Dermatologic Manifestations of Leprosy

Dermatologic Manifestations of Leprosy

No Results

No Results


Leprosy is a chronic granulomatous disease principally affecting the skin and peripheral nervous system. Leprosy is caused by infection with Mycobacterium leprae. Although much improved in the last 25 years, knowledge of the pathogenesis, course, treatment, and prevention of leprosy continues to evolve. The skin lesions and deformities were historically responsible for the stigma attached to leprosy. However, even with proper multidrug therapy (MDT), the extensive sensory and motor damage can result in the deformities and disabilities associated with leprosy. See the image below.

The earliest description of leprosy comes from India around 600 BCE. Leprosy was then described in the Far East around 400 BCE. In the fourth century, leprosy was imported into Europe, where its incidence peaked in the 13th century. Leprosy has now nearly disappeared from Europe. Affected immigrants spread leprosy to North America.

Armauer Hansen discovered M leprae in Norway in 1873. M leprae was the first bacillus to be associated with human disease. Despite this discovery, leprosy was not initially thought to be an infectious disease.

In 2008, the discovery of a new cause of leprosy, Mycobacterium lepromatosis, was announced. Genetically, M leprae and M lepromatosis are very similar, but M lepromatosis causes the diffuse form of lepromatous leprosy found in Mexico and the Caribbean. [1]  

Leprosy is included among the Neglected Tropical Diseases as designated by the World Health Organization. [2] In 2016, the WHO released a 5-year global leprosy strategy, running through 2020, to “strengthen government ownership, coordination, and partnership; stop leprosy and its complications, and to stop discrimination and promote inclusion.” [3]

Other articles on leprosy include Leprosy Neuropathy and Leprosy.

Leprosy is not a highly infectious disease. The principal means of transmission is by aerosol spread from infected nasal secretions to exposed nasal and oral mucosa. Leprosy is not generally spread by means of direct contact through intact skin, although the most vulnerable are close contacts of patients with untreated multibacillary disease.

However, in 2011, a unique strain of M leprae was genotyped in both humans and wild armadillos infected in the southern United States, suggesting a direct means of transmission. Several people had distinct contact with armadillos, including hunting, cooking, or eating armadillos. [4]

The incubation period for leprosy is 6 months to 40 years or longer. The mean incubation period is 4 years for tuberculoid leprosy and 10 years for lepromatous leprosy.

The areas most commonly affected by leprosy are the superficial peripheral nerves, skin, mucous membranes of the upper respiratory tract, anterior chamber of the eyes, and the testes. These areas tend to be cool parts of the body. Tissue damage depends on the degree to which cell-mediated immunity is expressed, the type and extent of bacillary spread and multiplication, the appearance of tissue-damaging immunologic complications (ie, lepra reactions), and the development of nerve damage and its sequelae.

M leprae is an obligate intracellular, acid-fast, gram-positive bacillus with an affinity for macrophages and Schwann cells. For Schwann cells in particular, the mycobacteria bind to the G domain of the alpha-chain of laminin 2 (found only in peripheral nerves) in the basal lamina, causing demyelination. Their slow replication within the Schwann cells eventually stimulates a cell-mediated immune response, which creates a chronic inflammatory reaction. As a result, swelling occurs in the perineurium, leading to ischemia, fibrosis, and axonal death. In vivo, M leprae has also been demonstrated to reprogram Schwann cells to de-differentiate into mesenchymal stem cells, which may explain the spread of bacteria to other non-neural tissues. [5]

With the completion of the genomic sequence of M leprae, one important discovery is that although it depends on its host for metabolism, the microorganism retains genes for the formation of a mycobacterial cell wall. Components of the cell wall stimulate a host immunoglobulin M antibody and cell-mediated immune response, while also moderating the bactericidal abilities of macrophages.

Research showed that M leprae also induces lipid droplet accumulation in macrophages and Schwann cells, with an increase in adipophilin/adipose differentiation-related protein (ADRP). ADRP opposes the action of hormone-sensitive lipase (HSL), which degrades lipids. Infected cells from slit-skin smears in lepromatous leprosy correlate with the findings, with expression of ADRP high and HSL low or undetectable. [6] Lipid metabolism, especially ω3 and ω6 polyunsaturated fatty acids, may also play a role. [7]

The strength of the host’s immune system influences the clinical form of the disease. Strong cell-mediated immunity (interferon [IFN]-gamma, interleukin [IL]–2) and a weak humoral response results in mild forms of disease, with a few well-defined nerves involved and lower bacterial loads. A strong humoral response (IFN-beta, IL-4, IL-10) but relatively absent cell-mediated immunity results in lepromatous leprosy, with widespread lesions, extensive skin and nerve involvement, and high bacterial loads. Therefore, a spectrum of disease exists such that cell-mediated immunity dominates in mild forms of leprosy and decreases with increasing clinical severity. Meanwhile, humoral immunity is relatively absent in mild disease and increases with the severity of disease. T regulatory cells also appear to suppress the normal immune response.

Toll-like receptors (TLRs) may also play a role in the pathogenesis of leprosy. [8]  M leprae activates TLR2 and TLR1, which are found on the surface of Schwann cells, especially with tuberculoid leprosy. Although this cell-mediated immune defense is most active in mild forms of leprosy, it is also likely responsible for the activation of apoptosis genes and, consequently, the hastened onset of nerve damage found in persons with mild disease. Alpha-2 laminin receptors found in the basal lamina of Schwann cells are also a target of entry for M leprae into these cells, while activation of the ErbB2 receptor tyrosine kinase signaling pathway has been identified as a mediator of demyelination in leprosy. [9]

The activation of macrophages and dendritic cells, both antigen-presenting cells, is involved in the host immune response to M leprae. IL-1beta produced by antigen-presenting cells infected by mycobacteria has been shown to impair the maturation and function of dendritic cells. [10] Because bacilli have been found in the endothelium of skin, nervous tissue, and nasal mucosa, endothelial cells are also thought to contribute to the pathogenesis of leprosy. Another pathway exploited by M leprae is the ubiquitin-proteasome pathway, by causing immune cell apoptosis and tumor necrosis factor (TNF)–alpha/IL-10 secretion. [11]

Research continues to explore the pathophysiology of leprosy, with the goal of identifying early markers of disease and new targets for treatment. The most current investigations focus on interferons, [12] the vitamin D – dependent antimicrobial pathway, [13] and NOD2-mediated signaling pathways, [14, 15] as well as the role of T regulatory cells, Th-17/IL-17a/IL-17F cytokines, CD163, and galectin-3. [6]

A sudden increase in T-cell immunity, particularly in the Th1 pattern, is responsible for type I reversal reactions. TLR2 and TLR4 have also been implicated. [6] Type II reactions (erythema nodosum leprosum, ENL) result from activation of TNF-alpha and the deposition of immune complexes in tissues with neutrophilic infiltration and from complement activation in organs. Activated memory T cells are also increased in untreated ENL. [16] One study found that cyclooxygenase 2 was expressed in microvessels, nerve bundles, and isolated nerve fibers in the dermis and subcutis during reversal reactions. [17] Another found high levels of TNF, IFN-γ, IL-1β, and IL-17A Th-17 and low levels of IL-10 and TGF-β in ENL that were reversed after a 24-week course of prednisolone. [18] Other cytokines, cortisol levels, CXC ligand 10, and matrix metalloproteinases may also have a role in both type I and II reactions. [6, 19, 20]

Leprosy is caused by M leprae, an obligate intracellular, acid-fast, gram-positive bacillus. Humans are the primary reservoir of M leprae. Animal reservoirs of leprosy have been found in three species: 9-banded armadillos, chimpanzees, and mangabey monkeys.

Most persons are immune to leprosy. Subclinical disease is common in endemic areas, and the infection progresses to clinical disease in only a select few.

Biopsies of nasal and oral mucosa of individuals who remain untreated for years have demonstrated M leprae positivity, [21, 22] suggesting respiratory secretions are the main cause of infection. However, transmission is not completely understood.

Exposure to insect vectors and infected soil has also been suspected as a possible mode of transmission.

In endemic countries, household contacts of patients are at increased risk for contracting leprosy. The relative risk is 8-10 times for lepromatous leprosy and 2-4 times for tuberculoid leprosy. In nonendemic countries, household contacts rarely acquire the disease.

HIV infection is not a risk factor for acquiring leprosy, nor does it increase the clinical symptoms or virulence of leprosy. However, latent cases of leprosy infections may emerge as part of the immune reconstitution inflammatory syndrome after starting highly active antiretroviral therapy. [23, 24]

One report describes 2 cases of leprosy developing after treatment with infliximab. [25] Both patients developed type I reversal reactions after stopping the TNF-alpha inhibitor. Another patient developed a type I reversal reaction after stopping adalimumab therapy, despite no prior diagnosis of leprosy. [26]

Several cases of tattoo inoculation leprosy have been reported, most in India. [27]

Leprosy has been reported in conjunction with visceral leishmaniasis (kala-azar).

Several reports have described leprosy developing in solid organ transplant recipients (especially kidney) and after bone marrow transplantation. It is not clear about the susceptibility of patients due to general immunosuppressive conditions (as with HIV infection); however, most affected transplant recipients developed multibacillary disease. [28, 29]

The following genes have been associated with leprosy; hence, susceptibility or resistance to leprosy may be at least partially inheritable [15] :

With the first genome-wide association study (GWAS), the following loci have markers with the strongest associations:

HLA-DR-DQ: HLA-DR2 and HLA-DR3 (tuberculoid disease), as well as HLA-DQ1 (lepromatous leprosy); HLA-DRB1*04 is associated with resistance, and HLA-DRB1*10 is associated with susceptibility to leprosy in Brazilian and Vietnamese patients. [30] RIPK2, TNFSFIS

LACC1, CCDC122, and NOD2

Additionally, there are numerous studies looking into the role of other HLA, KIR, MICA and cytokine genes in contracting leprosy. [31]

Genetic variants have been found in the shared promoter region of the PARK2 (parkin) and PACRG genes expressed on monocytes.

Lymphotoxin-alpha (LTA) + 80 expressed on dendritic cells appears to be a risk factor for early-onset leprosy, independent of PARK2/PARCG and HLA class I and HLA-DRB1 genes. [32, 33]

Polymorphisms in the gene promoter regions of TNF (multibacillary leprosy) and IL-10 (-819T allele) are noted in leprosy susceptibility.

Mutations in TLR1 and TLR2 may be involved in susceptibility and/or resistance to other infectious diseases.

Polymorphisms in the NRAMP1 gene appear on macrophages in multibacillary disease in African patients.

TaqI polymorphism (tt genotype) at exon 9 of the vitamin D receptor gene is noted. [34]

IFGR1 gene promoter polymorphisms found in one family demonstrated an autosomal recessive susceptibility to leprosy. [35]

Genetic markers that may identify those more susceptible to T1R and T2R include polymorphisms in vitamin D receptor, IL-6, complement component C4b, TLR1 and TLR2, and natural resistance-associated macrophage protein 1 (NRAMP1). [36]

United States

Approximately 6500 patients with leprosy live in the United States, about 50% of which require active medical management. Approximately 95% of these patients acquired their disease in developing countries. In the United States, 200-300 cases of leprosy are reported each year. States with large immigrant populations (eg, California, New York, Florida) have the largest number of new cases of leprosy. Small endemic foci of leprosy exist in Texas, Louisiana, and Hawaii.


Overall, the worldwide prevalence of leprosy (defined as the number of people on multidrug therapy at a particular point) has decreased  significantly since the introduction of short-course multidrug therapy in 1982. The WHO’s elimination goal of less than 1 case per 10,000 population was reached in the early 2000s. Approximately 95% of affected persons are found in 16 countries, most of them in the tropics and subtropics: Bangladesh, Brazil, China, Democratic Republic of the Congo, Ethiopia, India, Indonesia, Ivory Coast, Madagascar, Myanmar, Nepal, Nigeria, Philippines, South Sudan, Sri Lanka, and the United Republic of Tanzania. [37]

Despite achieving the elimination goal quickly, eradication has proved to be more elusive. Globally, annual new case detection rates for leprosy remain unchanged, and even increased slightly from 2015 to 2016. While this increase is at least partially due to active methods of case-finding and new methods of reporting and data collection, there are still gaps and inconsistent reporting, especially from countries with endemic populations. [38] Clinically, transmission remains an issue. Twenty-two countries, including most of the ones listed above, account for 94-96% of new cases and have been deemed by the WHO as “global priority countries”. [3]

Leprosy occurs in persons of all races. African blacks have a high incidence of the tuberculoid form of leprosy. People with light skin and Chinese individuals tend to contract the lepromatous type of leprosy. Leprosy is endemic in Asia, Africa, the Pacific basin, and Latin America (excluding Chile). Leprosy is more a rural than urban disease.

In adults, the lepromatous type of leprosy is more common in men than in women after puberty, with a male-to-female ratio of 2:1. In children, the tuberculoid form of leprosy predominates and no sex preference is reported. Women tend to have a delayed presentation, which increases rates of deformity.

Leprosy has a bimodal age distribution, with peaks at ages 10-14 years and 35-44 years. Leprosy is rare in infants. Children appear to be most susceptible to leprosy and tend to have the tuberculoid form.

The prognosis depends on the stage of disease. Borderline tuberculoid leprosy usually involves rapid and severe nerve damage. Reversal reactions are uncommon with lepromatous disease; therefore, lepromatous leprosy is a chronic state with long-term complications. Even with MDT, patients have long-term nerve damage and disability.

The prognosis also depends on the patient’s access to therapy, the patient’s compliance, and the early initiation of treatment.

Relapse (new disease after adequate MDT is completed) occurs in 0.01-0.14% of patients per year in the first 10 years. Dapsone and/or rifampin resistance should be considered. [39]

Approximately 5-10% of patients have a type I reversal reaction in the first year after completing MDT.

Because of reduced cell-mediated immunity, pregnancy can precipitate a relapse or reaction of the disease, especially type II reactions in pregnant women younger than 40 years. Dapsone is generally thought to be safe in pregnancy; the safety of clofazimine and rifampin are controversial, and thalidomide (used in type II reactions) is contraindicated during pregnancy.

Type I and type II reactions can precipitate a relapse of the disease.

Perineural granulomas have been reported to persist 18 months after MDT and clinical improvement, and they are not considered to be a relapse of the disease. [40]

Overall, children have a good prognosis because multibacillary disease and leprous reactions are uncommon.

Patients first need an explanation of the diagnosis and prognosis. Their fears should be addressed because of the cultural stigma associated with leprosy. Importantly, refute any myths that the patient may have about leprosy. Patients may need psychological counseling because they may have difficulty coming to terms with the disease or may feel rejected by society. The patient should be reassured that within a few days of starting MDT, they are not infectious and can lead a normal life.

Patients need education about how to deal with anesthesia of a hand or foot. They must learn to carefully inspect their extremities for trauma each day. Patients should also be told to wear proper footwear and protective equipment as necessary. Inexpensive canvas shoes with protective insoles are as effective as special orthopedic shoes. Inspecting limbs and eyes for the onset of anesthesia or weakness is also important. Physical therapy and occupational therapy are important tools in rehabilitation.

Patients must learn how to recognize the onset of lepra reactions, and they should be told to seek immediate medical attention if these reactions develop.

Potential deformities can be prevented by educating patients about how to deal with existing nerve damage and by treating any sequelae of this damage.

Han XY, Sizer KC, Thompson EJ, Kabanja J, Li J, Hu P, et al. Comparative sequence analysis of Mycobacterium leprae and the new leprosy-causing Mycobacterium lepromatosis. J Bacteriol. 2009 Oct. 191(19):6067-74. [Medline]. [Full Text].

Neglected tropical diseases. World Health Organization. Available at 2018; Accessed: May 14, 2018.

Global leprosy update, 2016: accelerating reduction of disease burden. Wkly Epidemiol Rec. 2017 Sep 1. 92 (35):501-19. [Medline].

Truman RW, Singh P, Sharma R, et al. Probable zoonotic leprosy in the southern United States. N Engl J Med. 2011 Apr 28. 364(17):1626-33. [Medline].

Masaki T, Qu J, Cholewa-Waclaw J, Burr K, Raaum R, Rambukkana A. Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli promotes dissemination of infection. Cell. 2013 Jan 17. 152(1-2):51-67. [Medline].

Polycarpou A, Walker SL, Lockwood DN. New findings in the pathogenesis of leprosy and implications for the management of leprosy. Curr Opin Infect Dis. 2013 Oct. 26(5):413-9. [Medline].

Silva CAM, Belisle JT. Host Lipid Mediators in Leprosy: The Hypothesized Contributions to Pathogenesis. Front Immunol. 2018. 9:134. [Medline].

McInturff JE, Modlin RL, Kim J. The role of toll-like receptors in the pathogenesis and treatment of dermatological disease. J Invest Dermatol. 2005 Jul. 125(1):1-8. [Medline].

Tapinos N, Ohnishi M, Rambukkana A. ErbB2 receptor tyrosine kinase signaling mediates early demyelination induced by leprosy bacilli. Nat Med. 2006 Aug. 12(8):961-6. [Medline].

Makino M, Maeda Y, Mukai T, Kaufmann SH. Impaired maturation and function of dendritic cells by mycobacteria through IL-1beta. Eur J Immunol. 2006 Jun. 36(6):1443-52. [Medline].

Fulco TO, Lopes UG, Sarno EN, Sampaio EP, Saliba AM. The proteasome function is required for Mycobacterium leprae-induced apoptosis and cytokine secretion. Immunol Lett. 2007 May 15. 110(1):82-5. [Medline].

Teles RM, Graeber TG, Krutzik SR, Montoya D, Schenk M, Lee DJ, et al. Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses. Science. 2013 Mar 22. 339(6126):1448-53. [Medline]. [Full Text].

Liu PT, Wheelwright M, Teles R, Komisopoulou E, Edfeldt K, Ferguson B. MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy. Nat Med. 2012 Feb. 18(2):267-73. [Medline].

Goulart LR, Goulart IM. Leprosy pathogenetic background: a review and lessons from other mycobacterial diseases. Arch Dermatol Res. 2009 Feb. 301(2):123-37. [Medline].

Zhang FR, Huang W, Chen SM, et al. Genomewide association study of leprosy. N Engl J Med. 2009 Dec 31. 361(27):2609-18. [Medline].

Negera E, Bobosha K, Walker SL, Endale B, Howe R, Aseffa A, et al. New Insight into the Pathogenesis of Erythema Nodosum Leprosum: The Role of Activated Memory T-Cells. Front Immunol. 2017. 8:1149. [Medline].

Pesce C, Grattarola M, Menini S, Fiallo P. Cyclooxygenase 2 expression in vessels and nerves in reversal reaction leprosy. Am J Trop Med Hyg. 2006 Jun. 74(6):1076-7. [Medline].

Negera E, Walker SL, Bobosha K, Bekele Y, Endale B, Tarekegn A, et al. The Effects of Prednisolone Treatment on Cytokine Expression in Patients with Erythema Nodosum Leprosum Reactions. Front Immunol. 2018. 9:189. [Medline].

Chaitanya VS, Lavania M, Nigam A, Turankar RP, Singh I, Horo I. Cortisol and proinflammatory cytokine profiles in type 1 (reversal) reactions of leprosy. Immunol Lett. 2013 Nov-Dec. 156(1-2):159-67. [Medline].

Pandhi D, Chhabra N. New insights in the pathogenesis of type 1 and type 2 lepra reaction. Indian J Dermatol Venereol Leprol. 2013 Nov-Dec. 79(6):739-49. [Medline].

Naves Mde M, Ribeiro FA, Patrocinio LG, Patrocinio JA, Fleury RN, Goulart IM. Bacterial load in the nose and its correlation to the immune response in leprosy patients. Lepr Rev. 2013 Mar. 84(1):85-91. [Medline].

Morgado de Abreu MA, Roselino AM, Enokihara M, Nonogaki S, Prestes-Carneiro LE, Weckx LL. Mycobacterium leprae is identified in the oral mucosa from paucibacillary and multibacillary leprosy patients. Clin Microbiol Infect. 2014 Jan. 20(1):59-64. [Medline].

Batista MD, Porro AM, Maeda SM, et al. Leprosy reversal reaction as immune reconstitution inflammatory syndrome in patients with AIDS. Clin Infect Dis. 2008 Mar 15. 46(6):e56-60. [Medline].

Menezes VM, Sales AM, Illarramendi X, et al. Leprosy reaction as a manifestation of immune reconstitution inflammatory syndrome: a case series of a Brazilian cohort. AIDS. 2009 Mar 13. 23(5):641-3. [Medline].

Scollard DM, Joyce MP, Gillis TP. Development of leprosy and type 1 leprosy reactions after treatment with infliximab: a report of 2 cases. Clin Infect Dis. 2006 Jul 15. 43(2):e19-22. [Medline].

Camacho ID, Valencia I, Rivas MP, Burdick AE. Type 1 leprosy reaction manifesting after discontinuation of adalimumab therapy. Arch Dermatol. 2009 Mar. 145(3):349-51. [Medline].

Ghorpade A. Ornamental tattoos and skin lesions. Tattoo inoculation borderline tuberculoid leprosy. Int J Dermatol. 2009 Jan. 48(1):11-3. [Medline].

Trindade MA, Palermo ML, Pagliari C, et al. Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature. Transpl Infect Dis. 2011 Feb. 13(1):63-9. [Medline].

Ardalan M, Ghaffari A, Ghabili K, Shoja MM. Lepromatous leprosy in a kidney transplant recipient: a case report. Exp Clin Transplant. 2011 Jun. 9(3):203-6. [Medline].

Vanderborght PR, Pacheco AG, Moraes ME, et al. HLA-DRB1*04 and DRB1*10 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients. Genes Immun. 2007 Jun. 8(4):320-4. [Medline].

Jarduli LR, Sell AM, Reis PG, Sippert EÂ, Ayo CM, Mazini PS. Role of HLA, KIR, MICA, and cytokines genes in leprosy. Biomed Res Int. 2013. 2013:989837. [Medline].

Alter A, Alcaïs A, Abel L, Schurr E. Leprosy as a genetic model for susceptibility to common infectious diseases. Hum Genet. 2008 Apr. 123(3):227-35. [Medline].

Schurr E, Alcaïs A, de Leseleuc L, Abel L. Genetic predisposition to leprosy: A major gene reveals novel pathways of immunity to Mycobacterium leprae. Semin Immunol. 2006 Dec. 18(6):404-10. [Medline].

Goulart LR, Ferreira FR, Goulart IM. Interaction of TaqI polymorphism at exon 9 of the vitamin D receptor gene with the negative lepromin response may favor the occurrence of leprosy. FEMS Immunol Med Microbiol. 2006 Oct. 48(1):91-8. [Medline].

Velayati AA, Farnia P, Khalizadeh S, Farahbod AM, Hasanzadh M, Sheikolslam MF. Interferon-gamma receptor-1 gene promoter polymorphisms and susceptibility to leprosy in children of a single family. Am J Trop Med Hyg. 2011 Apr. 84(4):627-9. [Medline]. [Full Text].

Fava V, Orlova M, Cobat A, Alcaïs A, Mira M, Schurr E. Genetics of leprosy reactions: an overview. Mem Inst Oswaldo Cruz. 2012 Dec. 107 Suppl 1:132-42. [Medline].

Global leprosy: update on the 2012 situation. Wkly Epidemiol Rec. 2013 Aug 30. 88(35):365-79. [Medline].

Salgado CG, Barreto JG, da Silva MB, Goulart IMB, Barreto JA, de Medeiros Junior NF, et al. Are leprosy case numbers reliable?. Lancet Infect Dis. 2018 Feb. 18 (2):135-137. [Medline].

Drug resistance in leprosy: reports from selected endemic countries. Wkly Epidemiol Rec. 2009 Jun 26. 84(26):264-7. [Medline].

Ludwig RJ, Henke U, Wolter M, et al. Persistence of peri-neural granulomas after successful treatment of leprosy. J Eur Acad Dermatol Venereol. 2007 Nov. 21(10):1414-6. [Medline].

Khambati FA, Shetty VP, Ghate SD, Capadia GD. Sensitivity and specificity of nerve palpation, monofilament testing and voluntary muscle testing in detecting peripheral nerve abnormality, using nerve conduction studies as gold standard; a study in 357 patients. Lepr Rev. 2009 Mar. 80(1):34-50. [Medline].

Rao PN, Jain S. Newer management options in leprosy. Indian J Dermatol. 2013 Jan. 58(1):6-11. [Medline]. [Full Text].

Cruz RCDS, Bührer-Sékula S, Penna MLF, Penna GO, Talhari S. Leprosy: current situation, clinical and laboratory aspects, treatment history and perspective of the uniform multidrug therapy for all patients. An Bras Dermatol. 2017 Nov-Dec. 92 (6):761-773. [Medline].

Gupta R, Kar HK, Bharadwaj M. Revalidation of various clinical criteria for the classification of leprosy–a clinic-pathological study. Lepr Rev. 2012 Dec. 83(4):354-62. [Medline].

Bhat R, Sharma VK, Deka RC. Otorhinolaryngologic manifestations of leprosy. Int J Dermatol. 2007 Jun. 46(6):600-6. [Medline].

Motta AC, Komesu MC, Silva CH, et al. Leprosy-specific oral lesions: a report of three cases. Med Oral Patol Oral Cir Bucal. 2008 Aug 1. 13(8):E479-82. [Medline].

Sehgal VN, Srivastava G, Singh N, Prasad PV. Histoid leprosy: the impact of the entity on the postglobal leprosy elimination era. Int J Dermatol. 2009 Jun. 48(6):603-10. [Medline].

Nascimento OJ. Leprosy neuropathy: clinical presentations. Arq Neuropsiquiatr. 2013 Sep. 71(9B):661-6. [Medline].

Rai D, Malhotra HS, Garg RK, Goel MM, Malhotra KP, Kumar V, et al. Nerve abscess in primary neuritic leprosy. Lepr Rev. 2013 Jun. 84(2):136-40. [Medline].

Garbino JA, Marques W Jr, Barreto JA, Heise CO, Rodrigues MM, Antunes SL, et al. Primary neural leprosy: systematic review. Arq Neuropsiquiatr. 2013 Jun. 71(6):397-404. [Medline].

Antunes DE, Araujo S, Ferreira GP, Cunha AC, Costa AV, Gonçalves MA. Identification of clinical, epidemiological and laboratory risk factors for leprosy reactions during and after multidrug therapy. Mem Inst Oswaldo Cruz. 2013 Nov. 108(7):901-8. [Medline].

Rao PS, Sugamaran DS, Richard J, Smith WC. Multi-centre, double blind, randomized trial of three steroid regimens in the treatment of type-1 reactions in leprosy. Lepr Rev. 2006 Mar. 77(1):25-33. [Medline].

Safa G, Darrieux L, Coic A, Tisseau L. Type 1 leprosy reversal reaction treated with topical tacrolimus along with systemic corticosteroids. Indian J Med Sci. 2009 Aug. 63(8):359-62. [Medline].

Aires NB, Refkalefsky Loureiro W, Villela MA, Sakai Valente NY, Trindade MA. Sweet’s syndrome type leprosy reaction. J Eur Acad Dermatol Venereol. 2009 Apr. 23(4):467-9. [Medline].

Chauhan S, D’Cruz S, Mohan H, Singh R, Ram J, Sachdev A. Type II lepra reaction: an unusual presentation. Dermatol Online J. 2006 Jan 27. 12(1):18. [Medline].

Fabi SG, Hill C, Witherspoon JN, Boone SL, West DP. Frequency of thromboembolic events associated with thalidomide in the non-cancer setting: a case report and review of the literature. J Drugs Dermatol. 2009 Aug. 8(8):765-9. [Medline].

Verma KK, Srivastava P, Minz A, Verma K. Role of azathioprine in preventing recurrences in a patient of recurrent erythema nodosum leprosum. Lepr Rev. 2006 Sep. 77(3):225-9. [Medline].

Kar BR, Babu R. Methotrexate in resistant ENL. Int J Lepr Other Mycobact Dis. 2004 Dec. 72(4):480-2. [Medline].

Faber WR, Jensema AJ, Goldschmidt WF. Treatment of recurrent erythema nodosum leprosum with infliximab. N Engl J Med. 2006 Aug 17. 355(7):739. [Medline].

Ramien ML, Wong A, Keystone JS. Severe refractory erythema nodosum leprosum successfully treated with the tumor necrosis factor inhibitor etanercept. Clin Infect Dis. 2011 Mar 1. 52(5):e133-5. [Medline].

Costa IM, Kawano LB, Pereira CP, Nogueira LS. Lucio’s phenomenon: a case report and review of the literature. Int J Dermatol. 2005 Jul. 44(7):566-71. [Medline].

Crawford CL. No role for thalidomide in the treatment of leprosy. J Infect Dis. 2006 Jun 15. 193(12):1743-4; author reply 1744-5. [Medline].

Nery JA, Bernardes Filho F, Quintanilha J, Machado AM, Oliveira Sde S, Sales AM. Understanding the type 1 reactional state for early diagnosis and treatment: a way to avoid disability in leprosy. An Bras Dermatol. 2013 Sep-Oct. 88(5):787-92. [Medline].

Sahay G, Kar HK, Gupta R. Effect of Steroid Prophylaxis on Nerve Function Impairment in Multi-bacillary Leprosy Patients on MDT-MB. Indian J Lepr. 2015 Jul-Sep. 87 (3):133-43. [Medline].

Bilodeau M, Burns S, Gawoski J, Moschella S, Ooi W. Co-morbid infections in Hansen’s disease patients in the United States: considerations for treatment. Am J Trop Med Hyg. 2013 Oct. 89(4):781-3. [Medline].

Sena CB, Salgado CG, Tavares CM, Da Cruz CA, Xavier MB, Do Nascimento JL. Cyclosporine A treatment of leprosy patients with chronic neuritis is associated with pain control and reduction in antibodies against nerve growth factor. Lepr Rev. 2006 Jun. 77(2):121-9. [Medline].

Nashed SG, Rageh TA, Attallah-Wasif ES, Abd-Elsayed AA. Intraneural injection of corticosteroids to treat nerve damage in leprosy: a case report and review of literature. J Med Case Reports. 2008 Dec 9. 2:381. [Medline]. [Full Text].

Rath S, Schreuders TA, Selles RW. Early postoperative active mobilisation versus immobilisation following tibialis posterior tendon transfer for foot-drop correction in patients with Hansen’s disease. J Plast Reconstr Aesthet Surg. 2009 Feb 19. [Medline].

Shah RK. Tibialis posterior transfer by interosseous route for the correction of foot drop in leprosy. Int Orthop. 2009 Dec. 33(6):1637-40. [Medline].

Kanaji A, Higashi M, Namisato M, Nishio M, Ando K, Yamada H. Effects of risedronate on lumbar bone mineral density, bone resorption, and incidence of vertebral fracture in elderly male patients with leprosy. Lepr Rev. 2006 Jun. 77(2):147-53. [Medline].

Pereira HL, Ribeiro SL, Pennini SN, Sato EI. Leprosy-related joint involvement. Clin Rheumatol. 2009 Jan. 28(1):79-84. [Medline].

Silva Junior GB, Daher Ede F, Pires Neto Rda J, Pereira ED, Meneses GC, Araújo SM, et al. Leprosy nephropathy: a review of clinical and histopathological features. Rev Inst Med Trop Sao Paulo. 2015 Jan-Feb. 57 (1):15-20. [Medline].

Bhushan P, Sardana K, Koranne RV, Choudhary M, Manjul P. Diagnosing multibacillary leprosy: a comparative evaluation of diagnostic accuracy of slit-skin smear, bacterial index of granuloma and WHO operational classification. Indian J Dermatol Venereol Leprol. 2008 Jul-Aug. 74(4):322-6. [Medline].

Silva EA, Iyer A, Ura S, et al. Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions. Trop Med Int Health. 2007 Dec. 12(12):1450-8. [Medline].

Parkash O, Kumar A, Pandey R, Nigam A, Girdhar BK. Performance of a lateral flow test for the detection of leprosy patients in India. J Med Microbiol. 2008 Jan. 57:130-2. [Medline].

van Hooij A, Tjon Kon Fat EM, van den Eeden SJF, Wilson L, Batista da Silva M, Salgado CG, et al. Field-friendly serological tests for determination of M. leprae-specific antibodies. Sci Rep. 2017 Aug 21. 7 (1):8868. [Medline].

Parkash O, Kumar A, Pandey R, Franken KL, Ottenhoff TH. Detection of Mycobacterium leprae infection employing a combinatorial approach of anti-45 kDa and modified anti-PGL-I antibody detection assays. J Med Microbiol. 2007 Aug. 56:1129-30. [Medline].

Duthie MS, Balagon MF, Maghanoy A, Orcullo FM, Cang M, Dias RF. Rapid Quantitative Serological Test for Detection of Infection with Mycobacterium leprae, the Causative Agent of Leprosy. J Clin Microbiol. 2014 Feb. 52(2):613-9. [Medline].

Bang PD, Suzuki K, Phuong le T, Chu TM, Ishii N, Khang TH. Evaluation of polymerase chain reaction-based detection of Mycobacterium leprae for the diagnosis of leprosy. J Dermatol. 2009 May. 36(5):269-76. [Medline].

Natrajan M, Katoch K, Katoch VM, Das R, Sharma VD. Histological diagnosis of early and suspicious leprosy by in situ PCR. Indian J Lepr. 2012 Jul-Sep. 84(3):185-94. [Medline].

Phetsuksiri B, Rudeeaneksin J, Supapkul P, Wachapong S, Mahotarn K, Brennan PJ. A simplified reverse transcriptase PCR for rapid detection of Mycobacterium leprae in skin specimens. FEMS Immunol Med Microbiol. 2006 Dec. 48(3):319-28. [Medline].

Duthie MS, Orcullo FM, Abbelana J, Maghanoy A, Balagon MF. Comparative evaluation of antibody detection tests to facilitate the diagnosis of multibacillary leprosy. Appl Microbiol Biotechnol. 2016 Apr. 100 (7):3267-75. [Medline].

Marçal PHF, Fraga LAO, Mattos AMM, Menegati L, Coelho ADCO, Pinheiro RO, et al. Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy. Mem Inst Oswaldo Cruz. 2018. 113 (5):e170467. [Medline].

Reja AH, De A, Biswas S, Chattopadhyay A, Chatterjee G, Bhattacharya B. Use of fine needle aspirate from peripheral nerves of pure-neural leprosy for cytology and PCR to confirm the diagnosis: a pilot study. Indian J Dermatol Venereol Leprol. 2013 Nov-Dec. 79(6):789-94. [Medline].

Ray R, Mondal RK, Pathak S. Diagnosis of erythema nodosum leprosum (type 2 reaction) by cytology. Acta Cytol. 2014. 58(1):29-32. [Medline].

Rothschild BM, Rothschild C. Skeletal manifestations of leprosy: analysis of 137 patients from different clinical settings in the pre- and post-modern treatment eras. J Clin Rheumatol. 2001 Aug. 7(4):228-37. [Medline].

Frade MA, Nogueira-Barbosa MH, Lugão HB, Furini RB, Marques Júnior W, Foss NT. New sonographic measures of peripheral nerves: a tool for the diagnosis of peripheral nerve involvement in leprosy. Mem Inst Oswaldo Cruz. 2013 May. 108(3):[Medline].

Garbino JA, Heise CO, Marques W Jr. Assessing nerves in leprosy. Clin Dermatol. 2016 Jan-Feb. 34 (1):51-8. [Medline].

Gupta SK, Nigam S, Mandal AK, Kumar V. S-100 as a useful auxiliary diagnostic aid in tuberculoid leprosy. J Cutan Pathol. 2006 Jul. 33(7):482-6. [Medline].

Reja AH, Biswas N, Biswas S, Dasgupta S, Chowdhury IH, Banerjee S. Fite-Faraco staining in combination with multiplex polymerase chain reaction: a new approach to leprosy diagnosis. Indian J Dermatol Venereol Leprol. 2013 Sep-Oct. 79(5):693-700. [Medline].

Reddy RR, Singh G, Sacchidanand S, et al. A comparative evaluation of skin and nerve histopathology in single skin lesion leprosy. Indian J Dermatol Venereol Leprol. 2005 Nov-Dec. 71(6):401-5. [Medline].

World Health Organization. WHO-recommended MDT regimens. World Health Organization. Available at

Jing Z, Zhang R, Zhou D, Chen J. Twenty five years follow up of MB leprosy patients retreated with a modified MDT regimen after a full course of dapsone mono-therapy. Lepr Rev. 2009 Jun. 80(2):170-6. [Medline].

World Health Organization. WHO Model Prescribing Information: Drugs Used in Leprosy, 1998. Available at

Health Resources and Services Administration. Recommended Treatment Regimens. US Department of Health and Human Services. Available at April 2018; Accessed: May 14, 2018.

Cambau E, Saunderson P, Matsuoka M, et al, on behalf of the WHO surveillance network of antimicrobial resistance in leprosy. Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15. Clin Microbiol Infect. 2018 Mar 1. [Medline].

Sapkota BR, Shrestha K, Pandey B, Walker SL. A retrospective study of the effect of modified multi-drug therapy in Nepali leprosy patients following the development of adverse effects due to dapsone. Lepr Rev. 2008 Dec. 79(4):425-8. [Medline].

Balagon MF, Cellona RV, Abalos RM, Gelber RH, Saunderson PR. The efficacy of a four-week, ofloxacin-containing regimen compared with standard WHO-MDT in PB leprosy. Lepr Rev. 2010 Mar. 81(1):27-33. [Medline].

Lakshmi C, Srinivas CR. Lepromatous leprosy treated with combined chemotherapy and immunotherapy (injection BCG): three case reports. Int J Dermatol. 2014 Jan. 53(1):61-5. [Medline].

Duthie MS, Hay MN, Rada EM, et al. Specific IgG antibody responses may be used to monitor leprosy treatment efficacy and as recurrence prognostic markers. Eur J Clin Microbiol Infect Dis. 2011 May 5. [Medline].

Moet FJ, Pahan D, Oskam L, Richardus JH. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial. BMJ. 2008 Apr 5. 336(7647):761-4. [Medline]. [Full Text].

Feenstra SG, Pahan D, Moet FJ, Oskam L, Richardus JH. Patient-related factors predicting the effectiveness of rifampicin chemoprophylaxis in contacts: 6 year follow up of the COLEP cohort in Bangladesh. Lepr Rev. 2012 Sep. 83(3):292-304. [Medline].

Smith WC. Chemoprophylaxis in the prevention of leprosy. BMJ. 2008 Apr 5. 336(7647):730-1. [Medline].

Felisa S Lewis, MD Dermatologist

Felisa S Lewis, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Texas Medical Association

Disclosure: Nothing to disclose.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Elyse Harrop, MD Clinical Instructor, Department of Dermatology, Metrohealth Medical Center

Elyse Harrop, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology

Disclosure: Nothing to disclose.

Theresa Dressler Conologue, DO, FAAD Physician, Department of Dermatology, Geisinger Medical Center

Theresa Dressler Conologue, DO, FAAD is a member of the following medical societies: American Academy of Cosmetic Surgery, American Academy of Dermatology, American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Dermatologic Manifestations of Leprosy

Research & References of Dermatologic Manifestations of Leprosy|A&C Accounting And Tax Services

Leave a Reply