Lepra (Hansen's disease, leprosy).

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

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Epidemiology

Although most cases are found in Asia, leprosy is also widespread in Africa. Endemic foci also exist in Mexico, South and Central America, and the Pacific Islands. Of the 5,000 cases in the United States, almost all have been found in immigrants from developing countries who 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 occur at any age, although the highest incidence is at ages 13-19 and in 20-year-olds.

Until recently, humans were considered the only natural reservoir of leprosy, but it turned out that 15% of armadillos are infected, and anthropoid primates may also be a reservoir for the infection. However, with the exception of the transmission route of infection (through bedbugs, mosquitoes), infection from animals is not a determining factor for human disease. M. leprae is also found in soil.

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Causes leprosy

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

The leprosy pathogen is thought to be transmitted by sneezing and secretions from the patient. An untreated patient with leprosy is a carrier of a large number of pathogens present on the mucous membrane of the nasal cavity and in secretions, even before clinical symptoms appear; about 50% of patients have had close contact with an infected person, often with family members. Short contact determines the low risk of transmission. Mild tuberculoid forms are usually not contagious. Most (95%) immunocompetent individuals do not become ill even after contact; those who become ill probably have a genetic predisposition.

Mycobacterium leprae grows slowly (doubling period 2 weeks). The incubation period is usually 6 months - 10 years. As the infection develops, hematogenous dissemination occurs.

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Symptoms leprosy

Approximately three-quarters of patients develop a single skin lesion during infection that resolves spontaneously; the remainder develop clinical leprosy. Symptoms of leprosy and the severity of the disease vary depending on the degree of cellular immunity to M. leprae.

Tuberculoid leprosy (paucibacillary Hansen's disease) is the mildest form of leprosy. Patients have strong cell-mediated immunity that limits the disease to a few areas of the skin or individual nerves. Lesions contain few or no bacteria. Skin lesions contain one or more hypopigmented spots, with sharp, raised edges, and decreased sensitivity. The rash, as with all forms of leprosy, is not itchy. Lesions are dry because autonomic nerve damage impairs the innervation of the sweat glands. Peripheral nerves may be damaged asymmetrically and are palpated as enlarged in adjacent skin lesions.

Lepromatous leprosy (polybacillary Haneian disease) is the most severe form of the disease. Affected patients have an insufficient immune response to M. leprae and a systemic infection with dissemination of bacterial infiltrates of the skin, nerves, and other organs (nose, testicles, etc.). They may develop macules, papules, nodules, and plaques on the skin, often symmetrical (stuffed with leprosy bacteria). Gynecomastia, loss of digits, and often severe peripheral neuropathy may develop. Patients lose their eyelashes and eyebrows. The disease in western Mexico and throughout Latin America causes diffuse cutaneous infiltration with loss of body hair and other skin lesions, but without focality. This is called diffuse lepromatosis or leprosy bonita. Patients may develop subacute erythema nodosum, and those with diffuse lepromatosis may develop the Lazio phenomenon, with ulcers, especially on the legs, often serving as a source of secondary infection, leading to bacteremia and death.

Borderline leprosy (multibacillary) is intermediate in nature and is the most common. Skin lesions resemble tuberculoid leprosy, but are more numerous and irregular; they affect the entire limb, peripheral nerves with the appearance of weakness, loss of sensitivity. This type has an unstable course and can develop into lepromatous leprosy or have a reverse development with a transition to the tuberculoid form.

Lepromatous reactions

Patients develop immunologically mediated reactions. There are two types of reactions.

Type 1 reactions are caused by spontaneous increases in cellular immunity. They occur in approximately one third of patients with borderline leprosy, usually after treatment has begun. Clinically, there is an increase in inflammation within existing lesions with the development of skin edema, erythema, neuritis with pain, and loss of function. New lesions may develop. These reactions are significant, especially in the absence of early treatment. Since the immune response increases, this is called a reversible reaction, despite possible clinical deterioration.

The second type of reaction is a systemic inflammatory reaction resulting from the deposition of immune complexes. It is also called leprous subacute erythema nodosum. It used to occur in about half of patients with borderline and lepromatous leprosy during the first year of treatment. It is now less common because clofazimine is added to the treatment. It can also develop before treatment. It is a polymorphonuclear vasculitis or panniculitis with possible involvement of circulating immune complexes and increased T-helper function. The level of tumor necrosis factor increases. Leprous subacute erythema nodosum is erythematous, painful papules or nodules with pustules and ulcers. It is accompanied by fever, neuritis, lymphadenitis, orchitis, arthritis (large joints, especially the knees), glomerulonephritis. As a result of hemolysis and bone marrow suppression, anemia and hepatitis with a moderate increase in functional tests may develop.

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Complications and consequences

Leprosy has complications that develop as a result of peripheral neuritis, as a consequence of infection or leprosy reaction; decreased sensitivity and weakness appear. Nerve trunks and microscopic nerves of the skin may be affected, especially the ulnar nerve, which leads to the formation of claw-like 4th and 5th fingers. Branches of the facial nerve (buccal, zygomatic) and the posterior auricular nerve may also be affected. Individual nerve fibers responsible for pain, temperature and fine tactile sensitivity may be affected, while larger nerve fibers responsible for vibration and positional sensitivity are usually less affected. Surgical tendon transfers can correct lagophthalmos and functional impairment of the upper limbs, but should be performed 6 months after the start of therapy.

Plantar ulcers with secondary infection are a major cause of disability and should be treated with debridement and appropriate antibiotics. Patients should avoid weight bearing and wear an immobilizing bandage (Unna boot) to maintain mobility. To prevent recurrence, calluses should be treated and patients should wear custom-made shoes or deep shoes that prevent friction of the foot.

The eyes can be very seriously affected. In lepromatous leprosy or leprous erythema nodosum, iritis can lead to glaucoma. Corneal numbness and damage to the zygomatic branch of the facial nerve (causing lagophthalmos) can lead to corneal trauma, scarring, and loss of vision. In such patients, artificial lubricants (drops) must be used.

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

Men with leprosy may develop hypogonadism, resulting from decreased serum testosterone levels and increased follicle-stimulating and luteinizing hormones, with the development of erectile dysfunction, infertility, and gynecomastia. Testosterone replacement therapy may alleviate symptoms.

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

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Diagnostics leprosy

The diagnosis of leprosy is based on the characteristic clinical picture of skin lesions and peripheral neuropathy and is confirmed by microscopy of biopsy samples; the microorganisms do not grow on artificial media. Biopsy is performed from the raised edges of tuberculoid lesions. In patients with the lepromatous form, biopsy should be performed from nodules and plaques, although pathological changes can occur even in normal areas of the skin.

The test for IgM antibodies to M. leprae is highly specific but has low sensitivity. These antibodies are present in almost all patients with the lepromatous form, but only in two-thirds of patients with the tuberculoid form. Since detection of such antibodies may indicate asymptomatic infection in endemic foci, the diagnostic value of the test is limited. They may be useful for monitoring disease activity, since antibody levels fall with effective chemotherapy and rise with relapse.

Lepramine (heat-inactivated leprae) is available for skin testing but lacks sensitivity and specificity and is therefore not recommended for clinical use.

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Treatment leprosy

Leprosy has a favorable prognosis if the disease is treated in a timely manner, but cosmetic deformity leads to ostracism of patients and their family members.

Medicines against leprosy

The mainstay of treatment for leprosy is dapsone 50-100 mg orally once daily (for children 1-2 mg/kg). Side effects include hemolysis and anemia (moderate), allergic dermatitis, which can be quite severe; rarely, a syndrome including exofergent dermatitis, high fever, and changes in the blood count (white blood cells) as in mononucleosis (dapsone syndrome). Although cases of dapsone-resistant leprosy have been described, resistance is low, and patients respond to usual drug doses.

Rifampin is the first bactericidal drug for the treatment of M. leprae. But it is very expensive for many developing countries when given at the recommended dose: 600 mg orally once daily. Adverse effects are associated with treatment interruption and include hepatotoxicity, flu-like symptoms, and, rarely, thrombocytopenia and renal failure.

Clofazimine has similar activity to dapsone against M. leprae at doses ranging from 50 mg orally once daily to 100 mg three times weekly; 300 mg once monthly is useful 1 (X for the prevention of type 2 and possibly type 1 leprosy reactions. Side effects include gastrointestinal disturbances and reddish-dark dichromacy of the skin.

Treatment of leprosy is also carried out with ethionamide in doses of 250-500 mg orally once a day. However, it can often cause gastrointestinal disturbances and liver dysfunction, especially when used together with rifampin, and is not recommended unless regular monitoring of liver function is possible.

Three antibiotics, minocycline (100 mg orally once daily), clarithromycin (500 mg orally twice daily), and ofloxacin (400 mg orally once daily), have recently been shown to rapidly kill M. leprae and reduce skin infiltration. Their combined bactericidal activity against M. leprae is greater than that of dapsone, clofazimine, and ethionamide, but not rifampin. Only minocycline has proven safety in long-term therapy, which is necessary in leprosy.

Recommended schemes

Although antimicrobial treatment for leprosy is effective, optimal regimens are unknown. In the United States, drug susceptibility testing in mice is often recommended for patients with lepromatous and borderline leprosy.

WHO recommends combination regimens for all forms of leprosy. Treatment of lepromatous leprosy requires more active regimens and duration than for tuberculoid leprosy. In adults, WHO recommends dapsone 100 mg once daily, clofazimine 50 mg once daily + 300 mg once monthly, and rifampin 600 mg once monthly for at least 2 years or until skin biopsy is negative (approximately 5 years). For tuberculoid leprosy without isolation of acid-fast bacilli, WHO recommends dapsone 100 mg once daily and rifampin 600 mg once monthly for 6 months. Many authors from India recommend treatment for more than 1 year.

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

Lepromatous reactions

Patients with the first type of reaction (excluding minor inflammations) are given prednisolone 40-60 mg orally once a day, starting with 10-15 mg once a day and then increasing over several months. Minor skin inflammations are not treated.

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

Prevention

The BCG vaccine and dapsone have limited efficacy and are not recommended for prevention. Since leprosy is minimally contagious, the historically used isolation has no scientific basis. Prevention of leprosy consists of avoiding direct contact with the secretions and tissues of infected patients.

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