USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 56-year-old man of Nepalese origin attends the clinic complaining of skin rashes which have been troubling him for years. On examination, there are numerous poorly demarcated skin lesions present on all parts of the body. There is also evidence of significant facial thickening, eyebrow loss, and symmetrical sensory neuropathy in a 'glove and stocking' distribution. An examination of the hands reveals bilateral weakness. A skin biopsy is taken from one of the lesions and the culture is positive for acid-fast bacilli. Which of the following pharmacological therapies is involved in the treatment of this condition?
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.
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.