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Mycobacterium leprae

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Mycobacterium leprae

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A 56-year-old man presents to the clinic due to nodular skin growth on the face and decreased sensation in both lower extremities. The patient immigrated from Southeast Asia ten years ago and has not seen a physician in many years. Physical examination shows erythematous macules, papules, and nodules on the face. There is also body hair loss, most notably in the eyebrows and eyelashes. Serum testing shows a CD4 count of 13 cells/mm3. A full-thickness skin biopsy is performed and shows polymorphonuclear leukocytes and bacteria. Which of the following is the most likely diagnosis in this patient?  

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Mycobacterium leprae is a rod-shaped bacteria which was first discovered in 1873 by Hansen.

Mycobacterium leprae is a non tuberculous mycobacteria and it causes a disease called leprosy, or Hansen disease. In US, the animal reservoir for Mycobacterium leprae are armadillos.

Now, Mycobacterium leprae it’s an acid-fast bacillus which means it’s resistant to decolorization by acids and it has a high content of mycolic acid in its cell wall, which makes it waxy, hydrophobic and impermeable to routine stain such as Gram stain.

So, it needs special staining methods to be visualized such as Ziehl-Neelsen staining which uses carbol fuchsin combined with phenol which is able to penetrate the waxy mycobacterial cell wall.

So, the stain binds to the mycolic acid in the mycobacterial cell wall and after staining, an acid decolorizing solution is applied which removes the red dye from the background cells, tissue fibres, and any organisms in the smear except Mycobacteria, which retain the dye.

So Mycobacterium leprae appears bright red on a blue background. Other staining methods can be used such as Kinyoun staining, in which the bacteria appear bright red on a green background and fluorescence microscopy using specific fluorescent dyes such as auramine-rhodamine stain.

Now, Mycobacterium leprae is an obligate intracellular microorganism, which means it can survive only inside cells, and it’s an obligate aerobe which means it can survive only in the presence of oxygen.

Finally, Mycobacterium leprae grows best at cool temperatures, between 27 to 33 degrees Celsius, and it proliferates slowly and it cannot be cultivated in vitro.

Instead, it can be inoculated in nine-banded armadillos, which have a much lower body temperature than most mammals and, like humans, are susceptible to leprosy.

Now, Mycobacterium leprae can enter the body through the lungs or broken skin.

Once inside the body, it goes for regions in which the temperature is lower than the rest of the body such as skin, peripheral nerves and mucosa of the upper respiratory tract.

So, the bacteria goes for the Schwann cells of peripheral nerves.

These cells wrap their plasma membrane around peripheral nerve axons forming the myelin sheath.

This is possible because of a virulence factor, called phenolic glycolipid 1, or PGL-1 for short, which attaches to a protein called laminin-2 which is found on the Schwann cells.

Binding to Schwann cells induces demyelination, affecting transmission of the electrical impulses through the nerve axon, and causing nerve injury.

Additionally, Mycobacterium leprae can also infect skin macrophages.

So, the bacteria is ingested by macrophages and wrapped up in a vesicle called a phagosome, which would normally merge with another intracellular organelle called a lysosome.

Inside the phagolysosome, the bacteria would normally be destroyed.

But, Mycobacterium leprae has the ability to inhibit the phagolysosomal fusion, which allows the bacteria to survive inside macrophages and replicate there.

Now, the host responds to leprosy through cell mediated immunity via T-helper cells.

These cells help the activity of other immune cells by releasing T cell cytokines, and there are two types of T-helper cells - Th1 and Th2.

Depending on which T-helper cells are involved in the immune response, there are two major forms of leprosy - lepromatous and tuberculoid.

Now, in the lepromatous form, the infection induces a Th2 cell response, and Th2 cells secrete IL-4, IL-5 and IL-10.

These molecules are cytokines, which means that they signal B cells to make antibodies against Mycobacterium leprae, so this is a type of humoral, antibody-based response.

Now, this response is not effective in killing intracellular pathogens like Mycobacterium leprae, that can escape humoral immune mechanisms and replicate inside macrophages.

So, the inefficient immune response seen in the lepromatous form is sometimes also called a low cell mediated immunity response.

This leads to extensive skin involvement and symmetric nerve involvement, and the lepromatous form is also called multibacillary leprosy because of the large number of bacteria found in the lesions.

On the other hand, with is tuberculoid form, the infection induces a Th1 response, and Th1 cells secrete IL-2 and interferon-gamma.

Summary

Mycobacterium leprae is a species of acid fast bacillus, obligate intracellular, aerobic bacteria, which primarily causes leprosy, a chronic and disfiguring skin disease. It is spread from person to person through contact with nasal secretions and skin lesions and can cause nerve damage and other organ damage if left untreated.

The diagnosis involves identifying Mycobacterium leprae bacteria in a skin biopsy with microscopy or PCR. Treatment typically involves a combination of antibiotics, such as dapsone or rifampin, and other drugs such as clofazimine or prednisone.