LK-4Erythema(St.Musafirah.pdf

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45J Med Nus Vol. 27 No.1 Januari-Maret 2006

ERYTHEMA NODOSUM LEPROSUM: CLINICAL FEATURES AND

HISTOLOGICALLY, REPORTED THREE CASES

St. Musafirah, Sri Vitayani M, Muh. Dali Amiruddin1, Mahmud Ghaznawie2

* Departement of Dermato-Venereology, Medical Faculty of Hasanuddin University/

dr.Wahidin Sudirohusodo General Hospital, Makassar, Indonesia

** Departement of Pathology Anatomy, Medical Faculty of Hasanuddin University, Makassar, Indonesia

RINGKASAN

Reaksi Erythema Nodosum Leprosum (ENL) dapat terjadi pada pasien kusta, sebelum, selama dan sesudah

terapi. Reaksi tersebut dapat menyebabkan sekuele yang disebut sebagai deformitas. Dilaporkan 3 kasus kusta

disertai reaksi ENL, dengan gambaran klinis berbeda dan dikonfirmasi dengan pem eriksaan histopatologik.

Kasus 1, ENL muncul pada penderita kusta setelah pengobatan Multi Drug Therapy (MDT) dan Kasus 2 muncul

pada penderita selama pengobatan MDT. Kedua penderita tersebut, memberikan gambarn klinis identik dengan

adanya nodul erytema dan demam, secara histopatologik ditemukan gambaran karakteristik reaksi ENL Kasus 3,reaksi ENL muncul pada penderita kusta sebelum pengobatan, dengan gambaran klinis adanya erosi dan ulcus

generalisata dan secara histopatologi ditemukan sebagai kusta lepromatous subpolar, dan ini merupakan kasus

yang tidak umum. Pada kasus 1 dan 2 diberikan terapi kortikostiroid oral dan memberikan perbaikan, akan tetapi

kasus ke 3 diberikan terapi kortikosteroid oral tetapi pasien meninggal dengan penyebab yang tidak diketahui.

(J Med Nus.2006;27:45-50)

SUMMARY

Erythema Nodosum Leprosum (ENL) reaction can appear in the leprosy patients before, during and after treatment.

The reaction may lead to neurologic sequele, then it will be deformities. We reported three cases of leprosy with ENL

reaction, whereas they have different clinical feature and have confirmed with histopathologically examination. Case

1, ENL appears to the leprosy patient after the treatment of Multi Drug Therapy (MDT) and the case 2, it appears to the

patients during tretament MDT. Both the patients, shown identical clinical featurs with pain nodul erythematous and fever, and histopathologically was found characteristic as ENL reaction. The case 3, ENL reaction appears to the

leprosy patients before the treatment, clinical feature shown erosion and ulcer generalized and histopathologically

was found as leprosy subpolar. It is the uncommon case. Case 1 and 2 were given corticosteroid orally and some

improvement, eventhough case 3 also was given corticosteroid orally bu she died with unknown causes

* This paper had been read as oral presentation in Australasian Dermatopathology Society 26 th Annual Conference,

Brisbane Convention Centre, 26 – 28 August 2005 (J Med Nus.2006;27:45-50)

INTRODUCTION

All patients with leprosy are liable to develop acut,

subacute or protrated inflammatory episodes called

“lepra reaction”, which are the result of a sudden

alteration of the host-parasite relationship.1-4

Lepra reaction may be of two types (Ridley & Jopling,

1981): 1, 3-6

1. Type 1 reaction is cell-mediated and occurs in

tuberculoid, boderline, and lepromatous leprosy.

There is inflammation of the existing leprosy

lesion. Histological examination will detect

improvement (reversal reaction) or worsening

(down grading reaction)

2. Type 2 reaction occurs in lepromatous leprosy

and some BL cases. It is possibly an Arthus –

like phenomenon due to circulating immune

complexes.

3. Type 3 reaction, is rare type, the Lucio

Phenomenon.

Erythema Nodosum Leprosum (ENL) , is named for

its most prominent clinical finding: an eruption of tender,

red nodules,1,2,4 usually involve the face, trunk, and

extremities.7 It is an immune complex disease, a Type III

hypersensitivity reaction, and occurs almost exclusively

Laporan Kasus



J Med Nus Vol. 27 No.1 Januari-Maret 200646

in patients with lepromatous leprosy (LLp and LLs) and

only occasionally in patients with boderline leprosy (BL).1,

2,4,5,7 Antigens of M. Leprae and antibodies form immune

complexes with complement, which precipitated in the

tissue of the skin, blood vessel walls, nerves, and other

organs these precipitates attract neutrophils, which further

damage the tissue.2,4,7 Erythema Nodosum Leprosum(ENL) reaction can appear in the leprosy patients before,

during and after treatment. The reaction may lead to

neurologic sequele, then it will be deformities.8

Histologically, ENL is characterized by vasculitis and

panniculit is. Polymorphonuclear leukocytes are

predominant early, and microabcess may form.4,7,8

We reported three cases of leprosy with ENL reaction,

whereas they have different clinical feature and have

confirmed with histopathologically examination.

CASE REPORTCase 1

A 17 ys old woman, came to the clin ic dermato-

venereology wahidin sudirohusodo general hospital with

complain ulcers in the extremities and plaque

erythematous generalized. She has been experinces

approximately 1 year and more seriously in 1 month

before came to the clinic. In the physical examination,

there was plaque erythematous generalized with shine

surface, well-demarcated, and no anathesia. In the

upper extremities, we found the ulcers and erosion

simmetrically. There was enlarged on the facialis, ulnarisand peroneus nerves. The patien has not get MDT or

other drugs. On histologically examination, we found that

atrophy epidermis with thinned in subepidermal area.

Granuloma in dermis contain histiocyte cells and foamy

cytoplasm, neutrofil extent to subcutis layer. Adnexa,

nerves and blood vessel were infiltrated of granuloma.

Fite Faraco stain, that was found M. Leprae in the globi

form. Conclusion: ENL, LLs type leprosy. Skin smear

for this case is (6+). She push hospitalization with the

reason she get lactation with 3 months old baby.

The treatment of the patient was given, oral

corticosteroid (metilprednisolon initially 40 mg/day to 2

weeks) and neuroroburamntia. The follow up was done

every 2 weeks and the corticostreoid oral tappered of 5 –10 mg every 2 weeks.Unfortunately, she passed out 3

weeks later, with unknown causes.




Case 2

A 35 ys old man, came to the cl in ic dermato-

venereology wahidin sudirohusodo general hospital with

complain nodul erythematous on face and all of the body,

and the fever and neuritis, 10 days ago. In the physical

examination, there was nodul erythematous generalisata.

Also we found hyperpigmentation macule anasthesi in

the chest, back and extremities. The extremities was found

anasthesia in. There was thickened and neuritis on the

ulnaris and peroneus nerves. The patien has getting MDT

5 months. On histologically examination, we found that

atrophy epidermis, with granulomas in nerves and

adnexa which contain histiocyte cells and foamy

cytoplasm, neutrofil cells extent to subcutis layer. Fite

Faraco stain, that was found M. leprae absent.

Conclusion: ENL, LLs type leprosy. Fite Faraco staining:

M. Leprae (+) fragmenetd. Conclusion: ENL, Boderline

Lepromatous. Skin smear of this case is negative.

The treatment was given oral corticosteroid

(metilprednisolon initially 40 mg/day to 2 weeks) and

neuroroburantia. The follow up was done every 2 weeks

and the corticostreoid oral tappered of 5 – 10 mg every 2

weeks. The patients was improve after 6 weeks but the

later weeks, nodul of the bodies appear again, so that

corticosteroid dose was increased. All of the number given

corticosteroid in this patients was 18 weeks.The patients

was improve after 10 months corticosteroid

Case 3

A 57 ys old woman, came to the clinic dermato-

venereology wahidin sudirohusodo general hospitalwith complain nodul erythematous on face and all of

the body, and the fever and arthralgia, 2 weeks ago. In

the physical examination, there was hyperpigmentation

macule on the face, limbs and extremities with simetris,

shiny and well-demarcated. Also nodul erythematous

generalisata. There was enlarged and neuritis on the

ulnaris, peeroneus and tibialis posterior nerves. The

patien have been finished MDT 6 months ago. On

histologically examination, we found that atrophy

epidermis, with granuloma in dermis which contain

histiocyte cells and foamy cytoplasm, neutrofil until

subcutis layer. Fite Faraco stain, that was found M.

leprae (+) and fragmented form. Conclusion: ENL, LLs

type . Skin smear of this case is negative.

The treatment of the patient similary of the patient’s

before, was given oral corticosteroid (metilprednisolon

initially 40 mg/day to 2 weeks) and neuroroburantia.

The follow up was done every 2 weeks and the

corticostreoid oral tappered of 5 – 10 mg every 2

weeks.. All of the number given corticosteroid in this

patients was 18 weeks.




HISTOPHATOLOGIC FEATURES

granuloma

M. Leprae solid M. Leprae fagmented




DISCUSSION

Erythema Nodosum Leprosum is a disease that

only appear in multibacciler leprosy patients, whether

they have been get or not the treatment of MDT.9 The

prevalence of ENL was reported more than 50% in the

lepromatouos leprosy and 25% in the borderlineleprosy. Usually 15-50% lepromatos leprosy is become

ENL within the first year of treatment and 90% occur

within the second year of treatment. 9-12 The re-

occurance symptoms of ENL and consequence of

dissability made it as health problem seriously.4,12,13

In the first cases, initial diagnosis as a pemfigus

vulgaris, because there was bulla and ulcer in the upper

extremitis that similar with pemphigus. Also, there was

small pink lesion and plaque erythema in her trunk

without anathesia. No fever and arthralgia. But we found

enlarged of ulnar and peroneus nerves. The patients

was not get drug yet. After histolpatologic axamination,

i t turned out of atrophic epidermis with thin of subepidermal area. There was very solid granuloma that

coat of all epidermis and dermis layer. The granuloma

without sitoplasma foamy (active lesion). Among

granulomas there was much multinucleated Giant cells.

Adnexa, sweat gland and nerve have been infi ltrated

by granulomas. Fite-faraco staining, AFB(+) in the

cluster form. Conclusion: lepromatous leprosy (LLp)

with ENL. End diagnosed as a lucio phenomenon.

According to the literature that a lucio phenomenon

is a unusual type II reaction that is sometimes

designated a type I I react ion, subtype of in a

lepromatous leprosy (la lepra bonita)3,6,14 that is

characterized by cutaneous hemorrhagic infarct in

patients with diffuse infiltration of the skin by a

granulomatous process heavi ly loaded with

mycobacterium leprae.3, 6,14,15 Also, lucio leprosy appear

often before treatment has been started.4,15 This is

shown in clinical features of cases above. And then after

the confirmed of histologically, the shown as LL.

Al thought, histolog ical ly was no t appropriate wi th

literatur, whereas it was mentioned that histologic

features in the lucio phenomenon was found ischemic

epidermal necrosis with necrosis of superficial blood

vessels and oedema and endothelial proliferation of

deeper vessels.4,15

Also, in this case, histologically as a lepromatous

leprosy. They agree with literature, histologic featureof lepromatous leprosy , there is Infiltrate celluler

axtensive that is almost invariably separated from the

flattened epidermis by grenz zone.4, 5,15-17 A macrophag

granuloma is seen with no epitheloid cells and scanty

lymphocytes and plasma cel ls unless there is

complicating ENL.5,17 The nerve sheaths are laminated

(onion peel appearance). 17 Acid fast baci l l i are

numerous and are found in packets (globi) within

macrophages. Older lesions show vacuolated

cytoplasm within macrophag due to lipid accumulation

(lepra cells of Virchow).2,4,15

In the second and third cases, initial diagnosed as

a ENL reaction, with clinical fatures was pain nodules

erythematous general ised as well as fever and

arthralgia. Also, we found thickened and neuritis on the

ulnaris, peroneus nerves. They ware according to the

literatur, that clinically ENL was commonly as pain

nodules eryuthematous with fever and neuritis.1,4,15

Histologically this cases, we found epidermis

atrophy and granulomas in dermis consisted of

histiocyte cells with foamy cytoplasma, Langhans, and

neutrophil cells extent to subcutis layers. Fite Faraco

staining was found M. leprae (+) and fragmented form.

In the literature, histopattologic feature of ENL isleukocytoclastic vasculitis in artery or vein, infiltrate

limphocyte polymorhonuclear and baccilli fragmented

form.(18) Vasculitis and panniculitis are characterize.

Predominantly of leukocyte polymorphonuclear and

may be microabhcesses form.2,5,17

Managemnet of leprosy reaction should be: firstly,

to control acut neuritis in order to prevent anasthesiaq,

paralysis and contracture, and the second, to kill the

bacilli and prevent extentsion of diseases. Early

diagnosis and treatment and energetic management of

reactional states should prevent to development of all

disabilities. A practical approach to management

involves, anti-inflammatory therapy, analgetic therapy,

splinting and exercise and antibacterial therapy.15,19

In cases of neuritis, the most rapid control is

essential, which to give the corticosteroid such asa

prednison or prednisolon is started with daily dose 40

– 80 mg, according to sever ity. The doses should be

reduced to 40 mg after a few days or 5 – 10 mg/ week

if the improve of neuritis.15,19 Many of drug may be used

to reduced to inflammation or as a anti inflammatory,

such as coticosteroid, thalidomide, and clofazimine,

non-steroidal anti inflamati on (NSAID), chloroquin,

antimonial, pentoxifilline.15,19-21

In this cases, all of the patients to improve with

corticosteroid therapy, although corticosteroid was

given in a long time in case 2 and three. And in patients3, patient was die, with unknown causes.

Side effect of corticosteroid is suppress immune

responses. Other side effects include salt and water

retention, development of Cushing’s syndrome with

osteoporosis, muscle wasting, and activation of peptic

ulcers.15 So that, long time follow up should be done to

prevent occuring the side effect.20




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