Acta Neuropathologica 9 by Springer-Verlag 1977
Acta neuropath. (Berl.) 40, 21 -39 (1977)
Ultrastructural Changes in Blood Vessels of Peripheral Nerves in Leprosy Neuropathy. II. Borderline, Borderline-Lepromatous and Lepromatous Leprosy Patients J. Boddingius 1 Department of Human Anatomy, Universityof Oxford, South Parks Rd, Oxford OX1 3 QX, Great Britain
Summary. The ultrastructure of blood vessels in endo-, peri- and epineurium was studied in peripheral cutaneous nerve biopsies of 16 borderline (BB), borderline-lepromatous (BL) or lepromatous (LL) leprosy patients some of whom were in reversal reaction. Comparable vessels in nerve biopsies of control cases and vessels in skin lesion biopsies of the leprosy patients were also studied. Vascular changes were found in nerves of all the leprosy patients. The changes were pronounced in endoneurial vessels and affected 1. endothelial continuity and surface structure, 2. basement membranes of endothelium and pericytes, and 3. the vessel lumen. In addition, intra-endothelial (IE) Mycobacterium leprae were a feature in some of the patients. Gaps occurring between endothelial cells and plasma insudation both noticed in vessels of fascicles with early to very early neuropathy suggested extensive leakage which, in all probability, causes early nerve fibre damage. Luminal and abluminal endothelial protrusions, which were frequently observed, may enhance transendothelial transport. Fenestrations and endothelial attenuation, possibly, lead to an increase in vascular permeability. Endothelial phagocytotic activity, particularly in small (epineurial) arteries, appeared to be stimulated, possibly, by circulating
M. leprae. Basement membrane multilayering (a "hyaline zone") was found peripherally to pericytes, as is the case in tuberculoid leprosy (Boddingius, 1976). In a number of patients, multilayering occurred also periendothelially. Perivascular zones, which are thought to initiate or aggravate neuropathological changes by impairment of diffusion of oxygen and nutrients or metabolites, were very wide in endoneurial vessels of patients in reversal reaction and this suggested an immunological aetiology. 1 PresentAddress: Dr. J. Boddingius,Cochrane Annexe, Slade Hospital, Briscoe 1, Headington, Oxford, Great Britain
Partial or total vessel lumen occlusion, seen in advanced lepromatous neuropathy, most likely contributes to final nerve fibre degeneration and endoneurial fibrosis. M. leprae were found intra-endothelially in endoneurial vessels, though only in fascicles with advanced neuropathy whereas bacilli were not seen in vessel lumina. By contrast, in fascicles with relatively early neuropathy, solid (viable) bacilli were frequently encountered intra-axonally in myelinated fibres. This suggests that, in many instances, primary infiltration of M. leprae into nerve fascicles may arise from intraaxonal (IA) bacilli which ascend from dermal nerves and are released within main nerve trunks after demyelination of the host fibre.
Key words: Leprosy neuropathy - Ultrastructure Angiopathy - Endothelium - Mycobacterium leprae - Immunology.
Introduction Vasa nervorum in various neuropathies or in nerves under experimental conditions have infrequently been examined in fine detail, despite reports on a) the importance of vascularization for normal functioning of nerves, b) frequent vessel involvement in neuropathies (see Olsson, 1972). In a recent ultrastructural study of peripheral nerves in tuberculoid (TT) and borderline-tuberculoid (BT) leprosy patients (Boddingius, 1976), endoneurial postcapillary venules and venules were found to be surrounded by a wide "hyaline zone" consisting of multiple parallel basement membranes and collagen, both probably laid down by pericytes in response to "blood-nerve barrier" defects. The zone was conceived to contribute to the degeneration of (unmyelinated) nerve fibres by eventually interfering with dif-
22
fusion, to or from endoneurial tissues, of oxygen and nutrients or metabolites, respectively. In the literature on borderline-lepromatous leprosy, there is only brief mention, for endoneurial vessels, of lumen obliteration (Job, 1970), basement membrane proliferation, intra-endothelial M. leprae (Job, 1971; Dastur et al., 1973), "hyaline thickening" (Finlayson et al., 1974) and '~ de la membrane basale" (Schmitt et al., 1976). Ultrastructural investigations on vessel changes in peripheral nerves, throughout the leprosy spectrum, presently were completed using biopsies of 16 patients with borderline (BB), borderline-lepromatous (BL) or lepromatous (LL) leprosy and control biopsies of nonleprosy patients. Other neuropathological features of epi-, peri- and, in particular, endoneurium were also studied and attention was given to the possible route of primary entry of Mycobacterium leprae into nerve fascicles. Skin lesions were occasionally examined by electron microscopy to see whether angiopathy was a general feature of leprosy lesions. Materials and Methods Radial or superficial peroneal nerve biopsies were examined from all 16 leprosy patients whose varying clinical histories and duration of anti-leprosy treatment are given in Table 1. Significant hypertension, gravitational stasis or diabetes mellitus were not a feature of the patients. For a histopathologicaI check of the clinical classification (Table 1), Triff-stained skin lesions and nerve biopsy sections were examined by light microscopy and assessed according to the Ridley and Jopling (1966), Ridley and Waters (1969) and Ridley (1974) scales (below). In borderline (BB) lesions, diffusely spread epithelioid cells, lymphoeytes and, commonly, Mycobacterium leprae but no giant cells are found. In borderline-lepromatous (BL) lesions, few lymphocytes or occasional areas with dense lymphocyte infiltration, many macrophages with M. leprae, but no distinct epithelioid cells occur. In leprornatous (LL) lesions, lymphocytes are scanty and diffusely spread while multiple "foamy" macrophages with globi of bacilli occur. In lepromatous subpolar leprosy (LLs; indefinite leproma or LI), clinically, LL feaiures but also some BB skin lesions and unilateral nerve lesions are found. Reactions (see Barnetson et al., 1975): Reversal reaction, occurring in borderline leprosy, with dense lymphocyte infiltration in skin and/or nerve may be due to a delayed hypersensitivity reaction (Coombs and Gell type IV). In LL patients with ENL (erythema nodosum leprosum), immune complex formation occurs (Coombs and Gell type III hypersensitivity reaction). Case Histories (see also Table 1) : Case 7: 3 years ago, annular lesions (ankle, buttock). Lesions later also on cheek, forearm. Two months ago, patient downgrading (BT--,BL) followed by (?) reversal reaction after (?) DDS treatment. Presently, slight asymmetrical peripheral nerve enlargement; poor sensory acuity (due to local skin lesion?) in skin area served by the r. radial (= r. radial area). Case 8: 18 months ago, reddish anaesthetic patches (scapular, knees). Over last half year, many new lesions. Enlarged r. radial, r and 1. post. final and great auricular nerves; impaired sensation (due to local skin lesion?) in r. radial area. Case 9. 2 months ago, erythematous infiltration (face, arm). Later, skin reaction (multiple nodulation) on
Acta neuropath. (Berl.) 40 (1977) face, hands, buttocks, legs. No peripheral nerve enlargement, neuritis, nor sensory deficits in 1. radial area. Case lO : 7 years ago, one papule (buttock). Treatment (irregular) stopped 18 months ago. Presently, vague early infiltrations (forearm, thigh) but nerves grossly normal; sensation in 1. radial area very slightly impaired. Case I1 : 4 years ago, numbness of r. index finger. Two years later, skin lesions (abdomen, thighs, 1. arm). Three months ago, rapid extension of disease (downgrading). Normal sensation in 1. radial area. Case 12:1 year ago, one pale patch (1. elbow). After 7 months it became red. New lesions (1. hand, feet). Four months ago, small active nodules and macules over whole body. Sensation in r. radial area very slightly impaired. Case 13:14 years ago (Pakistan), hypopigmentation and anaesthesia (upper arm), treatment (DDS) commenced but discontinued. Ten years ago (Britain), anaesthetic patch (1. elbow), thickened ulnar nerves; treatment (DDS, 1 year), patient discharged (!). Presently, eyebrow loss, nodular eruptions (face, ears), widespread infiltration (skin), ulceration (hands, feet), wasting of small muscles (1. hand), bilateral stocking anaesthesia, dense sensory loss (feet), weakness (1. foot); ulnar, radial, sural, r. superfi peron, nerves palpable. Case 14:8 months ago, nodules (face, trunk, limbs). One week ago (after 3 weeks DDS treatment), exacerbation of skin lesions and nerve tenderness. Reaction continued despite Prednisolone (1 week). Data on skin sensation: n. av. Case 15:5 years ago, one small white patch (scapular) which became red and grew slowly 2 years ago. Many new, tiny, lesions over whole body 2 months ago (downgrading~ LL). Normal sensory acuity in 1. radial area. Case 16. 1 - 2 years ago, nodules (face). Presently, also widespread macules (trunk, limbs); slightly enlarged ulnar and radial nerves; normal sensation in r. radial area. Case 17:45 years ago (India), discharging lesion (1. elbow), buttock sores. Leprosy diagnosed 15 years later (1 year chaulmoogra). Relapse after 5 years (6 months chaulmoogra, diasone). Two years ago (Britain), leprosy diagnosed: infiltrated skin lesions, clawing toes, r. foot drop, enlarged r. great auricular, 1. peroneal, tender I. and r. ulnar, 1. radial and r. peroneal nerves. Sensory impairment in glove and stocking areas. Lower r. leg amputated because foot badly deteriorated. Case 18:11/2 years ago, numbness (r. upper arm). One month ago, papules (cheek, trunk), thickening of hands. Presently, hypopigmented confluent macules (trunk, buttocks, back of thighs); enlarged 1. ulnar, 1. and r. common peroneals, finals. Sensation in r. radial area slightly impaired. Case 19:1 year ago, a small, slowly spreading, anaesthetic patch (knee). Ears, nose, affected, swollen 7 months later. Three months ago, lesions over whole body. Normal sensation in r. radial area. Case 20: Weakness and numbness (1. hand) for 1 - 2 years, nerves thus involved early on. Presently, enlarged ulnar, radial, peroneal nerves; no definite skin lesions but skin in 1. ulnar area dry, anaesthetic; only earlobes weakly positive for M. leprae. Data on skin sensation: n. av. Case 2 1 : 4 years ago, conjunctivitis (r. eye). One year later, painless swelling (1. nostril), occasional nose bleeding. Iritis, rash (face), ulcerations (legs) 2 years ago. Four months later, burning sensation and pigmented papules (lower legs). Leprosy diagnosed 1 year ago: nerves tender, enlarged (back of hands, neck), reduced sensory nerve velocity and motor conduction (lower limbs). Two months ago, ENL lesions; chloroquin given. Palpable branch (superf. peron.) biopsied on dorsum 1. foot. Case 2 2 : 3 months ago, lesion (r. leg), swelling (face, ear), burning feeling (eyes), skin dryness (hands, feet); nasal discharge, blockage. Presently, maculopapular rash, paresthesia (fingers), enlarged radials, common and sup. peroneals; reduced sensation over distal limb parts. Biopsies taken after 3 weeks treatment. Control Nerve Biopsies from non-leprosy patients A - - F (data in Boddingius, 1976) and G (male, 26 years, Ethiopian, suffering from mycetoma; left radial nerve biopsy). Methods for nerve biopsy dissection - sometimes with hyalase added to the local anaesthetic-and methods for processing, embedding and staining of ultrathin and semithin or paraffin sections for elec-
male
male
male
male
male
male
female
male
female
female
male
male
female
male
male
8
9
10
11
12
13
14
15
16
17
18
19
20
2J
22
34
22
15
16
15
53
12
27
26
48
60
18
16
36
60
42
Age (years)
Clinical diagnosis
female
7
!
Sex
Case no.
U.S.A.
LL
LL (ENL)
LL (early)
LLs
LLs (early)
BL-LL (advanced)
BL-LLs
BL-LLs
BL (reversal reaction)
BL (advanced)
BL (early reversal reaction)
BB-BL
BB-BL
BB (skin reaction)
BB
BB (reversal reaction)
Type of leprosy!
** Chaulmoogra, diasone
England
Ethiopia
Malaysia
Malaysia
England
Ethiopia
Malaysia
Ethiopia
England
Malaysia
Malaysia
Malaysia
Ethiopia
Malaysia
Malaysia
Country of residence
* Drug unspecified
Indian
Pakistani
Ehiopian
Malaysian
Indian
Indian
Ethiopian
Malaysian
Ethiopian
Pakistani
Chinese
Chinese
Chinese
Ethiopian
Chinese
Chinese
Ethnic group
1. sup. peron,
i. sup. peron,
1. radial
r. radial
r. radial
r. sural
r. radial
1. radial
r. radial
r. sup. peron,
r. radial
1. radial
1. radial
1. radial
r. radial
r. radiaP
swollen
swollen
palpable
swollen
normal
swollen
enlarged
slightly enlarged
swollen
swollen
normal
enlarged
normal
normal
swollen
not known
Gross condition of nerve
+ Dose not specified
Cutaneous nerve biopsied
*** B 663
Table 1. Type of leprosy, history of symptoms, drug treatment etc, of leprosy cases 7 - 22
~ At wrist
3 months
2 - 4 years
1 - 2 years
3 weeks (20 mg/week)
1 year ( 1 0 - 2 0 mg/day)
none
10 days +
none
11/2 years i year
7 years irreg.** 21 years none 2 years***
3 months (25 rag/day)
3 weeks * 2 weeks (2 • 200 mg/week)
4 weeks (25 rag/day)
5 years irreg. 9 years none
1 month (2 x 200 nag/week)
1 month (2 x 100 mg/week)
51/2 years irreg. *
none
irreg. *
?+
Drug (DDS) treatment; duration and dose
30--45 years
2 years
5 years
8 months
14 years
1 year
4 years
7 years
2 months
11/2 years
3 years
History of leprosy symptoms
t~
,
Acta neuropath. (Berl.) 40, 21 -39 (1977)
Ultrastructural Changes in Blood Vessels of Peripheral Nerves in Leprosy Neuropathy. II. Borderline, Borderline-Lepromatous and Lepromatous Leprosy Patients J. Boddingius 1 Department of Human Anatomy, Universityof Oxford, South Parks Rd, Oxford OX1 3 QX, Great Britain
Summary. The ultrastructure of blood vessels in endo-, peri- and epineurium was studied in peripheral cutaneous nerve biopsies of 16 borderline (BB), borderline-lepromatous (BL) or lepromatous (LL) leprosy patients some of whom were in reversal reaction. Comparable vessels in nerve biopsies of control cases and vessels in skin lesion biopsies of the leprosy patients were also studied. Vascular changes were found in nerves of all the leprosy patients. The changes were pronounced in endoneurial vessels and affected 1. endothelial continuity and surface structure, 2. basement membranes of endothelium and pericytes, and 3. the vessel lumen. In addition, intra-endothelial (IE) Mycobacterium leprae were a feature in some of the patients. Gaps occurring between endothelial cells and plasma insudation both noticed in vessels of fascicles with early to very early neuropathy suggested extensive leakage which, in all probability, causes early nerve fibre damage. Luminal and abluminal endothelial protrusions, which were frequently observed, may enhance transendothelial transport. Fenestrations and endothelial attenuation, possibly, lead to an increase in vascular permeability. Endothelial phagocytotic activity, particularly in small (epineurial) arteries, appeared to be stimulated, possibly, by circulating
M. leprae. Basement membrane multilayering (a "hyaline zone") was found peripherally to pericytes, as is the case in tuberculoid leprosy (Boddingius, 1976). In a number of patients, multilayering occurred also periendothelially. Perivascular zones, which are thought to initiate or aggravate neuropathological changes by impairment of diffusion of oxygen and nutrients or metabolites, were very wide in endoneurial vessels of patients in reversal reaction and this suggested an immunological aetiology. 1 PresentAddress: Dr. J. Boddingius,Cochrane Annexe, Slade Hospital, Briscoe 1, Headington, Oxford, Great Britain
Partial or total vessel lumen occlusion, seen in advanced lepromatous neuropathy, most likely contributes to final nerve fibre degeneration and endoneurial fibrosis. M. leprae were found intra-endothelially in endoneurial vessels, though only in fascicles with advanced neuropathy whereas bacilli were not seen in vessel lumina. By contrast, in fascicles with relatively early neuropathy, solid (viable) bacilli were frequently encountered intra-axonally in myelinated fibres. This suggests that, in many instances, primary infiltration of M. leprae into nerve fascicles may arise from intraaxonal (IA) bacilli which ascend from dermal nerves and are released within main nerve trunks after demyelination of the host fibre.
Key words: Leprosy neuropathy - Ultrastructure Angiopathy - Endothelium - Mycobacterium leprae - Immunology.
Introduction Vasa nervorum in various neuropathies or in nerves under experimental conditions have infrequently been examined in fine detail, despite reports on a) the importance of vascularization for normal functioning of nerves, b) frequent vessel involvement in neuropathies (see Olsson, 1972). In a recent ultrastructural study of peripheral nerves in tuberculoid (TT) and borderline-tuberculoid (BT) leprosy patients (Boddingius, 1976), endoneurial postcapillary venules and venules were found to be surrounded by a wide "hyaline zone" consisting of multiple parallel basement membranes and collagen, both probably laid down by pericytes in response to "blood-nerve barrier" defects. The zone was conceived to contribute to the degeneration of (unmyelinated) nerve fibres by eventually interfering with dif-
22
fusion, to or from endoneurial tissues, of oxygen and nutrients or metabolites, respectively. In the literature on borderline-lepromatous leprosy, there is only brief mention, for endoneurial vessels, of lumen obliteration (Job, 1970), basement membrane proliferation, intra-endothelial M. leprae (Job, 1971; Dastur et al., 1973), "hyaline thickening" (Finlayson et al., 1974) and '~ de la membrane basale" (Schmitt et al., 1976). Ultrastructural investigations on vessel changes in peripheral nerves, throughout the leprosy spectrum, presently were completed using biopsies of 16 patients with borderline (BB), borderline-lepromatous (BL) or lepromatous (LL) leprosy and control biopsies of nonleprosy patients. Other neuropathological features of epi-, peri- and, in particular, endoneurium were also studied and attention was given to the possible route of primary entry of Mycobacterium leprae into nerve fascicles. Skin lesions were occasionally examined by electron microscopy to see whether angiopathy was a general feature of leprosy lesions. Materials and Methods Radial or superficial peroneal nerve biopsies were examined from all 16 leprosy patients whose varying clinical histories and duration of anti-leprosy treatment are given in Table 1. Significant hypertension, gravitational stasis or diabetes mellitus were not a feature of the patients. For a histopathologicaI check of the clinical classification (Table 1), Triff-stained skin lesions and nerve biopsy sections were examined by light microscopy and assessed according to the Ridley and Jopling (1966), Ridley and Waters (1969) and Ridley (1974) scales (below). In borderline (BB) lesions, diffusely spread epithelioid cells, lymphoeytes and, commonly, Mycobacterium leprae but no giant cells are found. In borderline-lepromatous (BL) lesions, few lymphocytes or occasional areas with dense lymphocyte infiltration, many macrophages with M. leprae, but no distinct epithelioid cells occur. In leprornatous (LL) lesions, lymphocytes are scanty and diffusely spread while multiple "foamy" macrophages with globi of bacilli occur. In lepromatous subpolar leprosy (LLs; indefinite leproma or LI), clinically, LL feaiures but also some BB skin lesions and unilateral nerve lesions are found. Reactions (see Barnetson et al., 1975): Reversal reaction, occurring in borderline leprosy, with dense lymphocyte infiltration in skin and/or nerve may be due to a delayed hypersensitivity reaction (Coombs and Gell type IV). In LL patients with ENL (erythema nodosum leprosum), immune complex formation occurs (Coombs and Gell type III hypersensitivity reaction). Case Histories (see also Table 1) : Case 7: 3 years ago, annular lesions (ankle, buttock). Lesions later also on cheek, forearm. Two months ago, patient downgrading (BT--,BL) followed by (?) reversal reaction after (?) DDS treatment. Presently, slight asymmetrical peripheral nerve enlargement; poor sensory acuity (due to local skin lesion?) in skin area served by the r. radial (= r. radial area). Case 8: 18 months ago, reddish anaesthetic patches (scapular, knees). Over last half year, many new lesions. Enlarged r. radial, r and 1. post. final and great auricular nerves; impaired sensation (due to local skin lesion?) in r. radial area. Case 9. 2 months ago, erythematous infiltration (face, arm). Later, skin reaction (multiple nodulation) on
Acta neuropath. (Berl.) 40 (1977) face, hands, buttocks, legs. No peripheral nerve enlargement, neuritis, nor sensory deficits in 1. radial area. Case lO : 7 years ago, one papule (buttock). Treatment (irregular) stopped 18 months ago. Presently, vague early infiltrations (forearm, thigh) but nerves grossly normal; sensation in 1. radial area very slightly impaired. Case I1 : 4 years ago, numbness of r. index finger. Two years later, skin lesions (abdomen, thighs, 1. arm). Three months ago, rapid extension of disease (downgrading). Normal sensation in 1. radial area. Case 12:1 year ago, one pale patch (1. elbow). After 7 months it became red. New lesions (1. hand, feet). Four months ago, small active nodules and macules over whole body. Sensation in r. radial area very slightly impaired. Case 13:14 years ago (Pakistan), hypopigmentation and anaesthesia (upper arm), treatment (DDS) commenced but discontinued. Ten years ago (Britain), anaesthetic patch (1. elbow), thickened ulnar nerves; treatment (DDS, 1 year), patient discharged (!). Presently, eyebrow loss, nodular eruptions (face, ears), widespread infiltration (skin), ulceration (hands, feet), wasting of small muscles (1. hand), bilateral stocking anaesthesia, dense sensory loss (feet), weakness (1. foot); ulnar, radial, sural, r. superfi peron, nerves palpable. Case 14:8 months ago, nodules (face, trunk, limbs). One week ago (after 3 weeks DDS treatment), exacerbation of skin lesions and nerve tenderness. Reaction continued despite Prednisolone (1 week). Data on skin sensation: n. av. Case 15:5 years ago, one small white patch (scapular) which became red and grew slowly 2 years ago. Many new, tiny, lesions over whole body 2 months ago (downgrading~ LL). Normal sensory acuity in 1. radial area. Case 16. 1 - 2 years ago, nodules (face). Presently, also widespread macules (trunk, limbs); slightly enlarged ulnar and radial nerves; normal sensation in r. radial area. Case 17:45 years ago (India), discharging lesion (1. elbow), buttock sores. Leprosy diagnosed 15 years later (1 year chaulmoogra). Relapse after 5 years (6 months chaulmoogra, diasone). Two years ago (Britain), leprosy diagnosed: infiltrated skin lesions, clawing toes, r. foot drop, enlarged r. great auricular, 1. peroneal, tender I. and r. ulnar, 1. radial and r. peroneal nerves. Sensory impairment in glove and stocking areas. Lower r. leg amputated because foot badly deteriorated. Case 18:11/2 years ago, numbness (r. upper arm). One month ago, papules (cheek, trunk), thickening of hands. Presently, hypopigmented confluent macules (trunk, buttocks, back of thighs); enlarged 1. ulnar, 1. and r. common peroneals, finals. Sensation in r. radial area slightly impaired. Case 19:1 year ago, a small, slowly spreading, anaesthetic patch (knee). Ears, nose, affected, swollen 7 months later. Three months ago, lesions over whole body. Normal sensation in r. radial area. Case 20: Weakness and numbness (1. hand) for 1 - 2 years, nerves thus involved early on. Presently, enlarged ulnar, radial, peroneal nerves; no definite skin lesions but skin in 1. ulnar area dry, anaesthetic; only earlobes weakly positive for M. leprae. Data on skin sensation: n. av. Case 2 1 : 4 years ago, conjunctivitis (r. eye). One year later, painless swelling (1. nostril), occasional nose bleeding. Iritis, rash (face), ulcerations (legs) 2 years ago. Four months later, burning sensation and pigmented papules (lower legs). Leprosy diagnosed 1 year ago: nerves tender, enlarged (back of hands, neck), reduced sensory nerve velocity and motor conduction (lower limbs). Two months ago, ENL lesions; chloroquin given. Palpable branch (superf. peron.) biopsied on dorsum 1. foot. Case 2 2 : 3 months ago, lesion (r. leg), swelling (face, ear), burning feeling (eyes), skin dryness (hands, feet); nasal discharge, blockage. Presently, maculopapular rash, paresthesia (fingers), enlarged radials, common and sup. peroneals; reduced sensation over distal limb parts. Biopsies taken after 3 weeks treatment. Control Nerve Biopsies from non-leprosy patients A - - F (data in Boddingius, 1976) and G (male, 26 years, Ethiopian, suffering from mycetoma; left radial nerve biopsy). Methods for nerve biopsy dissection - sometimes with hyalase added to the local anaesthetic-and methods for processing, embedding and staining of ultrathin and semithin or paraffin sections for elec-
male
male
male
male
male
male
female
male
female
female
male
male
female
male
male
8
9
10
11
12
13
14
15
16
17
18
19
20
2J
22
34
22
15
16
15
53
12
27
26
48
60
18
16
36
60
42
Age (years)
Clinical diagnosis
female
7
!
Sex
Case no.
U.S.A.
LL
LL (ENL)
LL (early)
LLs
LLs (early)
BL-LL (advanced)
BL-LLs
BL-LLs
BL (reversal reaction)
BL (advanced)
BL (early reversal reaction)
BB-BL
BB-BL
BB (skin reaction)
BB
BB (reversal reaction)
Type of leprosy!
** Chaulmoogra, diasone
England
Ethiopia
Malaysia
Malaysia
England
Ethiopia
Malaysia
Ethiopia
England
Malaysia
Malaysia
Malaysia
Ethiopia
Malaysia
Malaysia
Country of residence
* Drug unspecified
Indian
Pakistani
Ehiopian
Malaysian
Indian
Indian
Ethiopian
Malaysian
Ethiopian
Pakistani
Chinese
Chinese
Chinese
Ethiopian
Chinese
Chinese
Ethnic group
1. sup. peron,
i. sup. peron,
1. radial
r. radial
r. radial
r. sural
r. radial
1. radial
r. radial
r. sup. peron,
r. radial
1. radial
1. radial
1. radial
r. radial
r. radiaP
swollen
swollen
palpable
swollen
normal
swollen
enlarged
slightly enlarged
swollen
swollen
normal
enlarged
normal
normal
swollen
not known
Gross condition of nerve
+ Dose not specified
Cutaneous nerve biopsied
*** B 663
Table 1. Type of leprosy, history of symptoms, drug treatment etc, of leprosy cases 7 - 22
~ At wrist
3 months
2 - 4 years
1 - 2 years
3 weeks (20 mg/week)
1 year ( 1 0 - 2 0 mg/day)
none
10 days +
none
11/2 years i year
7 years irreg.** 21 years none 2 years***
3 months (25 rag/day)
3 weeks * 2 weeks (2 • 200 mg/week)
4 weeks (25 rag/day)
5 years irreg. 9 years none
1 month (2 x 200 nag/week)
1 month (2 x 100 mg/week)
51/2 years irreg. *
none
irreg. *
?+
Drug (DDS) treatment; duration and dose
30--45 years
2 years
5 years
8 months
14 years
1 year
4 years
7 years
2 months
11/2 years
3 years
History of leprosy symptoms
t~
,
![[Borderline lepromatous leprosy].](/assets/img/hold.png)
