Actas Dermosifiliogr.



Leprosy. An Update: Definition, Pathogenesis, Classification,
Diagnosis, and Treatment夽
K. Eichelmann,∗ S.E. González González, J.C. Salas-Alanis, J. Ocampo-Candiani

Servicio de Dermatología, Hospital Universitario José Eleuterio González, Monterrey Nuevo León, Mexico

Received 29 July 2011; accepted 11 March 2012
Available online 17 July 2013

KEYWORDS Abstract Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium
Leprosy; leprae. It primarily affects the skin and peripheral nerves and is still endemic in various
Paucibacillary; regions of the world. Clinical presentation depends on the patient’s immune status at the
Multibacillary; time of infection and during the course of the disease. Leprosy is associated with disability and
Multidrug therapy; marginalization.
Hansen disease; Diagnosis is clinical and is made when the patient has at least 1 of the following cardinal
Mycobacteria leprae; signs specified by the World Health Organization: hypopigmented or erythematous macules
Disability; with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear or skin biopsy
Smear test with loss of adnexa at affected sites.
Leprosy is treated with a multidrug combination of rifampicin, clofazimine, and dapsone. Two
main regimens are used depending on whether the patient has paucibacillary or multibacillary
© 2011 Elsevier España, S.L. and AEDV. All rights reserved.

PALABRAS CLAVE Lepra: Puesta al día. Definición, patogénesis, clasificación, diagnóstico y tratamiento
Paucibacilar; Resumen La lepra es una enfermedad granulomatosa crónica causado por una micobacteria
Multibacilar; (M. leprae) que presenta predisposición por la piel y nervios periféricos. La lepra continúa
Multiterapia; siendo endémica en distintas regiones del mundo. La presentación clínica de la enfermedad
Enfermedad de depende del estado inmunológico del paciente al adquirirla y durante la evolución de la misma.
Hansen; Es una infección que se asocia a discapacidad y marginación.
M. leprae; El diagnóstico de lepra es clínico y se hace al tener uno o más de los signos cardinales estable-
Discapacidad; cidos por la OMS; máculas hipopigmentadas o eritematosas con disminución de la sensibilidad,
Baciloscopia engrosamiento de los nervios periféricos y la demostración de bacilos ácido alcohol resistente
en una baciloscopia o biopsia de piel, con pérdida de anexos en los sitios afectados.

夽 Please cite this article as: Eichelmann K, et al. Lepra: Puesta al día. Definición, patogénesis, clasificación, diagnóstico y tratamiento.

Actas Dermosifiliogr. 2013;104:554---63.
∗ Corresponding author.

E-mail address: (K. Eichelmann).

1578-2190/$ – see front matter © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

A new pathogen. Mycobacterium lepromatosis. where nerves.L. at the beginning of 2010 the worldwide prevalence was 211 903 cases. y AEDV. The taxonomic order is new antibiotics of proven efficacy have made it possible Actinomycetales. and 2007 saw 254 252 new 299 036 cases registered. The reported prevalence of lep. Classification.5 19th century by the Norwegian physician Gerhard Henrik Armauer Hansen. World Incidence of Leprosy with southeast Asia having the largest number (166 115 new 600 000 cases). Existen principalmente dos modalidades de tratamiento dependiendo de la presentación clínica del paciente como paucibacilar o multibacilar. and Birmania. and Treatment 555 El tratamiento es con tres drogas. Brasil. A total of 244 796 new cases were registered in 2009.3 These collecting in intracellular groups called globi. Mycobacterium leprae. rifampicina. which was identified in the Saharan Africa. cause endemic disease in Mexico and the Caribbean. An Update: Definition. is a chronic granulomatous bac.3 ␮m in diameter. © 2011 Elsevier España.4 Currently this mycobacterial infection 514 718 500 000 is endemic in more than 15 countries. like other mycobacteria.4 India 407 791 registered 64% of all cases. has recently been found to The leprosy bacillus has a predilection for macrophages. the WHO proposed their 200 000 ‘‘final push strategy’’ for leprosy with the clear purpose of elimination. reticuloendothelial system and peripheral nervous system thickened peripheral nerves. The disease is caused by an obligate intracellular most imported cases have come from South America or sub- bacillus. 1). Diagnosis. M leprae has been grown in the cope with a problem that is still far from resolved. M leprae to meet the WHO’s targeted reduction in the incidence of organisms are slightly curved. Pathogenesis. S. Todos los derechos reservados. but the disease remains highly prevalent 0 2003 2004 2005 2006 2007 2008 2009 in other parts of the world. Source: period of treatment recommended by the WHO or to the Global Leprosy Situation 2010. this mycobacterium is the only fast smear or skin biopsy. Replication takes from 11 to 13 days. Lower prevalence rates are unre- lated to the reduction in the number of new cases found. but 83% of the cases are found in 3 countries: India. they replicate by binary fission. Reports on the situations in 141 countries were sent to the WHO in the final months of 2010. This change in prevalence does not reflect a decrease in Figure 1 Number of new cases registered from 2003 to 2009 in M leprae transmission. gram-positive obligate signs specified by the World Health Organization (WHO): intracellular bacillus that shows tropism for cells of the hypopigmented or erythematous macules with sensory loss. it is related to the shorter 16 countries reporting more than 1000 cases each year. countries where the disease is endemic.4 Countries like the Democratic Republic of the Congo and Mozambique reported reaching the goal. 244 796 At the beginning of the 1990s. 400 000 rosy was 212 802 cases in 2008. or leprosy. rather. clofazimina y dapsona. The number of cases fell by 11 100 (4%) 300 000 265 661 258 133 249 007 from 2006 to 2007 (Fig.4 . The effi- National leprosy programs implemented from 2006 through cacy of this pathogen within a narrow ecological niche is 2010 were successful in meeting the WHO’s target for regions where leprosy is endemic. one example is Spain. and a positive acid-alcohol.2.2 Modern multidrug therapy and one with these characteristics. Countries where leprosy had previously been eliminated terial infection that primarily affects the skin and peripheral report a rise in imported cases. Although developments call for new medical perspectives on how to never cultured in vitro.1 The clinical presentation and histopatho- logic changes depend on the immune status of the patient Microbiology and Immunology at the time of infection and over the natural course of the disease. Predisposed to infect cold areas of the body such as the skin. foot pads of 9-banded armadillos. Hansen disease. Introduction exclusion from registries of patients who have been cured or who have died. defined as a prevalence below a single case per 100 000 10 000 inhabitants in endemic regions. (notably Schwann cells). the family Mycobacteriaceae.Leprosy. nasal mucosa and periph- Epidemiology eral nerves (especially superficial ones). Diagnosis is currently based on 3 cardinal M leprae is an acid-alcohol-fast. considerably longer than the 20 hours required by Mycobacterium tuberculosis. M leprae grows best at temperatures between 27 ◦ C and 30 ◦ C. measure from 1 to 8 ␮m in M leprae infection to a single case per 10 000 inhabitants in length and 0.

and increased neutrophilic infiltration a patient develops.2 The immune response to M leprae is variable and gives rise to spontaneously changing clinical manifestations. Immunohis- tochemical findings in skin biopsies show mainly interleukins 4 and 10.10 The possibility may affect any area of the body. in lepromatous lep. A type histiocytes arranged in a concentric pattern. thereby inactivating func- tions such as extracellular reproduction. Hematoxylin-eosin. Although the mechanism by which the pathogen is trans- rosy. mosome 10p13 near the mannose receptor 1 gene.556 K. primarily explained by the properties conferred by 2 struc- tural elements: the capsule and the cell wall. showing foamy necrosis factor----rise and CD4+ T cells are activated. deposition associated with systemic toxicity. a type III hypersensitivity reaction due to immune complex class II HLA/major histocompatibility complex genes at chro. One of the most important findings is the scarcity or absence of acid-alcohol-fast bacilli (Figs. mainly phthiocerol dimycocerosate and phenolic glucolipid- 1. with clinical manifesta. 4 and 5). Overcrowding and pro- annular or ovoid. which is an antigen for the macrophage.9 Blood levels of cytokines----such as interferon-␥ and tumor Figure 3 Granuloma in tuberculoid leprosy. few CD4+ and CD8+ T cells are present.7 Development of the disease. associated with a susceptibility locus at chro. multinucleated giant cells.6. depends on the patient’s immune status. other immune system components have been associated with clinical phenotype and course of disease. original magnification ×100. Reac- tions are related to immune system changes. The HLA-DR2 and HLA-DR3 genes have and complement deposition in the skin.8 In addition. M leprae has a predilection for Schwann cells. This type devel- been linked to tuberculoid leprosy whereas HLA-DQ1 is most ops mainly in cases of dimorphous (borderline) leprosy and often found in patients with the lepromatous form. elevated tumor mosome 6 have also been implicated in the type of leprosy necrosis factor levels. stress. The lepromatous form affects the skin and peripheral mitted is poorly understood. which is expressed specifically in the basal lam- ina of peripheral nerves. causing well-defined infiltrated plaques that are transmissibility of M leprae is low. A role for the dermis is composed of epithelioid cells surrounded by T genetics. Thus. original magnification ×400. mannose receptors on the surface of macrophages are important in phagocytosis. has now been suggested. which may present as type 1 or 2 leprosy reactions. specific cellular response is seen in cases at the Contagion tuberculoid pole. a set of metabolic and reproductive functions make M leprae an obligate intracellular bacterium with a long reproductive cycle. cells. . Hematoxylin- 2 (or erythema nodosum leprosum) reaction corresponds to eosin. such as those caused by antileprosy medication. Many lepromatous leprosy. Eichelmann et al. Once the pathogen penetrates a cell. 2 and 3). Figure 2 Tuberculoid leprosy. we do know that the nerves. although a few may sometimes be observed. Granulomatous inflammation in tions. organized.6 The capsule is made up of a large number of lipids.2. An intense. replication proceeds slowly until T cells recognize the mycobacterial antigens and a chronic inflammatory reaction begins. or pregnancy. explained by specific binding to the G domain of the laminin-␣2 chain. and CD4+ T cells that secrete interferon-␥.7 Another impor- tant component of the cell wall is lipoarabinomannan. A type 1 reversal reaction involves type IV hypersensitivity. which is the target of an intense immunoglobulin M-mediated humoral immune response. and granulomas do not usually form (Figs. The immunologic and clinical situation is different in lep- romatous leprosy as there is no specific immune response. Many of the functional genes found in other mycobacteria have been silenced or transformed into pseudogenes. whereas an absence of a specific immune response is seen at the opposite pole. These lesions are usually anesthetic and longed contact are known risk factors. Biopsy of the skin and region surrounding nerves reveals granulomas with an abundance of epithelioid histiocytes. Bacilli proliferate in the tissues and foamy macrophages can be observed.

as a large number of multibacillary cases a role in transmission. initial stage of the disease. Lepromatous leprosy (Fig. borderline tuberculoid. Bacteriology will be pos- itive and the Mitsuda reaction (intradermal lepromin test) will be negative due to the absence of specific cell-mediated immunity. tuberculoid and dimorphous (borderline) leprosy. systemic. but the Mitsuda reaction will be positive and granulomas are typically found on biopsy. Tuberculoid leprosy (Fig. the WHO’s reported to harbor as many as 7000 million bacilli in a Expert Committee on Leprosy determined that treatment gram of tissue. tion has been shown to be possible in immunodeficient mice. Lesion borders are ele- tous leprosy. or borderline border- Grenz zone. vated and erythematous and the centers are atrophic. usually becoming lepromatous. however. A disseminated skin condition is often the reason patients seek care. on the order of a practical. original magnification ×100. M leprae has been found in high num.13 Classification The Ridley-Jopling clinical classification system (Fig. mother-child dyads should be followed. The bacterial load is All dimorphous or indeterminate cases progress toward a high in patients with lepromatous leprosy. These unstable cases eventu- ally move toward one of the poles but progression can be halted with treatment and a cure is possible. and aerosol inocula. is the most widely used. rapid means of classification was established for million bacilli in total. mainly in India. In fact. fomites can play fect. superficial peripheral As leprosy is not a highly contagious disease. Hematoxylin-eosin. could be started before smear tests were done.15 This system is imper- period ranging from 36 hours to 9 days.12 As vertical trans- mission has been reported.2. cases are borderline Figure 4 Lepromatous leprosy. ber no more than 5. but the possibility cannot be ruled out. who have been pole. certain nerves. Figure 5 Abundance of acid-alcohol-fast bacilli in leproma. based on the patient’s clinical state and immune status. and certain organs (e. with repercussions on a point of entry for the bacillus. mission has recently been studied. this hypothesis has never been proven. 6). Tuberculoid Leprosy At the tuberculoid pole (tuberculoid and borderline tuber- culoid cases) the disease manifests with a few well-defined. 7) is con- sidered to be at the dynamic. referring to lepromatous.g. is easy in this stage. Diagnosis.14 The disease is organized in 2 poles and an intermediate state. Clinical Findings No relationship between the bacillus and a vector has been established. Fite-Faraco. Cases of tuberculoid leprosy transmitted through tattooing have been reported.4. The bacillus is not detectable on bacteriology. cases with 6 or more skin lesions As the viability of bacilli outside the body extends over a are classified as multibacillary. Classification. and infectious end of the spectrum. 8) is stable. Leprosy affects primarily the skin. pre- ceded by the word borderline (thus. Macrophages and foamy areas around blood vessels line). treatment. original magnification ×400. Pathogenesis. and may even be self-limiting. and Treatment 557 conditions must be met before a host can be infected. the testicles).10 Although the skin has been suggested to be a possible route Paucibacillary cases are those in which skin lesions num- of transmission. although clinical diagnosis is difficult. Indeterminate cases are considered to represent the can be seen. although they may also complain of numbness and other types of paresthesia or systemic signs such as fever and weight loss. hypopigmented anesthetic macules. respec- tively. the eyes. whereas in other forms of the disease.. progressive. In 1998. worldwide application without need for diagnostic equip- bers (100 million viable bacilli per day) in nasal mucosa. rarely con- tagious. The respiratory tract may provide are misclassified as paucibacillary. An Update: Definition. thus. a the load is known to be much lower. a cure that the respiratory tract plays a significant role in trans. Epidermal atrophy with a lepromatous.Leprosy. .11 ment and without putting health care workers at risk. Dimorphous cases are classified according to which pole (lepromatous or tuberculoid) they tend toward.

IFN-γ Tuberculoid leprosy Figure 6 Clinical and immunologic classification system for leprosy. interleukin. and this type of leprosy Lepromatous Leprosy The lepromatous pole of the spectrum (lepromatous lep- rosy and borderline lepromatous cases) is characterized by confluent papules and nodules. Figure 8 Tuberculoid leprosy: a single. diffuse infiltration of the skin and giving rise to leonine facies and madarosis. This form strong. hairless plaque with Figure 7 Typical leonine facies in lepromatous leprosy.558 K. Nodular and diffuse forms of lepromatous disease have been observed. Lepromatous leprosy Humoral immunity IL-4. Early in the disease the skin appears infiltrated and waxy. This pole of the leprosy spectrum is characterized by greater nerve involvement and more severe disability. well-defined borders. IL. Because the patient is immunocompetent. is associated with anhydrosis and loss of adnexal struc- tures. possibly resulting in marked. There is usually no loss of sensation on the face because may resolve spontaneously if the host’s immune system is of the abundant sensory innervation there. Lesions are usually symmetrical and bilat- eral. . IFN-␥ refers to interferón gamma. IL-10 Cell-mediated immunity Reversal reaction INDERTERMINATE DIMORPHOUS CASES CASES IL-2. lesions are not usually large or numerous. Eichelmann et al.

An Update: Definition. When small cutaneous nerve fibers become involved. and cases progress to lepromatous disease. several times along the course of disease. A thickened peripheral nerve and is due to a cell-mediated hypersensitivity mechanism 3. fever. mak- erythematous. involvement causes thickening. Dejerine-Sottas.20 phous leprosy present with scaly. orchitis related to erythema nodosum. ulceration. mainly atrophy and acute disease.24 The main ocu- 60% of patients with lepromatous leprosy and may recur lar manifestations of leprosy are lagophthalmos. namely primary amyloidosis and other hereditary phous leprosy requires appropriate treatment. 1. ation that peripheral nerve thickening also occurs in other Considered an unstable. Clinical Signs and Symptoms The leprosy bacillus targets the peripheral nervous system.. the result is numbness. before irreversible damage has occurred.g. Nerve well-defined internal borders and atrophic centers.22 The most common skeletal signs are nonspecific. Charcot-Marie-Tooth.16 the following signs: A reversal reaction (type 1) can develop in interpo- lar cases and is associated with hormonal changes. Differential diagnosis must take into consider- be acute or subacute and cases are initially indeterminate. Typical manifestations are erythe- matous macules with a congestive appearance and blisters. Patients with the lepromatous form have been reported defined internal borders predict progression to lepromatous to develop testicular compromise. cubital. the leprosy. primarily the poste- rior tibial. and sensory and motor impairment. diseases.19 A Figure 9 Dimorphous leprosy characterized by infiltrated. It is important to remember that occasion. This leprosy reaction develops in around skin. Timely start of effec- tive treatment. The course of these nodules is subacute. mainly on the lower limbs but occasionally on the trunk. anhydrosis. This antigenic reaction lesion is caused by variations in the patient’s immune status 2. is diffuse leproma- nied by systemic symptoms with changes in the patient’s tous leprosy.15 Painful nod.15 The diagnosis is made when an individual who between Lucio’s phenomenon and M lepromatosis is under has not completed a course of treatment has 1 or more of study. Immune complex signs set out by the WHO’s Expert Committee on Leprosy deposition is the mechanism of action. The relationship in 1997. which is characterized by diffuse infiltration general state of health: fatigue. and thermal Dimorphous Cases sensory impairment. due to direct infiltration or through damage to the optic nerve. transient clinical state. with singular projections on the ears. Patients with dimor. Refsum diseases). A positive skin smear or bacilli observed in a biopsy . which consists of red congestive macules that progress to blisters and necrotic Leprosy is diagnosed clinically on the basis of 3 cardinal slough. and/or necrosis. A variant of a type 2 leprosy reaction causes necrotic Diagnosis erythema. Diagnosis.Leprosy. Pathogenesis. erythematous plaques The musculoskeletal system is affected in 95% of that may be circular or annular. and fractures. joint pain. Nearly all diseases (e. the lesion atrophies and there is loss of adnexa. Classification. osteoporosis is the second most common sign in patients with nal borders of annular lesions are well defined. with borders that are cases. scaly plaques that are annular in shape and have ing the nerves palpable during physical examination. ules appear. such as occur in the puerperium. it has been suggested that when the exter. superficial perineural osteofibrotic reaction develops. An important aspect to watch for in these patients is neuritis. weakness.18 Lesions may affect cutaneous peripheral nerves. described by Lucio and Alvarado in 1851.17 or with drug treatments. On deformities.2. keratitis.19 A frequent variety in Mexico. dimor. diffuse externally and well defined internally. A hypopigmented (or erythematous) anesthetic skin particularly antileprosy regimens. and entropion. 9) may and Nepal. The eye may become involved. In pure neuritic leprosy the neurop- athy is asymmetrical. or Lucio’s phenomenon. whereas well.21. pain. Erythema nodosum leprosum (type 2 reaction) is accompa. medial and lateral peroneal nerves. followed by atrophic scarring. With time as sensory loss secondary to nerve damage leads to ulcers. that gives a myxedematous and atrophic appearance to the and weight loss.23 disease progresses to tuberculoid leprosy. is essential. Eleven percent of patients with multibacillary Acute Reactions disease have been reported to present with loss of vision at the time of diagnosis. and Treatment 559 that develops within months of starting treatment or after treatment has stopped. leading to the wide variety of clinical manifestations that characterize this mycobacterial infection. This variety is most often seen in India The clinical presentation of dimorphous leprosy (Fig.

understood. Currently. reaction is read at 21 days and indicates resistance to the sis. A smear can be obtained from nasal mucosa. giant Langerhans cells. This drug is thought to generate cytotoxic tivity but cross-reactivity with other mycobacteria is known superoxide radicals and to have anti-inflammatory proper- to occur. matous pole show an inflammatory infiltrate with Virchow the rapid decline of infectivity of infected individuals. the likelihood of resurgence is visualize mycobacteria. and Treatment of Leprosy. and cells replete with bacilli and loss of adnexal structures. but per field. By to express the degree of abundance or scarcity of bacteria 2003 leprosy had been eliminated from 117 countries. The strengths of mul- with nerve involvement. Source: Britton et al. the low rate of recurrence and reactions.25---27 Ziehl-Neelsen stain is used to level in a population. Among the requirements leprosy meets are its spread by Smear Test a single means of transmission (from untreated infected individuals) and the possibility of diagnosis by means of The smear test has a specificity of 100% and a sensitivity of simple. effective therapy 50%.15 Although 90% stand in the way of routine use. Minocycline. diagnosis can be based on the phenolic glycolipid ical classification for guiding treatment according to the World 1 (PGL-1) antibody titer and on polymerase chain reaction Health Organization (WHO). and/or skin lesions. This reaction is read at 24 or 48 hours. The gold standard continues to be histopathol- the disease continues to present a public health problem ogy. Eichelmann et al. technique. unlike the situation with tubercu- terial index. practical tools.2 In 1981 the WHO introduced multidrug therapy with rifampicin. Finally.31 All patients should receive this drug combination monthly under super- A skin lesion is biopsied and stained using the Fite-Faraco vision (Table 2). After intradermal injection of 0. rather. Ridley’s logarithmic scale. rash. Under the global initiative for eradicating Hypopigmented or slightly Paucibacillary (1 to 5 skin leprosy in countries where the disease is endemic. have become Thickened peripheral nerves Multibacillary (6 or more available. Although it is for an early (Fernández) reaction and the other for a late known to bind DNA. the usual finding will be granulomas. Treatment thetic macules have appeared. they are used for classification and pro- Treatmenta gnostic purposes. PGL-1 antibody detection is useful in multibacillary cases but is of little use in paucibacillary patients. Table 1 The WHO’s Cardinal Signs for the Clinical Diagno. vomiting. bacilli are not observed.2 (PCR). commonly drugs used as second-line treatments. and clarithromycin are among the rather. leprosy infection does not seem to be unfavorably which are recorded as a number followed by a plus mark influenced by human immunodeficiency virus infection. The Mitsuda ties. the fever are among this drug’s principal adverse effects. It is important to remember that these tests are not Cardinal Signsa Classification for diagnostic. epithelioid cells. its mechanism of action is still poorly (Mitsuda) reaction. clofazimine. Nerve involvement follows a characteristic pattern of distribution and is more marked in The elimination of leprosy as a world health problem multibacillary cases.32 Nonetheless. but When all 3 signs are present diagnostic sensitivity has the cost of this technique and the required infrastructure been reported to be as high as 97% (Table 1). nausea.1 mL of the anti. of paucibacillary cases are diagnosed based on lesion count. as this infectious disease is one of the few that meet certain strict requirements for eradication. Classification. Hepatotoxicity. is used to interpret the smear test results. even though with evident sensory loss more sophisticated tools. or bac- very remote. ofloxacin. and gen (lepromin) in the flexor surface of the forearm. bacillus. A nodule measuring more than 5 mm indicates pos- itivity.560 K. Peripheral nerve thickening normally occurs after anes. this In cases at the tuberculoid pole. up to 30% of multibacillary patients are underdiagnosed. Furthermore. The Fernández reaction has good sensi. in 17 countries. diagno- erythematous macules lesions) sis is based on clinical signs and smear tests. which is derived The lepromin test uses inactivated M leprae extracted from from Streptomyces fungi. tidrug therapy are the prevention of resistance to dapsone. is based on the inhibition of lepromas. is feasible. and a lymphocytic adherence is difficult to achieve. One inspection looks antibacterial activity of clofazimine is low. The reaction is interpreted at 2 moments. RNA synthesis. skin lesions) Positive acid-alcohol-fast Serology smear or skin biopsy a Any single cardinal sign is diagnostic and indicates the clin.28---30 PCR detection of the bacillus is highly specific and sensitive. First-Line Drugs Reaction to Intradermal Lepromin Injection The antibacterial action of rifampicin. an ear is available and once prevalence falls below a certain lobe. Cases that tend toward the lepro. such as serology. the granulomas contain treatment period is long and presents logistical problems. losis. and dapsone (diamin- Skin Biopsy odiphenyl sulfone) for first-line treatment. Its use is associated with a lower incidence of erythema . At the tuberculoid pole. infiltrate.

2. Neuritis is managed with prednisone failure. but their cost pro. but adverse neu. It is also necessary to insist that deformity p-aminobenzoic acid (PABA) antagonism and inhibition of is preventable. The prophy- clofazimine can sometimes be prescribed. in 1992. Like diabetes mellitus. neuritis. 1997). and erythema nodosum. skeletal pain. Mycobacterium avium-intracellulare). presents with erythema. and ciency). and neuritis. study in India found that the combination of BCG with heat- inactivated M leprae conferred 64% protection. although starting the immune system against shared mycobacterial antigens.36 Erythema nodosum is accompanied by fever. and Vaccines dactylitis. in 1995) and one using Mycobacterium habana (see Singh and it can be prescribed at a dosage of 300 mg/d in women of and coworkers. it is the result of secondary infections 2 months of starting treatment. Several vaccines have proven effective to one degree or The treatment of choice is thalidomide. and taught about appropriate Management of Leprosy Reactions footwear and how to care for the feet. reported to confer up to 50% protection against leprosy. but it is known to inhibit tumor necrosis factor. An Update: Definition. Histopathology should be performed at response to current therapies. ties. and Mycobacterium ICRC (based on Thalidomide’s mechanism of action is still poorly under. Pathogenesis.15 The patient should be examined periodically and repeatedly. amyloidosis. especially the feet. It is Hansen disease remains a concern today. Preventing Disability Conclusion Patient education is a crucial aspect of treatment.41 The BCG vaccine itself has been childbearing age or in patients who cannot tolerate thalido. Ulcers that develop secondary to leprosy improve when pressure is eliminated. nodules. ideally. An epidemiologic study of patients with lep- folate synthesis.37. and/or kidney edema. It is associated with hemolysis (mainly rosy in Ethiopia found disability in 61.39 in patients with glucose-6-phosphate-dehydrogenase defi.Leprosy. (pneumonia and tuberculosis).35. there A complete physical examination and smear test should have been reports of accelerated clinical regression and be scheduled every 6 months while multibacillary cases improvement in the bacterial index in patients with a partial are being treated.38 On relapse. the Resistance to rifampicin and to dapsone has been described prevention of sequelae is an important part of the therapeu- in association with the rpoB and folP1 genes. which is the Bacillus Calmette-Guérin (BCG) com- ropathic and teratogenic effects should be watched for. In regions Follow-Up where the Mycobacterium w vaccine has been used along with antileprosy treatment in multibacillary leprosy. Some of the vaccines currently in use are Mycobacterium w ment is ideally withdrawn after 3 to 4 weeks.34 tic agenda for patients with leprosy. on Mycobacterium tufu (proposed by Iushin and Kalianina Clofazimine is a good choice for its anti-inflammatory effect. Thalidomide is lactic effect of a leprosy vaccine is achieved by resetting started at a dosage of 100 to 200 mg/d. and Treatment 561 Table 2 Treatment Stipulated by the World Health Organization. Thus. A type 1 leprosy reaction. dosages as high as 400 mg/d have been described. Clofazimine is contraindicated in kidney failure disease. Dapsone An informed patient will take greater responsibility for fol- is a sulfonamide whose antibacterial mechanism relies on lowing treatment. In paucibacillary cases. proposed by Talwar in 1978. Presentation Monthly. Leprosy should not be a life-threatening disease at this time. Classification. Others are one based stood.33 appropriate care is required to prevent disability. the Convit vaccine introduced the treatment period can be lengthened. but prednisone or another in countries where leprosy is endemic. All physicians important to avoid the stigmatizing of patients with this must have a basic understanding of this disease in order to . Particular care should The second-line drugs are highly active. Supervised Daily Duration Paucibacillary Rifampicin 600 mg Dapsone 100 mg 6 mo Multibacillary Rifampicin 600 mg Clofazimine 50 mg 12 mo Clofazimine 300 mg Dapsone 100 mg Single-lesion paucibacillary Rifampicin 600 mg Single dose Ofloxacin 400 mg Minocycline 100 mg Source: World Health Organization43 nodosum. and is associated with changes in skin coloring. leprosy causes neuropathy.42 A mide. therapy should be withdrawn after a few weeks. which usually occurs in the first When death occurs. who are in contact with relatives who have leprosy. be taken to avert trauma and microtrauma to the extremi- hibits their use as first-choice treatments. respectively. bined with M leprae. In some regions the BCG vac- the end of each treatment cycle. emphasizing that leprosy is not highly contagious.5%. This condition usually develops between the first and second year and there are intermittent relapses.40 at a dosage of 40 to 60 mg/d. cine is administered to children under the age of 12 years histopathology is performed only at the end of treatment. peripheral neuropathy. Diagnosis. treat.

Com. neopterin Dermosifiliogr.191:6067---74. Schurr E. Nasal mucosa study of 9. and genetics of leprosy. Fischetti V.100:756---8. Hu P. 34. Am J Trop colipid 1 antigen. from India. Gidoh M. Bone changes We wish to thank Dr Rodrigo Cepeda Valdés for his valuable in leprosy. Bone changes in leprosy. Dogra S. Thompson EJ.343:432---3. The nasal discharge in leprosy: clinical and Azúa.20:378---80. kDa surface protein of Mycobacterium leprae binds peripheral et al. Indian J Lepr. Herrera-Acosta E. that should no longer exist. Edward VK. J Dermatolog Treat. Fitness J. Rodríguez-Pazos L. Massone C. Lepra importada y su 28. 2010. Leprorreacción tipo 1 y embarazo. Galetta SL. 2002. 23. and C-reactive protein in monitoring leprosy patients dur- 6. P. Reactions following leprosy contacts with positive serology for the phenolic gly- completion of 1 and 2 year multidrug therapy (MDT). lepromatous leprosy. Singh P. Terencio de las Aguas J. J Am Acad Dermatol.76:579--- Med Hyg. 20. Jopling W. a goal that 2010. Pearson JM. Ornamental tattoos and skin lesions. da Silva J. 1997. Alcaïs A. two of whom developed leprosy in infancy. Escalante-Fuentes WG. Duncan ME. 2007. infection. F1000 Medicine Reports. The management of leprosy reversal reactions. 19. Actas Dermosifiliogr. 2011. 87. Shimoji Y. 1998. J Bacteriol. et al. Maeda S. parative sequence analysis of Mycobacterium leprae and the 26. Jakeman P. 18. Indonesia.83:637---44. Lepr 14. 38.102:106---13. social. Smith WC. Weekly epidemiological record. 25. Lepr Rev. 2009. Distribution and persistence of Mycobacterium leprae nasal 2004. 27. 9. Genes Inmmun. Guha S.6:118---25. Britton WJ. 2009. 29. DCMQ. Our current level of J. Sardana K. Busch RJ. Util- dificultad en el medio actual: a propósito de 7 casos.96:9857---62. Garg R. Maeda Y.42:1--- Acknowledgments 13. et al. Methe- 12. Gomez-Flores M. Tattoo moglobinemia and dapsone levels in patients with leprosy. Gelber R. 1999. Pandey A. Corcoran C. A five-group system. et al. 2004.48:11---3. 1983. ML. Actas ity of measuring serum levels of anti-PGL-I antibody. Fernando A. Abalos R. FEMS Microbiol Lett. Proc Natl for early detection of leprosy among close contacts–a pilot study Acad Sci U S A. calls for the concerted efforts of medical.14:319---21. knowledge makes it possible to eliminate leprosy. Riveira J. Braz inoculation borderline tuberculoid leprosy. complexity of certain diseases and provides the basis for 17. Hill A. 1974. Leprosy. Ura S. Rambukkana A. Minerva Anestesiol. Vieira J. Trop Med Int Health. Klatser 2. MR imag- ing of Dejerine-Sottas disease. López-Navarro N.89:381---5. Gulia A. Ng V. BMC Infect Dis. Contreras-Steyls M. Int J Dermatol. political. González-Pérez R. Han XY. Maki DD. Rees RJ. 2008. Fried I. Leprosy as a genetic 30.10:252.76:758--- and scientific resources to prevent the spread of an infection 60. 2010. Matsuoka M. Talidomida en dermatología. Wan-del-Rey de Oliviera disease. Lauris JR.68: 5.25:121---34. Melsom R. Samson PD. An update on the diagnosis and treatment of lep. Ocampo-Candiani J. Thalidomide in leprosy reaction. 13. bacteriological aspects. 1994. Heriberto V. 2011. Kai M.562 K. New insights in the pathogenesis ing multi-drug treatment and reactions. Lepr Rev. 2010. Contagiosidad de la lepra. Leprosy type 1 (reversal) reactions 1966. Chhabriya BD. Ridley D. 2004. Barnetson RS. A et al. Soloeta-Arechavala R. Diaminodiphenylsulfone resistance of Mycobacterium lep- clinical and immunological study of four babies of mothers with rae due to mutations in the dihydropteroate synthase gene. Gupta S. Salgado C. Sharma NC. A study of 50 cases. Complicaciones óseas en un paciente con References lepra lepromatosa. Lancet.51:417---26. 4. Sánchez-Aguilar D. Bührer Sékula S. Global leprosy situation. 2007. 1985. Lepr Rev. Busso P. of leprosy. 36. Vera-Cabrera L. Rao JR. rosy. Nakata N.79:372---86. 21. 2010. Iyer A. Mamm Genome. Diffuse leprosy of Lucio and Latapí: a histo- 1. Vargas-Ocampo F. Naafs B. p.363:1209---19. Inverse sampling to study disease burden new leprosy-causing Mycobacterium lepromatosis. Castillo 301---15. Lepr Rev. Kabanja J. Davey TF. Actas Dermosifiliogr.12:1450---8. a clinical and roentgenological study of 505 cases. Actas Dermosifiliogr. Roberto A. Agrawal GR. Djumadi A. Hatta M. Estado Actual de la Terapéutica de la mine risk factors for Mycobacterium leprae transmission and Lepra. Silva E. 2011. Faget GH. Classification of leprosy according to Rev. 33. 22.132:438---41. R. Kwenang A. Radiology. Martins AN. Dehran M. Britton WJ. Moschella SL. Arrieta-Egurrola A. Martinez A. 2010. Grant A. su actual redescubrimiento y . Aggarwal A. Int J Epidemiol. Lockwood DN.33:1329---36. Gupta S. 37. Ghorpade A. Walker SL. Population survey to deter. 337---48. 1944.18:366---74. 2010. Terencio de las Aguas J.27:2. 2009.22:19---31. Martínez de Lagrán Z. A 21. Balagon M. Menzel S. Int J Lepr Other Mycobact Dis. Conflicts of Interest 2007. 10.51:7---17. Int J Lepr Other Mycobact Dis. cations of the role of mucosal immunity. 2010.57:632--- contribution of reviewing the literature for this article. Genetics of suceptibility to leprosy. 2008. 7. Toribio understanding and treating them. Sehgal V. logic study. Cellona R. The Lancet. Hatta M. Sarkar K. Li J. Matsumura K.49:4366---8. Bakker M. Yousem DM. Madhale S.3:441---53. Management of complications following leprosy: an evolving scenario. Sizer KC.100:615---7. J Clin Microbiol. Transmission and protection in leprosy: indi- Switzerland: World Health Organization. 35. 1995. et al. van Beers S. Trans R Soc Trop Med Hyg. Lockwood DN. por Juan de 11.34:255---73.177:231---5. 16. Das PK. J Infect Dis. Case of Diffuse Revisión de sus orígenes.101:190---1. Lepromatous Leprosy Associated with Mycobacterium lepro- Knowledge of immunopathologic mechanisms reveals the matosis. 31. The authors declare that they have no conflicts of interest. 2009. 1999. Alter A. carriage among a population in which leprosy is endemic in 3. 8. Indian J Med Res. diagnose it and prevent disability and/or contagion. da Costa Martins AC. Gómez-Bernal S. de Wit M. 1999. Eichelmann et al.69:225---34. Ruiz del Portal G. Leprosy: a precipitating factor for com- plex regional pain syndrome. Tosh K. et al. 2010. and their management. AJNR Am J Neuroradiol. Abel L. Braz J Otorhinolaryngol. Miranda A. Mayoral A. Banerjee S. Mahapatra PS.78:248---60. Multiplex PCR technique could be an alternative approach nerve laminin-2 and mediates Schwann cell invasion. Bansal NK. immunity. 24. 32. Madjid B. Ramaprasad P. 15.

Azulay DR. A study of one hundred and fifty autop.42:252--.html# . Pönnighaus JM. Pathogenesis. Int J Lepr Other Mycobact Dis. 2012 [consultado 04 Feb 2011]. Belinchón I.Leprosy.339:636---9. Wilson RJ. Disability 42. Efficacy of BCG vaccine against leprosy and tuberculosis centre in Ethiopia during 1999-2009. 40. Ramos JM. An Bras Dermatol. Available from http://www. 1937. and Treatment 563 sus nuevas aplicaciones. Ogawa M. Classification. Reyes F. Gomez JR. WHO recommended MDT regimens. 41. Diagnosis. Vacinação anti-hansênica. 2011.5:53---60. profile in leprosy patients’ diagnoses in a rural reference leprosy et al. 65. 39. 43. Sterne JA. Msosa E. Gruer PJ. World Health Organization. Dermatología Rev Mex. sies on cases of leprosy. in northern Malawi.77:489---94. Lancet. 1992. An Update: Definition. 1998. who. Lemma D. Mitsuda K. Fine PE.41:51---3. Trop Doct.