (13) 2.13 (096-4.73) 1.09 (0.45-2.63)Morphological

index positive 10/89 (II) 27/168 (16) 0.66 (0.3-1.44) ND

Includes ali confounders and age and BI as categories.Statistically significant, p <0.05.Statistically signilicant, p <0.01.Statistically signilicant, p <0.001.ND = Not done.

20

15

10

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67, 3^Manandhar, et al.: Risk Factors for ENL^275

25

<=20^21-30^31-40^41-50^

51-60^>60

Age Group

Fie. 3. Relationship between age and the prevalence of ENL.

sociated with increased risk (OR = 2.94, p =0.052).

DISCUSSIONThis study has described a relativeiy

high prevalence of ENL (19%) among new,previously untreated, borderline leproma-tous (BL) and lepromatous leprosy (LL) pa-tients trcated with MDT. This reflectsprevalence in a specialist leprosy hospital towhich paticnts suffcring from ENL will bereferred from ali over Nepal. Before the in-troduction of MDT, as many as 50% of LLand 30% of BL patients developed ENL (`).The introduction of WHO/MB MDT hasreduced both the frequcncy and severity ofENL, and Chis reduction may be attributableto the clofazimine component of MDTsince MB patients trcated with drug regi-mens without clofazimine continucd to ex-press high leveis of ENL (`). In a field pro-gram in Ethiopia, incidence rates of 2.7%and 11.1% wcre found in BL and LL pa-tients, respectively, trcated with MDT ( 2 ).

ENL has been recognized to frequentlyrecur in the patients it affects. In the prescntstudy, nearly half the paticnts with ENL hadmore than one episode. While ENL has pre-viously been recognized as occurring late,during or even after treatment, this study in-dicates that 9% of ENL reactions will occurafter the completion of MDT. It should benoted that in cach case this was the first re-actional event in there paticnts.

ENL has been recognized to be more fre-quent in LL paticnts than in BL paticnts (e).In the prescnt study, LL patients had a sig-nificantly higher prevalence of ENL (33%)than did BL paticnts (11%, p <0.001). Dueto variation in classification between cen-ters, the prevalence of ENL in BL paticntsmay differ somewhat from that describedhere, but it will always be less frequent thanamong LL patients.

Patients with highly positive smears(mean BI >4+) were also found to be at a39% higher risk of ENL. This accords withprevious studies implicating a high BI inENL patients ( 4 ). It has been hypothesizedthat a high bacterial antigen load will leadto immune complex formation which, inturn, will cause vasculitis and tumor necro-sis factor-alpha (TNF-a) secrction frommacrophages, which typify the immunolog-ical picture of ENL (`' ").

Histologically, bacteria in ENL have be-come downgraded and granular (`,), hencewe found no association between bacterialviability as measured by the solid-stainingratio (MI) and ENL. Previous studies (' 4 )have suggested that ENL is more commonwhen the MI is <5%, i.e., when there is alarge number of dcad bacilli. This could ex-plain the prevalence of ENL relatively latein both dapsone monotherapy C) and in theprescnt study whcre 9% of the reactions oc-curred for the first time in paticnts who hadcompleted 2 ycars MDT.

276^ International Journal o/'Leprosv^ 1999

Rclated to a high mcan BI is diffuse skininfiltration, which was associated in ourstudy with a 2.7-times grcater risk of ENL.Widespread diffusion of Mvcobacteriunlleprae antigens in the skin could expiam theoccurrcncc of crops of ENL nodules in theskin. The occurrence of ENL in paris of theskin with prcvious lepromatous infiltrationhas beco observed previously ( 5 ).

Thc finding of a lower prevalence ofENL among older paticnts and of a signifì-cant decline with increasing age (Fig. 3) isof importance to leprosy management. Thisis supported by an earlier study (4 ) whichfound that more patients aged 15-44 devei-opcd a reaction than did older paticnts orpatients with a lower BI. Another study ( 12)

found that paticnts with an onset of leprosyin the second decade of life were morelikely to develop ENL. Our data based onage at first presentation could reflect a dif-ference in the age of disease onset betweenENL and non-ENL patients. The relation-ship between age and risk of ENL could re-flect either an age-associated decline in im-munity or an increased prevalence in youngor adolescent patients.

Previous studies have implicated preg-nancy, puberty, intercurrent illness, vacci-nation and stress to be associatcd with thedevelopment of ENL ( 5). There may, in ad-dition, be a genetic basis for the develop-ment of ENL. Individuais with a geneticpolymorphism in the promoter region of thetumor necrosis factor gene (TNF2) are athigher risk of developing lepromatous lep-rosy ( 10). This gene polymorphism may alsobe associated with increased leveis of TNF,a finding in the sera of ENL patients ( 11 ).

Patients with LL have a high concentra-tion of mycobacterial antigen in their tis-sues and make high leveis of both IgM andIgG antibodics. The formation of immunecomplexes and the activation of the com-plement pathway along with release of in-flammatory mediators may expiam thepathology and clinicai symptoms associatedwith ENL ( 15). During ENL episodes, a faliin circulating IgM anti-phenolic glycolipidantibody leveis has been noted, which re-turns to pre-reactional leveis after the pa-tient has recovered ('), suggesting that IgManti-PGL-I may forro immune complexeswith the abundant PGL in the tissucs. In

this study, the scropositivity for anti-PGL-1antibodies was associated with an increasedunadjusted OR (Table 2). Howevcr, in thelogistic regression model, probably chie tolhe strong association between the antibodylevei and the Bi, the adjusled OR for anti-bodies did not reach statistical significance.

In summary, this study has shown impor-tant characteristics of ENL reactions in pa-tients heing trealed with MDT. Cliniciansneed to be awarc that a significam numberof ENL reactions will occur after comple-tion of MDT. In addition, paticnts youngerthan 40 with LL disease, skin infìltrationand a mean BI of >4+ are at a significantlyhigher risk of ENL and should be moni-tored throughout MDT. Shortening of theWHO/MDT MB regimen from 2 years to 1ycar may also influcnce both the prevalenceand timing of ENL reactions.

SUMMARYA retrospective study of new horderline

lepromatous and lepromatous patients re-porting for multidrug thcrapy (MDT) forleprosy at the Anandaban Leprosy Hospital,Kathmandu, Nepal, over an 8-year periodwas conducted to determine the prevalenceof erythema nodosum leprosum (ENL), thetime and frequency of reactions, and clini-cai and laboratory parameters associatedwith ENL. An overall prevalence of ENL inthis cohort of 19% was found. One third ofthese reactions occurred in patients beforeMDT was given, one third in the first 6months and one third after 6 months oftreatment. Nearly 1 in 10 of the ENL reac-tions occurred in patients who had com-pleted 2 years of MDT; 45% of patientswith ENL had more than one episode. Datacollected at the paticnts' first presentationwas used to identify four major risk factors.Patients with lepromatous disease, skin in-filtration or a bacterial index (BI) of >4+were at significantly increased risk. Patientsolder than 40 were at significantly de-creased risk of ENL. There was a linear re-lationship in the risk of ENL with an in-creasing BI and an inverse relationship toincreasing age. There observations shouldenable clinicians to recognize paticnts atfirst presentation who will be likely to de-velop ENL.

67, 3^~anilhar, et al.: Risk Factors for ENL^ 277

RESUMENSe hizo un estudio retrospectivo de los casos

nuevos de lepra lepromatosa y lepromatosa subpolarque fueron tratados con poliquimioterapia (PQT) en el1lospital Anandaban de Kathmandu, Nepal, a lo largode un periodo de 8 anos, para determinar la prevalen-cia de eritema nodoso leproso (ENL), cl tiempo y lafrecuencia de las reacciones y los parámetros clínicosy de laboratorio asociados con ENL. Se encontró unaprevalencia global de NEL en este cohorte de 19%. Untercio de estas reacciones ocurrieron en los pacientesantes de iniciar el tratamiento con PQT, un tercio enlos primeros 6 meses de tratamiento, y un tercio des-pués de 6 meses de tratamiento. El 10% de las reac-ciones ENL ocurrieron en pacientes que habian com-pletado 2 anos de tratamiento; 45% de los pacientescon ENL habian tenido más de un episodio reaccional.Los datos colectados de la primera entrevista con lospacientes se usaron para identificar los 4 factores deriesgo principales. Los pacientes con lepra lepro-matosa y con indices bacterianos (BI) de >4+ fueronlos de mayor riesgo. Los pacientes mayores de 40 anosfucron los de menor riesgo. La relación entre el riesgode ENL y el incremento en el BI fue lineal gero larelación fue inversa entre el riesgo de ENL y la edadde los pacientes. Estas observaciones podrían permitira los clínicos reconocer, en la primera entrevista, a lospacientes en riesgo de desarrollar ENL.

RÉSUMÉUne étude rétrospective des nouvcaux cas souffrant

de lèpre lépromateuse et borderline lépromateuse, sedéclarant afin d'ctre traités par la poly-chimiothérapie(PCT) à l'hôpital Anandabane contre le lepre à Kat-mandou au Népal, pendant une période de 8 années,fut effectuée afin dc déterminer la prévalence dc I'éry-thème noueux léprcux (ENL), la duréc et la fréquencede ces réactions, et les paramètres cliniques et de lab-oratoire associés à I'ENL. Une prévalence générale del'ENL dans cette cohort fut déterminée être de 19%.Un tiers de ces réactions se sont produites avant lamire en reuvre de la PCT, un tiers pendant les 6 pre-miers mois qui ont suivi le début du traitemcnt et untiers après les premiers 6 mois de traitement. Environ1 sur 10 des réactions de ENL furent observées chezdes patients qui étaient sous PCT depuis plus de deuxannées; 45% de ces paitents ayant des ENL eurent plusd'un épisode. Les données collectées durant la pre-mière consultation des patients furent analysées et per-mirent d'idenifier 4 facteurs de risque majeurs. Les pa-tients avec maladie lépromateuse, infiltration cutanéeou un indice bactérioscopique (IB) de >4+ présen-taient un risque d'ENL significativement plus élevé.Les patients âgés de plus de 40 ans avaient un risquesignificativement diminué de développer I'ENL. 11 yavait une relation linéaire entre le risque de développerun ENL et un IB croissant et une relation inverse avecl'âge. Ces observations devraient permettrent d'aider

les cliniciens à rcconnaitre dès la premiére consulta-tion les patients qui vont probablement développerl'ENL.

Acknowlcdgment. This work was supported byThe Leprosy Mission International. The authors wouldlike to thank the staff and patients of Anandaban Hos-pital for their cooperation in this study. This materialwas presented at the 15th international Leprosy Con-gress, Beijing, China, September 1998 (AbstractCL30) (int. J. Lepr. 66:24A, 1998).

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