DOI: 10.1111/jdv.

15569 JEADV

POSITION STATEMENT

Position statement: LEPROSY: Diagnosis, treatment and

follow-up
W. Alemu Belachew,1 B. Naafs1,2,3,4,*
1
Department of Dermatovenereology, Ayder Referral Hospital Mekelle University, Mekelle, Tigray, Ethiopia
2
Regional Dermatology Training Centre (RDTC), Moshi, Tanzania
3
Instituto Lauro de Souza Lima (ILSL), Bauru, SP, Brazil
4
Foundation Global Dermatology, Munnekeburen, the Netherlands
*Correspondence: B. Naafs. E-mails: benaafs@dds.nl; benaafs@hotmail.com

Abstract
Background Leprosy or Hansen’s disease is a chronic infection caused by Mycobacterium leprae (M. leprae) or
Mycobacterium lepromatosis (M. lepromatosis). In Europe, most of the leprosy cases are imported. However, occasion-
ally a case is diagnosed in one of the old endemic foci. Leprosy is often not suspected because it is no longer empha-
sized in the medical curricula. Attention shifted from leprosy to tuberculosis and human immunodeficiency virus
infections in the late 20th century, whereby the WHO leprosy programme was toned down in the conviction that leprosy
was all but eliminated. The result of unawareness is a harmful doctor’s delay.
Material and methods This paper focusses on clinical diagnosis, complications and treatment based on literature
and experience.
Results It mentions the value of laboratory tests in classification, follow-up and detection of relapses. It discusses the
etiopathology.
Conclusion This is a position statement.
Received: 4 August 2018; Accepted: 27 February 2019

Conflicts of interest
None declared.

Funding sources
None declared.

Introduction differently as compared with the immigration in the recent past.

Leprosy or Hansen’s disease is a chronic infection caused by
Mycobacterium leprae (M. leprae) or Mycobacterium lepromatosis
(M. lepromatosis). In Europe, most of the leprosy cases are
imported. However, occasionally a case is diagnosed in one of
the old endemic foci.1 Leprosy is often not suspected because it
is no longer emphasized in the medical curricula.2 Attention
shifted from leprosy to tuberculosis (TB) and human immunod-
eficiency virus (HIV) infections in the late twentieth century,
whereby the WHO leprosy programme was toned down in the
conviction that leprosy was all but eliminated.3
In 2005, the WHO reported that leprosy was eliminated as a
world public health problem. Unfortunately, this is not the case.4
To date, the incidence remains stable worldwide at around
250 000 new patients annually, whereby the prevalence has also
stopped decreasing. However, the disease may become more
prevalent in Europe with the increasing migration from develop-
ing countries. Leprosy may start spreading because many of the
immigrants at present live under poor and crowded conditions,
Patients are now diagnosed everywhere in the Western world,
unfortunately often after long doctors’ delay and are thus handi-
capped for life. Very little attention is paid to Leprosy in the
medical curriculum, whereby even dermatologists, neurologists
and rheumatologist, who may see patients in the second and
third line are generally poorly trained in leprosy. Non-awareness
is one of the main reasons for missing the diagnosis.5 This paper
may help to increase the awareness of physicians on leprosy in
Europe.
Diagnosis
Leprosy is primarily a disease of peripheral nerves, skin and
mucosa particularly the upper respiratory tract. Skin lesions are
usually the first sign noticed and thus is one of the reasons that
it is considered to be a dermatological disease. Left untreated,
leprosy may progress causing permanent damage to the skin, the
nerves, the limbs and the eyes. Tissue damage may occur because
of M. leprae infiltration,6 but most of the damage is secondary to

JEADV 2019 © 2019 European Academy of Dermatology and Venereology

2 Alemu Belachew and Naafs

Figure 1 Deformed hands due to nerve damage and secondary Figure 2 Sensory testing.
infection.

immunological reactions.7 Secondary infections because of

trauma after sensory loss may result in tissue loss as bone and
cartilage are absorbed causing fingers, toes and nose to become
shortened and deformed (Fig. 1).
Patients may complain of loss of sensation in the skin lesions
or the hands or the feet. They may have aches and pains in the
face or the limbs or mention a numb, sleepy, or dead feeling or
sensations like ‘ants running under their skin’ in the affected
areas. Skin lesions are usually hypopigmented or erythematous
macules or papules and nodules and plaques, which are skin
coloured or slightly red. Clinically, leprosy is diagnosed when
the patient shows two out of the three cardinal signs. The WHO
considers one cardinal sign enough in endemic countries conve-
niently forgetting the nerve enlargement.8
The over 100 years known cardinal signs of leprosy are:
1 Loss of sensation in a skin lesion
2 Enlarged peripheral nerve
3 Positive skin smears
Up to now, there are no laboratory tests to diagnose leprosy.
The available tests are only helpful in the classification, the fol-
low-up and the detection of relapse.
Loss of sensation is tested with a wisp of cotton wool. The
lesions are tested by touch not brushed. With closed eyes, the Figure 3 (a) Nerves to be felt and appreciated. (courtesy: drs R.
patient points to where he or she is touched. To make sure, the Hastings and DVA Opromolla). (b) Feeling of radiocutaneus nerve.
area outside the lesions is tested as well (Fig. 2). Alternatively, it
is possible to test for warm and cold sensation or test for dimin-
ished sweating with for instance an iodide test. One can also use It is important to mention that the enlarged fasciculi in the nerve
a histamine test on the affected area and compare it with the may present a diagnostic pattern.9 It may be helpful to look for
same test on the surrounding skin. This is an axonal reflex. All loss of sensation or loss of strength in the distribution of the
these tests test damage to the dermal nerves. Leprosy in the skin investigated nerve too, realizing that these are not always detect-
is also primarily a neural disease. able. Nerve conduction studies may then contribute.10
Enlarged nerves may be cutaneous nerves, subcutaneous Smears to detect acid-fast bacilli are taken from the earlobes
nerves in the vicinity of the skin patches or nerve trunks. At least and other cooler areas and from the rim of the lesion in pau-
the posterior auricular nerves, the ulnar, the radiocutaneous, the cibacillary (PB) and from the centre of the lesions in multibacil-
median, the lateral popliteal and the posterior tibial nerves lary (MB) patients. The smear is taken while squeezing the skin,
should be palpated. Nerve thickness, consistency and tenderness to numb and to diminish the bleeding, while incising into the
should be evaluated (Fig. 3a,b). Ultrasound is a good alternative. dermis. Only tissue fluid is required, blood dilutes the number

JEADV 2019 © 2019 European Academy of Dermatology and Venereology

Leprosy: diagnosis and treatment 3

of bacilli in the smear. The bacilli are counted and graded
according to a logarithmic scale (BI, bacillary index) and the
percentage of solid bacteria considered living (viable) bacilli is
estimated (MI, morphological index).11 It is important to decol-
orize shortly with 1% hydrochloric acid in isopropyl alcohol (as
in Fite stain), as opposed to the 3% solution used for TB,
because M. leprae is less acid-fast than M. tuberculosis. Using the
common Ziehl–Neelsen stain (3% hydrochloric acid) may ren-
der the smear negative.12 Another way to detect bacilli is by PCR
or NASBA, which like the smear is often negative in PB patients.
However, smears, immunological and molecular techniques can
be very useful in the diagnosis of MB leprosy, in the follow-up
and in detection of relapses.13,14
Other laboratory investigations are also of some help in the
diagnosis of leprosy, but none will be diagnostic over the whole
spectrum. The antibody titre against phenolic glycolipid 1(PGL-
1), a cell wall species-specific glycolipid, is useful in MB leprosy.
However, this test may be positive in contacts and negative in
PB leprosy. It helps to classify leprosy into PB and MB and it
can be used to follow the effect of treatment in MB patients and
to detect relapses.15 The value of the recently introduced syn-
thetic ‘LID-1’ seems to add little. Lymphocyte transformation
or Interleukin (IL)-c or IL- 2 release essays against different
antigenic determinants have been a disappointment up to now,
at least for diagnostic purposes. The lepromin test (Mitsuda),
an old test, is positive in PB leprosy and negative in MB leprosy.
However, it can be positive and negative in healthy people.
Thus, it helps only with the classification.16 Since it is made
from biological material, theoretically it may sensitize and
therefore, many oppose its use. Histopathology can be very
helpful in diagnosis, classification and detection of reactions, as
can immunopathology, but the latter is still experimental.
Important is to take the biopsies from the right place, from the
rim of the lesion in tuberculoid leprosy and centre of the lesion
in lepromatous leprosy and do the proper M. leprae staining
(Fite-Faraco). Pure neural leprosy can be diagnosed by nerve
biopsy taken from a small cutaneous or subcutaneous nerve.17
From a larger nerve, a fine-needle aspiration can be done for
cytology and bacteriology with PCR.18,19 A problem is that even
within one biopsy, the histopathology of one site may differ
from the other.
Infection and Classification
Leprosy is highly infectious,20 but the attack rate is low.16 The
major reason for this low attack rate is that most people are
genetically unable to provide the mycobacteria with what they
need to survive, because they lack the type of genes the bac-
terium needs to re-programme the cell in order to survive and

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INDETERMINATE

THE SPECTRUM OF LEPROSY

(Ridley - Jopling Classification)

Figure 4 Leprosy spectrum according Ridley and Jopling. (courtesy: dr DL Leiker.).

JEADV 2019 © 2019 European Academy of Dermatology and Venereology

4 Alemu Belachew and Naafs

multiply.16,21 The cell-mediated immunity (CMI) is important

in the patients who develop leprosy. In order to predict compli-
cations and to stratify according to CMI, the Ridley–Jopling
scale22 (Fig. 4) is important, with on one side of the spectrum
polar tuberculoid (TT) (Fig. 5) with a single well-described
lesion or an enlarged nerve and with no bacilli detectible and a
high CMI against M. leprae antigenic determinants, and on the
other side, polar lepromatous (LL) leprosy with nodules and/or
plaques (Fig. 6a,b) with symmetrically enlarged nerves or even Figure 7 BT leprosy. (a) erythematous macule with loss of feeling
for hot and cold. (Courtesy: taken at Hospital das Clinicas Sao
only an infiltrated skin (Lepra bonita) with many bacilli and Paulo) (b) hypopigmented near anaesthetic macule with an erythe-
with an absence of CMI against M. leprae antigenic determi- matous border and streaming.
nants. In-between is the borderline group, which comprises the
majority of the patients: borderline tuberculoid (BT) (Fig. 7a,b)
with predominantly tuberculoid features and borderline lepro-
matous (BL) (Fig. 8a,b) with predominantly lepromatous fea-
tures. Between these two is a small group of mid-borderline
(BB) (Fig. 9) patients with typical punched out(centrally non-
involved skin), or dome-shaped lesions.22 Sometimes it is not
possible to classify leprosy and the lesions in such cases are then
clinically and histologically indeterminate (I) (fig 10). Indeter-
minate leprosy is either an early stage of the disease, which may

Figure 8 BL leprosy (a) hypopigmented, slightly coppery macule.

( Courtesy: taken at RDTC) (b) Nodules in a child, particular acral.
This is typical for a child. (courtesy: taken at ALERT Ethiopia).

Figure 5 TT leprosy.

Figure 6 LL leprosy (a) nodules (courtesy: dr F Dassoni) (b) ery-

thematous plaques (courtesy: taken at RDTC). Figure 9 BB leprosy (courtesy: dr DL leiker).

JEADV 2019 © 2019 European Academy of Dermatology and Venereology

Leprosy: diagnosis and treatment 5

clofazimine.29 WHO-multidrug therapy (MDT) is the current

standard treatment and continues to be widely administered.

Multidrug therapy (MDT)

Paucibacillary leprosy Old, but still used by most physicians:

Figure 10 Indeterminate(I) leprosy.
resolve by itself (mostly) or continue into one of the types
described in the Ridley–Jopling classification22 depending on the
development of the CMI. Another difficult to classify group is
pure neural leprosy: leprosy without skin signs, which frequency
may range from 1 to 10%, depending on the area and aware-
ness.23 The WHO classified leprosy into just two groups for
practical purposes in the field (just count the number of lesions):
five or less classified as paucibacillary leprosy (PB leprosy) and
more than five as multibacillary leprosy (MB leprosy).24
Although this is a very practical approach, several reports
showed that by just counting up to 30% of the patients might be
wrongly classified as PB and therefore undertreated.25
Treatment
The first known treatment that had some effect was chaul-
moogra oil, mentioned already in the Sushruta Samhita 600 BC.
The effect was minimal in different preparations used, but some
success was obtained in PB leprosy.26 The first effective antibi-
otic, intravenous sulfone – promin appeared in 1943.27 Soon
afterwards, a new oral derivate called dapsone (diamin-
odiphenylsulfone, DDS) became the standard treatment. Upon
the appearance of secondary DDS resistance in the 1970s
together with the ready availability of rifampicin (RMP), the use
of combined regimens was recommended.28 However, it was not
until 1982 that the WHO’s Chemotherapy Study Group recom-
mended the combined use of RMP and DDS with or without
600 mg rifampicin once monthly for 6 months under supervi-
sion and daily 100 mg dapsone, unsupervised. The dose is for a
60 kg patient. In order to be allowed to discontinue the treatment
6 supervised monthly doses should be given in 9 months
(Table 1).30 Recently, the advice is to add Lamprene to the 6-
month treatment, to prevent undertreatment and make treatment
more uniform between the leprosy patients and classification less
necessary. Among clinicians, this is still under discussion.
Multibacillary leprosy 600 mg rifampicin and 300 mg Lam-
prene (clofazimine) once monthly under supervision and
100 mg dapsone and 50 mg Lamprene daily, unsupervised. The
official WHO advise is still that twelve supervised monthly (see
above) doses should be given within 18 months. Many physi-
cians do not follow this recommendation, they advise 12 super-
vised monthly doses in 18 months only for low-BI patients and
24 supervised monthly doses in 36 months for patients with a BI
of 4 or more.24,31 The doses are for 60 kg patients.
At present, the WHO even considers Uniform MDT (U-
MDT)30 a 6-month treatment for all classifications with the
three above-mentioned drugs. No classification is needed any-
more. This recommendation is questioned and strongly opposed
by clinicians.32,33
The old MDT regimens have proved sturdy. Hardly any
relapses (4%) have been seen, but in multibacillary leprosy the
follow-up generally is too short. One is advised to be careful with
dapsone in Nordic Caucasians who easily develop haemolysis
independent of their G6PD status. Fifty milligrams of dapsone is
effective in the majority of patients and causes much less anae-
mia. It is probably genetically determined. Caution: Nepalese
and Chinese patients have a higher risk of developing dapsone
hypersensitivity syndrome.34 As an alternative for daily

Table 1 Treatment of leprosy as advised by the WHO

Age group Drug Dosage and frequency Duration
MB PB
Adult Rifampicin 600 mg once a month 12 months 6 months
Clofazimine 300 mg once a month and 50 mg daily
Dapsone 100 mg daily
Children (10–14 years) Rifampicin 450 mg once a month 12 months 6 months
Clofazimine 150 mg once a month and 50 mg daily
Dapsone 50 mg daily
Children (<10 years old or <40 kg) Rifampicin 10 mg/kg once a month 12 months 6 months
Clofazimine 6 mg/kg once a month and 1 mg/kg daily
Dapsone 2 mg/kg daily

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6 Alemu Belachew and Naafs

Table 2 Treatment of resistant leprosy according WHO

Resistance type Drug
First 6 months Next 18 months (daily)
(daily)
Rifampicin Levofloxacin 500 mg + Levofloxacin 500 mg OR
resistance minocycline 100 mg + minocycline 100 mg +
clofazimine 50 mg clofazimine 50 mg
Levofloxacin 500 mg + Levofloxacin 500 mg +
minocycline 500 mg + clofazimine 50 mg
clofazimine 50 mg
Rifampicin and Clarithromycin 500 mg + Clarithromycin 500 mg OR
ofloxacin minocycline 100 mg + minocycline 100 mg +
resistance clofazimine 50 mg clofazimine 50 mg

treatment and as once-only treatment for single-lesion leprosy, a

combination of RMP, ofloxacin and minocycline (ROM) was
advocated. It was also given once per month for tuberculoid and Figure 11 Type I leprosy reaction (a) Erythematous swollen
enlarging plaques. ( Coutesy: dr Kelvin Mponda taken at RDTC).
lepromatous leprosy, but it showed to be less effective than
WHO-MDT.35

Reoccurrence After treatment the disease may come back

either due to undertreatment, resistance, persisters or new infec-
tions. In general, the reoccurrence is sensitive to the original
MDT treatment. But resistance to dapsone, rifampicin and
ofloxacin has been proven. A PCR test is available. Resistance
against clofazimine is never convincingly proven. The WHO
advises for the use of resistant M. leprae, depending on the resis-
tance, MDT with 3 drugs; either ofloxacin, clarithromycin,
minocycline and clofazimine (Table 2).30

Reactions
Reactions belong to the normal course of a leprosy infection. Figure 12 Type I reaction. Swollen tender cutaneous nerves.
Treatment can prevent or precipitate them. There are three types
of reactions: type I leprosy reaction (T1R) also called reversal
reaction (RR); type II leprosy reaction (T2R), also called ery-
thema nodosum leprosum (ENL); and Lucio’s phenomenon, a
reaction occurring specifically in multibacillary patients from
Mexico.
T1R is a CMI reaction, a type IV Gell and Coombs reaction
against M. leprae antigenic determinants.36,37 Clinically, there is
increased inflammation of lesions, which become more visible
and erythematous are raised and/or enlarged (Fig. 11), and even
may ulcerate. Nerves may be inflamed, enlarged and tender
causing reduced strength, sensitivity and sweating (Fig. 12).
There may be acro-oedema. Even the joints and the liver may be
involved. Figure 13 Type II reaction. Red erythematous tender nodule
beside the eye. (courtesy: taken at RDTC).
T2R seems to be an antigen-antibody immune complex reac-
tion in the tissues, particularly in the skin and the nerves.38
However, the CMI is also involved,39 particularly T-cell regula-
tion.40 The skin shows the characteristic red painful, tender nod- tissues may be inflamed. There may be a.o. neuritis, lymphadeni-
ules (Fig. 13) which may ulcerate, be erythema multiforme-like tis, orchitis, iridocyclitis, arthritis and hepatitis. Generally, there
or even bullous (Fig. 14). It is a multi-organ disease; all types of is fever and leucocytosis, sometimes lymphocytes in the urine.

JEADV 2019 © 2019 European Academy of Dermatology and Venereology

Leprosy: diagnosis and treatment
Figure 14 Type II reaction. Bullous leasions.(courtesy LUMC)
The treatment of T1R primarily consists of corticosteroids,
30–40 mg prednisone starting dose, tapering down guided by
for instance graded sensory testing41 (Semmes Weinstein
mono-filaments) or voluntary muscle testing42 over a 4–
12 months period during which the dose needs to be at least
15–20 mg to be effective. Adequate immune suppression
(>0.25 mg/kg) should be given at least for 3 months for BT
leprosy to 6–12 months or even longer for BL leprosy.43 In
some cases, dapsone helps to prevent a reaction.44 The WHO
advises only 3 months steroids but this is not accepted by
most clinicians.
T2R treatment is difficult. The reaction is episodic, 95% of
ENL episodes last less than 1 month.45 Mild reactions can be
treated with NSAIDs; arthritis with anti-malarials. The WHO
advises for more severe reactions:46 ‘A standard course of pred-
nisolone in dosage per day not exceeding 1 mg per Kg body
weight. Total duration 12 weeks’. However, in our experience
severe reactions need high dose steroids (60–120 mg) for a short
period, diminishing to zero in a month or less. A new attack
should be treated in the same way.47 This way of treatment is
not yet generally accepted. One may try to prevent a new reac-
tion using steroids, but since it is an immune complex-related
reaction, this is not very effective and many patients are now
steroid dependant and some even died.48 Patients may suffer
from severe steroid side effects. However, clofazimine may pre-
vent a T2R or can be used for treatment.49 Thalidomide as treat-
ment is superior above all and can be used as prophylaxis.
However, even thalidomide may not be effective in every T2R.
The combination of low-dose steroids with low-dose thalido-
mide is counter-productive.50 One of the problems using
thalidomide is the adverse effect causing sensory loss,51 which is
nearly impossible to delineate from leprosy damage. When
thalidomide is not available, prevention of new ENL episodes
can be tried using methotrexate (MTX)52,53 with or without
extra clofazimine.
When nerves continue to deteriorate despite proper medical
treatment, a nerve release operation needs to be considered.54,55
JEADV 2019
7
This can also be considered for nerves without a reaction that
remain tender after treatment.
The Lucio’s phenomenon presents as an infarction, with bizarre
shaped well demarcated superficial ulcerations with slough
(eschar) formation in the skin when a large number of bacilli
block the venous return in the small venules.56 This is only seen
in untreated diffuse lepromatous leprosy and may be triggered
by a sudden cold. The treatment is MDT; RMP is the crucial
drug.
The results of nerve damage, loss of sensation and muscle
strength are the sequelae or the stigmata of leprosy. These should
be countered with supplying special padded tools, utensils and
shoes. Sometimes in order to increase grip or to improve foot
movement, a tendon transfer may be considered, but always in
the presence of an experienced physiotherapist. The stigma
should be diminished by education. It is important to show that
correctly treated patients have the least problems.
Prevention
Despite many efforts to develop a universal active vaccine
involving DNA techniques, BCG vaccination remains the best
prophylactic in many areas. Protection ranges from less than
20% in some areas to up to 80% in others probably depend-
ing on the presence and the characteristics of environmental
microorganism.57 Treating of contacts with a single 600 mg
dose of rifampicin is recommended by the WHO and has
proven to be effective for a few years, and BCG vaccination
may extend this.58 A new proposal has been accepted by
WHO, a longer initial Rifampicin dose with drugs like moxi-
floxacin or clarithromycin.59 A promising drug under trial is
Bedaquiline, which however may be too toxic60 A problem is
to trace and identify the contacts that need protection
because the majority of the contacts (80%) will not develop
leprosy due to genetic protection. M. leprae may not be able
to re-programme the host cell as was shown for other bacte-
rial and viral infections;16 thus, these contacts may receive
unneeded treatment.
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