Definition and Cutaneous Features
|FIgure X-1 | Photo courtesy of Web Pathology Opens in new window|
Leprosy (also known as Hansen disease) is a chronic, slowly progressive infection caused by Mycobacterium leprae Opens in new window that mainly affects the skin and peripheral nerves and results in disabling deformities. Despite its low communicability, leprosy remains endemic among an estimated 10 to 15 million people living in poor tropical countries.
Persons of any age may become infected. Leprosy has a modal age distribution with peaks at 10–14 years and 35–44 years. The male to female ratio is 2:1, and infants are rarely affected.
A distinctive feature of leprosy is involvement of nerves, which may occur during any phase of the disease. M. leprae Opens in new window is the only mycobacterium that regularly invades nerves.
M. leprae multiplies in the skin histiocytes and the Schwann cells of nerves. Thus, the most characteristic clinical feature of leprosy is the association of skin and nerve lesions.
Another distinctive feature of leprosy is the distribution of lesions in cooler parts of the body, particularly the skin, mucous membranes of the upper respiratory tract (turbinates, nasal septum, larynx), anterior part of the eye, testes, nerve trunks that are close to the skin surface, and lymph nodes that drain dermal lesions.
Occasionally, lymphadenopathies Opens in new window may be the initial manifestation of the disease in the absence of skin and nerve lesions.
When tests for syphilis are performed on the sera of patients with moderate or advanced lepromatous leprosy, the results are frequently false-positive.
Epidemiology: Incidence and Prevalence
About 5.5 million people are estimated to have leprosy around the world, with the majority of cases occurring in the tropics. Sixty percent of cases occur in Asia, and 3.5 million of these are in India.
The prevalence is not high—1% to 5%, even in endemic areas. In the United States, the number of cases has increased, and leprosy is reported among immigrants from countries where the disease is endemic.
Approximately 6,000 cases exist in the United States, with 200 to 300 new cases added annually. Small endemic foci exist in Hawaii, Louisiana, and Texas.
The human leprosy bacillus is an obligate intracellular that is notable for its limited host range, its unique ability to enter nerves, and its failure to grow in vitro, which has prevented progress in research and the development of vaccines.
A leprosy-like disease was reproduced in armadillos, and the leprosy bacillus was grown in the mouse footpad.
In humans, the transmission of leprosy is by direct contact through skin abrasion or mucous membranes of the mouth or nose. Infectivity is not high, even among close family contacts.
Classification of Leprosy
Although there is no universal agreement on the classification of leprosy, the disorder is usually divided into several clinical subtypes depending on the patient’s degree of immunity to M. leprae (Table X-1).
|Table X-1 | Classification of Leprosy (in Order of Decreasing Host Resistance)|
|Tuberculoid (TT) (mildest; high resistance)||A single or few localized anesthetic macules or plaques; hair loss within lesions; few if any organisms; peripheral nerve involvement common|
|Borderline tuberculoid (BT)||Lesions similar to TT but more numerous; satellite papules around larger lesions (at times); hair and sensation diminished (but nor absent) within lesions; peripheral nerve involvement common|
|Borderline borderline (BB)||Features of both TT and LL; more lesions than BT; borders more vague; nerve involvement and satellite lesions common; many bacilli usually present|
|Borderline lepromatous (BL)||Multiple nonanesthetic asymmetrically distributed annular plaques; may be surrounding papules; late neural lesions; leonine facies|
|Table X-1 continues ...|
|Lepromatous (LL) (most severe; low or no resistance)||Generalized involvement (skin, mucous membranes, upper respiratory tract, reticuloendothelial system, adrenal glands, and testes); no neural lesions until late; no sensory or hair growth impairment; many bacilli in tissue|
|Indeterminate||Small number of hypopigmented macules; no thickened nerves or sensory impairment|
|Note that the three intermediate variants (BT, BB, and BL) are clinically unstable and may pass from milder to more severe states and vice versa.|
At one end of the spectrum is the lepromatous (LL) form of the disorder, the disfiguring disease most familiar to the public.
In the lepromatous leprosy, cellular resistance against Mycobacterium leprae is minimal, and patients may present with erythematous or hypopigmented skin macules, papules, nodules, plaques, or diffuse infiltrations.
In addition, patients may develop widespread disease involving the upper respiratory tract, sensory and motor nerves, eyes (superficial keratis), testes, lymph nodes, and bone.
Many bacilli are present in the tissues. Nodules Opens in new window or diffuse infiltrates, especially on the face and earlobes, produce the characteristic leonine facies Opens in new window. Loss of eyebrows and eyelashes may also occur.
The lepromatous lesions are poorly defined and tend to become confluent. In the progressive phase of the disease, the lesions contain numerous lepra cells Opens in new window and large numbers of acid-fast bacilli Opens in new window.
There is a deficiency of helper T cells specific for M. leprae antigens, and of suppressor T cells specific for M. leprae Opens in new window. The romin test result is generally negative.
At the opposite pole is tuberculoid leprosy (TT), a form that occurs in patients with a very high degree of immunity against M. leprae. Opens in new window
In tuberculoid leprosy, patients have only a single (or occasionally a few) large well-defined macule(s) or infiltrative plaques that show hypopigmentation Opens in new window and loss of sensation.
The peripheral nerves, most commonly the ulnar, external popliteal, and great auricular nerves, are thickened and palpable, and patients may develop trophic disturbances and paralyses. Between these ends of the spectrum, borderline forms of the disorder are seen.
Borderline Lepromatous Leprosy
Patients with borderline lepromatous leprosy tend to have the most extensive involvement of nerves. Owing to the decreased sensation in affected areas, these patients are at risk for secondary infections and digital ulceration. Blindness occurs in around 5% of patients with leprosy.
The clinical signs and symptoms of leprosy directly reflect the relationship between infectious agent and host.
The host response is determined by the host immune status, which appears to be affected in leprosy by a diminished number of circulating T cells.
The disease takes two principal forms, lepromatous and tuberculoid, which represent opposite extremes of the immune response; a spectrum of intermediate lesions and manifestations is seen.
Studies in which HLA typing is used to indicate that individual receptivity for leprosy is genetically determined and that the tuberculoid form is related to an HLA-linked recessive gene.
A critical problem in leprosy is the relative deficiency of antigen-specific, T-cell-mediated immunity. These T cells are generated in the lymph nodes, but are not present in the peripheral blood of patients with lepromatous leprosy.
Like those of other organs, lymph node lesions show a spectrum of changes that extend from lepromatous to tuberculoid leprosy.
In a study of 77 lymph nodes from 62 patients with leprosy, representing the entire disease spectrum, Turk and Waters documented the correlation of histologic lesions with clinical stage and lepromin test results.
In order of frequency, the lymph nodes that are enlarged and have similar lesions to those in the skin are inguinal, cervical, axillary, epitrochlear, and preauricular.
In lepromatous leprosy lymphadenitis, the lymph nodes may be considerably enlarged. The paracortical areas are largely depleted of lymphocytes, which are replaced by sheets of histiocytes, including frequent lepra cells that contain large numbers of mycobacteria.
In early lesions, only one or a few bacilli are present in the cytoplasm of histiocytes. In advanced cases, typical foamy histiocytes or lepra cells containing masses of acid-fast bacilli (globi) are commonly seen.
Cells situated in the subcapsular region of the lymph nodes appear to be more heavily parasitized with bacilli than do those in deeper areas.
The number of bacilli in histiocytes vary between microglobi and large globi, but after the containing cells degenerate, the bacilli are released free in the tissues.
The germinal centers are prominent, and large aggregates of plasma cells are present at the corticomedullary junction and in the medullary cords.
In the skin, diffuse infiltrates of foamy macrophages are present in the dermis below a subepidermal zone (grenz zone) of uninvolved dermis. Nerves are invaded by numerous bacilli, but are fairly well preserved with few cellular infiltrates.
In tuberculoid leprosy lymphadenitis, the lymph nodes are generally smaller and the germinal centers inconspicuous. Non-necrotizing granulomas, similar to those of sarcoidosis, are scattered throughout the nodal parenchyma.
The histiocytes have the typical appearance of epitheloid cells and are arranged concentrically.
Multinucleated giant cells of the Langhans type are present in the center of granulomas.
The periphery is occupied by thick cuffs of lymphocytes that separate the granulomas, although these may occasionally coalesce.
Nerves in the adjacent tissues may be surrounded by granulomas and are swollen and degenerate. Lepra cells are not seen, and acid-fast bacilli are very rare, if they are present at all.
In borderline leprosy, intermediate histologic patterns develop, whereas in patients treated for long periods, the lepromatous infiltrates are broken up by broad bands of lymphocytes that progressively repopulate the paracortical areas.
The histoid leprosy, another variant kind of leprosy, one described by Wade, is characterized by spindle-shaped histiocytes containing phagocytosed bacilli oriented parallel to the long axis of the cell.
This form of leprosy appears to develop after prolonged medical treatment. Antileprosy BCG vaccines may result in regional suppurative lymphadenitis.
Treatment should be directed by a clinician experienced in the care of patients with leprosy and preferably in a Hasen-disease center where feasible.
Although therapeutic recommendations of the past called for monotherapy with dapsone, given increasing resistance to this approach MDT is now recommended and includes other agents such as rifampin and clofazimine.
In treated patients, 95% of all nerve function impairment develops within 2 years, supporting a decreased frequency for neurologic follow-up examination in patients without neurologic findings by that time.
Leprosy reactions are fairly commonplace during treatment for the disease are related to immune-mediated inflammation. These reactional states, which include reversal reactions and erythema nodosum leprosum (ENL), may results in worsening of neural and skin lesions and significantly tissue damage.
These reactions are often treated with systemic corticosteroids and in the case of ENL, thalidomide is a very effective agent. Although there is no effective vaccination for leprosy, BCG vaccination has been demonstrated to be effective at protecting some populations from infection.
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