Leprosy

Moetaz El-Domyati, Basma Mourad, and Hossam Abdel-Wahab

Contents1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

2 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

3 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

4 Different Types of Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.1 Tuberculoid Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44.2 Lepromatous Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54.3 Borderline Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64.4 Pure Neuritic Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

5 Reactions of Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135.1 Type I (Reversal Reaction) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135.2 Type II (Erythema Nodosum Leprosum) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145.3 Lucio Reaction (Lucio Phenomenon) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

AbstractLeprosy is a chronic granulomatous disease caused byMycobacterium leprae, principally affecting the periph-eral nerves and skin. Leprosy is a serious health issue in anumber of low socioeconomic classes and overcrowdedcountries. Although it seldom kills, leprosy represents adeforming, disabling, and stigmatizing disease. It has awide spectrum of clinical findings, including lepromatous,tuberculoid, borderline, and indeterminate poles. Thediagnosis is usually made by characteristic clinical find-ings (typical skin lesions, skin anesthesia, or thickened

nerves), slit-skin smears, skin and nerve biopsy, andlepromin test.

Antibacterial treatment (multidrug regimen) for leprosyis highly effective, with low relapse rate, but needs to betaken over many months. If left untreated, borderlinepatients will downgrade toward the lepromatous end ofthe spectrum, and lepromatous patients will suffer fromthe numerous complications of bacillary invasion.

M. El-Domyati (*) · H. Abdel-WahabDepartment of Dermatology and Venereology, Minia University,Al-Minya, Egypte-mail: moetazeldomyati@yahoo.com; moetazeldomyati@gmail.com;semsem1972@yahoo.com; hossamabdelwahab1972@mu.edu.eg

B. MouradDepartment of Dermatology and Venereology, Faculty of Medicine,Tanta University, Tanta, Egypte-mail: basmamourad@gmail.com

© Springer Nature Switzerland AG 2019B. Smoller, N. Bagherani (eds.), Atlas of Dermatology, Dermatopathology and Venereology ,https://doi.org/10.1007/978-3-319-45134-3_74-1

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KeywordsLeprosy · Granulomatous disease · Mycobacteriumleprae · Slit-skin smear · Lepromin test · Tuberculoidleprosy · Anesthesia · Tuberculoid granulomas ·Lepromatous leprosy · Leonine facies · Madarosis · Gloveand stocking anesthesia · Borderline leprosy · Epithelioidcell granuloma · Acute neuritis · Small granuloma · Pureneuritic leprosy · Active neuritis · Permanent nervedamage · Type I reaction · Reversal reaction ·Constitutional symptom · Type II reaction · Erythemanodosum leprosum · Uveitis · Dactylitis · Arthritis ·Neuritis · Lymphadenitis · Myositis · Orchitis · Lucioreaction · Lucio phenomenon · Vasculitis · Disseminatedintravascular coagulation · Septicemia

1 Introduction

Leprosy is a chronic granulomatous disease caused byMyco-bacterium leprae, principally affecting the peripheral nervesand skin. It is characterized by an average incubation time of2–5 years for tuberculoid cases and 8–12 years for leproma-tous cases (Levy and Ji 2006). It is an important health issuein a number of poor classes and overcrowded countries.Although it seldom kills, leprosy represents a deforming,disabling, and stigmatizing disease (Ramos-e-Silva andRebello 2001; Sugita 1995). Official figures from 138 coun-tries of 6 World Health Organization (WHO) regions showedthat the global reported new cases were 2,011,973 at the endof 2015 (World Health Organization 2017).

Age, sex, household contact, and bacille Calmette–Guérin(BCG) vaccination are important determinants of leprosyrisk. Leprosy incidence reaches a peak at the age of10–14 years (Storrs 1971). A male predominance has regu-larly been found, although this may be due to women beingreluctant to present to health workers with skin lesions (Reesand Young 1994).

Nasal discharges from untreated lepromatous leprosy(LL) patients, who are often undiagnosed for many years,are the main source of infection in the community. Mean-while, the skin is unimportant in leprosy transmission (Pedley1973).

2 Classification

Leprosy has a wide spectrum of clinical findings. Afteradvancing the notion of polar forms of leprosy in 1938,Rabello, a Brazilian dermatologist, divided leprosy into four

types: lepromatous, tuberculoid, dimorphous, and indetermi-nate. In 1966, Ridley and Jopling created a classification alsobased on polar forms, with lepromatous (LL) at one end,tuberculoid (TT) at the other end, and three types of border-line leprosy in between: borderline lepromatous (BL), bor-derline borderline (BB), and borderline tuberculoid(BT) (Azulay and Azulay 2006; Britton 2003; Canizareset al. 1992; Ridley and Jopling 1966) (Table 1).

In 1997, the WHO created an operational simplified clas-sification based solely on the number of cutaneous lesions,independent of their size, location, or histologic features inorder to facilitate the classification and therapy of leprosy inendemic areas with no access to laboratory facilities. It clas-sifies leprosy into three groups: paucibacillary single-lesionleprosy, paucibacillary leprosy, and multibacillary leprosy(World Health Organization 2017) (Table 2).

3 Diagnosis

The diagnosis of leprosy is usually made clinically on thebasis of two out of three characteristic findings, or by thedemonstration of acid-fast bacilli (AFB) in slit-skin smears,

Table 1 Classification of leprosy according to immune status ofpatients (Azulay and Azulay 2006; Britton 2003; Canizares et al.1992; Ridley and Jopling 1966)

Spectrum ofleprosy Immune status

Lepromatous Depressed cell-mediated immunity

Tuberculoid Intact cell-mediated immunity

Dimorphous Unstable and capable of evolving intolepromatous or tuberculoid forms, dependingupon whether there is improvement or worseningof cell-mediated immunity

Indeterminate Normal cell-mediated immunity

Borderlinelepromatous

Immunodepressed end

Borderlinetuberculoid

Immunocompetent end

Borderlineborderline

In the middle between borderline lepromatous andborderline tuberculoid

Table 2 WHO classification of leprosy, 1997 (World Health Organiza-tion 2017)

Group Number of lesions

Paucibacillary, single-lesion leprosy One skin lesion

Paucibacillary leprosy Two to five skin lesions

Multibacillary leprosy More than five skin lesions

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or by histology typical of leprosy. The following diagnosticitems are:

– Clinical feature: The cardinal manifestations are:(i) Anesthesia of a skin lesion, or in the distribution of a

peripheral nerve, or over dorsal surfaces of the handsand feet

(ii) Thickened nerves, especially at the sites ofpredilection

(iii) Typical skin lesions (Lockwood 2010)

– Slit-skin smear: Fluid and pulp from the dermis of a skinfold that is gripped firmly between the thumb and forefin-ger to render it blood-free, collected on one side of theblade, are gently smeared onto a glass slide. The smear isthen fixed over a flame and stained (Ridley 1958). TheAFB load of a patient is determined by modifiedZiehl–Neelson staining of slit-skin smears (Fig. 1).

– Skin biopsy: Deep biopsy, including the whole dermis,should be taken down to subcutaneous fat; otherwise,leprous changes in the deeper layers of the dermis willbe missed (Ridley 1977).

– Nerve biopsy: In pure neural leprosy, a nerve biopsy isnecessary to confirm diagnosis (Lockwood 2010).

– Lepromin test: Lepromin is a crude, semi-standardizedpreparation of heat-killed bacilli from a lepromatous nod-ule or infected armadillo liver. It is a nonspecific test ofoccasional value in classifying a case of leprosy. It isstrongly positive in TT; weakly positive in BT; negativein BB, BL, and LL; and unpredictable in indeterminate

leprosy. It is not diagnostic, since it may be positive inpeople with no evidence of leprosy (Lockwood 2010).

4 Different Types of Leprosy

Early lesion of leprosy may present as an area of numbness onthe skin. Meanwhile, the classic early skin lesion (indetermi-nate leprosy) consists of one or more slightly hypopigmentedor erythematous macules, a few centimeters in diameter, withill-defined margins and most commonly found on the face,extensor surface of the limbs, buttocks, or trunk (Sehgal andSrivastava 1987) (Fig. 2). Clinically, the established cases ofleprosy may be presented with one of the following:

Fig. 1 Slit-skin smear of a case of lepromatous leprosy revealed AFB(X1000 – under oil immersion; MZN stain). (Courtesy of Dermatologyand Venereology Department, Minia University, Al-Minya, Egypt)

Fig. 2 Indeterminate leprosy; hypopigmented patches and maculeswith poorly defined margin affecting the left buttock and back of thethigh of a 6-year-old child. (Taken by Dr. Hossam Abdel-Wahab, Der-matology and Venereology Department, Minia University, Al-Minya,Egypt)

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4.1 Tuberculoid Leprosy

– Definition: In TT, only the nerves and skin show clinicalevidence of disease.

– Clinical feature: Lesions are few (one to three) conspic-uous, erythematous, copper-colored, or purple plaque,with raised and clear-cut edges sloping toward a flattenedand hypopigmented center. The surface is dry or scaly,insensitive, and hairless (Figs. 3, 4, 5, and 6). Some casesmay be purely neural, with pain and swelling of theaffected nerve followed by anesthesia and/or muscleweakness and wasting. Alternatively, a skin lesion appearswith or without evidence of nerve involvement. Erythemamay be absent in dark-skinned people. Sensory impair-ment may be difficult to demonstrate due to generoussensory nerve supply of the face. Thickened sensorynerve can be palpated in nearby lesions (Lockwood 2010).

– Pathological manifestation: Tuberculoid granulomascollect in foci surrounding neurovascular elements. Thegranuloma invades the papillary zone and may even erodethe epidermis, but AFB are not seen. Cutaneous nervesthat are not completely destroyed appear greatly swollenby epithelioid cell granulomas and surrounded by a zoneof lymphocytes; occasionally there may be caseationwithin the nerve (Antia et al. 1975) (Figs. 7 and 8).

Fig. 4 Tuberculoid leprosy; a6-year-old girl presented with fewasymptomatic rounded,erythematous, well-definedplaques of variable sizes andelevated borders over both thecheeks and chin of 1-yearduration. (Taken by Dr. HossamAbdel-Wahab, Dermatology andVenereology Department, MiniaUniversity, Al-Minya, Egypt)

Fig. 3 Tuberculoid leprosy; erythematous plaque with raised scalyedge and hypopigmented center over the right cheek of a 5-year-oldchild. (Taken by Dr. Hossam Abdel-Wahab, Dermatology andVenereology Department, Minia University, Al-Minya, Egypt)

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– Prognosis and treatment: Antibacterial treatment forleprosy is highly effective, with low relapse rates, butneeds to be taken over many months (Lockwood 2010).Rifampicin and dapsone are used for treatment of TT(Maiberger et al. 2018).

– Differential diagnosis: Birthmarks; pityriasis versicolor;hypopigmented lesions of eczema like pityriasis alba andringworm; and granuloma annulare and sarcoidosis forplaques and annular lesions.

4.2 Lepromatous Leprosy

– Definition: The first clinical manifestations of LL areusually dermal (because of asymptomatic early nerveinvolvement); hence, they may go unnoticed by thepatient, who often complains of other early symptoms.These symptoms include nasal stuffiness, nasal discharge,and epistaxis and edema of the legs and ankles due to

Fig. 5 Tuberculoid leprosy; (a)three erythematous plaques withraised edge over the left cheek of a32-year-old woman, and (b) theedge of the lesion is erythematous,raised, and well defined. (Takenby Prof. Moetaz El-Domyati,Dermatology and VenereologyDepartment, Minia University,Al-Minya, Egypt)

Fig. 6 Tuberculoid leprosy; (a)three erythematous plaques withraised edge over the face of a46-year-old woman, and (b) theedge of the lesion is erythematous,raised, and well defined. (Takenby Prof. Moetaz El-Domyati,Dermatology and VenereologyDepartment, Minia University,Al-Minya, Egypt)

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increased capillary stasis and permeability (Lockwood2010).

– Clinical feature: Dermal lesions of LL include macules,diffuse papules, infiltration, or nodules. Macules are small,multiple, erythematous, or faintly hypopigmented, withvague edges and shiny surface. Skin-colored or erythem-atous papules and nodules have bilateral symmetrical dis-tribution on the face, arms, legs, and buttocks. Theyusually spare areas of highest temperature including thehairy scalp, axillae, groins, and perineum (Lockwood2010).Oral lesions include papules on the lips and nodules on thepalate (which may perforate), uvula, tongue, and gums.The nasal mucosa is hyperemic or ulcerated and bleedseasily. Nerve affection usually presents with numbnessand anesthesia on the dorsal surfaces of the hands andfeet, later on extensor surfaces of the arms and legs, andfinally over the trunk (Lockwood 2010).

Forehead lines become deeper as the skin thickens(leonine facies) with many nodular and pigmented lesions,eyebrows and eyelashes become thinned or lost(madarosis), ear lobes are thickened, the nose becomesmisshapen, and the voice becomes hoarse. The skin of thelegs becomes ichthyotic and thickened. It may ulceratewith nerve thickening and bilateral “glove-and-stocking”anesthesia. Neuropathic changes, vasomotor alterations,and secretory disturbances may occur (Azulay and Azulay2006) (Figs. 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18).

– Pathological manifestation: Histological examination ofskin lesions shows thinning of the epidermis and flatteningof rete ridges. The papillary layer of the dermis appears asa clear band, while deeper in the dermis lies the typicaldiffuse leproma consisting of foamy macrophages, withthe addition of a few lymphocytes and plasma cells. Thedermis contains enormous numbers of AFB, singly or inclumps (Ridley 1988) (Figs. 19, 20, and 21).

– Prognosis and treatment: Antibacterial treatment forleprosy is highly effective, with low relapse rates, butneeds to be taken over many months (Lockwood 2010).Rifampicin, dapsone, and clofazimine are used for treatingLL. Discoloration of the skin (diffuse red–brown or bluishto violet–brown) in lesional sites is a common side effect(Maiberger et al. 2018) (Fig. 22).

– Differential diagnosis: Birthmarks; pityriasis versicolor;hypopigmented lesions of eczema like pityriasis alba,ringworm, and tinea corporis for lepromatous macules;granuloma annulare and sarcoidosis for plaques and annu-lar lesions; and cutaneous leishmaniasis for nodularlesions.

4.3 Borderline Leprosy

– Definition: Skin lesions of borderline leprosy are inter-mediate in number between those of the two polar types.

– Clinical feature: The lesions are usually distributedasymmetrically and depend on the position in the

Fig. 7 Histopathological featureof tuberculoid leprosy revealedlinear granulomas following thecutaneous nerves and reach thelevel of papillary dermis (A,X200, and B, X400; H&E).(Taken by Prof. MoetazEl-Domyati, Dermatology andVenereology Department, MiniaUniversity, Al-Minya, Egypt)

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Fig. 8 Histopathological feature of tuberculoid leprosy revealed mul-tiple granulomas consisting of epithelioid cells surrounded by denselymphocytic infiltrates in the dermis and around adnexal structures

(sebaceous glands) (A, X100; B, X200; and C, X400; H&E). (Takenby Dr. Hossam Abdel-Wahab, Dermatology and Venereology Depart-ment, Minia University, Al-Minya, Egypt)

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borderline spectrum. They may take the form of macules,plaques, annular lesions, or bizarre-shaped bands. Plaqueswith a “punched-out” appearance are characteristic of themiddle of the spectrum. Lesions are few, insensitive, andanhidrotic, with extensive hair loss. Neural symptomsmay precede the appearance of skin lesions by even8 years in which one or more nerves become thickenedand nonfunctional (Suneetha et al. 1998). When border-line leprosy downgrades to lepromatous one, the resultingsubpolar LL can be differentiated from polar LL throughhaving several asymmetrical thickened nerves and one or

more typical borderline skin lesions. Borderline leprosy isthe commonest type of disease encountered and is unsta-ble and can downgrade toward LL, especially if untreated,or upgrade toward TL (Lockwood 2010) (Figs. 23, 24, 25,and 26).

– Pathological manifestation: In comparison with TT, inBT, epithelioid cell granuloma is more diffuse, with moreLanghans-type giant cells. Dermal nerves are moderatelyswollen by cellular infiltration or may show only Schwanncell proliferation. AFBs are usually absent or rare (Antiaet al. 1975) (Figs. 27 and 28).

Fig. 9 Lepromatous leprosy; (a) a 25-year-old female patient presentedwith multiple symmetrically distributed brownish–red, non-itchy pap-ules and nodules of variable sizes of 1-year duration over the face along

with thinning of lateral thirds of both eyebrows, (b) right cheek, and (c)external ear. (Taken by Prof. Moetaz El-Domyati, Dermatology andVenereology Department, Minia University, Al-Minya, Egypt)

Fig. 10 Lepromatous leprosy;(a) a 36-year-old male patientpresented with multipleerythematous papules, plaques,and nodules of 2-month durationover the forehead and (b) externalear. (Taken by Prof. MoetazEl-Domyati, Dermatology andVenereology Department, MiniaUniversity, Al-Minya, Egypt)

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In BB, there are diffuse epithelioid cell granulomas withvery scanty lymphocytes and no giant cells, clear papillaryzone, slightly swollen nerves by cellular infiltrate, andmoderate number of AFBs (Ridley 1988).

In BL, macrophages may show slight foamy change.Dense clumps of lymphocytes are widely distributed inparts of the granuloma with occasional epithelioid cells.

The formation of small granulomas is characteristic ofborderline leprosy, and granulomatous regions may abutstrands of normal looking but heavily bacillated Schwanncells (Job 1973). Nerve damage results from a combina-tion of lepromatous bacillation and tuberculoid tissue-damaging response. Acute neuritis damage occurs partic-ularly during reversal reactions. Edema of the epithelioid

Fig. 11 Lepromatous leprosy;(a–c) erythematous and flesh-colored papules and plaques overthe trunk and (d) lowerextremities. (Taken by Prof.Moetaz El-Domyati, Dermatologyand Venereology Department,Minia University, Al-Minya,Egypt)

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cell granulomas compresses the remaining Schwann cellscausing rapid functional loss in an already compromisednerve (Antia et al. 1975).

– Prognosis and treatment: Left untreated, borderlinepatients will downgrade toward the lepromatous end ofthe spectrum, and lepromatous patients will suffer thenumerous consequences of bacillary invasion. They areat risk of developing type I reactions, which may result indevastating nerve damage (Lockwood 2010). Rifampicin,

dapsone, and clofazimine are used for the treatment(Maiberger et al. 2018).

– Differential diagnosis: Birthmarks; pityriasis versicolor;hypopigmented lesions of eczema like pityriasis alba,ringworm, and tinea corporis for lepromatous macules;granuloma annulare and sarcoidosis for plaques and annu-lar lesions; and cutaneous leishmaniasis for nodularlesions.

Fig. 12 Lepromatous leprosy;(a) a 30-year-old male patientpresenting with thickening of theskin of the face with furrowing ofthe forehead and nodular lesionsof the nose and (b–d)erythematous nodules on thetrunk, upper and lowerextremities, and buttocks withthickened skin of 2-year duration.(Taken by Dr. Hossam Abdel-Wahab, Dermatology andVenereology Department, MiniaUniversity, Al-Minya, Egypt)

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4.4 Pure Neuritic Leprosy

– Definition: Pure neuritic leprosy is a kind of leprosy withnerve involvement.

– Clinical feature: Pure neuritic leprosy presents withasymmetrical involvement of peripheral nerve trunks inabsence of visible skin lesions (Mahajan et al. 1996)(Fig. 29).

– Pathological manifestation: On histology of a cutaneousnerve biopsy, all types of leprosy are seen (Mahajan et al.1996).

– Prognosis and treatment: Established nerve damage isirreversible in many cases. Treatment of the neuritis iscurrently unsatisfactory, and some patients with activeneuritis will develop permanent nerve damage despitetreatment with corticosteroids (Lockwood and Sinha1999).

– Differential diagnosis: Hereditary sensory motor neurop-athy type III and amyloidosis.

Fig. 13 Lepromatous leprosy;(a and b) nodular lesions over thelower limbs with hyperpigmentedlesions and (c and d) dry andichthyotic skin of the legs. (Takenby Dr. Hossam Abdel-Wahab,Dermatology and VenereologyDepartment, Minia University,Al-Minya, Egypt)

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Fig. 14 Old lepromatousleprosy; (a–d) muscular atrophy,deformity, and pigmentarychanges. (Taken by Prof. BasmaMourad, Dermatology andVenereology Department, TantaUniversity, Egypt)

Fig. 15 Old lepromatousleprosy; (a) loss of teeth and (b–d)muscular atrophy, neuropathiculcer, and lost terminal phalangesin a 60-year-old man. (Taken byProf. Basma Mourad,Dermatology and VenereologyDepartment, Tanta University,Egypt)

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5 Reactions of Leprosy

5.1 Type I (Reversal Reaction)

– Definition: Type I or reversal reactions occur in borderlinedisease.

– Clinical feature: Type I or reversal reactions are charac-terized by acute neuritis and/or acutely inflamed skinlesions. Nerves often become tender with loss of sensoryand motor functions. Existing lesions may be erythema-tous, edematous, or desquamated and rarely ulcerated(Figs. 30, 31, and 32). New lesions may appear. Occasion-ally, edema of the face, hands, or feet is the presentingsymptom; however, constitutional symptoms are unusual(Lockwood et al. 1993).

– Pathological manifestation: Type I reactions are charac-terized by an increase in lymphocytes within lesions andsevere edema with disruption of the granuloma(Lockwood et al. 2008; Ridley and Radia 1981).

– Prognosis and treatment: Reactions and nerve damageare unpredictable. Nerve damage and its complicationsmay be severely disabling (Lockwood and Sinha 1999).The reactions should be treated to control acute inflam-mation, ease pain, and reverse nerve and eye damage.Neuritis and moderately inflamed skin lesions should betreated with corticosteroids (Kiran et al. 1985). Prednisoneand cyclosporine are used for this type of reactions(Prasad and Kaviarasan 2010). The patients should beeducated to cope with existing nerve damage and treat

Fig. 16 Old lepromatousleprosy; (a) loss of teeth and (b–d)muscular atrophy, neuropathiculcer, and lost terminal phalangesin a 55-year-old woman. (Takenby Prof. Basma Mourad,Dermatology and VenereologyDepartment, Tanta University,Egypt)

Fig. 17 Old lepromatous leprosy; (a and b) muscular atrophy, defor-mity, and lost phalanges. (Taken by Prof. Basma Mourad, Dermatologyand Venereology Department, Tanta University, Egypt)

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its complications. Social and psychological rehabilitationof patients is necessary.

– Differential diagnosis: Hereditary sensory motor neurop-athy type III and amyloidosis.

5.2 Type II (Erythema Nodosum Leprosum)

– Definition: Type II reactions or erythema nodosumleprosum (ENL) occurs in patients with multibacillarydisease (LL and BL). They may occur spontaneously(roseolar leprosy) or while on treatment. Up to 50% ofLL and 15% of BL patients may experience ENL reactions(Pocaterra et al. 2006).

– Clinical manifestation: Skin lesions include painful rednodules on the face and extensor surfaces of the limbs(Figs. 33 and 34). The lesions are variable and may besuperficial or deep with suppuration, ulceration, or indu-ration when chronic. Desquamation and fading of lesionsoccur over several days. ENL is a systemic disorder pro-ducing constitutional symptoms as fever and malaise andmay be associated with uveitis, dactylitis, arthritis, neuri-tis, lymphadenitis, myositis, and orchitis (Lockwood2010).

– Pathological manifestation: In type II reactions, poly-morphs infiltrate the granuloma, and vasculitis and mac-rophage degeneration occurs with breakdown of foamcells (Fig. 35). Nerve damage occurs more slowly and is

Fig. 19 Histopathologicalfeature of lepromatous leprosyrevealed: (a) diffuse granulomaseparated from flattened epidermisby a grenz zone and (b) numerousAFB in lesional skin (A, X200;H&E; and B, X400; MZN).(Courtesy of Dermatology andVenereology Department, MiniaUniversity, Al-Minya, Egypt)

Fig. 18 Old lepromatous leprosy; muscular atrophy, deformity, and lostphalanges in a 69-year-old man. (Taken by Prof. Basma Mourad, Der-matology and Venereology Department, Tanta University, Egypt)

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probably due to inflammation associated with ENL noduleformation in nerve trunks (Ridley 1988).

– Prognosis and treatment: Reactions and nerve damageare unpredictable. Nerve damage and its complicationsmay be severely disabling, especially when all four

limbs and both eyes are affected. Women are at risk ofreactions during the puerperium (Lockwood and Sinha1999). Thalidomide is the principal therapy for type IIreactions. Additional drugs with possible benefit includeclofazimine, cyclosporine, chloroquine, pentoxifylline,and phosphodiesterase type-4 inhibitors (e.g., roflumilast)(Prasad and Kaviarasan 2010). The patients should beeducated to cope with existing nerve damage and treatits complications. Social and psychological rehabilitationof patients is necessary.

– Differential diagnosis: Amyloidosis and leishmaniasis.

5.3 Lucio Reaction (Lucio Phenomenon)

– Definition: Lucio reaction or phenomenon is character-ized by severe, even fatal systemic upset.

– Clinical feature: Cutaneous vasculitis with subsequentinfarction and appearance of irregularly shaped erythem-atous patches is seen in Lucio reaction which becomesdark and heals or forms bullae and necrosis, leaving deeppainful slowly healing ulcers (Lockwood 2010) (Fig. 36).

– Pathological manifestation: In histological view, AFBsare seen through the dermis and around blood vesselswhich invade the vascular wall and endothelial cellsresulting in decreased vascular lumen, endothelial prolif-eration, and occlusion by thrombi. Inflammatory infiltratewith lymphocytes and neutrophils, leakage of red bloodcells, and perivascular histiocytic granulomas are seen(Monteiro et al. 2012).

– Prognosis and treatment: Lucio phenomenon is a rareevent causing death by disseminated intravascular coagu-lation and septicemia. There is no consensus for the besttreatment of this reaction. Balanced meals, local hygiene,dapsone, clofazimine, corticosteroids, and thalidomidehave been used for this case (Monteiro et al. 2012).

– Differential diagnosis: Sepsis, bacterial infections, dis-seminated intravascular coagulopathy, and vasculitis(Monteiro et al. 2012).

Fig. 20 Histopathological feature of lepromatous leprosy revealed: (a)infiltrate of foamy histiocytes filling the entire dermis separated from aflattened epidermis by a narrow grenz zone, and (b) foamy histiocytesshowed multiple vacuoles in the cytoplasm (A, X100, and B, X400;H&E). (Taken by Prof. Moetaz El-Domyati, Dermatology andVenereology Department, Minia University, Al-Minya, Egypt)

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Fig. 21 Histopathologicalfeature of lepromatous leprosyrevealed numerous lepra bacilliwithin the foamy histiocytes (A,X200, and B, X400; MZN).(Taken by Prof. MoetazEl-Domyati, Dermatology andVenereology Department, MiniaUniversity, Al-Minya, Egypt)

Fig. 22 A 20-year-old female, formerly diagnosed as leprosy andintermittently received clofazimine and dapsone for 2 years; the patientpresented with diffusely hyperpigmented, bluish to violet–brown in

lesional sites on the face and ears (side effect of clofazimine). (Takenby Dr. Hossam Abdel-Wahab, Dermatology and Venereology Depart-ment, Minia University, Al-Minya, Egypt)

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Fig. 23 Borderline tuberculoidleprosy; (a and b) a 35-year-oldmale patient presented withmultiple scaly erythematouslesions of 3-month duration withasymmetrical distribution over thetrunk, (c) buttocks, and (d)thickened superficial nerve (redarrow). (Courtesy of Dermatologyand Venereology Department,Minia University, Al-Minya,Egypt)

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Fig. 24 Borderline leprosy; (a–e)many shiny macules, papules,plaques, and nodules aredistributed in the upper limb,trunk, buttocks, and thigh of a31-year-old female. (Taken byProf. Moetaz El-Domyati,Dermatology and VenereologyDepartment, Minia University,Al-Minya, Egypt)

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Fig. 25 Borderline leprosy;(a and b) two anestheticerythematous plaques with partialhair loss and raised scaly edge.(Taken by Dr. Hossam Abdel-Wahab, Dermatology andVenereology Department, MiniaUniversity, Al-Minya, Egypt)

Fig. 26 Borderline lepromatousleprosy; (a) thickening of the skinof the face with furrowing of theforehead, and (b–d) multiplemacules, papules, plaques, andnodules are distributed in theupper limb, back, and buttocks ofa 58-year-old male. (Taken byDr. Hossam Abdel-Wahab,Associate Professor ofDermatology and VenereologyDepartment, Minia University,Al-Minya, Egypt)

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Fig. 27 Histopathologicalfeature of borderline tuberculoidleprosy revealed epithelioid cellgranulomas following theneurovascular bundle with anarrow free papillary zone (A,X200, and B, X400; H&E).(Taken by Dr. Hossam Abdel-Wahab, Dermatology andVenereology Department, MiniaUniversity, Al-Minya, Egypt)

Fig. 28 Histopathologicalfeature of borderline lepromatousleprosy showing (a) foci ofgranulomatous infiltrate separatedfrom flattened epidermis by anarrow grenz zone, (b) cellularinfiltrate of foamy macrophageswith lymphocytes distributed inparts of granuloma (A, X200,and B, X400; H&E). (Taken byDr. Hossam Abdel-Wahab,Dermatology and VenereologyDepartment, Minia University,Al-Minya, Egypt)

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Fig. 30 Type I reaction; (a–d) a40-year-old male patient withborderline lepromatous leprosypresented with sudden erythemaand edema with inflamed lesionsover the trunk. (Taken by Prof.Moetaz El-Domyati, Dermatologyand Venereology Department,Minia University, Al-Minya,Egypt)

Fig. 29 Pure neuritic leprosy; thickened visible ulnar nerve on the leftarm of a 36-year-old male in absence of visible skin lesions (red arrows).(Taken by Dr. Hossam Abdel-Wahab, Dermatology and VenereologyDepartment, Minia University, Al-Minya, Egypt)

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Fig. 31 Type I reaction in a40-year-old male patient with (a)borderline lepromatous leprosywith edematous and erythematouslesions, (b and c) hypopigmentedmacules, and (d) infiltration ofglans penis. (Taken by Prof.Moetaz El-Domyati, Dermatologyand Venereology Department,Minia University, Al-Minya,Egypt)

Fig. 32 Type I reaction: (a and b) a 40-year-old male patient with borderline lepromatous leprosy; edema affecting both the hands and feet whichappear dry. (Taken by Prof. Moetaz El-Domyati, Dermatology and Venereology Department, Minia University, Al-Minya, Egypt)

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Fig. 33 Erythema nodosumleprosum; (a) painful tendererythematous nodules affectingthe extensor surface of both handsand (b) wasting of muscles of thehands. (Taken by Dr. HossamAbdel-Wahab, Dermatology andVenereology Department, MiniaUniversity, Al-Minya, Egypt)

Fig. 34 Erythema nodosumleprosum; (a) a 50-year-old malepatient suffering painful tendererythematous nodules of 2-weekduration, (b) loss of the outer thirdof eyebrows, and (c–e)erythematous nodules are presentall over the body, especially theextremities. (Taken byDr. Hossam Abdel-Wahab,Dermatology and VenereologyDepartment, Minia University,Al-Minya, Egypt)

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Fig. 35 Histopathological feature of erythema nodosum leprosum revealed polymorphs infiltrate of the granuloma with vacuolated macrophages(X200; H&E). (Taken by Prof. Moetaz El-Domyati, Dermatology and Venereology Department, Minia University, Al-Minya, Egypt)

Fig. 36 Lucio phenomenon; (a) a70-year-old leprotic female withan ulcer surrounded by erythemaon the arm and (b) a deep painfululcer with dark necrotic floorsurrounded by vasculitic changeson the upper back. (Taken by Prof.Moetaz El-Domyati, Dermatologyand Venereology Department,Minia University, Al-Minya,Egypt)

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