1387CHAPTER 179 Leprosy

DIFFUSE LEPROSY OF LUCIO AND LATAPÍ This rare form of non-nodular

LL leprosy occurring in Mexico and Central America is characterized

by diffuse shiny infiltration of the skin and widespread sensory loss.

The skin looks waxy and has a shiny appearance (“lepra bonita,” or

beautiful leprosy), with obvious diffuse induration of the earlobes and

forehead as well as loss of eyebrows, sometimes eyelashes, and not

infrequently all body hair. This form of leprosy can be complicated by

an unusual reaction known as Lucio’s phenomenon (see below).

Primary Neuritic Leprosy In some countries, such as India and

Nepal, primary neuritic disease is observed in 2–10% of all leprosy

cases, with only peripheral nerve involvement and no skin lesions.

Nerve thickening and sensory loss occur in the affected area, with or

without a motor deficit. Primary neuritic leprosy, even though not

described by Ridley and Jopling, can manifest at different points along

the disease spectrum. For practical purposes, primary neuritic leprosy

is classified as paucibacillary or multibacillary on the basis of the

absence or presence of AFB in nerve biopsy sections or the number of

thickened nerves (single or multiple).

■ LEPROSY REACTIONS

Leprosy reactions are immunologic phenomena that occur before,

during, or after treatment. They are severe complications that need to

be diagnosed and treated early to prevent nerve function impairment

and subsequent disfigurement as well as blindness.

Type 1 Leprosy Reaction (T1R) T1R is a delayed hypersensitivity reaction associated with sudden alteration of CMI status and

leading to a shift in the patient’s position on the leprosy spectrum.

This reaction is marked by infiltration of lesions by activated CD4+

T lymphocytes, especially T helper cells. T1R is also called a reversal reaction because of the upgrading of CMI status. T1R is usually

observed in the borderline portion of the spectrum. Skin lesions are

characterized by acute swelling and redness (Fig. 179-7). Nerves may

be painful and tender because of neuritis, with consequent nerve

damage and disfigurement. In the severe form of T1R, nerve abscesses

may be formed. Loss of nerve function can be much less obvious than

usual when it occurs without other signs of inflammation. This “silent

neuritis” may lead to sensory and motor impairment in the hands, feet,

and face. Arthralgia or arthritis sometimes occurs. Rarely, the patient

may develop fever and malaise, tenosynovitis, and edema of the feet

and hands.

Type 2 Leprosy Reaction (T2R) T2R, also known as ENL

(erythema nodosum leprosum), is an immune complex–mediated

syndrome (i.e., an antigen–antibody reaction involving complement)

that causes inflammation of the skin, nerves, and other organs as well

as general malaise. ENL is an example of a type III hypersensitivity

reaction (Coombs and Gell classification) or Arthus phenomenon.

This reaction occurs mostly during multidrug therapy but can also

develop in untreated patients. Evanescent, pink-to-red maculopapular,

papular, nodular, or plaque lesions suddenly appear and are usually

accompanied by constitutional symptoms like malaise and fever, with

or without painful swelling in the joints (Fig. 179-8). These crops of

skin lesions present on the outer aspects of the thighs, legs, and face.

They are painful or tender and warm, blanch with light finger pressure, and last for a few days. The lesions change in color from pink/

red to bluish and brownish after 24–48 h and turn dark in a week.

Rarely, ENL lesions become vesicular, pustular, bullous, and necrotic

and break down to produce ulceration (erythema nodosum necroticans). The patient may have other associated signs such as lymph node

enlargement, myositis, arthritis, synovitis, rhinitis, epistaxis, laryngitis,

iridocyclitis, glaucoma, painful dactylitis, acute epididymoorchitis,

nephritis and renal failure, hepatosplenomegaly, anemia, and—at a

later stage—amyloidosis. Severe T2R may include swollen, painful, and

tender nerve trunks with sensory and motor deficits.

Lucio’s Phenomenon Lucio’s phenomenon is observed in diffuse

leprosy of Lucio and Latapí and may be a variant of erythema nodosum

necroticans. Marked vasculitis and thrombosis of the superficial and

deep vessels result in hemorrhage and infarction of the skin. Clinically,

the skin reaction begins as slightly indurated, bluish-red, ill-defined,

painful, and rarely palpable plaques with an erythematous halo, usually developing on one limb but sometimes on other areas of the body.

The lesions are irregular or triangular. After a few days, they become

purplish at the center; a central hemorrhagic infarct may develop with

or without blister formation, and a necrotic eschar that detaches easily

and leaves an ulcer of irregular shape may follow later. The ulcer heals,

leaving a superficial scar. Patients remain afebrile throughout.

Nerve Function Impairment, Neuritis, and Disfigurement

The terms nerve function impairment, nerve damage, neuropathy, and

neuritis are often used interchangeably for the sensory, motor, and/

or autonomic nerve deficits that occur because of the pathologic processes resulting from M. leprae infection of the nerve. Neuritis (nerve

inflammation) in leprosy is usually a subacute, demyelinating, and

unremitting event involving cutaneous nerves and larger peripheral

nerves. “Silent neuritis” or “quiet nerve paralysis” is defined as progressive sensory or motor impairment in the absence of symptoms such as

pain, paresthesia, or tenderness of the nerve and with no obvious signs

of leprosy reactions. Neuritis can occur at any time during leprosy but

is more common and severe during leprosy reactions, mainly in T1R.

Sensory and motor neuropathy can lead to secondary impairments in

the upper and lower extremities, such as muscle atrophy, mobile- and

fixed-joint contractures, bone absorption of digits, and cracks and

wounds.

FIGURE 179-7 Type 1 leprosy reaction. Increased inflammation of existing lesions.

(From Dr. W. H. van Brakel, with permission from NLR.)

FIGURE 179-8 Type 2 leprosy reaction. Erythema nodosum leprosum, with pustular

lesions. (From Dr. H. K. Kar, with permission.)

1388 PART 5 Infectious Diseases

■ DIAGNOSIS

Clinical Diagnosis Three cardinal signs indicate a diagnosis of

leprosy. The diagnosis can be established when two of these three signs

are present:

1. Hypopigmented or erythematous skin lesion(s) with definite loss or

impairment of sensation: The clinical presentation of skin patches

or plaques is diagnostic when it is associated with a definite loss or

impairment of sensation (light touch, pain, and/or temperature).

Diagnostic dilemmas arise in the indeterminate stage of leprosy

because of variable loss of sensation and the presence of facial

lesions (i.e., because the density of innervation in the face can compensate for damage to certain nerve branches).

2. Involvement of the peripheral nerves, as demonstrated by definite

thickening with sensory impairment: Thickening of a peripheral

nerve should be assessed by palpation of the affected nerve and

comparison with the corresponding contralateral nerve. In multibacillary leprosy, thickening of nerves is often bilateral. Nerve

tenderness is established by the application of mild pressure on the

nerve during palpation with the fingertips. The peripheral nerves

commonly palpated in a leprosy patient are the greater auricular,

ulnar, radial, radial cutaneous, median, lateral popliteal, posterior

tibial, sural, and superficial peroneal nerves.

3. A positive result for AFB in slit-skin smears, establishment of the

presence of AFB in a skin smear or biopsy sample, or a positive

result in a biopsy PCR.

Diagnostic Tools •  TESTING OF SKIN SENSATION Light-touch

sensation is tested with cotton wool or a feather. Pain is assessed as

the patient’s ability to distinguish between the sharp and blunt ends

of a wooden or bamboo toothpick. Thermal sensation thresholds are

assessed with computer-assisted sensory testing equipment.

SLIT-SKIN SMEAR Normally a slit-skin smear is taken from four sites:

the right earlobe, the forehead above the eyebrows, the chin, and the

left buttock in men or the left upper thigh in women. The material

is stained with Ziehl-Neelsen reagent and examined with a light

microscope. The bacteriologic index is determined with a standard

logarithmic scale and graded from 0 to 6. The microbiologic index is

determined as the percentage of solid, stained AFB.

SKIN BIOPSY A skin biopsy is done to confirm the diagnosis of leprosy, to classify the disease, to support the diagnosis of reactions, and

to determine cure after the completion of multidrug therapy. When

macular lesions are suspected of reflecting IL, a biopsy sample should

be taken from the middle of a lesion; with plaques, a sample should be

obtained from the active indurated edge. When there are numerous

skin lesions with different morphologies, more than one biopsy sample

is required for proper evaluation of the disease spectrum. Identification

of early lesions of leprosy by histopathologic techniques is enhanced

by immunochemical staining, which reveals the presence of M. leprae

antigens.

PGL-1 ANTIBODY TEST PGL-1 is a specific lipid on the M. leprae cell

wall. A PGL-1 ELISA has been used for serologic diagnosis of leprosy,

yielding positive results in 90–95% of multibacillary cases and in

25–60% of paucibacillary cases. Using PGL-1 antigen and adopting an

immunochromatographic technique, a rapid lateral-flow assay—the

ML flow test—has been developed for detection of antibody to PGL-1.

This assay gives positive results in 92–97% of patients with multibacillary leprosy and in 32–40% of patients with paucibacillary disease.

LEPROMIN TEST The lepromin (or Mitsuda) skin test measures cellular

immunity against lepromin. A bacillary suspension standardized by

the number of inactivated M. leprae it contains is injected just under

the skin. The reaction to lepromin is measured as induration in millimeters 3–4 weeks after intradermal inoculation. The result provides

information about the ability of an individual’s T cells to respond to M.

leprae and the likelihood of granuloma formation in that individual.

A negative lepromin test is generally seen in patients with LL or BL

leprosy, indicating the lack of a protective cellular response.

GENE AMPLIFICATION (PCR) TECHNIQUE Gene amplification significantly enhances the detection of M. leprae, especially in bacteriologic

index–negative leprosy and cases that do not fulfill the criteria for

the cardinal signs of leprosy. The several PCR methods developed

to amplify different gene stretches in M. leprae include conventional

DNA-based PCR, reverse-transcription PCR, and multiplex PCR.

As major genes for detection of disease targets, PCR uses M. leprae–

specific genes encoding 36-kDa antigen, 18-kDa antigen, 65-kDa antigen complex 85, 16S ribosomal RNA (rRNA), and repetitive sequences.

These assays are sensitive to as few as 1–10 bacilli and yield positive

results in 60–75% of smear-negative cases. Multiplex PCR employing

the genes encoding the repetitive element RLEP, SodA, and 16S rRNA

can be used for early diagnosis and for the diagnosis of subclinical

infection among household contacts.

Differential Diagnosis Leprosy is often diagnosed late, with a

consequent increase in the risk of nerve damage and its ensuing disabilities. The hypopigmented macules of leprosy must be differentiated

from a variety of conditions, including pityriasis alba, vitiligo, progressive macular hypomelanosis, pityriasis versicolor, pityriasis rosea,

postinflammatory hypopigmentation, sarcoidosis, post–kala-azar dermal leishmaniasis, and morphea. In the analysis of plaques and nodular

lesions, conditions such as granuloma annulare, cutaneous sarcoidosis,

cutaneous leishmaniasis, lupus miliaris disseminatus faciei, nodular histiocytosis, lupus erythematosus, cutaneous T–cell lymphomas

(especially mycosis fungoides), and secondary syphilis should be kept

in mind. ENL lesions must be differentiated from erythema nodosum

of other etiologies, nodular vasculitis, and cutaneous polyarteritis

nodosa. In the case of mononeuropathy lesions, diabetes, amyloidosis,

and myxedema must be considered. With polyneuropathy lesions of

acute onset, Guillain-Barré syndrome and toxic polyneuropathy must

be given consideration.

Diagnostic Tools for Nerve Function Impairment All sensory modalities, autonomic function, and motor function of motor

nerves may be affected in leprosy to varying degrees. The modalities

mediated by small unmyelinated fibers, such as pain and warm temperature sensation and autonomic function, are often affected first.

Clinically detectable impairment of touch sensation and motor function frequently follows after several months. Unfortunately, tools that

allow reliable and safe testing of pain and temperature sensation and

autonomic function often are not available at peripheral health facilities, but simple and reliable tests of touch sensation and motor function

do provide a reflection of the underlying neuropathy.

TOUCH SENSATION TESTING The ulnar and median nerves and the

posterior tibial nerve are usually tested for touch sensation. The most

reliable test is the Semmes-Weinstein monofilament (SWM) test. If

the impairment is of <6 months’ duration and/or new nerve function

impairment is diagnosed, glucocorticoid treatment should be given.

Because filaments are not available in most peripheral health centers,

the WHO recommends that a ballpoint pen be used instead. The testing protocol is the same as in the SWM test: the stimulus is delivered

by touching the test sites with the tip of a ballpoint pen held at an angle

of ~45° relative to the skin.

VOLUNTARY MUSCLE TESTING Motor function of the hands and feet

should be evaluated by voluntary muscle testing. The muscle functions

most affected in leprosy are eye closure (facial nerve), finger abduction (ulnar nerve), thumb opposition (median nerve), wrist extension (radial nerve), and ankle extension (common peroneal nerve).

Strength is assessed with a WHO-recommended system as strong,

weak, or paralyzed.

NERVE CONDUCTION TESTS Testing of nerve conduction parameters

is sensitive in detecting early signs of peripheral neuropathy in leprosy. Sensory nerve conduction parameters are often affected several

months ahead of clinical tests (e.g., the SWM test). However, a trial of

glucocorticoid treatment of such early changes did not show improved

long-term outcomes, perhaps suggesting that the glucocorticoids are

unable to switch off or reverse the pathologic process.

1389CHAPTER 179 Leprosy

ULTRASOUND TESTING OF NERVES Palpable enlargement of certain

peripheral nerves is one of the cardinal signs of leprosy. Definite

enlargement is easy to establish, but milder degrees are much harder to

diagnose by palpation. Ultrasound imaging and measurement of nerve

diameters—even with portable equipment—can detect nerve enlargement accurately. This technique may be used to support the diagnosis

of leprosy and may indicate the onset of neuropathy that warrants

anti-inflammatory treatment.

OTHER TESTS OF PERIPHERAL NERVE FUNCTION Pain and temperature

sensation are commonly affected in leprosy neuropathy. However,

these sensations are difficult to test safely and reliably under field

conditions. Studies have shown that heat detection thresholds are

often affected several months before touch sensation is impaired. Laser

Doppler measurement of autonomic vasomotor reflexes is a sensitive

method for detection of peripheral autonomic nerve damage in leprosy

patients.

TREATMENT

Leprosy, Leprosy Reactions, And Other

Major Manifestations

TREATMENT OF LEPROSY

Multidrug Therapy Only one multidrug regimen is recommended

by the WHO for the treatment of leprosy. This regimen consists

of a combination of two or three of the following drugs: rifampin, dapsone, and clofazimine (Table 179-1). The keystone of

WHO-recommended multidrug therapy for multibacillary leprosy

is a monthly dose of rifampin together with daily doses of dapsone

and daily and monthly doses of clofazimine. Patients with paucibacillary leprosy are treated with two drugs, receiving monthly doses

of rifampin and daily doses of dapsone. The treatment duration is

12 months for multibacillary disease and 6 months for paucibacillary disease. Provided that patients complete therapy, treatment

failure rates are very low.

Some studies have investigated a uniform regimen of three

drugs for 6 months. In a recent systematic review of evidence on

the potential benefits and risks of this shorter regimen, the WHO

concluded that relevant evidence is limited and inconclusive, with a

potential increase in the risk of relapse. Therefore, the WHO does

not recommend a shortened treatment duration for multibacillary

leprosy.

The WHO further recommends supervised intake, but actual

practice varies among countries. Through the WHO, multidrug

therapy is provided free of charge as blister packs for adults to all

countries reporting leprosy. Blister packs are also provided for 10-

to 14-year-olds, while younger children are given doses adjusted

according to body weight (Table 179-1).

Adverse Events •  Rifampin Rifampin acts by inhibiting

DNA-dependent RNA polymerase, thereby interfering with bacterial RNA synthesis. Rifampin is well absorbed orally. Hepatotoxicity

may occur with a mild transient elevation of hepatic aminotransferases, but this reaction is rare at the dosages and intervals recommended for leprosy and is not an indication for discontinuation

of treatment. Because rifampin is given only monthly in WHOrecommended multidrug therapy regimens, the adverse effects

recognized from its use in tuberculosis probably do not occur. A

monthly dose of rifampin probably does not cause induction of

hepatic cytochrome p450, but this outcome has not been formally

assessed. Urine discoloration occurs but is harmless.

Dapsone Dapsone (4,4-diaminodiphenyl sulfone [DDS]) acts by

blocking folic acid synthesis and is only weakly bactericidal. Oral

absorption is good, and the drug has a long half-life averaging 28 h.

Dapsone has a poor safety profile, and its use should be monitored

carefully. In the doses recommended for leprosy, it can cause mild

hemolysis and may cause anemia or, rarely, psychosis. Glucose-6-

phosphate dehydrogenase deficiency seldom causes a problem, and

enzyme levels are not routinely tested before the start of multidrug

treatment. On the other hand, the “DDS syndrome” (also called the

dapsone hypersensitivity syndrome) is a severe adverse event that

is not uncommon in some countries. It usually develops 6 weeks

after the commencement of dapsone administration and manifests

as fever, skin rash, eosinophilia, lymphadenopathy, hepatitis, and

encephalopathy. Other rare but severe cutaneous adverse reactions

are erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis. The fatality rate for DDS

syndrome is 10%, with death occurring from liver failure, sepsis,

and bone marrow failure. Most patients require treatment with

systemic glucocorticoids. In all cases, dapsone treatment must be

stopped. Agranulocytosis, hepatitis, and cholestatic jaundice occur

rarely with dapsone therapy.

Clofazimine Clofazimine is a brick-red, fat-soluble crystalline

dye. The mechanism of its weakly bactericidal action against

M. leprae is not known. High drug concentrations are found in the

intestinal mucosa, mesenteric lymph nodes, and body fat. The most

noticeable adverse event is skin discoloration ranging from red to

purple or black, with the degree of discoloration depending on the

dosage. Clofazimine can accumulate in active leprosy skin lesions,

thus making them more prominent. The abnormal pigmentation

usually fades within 6–12 months of clofazimine discontinuation,

although traces of discoloration may remain for up to 4 years. The

skin discoloration associated with clofazimine is psychologically

distressing for many people. Patients often stop taking the drug

because the discoloration is socially disabling for them, alerting

their social environment to the fact that they are taking anti-leprosy medication and thus breaking confidentiality about treatment.

Urine, sputum, and sweat may become pink during clofazimine

administration. Clofazimine also produces a characteristic ichthyosis on the shins and forearms. Adverse gastrointestinal events

ranging from mild cramps to diarrhea and weight loss may result

from clofazimine crystal deposition in the wall of the small bowel.

Relapse The cure rate for leprosy with multidrug therapy is 99%,

but relapse is possible. In multibacillary leprosy, relapse is defined

as the multiplication of M. leprae, with an increase of at least 2+

over the previous value in the bacteriologic index at any single site;

TABLE 179-1 WHO-Recommended Multidrug Treatment for Leprosy

DRUG, AGE GROUP

PAUCIBACILLARY

LEPROSYa

MULTIBACILLARY

LEPROSYb

Dapsone

Adult 100 mg/d 100 mg/d

Child age 10–14 years 50 mg/d 50 mg/d

Child <10 years Dose adjusted to body

weight

Dose adjusted to body

weight

Rifampin

Adult 600 mg monthly 600 mg monthly

Child 10–14 years 450 mg monthly 450 mg monthly

Child <10 years Dose adjusted to body

weight

Dose adjusted to body

weight

Clofaziminec

Adult — 50 mg/d plus 300 mg

monthly

Child 10–14 years — 50 mg/d plus 150 mg

monthly

Child <10 years — Dose adjusted to body

weight

a

Duration: 6 doses (6 blister packs). b

Duration: 12 doses (12 blister packs). c

In

2018, the World Health Organization (WHO) suggested including clofazimine in the

multidrug therapy regimen for paucibacillary leprosy as well, but it is questionable

whether this suggestion will be implemented because of the possibility that skin

discoloration might compromise compliance. In addition, this alteration would

involve a major change in the production of blister packs, which currently do not

include clofazimine for paucibacillary leprosy patients (in line with the original WHO

recommendation).

1390 PART 5 Infectious Diseases

this change usually occurs in conjunction with evidence of clinical

deterioration (e.g., new skin patches or nodules and/or new nerve

damage). Relapse rates are well below 1% except among a small proportion of patients who have a very high bacillary load at the start

of treatment (bacteriologic index ≥4). In different studies, four to

seven relapses were recorded per 100 person-years. These relapses

usually occurred <5 years after the end of multidrug therapy. Since

antimicrobial resistance to the combination of drugs used in multidrug treatment is rare, patients with relapse can be re-treated with

the same multibacillary regimen.

Recognizing a relapse in paucibacillary leprosy can be difficult,

as symptoms may resemble T1R. However, relapse of paucibacillary disease is very rare. Administration of a therapeutic trial with

glucocorticoids to patients with new lesions may help distinguish

between these two phenomena: a definite improvement within

4 weeks of initiation of glucocorticoid therapy indicates T1R,

whereas a lack of response favors the diagnosis of a clinical relapse.

Patients with multibacillary disease who present with a relapse are

re-treated with the multidrug regimen regardless of any change in

classification. Patients with paucibacillary disease require 2 years of

monitoring after treatment and patients with multibacillary disease

at least 5 years. Re-infection by different strains of M. leprae is possible and can be confused with relapse.

Rifampin Resistance and Second-Line Drugs Resistance to rifampin has been reported from several countries, although the number

of patients involved is small. Evidence on the potential benefits

and risks of using alternative regimens for drug-resistant leprosy

is not available. Therefore, recommendations provided by the

WHO for second-line regimens are based on expert opinion and

the known activity of alternative drugs, including the likelihood of

cross-resistance. For rifampin-resistant leprosy, the WHO guidelines recommend daily treatment with at least two second-line

drugs—clarithromycin, minocycline, or a quinolone (ofloxacin,

levofloxacin, or moxifloxacin)—plus clofazimine for 6 months,

followed by clofazimine plus one of the second-line drugs daily for

an additional 18 months. Leprosy patients infected with M. leprae

resistant to both rifampin and ofloxacin may be treated daily with

the following regimen: clarithromycin, minocycline, and clofazimine for 6 months, followed by clarithromycin or minocycline plus

clofazimine for an additional 18 months.

TREATMENT OF LEPROSY REACTIONS

Type 1 Reactions Oral, short-acting glucocorticoids are the

treatment of choice for T1R. Prednisolone is used most often in

an initial dose of 1 mg/kg of body weight once a day, usually with

a maximum of 60–80 mg. If standard treatment protocols are

followed, as they are in most leprosy programs in endemic countries, an initial dose of 40 mg of prednisolone is recommended

by the WHO. The dose is tapered slowly, usually by 5 mg every

2 weeks over a period of 20 weeks—a schedule that results in better

outcomes and lower reaction relapse rates than the previously recommended 12-week glucocorticoid regimen. However, the clinical

response should guide treatment. Patients should be examined

every 2 weeks, and the examination should include a quick nerve

function assessment. Not infrequently, the reaction flares up again

once the daily glucocorticoid dose is tapered to <10–20 mg. The

potential benefits of longer treatment should be balanced against

the risks of prolonged glucocorticoid use, especially at higher doses.

Type 2 Reactions Mild first-time T2R (or ENL) reactions with

localized skin nodules may be treated with aspirin and pentoxifylline. If a rapid effect is needed, the most effective drug to date is thalidomide, which rapidly suppresses clinical signs, including nerve

impairment and iritis. However, the drug is blacklisted in many

countries because of its teratogenicity. If available, it should be given

with great caution to women of childbearing age—only after careful

counseling and a negative pregnancy test and with strict adherence

to contraception. A dose of 100–200 mg is given either once or

twice daily. In acute first episodes, thalidomide treatment should

be tapered down and stopped after 1–2 weeks. If tissues other than

the skin are affected—e.g., the eyes (iritis/uveitis), testes (orchitis),

kidneys (nephritis), or joints (arthritis)—longer treatment may be

needed until signs and symptoms have resolved. In patients with

severe recurrent ENL, a daily thalidomide maintenance dose of

50 mg may be effective in suppressing new episodes. Because of

the restricted availability and use of thalidomide, patients with

acute ENL are usually treated with glucocorticoids. T2R tends to

be transient, often resolving in ~2 weeks. The treatment strategy is

therefore to suppress the acute signs and symptoms with high-dose

oral prednisolone, quickly tapering treatment in 2–3 weeks either

to zero or to a low maintenance dose if the patient has had previous attacks. High-dose clofazimine also is effective in preventing

recurrent ENL, but attainment of a maximal effect takes several

weeks. The usual regimen is 300 mg daily for 1 month, followed by

200 mg daily for 1 month and, subsequently, 100 mg daily as a

maintenance dose for as long as necessary. Prolonged use of highdose clofazimine may cause significant adverse gastrointestinal

effects. An important side effect of clofazimine is a dark discoloration of the skin. While discoloration resolves gradually after the

drug is discontinued, it is one main reason that patients dislike or

even refuse to take clofazimine.

TREATMENT AND PROGNOSIS OF NERVE

FUNCTION IMPAIRMENT

Episodes of sensory or motor nerve function impairment without

skin signs are common. Neuropathy may occur without obvious

neuritis. Still, the treatment of such “silent neuropathy” is the same

as that for T1R. High-dose prednisolone is the drug of choice. Some

experts think that patients will benefit from nerve decompression

surgery, but evidence from randomized controlled trials is lacking.

If glucocorticoid treatment is started shortly after the development of nerve function impairment, the prognosis for full recovery is good. Generally, some recovery can still be expected up to

6 months after onset, but the likelihood of recovery diminishes

with every new episode. Generally, nerve function impairment that

has persisted for >6 months does not benefit from glucocorticoid

treatment.

TREATMENT OF (NEUROPATHIC) PAIN

Pain is common in people affected by leprosy and is often of neuropathic origin. Little evidence-based information is currently available on the origin and treatment of pain in leprosy. Generally, for the

treatment of neuropathic pain, three classes of medication are available: tricyclic antidepressants, phenothiazines, and anticonvulsants

(carbamazepine, oxcarbazepine, gabapentin, and pregabalin). These

agents can be combined with analgesics and anti-inflammatory

drugs according to the patient’s needs.

DISEASE MANAGEMENT DURING TREATMENT

Leprosy can be cured effectively, but the long duration of multidrug

therapy means that careful management is needed to help the patient

complete treatment. Regular visits to a health center may invoke

questions from community members that may threaten the patient’s

privacy, thus causing the patient mental distress and jeopardizing

treatment adherence. Counseling is essential, as are patient-friendly

arrangements for collecting treatment drugs. The disease, its treatment, and its possible complications should be discussed, including

a consideration of disease prognosis, the resolution of skin patches,

skin discoloration by clofazimine, the lack of contagiousness during

multidrug therapy, and the capacity for unrestricted family relations,

including marital life and sexual activity. Possible stigmatization,

including self-stigmatization, also should be discussed.

Because of the diverse complications that are possible, especially

in patients with multibacillary leprosy, a multidisciplinary approach

to patient management is required. In low-income countries, the

responsibility for treatment usually lies with a leprosy control officer or a general medical practitioner. In middle- and high-income

countries, the main treatment responsibility usually falls to a dermatologist. Additional support should come from a neurologist or

1391CHAPTER 179 Leprosy

neurophysiologist for the diagnosis of nerve function impairment,

and a rehabilitation physician, physiotherapist, infectious disease

specialist, and/or psychologist may be needed. Occasionally, specialist support with regard to orthotics as well as in ophthalmology,

occupational therapy, reconstructive surgery, and/or communitybased rehabilitation is indicated.

Supervised Multidrug Therapy Regular treatment is important,

especially the supervised 4-weekly dose of rifampin and clofazimine. However, treatment adherence can be facilitated by flexible

arrangements; for example, patients can be allowed to take home

more than one 4-week blister pack if they will be away for travel or

seasonal labor. In such cases, a family member or another responsible person can be asked to supervise the monthly dose.

Monthly Nerve Function Assessment Since nerve damage can be

insidious and silent, it is important to conduct a brief nerve function

assessment at each clinic visit during multidrug therapy. This regular

assessment is especially important in patients with known risk factors for nerve function impairment. At highest risk are patients with

multibacillary disease, who already have nerve damage at the start of

treatment. Their risk of additional nerve damage is as high as 65%.

Multibacillary leprosy patients without nerve function impairment

at diagnosis and paucibacillary leprosy patients with such impairment at diagnosis have a 16% chance of developing damage and

additional damage, respectively. Patients with paucibacillary disease

who do not have nerve function impairment at diagnosis are at

lowest risk (3%); for them, an assessment at the start and completion of multidrug therapy can be sufficient. Leprosy reactions and

new nerve damage may also occur after completion of multidrug

treatment. While the risk diminishes with time, these manifestations can occur up to 3 years after the conclusion of therapy.

Health Education During treatment, patients will have questions

that need to be addressed in order to ensure their treatment adherence. Sensitive questions may arise regarding everyday life within

the family and at work that, if not addressed properly, could lead

to social withdrawal and mental health issues. Crucial points for

health education are at diagnosis and at completion of treatment.

When communicating the diagnosis, the physician must explain

that the disease is caused by a curable microbial infection and must

cover the possible discomforts of drug intake, the interruption

of disease transmission through drug intake, and the importance

of adhering to treatment to achieve a cure. At the completion of

multidrug therapy, the emphasis should be on separating the concept of cure (bacterial activity) from the sequelae of the disease

(nerve function impairment, leprosy reactions, and disabilities) and

explaining that the patient may need to continue receiving health

care, including reconstructive surgery, for the sequelae. Patients

often associate cure with the absence of symptoms, which is not

accurate in leprosy. Some patients will experience discomfort during bacterial activity but will have no sequelae after treatment. In

others, nerve function impairment or leprosy reactions may cause

disfigurement with physical discomfort after cure; these sequelae

will need further management. Disabilities such as claw hand or

neuropathic foot require chronic care.

Guidelines after the Completion of Multidrug Therapy Patients

should receive counseling at release from treatment. The topics

covered should include reassurance that the person is no longer

contagious, that in some patients hypopigmentation in skin lesions

may not resolve for a long time, and that skin discoloration due to

clofazimine will gradually disappear in the following months. Nerve

impairment may continue to improve after release from treatment,

but this is by no means certain. Most important, patients should

be instructed to return to the clinic if any new skin signs or fresh

nerve damage occurs. This situation is not uncommon, is usually

due to a leprosy reaction, and should be managed carefully from

both a medical and a social perspective, since patients and persons

in their environment will interpret this development as “leprosy

coming back.” Patients at risk of further episodes of reaction and/

or additional nerve function impairment (e.g., patients with preexisting nerve function impairment and multibacillary infection or

patients who have experienced a reactional episode during therapy)

should be asked to return for a check-up every 6 months for at least

3 years after being released from treatment.

■ REHABILITATION AND SOCIAL ASPECTS

Physical Rehabilitation Peripheral neuropathy and its secondary disabling consequences often require physical rehabilitation. This

effort may include reconstructive surgery in the case of facial, ulnar,

median, or posterior tibial paralysis. In this case, pre- and postoperative physical therapy is of crucial importance. Physical therapy is also

indicated when muscles are not completely paralyzed or when contractures are too stiff to allow surgery. Since paralysis is usually accompanied by sensory and autonomic neuropathy, occupational therapy

also is helpful; therapists teach patients how to minimize the risk of

further injury and other techniques for prevention of disabilities. The

key principle is teaching patients and former patients to self-manage

their disabilities. In many programs, this teaching occurs in the setting

of self-care groups. A well-tested and evidence-based self-care routine

for hands and feet consists of inspection, soaking, scraping, and oiling

(ISSO). Specifically, in ISSO, the person inspects the affected limbs

for hotspots (evidence of too much stress on an area of skin): wounds,

cracks, and calluses. Next the affected limb(s) are soaked in plain water

for 15 minutes. While the skin is wet, areas with excess calluses are

scraped with a rough stone or another rough object. The skin is then

rubbed with petroleum jelly or another nonfragrant oil in order to trap

moisture in the skin. If this routine is performed daily, the skin can

be kept supple and in good condition, despite sensory and autonomic

damage. If sensation on the soles of the feet is impaired, the person

must wear protective footwear. Simple footwear (e.g., sandals or sneakers) available at the local market is adequate as long as it has a strong

sole and a soft insole of ethylene-vinyl acetate or microcellular rubber

that distributes pressure—an especially important feature when foot

muscles are weak or paralyzed or the architecture of the foot is damaged, as is often the case with neuropathy. In high-resource settings,

tailor-made orthopedic shoes can be provided.

Mental and Social Support Like other chronic health conditions,

leprosy requires patients to cope with the burden of new routines in

everyday life. In addition to coping with stigma, they must organize

themselves for prolonged treatment, prevention of disabilities, and

rehabilitation activities. Moreover, like other neglected tropical diseases (see “Neglected Tropical Diseases,” below), leprosy may lead to

poor mental health. Such diseases are accompanied by social exclusion

in the form of poor access to services such as health care, education,

employment, and housing. This exclusion accounts for common

mental health comorbidities in leprosy patients and their family members, including depression, anxiety, and suicidal thoughts. Leprosy is

probably the most notorious of all stigmatized health conditions, and

social stigmatization is the most common issue that triggers mental

suffering. Other infectious diseases that raise this issue include HIV

infection, tuberculosis, and neglected tropical diseases like lymphatic

filariasis, Buruli ulcer, and dermal leishmaniasis. Although the reasons for stigmatization vary, the manifestations and interventions that

effectively reduce stigma are similar across conditions and countries.

Therefore, joint interventions addressing health-related stigmas for

multiple conditions would be strategically and financially attractive.

The need to introduce mental health care in leprosy services is pressing. Therapeutic group meetings among institutionalized patients and

self-care groups at the community level, with a focus on prevention of

disabilities and mental well-being, are known to ameliorate depression,

encourage self-acceptance, and promote confidence.

NEGLECTED TROPICAL DISEASES Leprosy is one of a medically diverse

group of 20 neglected tropical diseases (NTDs). This group includes

infectious diseases caused by bacteria, viruses, fungi, and parasites

as well as some noninfectious conditions, such as podoconiosis and

snakebite. NTDs have been grouped together because they affect