Clinics in Dermatology (2015) 33, 26–37

Clinical aspects of leprosy

Carolina Talhari, MD, PhDa,b, Sinésio Talhari, MD, PhD c,Gerson Oliveira Penna, MD, PhDd,⁎

aTeaching and Research Department, Fundação Alfredo da Matta, Manaus, Amazonas, BrazilbAmazon State University, Manaus, Amazonas, BrazilcDepartment of Dermatology, Universidade Nilton Lins, Manaus, Amazonas, BrazildTropical Medicine Centre, University of Brasília, Asa Norte, Brazil

Abstract Leprosy is a chronic, infectious disease caused by Mycobacterium leprae. It mainly affects theperipheral nervous system, skin, and certain other tissues such as the reticulo-endothelial system, bonesand joints, mucous membranes, eyes, testes, muscles, and adrenals. Leprosy clinical presentation variesfrom few to widespread lesions. In most patients, early leprosy presents as macular and hypopigmentedlesions. This initial clinical presentation is known as indeterminate leprosy and occurs in individualswho have not developed cell-mediated immunity against M leprae yet. The number of lesions dependson the genetically determined cellular immunity of the patient. Individuals presenting a vigorous cellularimmune 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 ofleprosy. Due to the inability to mount an effective cellular-mediated response toM leprae and the consequenthematogenous spread of the bacilli, some patients may present with numerous and symmetrically distributedhypochromic 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 byMycobacterium leprae. It mainly affects the peripheralnervous system, skin, and certain other tissues such as thereticulo-endothelial system, bones and joints, mucousmembranes, eyes, testes, muscles, and adrenals. The clinicalpresentation of leprosy clinical presentation varies from fewto widespread lesions.1 Similarly, histopathology of skinlesions varies from compact granulomas to diffuse infiltra-tion of dermis, which largely depend upon the immune statusof the patient and may not be in agreement with the clinicaldiagnosis.2–4 Leprosy classification has been a matter of

⁎ Corresponding author.E-mail address: gpenna@gpenna.net (G.O. Penna).

http://dx.doi.org/10.1016/j.clindermatol.2014.07.0020738-081X/© 2015 Elsevier Inc. All rights reserved.

debate for many years.4 The first classifications were basedonly upon clinical parameters, generating confusion andcontroversies. In 1953, during the Madrid congress, aclassification based on four main disease groups wasproposed: lepromatous leprosy, tuberculoid leprosy, indeter-minate leprosy, and borderline or dimorphous leprosy.5,6

In 1962 2 and 1966 3, Ridley and Jopling proposed a newclassification based not only on the clinical features, but alsoon histopathology, bacterial load and the degree of cell-mediated immune response (CMI) against M leprae, which isevaluated by the result of Mitsuda's intradermal test. Based onthese immunopathological criteria, patients are divided into afive-group spectrum that extends from tuberculoid leprosy(TT) with heightenedCMI (hyperegic pole) through borderlinetuberculoid (BT), borderline-borderline (BB), borderlinelepromatous (BL), to the poorly resistant (anergic) lepromatous

Fig. 1 Indeterminate leprosy. A single, irregular and hypochromicpatch on the left elbow.

27Clinical aspects of leprosy

type (LL) characterized by increased humoral immunity.Indeterminate (I) leprosy does not fall into this spectrumbecause there is a lack of correlation between the clinical andhistopathological features. This clinical form represents anearly stage of the disease in which the degree of CMI is stillnot clear.1

In 1982, the World Health Organization (WHO) advo-cated the use of two different regimens of multidrug therapyfor the treatment of leprosy.7 Patients are classified aspaucibacillary if the bacterial index (BI) is less than 2+ or asmultibacillary if the BI is equal or higher than 2+.7–9 BI is aparameter directly related to bacterial load, being theestimated number of all bacteria, regardless of their shape,present in a smear. The results are expressed on a logarithmicscale: 1+ (at least 1 bacillus in every 100 fields), 2+ (at least1 bacillus in every 10 fields), 3+ (at least 1 bacillus in everyfield), 3+ (at least 1 bacillus in every field), 4+ (at least 10bacillus in every field), 5+ (at least 100 bacillus in everyfield), and 6+ (at least 1000 bacillus in every field).7,8

In this contribution, the authors have decided to describeleprosy clinical manifestations based on Ridley and Joplingclassification. One must remember that the first signs thatlead leprosy patients to seek for medical attention are mostoften dermatological. Careful examination of skin is a keyelement in leprosy diagnosis.

ig. 2 Indeterminate leprosy. An irregular, hypochromic patchn the lower limb.

I leprosy

In most patients, early leprosy presents as macular andhypopigmented lesions. This initial clinical presentationis known as I leprosy and occurs in individuals who havenot developed cell-mediated immunity against M lepraeyet.1,10 The single (Figure 1) or multiple macules have nomore than 3–4 cm wide, present with a smooth surface andare not scaling or pruriginous (Figure 2). The lesions mayalso be red in light-skinned patients or coppery in dark-skinned patients. There is normal sweating and body hairsare present.11–14

A very important characteristic of leprosy lesions is theimpaired sensation (anesthesia). On I leprosy lesions thepatient commonly presents with loss of thermal sensation,not being able to distinguish between a cold and a hot tubof water. Hyperalgesia often precede the detection of skinlesions.12,13

The number of lesions depends on the geneticallydetermined cellular immunity of the patient. Individualspresenting a vigorous cellular immune response and limitedhumoral immune responses to M leprae, usually present fewskin lesions.12 Without treatment, those patients tend toevolve into the polar T or BT form of leprosy. Individualswithin the tuberculoid pole may present a tendency towardsspontaneous healing. Patients presenting with numerous orcountless number of hypochromic lesions, without treatment,tend to evolve into BB, BL, or LL forms.13,14

The diagnosis of indeterminate patients may be difficult.Besides sensory tests already mentioned, the histamine test isa very useful diagnostic tool for light-skinned patients. Itconsists in the application of one drop of histamine (dilution -1/1000) within and around the suspected hypochromiclesion. After 1–2 minutes, a triphasic skin reaction knownas Triple Response of Lewis will occur: first a red linedevelops at the site due to histamine release, then a flaredevelops around the red line, and lastly a wheal is formed asa result of local edema. This triple reaction is only observedin the normal skin or hypochromic lesions caused by otherdiseases; if the lesion is due to leprosy the response of theskin to histamine will be incomplete once this local reflexdepends upon the integrity of sympathetic nerve fibers.12

Fo

ig. 4 Solar hypochromiant dermatosis with irregular lesions andugh surface.

28 C. Talhari et al.

In patients presenting with indeterminate leprosy, bacilloscopy(slit-skin smear and Ziehl-Nielsen staining) is negative.13–15

The following diseases may mimic the hypopigmentedmacule due to I leprosy 1,10,16,17:

1. Pityriasis alba. Characterized by the presence of a variablenumber of hypochromic, round patches with undefinededges on the trunk and upper limbs; in general, it presentsa rough surface.

2. Hypochromic variant of pityriasis versicolor. Initially itmay present as a small hypopigmented macule thatusually grows in size and tend to coalesce; superficialdesquamation is important to differentiate this superficialmycosis 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 roughsurface (Figure 4).

Achromic nevus, nevus anemicus, vitiligo, and postin-flammatory hypopigmentation may also mimic I leprosy.

The erythematous leprosy macule must be distinguishedfrom the macules occurring in seborrhoeic dermatitis, whichis clinically characterized by the presence of squamouslesions 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 Gilbert’spityriasis rosea should also be distinguished from I leprosy.Differential diagnosis of hyperchromic macule due toindeterminate leprosy may include residual lesions ofpostinflammatory hyperpigmentation, Kaposi’s sarcoma,morphea, tinea nigra, hyperchromic form of pityriasisversicolor, erythema dyscromicum perstans, and fixed drugeruption.1,10,16,17

Fig. 3 Hypochromic variant of pityriasis versicolor. Superficialdesquamation is important to differentiate this superficial mycosisfrom indeterminate leprosy.

Fro

Tuberculoid leprosy

Tuberculoid leprosy (TT) is characterized by the presenceof unique or few small-sized lesions showing well-definedand elevated borders (papules and plaques) (Figure 6).18 Theelevated border indicates either central healing or peripheralspread.13 Typical TT lesions have decreased sweating,rarefied body hair, and are anesthetic: first thermal, thentactile, and pain sensitivity is lost. There are patients withtuberculoid leprosy that presents anesthetic areas withoutchanges in the skin color or peripheral trunk nerveenlargement, with or without skin lesions.19 It is veryimportant to remember that lesions on the face may presentnormal sensitivity, in this area the rich sensory innervationscompensates for the damaged nerves.1,11

In early cases of TT, macules may be observed; in light-skinned patients these lesions are erythematous or coppery indark-skinned individuals; it may also be homogeneouslyhypopigmented. These macules show a dry surface and dueto anhidrosis are rough to the touch. Due to the intensecellular-mediated immunity, papules can appear on the edgesof the macule (Figure 7).10,13

Fig. 5 Seborrhoeic dermatitis. Hypochromic lesion on the face.

Fig. 6 Tuberculoid leprosy. Unique lesion showing well-definedand elevated borders on the hand.

ig. 8 Infantile nodular tuberculoid leprosy. A nodular lesion one face of a child.

29Clinical aspects of leprosy

A particular type of leprosy, usually characterized by thepresence of nodular lesions may be observed in children and isknown as infantile nodular tuberculoid leprosy (Figure 8).20 Itexclusively appears during infancy and affects children youngerthan 5 years of age. It is considered the most benign of all formsof 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, involvementof peripheral trunk nerves such as ulnar, median, radial, andcommon peroneal or posterior tibial may be severe and causedisabilities 1. In TT leprosy, the possibility of peripheralnerve 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 diseases1,10,16,17:

1. Tinea. As in T leprosy, there is a tendency to centralhealing; the presence of pruritus, local excoriation andsuperficial scars is important to differentiate such lesionsfrom T leprosy (Figure 9).

2. Cutaneous erythematous lupus. The lesions are localizedmainly on the face and other exposed areas of the body;there is a tendency to spontaneous healing with residual

Fig. 7 Tuberculoid leprosy. An unique macule showing papuleson the edges of the lesions.

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hyperchromic, atrophic and scarring aspect; sensitivitytests are preserved.

3. Annular granuloma. The lesions are characterized by thepresence of anular plaques very similar to T leprosy butwith normal sensitivity tests (Figure 10).

4. Secondary syphilis. The previous history of penial orvulvar ulcerated lesion is important when differentiatingsuch lesions from T leprosy; however, lesions on thecervix may not be acknowledge by most of the women;anti-treponemal screening is mandatory.

5. Gilbert’s pityriasis rosea. This disease of viral etiology ischaracterized by erythematous and round lesions present-ing with collarette desquamation; these lesions evolverapidly, usually beginning with patch that heralds theeruption, the so-called “herald patch” (Figure 11); thelesions usually disappear in 1 to 2 months.

Seborrhoeic dermatitis, lobomycosis, chromomycosis, pso-riasis, parapsoriasis, sarcoidosis, mycosis fungoides, morphea,necrobiosis lipoidica, Kaposi’s sarcoma, cutaneous tuberculosisand leishmaniasis are other diseases that may mimic T leprosy.

Borderline leprosy

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

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

F the forehead; differential diagnosis of tuberculoid leprosy.

Fig. 10 Annular granuloma. Anular plaques on the upper limbthat are very similar to T leprosy but present with normal sensitivity.

30 C. Talhari et al.

multiple and severe peripheral nerve involvement and mostof disabled patients are within the borderline spectrum ofleprosy.1

Instability is the predominant characteristic of borderlinegroup. Without treatment borderline patients may down-grade in the direction of lepromatous leprosy and aftersometime may present the typical clinical aspect oflepromatous leprosy. During and after treatment patientsmay upgrade. Borderline patients frequently present reversalreactions when upgrading or downgrading and not necessarilythese changes are related with treatment or not. Reversalreactions are characterized by worsening of skin lesions andnerves. Without adequate treatment paralysis are frequentlyobserved during these reactions.23

Fig. 11 Gilbert’s pityriasis rosea. Erythematous and round lesionspresenting with collarette desquamation; in this image is possible tonote the “herald patch,” which is usually the larger lesion.

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 arelarger than those observed in TT. It is frequent to observesatellite lesions near the larger lesions or “finger-like” whichextends from the edges of the plaques or macules (Figure 12)into the normal skin, and the color varies from hypochromicto reddish. Lesions may vary in size, shape and color in thesame patient. Reactions (type 1) are frequent and swollen/ulceration of the cutaneous lesions may occur.1,10,11 Nervesare severely involved during reactions in BT leprosy(Figure 13).24 Nerve function may deteriorate rapidly, andurgent treatment to prevent permanent deformity anddisability is necessary.

Some patients may present only anesthetic macules andnerve enlargement. They are called “maculoanestheticborderline”.1,10,11

The bacilloscopy varies from negative to positive (2+).22

Borderline leprosy (BB) or mid-borderline leprosyBB 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 vaguedefined 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 combinationwith thetypical lesions. In BB leprosy there are disseminated reddishcoppery lesions, usually symmetrically distributed.10,11

BB leprosy is rare and considered the most unstable partof the spectrum. It moves rapidly towards one of the polarforms (TT or LL). Nerve involvement is variable in thesepatients. It may be severe during the frequent type 1 reactionor 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

ig. 12 Borderline tuberculoid leprosy. A hypochromic lesionresenting with infiltrated and erythematous borders.

Fp

Fig. 13 A reactional borderline tuberculoid leprosy presentingwith infiltrated and erythematous plaques on the face.

ig. 15 Borderline-borderline leprosy. Multiple lesions on theunk giving a “Swiss cheese like” aspect.

31Clinical aspects of leprosy

size, become erythematous and infiltrated. The lesion edgesare irregular and invade normal skin (Figure 16).23 Progres-sively, extensive areas become infiltrated (Figure 17). Plaque-like lesions, papules and nodules may appear simulatinglepromatous leprosy.11

Type 1 and 2 leprosy reactions are frequently observed inthese patients.24

Peripheral nerve enlargement is observed in most of thepatients (Figure 18). Nerves are less commonly tender than inBT 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-mediatedresponse to M leprae and the consequent hematogenous

Fig. 14 Borderline-borderline leprosy. The lesion shows acentral apparently spared skin with well-defined inner edge andvague defined outer edges. This patient was treating the lesion as afungal infection.

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spread of the bacilli, some patients may present with numerousand symmetrically distributed hypochromic lesions. Withouttreatment these patients evolve to a nonresistant formof leprosy - polar lepromatous (LL). This leprosy form mayalso occur as a result of downgrading BB and BL withouttreatment.1,10,11

There are two clinical subforms of lepromatous leprosy,subpolar (LLs) and polar (LLp). LLs patients are notcompletely anergic and after treatment become bacteriologi-cally negativemore rapidly when comparedwith LLp. Patientspresenting with the first clinical form can develop type 1reaction.25

In LLs the macules, nodules and plaques have well-definedborders. LLp occur in extremely anergic patients and arecharacterized by the presence of diffuse infiltration of the skinwith indistinct edges.11 In such patients, a diffuse infiltration ofthe hypochromic lesions and the apparently normal skinslowly involves extensive areas or the entire body. Withouttreatment, the skin becomes more and more infiltrated, the

ig. 16 Borderline lepromatous leprosy. Erythematous andfiltrated lesion with irregular edges that invade normal skin.

Fin

Fig. 17 Borderline lepromatous leprosy. Erythematous and infiltratedlesion with irregular edges on the face that had been treated aserysipela repeated times.

ig. 19 Lepromatous leprosy. Diffuse infiltration of the face withss of skin ceases.

32 C. Talhari et al.

skin creases may be lost and erythema increases (Figures 19and 20).24 Hair loss is progressively observed on the infiltratedareas. Loss of eyebrows, typically beginning from the externalpart of eyebrows, gives the typical aspect known asmadarosis.Eyelashes loss is also observed in these patients.10,11

The progressive infiltration of the face makes skinfolds more evident giving a typical clinical aspect knownas facies leonina. Infiltration of hands and feet also occursgiving the skin a shiny and succulent appearance. Slowly,solitary or numerous papules and nodules appear on theinfiltrated skin. Warmer areas of the skin such as the axillae,the mid-line of the back, the perineum, groin and scalp areless involved than the rest of the body.24

As the disease progresses, the peripheral nerves maybe enlarged and impaired sensation may occur on the hands,feet and other involved areas. Disabilities may occur as aconsequence of this process.24

Fig. 18 Borderline lepromatous leprosy.Erythematous and infiltratedauricular pavilion with auricular nerve enlargement.

Flo

There is a subgroup of LL patients characterized by thepresence of nodular lesions showing well-defined edges andsmooth bright surface (Figure 21). This particular clinicalaspect is called Wade’s Histoid Leprosy or Histoid leprosy. Itwas frequently observed in dapsone-resistant patients.26 Theterm histoid is due to the histopathological similarity todermatofibroma (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, shinyand diffuse skin infiltration giving a brilliant, moist andmyxedematous complexion.28,29 These characteristics give

ig. 20 Lepromatous leprosy. Diffuse infiltration of the face withilateral involvement of auricular pavilions.

Fb

Fig. 21 Histoid leprosy. Presence of nodular lesions showingwell-defined edges and smooth bright surface on the trunk.

33Clinical aspects of leprosy

a healthy aspect to the patient, therefore, this clinical type ofLL is was also called “lepra bonita” (pretty leprosy). Lucio’sphenomenon (a necrotizing panvasculitis) and extensiveulcerations are observed as disease progresses in these patients(Figure 22).30 Nodules or plaques as typically observed inLL leprosy are not found in Lucio-Latapi leprosy.31

Lucio-Latapi leprosy is more frequently diagnosed inMexico. Recently, a probably new strain of mycobacterium,namedMycobacterium lepromatosis was reported in patientswith severe LL from this country.32

In LL patients, mucosal involvement of the upperrespiratory 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 inlate phases of the disease.34

Ophthalmological involvement may also occur in LLleprosy. Lagophthalmos exposes the cornea to the risk ofdrying, trauma, secondary infection, ulceration and perforation.Corneal anesthesia, iritis, uveitis, glaucoma, and blindness mayoccur as a consequence of late diagnosis and inadequateprevention and treatment.35,36

Liver, spleen, adrenals, and bonemarrowmay also be affectedduring hematogenous spread of M leprae.37 Testicular

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

damage 38 and gynecomastia 39 are also associated withlepromatous leprosy. Bones of the face, hands, feet, andothers may also be affected and contribute to disabilities.40

In LL patients the bacilloscopy is strongly positive withglobi and a bacterial index of 6+ (the maximum of thislogarithmic scale as mentioned above).22

The following diseases should be differentiated from LLand BL leprosy 1,10,16,17:

1. Secondary syphilis. The previous history of unprotectedsexual intercourse and genital ulcer along with thepresence of moth-eaten alopecia, palmoplantar erythem-atous papules and mucosal lesions may help in thedifferential diagnosis with leprosy.

2. Drug eruptions. Several drugs may induce the appearanceof various lesions that may resemble BL and LL leprosy;it’s mandatory to investigate the possibility of drug intake.

3. Anergic cutaneous leishmaniasis. This rare variant ofleishmanisis may present with several papules, tuberclesand isolated or confluent plaques; skin slit smear andMontenegro’s test are negatives e direct smear is positivefor amastigotes.

4. Lobomycosis. This subcutaneous mycosis is foundmainly in the Amazon region and is characterized bythe presence of tubercles, nodules and brown plaques thathad a keloidal appearance; it affects mainly the auricularregion, upper and lower limbs; usually the auricularinvolvement is unilateral (Figure 23) in lobomycosis andbilateral in BL and LL leprosy.

5. Systemic erythematous lupus. The cutaneous involvement inassociation to fever, arthralgia, madarosis, and anorexia maymimic LL leprosy; the hypergammaglobulinemia, elevatedsedimentation rate and positivity of rheumatoid factor, LEcells and VDRL in up to 60% of LL patients may add moredifficulty to the differential diagnosis of these diseases.

6. Neurofibromatosis (Recklinghausen disease). This geno-dermatosis is characterized by the presence of variousfibroelastic nodules; cafè-au-lait patches are also seen.

The widespread nodules found in LL and BL leprosy mayalso resemble, sarcoidosis, post-kalazar dermatitis, oncho-cerciasis, Kaposi’s sarcoma, mycetoma, and skin lymphoma.The latter and other conditions such as actinic reticulosisand anergic cutaneous leishmaniasis should be consideredas differential diagnosis when dealing with patients showingdiffuse skin infiltration. The differential diagnosis of otorhino-laryngological manifestations due tomultibacillary leprosymayinclude massive bacterial infiltration of the upper respiratorymucosa and of the nose, mucocutaneous leishmaniasis andtertiary yaws.1,10,16,17

Pure neural leprosy (PNL)

Pure neural leprosy or neural leprosy is a relatively rareform of leprosy that is characterized by single or multipleperipheral nerve enlargements. Usually it is accepted that

Fig. 23 Lobomycosis. Unilateral auricular involvement withkeloidal and ulcerated lesions.

ig. 24 Ulnar claw. Fourth and fifth fingers flexion due to ulnarerve damage in a leprosy patient.

34 C. Talhari et al.

patients with one or two enlarged nerves are PB and thosewith 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 ofnerve damage in PNL. It is not always easy to confirm if anerve is enlarged or not. Whenever possible a biopsy (fineneedle aspiration and PCR) or electroneuromiography ishelpful 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 invasionwill depend on the affected nerves, individual immunolog-ical response, type of leprosy and reactions.1,10,44

Nerve damage is usually characterized by impairment orcomplete sensory loss in the areas related to the peripheralnerves. Nerve damage may occur at the cutis level (wherenerves endings are affected), at the level of subcutaneousnerves and at the level of the nerve trunks. Motor andautonomic functions may be equally affected. Autonomicdamage causes cyanosis, dryness and reduction or absence ofswearing in the affected areas.44 Paresis or paralysis andatrophy of muscles may also occur as consequence of nerveinvolvement. The most frequently affected peripheral nerves(symmetrical or asymmetrical) in leprosy patients are 45:

• Ulnar nerve. This nerve is frequently damaged proximal tothe olecranon groove. Without adequate treatment, sensa-tion is completely lost and progressive muscle atrophy isobserved on hypothenar eminence. With time, the 4th and5th fingers become flexed at the proximal interphalangealjoints and extended at the metacarpophalangeal joints.

This clinical aspect is called minimal or ulnar claw(Figure 24). Without treatment and prevention of disabil-ities, ulcerations, bone involvement and loss of fingers areobserved at late stages of disease.1,10,46,47

• Median nerve. It may be affected at the bend of the elbowor just proximal to the carpal tunnel. Most frequently it isenlarged and damaged at the area of carpal tunnel andcauses sensory and autonomic loss over the lateral half ofthe hand, and weakness or paralysis of thenar eminenceand the two lateral lumbricals. In advanced disease, thehand and thenar eminence become flat, the thumb lies inthe plane of the hand and cannot abducted or opposed, butflexion is intact. Progressively, the index and middlefinger stay in the same position as described in ulnar claw.The ulnar and median nerve damage is frequentlyassociated in the same patient, giving the clinical aspectof claw hand. At this stage there is an important loss offunction and without treatment/prevention of disabilities,ulceration, infection, bone involvement and loss of fingersmay occur.1,10,46,47

• Radial nerve. It is damaged at the upper arm (beneath thedeltoid insertion) and if severely damaged causesdisabling wrist drop. Sensory impairment/loss of thedorsomedial region of the hand is observed. The radialnerve is rarely damaged.1,10,46,47

• Common peroneal nerve. It is frequently damaged in thepopliteal fossa or proximally and around the neck of thefibula. Dorsiflexion and eversion of the foot againstresistance or spontaneously are the first signs of motordeficit. Hypotrophy of the right anterior tibial muscle, dropfoot, stepping gait, hyperkeratosis, ulcers and infection on theantero/lateral surface of plantar area observed in late phase ofdisease. This is called “perforating plantar disease. Anesthe-sia of the lateral side of the leg, dorsum and latero/plantarsurface is also found. Hair loss, dryness and impaired/absentswearing of the skin may also be found in the affectedareas.1,10,46,47

• Posterior tibial nerve. This nerve is frequently damagedproximal to where it passes around the medial malleolus(tarsal tunnel). Parestesia and later, anesthesia of the sole,dryness, impairment/absence of swearing, hyperkeratosis,

Fn

35Clinical aspects of leprosy

ulcers (perforating plantar disease), infection, boneinvolvement (osteomyelitis), clawing and loss of thetoes, and severe disabling are progressively observedwithout adequate treatment/prevention of the nervedamage.1,10,46,47

• Facial nerve. The temporal and zygomatic branches maybe damaged. Lagophthalmos is a very important andfrequent complication. Rarely and in advanced disease,paralysis of bucal, mandibular and cervical branches, maycause loss of facial expression and inability to close themouse.1,10,46,47

Differential diagnosis of nerve involvementThe most important diseases include in the differential

diagnosis of nerve involvement in leprosy are the polyneuro-pathy associated with Aids, Déjérine-Sottas’s disease (periph-eral nerves may be thickened!), diabetes, amyloidosis, systemiclupus erythematosus, systemic scleroderma, etc.; neurotoxicityassociated with drugs (isoniazid, poisoning with arsenic,mercury, thallium and others). Nerve compression (carpaltunnel syndrome, cervico-brachial syndrome and others),neurogenic muscular atrophy (Tooth-Charcot-Hoffman),hereditary sensory neuropathy (Thevenard’s syndrome),and syringomelia are among the many differential diagnosiswith leprosy.43–47

Coinfection HIV/AIDS/leprosy

ig. 25 Borderline tuberculoid leprosy in an AIDS patient. Anrythematous and infiltrated lesion with well-defined edges on the trunk.

HIV prevalence rates are still increasing in many countrieswhere leprosy is endemic.According to the JointUnitedNationsProgramme on HIV/AIDS (UNAIDS), in 2011, the number ofpeople living with HIV worldwide continued to grow, reachingan estimated 34 million (31.4-35.9 million).48

In such scenario, it would be expected that thegeographical overlap of these two diseases would result inan increasing number of co-infected individuals.49 Globaldata indicates that, contrary to the early expectations, thereseems to be no significant increase in leprosy and HIV co-infection.50 Most of the larger studies on the subject weredone in the early to mid-1990s, examining the rate of HIVserum positivity among leprosy patients.51–57

An interesting aspect of the pathogenesis of leprosy in Aidspatients with low T-CD4+ cell count is what has been calledthe granuloma paradox: an apparent preservation of the abilityto form granuloma among these patients, in clear contrast withwhat is observed in M tuberculosis and HIV co-infectedpatients. It has been shown that histopathologic features ofleprosy appear to be maintained in co-infected patients.49

Recent findings demonstrate a possible impact of HIV-infection, HAART, and MDT over leprosy granulomaformation, contrasting with the granuloma paradox initiallyproposed and reinforce the need of careful follow-up of co-infected patients.58

The most often observed clinical form of leprosy in co-infected patients is BT (Figure 25). The large majority of

these cases have been reported in association with animmunopathological phenomenon called Immune Reconsti-tution Inflammatory Syndrome (IRIS).58–64 IRIS occurs in asubgroup of AIDS patients with apparent clinical deteriorationdespite the T-CD4+ cell count improvement induced byhighly active antiretroviral therapy (HAART).59

One particularly challenging aspect of leprosy-HIV/AIDSco-infection is the diagnosis of patients with peripheralneurological manifestations. It may be confounded byneuropathy associated with HIV itself or with stavudineand other nucleoside-analogue reverse-transcriptase inhibi-tors. The clinical findings such as nerve enlargement,sensory loss, muscle force impairment, and electromyoneur-omyography results are important for the diagnosis.58

Recently, it was suggested that even though leprosy-HIV/AIDS co-infection does not manifest homogenouslyacross affected populations, immunological features seemto be shared by certain sub-groups. In this context, a clinicalclassification of M leprae and HIV/AIDS co-infectedpatients was proposed and include the following: 1

M leprae-HIV true co-infection: this group is composedby HIV-positive individuals that do not fulfill AIDScriteria, therefore, not under HAART; behaving similarlyto immunocompetent subjects; 2 opportunistic leprosydisease: composed by AIDS patients not receivingHAART, presenting usually multibacillary leprosy; thisgroup would be composed by individuals manifestingleprosy as an opportunistic mycobacteriosis, as expected inimmunosuppressed individuals; and 3 HAART relatedleprosy: including AIDS patients presenting all clinicalforms of leprosy related or not to IRIS. Combined HAARTand multidrug therapy might cause upgrading shiftwithin the leprosy clinical spectrum, as may be revealedby long-term follow-up.58

Finally, there is still a lot to learn about this ancientdisease that, despite intense research efforts throughout thepast centuries 65,66, is yet not fully understood. Althoughimportant progress has been made concerning the treatment

Fe

36 C. Talhari et al.

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

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