Aetiology

Mycobacterium leprae is an acid-fast, gram-positive bacillus and an obligate intracellular organism that has not been successfully grown in culture media. The bacillus multiplies very slowly in macrophages and Schwann cells and prefers low temperatures (27ºC to 33ºC), as occur in the skin, peripheral nerves, and upper respiratory tract. The genome of M leprae has been sequenced and a different species called M lepromatosis has been described; however, more studies are necessary to determine the clinical implications.[8][9]

Pathophysiology

The mode of transmission is uncertain; however, entry through the respiratory route appears most probable (although other routes, particularly broken skin, cannot be ruled out).[10][11][12][13]

M leprae and M lepromatosis have been found in red squirrels in the UK and Ireland and in wild chimpanzees in West Africa.[14][15] In the southern United States, patients with leprosy and no foreign exposure have been found to be infected with the same strain of Mycobacterium leprae as wild armadillos in the region, suggesting zoonotic transmission.[16]

Leprosy presents as a clinical spectrum that correlates with the level of the immune response to Mycobacterium leprae. At one end of the spectrum, patients with tuberculoid leprosy have a localised disease and lesions are characterised by Th1 cytokines (IFN-gamma, IL-2, and TNF-beta), Th17 cells, and CD1a restricted T cells, indicative of cell-mediated immunity. At the other end of the spectrum, patients with lepromatous leprosy have a more disseminated form of the disease and the lesions are characterised by Th2 cytokines with increased humoral response and suppressed macrophage activity (IL-4, IL-5, IL-10, IL-13).[17] Type I IFN and CD4 + T regs, predominate in these patients.[18]

Most people exposed to M leprae do not acquire the disease, which suggests that disease development depends on immunological, genetic, and environmental factors. Possible genetic factors include the PARK2 and PACRG genes, and genes in the NOD2 pathway. Some genes are also associated with different forms of leprosy: HLA-DR2 has been associated with the tuberculoid form, and HLA-DQ1 has been associated with the lepromatous form.[19][20]

Classification

Ridley Jopling Classification[2]

Leprosy presents as a clinical spectrum that correlates with the level of the immune response to Mycobacterium leprae. At one end of the spectrum, patients with tuberculoid leprosy are resistant to the pathogen and the infection is localised. In contrast, patients with lepromatous leprosy are more susceptible to the pathogen and the infection is systemically disseminated.

Lepromatous leprosy (LL)

  • Multiple papules, plaques, or nodular lesions, symmetrical and disseminated.

  • Can have absence of eyebrows and eyelashes and infiltration of the ears.

  • The disease can involve mucous membranes of the mouth, nose, pharynx, larynx, trachea, eyes, testes, liver, and bones.

Borderline leprosy

  • Can be unstable and move between types.

  • Borderline lepromatous (BL): similar to lepromatous leprosy.

  • Mid-borderline leprosy (BB): annular plaques, punched out lesions.

  • Borderline tuberculoid (BT): asymmetric lesions, macules, or plaques.

Tuberculoid leprosy (TT)

  • Few lesions, mostly macular with sharp margin, can be erythematous or hypopigmented. Lesions are localised and asymmetric.

Indeterminate leprosy

  • This is an early phase in the natural history of leprosy. At this stage the disease has not yet determined into which type it will evolve.

  • Usually presents as a single hypopigmented macule with anaesthesia.

World Health Organization (WHO) Classification[3]

Based on the number of skin lesions. Designed to be used in areas with no access to other diagnostic methods and to serve as a basis for treatment.

  • Multibacillary (MB) leprosy includes polar lepromatous (LL), borderline lepromatous (BL), and mid-borderline (BB) cases in the Ridley-Jopling classification and is defined as having 6 or more skin lesions and a positive skin smear if available.

  • Paucibacillary (PB) leprosy includes indeterminate (I), polar tuberculoid (TT), and borderline tuberculoid (BT) in the Ridley-Jopling classification and is defined as having up to 5 skin lesions and a negative smear if available.

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