Leprosy: causes, symptoms, types, diagnosis, treatment, and prevention

Leprosy, also known as Hansen's disease, is a chronic contagious disease caused by mycobacterium leprae, which mainly invades human skin and nerves, causing progressive and permanent damages of skin, nerves, extremities, and eyes if untreated.


Causes

The pathogen is mycobacterium leprae. The isolated mycobacterium leprae loses its fecundity after 2 to 3 hours of sunlight exposure in summer, and can be inactivated at 60 °C for one hour or in ultraviolet irradiation for two hours. Generally, it can be killed by boiling, high pressure steam, and ultraviolet irradiation.

Leprosy patients are the natural host of mycobacterium leprae. Mycobacterium leprae is widely distributed in patients, mainly in some cells of reticuloendothelium such as skin, mucous membrane, peripheral nerve, lymph node, liver, and spleen, mainly in nerve endings, macrophages, smooth muscles, ciliary bands, and blood vessel walls, more common in mucous membranes. In addition, bone marrow, testis, adrenal glands, and anterior segment of eye are also areas where mycobacterium leprae invades and resides, and a small amount of mycobacterium leprae can also be found in the peripheral blood and striated muscles. Mycobacterium leprae is mainly excreted by ruptured skin and mucous membranes and can also be seen in milk, tears, semen, and vaginal secretions.

The source of leprosy infection is untreated leprosy patients, the skin and mucosa of patients with multibacillary leprosy contain a large number of mycobacterium leprae and are the most important source of infection.

Mode of transmission

Direct contact between breached skin or mucosa in healthy persons and ruptured skin or mucosa in patients with leprosy is an important mode of transmission of leprosy. It is currently believed that droplets and hanging drops from leprosy patients in the cough and sneeze entering the healthy human body through the upper respiratory tract mucosa is the main route.

Persons are also infected through certain media, such as clothes, bedclothes, hand towels, and tableware used by infected patients.

There are also other possibilities such as transmission through insects which cannot be completely ruled out.


Types

According to the count and type of skin lesions, leprosy can be divided into 2 types:

  • Paucibacillary leprosy: ≤5 skin lesions, no mycobacterium leprae in the lesions
  • Multibacillary leprosy: ≥6 skin lesions or mycobacterium leprae seen in the lesions or both

Based on the clinical presentations and severity, leprosy can be divided into 6 types:

  • Indeterminate leprosy (IL)
  • Tuberculoid leprosy (TT)
  • Borderline tuberculoid leprosy (BT)
  • Borderline borderline leprosy (BB)
  • Borderline lepromatous leprosy (BL)
  • Lepromatous leprosy (LL)

Signs and Symptoms

The incubation period of leprosy is 2 to 5 years, as short as 3 months, as long as more than 10 years. The duration of incubation period is often related to the type of exposure, and children with long-term exposure to lepromatous leprosy have an incubation period of 9 months to 6 years. The incubation period can be as long as 20 years.

Tuberculoid leprosy (TT)

Skin lesions are limited in number and area, generally only 1 - 2 light colored maculae, erythema, papules, or plaques are present. Skin lesions are large, annular or geographic, sharply demarcated, and asymmetric. Dry surface, loss of lanugos, numbness, and anhidrosis are present, mainly in the face, extremities, and buttocks. Except for the scalp, groin, and armpits, leprosy can occur in any areas. Superficial facial skin lesions, mild sensory disturbance, and sometimes thickened cutaneous nerves are present.

There may be 1 - 2 thickened and solid peripheral nerves, often ulnar nerve, common peroneal nerve, and great auricular nerve. Neurological dysfunction appears early and obviously, and severe muscle atrophy, motor skills dysfunction, and deformity can be seen. Only neurological damage and no skin lesions are present in few patients, which is called pure neuritic leprosy, mostly TT, but also other types.

In addition to local skin lesions, loss of eyebrows and hair is generally absent, and mucous membranes, lymph nodes, testicles, eyes, and internal organs are not invaded.

Negative results in acid-fast bacilli test, positive results in late reaction of lepromin test, and normal or near normal results in cellular immunoassay can be seen.

Patients have strong resistance, can be cured in a short period of treatment, and some can also spontaneously heal. Due to the strong tissue reaction of leprosy, peripheral nerve trunks are often involved severely, often with deformity in the corresponding parts, such as claw finger deformity, wrist drop, foot drop, and facial palsy .

Borderline tuberculoid leprosy (BT)

Skin lesions are more than TT. Different sized, partially sharply demarcated, light colored maculae, erythema, or plaques are asymmetrically distributed, with satellite lesions around large lesions. Some lesions are annular, with clear inner and outer edge, with a circular or elliptical immune zone in the center. In addition to the face, skin lesions are generally superficial and sensory disturbance is obvious.

Multiple asymmetrical peripheral nerve trunk lesions are present. Nerve thickness is not as obvious as TT, texture is not as solid as TT, and deformity occurs early and severely.

Unless localized skin lesions, loss of hair and eyebrows is absent. Mucosa, lymph nodes, testicles, internal organs are less involved and symptoms are mild.

Positive results (++ - +++) in acid-fast bacilli test are generally present.

Suspicious or weakly positive results can be seen in late reaction of lepromin test.

Good prognosis is present, duration of treatment is longer than that of TT, and few BT can spontaneously heal. Untreated patients may downgrade and evolve into BB, and treated patients may upgrade and evolve into TT.

Borderline borderline leprosy (BB)

The number and size of skin lesions are between TT and LL. Pleomorphic and pleochroic, different sized, widely distributed, asymmetrical skin lesions are present. Skin lesions are partially sharply demarcated, or with clear inner edge and indistinct outer edge. Some plaques or infiltrations are with an immune zone in the center. Some facial skin lesions are symmetric bat-like, some skin lesions are target shaped, and are called target maculae, and some skin lesions are banded, rope shaped, or irregular. Some patients have clinical features of TT and LL, such as facial skin lesions in LL, skin lesions of trunk and extremities in TT, or skin lesions with features of both TT and LL.

Nerve lesions are multiple but asymmetrical. The degree of nerve thickness and dysfunction is between TT and LL, more severe than LL but milder than TT, with moderate thickness, with soft and homogeneous texture.

Loss of eyebrows is present, often asymmetrically, and eyebrows are regenerative after treatment. Mucosa, lymph nodes, testis, and internal organs may be invaded.

Positive results (+++ - ++++) in acid-fast bacilli test and negative results in late reaction of lepromin test can be seen. The results of cellular immune function tests are between TT and LL.

The prognosis is between TT and LL, and the condition is very unstable and may evolve into BT or BL.

Borderline lepromatous leprosy (BL)

Numerous, pale red, dark red, or brown, poorly demarcated, widely distributed but not completely symmetrical macules, plaques, infiltrations, or nodules are present. The surface of the skin lesions is not as bright as LL. Some skin lesions are annular, with clear inner edge, with indistinct outer edge, with an immune zone in the center. Superficial sensory disturbance occurs lately, with mild symptoms.

Multiple evenly thickened peripheral nerve lesions are present, with soft texture, not as completely symmetric as LL. Deformities occur lately and are not completely symmetrical.

Loss of eyebrows is present and asymmetric. In late stage of BL, hair loss is present. Nasal mucosa, eyes, lymph nodes, testicles, and internal organs can be involved early, forming saddle nose.

Positive results (++++ - +++++) in acid-fast bacilli test and negative results in late reaction of lepromin test can be seen. Defects can be found in cellular immune function test.

Most evolves into LL, and some evolves into BB.

Lepromatous leprosy (LL)

In the early stage, many, small, widely and symmetrically distributed, poorly demarcated, pale red maculae or light colored maculae are present, with bright surface, without obvious sensory disturbances and anhidrosis, without immune zone. In the middle and late stage, widely and symmetrically distributed macules, nodules, plaques, and diffuse infiltrations are visible, with bright surface, without immune zone, with mild or obvious sensory disturbances and anhidrosis, with leontiasis, nasolabial hypertrophy, and hypertrophy of auricular lobule. In the early stage, nerve lesion is not obvious. In the middle and late stage, widely and symmetrically distributed, evenly thickened nerve trunks are present, with soft texture, causing severe deformity.

The eyebrows and eyelashes can totally fall off symmetrically, and the armpit hair and pubic hair can be sparse or completely lost. In the late stage, hair can fall off from the hairlines. Mucosa, lymph nodes, testicles, and internal organs are involved early and obviously. Perforation of nasal septum, saddle nose, lymph node enlargement, testicular atrophy, impotence, and gynecomastia can occur. Conjunctivitis, keratitis, and iridocyclitis can occur, and blindness may occur in severe patients. The liver, spleen, and kidney are also often involved.

Positive results (+++++ - ++++++) in acid-fast bacilli test and negative results in late reaction of lepromin test can be seen, and obvious defects can be found in cellular immune function test.

Early detection and immediate treatment can produce a good prognosis, otherwise irreducible deformity and disfigurement can occur.

Indeterminate leprosy (IL)

Indeterminate leprosy is the early manifestation of all types of leprosy, and the clinical and pathological features are different from LL and TT. It can spontaneously heal and often evolve into other types of leprosy.

In the early stage, single or multiple, one to several centimeters in diameter, sharply or poorly demarcated, light colored or pale red maculae are present, with mild sensory disturbance on the surface. Numerous small poorly demarcated skin lesions may evolve toward LL, and few sharply demarcated skin lesions may evolve toward TT.

Generally nerve lesion and hair loss are absent, and mucous membranes, lymph nodes, testicles, and internal organs are generally not involved.

Negative results in acid-fast bacilli test are visible, and occasionally 1 or 2 bacteria can be found. Positive or negative results in late reaction of lepromin test can be seen. Normal or near normal results in some cellular immune function tests are present, and obvious defects can be found in some cellular immune function tests.

In general, most can spontaneously heal, but can also evolve into other types of leprosy, depending on the body resistance. If positive results in late reaction of lepromin test, negative in acid-fast bacilli test, and normal or near normal in cellular immune function test, the prognosis is good, and the lesion can resolve spontaneously or evolve toward TT, otherwise evolve toward LL.

Less common manifestations of leprosy

Pure neuritic leprosy

Pure neuritic leprosy is with only asymmetric involvement of peripheral nerve trunks but without any specific skin lesions or a history of skin lesions, more common in India and Nepal. It is generally believed that pure neuritic leprosy may be an early stage of leprosy, and its diagnosis is usually based on an obvious neurological thickness and dysfunction, absence of typical skin lesions, and negative results in acid-fast bacilli test. It is difficult to classify correctly by clinical examinations, and it is generally necessary to have a nerve biopsy. Pathological studies show that 1/5 present with changes of BL/LL and some mycobacterium leprae in the nerve in patients with single nerve involvement, and about 42% present with changes of TT/BT in patients with multiple nerve involvement. If nerve abscesses are formed, its histological suggestion is tuberculoid leprosy. Pure neuritic leprosy is generally BT, so the initial treatment is suppression of hypersensitivity reactions to block the progression of nerve lesion, and leprosy should also be treated. Good prognosis is generally present, but if nerve lesion has occurred, it is difficult to reverse, and a certain degree of deformity can occur.

Tenosynovitis

Tenosynovitis is manifested by moderate swelling and pain in the unilateral or bilateral dorsal hand, sometimes dorsal foot, and is a manifestation of a type I lepra reaction often difficult to identify. Other manifestations of BT, occasionally BL, can be found in careful examinations. The treatment is control of type I lepra reaction.

Idiopathic skin ulcers in BT and LL

Idiopathic skin ulcers are one of the less common manifestations of BT, and may be caused by enhanced hypersensitivity response to type I lepra reaction. Occasionally, idiopathic skin ulcers of BT occur on the basis of absence of a history or clinical manifestations of skin lesions or neuropathy. This condition does not look like leprosy at all, and is easily confused with other diseases. Skin necrosis can be seen in histopathological examination due to severe cellular hypersensitivity in BT. Glucocorticoids can heal ulcers, and typical skin and nerve lesions can be present later.

Idiopathic skin ulcers of LL are found in severe long-term untreated LL patients and are currently rare. Ulcers are located in areas with chronic panniculitis, which adheres to subcutaneous muscles and bones through dense inflammatory tissue, most common in the anterior thighs, calves, triceps brachii, and dorsal forearms. These ulcers are caused by not trauma but skin necrosis and exfoliation of necrotic tissue, leaving irregular, often triangular defects that look like third degree burn.

Less common clinical manifestations associated with multibacillary leprosy

Localized lepromatous leprosy or borderline lepromatous leprosy

It is manifested by single or multiple localized nodules, papules, or plaques, with normal body surface. Strong positive results in acid-fast bacilli test in nodules or papules and negative or weak positive results in other areas are present. Treatment regimen is the same as multibacillary leprosy, with satisfactory results.

Histoid leproma

Histoid leproma is a special manifestation of LL or BL. Patients often get better after the initial treatment against leprosy, and then deteriorations or relapses cause histoid lesions. Skin lesions are mostly one to hundreds, pea sized to walnut sized, round or elliptical, pale red or deep red, sharply demarcated, solid dermal nodules, fusing with each other. New nodules are often pale red, shiny, and transparent. Matured nodules are mostly brownish red with dry and scaly surfaces. Skin lesions are mainly in the buttocks, trunk, and extremities, but also isolated, scattered, or in groups, generally without subjective symptoms. Some patients present with pea sized to walnut sized, irregular, sharply demarcated, moveable subcutaneous nodules, without tenderness. Histoid skin lesions can also be few, coin sized, round or oval, reddish brown, sharply demarcated, solid, slightly raised, flat plaques, sometimes with raised edge and depressed center. Few patients present with histoid papules on the basis of diffuse active or regressive lesions during rapid deterioration. Urtocation or sharp pain occurs initially, numerous, small, pale red, flat papules occur and expand, some fuse into plaques, and some are still flat papules. In few patients, histoid nodules can be ruptured and numerous mycobacterium leprae are discharged, leaving scars after healing.

Histoid leproma is most common in recurrent patients cured by dapsone monotherapy, often in dapsone-resistant patients, but also in untreated patients. Treatment regimen is the same as multibacillary leprosy.

Lucio leprosy

Lucio leprosy is pure diffuse leprosy. Patients present with sensory impairment of hands and feet, followed by gradual loss of eyebrows, eyelashes, and body hair, as well as diffuse thickness, stiffness, and smoothness in the whole body skin, resembling scleroderma. Hair loss, nasal congestion, nasal bleeding, hoarseness, bipedal edema, and extensive microvascular dilatation are present, but skin nodules and plaques are absent.

Nerve lesions of leprosy

In the clinical manifestations of leprosy, almost all patients have varying degrees of peripheral nerve lesion, but the appearance of thickened nerves is generally later than skin lesions. In addition to cutaneous nerve, the invaded peripheral nerves are mostly the ulnar nerve, common peroneal nerve, and great auricular nerve, followed by the median nerve, supraorbital nerve, and facial nerve, merely radial nerve. Symptoms of nerve lesion include nerve thickness and dysfunction, and thickened nerves can be several to dozens of times thicker than normal nerves. Even or segmented thickness may be present. In the sensory, motor, and autonomic nerve functions, the sensory function is involved at the earliest and at the most severe. Simple motor dysfunction occurs occasionally. In severe neurological lesions, autonomic dysfunction is always present.

Sensory dysfunction is mainly superficial sensory disturbances, including temperature sense, pain sense, and touch sense. Because the facial sensory nerve fibers are rich and the nerve fibers are cross distributed, the facial sensory dysfunction in all types of leprosy is not obvious. The sensory disturbance of leprosy is divided into dysfunction in nerve trunk and disturbance in nerve endings. The former is manifested by a sensory disorder in the regions dominated by a single nerve trunk involved, such as numbness caused by pure neuritic leprosy. The latter is manifested by numbness in the skin lesions, or symmetric sensory disturbance from the distal to the proximal extremities due to diffuse infiltration. The deep sensory disturbance of leprosy is generally absent.

Dyskinesia occurs later than sensory dysfunction, often causing muscle atrophy, muscle weakness, and various deformities. Common movement disorders are present in the hands, feet, and face. The most involved is posterior tibial nerve, followed by the ulnar nerve, median never, common peroneal nerve, and facial nerve. The ulnar nerve lesion is located in the posterior elbow and is characterized by flexion joint deformity between the little finger and the ring finger, hypothenar compartment muscles and interosseous muscles atrophy, and finger-to-finger movement disorder, numbness of ulnar side, and formation of claw hand. The median nerve is mostly damaged in the wrist, which is characterized by palsy and atrophy of the thenar muscles affecting thumb opposition and abduction, flattened palm, and formation of ape hand. Simple median nerve lesion is rare. Radial nerve lesion is less common and is manifested by palsy of wrist extensors and extensor digitorum muscles, and wrist drop and finger drop deformity. Common peroneal nerve lesion can cause atrophy and palsy of tibialis anterior muscles and extensor digitorum muscles, causing difficulty in dorsiflexion and valgus of the foot, foot drop, and lateral numbness of the foot. Posterior tibial nerve lesion can cause spasm and palsy of small muscle of the foot and plantar numbness. Facial nerve involvement can cause palsy of the frontal muscles, ocular muscles, and orbicularis oris muscles, causing disappearance of wrinkles on the forehead, resulting in symptoms of lacrimation and salivation. The unilateral nerve palsy causes the mouth to be skewed to the healthy side, and the bilateral lateral nerve palsy can cause mouth drop and lower lip eversion.

In severe neurological lesions, autonomic nervous dysfunction is always present, skin lesions and dysfunction of hair growth, sebaceous gland, and sweat gland secretion are present, and chromogenesis is reduced. Capillary deposition, cyanosis and dryness of skin, and chapping are visible.

Ocular lesions of leprosy

Blindness caused by leprosy is a serious complication. The ocular lesion can be primary and secondary. The former is due to direct invasion of mycobacterium leprea, such as corneal lepromata, iridic lesions, and ciliary lesions. The latter is secondary to the palpebral motor nerve lesion or ocular sensory nerve lesion. Primary lesions are generally limited to lepromatous leprosy, while secondary lesions can be found in various types of leprosy. Lagophthalmus occurs late in LL, usually bilateral. The ocular branch lesion of the trigeminal nerve can cause numbness of the cornea and conjunctiva, resulting in corneal xerosis and the risk of minor trauma and ulceration of the cornea. The involvement of trigeminal nerve and facial nerve is most likely to cause exposure keratitis. Mycobacterium leprae invades the iris and ciliary body, leading to reactions. Iridocyclitis is mostly part of the type II lepra reaction and can also be the only initial manifestation of type II lepra reaction, which is related to circulating immune complexes, mainly in LL, and is one of the important causes of blindness resulting from leprosy.

Ocular lesion duration can be divided into acute, subacute, and chronic phases. In the acute phase, it is characterized by ocular irritation, ophthalmalgia, headache, and blurred vision. Ciliary congestion, turbid aqueous humor, miosis, sluggish pupillary response, iridoncus, blurred texture, and inflammatory exudate deposition can be seen in examinations. Symptoms in the chronic phase are milder, but with a greater impact on vision. Scieropia may be present in the early stages. Posterior synechia of the iris and petaloid pupils can be seen in examinations. Repeated inflammation can cause atretopsia, and secondary glaucoma and cataract, resulting in blindness.

Lepra reactions

Lepra reaction refers to the sudden activity or aggravation of the disease due to changes in the immune status in the chronic stage of leprosy. For example, the original lesions are rapidly reddened and spreading, many new skin lesions suddenly appear, or severe peripheral nerves swelling and pain, iridocyclitis, lymphadenitis, orchitis, or fever occur suddenly. Lepra reaction can be divided into type I reaction, type II reaction, and mixed reaction. Failure to properly handle often leads to deformity.

Type I reaction

Type I reaction is a cell-mediated delayed hypersensitivity reaction (DHR), mainly in patients with BT, BB, and BL and in unstable immune status. With the development of reaction, the patient's immunity can change, and clinical manifestations can be an evolution toward TT or LL. If the reaction is accompanied by specific cellular immunity enhancement, the disease evolves toward TT after reaction, which is called reversal reaction (RR) or upgrading reaction. If the reaction is accompanied by a decrease in specific cellular immunity, the condition tends to evolve toward LL, which is called downgrading reaction. Occasionally, there is no visible change in the immune status after reaction.

Although the mechanisms of reversal reaction (upgrading reaction) and downgrading reaction are fundamentally different, they are difficult to be distinguished clinically. Type I reaction are seen in patients with BT, BB, and BL. The main clinical manifestations are partially or completely reddened, congested and edematous, elevated skin lesions, with local fever, sometimes with tenderness, resembling erysipelas. Maculae can develop into plaques, or the edge of the skin lesions is raised, infiltrates, and expands. In severe reaction, severe congestion, swelling, shine, and brittleness may be visible, resulting in necrosis and ulceration. After the reaction subsides, the skin lesions dry, desquamate, and flatten, leaving sharply demarcated light colored maculae or pigmentation. In addition to the increased activity of the original lesions, new skin lesions may occur in the neighborhood of the old lesions or in other areas. In type I reaction, one or more nerve trunks are often swollen rapidly, with obvious pain and tenderness. Neuritis can coexist with skin lesions or exist alone. Sensory abnormalities and pain can occur rapidly in the affected innervation area, and motor dysfunction can also occur rapidly. If nerve pain is not treated in time, foot drop, wrist drop, facial palsy, and lagophthalmus may occur. Patients with red patches on the cheeks or around the eyes are susceptible to facial nerve lesion and lagophthalmus. Generally systemic symptoms are not obvious, severe patients may present with fever and edema of hands, feet, and face. Mucosal and visceral lesion is rare, and lymph nodes can be slightly enlarged.

It must be noted that in few patients, involvement of the pharyngeal plexus composed of the branches of vagus nerve and glossopharyngeal nerve causes palsy of palatine muscle and the pharyngeal muscle, resulting in acataposis, rhinolalia, and laryngopharyngeal reflux. Acute laryngeal edema and asphyxia may occur during type I reaction and tracheotomy is required. Superior laryngeal nerve palsy causes chocking when swallowing. Recurrent laryngeal nerve palsy can cause hoarseness, chocking, and tachypnea.

Type I reaction persists generally from few months to a year or even longer. The reversal (upgrading) reaction occurs mostly 6 months to 1 year after treatment. Bright red or dark red, sharply demarcated skin lesions occur in the reversal (upgrading) reaction, with a tendency to evolve toward TT, that is, BL evolving to BB and BB evolving to BT, with reduced acid-fast bacilli or absence of acid-fast bacilli. The reversal (upgrading) reaction can increase the body immunity, but the tissue trauma is more serious. Failure to treat in time often leads to severe deformity. Downgrading reaction often occurs in patients untreated or irregularly treated. Contrary to the reversal (upgrading) reaction, downgrading reaction presents with poorly demarcated, pale yellow or orange skin lesions. Increased in number and size, bright, tight skin lesions and even skin rupture under severe conditions are present in patient with BB or BL during downgrading reaction. Poorly demarcated new skin lesions can occur. Increased acid-fast bacilli and decreased immunity are present after reaction, with a tendency to evolve toward LL, that is, BT evolving to BB and BB evolving to BL.

Severe type I reaction includes:

  • Skin lesions with obvious redness and swelling, tenderness, and rupture
  • Facial edematous raised skin lesions
  • One or more nerve trunk thickness, with severe pain and obvious tenderness, with loss of nerve function
  • Weakened muscle strength of hands and feet in the past 6 months
  • Sensation loss of more than 2 sites in unilateral hands and foot in the past 6 months
  • Type I reaction lesions in the main innervation area or in the eye.

Type II reaction

Type II reaction, aslo known as erythema nodosum leprosum (ENL), is allergy of vasculitis or immune complexes. The mycobacterium antigen in vivo binds to the corresponding antibody to form an immune complex. Immune complexes in the bloodstream deposit on the basement membrane and other tissues of capillaries. The immune complex activates complement, produces chemotactic substances, attracts leukocytes to engulf immune complexes, and releases various enzymes, such as proteolytic enzymes, collagenase, acid protease, cathepsin, causing vasculitis and perivesical tissue necrosis. Significant reductions in suppressor T cells and inhibition of helper T cells in acute ENL suggest that T cell imbalance may be a contributing factor to ENL. TNF-α is also involved in the process of ENL, and the level of TNF-α is elevated during reaction, and is declined after reaction.

Type II reaction is common in LL and BL patients treated with anti-leprosy medication for several months or years, and can occur in newly diagnosed patients, and can cause acute inflammation in any organ and tissue with mycobacterium leprae. ENL lesion is one of the manifestations of type II reaction, and neuritis, iridocyclitis, orchitis are also manifestations of type II reaction. The main clinical feature is the sudden appearance of hemispherical, raised, poorly demarcated, initially bright red, shiny, and tender and lately dark red, painful papules or red nodules with a diameter of 2 - 5mm on the normal skin of the extremities, face, and trunk, persisting for several days, leaving pigmentation after regression. ENL can also occur in deep dermis or subcutaneous tissue, and rupture causes discharge of thick yellow pus. Usually, ENL skin lesion subsides in several days, new skin lesions occur in groups, and repeated relapses are present. If not treated, solid indurations can be formed over time. In addition to ENL, skin lesions of type II reaction can be characterized by polymorphic erythema and necrotic erythema. Positive results in acid-fast bacilli test are present, mostly granular bacteria.

Type II reactions often cause neuritis, with thickened peripheral nerves, with pain and tenderness. Compared with type I reaction, the neurological lesion of type II reaction occurs slowly and symptoms are milder. However, permanent neurological damage may occur if without immediate treatment.

In addition, type II reactions can also occur in lymph nodes, muscles, joints, synovium, iris, testis, and liver, and can are characterized by iridocyclitis, orchitis, arthritis, anterior tibial periostitis, and lymphadenopathy. Systemic symptoms include fever, general malaise, fatigue, headache, aching pain of extremities, proteinuria, hematuria, and even kidney failure.

Severe ENL reaction refers to many ENL with hyperthermia, ENL with neuritis, ENL rupture and suppuration, recurrent ENL, involvement of other organs such as eyes, testicles, lymph nodes, and joints.

Lucio phenomenon

The long-term untreatedness of Lucio leprosy resulting in a reaction phenomenon is called Lucio phenomenon, which is a special type of type II reaction. Most patients have serum-precipitating antibodies against mycobacterial antigens. Lucio phenomenon is an acute allergic vasculitis. There is a large amount of acid-fast bacilli in the endothelial cells of the cutaneous blood vessels. The histology of lesions suggests immune complex formation and deposition in the blood vessel wall, followed by obvious vasculitis and thrombosis in the superficial and deep blood vessels, resulting in dermatorrhagia and infarction. Scattered, poorly demarcated, tender, irregular erythema occurs in the skin, healing after darkening. Bullae and necrosis may occur and cause deep, irregular, triangle or polygonal, painful ulcers, leaving distinct curvilinear scars after exfoliation of brownish black crusts. Systemic symptoms are severe and can cause death.


Histopathology

Histopathology of TT

Severely damaged epidermis, noninfiltrated zones under the epidermis, typical epithelioid cell granulomatous changes, and some Langhans giant cells in the dermis are seen. Many lymphocytes surrounding the lesion, severely damaged small branches of nerves, and connective tissue surrounding the lesion are visible. Negative results in acid-fast bacilli test are present.

Histopathology of BT

Intact basal layer of the epidermis and narrow noninfiltrated zones under the epidermis are visible. Epithelioid cells granulomatous changes, few lymphocytes, and few scattered Langhans giant cells in the dermis can be seen. Epithelial and histiocytic infiltration in the small branches of nerves is present. Positive results (+ - ++) in acid-fast bacilli test can be seen.

Histopathology of BB

Intact basal layer of the epidermis and obvious noninfiltrated zones under the epidermis are visible. Epithelial cell granuloma, no lymphocytes infiltration, few scattered lymphocytes, and no Langhans giant cells in the dermis can be seen. Histiocytes and atypical foam cells may be present. Varying degrees of destruction of nerve branches, thickened nerve bundles, and onion skin pattern of the perineurium are visible. Positive results (+++ - ++++) in acid-fast bacilli test can be seen.

Histopathology of BL

Epidermal atrophy and noninfiltrated zones under the epidermis are visible. Macrophage granuloma with tendency of differentiation to epithelial cells, typical foam cells, and stacked lymphocytes in the granuloma in the dermis can be seen. Small nerve branches are damaged mildly and lately. Onion skin pattern of the perineurium can be seen. Positive results (++++ - +++++) in acid-fast bacilli test are present.

Histopathology of LL

Epidermal atrophy and noninfiltrated zones under the epidermis are visible. Macrophage or foam cell granuloma, few scattered lymphocytes, and typical foam cells in the dermis can be seen. Nerve branches are damaged mildly and lately. Onion skin pattern of the perineurium can be seen. Positive results (+++++ - ++++++) in acid-fast bacilli test are present.

Histopathology of IL

Non-specific inflammatory manifestations are visible, and negative results in acid-fast bacilli test are generally present.

Histopathology of type I reaction

In the epidermis, intracellular and intercellular edema can be seen. Loose and edematous fibrous tissue and dilated lymphatic vessels in the superficial dermis are visible. Extensive fibroblast proliferation and swelling in the dermis is present. When macrophages differentiate into epithelioid cells, due to intracellular edema of epithelioid cells, cytoplasm may have vesicular changes, resulting in atypical epithelial cells. In the lesion, inflammatory cells expand, and due to severe edema, the intercellular distance is larger, so that the original granuloma cells are deformed and dispersed, and the granuloma structure is unclear. Sometimes a large number of giant cells are seen, mostly foreign body giant cells. The number of lymphocytes is variable, lymphocytes are generally increased in the late stage of reaction, and sometimes mild scattered neutrophil infiltration is seen. Fibrinoid degeneration can occur in collagen tissue, and small focal necrosis can occur in severe reactions.

Histopathology of type II reaction

Dense neutrophil infiltrations in the lepromatous granuloma of the superficial and deep dermis and subcutaneous tissues are visible, especially during the acute phase of 2 - 3 days after onset. Neutrophils tend to deposit intensively to form small abscesses. In addition to neutrophil infiltration, there are many mast cells and eosinophils. In the subacute stage of 4 - 5 days after onset, the infiltration amount of neutrophils, lymphocytes, plasma cells, and macrophages is approximately equal. In the chronic stage of 9 - 12 days after onset, neutrophils, mast cells, and eosinophils are decreased rapidly, lymphocytes are increased, finally lymphocytes and plasma cells are dominated, and proliferation of fibrous tissue is present. About half of patients are with vasculitis characterized by obvious panangiitis of the arteries and veins. The presence of vasculitis indicates that the condition is more severe and skin necrosis and ulceration can occur. Mild vasculitis is only simple edema, and severe vasculitis is characterized by significant swelling of blood vessel walls, intima, and endothelial cells, and even narrowed lumen and occlusion of the lumen. Infiltration of neutrophils, lymphocytes, eosinophils can be seen in all parts of the vessel wall, and neutrophils can be ruptured into nuclear dust. Fibrinoid degeneration can occur in the vessel wall and perivascular infiltration is also present. Extravasation of red blood cells on some areas can be seen. Vascular lesions are more common in the early acute phase. The lesions of large blood vessels persist for a long time. Positive results are generally present in acid-fast bacilli in ENL lesions, mostly granular.

Histopathology of histoid leproma

Typical histoid leproma is sharply demarcated nodular infiltrating masses in the dermis or subcutaneous tissue, composed of dense fusiform or polygonal tissue cells. These cells are often arranged in bundles, with pseudocapsules around the nodules. Numerous acid-fast bacilli can be found in acid-fast stain, mostly stained completely.

Atypical histoid leproma is lepromatous infiltration with foam cells and is indistinguishable from the general lepromatous leprosy. Pseudocapsule formation around the infiltrated mass is absent. Numerous acid-fast bacilli can be found in acid-fast stain, mostly stained completely, whereas in LL or BL infiltration, bacterial density is often low, and mostly granular.


Diagnosis

Diagnosis is mainly based on skin lesions with obvious sensory loss, peripheral nerve thickness with dysfunction, positive results in acid-fast bacilli test, results of histopathology, and results of lepromin test.


Treatment

Antibiotic treatment can alleviate disease progression but cannot reverse nerve damage and deformation. Therefore, early diagnosis and immediate treatment are extremely important. Due to the presence of drug resistance, polypharmacotherapy is necessary. The choice of medication depends on the type of leprosy. Compared with paucidacillary leprosy, multibacillary leprosy requires intensive treatment and long-term treatment.

Treatment of multibacillary leprosy

WHO guidelines recommend dapsone, rifampicin, and clofazimine. Treatment regimen is rifampicin 600mg and clofazimine 300mg orally once a month in directly observed therapy or dapsone 100mg and clofazimine 50mg orally once a day in self administered treatment for 12 months.

Treatment of paucidacillary leprosy

WHO standard treatment regimen is rifampicin 600mg orally once a month or dapsone 100mg once daily in self administered treatment for 6 months. Patients with only a lesion can take rifampicin 600mg, ofloxacin 400mg, and minocycline 100mg orally in a single dose.

Treatment of type I lepra reaction

The treatment regimen is prednisone with a loading dose of 40 - 60mg orally once a day and a maintenance dose of usually 10 - 15mg orally once a day for several months. Mild skin inflammation does not require treatment.

Treatment of type II lepra reaction

Aspirin is generally used. Under severe conditions, treatment regimen is prednisone 40 - 60mg orally once a day combined with antibiotics for 1 week. Recurrent patients can take thalidomide 100 - 300mg orally once a day. Pregnant women are contraindicated because of teratogenic and sedative effects. Adverse reactions are mainly mild constipation and lymphopenia as well as sedation.


Prevention

The best prevention is to avoid exposure to body fluids and wounds in leprosy patients