248 Diffuse leprosy of Lucio and Latapi - LEPRA Health in Action

Lepr Rev (2007) 78, 248–260 

Diffuse leprosy of Lucio and Latapí: a histologic 

study 

FRANCISCO VARGAS-OCAMPO 

Instituto de Diagnóstico y Referencia Epidemiológicos (InDRE). 

México, D.F., México 

Accepted for publication 28 August 2007 

Summary 

Background and purpose Ladislao de la Pascua described the spotted or lazarine 

leprosy for first time in 1844. Later on, Lucio and Alvarado studied and published it with 

the same names in 1852. Latapí re-discovered it in 1938 and reported it as ‘Spotted’ 

leprosy of Lucio in 1948. Frenken named it diffuse leprosy of Lucio and Latapí in 1963. 

Latapí and Chévez-Zamora explained that the fundamental condition of this variety of 

leprosy was a diffuse generalised cutaneous infiltration, naming it pure and primitive 

diffuse lepromatosis, upon which necrotising lesions develop, calling these lesions 

Fenómeno de Lucio or erythema necrotisans. A great number of histopathological 

reports have addressed the study of Lucio’s phenomenon, and few about the histologic 

changes that take place in the course of diffuse lepromatous leprosy. The purpose of this 

work is to report the histologic findings observed in the study of l70 cutaneous biopsies 

of diffuse leprosy of Lucio and Latapí and 30 of Lucio’s phenomenon. 

Methods This is a retrospective study, which included the examination of 200 biopsy 

skin specimens from 199 patients with diffuse leprosy at different course of the 

disease. These cases were diagnosed in Mexico from 1970 to 2004. 

Results The histologic examination revealed a vascular pattern affecting all cutaneous 

vessels, characterised by five outstanding features: a) colonisation of endothelial cells 

by acid-fast bacilli, b) endothelial proliferation and marked thickening of vessel walls 

to the point of obliteration, c) angiogenesis, d) vascular ectasia, and e) thrombosis. 

Necrotising lesions seen in diffuse lepromatous leprosy displayed two 

histopathological patterns: one of them, non-inflammatory occlusive vasculopathy 

and, the other one, occlusive vasculopathy, leukocytoclastic vasculitis, large 

neutrophilic infiltrate and lobular panniculitis. The first appeared as a result of the 

course of the occlusive vasculopathy produced by the colonisation of endothelial cells 

by Mycobacterium leprae. The second, as a result of a previous occlusive vasculopathy 

plus a leprosy reaction which is considered here as variant of ENL. 

Conclusions Endothelial cell injury appears to be the main event in the pathogenesis 

of diffuse leprosy of Lucio and Latapí. Once M. leprae has entered the endothelial 

cell, the micro-organism damages the blood vessels, leading to the specific changes 

seen in this variety of lepromatous leprosy. 

Correspondence to: F. Vargas-Ocampo, Laboratorio de dermatopatología, InDRE Carpio 470, México, D.F., 

11340. México (e-mail: vargasocampo@correo.unam.mx) 

0305-7518//064053+13 $1.00 q Lepra 248

Introduction 

In 1844, Ladislao de la Pascua, when Director of the ‘Hospital de los Lazarinos’ in Mexico 

City, described three clinical forms of leprosy, tuberculous (nodular), anaesthetic and a third 

characterised by the production of painful red spots that went on to ulcerate. These patients 

were known in Mexico as ‘Lazarinos’. 1 Later on, Rafael Lucio, in collaboration with Ignacio 

Alvarado, published in 1852 a paper entitled ‘Opúsculo de la Enfermedad de San Lázaro o 

Elefanciasis de los Griegos’, 2 in which Lucio described his observations, made during 8 years 

at the same ‘Hospital de los Lazarinos’ in Mexico City, of which he was Director after de la 

Pascua. He also distinguished three clinical forms of leprosy: tuberculous (nodular), 

anaesthetic, and spotted (manchada), and paid special attention to the spotty form, 

characterised by the presence of red and painful spots undergoing necrosis, and which was 

striking because the skin underwent characteristic changes according to the stage of the 

condition. This landmark paper by Lucio and Alvarado was gradually forgotten and this 

variety of leprosy was completely unknown among leprologists outside Mexico until Latapí 

and Chevez-Zamora 3 brought it to attention at the 5th International Congress of Leprosy held 

in Havana in 1948. That the authors explained that the underlying condition of this clinical 

form, unnoticed by Lucio and Alvarado, was generalised diffuse cutaneous infiltration, which 

Latapí and Chevez-Zamora named ‘pure and primitive diffuse lepromatosis’, upon which 

secondary cutaneous outbreaks developed. These outbreaks were regarded as a form of lepra 

reaction produced by multiple, acute, necrotising vasculitis for which Latapí proposed the 

name of ‘Fenómeno de Lucio or erythema necrotisans’. Before Latapí and Chevez-Zamora’s 

report, Martinez Baez had studied spotted lesions of five patients in 1941, 1,3 – 6,20 noting the 

basic lepromatous structure, acute vasculitis with nuclear dust, and thickening and occlusion 

of the larger vessels producing necrosis. He described for the first time the histological 

changes that occurred in what Latapí would later name Lucio’s phenomenon. 

About 1943, Latapí distinguished the pure and primitive diffuse leprosy that always 

begins as diffuse leprosy, and the secondary diffuse leprosy, which arises from an 

indeterminate form; both display the same clinical aspect and the same histologic changes 

during their course. 5,7 In 1963, Frenken included both under the name of diffuse leprosy of 

Lucio and Latapí, having as fundamental characteristic, that the generalised infiltration never 

develops nodules. 1,5,7 

Diffuse leprosy of Lucio and Latapí is characterised by a diffuse cutaneous infiltration, 

without nodules, succulent or atrophic according to the stage of progression. Dysesthesia, 

anhidrosis, alopecia, destructive rhinitis and telangiectasia, and a special variant of lepra 

reaction named Lucio’s phenomenon or erythema necrotisans (erythema necroticans). 

Histologically it has been reported that the finding of heavy endothelial parasitisation by 

Mycobacterium leprae is a peculiar feature to diffuse leprosy. 

Diffuse leprosy of Lucio and Latapí 249 

4,5,8 – 12 

Lucio’s phenomenon is clinically characterised by crops of wine-red irregular spots 

(manchas) with burning sensation, sharply delineated, and capricious centre, which turn 

purpuric and become necrotic leaving atrophic stellar scars. Histopathologically Lucio’s 

phenomenon has been reported to have two types of patterns. One of them involves 

leukocytoclastic vasculitis as the underlying pathologic change, 5,13,14 and the other, 

endothelial cell proliferation, thrombosis, a mild mononuclear cell infiltrate and ischemic 

necrosis. 15,16 The first pattern is thought to be due to an immune complex disease caused by 

leprae or skin antigens. 17 In the second pattern, vascular damage is thought to be due to direct 

invasion of M. leprae. 15,16

250 

Diffuse leprosy is considered to be the most anergic of the all-immunological spectrum of 

leprosy. 18 In a study on lepromin responsiveness, Leiker reported that not all lepromatous 

patients are completely anergic to lepromin, as a weak response to lepromin had been 

observed in many such cases and it seemed that the diffuse lepromatous variety was the only 

truly anergic type of leprosy. 19 Lucio and other authors believed that this variety of the 

disease was exclusive to Mexico. Yet it is found not only in Mexico, but also in other 

countries. 8,13,21 – 24 The purpose of this study is to describe histological changes seen in 170 

cutaneous biopsies of diffuse leprosy of Lucio and Latapí and 30 of Lucio’s phenomenon. 

Materials and methods 

This is a retrospective study, which included the examination of 200 biopsy specimens of 

diffuse leprosy of Lucio and Latapí obtained from 199 patients. In one patient two biopsy 

specimens were taken, one was from infiltrated skin and other from a necrotic skin lesion. The 

cases were diagnosed between 1970 and 2004 at the Laboratory of Dermatopathology of the 

Institute for Epidemiologic Diagnosis and Reference (InDRE) in Mexico City. Twenty-six 

cases were from the archive of the InDRE; 174, were included in a previous report by the 

National Leprosy Control Programme. 25 Biopsies selected for this study were those that were 

taken from patients who had two or more physical signs of diffuse lepromatous leprosy 

without nodules (DLL). The clinical data were obtained from the histology request forms. 

Specimens were dispatched in glass or plastic vials containing 10% formalin solution from 

different provinces of the country to the InDRE in Mexico City where all histological 

processing was carried out. Specimens were processed routinely and stained with 

haematoxylin and eosin; the first 125 specimens with Fite-Faraco stain, and the other 75 

specimens with a modified Fite-Faraco stain using carbol-fuchsin solution to stain acid-fast 

bacilli, Weigert’s iron haematoxylin to stain nuclei, and metanil yellow solution to stain other 

tissue elements. 26 The leprosy programme uses the Madrid classification, 27 which considers 

two polar types: lepromatous and tuberculoid; and two groups: indeterminate and 

dimorphous. This classification does not include the variety diffuse lepromatous leprosy. 

Results 

F. Vargas-Ocampo 

The series was composed of 128 males and 71 females, with a male to female ratio 1·8:1; the 

ages ranged from 12 to 88 years, with a median age of 37 years and an average of 28.8 years. 

The elapsed time from the appearance of the first sign or symptom referable to leprosy ranged 

from 1 week to 12 years, with a median of 3 years and an average of 4.2 years. Out of the 200 

cases, 181 (90·5%) were from Pacific Coast states of Mexico and 19 (9·5%) from other states 

of Mexico. 

The biopsy specimens were obtained at different times in the course of the illness, and 

included those that showed apparently normal skin and those with necrotising lesions; 170 

were from patients with diffuse leprosy without necrotising lesions, and 30 were from patients 

with diffuse leprosy with Lucio’s phenomenon. All patients had physical signs of DLL), 

mainly diffuse infiltration of the skin, impairment of sensation (numbness of the dorsal aspects 

of the extremities, hypaesthesia, or aesthesia), alopecia of eyebrows and eyelashes, anhidrosis, 

and destructive rhinitis. All the biopsy specimens were obtained from skin with sensory

impairment associated with another or other physical signs of DLL: 32 from apparently normal 

skin, 82 from skin with diffuse infiltration, 13 from atrophic skin, 9 from hypochromic macules, 

7 from erythematous macules, and 30 from skin with Lucio’s phenomenon, data on 27 cases 

were missing. Biopsy sites were: 141 from the limbs, 33 from the ear lobe, 12 from the trunk, 

data on 14 cases were missing. As the clinical diagnosis made by physicians of the control 

programme did not include diffuse leprosy, 86 of the request forms for histological study only 

had the clinical diagnosis ‘lepromatous’. Nonetheless, 62 had the clinical diagnosis of DLL and 

8 the clinical diagnosis of pure and primitive diffuse lepromatosis (PPDL), because, these 

specific diagnoses were made by physicians with several years working in the programme. 

There were other clinical diagnoses: 7 of indeterminate leprosy, 4 of dimorphous leprosy 1 of 

tuberculoid leprosy, 30 of Lucio phenomenon, and 2 were without clinical diagnosis. The 

physical signs of leprosy reported by medical staff in the request forms for histological exam, 

apart from the lesions of Lucio’s phenomenon, correspond closely with DLL, thus, none of the 

199 patients had nodular lesions. The 199 (100%) presented impairment of sensation 

(hypaesthesia or anaesthesia or numbness of the extremities), 132 diffuse cutaneous infiltration 

with absence of nodules, 36 apparently normal skin, 15 atrophic skin, 9 hypochromic macules, 

7 erythematous macules, 87 anhidrosis, 126 alopecia of eyebrows, and 63 destructive rhinitis. 

The histopathological features were divided into five stages: (1) early, (2) bacillary 

dissemination, (3) well-developed, (4) necrosis by vascular occlusion and (5) necrosis by 

vascular occlusion plus leprosy reaction. The changes observed during these different 

histologic stages are described below. 

STAGE 1. EARLY 

Fifty-three biopsies comprised 33 males and 20 females (M:F ratio 1·7:1), age range 15 to 88 

years, (median 43 years and mean 43). The delay from the appearance of the first sign referable 

to leprosy was 2 months to 17 years (median 1 year, mean 1.4 years). The skin where the 

specimens were taken was: diffuse infiltration 36, apparently normal with dysesthesia 3, 

atrophic 2, hypocromic macule 1, erythematous macule 2, no information 9. Biopsy sites were: 

inferior extremity 18, upper extremity 19, thorax 4, and ear lobe 9, no information 3. 

Histology 

Blood vessels looked dilated with a thick wall lined with normal or plump proliferative 

endothelial cells. Slight and apparently insignificant foci of infiltration were present in the 

dermis, arranged around dilated blood vessels. Very scarce bacilli could be observed in the 

endothelial cells in few of the large vessels and in some nerve trunks of the deep dermis. 

STAGE 2. BACILLARY DISSEMINATION 


Sixty-two biopsies comprised 32 males and 30 females (M:F ratio 1·1:1; the age range 15 

years to 85 years, (median 39 years). The delay from the appearance of the first sign referable 

to leprosy ranged from 1 month to 22 years (median 3 years, mean 3.4 years). The skin where 

the specimens were taken were: diffuse infiltration 34, dysesthesia, anhidrosis and alopecia 5, 

atrophic 5, hypochromic macule 7, erythematous macule 3, no information 8. The biopsy 

sites were: inferior extremity 20, upper extremity 22, thorax 2, abdomen 1, ear lobe 13, no 

information 4.

252 


Histology 

Dissemination of acid-fast-bacilli (AFB) extended progressively from the deep plexus to all 

cutaneous blood vessels, first, into the blood vessels of the subcutis and reticular dermis; then 

to vessels of the superficial plexus; and finally to capillaries of the papillary dermis. The 

vessels showed acid-fast bacilli inside swollen endothelial cells, thrombosis, passive 

congestion and ectasia. The lumen of the large vessels was reduced in size by intimal 

proliferative thickening. Small infiltrates of mononuclear cells were arranged around blood 

vessels of the dermis and subcutaneous fat tissue. 

STAGE 3. WELL-DEVELOPED 

Fifty-five biopsies comprised 34 males and 21 females, M:F ratio 1·6:1; age range 12 years to 

77 years, (median 28 years, mean 34·6. The delay from the appearance of the first sign 

referable to leprosy ranged from 4 months to 20 years (median 2 years, mean 3.4 years). The 

skin where the specimens were taken were: diffuse infiltration 29, dysesthesia, anhidrosis and 

alopecia) 7, atrophic skin with dysesthesia, anhidrosis and alopecia 6, hypocromic macule 1, 

erythematous macule 2, no information 10. Biopsy sites were: inferior extremity 26, upper 

extremity 9, thorax 5, ear lobe 7, no information 8. 

Histology 

Well-developed lesions were characterised by vascular ectasia, focal passive congestion, 

thrombi and an increase in capillaries. The blood vessels of the dermis and the subcutis 

showed a swollen and prominent endothelium, thick wall and narrowed or obliterated lumen 

(Figure 1A). 

The infiltrate, which was composed of lymphocytes and macrophages, was slight, in the 

dermis cuffing the blood vessels (Figure 1A), and in the subcutis invading the subcutaneous 

fat. Variable numbers of Virchow cells were diffusely distributed around blood vessels in the 

dermis and subcutaneous fat. Acid-fast staining showed bacilli in the perivascular 

inflammatory infiltrate (Figure 1B) and, in the most cases within one or more of the 

endothelial cells of the cutaneous blood vessels (Figures 1C–1E). 

STAGE 4. ISCHAEMIC NECROSIS DUE TO NON-INFLAMMATORY VASCULAR 

OCCLUSION 

Eight biopsies comprised 6 males and 2 females, M:F ratio 3:1; age range 29 years to 67 

years, (median 38 years mean 3.1 years). The delay from the appearance of the first sign 

referable to leprosy ranged from 6 days to 14 years (median 2 years, mean 3.1 years). All had 

necrotic lesions of the skin, from which the specimens were taken. Biopsy sites were: inferior 

extremity 2, upper extremity 3, and abdomen 1, no information 2. 

Histology 

The main feature in this fourth stage was a severe damage of blood vessels. The presence of 

M. leprae in endothelial cells seemed responsible for this change. Histological appearance 

was characterised by necrosis of epidermis and superficial dermis, angiogenesis, ectasia,


Figure 1. Each section is from a different third stage case. 1A) shows a large and thick subcutaneous blood vessel, 

and in the dermis, thin perivascular inflammatory cuffs with a streak-like appearance. 1B) A band of inflammatory 

infiltrate is composed of mononuclear cells, without foam cells, containing numerous bacilli. Two capillaries in 

transverse section with bacilli (ca) can be seen. 1C–1E) shows high power views of blood vessels with numerous 

bacilli in endothelial cells and absence of infiltrated inflammatory, (1C) in superficial dermis, 1D) in mid dermis, and 

1E) in deep dermis (1A. H&E; £ 35, 1B. Fite-Faraco; X400, !C-1E. Fite-Faraco; £ 1000). 

passive venous congestion and vascular occlusion caused by luminal thrombi and/or by 

thickening of the vessel wall. Angiogenesis, ectasia, passive venous congestion, and luminal 

thrombi were most evident in superficial dermis (Figures 2B, 2C, 3F) and in middle dermis 

(Figure 2A). 

Thickening of vessel wall with reduction of the lumen and sometimes with obliteration 

was seen in vessels of the dermis (Figures 3B-3E) and of the subcutis (Figure 3A). The 

inflammatory infiltrate and the presence of bacilli were similar to that of the previous third 

stage. 

STAGE 5. ISCHAEMIC NECROSIS DUE TO INFLAMMATORY VASCULAR OCCLUSION 

PLUS LEPROSY REACTION 

Twenty-two biopsies comprised 9 males and 13 females, M:F ratio of 1:1·4; age range 12 

years to 75 years, (median 39 years, mean 7.8 years). Delay from the appearance of the first 

sign referable to leprosy ranged from 3 months to 28 years (median 3 years, mean 7.8 years). 

All had necrotic lesions of the skin, from which the specimens were taken. The part of the 

body where the biopsies specimens were taken was: inferior extremity 9, upper extremity 11, 

no information 2.

254 


Figure 2. 2A) third stage lesion, showing a blood vessel distended by thrombus. 2B) this is a transition lesion between 

third and fourth stages. The epidermis appears stretched and thinned with pyknotic malpighian cells. In the 

dermis, beneath of epidermis, thrombi (T) occlude the lumina of some superficial capillaries; there is no 

inflammatory infiltrate. 2C) from a lesion in fourth stage. This superficial lesion shows loss of epidermis, thrombosis 

and congestion of capillaries papillae Note the absence of inflammatory cells. This lesion heals “restitutio ad 

integrum”. 2D) from a case in fourth stage, exhibits loss of tissue that includes the epidermis and some superficial 

dermis, and a superficial vessel occluded by an amorphous homogeneous and acidophilic substance. (2A. H&E; 

£ 100, 2B–2D. H&E; £ 250). 

Histology 

This fifth stage showed changes superimposed on the pre-existing occlusive vascular damage. 

They included necrosis of epidermis (Figure 4B) and superficial dermis, hyalinisation and/or 

deposits of fibrin in small blood vessel walls of the dermis and the subcutaneous fat tissue. 

(Figures 4A–4E). 

The cellular infiltrate around these vessels consisted of neutrophils, nuclear dust, a few 

eosinophils, lymphocytes, and in rare cases red blood cells. Large vessels in the deeper 

reticular dermis and in the subcutis showed pronounced thickening and intimal proliferation 

causing reduction in vascular lumen and sometimes complete occlusion; their wall was 

infiltrated by neutrophils and lymphocytes (Figure 4E). In addition, a dense predominantly 

neutrophil infiltrate was seen involving the deeper dermis and the lobular portion of the

subcutaneous fat tissue as a lobular panniculitis. In one case there was a granulomatous 

reaction within and around a large blood vessel of the subcutis. 

CHANGES FOUND IN OTHER STRUCTURES OF THE SKIN 

AFB were found not only in blood vessels, but also in lymph vessels, nerves, hair follicles, 

erector pili muscles, sebaceous glands, sweat glands, and in a few cases in the different layers 

of the epidermis (Table 1). 

Usually, bacilli were more abundant in sections of the biopsy specimens taken from the 

ear lobe. Nerves and epidermal appendages showed different degrees of invasion, 

degeneration and destruction by the inflammatory infiltrate, these changes being more 

noticeable in the ischaemic tissue necrosis stages. 

Discussion 


Figure 3. 3A) from a biopsy of a third stage lesion, showing a large vein in the subcutis with very thick wall, lumen 

almost occluded and bacilli within endothelial cells. There is no inflammatory infiltrate. (3B–3D) three illustrations 

from different third stage cases. They show vessels in the reticular dermis with prominent endothelial proliferation 

and numerous bacilli within a small (L in 3B) or obliterated vascular lumen. 3E) from fourth stage biopsy, shows a 

blood vessel occluded by extensive intimal proliferation and dermal necrosis. 3F) another example from a fourth 

stage lesion, exhibits superficial necrosis with loss of epidermis, obliterative changes of two superficial blood vessels 

with homogenization and hyalinization of their walls. (3A. Fite-Faraco stain; £ 250, 3B–3D. Fite-Faraco stain; £ 

1000, 3E. H&E; £ 250, 3F. H&E; £ 400). 

Histopathologically, five stages of DLL were considered in this study, each of them having 

different features. When the clinical data are correlated with the histological changes, the 

three first stages, early, disseminated, and well-developed, correspond to the phase in which 

patients have diffuse infiltration of entire skin The fourth and fifth stages of ischaemic 

necrosis correspond to Lucio’s phenomenon or erythema necroticans. Endothelial cells seem 

to be the main targets of the organism, and following invasion of M. leprae vascular damage

256 


Figure 4. All sections are from a fifth stage case. 4A) shows necrosis of the epidermis, leukocytoclastic vasculitis in 

small blood vessels of the dermis and subcutis. In the lower left is an almost occluded blood vessel infiltrated by 

inflammatory cells. 4B) necrosis of the epidermis and leukocytoclastic vasculitis. 4C) leukocytclastic vasculitis in the 

upper dermis. 4D) This illustration shows two small vessels, in the lower dermis, stained acidophillicaly (v) and 

surrounded by inflammatory infiltrate composed largely by neutrophils mixed with mononuclear cells. 4E) 

leukocytoclastic vasculitis in the subcutis. 4F) the subcutaneous blood vessel seen in 4A, shows endothelial 

proliferation and heavy infiltration by neutrophils, lymphocytes and histiocytes. (4A. H&E; £ 35, 4B. H&E; £ 160, 

4C. H&E; £ 400, 4D. H&E; £ 160, 4E. H&E; £ 400, 4F. H&E; £ 250).

Table 1. Presence of Mycobacterium leprae in different structures of the skin in the 200 cases of this study 

Structure 

Cases with the structure 

present in sections Percentage 


Cases with M. leprae 

in the structure Percentage 

Epidermis: 200 100 3 1·5 

Basal cells 200 100 3 1·5 

Melanocytes 200 100 2 1 

Spinous cells 200 100 2 1 

Granulous cells 200 100 1 0·5 

Corneocytes 200 100 1 0·5 

Hair follicles 102 51 47 46 

Sebaceous glands 81 40,5 6 7·4 

Pilli-erector muscles 101 50,5 51 50·5 

Sweat glands 155 77,5 12 7·7 

Nerves 43 21,5 40 93 

Lymp vessels 23 11·5 15 65·22 

Blood vessels 200 100 100 100 

occurs, suggesting that the colonisation of the endothelial cells by acid-fast bacilli could be 

responsible for this damage. At the early stage, the changes consist of dilated vessels, 

angiogenesis, and congestion. Endothelial bacillation varies considerably with the 

progression of lesions. In the beginning, there are very few bacilli in the endothelial cells 

of large blood vessels. As time goes by, organisms increase within the endothelial cells. Later, 

bacilli spread progressively from the deep plexus to mid and small-sized vessels of the dermis 

and subcutis to give rise to a well-developed histological lesion in which most of the sections 

show all blood vessels having a bacillated endothelium, a finding already reported by 

Martinez-Baez, who said: “: ::every time one sees the picture of a blood-vessel, one can 

observe that the mentioned bacilli are present in one or more to the endothelial cells”. 4 

The presence and constitution of the infiltrate were variable and did not seem to be related 

to the age of the lesion. Biopsies of some patients at a well-developed histological stage and 

with a long clinical evolution up to 10 years showed only a slight perivascular mononuclear 

infiltrate, while other cases with well-developed histological lesions but with a short clinical 

history showed a dense mononuclear infiltrate. Relatively few Virchow-cells were seen 

compared with the great number of bacilli. 

The fourth stage of ischaemic necrosis due to non-inflammatory vascular occlusion is 

characterised histologically by the presence of necrotic cutaneous lesions due to vascular 

occlusion by endothelial proliferation or thrombosis, and clinically it coincides with the 

appearance of discrete purple-coloured painful spots, which lead to ulceration of the skin 

without systemic symptoms. It should be stressed that the fourth stage of ischaemic necrosis 

due to non-inflammatory vascular occlusion seems to be caused by vascular injury induced by 

invasion of the endothelial cells by Mycobacterium leprae 15,16 and that tissue necrosis is due 

to vascular occlusion by proliferative endothelium or thrombosis. At this stage systemic 

symptoms do not develop and these are the cases that do not respond to thalidomide. This 

pattern, the damage of which is seen with or without sparse inflammatory cells, seems to 

correspond to the one that Rea used the term vasculosis. 28 

The fifth stage of ischaemic necrosis appears as an acute reactional state that may 

supervene in such patients and aggravates the existing vascular damage. It is manifested 

microscopically by necrosis of the superficial dermis and epidermis, leukocytoclastic

258 

vasculitis in small blood vessel of the dermis and of the subcutis, and lobular panniculitis. 

Mid-sized and large blood vessels show intimal proliferative thickening, a narrow vascular 

lumen, and walls infiltrated by neutrophils and lymphocytes. 

The fifth stage of ischaemic necrosis is considered here as a severe variant of ENL. 29 

When this happens the clinical disease is exacerbated; the number of spots increases suddenly 

in several parts of the body, the pre-existing necrotic cutaneous lesions become aggravated 

and systemic symptoms appear. It is suggested that ENL and Lucio’s phenomenon may result 

from similar immunological mechanisms, 10 both show immune-vasculitis resulting from 

deposits of complement-fixing immune complexes in small blood vessel walls, 17,29 and both 

are may respond to thalidomide. In patients with either ENL or Lucio’s Phenomenon, 

deposits of IgG and C3, as well as circulating immune complexes have been found in the wall 

of small blood vessels. 17 It is known that immune complexes activate the complement system 

and become chemotatic for neutrophils, which ingest the immune complexes 30 and are 

subsequently destroyed in the form of nuclear fragmentation. Activation of the clotting 

system results in the conversion of fibrinogen to fibrin. The histological picture shows 

neutrophils, nuclear dust, and fibrin in the wall of small blood vessels, features that establish 

the diagnosis of leukocytoclastic vasculitis (LCV). 31 Clinically different manifestations are 

described to LCV, including macules, papules, nodules, vesicles, bullae, and ulcers. 32 

Some immunological, histological and clinical aspects distinguish Lucio’s phenomenon 

from ENL. Immunologically, Lucio’s phenomenon occurs in patients considered the most 

anergic of the all-immunological spectrum of leprosy. Histologically, Lucio’s phenomenon 

starts with heavy colonisation of the endothelial cells by acid-fast bacilli. It develops in a 

tissue that already has severe vascular damage, and it is always associated with skin necrosis. 

Clinically, Lucio’s phenomenon is an erythema necorcitans, characterised by red and painful 

spots (manchas) that progress to necrosis and ulceration leaving atrophic stellar scars, 

occurring in a skin with diffuse generalised infiltration and complete absence of nodules, and 

appearing in untreated patients. In this study, one case of granulomatous vasculitis in the 

subcutis was only observed in patients in this stage; a change that could contribute to 

anoxia. 12 

Another noteworthy fact, in stages four and five, was the finding of vascular occlusion by 

thrombi, with no signs of perivascular inflammation. The endothelium has on its surface a 

number of anticoagulant and procoagulation properties which, when perturbed, may lead to 

intravascular coagulation. 33 Therefore the activation of the endothelial cell by organisms can 

trigger a cascade of events leading to the conversion of fibrinogen to fibrin intravascular and 

thrombosis that occlude arterioles and capillaries. 34 – 36 Lucio and Alvarado remarked in their 

work that in these patients the level of fibrin was always elevated, and the patients bleed less 

during a surgical amputation. 2 

The nasal mucosa is involved early in the course of Lucio’s leprosy 2 and at least 95% of 

all patients with lepromatous leprosy have nasal involvement too. 37 Leprosy bacilli may 

spread though the bloodstream from the nose to another area of the body, among them the 

skin. 

38 – 41 


The results of this study support the hypothesis that in Lucio’s leprosy there are leprosy 

bacilli in endothelial cells throughout the vasculature that promote the liberation of 

substances by the endothelium that induce vascular reactivity as manifested by distended 

vessels, morphological changes of the endothelial cells, areas of passive venous congestion 

and foci of intravascular clotting, which proceed to disseminated intravascular coagulation 

(DIC). DIC is one of the causes of death among these patients. 14,21,22

It is suggested here that in all cases of lepromatous leprosy, be they nodular or diffuse, the 

first lesion is the same: the colonisation of the endothelium by bacilli and that the course of 

the disease be determined by the resistance of each patient to the micro-organism. 

Suitable treatment can reverse the obliterative changes. Skin biopsies from treated 

patients show vessels cleared of organisms. Some solid bacilli, however, can remain in the 

media of great blood vessels, and persist in spite of treatment. In vessels of treated patients 

thickness of the walls diminishes gradually and the lumen becomes wide and clean, the 

disease does not progress and necrosis does not occur. Treatment with dapsone and 

rifampicin 3,6,15,16,42,43 is associated with the prompt cessation of new acute lesions. 3,6,15,43 

Consequently, the restoration of a normal endothelial cell state would be an important 

objective in the treatment of a patient with diffuse leprosy of Lucio and Latapí. The two 

important criteria for this diagnosis are: 1) diffuse non-nodular infiltration, and 2) heavy 

vascular endothelial parasitisation by M. leprae. 12 

Conclusions 

Histopathological findings suggest that diffuse leprosy of Lucio and Latapí is a vascular 

disorder produced by the invasion of vascular endothelial cells by Mycobacterium leprae. It 

would seem that once the bacilli have entered the endothelial cell, they induce endothelial cell 

activation that leads to specific morphologic and functional changes, among which are 

vascular ectasia, proliferation and swelling of the endothelium with thickness of the vessel 

walls, angiogenesis, and activation of clotting which gives rise to thrombosis. These changes 

characterise this variety of lepromatous leprosy. 3 – 5,7 – 16,18,20 – 25,28,41,43 The necrotising 

lesions of Lucio’s phenomenon are due first, to occlusive vasculopathy, without systemic 

symptoms, 16,17 and secondly, to a lepra reaction that aggravates vascular damage and causes 

systemic signs and symptoms. 

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248 Diffuse leprosy of Lucio and Latapi - LEPRA Health in Action

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