bubble_chart Overview

Leprosy (Leorsy, Lepra) is a chronic infectious disease caused by the leprosy bacillus. It primarily affects the skin, mucous membranes, and peripheral nerves, and can also invade deep tissues and organs. The disease is widespread globally, with an estimated 10 million cases worldwide, mainly distributed in Asia, Africa, and Latin America. Leprosy is a chronic infectious disease caused by the leprosy bacillus, with primary lesions occurring in the skin and peripheral nerves. Clinical manifestations include numb skin lesions and thickened nerves, with severe cases leading to limb deformities. The disease is prevalent worldwide, and in China, it is endemic in provinces and autonomous regions such as Guangdong, Guangxi, Sichuan, Yunnan, and Qinghai. Since the founding of the People's Republic of China, active prevention and treatment efforts have effectively controlled the disease, leading to a significant decline in incidence rates.

bubble_chart Etiology

disease cause

The causative agent is the leprosy bacillus. Under a light microscope, intact bacilli appear as straight or slightly curved rods, approximately 2–6 micrometers in length and 0.2–0.6 micrometers in width, lacking flagella, spores, or a capsule. Incomplete forms may appear as short rods, diplococci, bead-like, or granular shapes. When present in large numbers, they tend to cluster, forming globular or brush-like aggregates. Under an electron microscope, new structures of the leprosy bacillus can be observed. The leprosy bacillus stains red with acid-fast staining and is Gram-positive. Once outside the body, the leprosy bacillus loses its reproductive capacity after 2–3 hours of sunlight exposure in summer, or loses viability after one hour at 60°C or two hours of UV irradiation. Common sterilization methods such as boiling, autoclaving, or UV irradiation can effectively kill the bacillus.

Humans are the natural hosts of the leprosy bacillus. In patients (particularly those with lepromatous leprosy), the bacillus is widely distributed, primarily found in the skin, mucous membranes, peripheral nerves, lymph nodes, and certain cells of the reticuloendothelial system such as the liver and spleen. In the skin, it is mainly located in nerve endings, macrophages, smooth muscle, hair follicles, and blood vessel walls. It is also commonly found in mucous membranes. Additionally, the bone marrow, testes, adrenal glands, and anterior segments of the eyes are susceptible to invasion and colonization by the bacillus. Small numbers of leprosy bacilli may also be detected in peripheral blood and striated muscle. The bacillus is primarily shed through broken skin and mucous membranes (especially the nasal mucosa). It can also be found in small quantities in breast milk, tears, semen, and vaginal secretions.

Animal inoculation of the leprosy bacillus: In 1960, Shepard achieved preliminary success by inoculating the bacillus into the footpads of mice, establishing a localized infection model. In 1966, Ress advanced the field by using immunosuppression to induce severe systemic infection. In 1971, Kirchheimer and Storrs successfully inoculated the bacillus into armadillos, creating an armadillo infection model. In 1976, Takemura and colleagues reported successful inoculation of the bacillus into nude mice (congenitally athymic mice).

Artificial cultivation of the leprosy bacillus has not yet been universally recognized as successful. Thus, in vitro cultivation remains a key focus for future research.

The primary mode of leprosy transmission is direct contact, followed by indirect contact.

1. Direct contact transmission occurs when a healthy individual comes into direct contact with an infectious leprosy patient, typically through exposure of broken skin or mucous membranes to lesions containing the bacillus. This mode of transmission is most common among close family members of patients. While the degree of contact correlates with the likelihood of infection, occasional contact can still result in transmission.
2. Indirect contact transmission involves exposure to the bacillus through contaminated objects used by infectious patients, such as
3. clothing,
4. bedding,
5. towels, or eating utensils. Although less common than direct transmission, indirect transmission cannot be overlooked.
6. Other theoretical modes of transmission include invasion through the skin,
7. respiratory tract, or
8. digestive tract. Recent emphasis has been placed on respiratory transmission, as the nasal mucosa is considered the primary route of bacillus shedding. Nasal secretions containing the bacillus can survive outside the body for extended periods, and contaminated dust or droplets may infect healthy individuals through inhalation. Some have also suggested blood-sucking insects as potential vectors. However, these theories remain debated and unconfirmed in leprosy epidemiology.

   It must be pointed out that although there is currently insufficient evidence to confirm the primary route of pestilence transmission, the body's resistance undoubtedly plays a dominant role in the process of pestilence. Although the chance of infection among people around a pestilence patient is similar, only a minority actually develop leprosy. In areas near leprosy hospitals (or villages), the incidence of leprosy is not particularly high, and even among spouses of leprosy patients, the disease rate generally does not exceed 5%. Furthermore, about two-thirds of leprosy patients report no history of leprosy contact. These observations indicate that most individuals with long-term close contact do not develop the disease. Whether leprosy bacilli cause illness after entering the human body, as well as the course and manifestations of the disease, primarily depend on the infected individual's resistance

9. That is, the immune status of the organism. In recent years, many people believe that leprosy, like many other pestilential diseases, has subclinical infections (Subclinical infection), which explains why the infection rate of leprosy is much higher than the incidence rate. The vast majority of individuals who come into contact with the disease develop specific immunity to the leprosy bacteria after infection, terminating the infection through subclinical infection.

   The pathogenesis

   of leprosy: Leprosy is a chronic pestilential disease model and also a model of chronic immune-pestilential disease. For a long time, it has been observed that there are two distinct polar types clinically: the subcutaneous nodular type and the lepromatous type. Each type of leprosy shows significant differences in histopathology and the amount of bacteria within the tissues. These differences are not due to different strains of leprosy bacilli but rather to the varying immune responses of the organism to the leprosy bacilli. In recent years, based on clinical

10. , bacterial
11. , pathological
12. , and immunological manifestations and characteristics, this gradual transition phenomenon can be observed. To vividly illustrate this immune-based state, the concept of an immune spectrum from physics has been borrowed to establish the immune spectrum phenomenon of leprosy. That is, from the subcutaneous nodular type
13. , borderline
14. (borderline leaning toward subcutaneous nodular type
15. , intermediate borderline
16. , borderline leaning toward lepromatous type) to the lepromatous type, it resembles a continuous spectrum. Some studies indicate that the organism's immunity determines the course of leprosy infection, such as whether the disease develops after infection
17. , the type of disease, and its outcome. From biopsies of the skin and lymph nodes of various types of leprosy, changes in histopathological images can be observed. The degree of lymphocyte infiltration in the lesions and the morphological changes in the tissue macrophage system cells can reflect the different immune responses of patients to the leprosy bacilli.

    The results of tests using humoral and cellular immune measurement methods indicate that most healthy adults have strong immunity to leprosy bacilli, while children have weaker immunity, which gradually strengthens with age. The immunity to leprosy bacilli also varies among different types of leprosy. At one end of the immune spectrum, subcutaneous nodular type leprosy (TT) shows only slightly higher humoral antibodies than normal individuals, while cellular immune function is normal or slightly reduced. At the other end of the spectrum, lepromatous type leprosy (LL) shows significantly higher humoral antibodies, while cellular immune function exhibits severe defects. In terms of humoral antibody production across the leprosy spectrum, the levels are ordered as follows: LL > BL > BB > BT > TT. The lepromatous type, with low immunity, has higher antibody levels than the immune-competent subcutaneous nodular type and normal individuals, which is an anomalous phenomenon. This suggests that although there are high levels of antibodies in the serum of leprosy patients, they seem to have no protective or beneficial effect on the body. In terms of the intensity of cellular immune responses, the order is: TT > BT > BB > BL > LL. The immune defense mechanism of leprosy is primarily cellular immunity. It should be noted that the suppression (or defect) of cellular immune responses has both specific and non-specific aspects. In lepromatous type leprosy, effective anti-leprosy treatment can improve non-specific cellular immune defects, but the unresponsiveness to leprosy bacilli (such as the lepromin test) remains unchanged even after years of treatment. The nature and mechanism of this specific defect require further study.

    Pathological changes

    Due to the varying cellular immunity of patients to leprosy bacilli infection, the affected tissues exhibit different histopathological reactions. Based on this, leprosy is classified into the following two types and two categories:

    1. Subcutaneous nodule-like leprosy (tuberculoid leprosy) This type is the most common, accounting for about 70% of leprosy patients. Because its lesions resemble subcutaneous nodular granulomas, it is called subcutaneous nodule-like leprosy. The characteristic of this type is that patients have strong cellular immunity, so the lesions are localized, with very few or even undetectable bacteria in the lesions. The disease progresses slowly and has low infectivity. It mainly affects the skin and nerves, rarely invading internal organs.
    (1) Skin: Lesions mostly occur on the face
18. Limbs
19. Shoulder
20. Back and buttock skin present with clearly demarcated
21. irregularly shaped macula and papule or slightly depressed center
22. slightly raised edge papule. Microscopically, the lesions are granulomas resembling subcutaneous nodule disease, scattered in the superficial dermis, with seasonal disease foci and epidermal contact. The granuloma components are mainly epithelioid cells, occasionally with Langhans giant cells, surrounded by lymphocyte infiltration (Figure 1). Central caseous necrosis is extremely rare in the lesions, and acid-fast staining generally does not reveal acid-fast bacilli. Since the lesions often surround small dermal nerves and skin appendages, they cause local hypoesthesia and anhidrosis. When the lesions regress, only a few lymphocytes or fibrosis remain locally, and eventually, the inflammatory cells may completely disappear.

    There are nodular lesions in the dermis composed mainly of epithelioid cells, among which Langhans cells can be seen, resembling subcutaneous nodule nodules, but without central caseous necrosis

    (2) Peripheral nerves: Most commonly affected are the great auricular nerve

23. ulnar nerve
24. radial nerve
25. peroneal nerve, and tibial nerve, often accompanied by skin disease changes. Pure nerve leprosy without skin disease lesions is relatively rare. The nerves thicken, and microscopically, subcutaneous nodule-like lesions and lymphocyte infiltration are observed. Unlike skin disease changes, the subcutaneous nodule-like lesions in nerves often exhibit caseous necrosis, which may liquefy to form so-called "nerve abscesses." During healing, epithelioid cells disappear, the lesions fibrose, and the nerves become harder in texture. Nerve lesions not only cause superficial sensory disturbances but also accompany motor and trophic disturbances. In severe cases, claw hand (ulnar nerve lesions cause paralysis of the lumbrical muscles, leading to hyperflexion of the finger joints
26. hyperextension of the metacarpophalangeal joints),
27. wrist drop,
28. foot drop,
29. muscle atrophy,
30. plantar ulcers, and even atrophy or absorption
31. disappearance of fingers and toes may occur. With effective prevention and treatment measures, the above limb changes are no longer seen.

    2. Lepromatous leprosy (lepromatous leprosy) This type accounts for about 20% of leprosy patients. Because the skin lesions often protrude from the skin surface, it is called lepromatous. The characteristic of this type is the patient's cellular immune deficiency to leprosy bacilli, with a large number of leprosy bacilli in the lesions, strong pestilence, and frequent involvement of the nasal mucous membrane

32. lymph nodes
33. liver
34. spleen, and testes in addition to the skin and nerves. The disease progresses relatively quickly.

    (1) Skin: The initial lesions are red macula and papule, which later develop into nodular lesions raised above the skin. The nodules are poorly demarcated, scattered, or clustered into masses, often ulcerating to form ulcers. They mostly occur on the face

35. limbs, and back. Facial nodules are symmetrical, and skin nodules on the earlobes
36. nose
37. eyebrow ridges alter the facial appearance, forming leonine facies (facies leontina).

    Microscopically, the lesions are granulomas composed of numerous foam cells (foamy cells), interspersed with a few lymphocytes. Foam cells originate from macrophages. After phagocytosing leprosy bacilli, the lipids of the bacilli accumulate in the macrophage cytoplasm, giving the latter a foamy appearance. Acid-fast staining reveals numerous leprosy bacilli within the foam cells, sometimes aggregated into clumps, forming so-called leprosy globi (globus leprosus). The lesions surround small blood vessels and appendages and later fuse into sheets as the disease progresses. However, there is a cell-free zone between the epidermis and the infiltrates (Figure 2), which is absent in subcutaneous nodule-like leprosy. Due to the patient's cellular immune deficiency to leprosy bacilli, epithelioid cells do not appear in the lesions, and lymphocytes are scarce. During treatment-induced regression, the number of leprosy bacilli decreases, their morphology changes from rod-shaped to granular, foam cells decrease or fuse into vacuoles, and fibrous tissue proliferates. Eventually, the lesions regress, leaving only scars.

    (2) Peripheral nerves: The affected nerves also become thickened. Microscopically, there are foam cells and lymphocyte infiltrations in the perineurium between nerve fibers. Acid-fast staining can reveal numerous leprosy bacilli within foam cells and Schwann cells. In advanced stages, nerve fibers disappear and are replaced by fibrous scars. The clinical manifestations of nerve lesions are similar to those of the subcutaneous nodular type.

    (3) Mucous membrane: The mucous membranes of the nose,

38. oral cavity, and even the throat and vagina can be affected, with the nasal mucous membrane being the most commonly involved.

    (4) Viscera: Organs such as the liver,

39. spleen,
40. lymph nodes, and testes are often affected by lepromatous leprosy, which may be accompanied by enlargement of the liver,
41. spleen, and lymph nodes. Microscopically, foam cell infiltration is observed in all cases. If the seminiferous tubules of the testes are infiltrated by foam cells, the semen may contain leprosy bacilli, which can transmit the disease to others through sexual contact.

3. Borderline leprosy: The immune response of patients with this type lies between that of lepromatous and tuberculoid leprosy. Lesions exhibit features of both lepromatous and tuberculoid types. Depending on the strength of the immune response, the disease may shift seasonally toward either the tuberculoid or lepromatous type. Foam cells and leprosy bacilli are present in lepromatous lesions.

4. Indeterminate leprosy: This type represents the early stage of leprosy, with nonspecific lesions showing only focal lymphocyte infiltration around skin blood vessels or small nerves. Acid-fast staining rarely detects leprosy bacilli. Most cases later progress to the tuberculoid type, while a few develop into the lepromatous type.

bubble_chart Clinical Manifestations

The classification of leprosy is of great significance in the prevention, treatment, and research of leprosy. With the deepening understanding of leprosy and the advancement of medical technology, the classification methods for leprosy have also been continuously evolving. Based on the immunological "spectrum" theory of leprosy, the "five-tier classification method" was proposed in 1962.

Tuberculoid leprosy (TT)

Borderline tuberculoid leprosy (BT)

Mid-borderline leprosy (BB)

Borderline lepromatous leprosy (BL)

Lepromatous leprosy (LL)

Indeterminate leprosy (I)

It must be noted that within the aforementioned immunological "spectrum," the most stable types are TT and LL, while the other types exhibit varying degrees of instability. A BT patient, especially if untreated, may "downgrade," meaning their immunity weakens and shifts toward BB or BL. Conversely, an atypical LL or BL patient may "upgrade" and shift toward BB or BT as their immunity strengthens. Patients who have moved along the "spectrum" (usually through leprosy reactions) can still regain or lose immunity again, shifting back to their original positions on the "spectrum." The most unstable point on the "spectrum" is BB, as few patients remain at this stage for long, often shifting toward BT or BL. Indeterminate leprosy is listed separately outside the "spectrum," considered an early stage of leprosy whose final classification characteristics remain unclear and may evolve into any type within the "spectrum."

After Mycobacterium leprae invades the body, the incubation period is generally considered to average 2–5 years, ranging from a few months to over a decade. If symptoms develop, they often appear insidiously. Before the onset of typical symptoms, some patients may experience nonspecific systemic prodromal symptoms such as general malaise, muscle and joint pain, and abnormal sensations in the limbs. Those with stronger immunity tend to develop tuberculoid leprosy, while those with weaker or deficient immunity tend to develop lepromatous leprosy. Below, the clinical characteristics of each type of leprosy are described according to the five-tier classification method:

1. Tuberculoid leprosy

   Patients with this type have strong immunity, and Mycobacterium leprae is confined to the skin and nerves. Skin lesions include macules, papules, and patches, typically numbering one

or two, with well-defined, clear edges and often significant sensory (temperature, pain, touch) impairment. The distribution is asymmetrical, and the affected areas often show loss of vellus hair, which is a crucial feature. These lesions commonly occur on friction-prone areas such as the limbs, face, shoulders, and arms. Macules and papules may be hypopigmented or faintly red, often without scales. Patches are typically dark red with distinct borders, sometimes raised at the edges and sloping inward toward a flattened, atrophic center, or forming semicircular, circular, or arcuate shapes with varying edge thickness. The surface is often dry and scaly, and sometimes lesions consist of clusters of small papules. Thickened cutaneous nerves may be palpable near the lesions, and nearby lymph nodes may occasionally enlarge. Eyebrows generally do not fall out.

In this type, when the peripheral nerves (such as the great auricular nerve, ulnar nerve, peroneal nerve, etc.) are affected, the nerve trunks become thickened, appearing spindle-shaped, nodular, or beaded. They are hard to the touch and tender, often unilateral. In severe cases, delayed-type hypersensitivity reactions may lead to abscess or fistula formation. Some patients exhibit neurological symptoms without skin lesions, known as pure neuritis. Clinically, this manifests as nerve thickening, sensory impairment in the corresponding skin areas, and muscle weakness. When nerve involvement is severe, disruptions in nerve nutrition and motor function occur, leading to atrophy of the thenar and hypothenar muscles and interosseous muscles. This results in various deformities such as "claw hand" (ulnar nerve involvement), "ape hand" (median nerve involvement), "wrist drop" (radial nerve involvement), "ulcer," "lagophthalmos" (facial nerve involvement), and "bone absorption of fingers (toes)." These deformities tend to develop relatively early.

This type of bacillus examination is generally negative. The leprosy bacillus test is strongly positive. Bacterial immune function is normal or nearly normal. The histopathological changes are subcutaneous nodule-like granulomas, characterized by the absence of an "uninfiltrated zone" under the epidermis, and no acid-fast bacilli are found by acid-fast staining. A few patients may recover without treatment, and if treated, the condition subsides relatively quickly. The prognosis is generally good, but the resulting deformities are often difficult to reverse.

2. Borderline-lepromatous leprosy

The occurrence of this type is similar to that of the subcutaneous nodule-like type, presenting as macules, papules, and patches with colors ranging from light red, purplish-red, to brownish-yellow. The borders are neat and clear, and some patches may have a "blank area" or "punched-out area" (also called the uninfiltrated zone or immune zone) in the center, forming ring-shaped lesions with clearly defined inner and outer edges. The skin within the punched-out area appears normal. Most lesions have a smooth surface, with some having a few scales. The lesions are numerous, vary in size, and may be scattered, predominantly on the trunk, limbs, and face, with a wide but asymmetrical distribution. Although sensory impairment is present, it is milder and slightly delayed compared to TT. Eyebrows and eyelashes generally do not fall out. Nerve involvement is thickened and asymmetrical, less coarse and irregular than in TT. Mucous membranes, lymph nodes, testes, eyes, and internal organs are less and mildly affected.

This type usually tests positive for bacilli, with a bacterial density index (logarithmic classification, same hereafter) of 1–3+. The leprosy bacillus test is weakly positive, doubtful, or negative. Cellular immune function tests are lower than normal. The histopathological changes resemble TT, but the lymphocytes around the epithelioid cells are fewer and more loosely distributed. A narrow "uninfiltrated zone" can be seen under the epidermis, and acid-fast staining of the sections shows no or few leprosy bacilli. The prognosis is generally good. "Upgrading reactions" may shift toward TT, while "downgrading reactions" may shift toward BB. Leprosy reactions can easily lead to deformities and disabilities.

3. Mid-borderline leprosy

The skin lesions of this type are characterized by polymorphism and multicolor. The rash types include macules, papules, patches, and infiltrations. Colors range from wine-red, sallow yellow, brownish-yellow, red, to brown. Sometimes, two colors appear on a single lesion. The borders are partially clear and partially unclear. The shapes of the lesions may be band-like, serpentine, or irregular. If strip-like, one side is clear while the other is infiltrated and unclear. If patch-like, there is a "punched-out area" in the center, with a clearly raised inner ring that slopes outward, and an infiltrated, unclear outer edge, giving a saucer-like appearance. Some lesions appear as red-white rings or multiple rings, resembling a target or badge, called "target-like patches" or "badge-like patches." Some patients have facial lesions shaped like spread-winged bats, grayish-brown in color, termed "bat-like faces." It is common to see lesions resembling both lepromatous and subcutaneous nodule-like types on different parts of the same patient. Sometimes, "satellite-like" lesions can be observed. Some patients may have thick, cushion-like plaques composed of nodules on the extensor surfaces of the elbows, knees, and hips. The lesions are smooth and soft to the touch. They are numerous, vary in size, and are widely but asymmetrically distributed. After nerve damage, grade I numbness occurs, milder than in the subcutaneous nodule-like type but more severe than in the lepromatous type. Eyebrows and eyelashes often do not fall out. Mucous membranes, lymph nodes, eyes, testes, and internal organs may be affected.

This type tests positive for bacilli, with a bacterial density index of 2–4+. The leprosy bacillus test is negative. Cellular immune function tests fall between the two polar types. The histopathological changes consist of histiocytic granulomas, with a mostly present "uninfiltrated zone" under the epidermis. Histiocytes show varying degrees of differentiation into epithelioid cells, generally smaller, and some sections may show typical or atypical foam cells. Lymphocytes are few and scattered. Acid-fast staining of the sections reveals a relatively large number of leprosy bacilli. The prognosis is intermediate between the two polar types. This type is the most unstable, with "upgrading reactions" shifting toward BT and "downgrading reactions" shifting toward BL.

4. Borderline-lepromatous leprosy

The skin lesions of this type include macula and papule, papule, nodules, patches, and diffuse infiltration. Most lesions resemble lepromatous lesions, being more numerous, smaller in size, with indistinct borders, a shiny surface, and a red or orange-red color. The distribution is relatively widespread, with a tendency toward symmetry. Sensory impairment within the lesions is mild and appears later. Some lesions are larger, with a central "punched-out area," clear inner edges, and blurred outer infiltration. Eyebrows, eyelashes, and hair may fall out, often asymmetrically. In the advanced stage, deep diffuse infiltration of the face can also form a "leonine facies." In mid-to-advanced stages, patients may experience mucosal congestion, infiltration, swelling, and tenderness in enlarged lymph nodes and testes. Nerve involvement tends to be bilateral and multifocal, relatively uniform, softer to the touch, and deformities appear later.

This type shows strongly positive bacilli findings, with a bacterial density index of 4–5+. The leprosy reaction is negative, and cellular immune function tests indicate defects. The histopathological changes show granulomatous characteristics leaning toward foam cell granulomas, with some histocytes developing into atypical epithelioid cells and others into foam cells. Lymphocytes often appear in focal clusters, interspersed among foam cell infiltrations, which is a pathological hallmark of this type. Acid-fast staining of tissue sections reveals abundant leprosy bacilli. The prognosis is better than LL but worse than TT, though still unstable; "upgrading reactions" may shift to BB, while "downgrading reactions" may shift to LL.

**Type V Leprosy**

Patients of this type lack immunity to leprosy bacilli, which spread throughout the body via the lymphatic and circulatory systems. Consequently, the invasion of tissues and organs is extensive. The skin lesions are characterized by their large number, widespread and symmetrical distribution, indistinct borders, tendency to merge, and a greasy, smooth surface. The skin color, aside from pale patches, mostly progresses from red to reddish-yellow or brownish-yellow. Sensory impairment is mild. In the early stages, thinning of the eyebrows and eyelashes is evident, starting from the outer edges of the eyebrows and later affecting the eyelashes—a clinical hallmark of lepromatous leprosy. Bacilli examination is strongly positive, and skin lesions include macules, papules, infiltrations, nodules, and diffuse lesions. Early macular lesions are distributed across the body, particularly on the face, chest, and back, appearing faintly red or pale with indistinct borders, requiring careful inspection under good lighting for identification. Later, in addition to increasing macular lesions, superficial and diffuse infiltrations and nodules gradually form. On the face, diffuse thickening due to infiltration results in grade I swelling, often accompanied by eyebrow and eyelash loss. Further progression leads to the fusion of lesions into large infiltrations or the appearance of nodules on existing lesions and diffuse infiltrations, which deepen and worsen, often spreading extensively. The face becomes diffusely thickened with deepened skin creases, thickened nose and lips, enlarged earlobes, complete loss of eyebrows and eyelashes, and patchy or extensive hair loss. Nodules and deep infiltrations merge, and conjunctival congestion creates a "leonine facies" appearance. Multiple nodules of varying sizes appear on the extensor surfaces of limbs, shoulders, back, buttocks, and scrotum. In later stages, partial absorption of diffuse lesions occurs, accompanied by significant sensory impairment and anhidrosis. On the lower legs, the skin becomes grade I hardened, smooth, and shiny, with persistent ichthyosis-like or snake-skin-like lesions. In severe cases, hair loss may be nearly complete, with residual hair often distributed along blood vessels.

Although nerve trunks are affected, sensory impairment is mild and appears later. Nerve trunks are grade I enlarged, symmetrical, and soft. In advanced stages, muscle atrophy, deformities, and disabilities may occur.

Nasal mucosal lesions appear early, initially with congestion and swelling, followed by nodules, infiltrations, and ulcers as the condition worsens. Severe cases may develop perforation of the nasal septum, leading to saddle nose deformity when the nasal bridge collapses. Lymph nodes are affected early, showing grade I enlargement that often goes unnoticed; by mid-advanced stages, the enlargement becomes obvious and tender.

Testicular involvement leads to initial swelling followed by atrophy, tenderness, and gynecomastia.

Ocular involvement may cause conjunctivitis, keratitis, and iridocyclitis. Visceral organs are also affected, such as hepatosplenomegaly.

This type shows strongly positive bacilli findings, 4–6+. Leprosy tests are negative, and cellular immune function tests reveal significant defects. The histopathological hallmark is a foam cell granuloma structure, primarily composed of typical foam cells with abundant cytoplasm. A "non-infiltration zone" lies beneath the epidermis. Acid-fast staining of tissue sections shows large numbers of leprosy bacilli, often clustered or ball-like. Early treatment yields a good prognosis with fewer deformities, but advanced stages may lead to disabilities. This type is relatively stable, with only a very few cases potentially shifting to BL under certain conditions.

**VI. Indeterminate Leprosy**

This type represents the early manifestation of leprosy, being primary and not included in the five-grade classification. Its nature is unstable, as it may resolve spontaneously or transform into other types. The direction of transformation depends on the patient's immune status, with most cases evolving into the subcutaneous nodule-like type and a minority progressing to borderline or lepromatous types. Clinical symptoms are mild, without visceral involvement. Skin lesions are simple, presenting as faint red patches or hypopigmented macules with a flat, non-infiltrated, and non-atrophic surface. Vellus hair may be shed. The lesions are round, oval, or irregular in shape, with clear or partially indistinct borders and asymmetric distribution. Grade I sensory impairment may be present. Nerve trunk involvement is mild, with slight enlargement and low hardness, rarely leading to motor dysfunction or deformity. Bacteriological examination is mostly negative, while the lepromin test is usually positive. Cellular immune function tests may show normal or near-normal results in some cases, while others exhibit significant defects. Histopathological changes consist of nonspecific inflammatory cell infiltration. The prognosis depends on the degree of cellular immune development. Patients with a positive lepromin test and normal cellular immune function have a favorable prognosis. Some cases may self-resolve, while others progress to other types.

Leprosy reaction (Lepra reaction) refers to the sudden activation of symptoms during the chronic course of leprosy, whether treated or not, presenting as acute or subacute sexually transmitted disease changes, exacerbating existing skin and nerve damage inflammation or causing new skin or nerve damage. The exact cause remains unclear, but certain triggers such as medications, climate, psychological factors, preventive injections or vaccinations, trauma, malnutrition, alcoholism, excessive fatigue, menstrual irregularities, pregnancy, childbirth, breastfeeding, and many other factors can induce it. In recent years, it has been suggested that leprosy reaction is an acute hypersensitivity reaction to Mycobacterium leprae antigens caused by immune imbalance. Leprosy reactions are classified into three types.

Type I leprosy reaction is an immune reaction or delayed-type hypersensitivity. It primarily occurs in subcutaneous nodular leprosy and borderline leprosy. Clinically, it manifests as worsening and expansion of existing skin lesions, along with the appearance of new erythema, patches, and nodules. Superficial nerve trunks suddenly become thickened and painful, especially at night. Existing numb areas expand, and new numb areas emerge. Old deformities worsen, and new deformities may develop. Blood tests show no significant abnormalities, and routine Mycobacterium leprae examinations are negative or reveal small to moderate amounts of the bacteria. This type of reaction develops and resolves slowly. Depending on whether cellular immunity is enhanced or weakened, it is further divided into "upgrading reaction" and "downgrading reaction." The "upgrading" reaction shifts the disease toward the subcutaneous nodular type, while the "downgrading" reaction shifts it toward the lepromatous type.

Type II leprosy reaction is an antigen-antibody complex hypersensitivity reaction, specifically a vasculitic reaction. It occurs in lepromatous and borderline-lepromatous leprosy. The reaction develops relatively quickly, and tissue injury is more severe. Common clinical manifestations include erythema, which may progress to necrotic erythema or multiform erythema in severe cases. It is often accompanied by systemic symptoms such as fear of cold, fever, etc. Additionally, it may cause neuritis, arthritis, lymphadenitis, rhinitis, iridocyclitis, epididymo-orchitis, tibial periostitis, nephritis, hepatosplenomegaly, and other symptoms affecting multiple tissues and organs. Laboratory tests may reveal leukocytosis, anemia, elevated erythrocyte sedimentation rate, increased gamma globulin levels, and significantly elevated anti-streptolysin "O" titers. Bacterial examination before and after the reaction shows no significant changes, with granular bacteria predominating. The reaction duration varies, lasting as short as

1. two weeks or as long as several months, gradually subsiding.

Type III leprosy reaction is a mixed-type leprosy reaction, involving both cellular immune and humoral responses simultaneously. It mainly occurs in borderline leprosy. Its clinical manifestations combine symptoms of the aforementioned two types.

bubble_chart Diagnosis

The diagnosis of leprosy must be meticulous and patient, aiming for early confirmation, avoiding missed or misdiagnosis. Early treatment leads to early recovery, preventing the worsening of the condition, which could result in deformities, disabilities, or the spread of pestilence.

Diagnosis is primarily based on a comprehensive analysis of medical history, clinical symptoms, bacterial tests, and histopathological examinations. For cases that are difficult to diagnose immediately, regular follow-ups or consultations with relevant departments can be arranged to either rule out or confirm the diagnosis.

1. When taking the medical history, focus on aspects related to leprosy, such as whether the patient is from an endemic area, whether family members, friends, or neighbors have similar conditions, and whether there is a history of contact with infected individuals.
2. Physical examinations should be systematic and thorough, inspecting the skin, nerves, and lymph nodes under natural light.

   When examining nerves, pay attention to changes in peripheral nerve trunks as well as sensory and motor functions.

   **Peripheral nerve trunk examination**: Typically, focus on the greater auricular nerve, ulnar nerve, and peroneal nerve, as well as others such as the supraorbital nerve, anterior cervical nerve, supraclavicular nerve, median nerve, radial nerve, superficial peroneal nerve, posterior tibial nerve, and cutaneous nerves around or beneath skin lesions. Note their hardness, thickness, nodules, presence of abscesses, and tenderness. **Nerve function examination** assesses the involvement of nerve endings and is divided into subjective and objective methods.

   1. **Subjective sensory examination**: The order of sensory impairment usually begins with loss of temperature sensation (cold/heat), followed by pain sensation, and finally touch sensation. Explain the procedure to the patient and demonstrate before testing: - **Temperature sensation**: Use two identical test tubes filled with cold and hot water (50°C). Test on healthy skin first, then alternate the tubes randomly on the affected area, asking the patient to identify the temperature. - **Pain sensation**: Use a pin or needle to prick healthy skin first, then the affected area, noting loss or dullness of pain sensation. - **Touch sensation**: Gently stroke the skin with a feather or cotton swab, asking the patient to point to the touched area immediately to assess loss or dullness of touch.
   **2. Objective testing methods**

   (1) **Histamine test**: Inject 0.1 mL of 1/1000 histamine phosphate solution into healthy skin and the lesion. Normally, a 10 mm erythema appears within 20 seconds, followed by a secondary 30–40 mm erythema with diffuse edges after 40 seconds, and finally a wheal at the center. Absence of the secondary erythema indicates abnormality, useful for examining hypopigmented or white patches. (2) **Pilocarpine test (sweat test)**: Apply iodine to healthy skin and the lesion. After drying, inject 0.1 mL of 1/1000 pilocarpine solution intradermally and sprinkle starch. In 3–5 minutes, normal sweat turns the starch blue-purple; no color change indicates impaired sweating. (3) **Arrector pili muscle test**: Inject 0.1 mL of 1:100,000 nicotine picrate solution into the lesion and healthy skin. Normal nerve endings cause goosebumps; absence indicates dysfunction.

   **3. Motor function examination**: Ask the patient to perform movements like raising the forehead, frowning, puffing cheeks, whistling, or showing teeth to observe facial nerve paralysis. Test wrist flexion/extension, finger abduction/adduction, opposition, and gripping to assess upper limb nerve function. Check foot dorsiflexion, metatarsal flexion, inversion, and eversion to evaluate peroneal nerve function.

3. The examination for leprosy bacilli primarily involves collecting samples from the skin and mucous membranes, and if necessary, lymph node puncture may be performed for bacterial detection. Skin sample collection procedure: Select active skin lesions and disinfect the skin. Wear sterilized gloves during the examination. Use the left thumb and index finger to pinch and lift the patient's skin tightly, causing the local skin to turn white. Then, with the right hand holding a scalpel, make a 5 mm long and 3 mm deep incision. Scrape the tissue fluid with the blade and smear it onto a slide. Fix it for acid-fast staining and microscopic examination. Apply a cotton ball to the incision for pressure. The number of sampling sites depends on the requirements.
4. Histopathological examination is of great significance for the diagnosis, classification, and efficacy evaluation of leprosy. Sampling should be performed on active lesions, preferably reaching the fat layer. If the lesions vary, two samples should be taken simultaneously for examination, which is valuable for the diagnosis of borderline leprosy.

Lepromin test: This is a simple method to assess the body's resistance to Mycobacterium leprae. It partially reflects the strength and presence of the cellular immune response to Mycobacterium leprae. Types of lepromin include crude lepromin, pure bacillus lepromin, and pure protein lepromin, with crude lepromin (also known as whole lepromin) being the most commonly used.

1. Test method and result interpretation: Intradermally inject 0.1 ml of crude lepromin on the flexor side of the forearm, forming a white隆起 about 6–8 mm in diameter, then observe the reaction. Early reaction: Observe and interpret the results 48 hours after injection. An infiltrative erythema larger than 20 mm in diameter is strongly positive (卅), 15–20 mm is moderately positive (廿), 10–15 mm is weakly positive (+), 5–10 mm is doubtful (±), and less than 5 mm or no reaction is negative (-). Advanced stage reaction: Observe and interpret the results 21 days after injection. A red infiltrative nodule with ulceration is strongly positive (卅), a nodule with infiltration diameter greater than 5 mm is moderately positive, a nodule with infiltration diameter of 3–5 mm is weakly positive (+), a grade I nodule infiltration or less than 3 mm is doubtful (±), and no local reaction is negative (-).
2. Clinical significance: The early reaction indicates the body's sensitivity to Mycobacterium leprae. A positive advanced stage reaction indicates a strong specific cellular immune response to Mycobacterium leprae, reflecting immunity. A negative advanced stage reaction suggests suppressed cellular immunity to Mycobacterium leprae, indicating a lack of immunity. The intensity of the lepromin advanced stage reaction is proportional to the body's resistance to Mycobacterium leprae. Therefore, the lepromin test has practical value for leprosy classification, prognosis assessment, and evaluating the body's resistance.

bubble_chart Treatment Measures

Early, timely, sufficient, full-course, and regular treatment can lead to faster recovery, reduce deformities and disabilities, and prevent recurrence. To minimize the development of drug resistance, the current approach advocates combination therapy with several effective anti-leprosy chemical drugs.

1. Chemical Drugs

   (1) Dapsone (DDS) is the first-choice drug. The initial dose is 50mg daily, increasing to 100mg daily after 4 weeks, taken continuously. The medication is taken for 6 days a week, with a 1-day break, and after 3 months of continuous use, a 2-week break is taken. Side effects include anemia

2. , drug rash
3. , granulocytopenia, and liver or kidney dysfunction. In recent years, due to the emergence of dapsone-resistant leprosy strains, combination therapy is widely recommended.

   (2) Clofazimine (B633) not only inhibits leprosy bacilli but also counteracts type II leprosy reactions. The dosage is 100–200mg/day, taken orally. The medication is taken for 6 days a week, with a 1-day break. Long-term use may cause skin redness and pigmentation.

   (3) Rifampin (RFP) has a rapid bactericidal effect on leprosy bacilli. The dosage is 450–600mg/day, taken orally.

4. Immunotherapy

   The specific immunotherapy under investigation, involving live BCG plus killed leprosy bacteria, can be administered concurrently with combination chemotherapy. Other adjunct therapies include transfer factor

5. and levamisole.
6. Treatment of Leprosy Reactions

   Appropriate options include thalidomide

7. , corticosteroids
8. , clofazimine
9. , Leigong vine
10. , intravenous block therapy, and antihistamines.
11. Management of Complications

    For chronic plantar ulcers, maintain local cleanliness, prevent infection, and ensure adequate rest. Debridement or skin grafting may be necessary if required. For deformities, strengthen exercises

12. , physiotherapy
13. , and acupuncture; orthopedic surgery may be needed if necessary.

To prevent relapse after recovery, dapsone is often used as consolidation therapy. For LL and BB, long-term or even lifelong medication is required; for TT, treatment should continue for over 3 years.

bubble_chart Prevention

To control and eliminate leprosy, it is essential to adhere to the principle of "prevention first," implement the strategy of "active prevention and control of the epidemic," and follow the approach of "simultaneous investigation, isolation, and treatment." The key lies in identifying and controlling the sources of infection, cutting off transmission routes, providing standardized drug treatment, and enhancing the immunity of the surrounding population to effectively control the epidemic and eradicate leprosy. Currently, there is a lack of effective preventive vaccines or ideal prophylactic drugs for leprosy. Therefore, various methods must be employed to detect cases early in prevention and control efforts. Patients identified should promptly receive standardized combined chemotherapy. For children in endemic areas, household contacts of patients, and close contacts who test negative for both lepromin and subcutaneous nodule bacillus reactions, BCG vaccination or effective chemoprophylaxis may be administered.

bubble_chart Differentiation

When making a differential diagnosis, it is essential to understand the characteristics of leprosy skin lesions. The lesions are often accompanied by sensory disturbances, and the peripheral nerve trunks are frequently thickened. Leprosy bacteria are commonly detected in the lesions of lepromatous leprosy. Using these features to differentiate from other diseases, identification is generally possible.

Skin diseases that require differentiation: Lepromatous leprosy should be distinguished from cutaneous melanoma Rebing, neurofibroma, alopecia areata, xanthoma tuberosum, ichthyosis, rosacea, seborrheic dermatitis, erythema nodosum, dermatomyositis, etc. Subcutaneous nodular leprosy should be differentiated from sarcoidosis, annular erythema, erythema elevatum diutinum, cutaneous melanoma Rebing hypopigmented type, granuloma annulare, lupus vulgaris, tinea corporis, centrifugal erythema, etc. Indeterminate leprosy should be distinguished from vitiligo, vascular nevus, cutaneous melanoma Rebing hypopigmented type, and tinea versicolor. Borderline leprosy should be differentiated from lupus erythematosus, cutaneous melanoma Rebing, and mycosis fungoides (infiltrative stage).

Neurological conditions requiring differentiation include syringomyelia, polyneuritis caused by other factors, traumatic peripheral nerve injury, progressive spinal muscular atrophy, progressive hypertrophic interstitial neuritis, progressive muscular dystrophy, lateral femoral cutaneous neuritis, facial nerve palsy, etc.