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Clinics in Dermatology (2015) 33, 2637

Clinical aspects of leprosy

Carolina Talhari, MD, PhD a,b , Sinsio Talhari, MD, PhD c ,
Gerson Oliveira Penna, MD, PhD d,

Teaching and Research Department, Fundao Alfredo da Matta, Manaus, Amazonas, Brazil
Amazon State University, Manaus, Amazonas, Brazil
Department of Dermatology, Universidade Nilton Lins, Manaus, Amazonas, Brazil
Tropical Medicine Centre, University of Braslia, Asa Norte, Brazil

Abstract Leprosy is a chronic, infectious disease caused by Mycobacterium leprae. It mainly affects the
peripheral nervous system, skin, and certain other tissues such as the reticulo-endothelial system, bones
and joints, mucous membranes, eyes, testes, muscles, and adrenals. Leprosy clinical presentation varies
from few to widespread lesions. In most patients, early leprosy presents as macular and hypopigmented
lesions. This initial clinical presentation is known as indeterminate leprosy and occurs in individuals
who have not developed cell-mediated immunity against M leprae yet. The number of lesions depends
on the genetically determined cellular immunity of the patient. Individuals presenting a vigorous cellular
immune response and limited humoral immune responses to M leprae, usually present few skin lesions.
Without treatment, those patients tend to evolve into the polar tuberculoid or borderline tuberculoid form of
leprosy. Due to the inability to mount an effective cellular-mediated response to M leprae and the consequent
hematogenous spread of the bacilli, some patients may present with numerous and symmetrically distributed
hypochromic lesions. Without treatment these patients evolve to a nonresistant form of leprosy,
polar lepromatous.
2015 Elsevier Inc. All rights reserved.

Clinical leprosy
Leprosy is a chronic, infectious disease caused by
Mycobacterium leprae. It mainly affects the peripheral
nervous system, skin, and certain other tissues such as the
reticulo-endothelial system, bones and joints, mucous
membranes, eyes, testes, muscles, and adrenals. The clinical
presentation of leprosy clinical presentation varies from few
to widespread lesions.1 Similarly, histopathology of skin
lesions varies from compact granulomas to diffuse infiltration of dermis, which largely depend upon the immune status
of the patient and may not be in agreement with the clinical
diagnosis.24 Leprosy classification has been a matter of
Corresponding author.
E-mail address: gpenna@gpenna.net (G.O. Penna).
0738-081X/ 2015 Elsevier Inc. All rights reserved.

debate for many years.4 The first classifications were based

only upon clinical parameters, generating confusion and
controversies. In 1953, during the Madrid congress, a
classification based on four main disease groups was
proposed: lepromatous leprosy, tuberculoid leprosy, indeterminate leprosy, and borderline or dimorphous leprosy.5,6
In 1962 2 and 1966 3, Ridley and Jopling proposed a new
classification based not only on the clinical features, but also
on histopathology, bacterial load and the degree of cellmediated immune response (CMI) against M leprae, which is
evaluated by the result of Mitsuda's intradermal test. Based on
these immunopathological criteria, patients are divided into a
five-group spectrum that extends from tuberculoid leprosy
(TT) with heightened CMI (hyperegic pole) through borderline
tuberculoid (BT), borderline-borderline (BB), borderline
lepromatous (BL), to the poorly resistant (anergic) lepromatous

Clinical aspects of leprosy

type (LL) characterized by increased humoral immunity.
Indeterminate (I) leprosy does not fall into this spectrum
because there is a lack of correlation between the clinical and
histopathological features. This clinical form represents an
early stage of the disease in which the degree of CMI is still
not clear.1
In 1982, the World Health Organization (WHO) advocated the use of two different regimens of multidrug therapy
for the treatment of leprosy.7 Patients are classified as
paucibacillary if the bacterial index (BI) is less than 2 + or as
multibacillary if the BI is equal or higher than 2 +.79 BI is a
parameter directly related to bacterial load, being the
estimated number of all bacteria, regardless of their shape,
present in a smear. The results are expressed on a logarithmic
scale: 1 + (at least 1 bacillus in every 100 fields), 2 + (at least
1 bacillus in every 10 fields), 3 + (at least 1 bacillus in every
field), 3 + (at least 1 bacillus in every field), 4 + (at least 10
bacillus in every field), 5 + (at least 100 bacillus in every
field), and 6 + (at least 1000 bacillus in every field).7,8
In this contribution, the authors have decided to describe
leprosy clinical manifestations based on Ridley and Jopling
classification. One must remember that the first signs that
lead leprosy patients to seek for medical attention are most
often dermatological. Careful examination of skin is a key
element in leprosy diagnosis.

I leprosy
In most patients, early leprosy presents as macular and
hypopigmented lesions. This initial clinical presentation
is known as I leprosy and occurs in individuals who have
not developed cell-mediated immunity against M leprae
yet. 1,10 The single (Figure 1) or multiple macules have no
more than 34 cm wide, present with a smooth surface and
are not scaling or pruriginous (Figure 2). The lesions may
also be red in light-skinned patients or coppery in darkskinned patients. There is normal sweating and body hairs
are present. 1114
A very important characteristic of leprosy lesions is the
impaired sensation (anesthesia). On I leprosy lesions the
patient commonly presents with loss of thermal sensation,
not being able to distinguish between a cold and a hot tub
of water. Hyperalgesia often precede the detection of skin
The number of lesions depends on the genetically
determined cellular immunity of the patient. Individuals
presenting a vigorous cellular immune response and limited
humoral immune responses to M leprae, usually present few
skin lesions.12 Without treatment, those patients tend to
evolve into the polar T or BT form of leprosy. Individuals
within the tuberculoid pole may present a tendency towards
spontaneous healing. Patients presenting with numerous or
countless number of hypochromic lesions, without treatment,
tend to evolve into BB, BL, or LL forms.13,14


Fig. 1 Indeterminate leprosy. A single, irregular and hypochromic

patch on the left elbow.

The diagnosis of indeterminate patients may be difficult.

Besides sensory tests already mentioned, the histamine test is
a very useful diagnostic tool for light-skinned patients. It
consists in the application of one drop of histamine (dilution 1/1000) within and around the suspected hypochromic
lesion. After 12 minutes, a triphasic skin reaction known
as Triple Response of Lewis will occur: first a red line
develops at the site due to histamine release, then a flare
develops around the red line, and lastly a wheal is formed as
a result of local edema. This triple reaction is only observed
in the normal skin or hypochromic lesions caused by other
diseases; if the lesion is due to leprosy the response of the
skin to histamine will be incomplete once this local reflex
depends upon the integrity of sympathetic nerve fibers.12

Fig. 2 Indeterminate leprosy. An irregular, hypochromic patch

on the lower limb.


C. Talhari et al.

In patients presenting with indeterminate leprosy, bacilloscopy

(slit-skin smear and Ziehl-Nielsen staining) is negative.1315
The following diseases may mimic the hypopigmented
macule due to I leprosy 1,10,16,17:
1. Pityriasis alba. Characterized by the presence of a variable
number of hypochromic, round patches with undefined
edges on the trunk and upper limbs; in general, it presents
a rough surface.
2. Hypochromic variant of pityriasis versicolor. Initially it
may present as a small hypopigmented macule that
usually grows in size and tend to coalesce; superficial
desquamation is important to differentiate this superficial
mycosis from I leprosy (Figure 3).
3. Solar hypochromiant dermatosis. In the majority of cases,
this transient dermatosis is observed after intense tanning;
the lesions are irregular and may present with a rough
surface (Figure 4).
Achromic nevus, nevus anemicus, vitiligo, and postinflammatory hypopigmentation may also mimic I leprosy.
The erythematous leprosy macule must be distinguished
from the macules occurring in seborrhoeic dermatitis, which
is clinically characterized by the presence of squamous
lesions located mainly on the face (Figure 5) and trunk.
Fixed drug eruption, early-stage morphea, Lyme disease,
cutaneous mycosis, and from the herald patch of Gilberts
pityriasis rosea should also be distinguished from I leprosy.
Differential diagnosis of hyperchromic macule due to
indeterminate leprosy may include residual lesions of
postinflammatory hyperpigmentation, Kaposis sarcoma,
morphea, tinea nigra, hyperchromic form of pityriasis
versicolor, erythema dyscromicum perstans, and fixed drug

Fig. 3 Hypochromic variant of pityriasis versicolor. Superficial

desquamation is important to differentiate this superficial mycosis
from indeterminate leprosy.

Fig. 4 Solar hypochromiant dermatosis with irregular lesions and

rough surface.

Tuberculoid leprosy
Tuberculoid leprosy (TT) is characterized by the presence
of unique or few small-sized lesions showing well-defined
and elevated borders (papules and plaques) (Figure 6).18 The
elevated border indicates either central healing or peripheral
spread.13 Typical TT lesions have decreased sweating,
rarefied body hair, and are anesthetic: first thermal, then
tactile, and pain sensitivity is lost. There are patients with
tuberculoid leprosy that presents anesthetic areas without
changes in the skin color or peripheral trunk nerve
enlargement, with or without skin lesions.19 It is very
important to remember that lesions on the face may present
normal sensitivity, in this area the rich sensory innervations
compensates for the damaged nerves.1,11
In early cases of TT, macules may be observed; in lightskinned patients these lesions are erythematous or coppery in
dark-skinned individuals; it may also be homogeneously
hypopigmented. These macules show a dry surface and due
to anhidrosis are rough to the touch. Due to the intense
cellular-mediated immunity, papules can appear on the edges
of the macule (Figure 7).10,13

Fig. 5

Seborrhoeic dermatitis. Hypochromic lesion on the face.

Clinical aspects of leprosy


Fig. 6 Tuberculoid leprosy. Unique lesion showing well-defined

and elevated borders on the hand.

Fig. 8 Infantile nodular tuberculoid leprosy. A nodular lesion on

the face of a child.

A particular type of leprosy, usually characterized by the

presence of nodular lesions may be observed in children and is
known as infantile nodular tuberculoid leprosy (Figure 8).20 It
exclusively appears during infancy and affects children younger
than 5 years of age. It is considered the most benign of all forms
of the disease. In many instances this is a difficult diagnosis.
The epidemiology and the biopsy are very helpful.21
In all types of leprosy, except indeterminate, involvement
of peripheral trunk nerves such as ulnar, median, radial, and
common peroneal or posterior tibial may be severe and cause
disabilities 1. In TT leprosy, the possibility of peripheral
nerve enlargement is low and if so, it occurs near the lesions.
Neuritis pain may be the first symptom of leprosy.19
The slit-skin smear of T leprosy is negative.22
TT leprosy lesions may mimic the following diseases

hyperchromic, atrophic and scarring aspect; sensitivity

tests are preserved.
3. Annular granuloma. The lesions are characterized by the
presence of anular plaques very similar to T leprosy but
with normal sensitivity tests (Figure 10).
4. Secondary syphilis. The previous history of penial or
vulvar ulcerated lesion is important when differentiating
such lesions from T leprosy; however, lesions on the
cervix may not be acknowledge by most of the women;
anti-treponemal screening is mandatory.
5. Gilberts pityriasis rosea. This disease of viral etiology is
characterized by erythematous and round lesions presenting with collarette desquamation; these lesions evolve
rapidly, usually beginning with patch that heralds the
eruption, the so-called herald patch (Figure 11); the
lesions usually disappear in 1 to 2 months.

1. Tinea. As in T leprosy, there is a tendency to central

healing; the presence of pruritus, local excoriation and
superficial scars is important to differentiate such lesions
from T leprosy (Figure 9).
2. Cutaneous erythematous lupus. The lesions are localized
mainly on the face and other exposed areas of the body;
there is a tendency to spontaneous healing with residual

Seborrhoeic dermatitis, lobomycosis, chromomycosis, psoriasis, parapsoriasis, sarcoidosis, mycosis fungoides, morphea,
necrobiosis lipoidica, Kaposis sarcoma, cutaneous tuberculosis
and leishmaniasis are other diseases that may mimic T leprosy.

Borderline leprosy
According to the Ridley and Jopling classification, the
vast majority of patients fit in this group.2,3 Usually there is

Fig. 7 Tuberculoid leprosy. An unique macule showing papules

on the edges of the lesions.

Fig. 9 Tinea. A pruriginous plaque showing local excoriation on

the forehead; differential diagnosis of tuberculoid leprosy.


Fig. 10 Annular granuloma. Anular plaques on the upper limb

that are very similar to T leprosy but present with normal sensitivity.

multiple and severe peripheral nerve involvement and most

of disabled patients are within the borderline spectrum of
Instability is the predominant characteristic of borderline
group. Without treatment borderline patients may downgrade in the direction of lepromatous leprosy and after
sometime may present the typical clinical aspect of
lepromatous leprosy. During and after treatment patients
may upgrade. Borderline patients frequently present reversal
reactions when upgrading or downgrading and not necessarily
these changes are related with treatment or not. Reversal
reactions are characterized by worsening of skin lesions and
nerves. Without adequate treatment paralysis are frequently
observed during these reactions.23

C. Talhari et al.
Borderline tuberculoid leprosy (BT)
The skin lesions (up to 10 or 20 or more) are similar to
those observed in tuberculoid leprosy. Usually the lesions are
larger than those observed in TT. It is frequent to observe
satellite lesions near the larger lesions or finger-like which
extends from the edges of the plaques or macules (Figure 12)
into the normal skin, and the color varies from hypochromic
to reddish. Lesions may vary in size, shape and color in the
same patient. Reactions (type 1) are frequent and swollen/
ulceration of the cutaneous lesions may occur.1,10,11 Nerves
are severely involved during reactions in BT leprosy
(Figure 13).24 Nerve function may deteriorate rapidly, and
urgent treatment to prevent permanent deformity and
disability is necessary.
Some patients may present only anesthetic macules and
nerve enlargement. They are called maculoanesthetic
The bacilloscopy varies from negative to positive (2+).22
Borderline leprosy (BB) or mid-borderline leprosy
BB leprosy is characterized by the presence of infiltrated
plaques of variable sizes, with a central apparently spared skin
(usually it is hypochromic), well defined inner edge and vague
defined outer edges, invading the normal skin in some areas
(Figure 14).1 The combination of these lesions gives the
Swiss cheese like aspect (Figure 15). Macules, plaques,
papules, and nodules are usually found in combination with the
typical lesions. In BB leprosy there are disseminated reddish
coppery lesions, usually symmetrically distributed.10,11
BB leprosy is rare and considered the most unstable part
of the spectrum. It moves rapidly towards one of the polar
forms (TT or LL). Nerve involvement is variable in these
patients. It may be severe during the frequent type 1 reaction
or up/downgrading evolution.23
The bacilloscopy is usually strongly positive (2+ to 4+).22
Borderline lepromatous leprosy (BL)
As in other types of leprosy, BL starts as hypopigmented
macular lesions. In these patients, the lesions are disseminated,
symmetrically distributed. With time the macula increase in

Fig. 11 Gilberts pityriasis rosea. Erythematous and round lesions

presenting with collarette desquamation; in this image is possible to
note the herald patch, which is usually the larger lesion.

Fig. 12 Borderline tuberculoid leprosy. A hypochromic lesion

presenting with infiltrated and erythematous borders.

Clinical aspects of leprosy

Fig. 13 A reactional borderline tuberculoid leprosy presenting

with infiltrated and erythematous plaques on the face.

size, become erythematous and infiltrated. The lesion edges

are irregular and invade normal skin (Figure 16).23 Progressively, extensive areas become infiltrated (Figure 17). Plaquelike lesions, papules and nodules may appear simulating
lepromatous leprosy.11
Type 1 and 2 leprosy reactions are frequently observed in
these patients.24
Peripheral nerve enlargement is observed in most of the
patients (Figure 18). Nerves are less commonly tender than in
BT but during reactions severe nerve damage may occur.11
Bacilloscopy is strongly positive.22

Lepromatous leprosy (LL)

Due to the inability to mount an effective cellular-mediated
response to M leprae and the consequent hematogenous

Fig. 14 Borderline-borderline leprosy. The lesion shows a

central apparently spared skin with well-defined inner edge and
vague defined outer edges. This patient was treating the lesion as a
fungal infection.


Fig. 15 Borderline-borderline leprosy. Multiple lesions on the

trunk giving a Swiss cheese like aspect.

spread of the bacilli, some patients may present with numerous

and symmetrically distributed hypochromic lesions. Without
treatment these patients evolve to a nonresistant form
of leprosy - polar lepromatous (LL). This leprosy form may
also occur as a result of downgrading BB and BL without
There are two clinical subforms of lepromatous leprosy,
subpolar (LLs) and polar (LLp). LLs patients are not
completely anergic and after treatment become bacteriologically negative more rapidly when compared with LLp. Patients
presenting with the first clinical form can develop type 1
In LLs the macules, nodules and plaques have well-defined
borders. LLp occur in extremely anergic patients and are
characterized by the presence of diffuse infiltration of the skin
with indistinct edges.11 In such patients, a diffuse infiltration of
the hypochromic lesions and the apparently normal skin
slowly involves extensive areas or the entire body. Without
treatment, the skin becomes more and more infiltrated, the

Fig. 16 Borderline lepromatous leprosy. Erythematous and

infiltrated lesion with irregular edges that invade normal skin.


C. Talhari et al.

Fig. 17 Borderline lepromatous leprosy. Erythematous and infiltrated

lesion with irregular edges on the face that had been treated as
erysipela repeated times.

skin creases may be lost and erythema increases (Figures 19

and 20).24 Hair loss is progressively observed on the infiltrated
areas. Loss of eyebrows, typically beginning from the external
part of eyebrows, gives the typical aspect known as madarosis.
Eyelashes loss is also observed in these patients.10,11
The progressive infiltration of the face makes skin
folds more evident giving a typical clinical aspect known
as facies leonina. Infiltration of hands and feet also occurs
giving the skin a shiny and succulent appearance. Slowly,
solitary or numerous papules and nodules appear on the
infiltrated skin. Warmer areas of the skin such as the axillae,
the mid-line of the back, the perineum, groin and scalp are
less involved than the rest of the body.24
As the disease progresses, the peripheral nerves may
be enlarged and impaired sensation may occur on the hands,
feet and other involved areas. Disabilities may occur as a
consequence of this process.24

There is a subgroup of LL patients characterized by the

presence of nodular lesions showing well-defined edges and
smooth bright surface (Figure 21). This particular clinical
aspect is called Wades Histoid Leprosy or Histoid leprosy. It
was frequently observed in dapsone-resistant patients.26 The
term histoid is due to the histopathological similarity to
dermatofibroma (presence of spindle-shaped cells).27
Another clinical type of LL is the Lucio-Latapi leprosy,
which is characterized by the presence of a massive, shiny
and diffuse skin infiltration giving a brilliant, moist and
myxedematous complexion.28,29 These characteristics give

Fig. 18 Borderline lepromatous leprosy. Erythematous and infiltrated

auricular pavilion with auricular nerve enlargement.

Fig. 20 Lepromatous leprosy. Diffuse infiltration of the face with

bilateral involvement of auricular pavilions.

Fig. 19 Lepromatous leprosy. Diffuse infiltration of the face with

loss of skin ceases.

Clinical aspects of leprosy

damage 38 and gynecomastia 39 are also associated with
lepromatous leprosy. Bones of the face, hands, feet, and
others may also be affected and contribute to disabilities.40
In LL patients the bacilloscopy is strongly positive with
globi and a bacterial index of 6 + (the maximum of this
logarithmic scale as mentioned above).22
The following diseases should be differentiated from LL
and BL leprosy 1,10,16,17:

Fig. 21 Histoid leprosy. Presence of nodular lesions showing

well-defined edges and smooth bright surface on the trunk.

a healthy aspect to the patient, therefore, this clinical type of

LL is was also called lepra bonita (pretty leprosy). Lucios
phenomenon (a necrotizing panvasculitis) and extensive
ulcerations are observed as disease progresses in these patients
(Figure 22).30 Nodules or plaques as typically observed in
LL leprosy are not found in Lucio-Latapi leprosy.31
Lucio-Latapi leprosy is more frequently diagnosed in
Mexico. Recently, a probably new strain of mycobacterium,
named Mycobacterium lepromatosis was reported in patients
with severe LL from this country.32
In LL patients, mucosal involvement of the upper
respiratory tract is frequent and may cause sneezing,
mucopurulent discharge, and epistaxis.33 In severe cases,
the palate and larynx are involved. Without treatment,
destruction of bones of the nasal pyramid may be observed in
late phases of the disease.34
Ophthalmological involvement may also occur in LL
leprosy. Lagophthalmos exposes the cornea to the risk of
drying, trauma, secondary infection, ulceration and perforation.
Corneal anesthesia, iritis, uveitis, glaucoma, and blindness may
occur as a consequence of late diagnosis and inadequate
prevention and treatment.35,36
Liver, spleen, adrenals, and bone marrow may also be affected
during hematogenous spread of M leprae.37 Testicular

1. Secondary syphilis. The previous history of unprotected

sexual intercourse and genital ulcer along with the
presence of moth-eaten alopecia, palmoplantar erythematous papules and mucosal lesions may help in the
differential diagnosis with leprosy.
2. Drug eruptions. Several drugs may induce the appearance
of various lesions that may resemble BL and LL leprosy;
its mandatory to investigate the possibility of drug intake.
3. Anergic cutaneous leishmaniasis. This rare variant of
leishmanisis may present with several papules, tubercles
and isolated or confluent plaques; skin slit smear and
Montenegros test are negatives e direct smear is positive
for amastigotes.
4. Lobomycosis. This subcutaneous mycosis is found
mainly in the Amazon region and is characterized by
the presence of tubercles, nodules and brown plaques that
had a keloidal appearance; it affects mainly the auricular
region, upper and lower limbs; usually the auricular
involvement is unilateral (Figure 23) in lobomycosis and
bilateral in BL and LL leprosy.
5. Systemic erythematous lupus. The cutaneous involvement in
association to fever, arthralgia, madarosis, and anorexia may
mimic LL leprosy; the hypergammaglobulinemia, elevated
sedimentation rate and positivity of rheumatoid factor, LE
cells and VDRL in up to 60% of LL patients may add more
difficulty to the differential diagnosis of these diseases.
6. Neurofibromatosis (Recklinghausen disease). This genodermatosis is characterized by the presence of various
fibroelastic nodules; caf-au-lait patches are also seen.
The widespread nodules found in LL and BL leprosy may
also resemble, sarcoidosis, post-kalazar dermatitis, onchocerciasis, Kaposis sarcoma, mycetoma, and skin lymphoma.
The latter and other conditions such as actinic reticulosis
and anergic cutaneous leishmaniasis should be considered
as differential diagnosis when dealing with patients showing
diffuse skin infiltration. The differential diagnosis of otorhinolaryngological manifestations due to multibacillary leprosy may
include massive bacterial infiltration of the upper respiratory
mucosa and of the nose, mucocutaneous leishmaniasis and
tertiary yaws.1,10,16,17

Pure neural leprosy (PNL)

Fig. 22 Lucio-Latapi leprosy. Extensive ulcerations on the trunk
resembling an erythema multiform.

Pure neural leprosy or neural leprosy is a relatively rare

form of leprosy that is characterized by single or multiple
peripheral nerve enlargements. Usually it is accepted that


C. Talhari et al.

Fig. 23 Lobomycosis. Unilateral auricular involvement with

keloidal and ulcerated lesions.

patients with one or two enlarged nerves are PB and those

with more than two are MB leprosy.41,42
Loss of sensation, loss of muscle strength, loss of swearing,
and enlarged or painful nerves are the most common signs of
nerve damage in PNL. It is not always easy to confirm if a
nerve is enlarged or not. Whenever possible a biopsy (fine
needle aspiration and PCR) or electroneuromiography is
helpful in difficult-to-diagnose PNL patients.43

Nerve involvement and complications

Cutaneous and peripheral nerve trunks are frequently
invaded by M leprae. The consequences of this invasion
will depend on the affected nerves, individual immunological response, type of leprosy and reactions.1,10,44
Nerve damage is usually characterized by impairment or
complete sensory loss in the areas related to the peripheral
nerves. Nerve damage may occur at the cutis level (where
nerves endings are affected), at the level of subcutaneous
nerves and at the level of the nerve trunks. Motor and
autonomic functions may be equally affected. Autonomic
damage causes cyanosis, dryness and reduction or absence of
swearing in the affected areas.44 Paresis or paralysis and
atrophy of muscles may also occur as consequence of nerve
involvement. The most frequently affected peripheral nerves
(symmetrical or asymmetrical) in leprosy patients are 45:
Ulnar nerve. This nerve is frequently damaged proximal to
the olecranon groove. Without adequate treatment, sensation is completely lost and progressive muscle atrophy is
observed on hypothenar eminence. With time, the 4th and
5th fingers become flexed at the proximal interphalangeal
joints and extended at the metacarpophalangeal joints.

This clinical aspect is called minimal or ulnar claw

(Figure 24). Without treatment and prevention of disabilities, ulcerations, bone involvement and loss of fingers are
observed at late stages of disease.1,10,46,47
Median nerve. It may be affected at the bend of the elbow
or just proximal to the carpal tunnel. Most frequently it is
enlarged and damaged at the area of carpal tunnel and
causes sensory and autonomic loss over the lateral half of
the hand, and weakness or paralysis of thenar eminence
and the two lateral lumbricals. In advanced disease, the
hand and thenar eminence become flat, the thumb lies in
the plane of the hand and cannot abducted or opposed, but
flexion is intact. Progressively, the index and middle
finger stay in the same position as described in ulnar claw.
The ulnar and median nerve damage is frequently
associated in the same patient, giving the clinical aspect
of claw hand. At this stage there is an important loss of
function and without treatment/prevention of disabilities,
ulceration, infection, bone involvement and loss of fingers
may occur.1,10,46,47
Radial nerve. It is damaged at the upper arm (beneath the
deltoid insertion) and if severely damaged causes
disabling wrist drop. Sensory impairment/loss of the
dorsomedial region of the hand is observed. The radial
nerve is rarely damaged.1,10,46,47
Common peroneal nerve. It is frequently damaged in the
popliteal fossa or proximally and around the neck of the
fibula. Dorsiflexion and eversion of the foot against
resistance or spontaneously are the first signs of motor
deficit. Hypotrophy of the right anterior tibial muscle, drop
foot, stepping gait, hyperkeratosis, ulcers and infection on the
antero/lateral surface of plantar area observed in late phase of
disease. This is called perforating plantar disease. Anesthesia of the lateral side of the leg, dorsum and latero/plantar
surface is also found. Hair loss, dryness and impaired/absent
swearing of the skin may also be found in the affected
Posterior tibial nerve. This nerve is frequently damaged
proximal to where it passes around the medial malleolus
(tarsal tunnel). Parestesia and later, anesthesia of the sole,
dryness, impairment/absence of swearing, hyperkeratosis,

Fig. 24 Ulnar claw. Fourth and fifth fingers flexion due to ulnar
nerve damage in a leprosy patient.

Clinical aspects of leprosy

ulcers (perforating plantar disease), infection, bone
involvement (osteomyelitis), clawing and loss of the
toes, and severe disabling are progressively observed
without adequate treatment/prevention of the nerve
Facial nerve. The temporal and zygomatic branches may
be damaged. Lagophthalmos is a very important and
frequent complication. Rarely and in advanced disease,
paralysis of bucal, mandibular and cervical branches, may
cause loss of facial expression and inability to close the
Differential diagnosis of nerve involvement
The most important diseases include in the differential
diagnosis of nerve involvement in leprosy are the polyneuropathy associated with Aids, Djrine-Sottass disease (peripheral nerves may be thickened!), diabetes, amyloidosis, systemic
lupus erythematosus, systemic scleroderma, etc.; neurotoxicity
associated with drugs (isoniazid, poisoning with arsenic,
mercury, thallium and others). Nerve compression (carpal
tunnel syndrome, cervico-brachial syndrome and others),
neurogenic muscular atrophy (Tooth-Charcot-Hoffman),
hereditary sensory neuropathy (Thevenards syndrome),
and syringomelia are among the many differential diagnosis
with leprosy.4347

Coinfection HIV/AIDS/leprosy
HIV prevalence rates are still increasing in many countries
where leprosy is endemic. According to the Joint United Nations
Programme on HIV/AIDS (UNAIDS), in 2011, the number of
people living with HIV worldwide continued to grow, reaching
an estimated 34 million (31.4-35.9 million).48
In such scenario, it would be expected that the
geographical overlap of these two diseases would result in
an increasing number of co-infected individuals.49 Global
data indicates that, contrary to the early expectations, there
seems to be no significant increase in leprosy and HIV coinfection.50 Most of the larger studies on the subject were
done in the early to mid-1990s, examining the rate of HIV
serum positivity among leprosy patients.5157
An interesting aspect of the pathogenesis of leprosy in Aids
patients with low T-CD4 + cell count is what has been called
the granuloma paradox: an apparent preservation of the ability
to form granuloma among these patients, in clear contrast with
what is observed in M tuberculosis and HIV co-infected
patients. It has been shown that histopathologic features of
leprosy appear to be maintained in co-infected patients.49
Recent findings demonstrate a possible impact of HIVinfection, HAART, and MDT over leprosy granuloma
formation, contrasting with the granuloma paradox initially
proposed and reinforce the need of careful follow-up of coinfected patients.58
The most often observed clinical form of leprosy in coinfected patients is BT (Figure 25). The large majority of

these cases have been reported in association with an
immunopathological phenomenon called Immune Reconstitution Inflammatory Syndrome (IRIS).5864 IRIS occurs in a
subgroup of AIDS patients with apparent clinical deterioration
despite the T-CD4 + cell count improvement induced by
highly active antiretroviral therapy (HAART).59
One particularly challenging aspect of leprosy-HIV/AIDS
co-infection is the diagnosis of patients with peripheral
neurological manifestations. It may be confounded by
neuropathy associated with HIV itself or with stavudine
and other nucleoside-analogue reverse-transcriptase inhibitors. The clinical findings such as nerve enlargement,
sensory loss, muscle force impairment, and electromyoneuromyography results are important for the diagnosis.58
Recently, it was suggested that even though leprosyHIV/AIDS co-infection does not manifest homogenously
across affected populations, immunological features seem
to be shared by certain sub-groups. In this context, a clinical
classification of M leprae and HIV/AIDS co-infected
patients was proposed and include the following: 1
M leprae-HIV true co-infection: this group is composed
by HIV-positive individuals that do not fulfill AIDS
criteria, therefore, not under HAART; behaving similarly
to immunocompetent subjects; 2 opportunistic leprosy
disease: composed by AIDS patients not receiving
HAART, presenting usually multibacillary leprosy; this
group would be composed by individuals manifesting
leprosy as an opportunistic mycobacteriosis, as expected in
immunosuppressed individuals; and 3 HAART related
leprosy: including AIDS patients presenting all clinical
forms of leprosy related or not to IRIS. Combined HAART
and multidrug therapy might cause upgrading shift
within the leprosy clinical spectrum, as may be revealed
by long-term follow-up. 58
Finally, there is still a lot to learn about this ancient
disease that, despite intense research efforts throughout the
past centuries 65,66, is yet not fully understood. Although
important progress has been made concerning the treatment

Fig. 25 Borderline tuberculoid leprosy in an AIDS patient. An

erythematous and infiltrated lesion with well-defined edges on the trunk.

of leprosy, as published by WHO in 2010 67, a major effort
is still necessary to seek an uniform and shorter multidrug
therapy with potent bactericidal drugs.68

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