Leprosy:
- Hansen’s disease (leprosy) is a chronic granulomatous disease of humans primarily involving the skin, peripheral nerves and nasal mucosa but capable of affecting any tissue or organ.
- Onset of leprosy is insidious.
- It affects nerves, skin and eyes. It may also affect mucosa (mouth, nose, pharynx), kidney, voluntary/ smooth muscle, reticulo-endothelial system and vascular endothelium.
Mode of transmission:
- Leprosy is an exclusively human disease but is not very contagious.
- Nasal secretions and discharges from nodular lesions are the most likely infections materials for family contacts.
- Transmission of leprosy is generally via:
- Inhalation of an infectious aerosol
- By direct contact with skin
Pathogenesis:
- Lepra bacilli enter the body usually through respiratory system.
- It has low pathogenicity, only a small proportion of infected people develop signs of the disease.
- After entering the body, bacilli migrate towards the neural tissues and binds to Schwann cells (Scs).
- Schwann cells are major target for infection by M. leprae leading to injury of nerve, demyelination and consequent disability.
- M. leprae invades Schwann cells by specific laminin-binding protein of 2.1 KDa in addition to Phenolic glycolipid-1 (PGL-1).
- Bacteria can also be found in microphages, muscles cells and endothelial cells of blood vessels.
- After entering the Schwann cells or macrophages, fate of the bacterium depends on the resistance of infected individuals towards the infecting organism.
- Bacilli start multiplying slowly (about 12-14 days for one bacterium to divide into two) within cells, get liberated from the destroyed cells and enter other unaffected cells.
- Till this stage, person remains free from signs and symptoms of leprosy.
- As the bacilli multiply, bacterial load increases in the body and infection is recognized by the immunological system.
- Lymphocytes and histocytes invades the tissue.
- At this stage clinical manifestation may appear as involvement of nerves with impairment of sensation and skin patch. If it is not diagnosed then it is determined by the strength of patient’s immune response.
- Specific and effective cell mediated immunity (CMI) provides protection to a person against leprosy.
- When specific CMI is effective in eliminating/controlling the infection in the body, lesions heal spontaneously or it produces paucibacillary (PBL) type of leprosy.
- If CMI is deficient the disease spreads uncontrolled and products multi-bacillary (MB) leprosy with multiple system involvement.
- Sometimes the immune response is abruptly altered, either following treatment (Multiple drug therapy) or due to improvement of immunological status which results in inflammation of skin and or nerves and even other tissue called as leprosy reaction.
- In person with good CMI, granuloma formation occurs in cutaneous nerve.
- This nerve swells and gets destroyed often only a few fascicles of the nerve are infiltrated, but inflammation within the epineurium causes compression and destruction of unmyelinated sensory and autonomic fiber.
- Myelinated motor fibers are the last to get affected producing motor impairments.
- Severe inflammation may result in caseous necrosis within the nerve.
- Clinical manifestation of sensory loss occurs when nearly 30% of sensory fibers are destroyed.
- Good CMI limits the disease to nerve Schwann cell resulting in occurrence of the pure neural leprosy.
- M. leprae may escape from nerve to adjacent skin at any time and cause classical skin lesions.
- In persons with depressed CMI, bacilli entering the Schwann cells multiply rapidly and destroy the nerve.
- Also, bacilli liberated by Schwann cells that also infected and destroyed are engulfed by histocytes.
- Histocytes with bacilli inside them become wandering microphages.
- Bacilli multiply inside these macrophages and travel to other tissues, through blood, lymph or tissue third.
- Toll like receptors (TLRs) play important role in the pathogenesis of leprosy. TLRs such as TLR-1 and TLR-2 are found on the surface of Schwann cells, especially in patients with tuberculoid leprosy. M. leprae activates this receptor on Schwann cells, which is suggested to be responsible for the activation of apoptosis gene and which enhances the onset of nerve damage seen in the mild disease.
Clinical features:
Incubation period:
- The incubation period varies from few months as long as 30 years and average 2-5 years.
Clinical forms of leprosy:
- There are two major extreme or polar forms of leprosy-tuberculoid form and lepromatous leprosy.
- Many patients occupy an intermediate position on the spectrum, which may be classified as borderline tuberculoid (BT), mid-borderline (BB) or borderline lepromatous (BL).
- The type of disease is a reflection of the immune status of the host. It is therefore not permanent and varies with chemotherapy and alterations in host resistance.
1. Tuberculoid leprosy:
- This is a localized form of the disease and found in patients with high degree of resistance where cell mediated immunity is intact and the skin is infiltrated with helper TH1 cells.
- There is usually only a single or very few well defined skin- lesions.
- The lesions may appear as a flattered area with raised edges and erythematous edges and a dry hairless center.
- It is without feeling and less pigmented than the surrounding skin.
- The lesions are commonly found on the face limbs, buttocks or elsewhere but not in the axilla, perineum or scalp.
- Neural involvement is common that is pronounced leading to deformities, particularly in the hands and feet. Affected nerves show marked thickening.
2. Borderline tuberculoid leprosy:
- Lesions in this form of leprosy are similar to those seen in the tuberculoid leprosy, but are smaller and more numerous.
- Skin lesions are few, asymmetric and with nearly complete anesthesia peripheral nerves are thickened and involved asymmetrically.
- This form of leprosy may remain at this stage or can regress to the tuberculoid form or it can progress to lepromatous form.
3. Mid- borderline leprosy:
- Skin lesions in this type of leprosy consists of numerous unequally shaped plagues that are less well defined than in the tuberculoid types.
- These skin lesions are distributed asymmetrically. Anesthesia is moderate and the disease can remain in this stage can improve or worsen.
4. Borderline lepromatous leprosy:
- Skin lesions are moderate to numerous.
- They are slightly asymmetrical with slight or no anesthesia.
- Peripheral nerves are enlarged moderately and symmetrical. Like the other forms of borderline leprosy, the disease may remain in this stage, improve or worsen.
5. Lepromatous leprosy:
- It is generalized form of the disease and found in individuals where the host resistance is low due to specific defect in their cellular response to M. leprae antigen.
- The bacteria disseminate in hematogenous manner although the disease does not appear to manifest in deeper organs.
- The lesions are small and many.
- They are shining with no loss of feeling.
- Superficial nodular lesions develop which consists of granulation tissue containing a dense collection of vacuolated cells to different stages of development from mononuclear cells to lepra cells.
- The nodules ulcerate become secondarily infected and cause distortion and mutilation.
- Facial disfigurement is commonly observed.
- The skin of the fact and forehead becomes thickened and corrugated giving rise to typical leonine face.
- The lateral part of eyebrows may be lost.
- Other disfigurement of lesions includes pendulous ear lobes, hoarseness of voice, perforation of nasal septum and nasal collapse.
- The reticuloendothelial system, eyes, kidneys and bones are also involved.
- The lepromatous type is more infective than other types.
- Patients often have a hemolytic anemia, a raised erythrocyte sedimentation rate due to abnormal serum albumin and globulin levels.
- Antinuclear factor and rheumatoid factor may be found in serum and LE cells can sometimes be selected in blood buffy coat preparation.