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Hansen's disease - Leprosy

Hansen's Disease

Chronic, typically non-fatal disease.
Major cause of peripheral neuropathy in areas where infection is endemic.
Treatment can include administration of dapsone, rifampicin, and clofazimine.

Be aware that Mycobacterium lepromatosis* is also associated with Hansen's disease; it causes diffuse lepromatous leprosy, and is endemic in Mexico and Costa Rica.

Infection produces a range of clinical manifestations

Disease severity is determined by the host's cellular immune response, which is influenced by genetic components and environmental conditions.
Tuberculoid leprosy is the milder, less infectious form; Lepromatous leprosy is the more severe, disseminated, and infectious form; Borderline leprosy is in the middle, and is characterized as "immunologically unstable."
Individuals move along this spectrum according to shifts in their immune system responses.

Be aware that there are additional clinically recognized stages that we have omitted for simplicity.

Tuberculoid leprosy

Associated with CD4+ T cell activation and type 1 cytokines, particularly IL-2 and interferon-gamma.

— This produces an effective immune response that restricts infection. — Low bacillary load = Paucibacillary Hansen's disease. — Negative slit-skin smear test

Tuberculoid leprosy is characterized by 5 or fewer lesions with granulomatous inflammation

— Over time, inflammation damages the peripheral nerves. — Lesions are dry and scaly with irregular edges; the center of the lesions is typically hypo-pigmented.

Ultimately, nerve damage results in the loss of sensation; hair loss and reduced sweating ability can also occur.

Lepromatous leprosy

Associated with CD8+ T cells and type 2 cytokines, particularly IL-4 and IL-10.
This response produces an ineffective cellular immune response that facilitates disseminated infection.
High bacillary load = Multibacillary Hansen's disease
Positive slit-skin test
Antibodies may be produced, but they form immune complexes that compound tissue damage.
Widespread lesions with thickened skin and nerve damage occurs.

— Facies leonina, aka, lion face, is the result of thickened skin around the ears, nose, and brows with loss of the eyebrows and eyelashes. — Major nerves are commonly affected, including the median and ulnar nerves of the upper extremity, and the common fibular nerve and posterior tibial nerves of the lower extremity. The facial nerve is also often damaged. — Nerve damage can lead to muscular atrophy and paralysis. — Additionally, some patients experience testicular damage.

Leprosy reactions

Immune reactions with acute inflammation that can cause permanent nerve damage, so they need to be treated right away.
Analgesics can help with pain, and corticosteroids are necessary to suppress the immune system if nerve damage is suspected.

Type 1 Reactions

Associated with tuberculoid and lepromatous leprosy

Reversal reactions are caused by delayed hypersensitivity immune responses*

Edema and inflammation
Damage to the peripheral nerve trunks is a major concern.

Type 2 Reactions

Associated with lepromatous leprosy
Characterized by erythema nodosum leprosum that presents as subcutaneous nodules of inflammation on the extensor surfaces of the extremities.
Brought on by humoral immune responses that result in immune complex deposition.
Vasculitis and other complications that damage nerves and organs.
In patients where corticosteroids are contraindicated, thalidomide can be administered; however, this drug is associated with severe birth defects, so caution is warranted in women of child-bearing age.

Mycobacterium leprae

Characteristics:

Acid-fast
Not grown in vitro; in the lab, it's often grown in mouse footpads.
14-day doubling time
Human pathogen

— Has also been found in armadillos and some other non-human primates.

Route of transmission is not entirely established

— Long-term contact is necessary. — It is thought that respiratory, and possibly skin secretions, transmit the bacteria.

Prefers cooler temperatures

— Tends to infect superficial structures such as the skin and peripheral nerves — In some individuals, the anterior eye chambers and nasal cavities are also affected.

Long incubation period: typically between 3-10 years.
Intracellular pathogen

— Macrophages and the Schwann cells of peripheral nerves. — In the histology image, we see foamy macrophages infected with Mycobacterium leprae — Schwann cell invasion causes demyelination and reduced conduction.

Image Credits

Leprosy in cutaneous nerve (CDC/Arthur E. Kaye).

Foamy macrophage w/Mycobacterium leprae (Wikipedia; Author Dr. Roshan Nasimudeen).

Facies leonina (Wikipedia; Pierre Arents).

Hansen's disease - Leprosy

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