Contents
Leprosy is an infectious bacterial disease that can manifest symptoms up to 20 years after infection. If they do appear, they are, for example, local skin discoloration, thickenings, and sensory disturbances. Leprosy causes deformation of the body.
The etiology of leprosy
The leprosy germ was discovered in 1871 by the Norwegian physician Gerhard Henrik Hanzen, hence the name “Hanzen’s disease” was used. Acid-fast Mycobacterium is an intracellular pathogen, found mainly in macrophages, in clusters next to numerous Aquatic Warblers. The optimal temperature for growth is 27-30 ° C, which means that the colder parts of the body (the skin of the face, limbs, auricles, peripheral nerves) are most often damaged. The leprosy bacillus divides very slowly, which explains the long brooding period of the disease. M. leprae cannot be cultivated on bacteriological media, but multiplies well when injected infected material into the foot of mice, which is used in the diagnosis of doubtful cases.
Epidemiology trądu
M. leprae mycobacteria attack humans, but have also been found in some species of monkeys and armadillos. Their presence in soil has also been proven. The transmission of mycobacteria by insects and human contamination through the skin, especially damaged skin, cannot be ruled out.
In cases of lepromatic leprosy, large amounts of acid-fast mycobacteria are found in the patient’s tissues, including in the nasal mucosa – hence the possibility of infection by droplets and dust. Infection occurs most often with close and long-term contact with the sick, especially with damaged skin. Leprosy is a weak pathogen and hardly overcomes the defenses of the infected organism. Therefore, the hatching period of the clinical form is many years, up to 10 years. Only in organisms that were not in contact with M. leprae, i.e. in young children, the incubation period may be several months. A big problem in the epidemiology of leprosy are individuals, inhabitants of endemic areas where leprosy was unknown, not showing symptoms of the disease, but in whom Mycobacterium leprae is detected in the tissues after careful examination. Leprosy bacteria were also found in the milk of nursing mothers.
Incidence of leprosy
A person can get leprosy at any age, but the highest incidence was found in the third decade of life. Currently, the greatest endemic outbreaks of leprosy are in Southeast Asia, South America and Central Africa. The highest incidence was found in India, Brazil, Nepal, Mozambique and Angola. Registration of patients covering one hundred and several dozen countries in the 80s conducted by the World Health Organization (WHO) indicated over 10 million patients. According to epidemiologists’ estimates, the same number of cases could not be included in the diagnosis and treatment. Leprosy in these countries posed a threat to public health. Therefore, WHO has taken action to eliminate leprosy as a social disease, assuming that such a state will be achieved with the incidence of less than 1 disease per 10 inhabitants. The campaign, carried out effectively thanks to the effort aimed at early detection of infected individuals and the use of multi-drug therapy, led to the achievement of the intended goal in over a hundred countries. However, leprosy is still a threat to public health in several endemic countries. India and Brazil are leading the way in this regard.
Leprosy – pathogenesis and pathological changes
The type and severity of changes in leprosy are determined by the reactivity of the immune system and genetic factors. In cases where the Th1 response is dominant, the tuberculoid form develops. In granulomatous changes in tissues, there are infiltrations of lymphocytes (predominance of CD4 cells), epithelial cells and giant cells. The concentration of IFN-gamma and inflammatory cytokines increases. The skin reaction with lepromin obtained from killed mycobacteria is most often positive, which is a cell-type response (tests of inhibition of macrophage migration and blast transformation of lymphocytes confirm this type of reaction).
In the second extreme clinical, lepromatic form, the reaction of the Th2 lymphocyte population predominates. The histological sections show infiltrates of macrophages, foam cells, and acid-fast mycobacterial clusters. The lepromin test is usually negative. This is explained by the excessive production of antibodies and autoantibodies due to the weakening of T-lymphocytes (CD8 and Th2). At the same time, the macrophage function, which phagocytized the leprosy bacilli, is weakened. As a result, there is an immune collapse against M. leprae. Nodular lesions appear in the skin and subcutaneous tissue of patients with lepromatic leprosy, which are called erytherma nodosum leprosum. As a result of the deposition of immune complexes in the blood vessels of the skin and subcutaneous tissue, inflammation of these tissues and the formation of deep ulcers (the so-called Lucia phenomenon) sometimes occurs. In neglected cases, ulcers become bacterial superinfections, which can lead to septic conditions and be fatal.
Clinical forms and symptoms of leprosy
Apart from the two extreme forms of leprosy, tuberculoid and lepromatic leprosy, we observe patients with indirect symptoms that partly include the features of both extreme forms, e.g. in damaged tissues there are infiltrations of lymphocytes and macrophages without giant cells. A more detailed clinical classification also distinguishes between intermediate forms with predominance of tuberculoid features and intermediate forms with predominance of lepromatic features, which in total gives the basis for distinguishing five forms of leprosy.
There are also patients whose changes affect only the nervous system. The vast majority of patients demonstrate the tuberculoid form with lesions in the skin that are in limited spaces. The skin is then dry, often discolored. The few changes called leprid are most common on the face, limbs, but also on the torso. Often these changes are accompanied by infiltration in the peripheral nerves, most often in the ulnar nerve, the accessory nerve (in the posterior triangle of the neck) and the peroneal nerve. Shallow hardened nerves are palpable. Critical sensations appear, and then the feeling of touch, temperature and pain disappear, which leads to severe injuries and burns. Neuropathies lead to muscle wasting, tendons, and bone deformities. Mycobacteria are usually not detected in tissue sections. However, in repeated nerve biopsies, the diagnosis can be confirmed by detecting mycobacteria. The method is rarely used due to its invasive nature and possible complications.
The lepromatic form leads to the formation of larger infiltrates in the tissues with a symmetrical distribution of lesions. Lumps and discoid incisions appear in the skin, which can reach deep into the tissues and destroy them. Early changes in the nasal mucosa, the secretion of which almost always contains a large amount of mycobacteria. There are also changes in the conjunctiva and corneas of the eyes. There are extensive flat lesions in the skin with hair loss called diffuse leprosy. In these cases, deep necrotic changes described in the literature as the Lucia phenomenon may occur. Thickening of the skin on the forehead (edema), on the border with the lips of the mouth, in the auricles and the collapse of the nose bridge leads to the characteristic lion’s face. Bones are destroyed, especially in the mandible, nasal septum and finger joints. Testicular involvement may occur, followed by aspermia and impotence.
Leprosy diagnosis
The basis of the leprosy diagnosis process is the correct assessment of the characteristic skin lesions, often associated with peripheral nerve infiltrates with disturbances in the sensation of pain, temperature and touch. Detection of M. leprae mycobacteria from sections of the nasal mucosa, from the skin (from the periphery of platelets, papules or ulcerations), and from biopsies of altered organs is a certain confirmation of the diagnosis. However, it should be remembered that in tuberculosis leprosy the results are usually negative.
Skin tests with lepromin, which are usually positive in the tuberculoid form, but often negative in the lepromatic form, have a lower diagnostic value. This is explained by the excess of antibodies and autoantibodies formed by a strong stimulation of the immune system with a very large amount of antigen from mycobacteria.
The basis of serological reactions is the reaction of specific IgM antibodies with the glycolipid antigen. Positive results are found in patients with the lepromatic form and in some people who are infected but do not show symptoms of the disease. Specific antibodies are not detected in patients with the tuberculoid form, so the diagnostic value of this test is questionable. This test is used to assess the progress of treatment and exacerbations, mainly in the so-called leprosy during treatment.
In special cases suspected of having a oligobacterial form (most often tuberculoid), when mycobacteria cannot be detected in scrapings and tissue biopsies, a biological test can be used by injecting the test material into the foot of mice.
A more reliable method in the above-mentioned cases will be an attempt to detect genetic material using the PCR technique.
Differentiation of leprosy
The differentiation of skin lesions should include: lupus erythematosus, dermatophytosis, secondary and tertiary syphilis lesions, stem nevi, cutaneous leishmaniasis, filariosis, sarcoidosis, annular granuloma, nodular granuloma, neurofibromatosis and scars. Leprosy neuropathies must be distinguished from diabetic neuropathy, hypertrophic neuropathy, congenital sensory disturbances, and changes in syringomyelia.
Leprosy – treatment
In the leprosy treatment program, the WHO made three main recommendations:
- early disease detection;
- rapid classification of the type of leprosy and implementation of an appropriate pharmacological treatment regimen;
- proper rehabilitation in terms of both somatic and mental.
Afflicted with leprosy painfully feel isolation in their own environment, and often fall into deep depression. Until the 70s, the primary drug was dapsone (diamino-diphenylsulfone). Monotherapy with dapsone or other antituberculosis drug turned out to be inappropriate due to the development of drug resistance, a high percentage of late leprosy reactions in the form of exacerbation of changes in the skin and other affected organs or the formation of new infiltrates, including leprosy erythema nodosum. Dangerous reactions occur in the case of inflammation of the peripheral nerves, leading to sensory disturbances and paresis.
In 1982, WHO introduced the principle of combination therapy based on rifampicin, an antibiotic with high bactericidal power against acid-fast mycobacteria. A single dose of 600 mg of rifampicin eliminates more than 90% of leprosy mycobacteria from the tissues. Patients with low-bacterial leprosy should be treated for at least 6 months with two drugs: rifampicin 600 mg given once a month and dapsone in a daily dose of 100 mg.
Patients with the rich bacterial form are treated with three drugs according to the following schedule: 600 mg of rifampicin and 300 mg of clofazimine, once a month, and a daily dose of 50 mg of clofazimine and 100 mg of dapsone over 12 months. If a monofocal lesion is detected, a single dose of three drugs is sufficient: 600 mg of rifampicin, 400 mg of ofloxacin and 100 mg of minocycline (semi-synthetic tetracycline). Other regimens are also used in various leprosy treatment centers. In the case of high-bacterial leprosy, multi-drug treatment is extended to 24 months or until the mycobacteria are no longer detected. A combination of clarithromycin 500 mg with minocycline 100 mg and ofloxacin 400 mg administered daily orally is also known.
Mild forms of leprosy, such as early erythema nodosum, can be treated with aspirin or NSAIDs. In more severe forms, especially when neuropathies are found, steroid therapy is required. Oral prednisone is recommended in initial doses of 40-60 mg gradually reduced to a maintenance dose of 15-5 mg over many months. In persistent relapses, thalidomide and clofazimine are sometimes used.
Various vaccines have been tried to prevent and treat leprosy, starting with BCG and later with vaccines obtained from killed mycobacteria of different species of mycobacteria. When methods for the multiplication of M. leprae were achieved, attempts were made to immunize the population with a vaccine from leprosy mycobacteria alone. The BCG combination vaccine with killed leprosy showed the best results in terms of protection against severe forms of leprosy. Attempts are being made to create new generation vaccines using M. leprae genes placed in recombinant BCG mycobacteria, producing secreted proteins with antigenic properties.
The prognosis of leprosy
Leprosy is treatable in cases detected early with appropriate treatment initiated early. Relief of symptoms, negative bacteriological test results, including negative biological test in mice, all indicate a cure. In cases with advanced lesions, the prognosis is careful. Late immune responses leading to multiorgan inflammatory changes (e.g. glomerulonephritis, iritis and glaucoma, and many others) are possible. Deeply penetrating infiltrates destroy cartilage and joints, causing deformation of the face and limbs. Fatal deaths are the most common result of additional infections, ulcerations and sepsis.
Summation
- Leprosy is a chronic infectious disease caused by Mycobacterium leprae.
- The infection is most often caused by direct and long contact with someone suffering from leprosy.
- The lesions mainly affect the skin, mucous membranes and the peripheral nervous system.
- Multi-drug treatments recommended by a group of WHO experts apply.
Literature
- Wayne M. Meyers: Leprosy, [w:] Hanter’s Tropical Medicine, W.B. Saunders Company, Philadelphia 1991.
- Ishi N.: Recent Advances of the Treatment of Leprosy, Dermatology Online Journal, Vol 9; Nr 225.
- Janaszek W .: Perspectives for the elimination of leprosy in the world, Przegląd Epidemiologiczny 2002; 56: 577, 86.
- Katoch V.M.: Advances in the diagnosis and treatment of leprosy, Expert Reviews in Molecular Medicine, Cambridge University Press JSSN, 1962-3994.
- Ardalan M., Ghaffari A., Ghabili K.: Lepromatous leprosy in a kidney transplant receipient: a case report, Exp Clin Transplant 2011 Jun 9 (3): 203-206.
- The Merck Manual. Handbook of Diagnostics and Therapy, Urban & Partner, Wrocław 2001, p. 1429.
Source: J. Cianciara, J. Juszczyk, Infectious and parasitic diseases; Czelej Publishing House