Leprosy (Hansen's disease, leprosy)

Leprosy (Latin lepra, Hansen's disease, hanseniasis, leprosy, St. Lazarus disease, ilephantiasis graecorum, lepra arabum, leontiasis, satyriasis, lazy death, black sickness, mournful disease) is a chronic infection with the acid-fast bacillus Micobacterium leprae, which has a unique tropism for peripheral nerves, skin and mucous membranes. Symptoms of leprosy (leprosy) are extremely diverse and include painless skin lesions and peripheral neuropathy. Diagnosis of leprosy (leprosy) is clinical and is confirmed by biopsy data. Treatment of leprosy (leprosy) is carried out by dapsone in combination with other antibacterial agents.

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Epidemiology

Although most cases are found in Asia, lepra is also widespread in Africa. Endemic foci also exist in Mexico, South and Central America, the Pacific Islands. Of the 5 thousand cases in the US, almost all have been detected in immigrants from developing countries who have settled in California, Hawaii and Texas. There are several forms of the disease. The most severe, lepromatous form, is more common in men. Leprosy can be at any age, although the highest frequency is between the ages of 13-19 and 20-year-olds.

Until recently, people were considered the only natural reservoir of leprosy, but it turned out that 15% of armadilloes were infected, human primates could also be a reservoir for infection. However, with the exception of the transmission route of infection (through bugs, mosquitoes), infection from animals is not a determinant factor for human disease. M. Leprae is also found in the soil.

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Causes of the leprosy

Leprosy (Hansen's disease, leprosy) is caused by Micobacterium leprae, which is an obligate intracellular parasite.

It is believed that the causative agent of leprosy is transmitted by sneezing and secretion of the patient. An untreated leprosy patient is the carrier of a large number of pathogens located on the nasal mucosa and in secrets, even before the appearance of the clinic; about 50% of patients had close contact with an infected person, often with family members. Short contact causes a low risk of transmission. The non-severe tuberculoid forms are usually not contagious. Most (95%) of immunocompetent individuals do not get sick even after contact; those who are ill probably have a genetic predisposition.

Micobacterium leprae grows slowly (the period of doubling is 2 weeks). Usually the incubation period is 6 months - 10 years. When the infection develops, hematogenous dissemination occurs.

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Symptoms of the leprosy

Approximately 3/4 of patients with infection develop a single skin lesion, which passes spontaneously; the remaining patients develop clinical leprosy. Symptoms of leprosy and the severity of the disease vary depending on the severity of cellular immunity to M. Leprae.

Tuberculoid leprosy (Hansen's oligobacillary disease) is the easiest form of leprosy. Patients have strong mediated cellular immunity, which limits the disease to several sites on the skin or to separate nerves. Damage contains a small amount of bacteria or does not contain any. Skin lesions contain one or more hypopigmented spots, with sharp raised edges, with reduced sensitivity. Rash, as well as with all forms of lepra, does not itch. The lesions are dry, since the disturbances of the autonomic nerves damage the innervation of the sweat glands. Peripheral nerves can be damaged asymmetrically and palpated by enlarged ones in adjacent foci of skin lesions.

Lepromatous leprosy (polybacillary disease of Haneana) is the most severe form of the disease. Affected patients have an insufficient immune response to M. Leprae, as well as a systemic infection with the spread of bacterial infiltrates of the skin, nerves and other organs (nose, testicles and others). They can appear on the skin spots, papules, knots and plaques, often symmetrical (stuffed with mycobacteria leprosy). Gynecomastia, loss of fingers and often severe peripheral neuropathy can develop. The patients drop eyelashes and eyebrows. Disease in Western Mexico and elsewhere in Latin America causes the development of diffuse cutaneous infiltration with hair loss on the body and other skin lesions, but without signs of foci. This is called diffuse lepromatosis or leptra bonita. Patients may develop subacute erythema nodosum, while in patients with diffuse lepromatosis - the phenomenon of Lazio, with ulcers, especially on the legs, which often serve as a source of secondary infection, leading to bacteremia and death.

Border leprosy (multibacillary) has an intermediate character and is the most frequent. Skin lesions resemble tuberculoid leprosy, but are more numerous and irregular; affect the whole limb, peripheral nerves with the appearance of weakness, loss of sensitivity. This type has an unstable course and can go into lepromatous leprosy or have an inverse development with the transition to tuberculoid form.

Lepromatous reactions

The patients develop immunologically mediated reactions. There are two types of reactions.

A type 1 reaction develops as a result of a spontaneous increase in cellular immunity. They occur in approximately one-third of patients with borderline leprosy, usually after starting treatment. Clinically, there is an increase in inflammation within already existing lesions with the development of skin edema, erythema, neuritis with pain, loss of function. New lesions may develop. These reactions play an important role, especially in the absence of early treatment. As the immune response increases, this is called the reversible reaction, despite the possible clinical deterioration.

The second type of reaction is a systemic inflammatory reaction as a result of the deposition of deposits of immune complexes. It is also called a leprosy subacute erythema nodosum. Previously, it occurred in about half of patients with borderline and lepromatous forms of leprosy during the first year of treatment. Now it has become less frequent, since clofazimine is added to the treatment. It can also develop before treatment. It is a polymorphonuclear vasculitis or panniculitis with the possible participation of circulating immune complexes and an increase in the function of T-helpers. The level of tumor necrosis factor increases. Leprosy subacute erythema nodosum is erythematous painful papules or nodes with pustules and ulcers. With it develops fever, neuritis, lymphadenitis, orchitis, arthritis (large joints, especially the knee), glomerulonephritis. As a result of hemolysis and bone marrow suppression, anemia, hepatitis with a moderate increase in functional tests can develop.

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Complications and consequences

Leprosy (leprosy) has complications that develop as a result of peripheral neuritis, as a result of infection or leprosy reaction; there is a decrease in sensitivity and weakness. Nerve trunks and microscopic nerves of the skin, especially the ulnar nerve, can be affected, which leads to the formation of clawlike 4th and 5th fingers. Also, the branches of the facial nerve (buccal, zygomatic) and the posterior ear nerve can be affected. Individual nerve fibers responsible for pain, temperature and fine tactile sensitivity may be affected, while the larger nerve fibers responsible for vibration and positional sensitivity are usually less affected. Surgical movements of the tendons allow adjustment of lagophthalmia and functional disorders of the upper limbs, but should be performed 6 months after the start of therapy.

Plantar ulcers with secondary secondary infection are the main cause of disability and should be treated with removal of necrotic tissues and appropriate antibiotics. Patients should exclude the weight load and wear an immobilizing bandage (Unna's boot), which allows to keep the ability to move. For the prevention of recurrence, corns should be treated, patients should wear special shoes made on an individual model, or deep shoes that prevent the foot from rubbing.

Your eyes can be very affected. With lepromatous leprosy or with leprosy erythema nodosum, irites can lead to glaucoma. Insensitivity of the cornea and lesion of the zygomatic branch of the facial nerve (which causes lagophthalmus) can lead to corneal trauma, scars and loss of vision. In such patients it is necessary to use artificial lubricants (drops).

The mucosal and cartilage of the nose may be affected, which leads to a chronic rhinorrhea and sometimes nosebleeds. Less often can develop perforation of nasal cartilage, deformation of the nose, which usually occurs in untreated patients.

In men with leprosy, hypogonadism may develop, as a result of lowering serum testosterone and increasing follicle-stimulating and luteinizing hormones, with the development of erectile dysfunction, infertility and genicomastia. Substitution testosterone therapy can alleviate symptoms.

In patients with severe recurrent course of leprosy subacute erythema, amyloidosis with progressive renal failure may develop.

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Diagnostics of the leprosy

Diagnosis of leprosy (leprosy) is based on the charateric clinical picture of skin lesions and peripheral neuropathy and is confirmed by microscopy of biopsy specimens; on artificial media, microorganisms do not grow. The biopsy is carried out from the raised edges of tuberculoid lesions. In patients with lepromatous form, a biopsy should be performed from nodules and plaques, although pathological changes may even occur in normal areas of the skin.

The test for the detection of IgM antibodies against M. Leprae is highly specific, but is low-sensitivity. These antibodies are practically in all patients with lepromatous form, but only in 2/3 patients with tuberculoid form. Since the detection of such antibodies may indicate an asymptomatic infection in endemic foci, the diagnostic value of the test is limited. They can be useful for monitoring the activity of the disease, as the level of antibodies falls with effective chemotherapy and increases with relapse.

Lepramine (thermoinactivated leprae) is available for skin tests, but it does not have sensitivity and specificity, so it is not recommended for clinical use.

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Treatment of the leprosy

Leprosy has a favorable prognosis provided timely treatment of the disease, but cosmetic deformation leads to ostracism of patients and their families.

Medicines against leprosy

The main drug for treating leprosy is dapsone 50-100 mg orally once a day (for children 1-2 mg / kg). Side effects include hemolysis and anemia (mild), allergic dermatitis, which can be quite severe; rarely a syndrome including exofoltative dermatitis, high fever and changes in blood analysis (leukocytes), as in mononucleosis (dapsone syndrome). Although cases of dapsone resistance of leprosy are described, resistance is low, and patients respond to usual doses of drugs.

Rifampin is the first bactericide to treat M. Leprae. But it is very expensive for many developing countries, if given in recommended doses: 600 mg orally once a day. Side effects are associated with discontinuation of treatment and include hepatotoxicity, influenza-like symptoms and, rarely, thrombocytopenia and kidney failure.

Clofazimine has a dapsone-like activity against M. Leprae at doses of 50 mg orally once a day to 100 mg 3 times per week; 300 mg once a month are useful 1 (X for the prevention of lethargic reactions of type 2 and, probably, type 1. Side effects include gastrointestinal disorders and reddish-dark dichromy of the skin.

Treatment of leprosy is also carried out with ethionamide at doses of 250-500 mg orally once a day. However, it can often cause gastrointestinal upset and liver dysfunction, especially when used with rifampin, and is not recommended if there is no possibility of regular monitoring of liver function.

Recently, three antibiotics, minocycline (100 mg orally once a day), clarithromycin (500 mg orally twice a day) and ofloxacin (400 mg orally once a day) rapidly kill M. Leprae and reduce skin infiltration. Their combined bactericidal activity against M. Leprae is higher than dapsone, clofazimine and ethionamide, but not rifampin. Only minocycline has proven safety in the long-term use of therapy, which is necessary for leprosy.

Recommended schemes

Despite the fact that antimicrobial leprosy treatment is effective, optimal schemes are unknown. In the US, for patients with lepromatous and borderline forms, leprosy is often recommended to perform a drug sensitivity test in mice.

WHO recommends a combination regimen for the use of drugs for all forms of leprosy. Treatment lepra in lepromatous form requires more active schemes and duration than for tuberculoid leprosy. In adults, WHO recommends dapsone 100 mg once a day, clofazimine 50 mg once a day + 300 mg once a month and rifampin 600 mg once a month for at least 2 years or until negative skin biopsy results (approximately after 5 years). With tuberculoid leprosy without isolation of acid-fast bacilli, WHO recommends dapsone 100 mg 1 time per day and rifampin 600 mg once a month for 6 months. Many authors from India recommend treatment more than 1 year.

In the US lepromatous leprosy is treated with rifampin 600 mg once a day for 2-3 years + dapsone 100 mg once a day for life. Tuberculoid leprosy is treated with dapsone 100 mg once a day for 5 years.

Lepromatous reactions

Patients with the first type of reaction (excluding minor inflammation) are given prednisolone 40-60 mg orally once a day, starting with 10-15 mg once a day, followed by a rise in several months. Small skin inflammations are not treated.

In the first or second episode of exacerbation of leprosy subacute erythema nodosum in mild cases, you can prescribe aspirin, in more severe cases - prednisolone 40-60 mg vagus 1 times a day for 1 week plus antimicrobials. If relapses are prescribed, thalidomide is 100-300 mg orally once a day, but given its teratogenicity, it should not be given to women who may have a pregnancy. Side effects include constipation, mild leukopenia and drowsiness.

Prevention

The BCG vaccine and dapsone have limited efficacy and are not recommended for prophylaxis. Since leprosy (leprosy) has minimal contagiousness, the historically used isolation has no scientific basis. Prevention of leprosy consists in the exclusion of direct contact with the secrets and tissues of infected patients.

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