The Unique Characteristic Skin Lesions of Borderline Leprosy

with Severe Reversal Reaction: The Uncommon Case

Eva Lydiawati, Febrina Dewi Pratiwi, Septiana Widyantari, Indropo Agusni

Department of Dermatology and Venereology, Faculty of Medicine, Universitas Airlangga/Dr. Soetomo General Hospital

Surabaya, Indonesia

Keywords: borderline leprosy, reversal reaction, multi drug therapy, leprosy reaction therapy

Abstract: Leprosy is a chronic granulomatous progresssive infectious disease caused by Mycobacterium leprae.

Clinical features of leprosy is dependent upon the equilibrium between bacillary multiplication and the host

cell-mediated immune response. Borderline leprosy is the immunologic intermediate of the granulomatous

spectrum and is the most unstable area. The characteristic skin changes in borderline leprosy are said to be

annular lesions with sharply marginated interior and exterior margins. It could be complicated by potential

intermittent hypersensitivity or leprosy reactions. Reversal reaction is one of leprosy reaction that most

commonly occurs in the borderline cases. We report here a case of the unique characteristic skin lesions of

borderline leprosy with reversal reaction. It was the uncommon manifestation because the lesions are

distributed in all over the body. Because of the reversal reaction, the lesions become more prominent and

have more sharply marginated borders. This case report aims to describe the characteristic of skin lesions

and clinical aspects of reversal reaction in leprosy. A 39-year-old man was diagnosed with borderline

leprosy with reversal reaction who was treated by methylprednisolone for 2 weeks adding up to the multi

drug therapy. There was clinical improvement and no side effect found during this study.

1 INTRODUCTION

Leprosy is one of a deliberately progresssive

infectious disease caused by Mycobacterium leprae.

It was complicated by potential intermittent

hypersensitivity reactions or lepra reactions. It is a

disease which primarily affects the skin and

peripheral nerve, and in highly bacillated state, any

internal organ except central nervous system can be

affected too. The damage to peripheral nerves results

in sensory and motor impairment with characteristic

dreadful abnormalities and debilities (Kumar and

Kar, 2017).

Leprosy reaction are considered as acute or

subacute episode, distinguished by cutaneous and

systemic involvement. Those are caused by changes

in the status of patient’s immune responses (Nery et

al., 2013). This immunologically mediated episodes

can be manifested as acute or subacute inflammation

affecting the skin, nerves, mucous membrane and/or

other sites which interrupt the chronic and placid

course of leprosy. It can results in deformity and

disability unless promptly and sufficiently treated.

Well-timed initiation of treatment for reaction can

reduce morbidity and prevent further deformities

(Kumar and Kar, 2017). So that, this case report

aims to describe the clinical aspects,

immunopathogenesis, and the therapy of reversal

reaction in leprosy.

2 CASE

A 39-year-old Indonesian man was referred to our

hospital in September 2017 with a 3-month history

of thickened red patches on almost all over his body.

It was also accompanied with pain sensation on the

site of lesions. Redness plaques appeared with

whitish fine scales. He was also have a slight

intermittent fever everytime he felt that the plaques

thickened. Firstly, he got red patches on his trunk

and face with thick sensation since about 8 months

befoe admission. He was diagnosed with

multibacillary leprosy for about 6 months in public

heath care and he have gotten the multidrug

treatment for lepromatous leprosy (MDTL) since th

368

Lydiawati, E., Pratiwi, F., Widyantari, S. and Agusni, I.

The Unique Characteristic Skin Lesions of Borderline Leprosy with Severe Reversal Reaction: The Uncommon Case.

DOI: 10.5220/0008157603680372

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 368-372

ISBN: 978-989-758-494-7

According to the patient, he felt that the macule

became thicker gradually after he took MDTL.

When the rash became thicker, he took some

medication from general practitioner (prednison) but

he forgot about the dose that he took. There were no

history of suffering from such disease before.

History of taking or applying any traditional

medicine before was denied. There were no history

of food or drug allergy. History of contact with other

persons who had leprosy was denied.

Figure 1: (A-D) The unique characteristic annular skin

lesions of borderline leprosy with severe reversal reaction

before management of leprosy reaction; (E-H) Clinical

improvement of reversal reaction after 2 weeks of oral

methylprednisolone along with MDT treatment. The

redness macules still persist but thinner than before.

Physical examination discovered slight fever and

multiple thick erythematous annular plaques that

sharply marginated, some punched out lesions, some

are covered with white fine scales and hypoaesthetic

(Fig. 1 A-D). No madarosis of the eyebrows or

eyelashes was observed. There were no saddle nose

or diffuse infiltrate on the face, and lagophthalmos.

Thickened peripheral nerves were detected on the

left and right ulnar nerves and accompanied with

tenderness on palpation. In addition, peripheral

neurological symptoms, including motoric, sensory

and autonomic nerve disturbance were not detected

based on a neurological assessment that

includedlight touch, pin – prick test, thermal sensory

test, manual muscle strength test and monofilament

test.

However, acid-fast bacilli were not detected by

the slit – skin smear test of the ear lobes and lesion

(Bacterial Index: 0; Morphological Index: 0).

Histological examination of the ear lobe skin

reveales atrophy and short-flattening of rete ridge on

the upper epidermis, there were some group of

hystiocyyte or foam cell on superficial to deep

dermis (Fig. 2 A-B). No specific microorganisms

were identified by Ziehl – Nielsen and Fite – Faraco

staining. Serologic test by detecting antiphenolic

glycolipid I (anti PGL-1) antibody was positive by

the score of IgM = 1553 (cutt off = 605 u/mL) and

IgG = 927 (cutt off = 630 u/mL). In addition, the M.

leprae deoxyribose – nucleic acid (DNA) was

detected from a skin sample by polymerase chain

reaction (PCR) (Fig. 2 C).

Based on theses findings, from physical and

laboratory examination, the diagnosis of

multibacillary, borderline (BB) leprosy was

established. The patient also had severe reversal

leprosy reaction but fortunately no disabilities was

detected at that time. The patient were observed for

Figure 2: (A) Histologic examination of ear lobe. There were atrophy and short-falttening of the rete ridge of the epidermis.

The group of histiocytes or foam cell on superficial to deep dermis and some bacteria are observed by Fite Farraco staining.

So the conclusion were borderline (BB) leprosy; (B) M. Leprae deoxyribose – nucleic acid (DNA) was detected from a skin

sample by polymerase chain reaction (PCR).

The Unique Characteristic Skin Lesions of Borderline Leprosy with Severe Reversal Reaction: The Uncommon Case

369

the period of time to observe the amendment of his

condition.

Adding up to the multi drug therapy (MDT) that

have been took by him for about 6 months, we added

methylprednisolone (32 mg/day) for a week. The

original regiment dose of MDT were rifampicin (600

mg/month), clofazimine (300 mg/month and 50

mg/day), and dapsone (100 mg/day). After that, we

found some improvement on the skin lesion,

The

redness macules still persist but thinner than before. So

we tappered off the dose of methylprednisolone

every 4-5 days to 4 mg/day. There was clinical

improvement of reaction after 2 weeks of oral

methylprednisolone along with MDT treatment (Fig.

1 E-H).

3 DISCUSSION

Leprosy is a chronic granulomatous infection caused

by M. leprae. Based on the immunological response

of the host to M. leprae, leprosy is classified into 5

major types: TT (tuberculoid), BT (borderline

tuberculoid), BB (borderline), BL (borderline

lepromatous), and LL (lepromatous) according to the

Ridley – Jopling scale (Hattori et al., 2016)

Clinical features of leprosy is dependent upon

the equilibrium between bacillary multiplication and

the host cell-mediated immune response. This can

reflect its pathology. The severity of the disease may

be different from the presence of a not worth

mentioning hypopigmented anesthetic skin patch to

widespread damage to peripheral nerves and sign

and symptoms suggestive of systemic involvement.

Leprosy is exceptional infectious disease for the

width of spectrum of signs and symptoms that it

demonstrates. (Kumar and Kar, 2017).

Borderline leprosy is the immunologic

intermediate of the granulomatous spectrum and is

the most unstable area. It means that the patients can

be quickly up- or downgrade to a more stable

granulomatous bearing with or without a clinical

reaction. Characteristic skin changes are said to be

annular lesions with sharply marginated interior and

exterior margins, large plaques with islands of

clinically normal skin within the plaque, giving a

“Swiss cheese” appearance, or the classic dimorphic

lesion. Because of its instability, the BB lesion is

short lived and such patients are rarely seen (Lee et

al., 2008). The characteristic skin lesions of

borderline leprosy can be seen in our case. It shows

us the unique annular plaque that become generalize

to all over his body. It has sharp borders in both

interior and exterior margins, it is also accompanied

with normal skin within the plaque. From the

clinical manifestation, our case simply show us the

characteristic of the diagnosis of borderline leprosy.

Leprosy reactions are periodic episodes of acute

inflammation caused by immune responses to M.

leprae or its antigen overlaid on the chronic course

of leprosy. These episodes have been classified into

two types: reversal reaction (RR) and erythema

nodosum leprosum (ENL). These are also known as

type 1 and type 2 reactions respectively. RR occurs

in the borderline cases and is a reflection of

immunological instability. It is because of increasing

in the delayed cellular hypersensitivity (DTH) or

type IV hypersensitivity which is reflected by

increase in lymphocyte transformation response

(Kumar and Kar, 2017).

Reversal reactions most commonly occur in

borderline and lepromatous forms of leprosy.

Clinically, patient display abrupt inflammatory

changes of the skin, nerves, or even both. Existing

skin lesions become erythematous and edematous

and may display ulcerative changes. Accompanying

edema is common, whereas systemic symptoms are

unusual (Kamath et al., 2014).

Reversal leprosy reaction result from the

activation of cell immunity, expressed clinically by

exacerbation of skin and pperipheral nerve

inflammation. It leads to sensory and motor

alterations. Inappropriately, the activation of

macrophages with the resulting obliteration of

bacteria that can cause irreversible nerve damage

and aggravating sensory and motor alterations.

There is predominance of the pattern of Th-1 (IL-1β,

TNF, IL-2, IFN-γ) in reversal reaction lesions. It is

more dominant over the pattern of Th-2 (IL-4, IL-5,

and IL-10), which predominates in multibacillary

leprosy (Nery et al., 2013).

The high level of TNF-α, soluble IL-2 receptor

and adhesion molecules indicate the concentration of

local inflammation. Increasing of the expression of

TNF-α mRNA in peripheral nerves and skin of

patients with the borderline form, was observed in

type 1 reactions. It seems that reversal reactions can

be facilitated through Th1 lymphocytes, and cells of

reactional lesions express the pro-inflammatory

cytokines interferon-gamma (IFN-γ), interleukin 12

(IL-12), and oxygen free radicals (Nery et al., 2013).

According to Nery et al. (2013) reversal reaction

episodes occur mainly during the first six months of

polychemotherapy. This reaction can occur at any

time but most frequently appears after starting

multiple drug therapy. This reaction may be resolved

spontaneously first, but worsen gradually. The

patient suffered from the leprosy lesions that became

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

370



more thick and pain in palpation. He got tenderness

on ulnar nerve as the symptom of neuritis.

Fortunately, we did not find any deformity yet.

Treatment of reversal reaction intends to supress

the cellular immune response during the reaction.

Early diagnosis and the initiation of the anti-

inflammatory therapeutic are fundamental in order

to avoid possible nerve damage. The identification

of risk factors is advantageous since it leads to a

more attentive monitoring of patients (Nery at al.,

2013). Athough, the exact events that trigger

reversal reaction are unknown. Risk factors for this

reaction include increasing age and the postpartum

period (Kamath et al., 2014). Nery at al. (2013) said

that the risk of reversal reaction was increasing due

to several factors, such as vaccination,

chemotherapy and puerperium. It can be happened

since there are factors such as improvement in cell

immunity among others, and this condition could be

happened right after pregnancy, intercurrent

infections, stress, trauma, and use of contraceptives.

Management of reversal reaction includes giving

antileprosy treatment. Multidrug therapy has to be

started or continued, if already started. This is

important since this is required for continuous

killing the M. leprae to reduce the

bacterial/antigenic load in the skin and nerves

(Kumar and Kar, 2017).

World Health Organization (WHO) recommends

corticosteroid as the drug of choice for reversal

reaction. It is because of its anti-inflammatory

effects (Andrade et al., 2015). The exact mechanism

of corticosteroid in reversal reaction has been

discussed in several studies.

Corticosteroids encourage reduction in vascular

permeability and vasodilatation through inhibition of

mediators, such as metabolites from arachidonic acid

(prostaglandins) and inhibition of the discharge of

platelet-activating factor (PAF), vasoactive amines,

neuropeptides, interleukin-1 (IL-1), tumor ecrosis

factor (TNF), and nitric oxyde. Glucocorticoid also

induce inhibition of the phagocytic capacity and

production of oxygen free radicals (burst cell) and

reduction in the number of eosinophils circulating in

peripheral blood that causes rough granulation in

polymorphonuclear neutrophils. It has a role in

inhibition of tissue migration of monocyte and

lymphocytes, with an increase in endothelial

adhesion of lymphocytes. Not only that, but it also

inhibit the vascular permeability as well as cellular

migration and activation (Nery et al., 2013).

High dose prednisone (1 mg/kg/day) provides

rapid symptomatic relief and helps reverse nerve

function impairment. The regimen must be

personalized individually based on whether nerve

tenderness and motor or sensory deficits are present.

Symptoms should be reconsidered every 2 weeks. If

nerve function improves, the dose can be decreased

by 2.5 to 5 mg; if there is no improvement or

worsening of nerve function, the dose should be

increased. Treatment may last up to 6 months or

even years for those with neuritis (Kamath et al.,

2014).

Initial dose of 40 mg prednisone was adequate to

control most of reversal reaction. The patients with

neural involvement may be need higher doses,

corresponding to 1 mg/kg/day (60 mg) and

sometimes even higher (2 mg/kg/day). The

prednisone dose should be reduced following

evidence of clinical improvement and upon reaching

the dose 20 mg/day. It should be maintained for a

long period of time until there is clinical regression

and complete recovery of neural functions (Nery et

al., 2013).

The standard dose of prednisolone schedule at

referral center uses starting dose 1 mg/kg body

weight/day to be continued until improvement of

skin lesions is visible or nerve tenderness and pain

diminishes. Then the dose should be decreased by 5

mg every 1-2 weeks. The crucial maintenance dose

should be around 15-20 mg for several weeks or

months. In the follow-up period, the dose should be

decreased by 5 mg every 2-4 months. Graded

sensory testing with monofilaments and voluntary

muscle testing can guide the tapering of

prednisolone. The duration should be long enough to

cover the period during which antigen load is able to

induce the CMI response. BT leprosy has to be 4-9

months, BB leprosy in 6-12 months, and BL leprosy

in 6-24 months (Kumar and Kar, 2017).

In acute phase the inflamed nerves must be

maintained in resting position. Appropriate splinting

and padding gives relief. When the acute phase is

over, passive and active exercises should be

initiated. Additional nonsteroidal anti-inflammatory

drugs (NSAIDs) may be required for relieveng pain

(Kumar and Kar, 2017).

In our case, we continued to give the multidrug

therapy (MDT) that have been took by him for about

6 months. We added methylprednisolone (32

mg/day) for a week. The original regiment dose of

MDT were rifampicin (600 mg/month), clofazimine

(300 mg/month and 50 mg/day), and dapsone (100

mg/day). But we did not continue to give

clofazimine treatment to the patient because of its

melanogenic side effect. After that, we found some

improvement on the skin lesion, so we tappered off

the dose of methylprednisolone every 4-5 days to 4

The Unique Characteristic Skin Lesions of Borderline Leprosy with Severe Reversal Reaction: The Uncommon Case

371



mg/day. There was clinical improvement of reaction

after 2 weeks of oral methylprednisolone along with

MDT treatment.

4 CONCLUSION

Leprosy is a chronic granulomatous progresssive

infectious disease caused by Mycobacterium leprae.

Borderline leprosy is the immunologic intermediate

of the granulomatous spectrum and is the most

unstable area. Characteristic skin changes are said to

be annular lesions with sharply marginated interior

and exterior margins, large plaques with islands of

clinically normal skin within the plaque, or the

classic dimorphic lesion. It was complicated by

potential intermittent hypersensitivity reactions or

lepra reactions. Leprosy reaction are considered as

acute or subacute episode, distinguished by

cutaneous and systemic involvement. These

episodes have been classified into two types:

reversal reaction (RR) or type 1 reaction and

erythema nodosum leprosum (ENL) or type 2

reaction. RR occurs in the borderline cases and is a

reflection of immunological instability. Management

of reversal reaction includes giving or continuing

antileprosy treatment, good rest, splinting or

padding, and analgetics. If it is accompanied by

neuritis or severe reaction we can treat the patient

with corticosteroids. If it is left untreated, surgical

decompression of nerve that is inflammed may be

useful for treating reversal reaction.

ACKNOWLEDGEMENT

The authors would like to express their genuine

thanks to the Dermatovenereology Ward and

Outpatient’s Clinic of Dr. Soetomo General Hospital

Surabaya and patient who participated in this study.

REFERENCES

Andrade PR., Pinheiro, RO., Sales, AM., Illarramendi, X.,

Barbosa, MGM., Moraes, MO., Jardim, MR., Nery,

JAC., Sampaio, EP., Sarno, EN., 2015. Tyoe 1

reaction in leprosy: a model for a better understanding

of tissue immunity under an immunopathological

condition. Expert Rev. Clin. Immunol. 11 (3): 391-407.

Hattori, M., Motegi, S., Amano, H., Ishii, N., Ishikawa,

O., 2016. Borderline lepromatous leprosy: cutaneous

manifestation and type 1 reversal reaction. Acta Derm

Venereol. 96: 422-3.

Kamath, S., Vaccaro, SA., Rea, TH., Ochoa, MT., 2014.

Recognizing and managing the immunologic reaction

in leprosy. J Am Acad Dermatol. 34: 1-9.

Kumar, B., Kar, HK., 2017. IAL Textbook of Leprosy, The

health sciences publisher. London, 2

edition.

Lee, DJ., Rea, TH., Modlin, RL. Leprosy in Goldsmith,

LA., Katz, SI., Gilchrest, BA., Paller, AS., Leffell,

DJ., Wolff, K., 2008. Fitzpatrick’s dermatology in

general medicine. Mc Graw Hill. London, 8th edition.

Nery, JAC., Filho, FB., Quintanilha, J., Machado, AM.,

Oliviera, SSC., Sales, AM., 2013. Understanding the

type 1 reacional state for early diagnosis and

treatment: a way to avoid disability in leprosy. An

Bras Dermatol. 88 (5): 787-92.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

372