1. Lepromatous Leprosy
高雄榮總 皮膚科
賴名耀 宗天一

2. Case Report  Present Illness
A 33 year-old Thai male suffered from yellowish to
flesh-color skin eruption with numbness and loss of light
touch sensation over face, trunk and 4 limbs for about 3
months. Throughout the whole course of disease, There
was no fever, no chills, and no lymphadenopathy.
 Past History
Denied any systemic disease.
 Family History
Non-contributory.

3. Multiple flesh to yellowish colored nodules with numbness
 Clinical Finding:
Multiple flesh to yellowish colored nodules with numbness
and loss of light touch sensation over face, trunk and 4
limbs.
 Pathological Findings:
 Several granulomas with foamy histiocytes in the dermis.
 Acid -fast stain: (+), Ziehl-Neelsen stain: (+),
Fite-Farraco stain(+).
 Inflammation involves the small nerve trunks confirmed
by S-100 staining.
 Diagnosis:
 Lepromatous leprosy
 Management:
 He was sent back to Thailand.

4. Discussion

5. Leprosy  Epidermiology  Fallen dramatically in the past decade.
 It is primarily a disease of developing countries
 Prevalence:
 Fallen dramatically in the past decade.
 Incidence (1992, WHO): 690,000 new cases per year.
 Subclinical infection is common in endemic areas.
 The route of infection:
 Human to human, favor respiratory transmission.
 Armadillo and sphagnum moss: non-human sources.

6.  Epidermiology disease is common. lepromatous patients.
 MHC class II antigens: influence disease expression.
 Lepromatous leprosy--- M : F = 2 : 1
 The tuberculoid form being dominant wherever the
disease is common.
 The median age of onset is less in tuberculoid than in
lepromatous patients.
 Leprosy is predominantly a young person’s disease
(median age of onset is < 35 years of age)
 Required for transmission: prolonged close contact.
 Incubation time of tuberculoid leprosy: up to 5 years;
lepromatous leprosy: 20 years or longer.

7.  Possibility of Leprosy:
 Risk Factors:
 Birth or residence in an endemic area
 A blood relative with the disease
 Armadillo (nine-banded) exposure in North Americans.
 Possibility of Leprosy:
 Simultaneous skin lesions and peripheral nerve
abnormalities
 Differential diagnosis includes granuloma, vasculitis
or lymphoma.
 A peripheral neuropathy of unknown type in a patient in
or from an endemic area, (so-called pure neuritic leprosy)
 Simultaneous palsies of cranial nerves V and VII,
considered to leprosy until proven otherwise.

8.  Criteria for Diagnosis
 The presence of a consistent peripheral nerve abnormality
or the demonstration of mycobacteria in tissues.
 Several kinds of peripheral nerve abnormalities in leprosy:
 Nerve enlargement (usually perceived as asymmetry).
 Sensory loss in skin lesions.
 Nerve trunk palsies (usually with both sensory and
motor loss).
 Acral distal symmetric anesthesia (type C fiber).
 Anhidrosis: sympathetic nerve involvement.
 Uncommon peripheral nerve abnormalities:
 Nerve abscesses (palisading granulomas formed about
cutaneous sensory nerves)
 The carpal tunnel syndrome.

9.  Identification and Quantitation of Bacilli
 Acid-fast stain: weak.
 Modifications of the Ziehl-Neelsen method
(collectively called Fite-Farraco stains)
 Bacilli are usually found in macrophage and nerves.
 Bacillary index (BI): the numbers of bacilli per oil-
immersion field (OIF) or OIFs sought to find one
bacillus
 Other Methods of Diagnosis
 Antibodies directly against phenolic glycolipid I or
lipoarabinomannan.
 Polymerase chain reaction (PCR).

10.  Classification  BT (borderline tuberculoid)
 The dichotomy: multibacillary or paucibacillary
 The Ridley system:
 TT (polar tuberculoid)
 BT (borderline tuberculoid)
 BB (borderline/midborderline)
 BL (borderline lepromatous)
 LLs (subpolar lepromatous)
 LLp (polar lepromatous)
 The paucibacillary: TT and most BT.
 The multibacillary: BB, BL, LLs and LLp.
 Lepromin skin test: classification of diagnosed patients
 Positive: all TT and most BT.
 Negative: others.

11.  Clinical Pathology of Leprosy
 Early, Indeterminate Leprosy
 Slight pandermal perineurovascular and peri-
appendageal chronic inflammation.
 Without demonstrating bacilli:
Diagnosis can only be presumptive
 Lepromatous leprosy (LL)
 The lesions usually are numerous and symmetrically
arranged.
 Three clinical types:
macular, infiltrative-nodular and diffuse.
 A distinctive variant of LL: histoid type.

12.  Clinical Pathology of Leprosy
 Lepromatous leprosy -- Infiltrative-nodular type
 The classical and most common variety.
 The patients are not notably hypoesthetic disturbances
of sensation and nerve paralyses develop after large
peripheral nerve involved.
 Most common involved nerve:
ulnar, radial and common peroneal nerves.
 Extensive cellular infiltrate with separated from the
epidermis by a narrow grenz zone of normal collagen.
 The macrophages have abundant eosinophilic cytoplasm
and contain mixed solid and fragmented bacilli .
 Lymphocyte infiltration is not prominent, but there may
be many plasma cells

13.  Clinical Pathology of Leprosy
 Lepromatous leprosy -- Diffuse type (Lucio leprosy):
 Most common in Mexico and Central America.
 Diffuse infiltration without nodules.
 Acral , symmetric anesthesia is generally present.
 Characteristic heavy bacillation of the small blood
vessels in the skin.
 Lepromatous leprosy -- Histoid type
 The occurrence of well-demarcated cutaneous and
subcutaneous nodules resembling dermatofibromas.
 It frequently follows incomplete chemotherapy or
acquired drug resistance, leading to bacterial relapse.

14.  Clinical Pathology of Leprosy
 Lepromatous leprosy -- Histoid leprosy
 The highest loads of bacilli.
 The majority are solid-staining, arranged in clumps
like sheaves of wheat.
 Macrophage reaction is unusual.
 Macrophages frequently become spindle-shaped
and oriented in a storiform pattern, similar to
fibrohistiocytoma.

15.  Clinical Pathology of Leprosy
 Lepromatous leprosy -- with antimycobacterial therapy
 Degenerate bacilli accumulate in the macrophages
(the so-called lepra cells or Virchow cells), which
have foamy or vacuolated cytoplasm, resembling
xanthoma cells
 Fite stain reveals that the bacilli are fragmented or
granular and disposed in large basophilic clumps
called globi especially in very chronic lesions.
 The nerves in the skin may contain considerable
numbers of leprosy bacilli, but remain well-
preserved for a long time and slowly become fibrotic.

16.  Clinical Pathology of Leprosy
 Lepromatous leprosy -- with antimycobacterial therapy
 When lepromatous leprosy is treated, the bacterial
debris to be cleared by host macrophages.
 The M lepra antigen may persist longer and can be
demonstrated by immunocytochemical stains
(Fite or silver) even when no bacilli are evident.

17.  Clinical Pathology of Leprosy
 Borderline lepromatous (BL) leprosy
 Less numerous and less symmetrical than LL lesions.
 Often display some central dimples.
 The lymphocytes are more prominent in BL and
there is a tendency for some activation of macrophages
to form poorly to moderately defined granulomas.
 Perineural fibroblast proliferation forming an typical
“onion skin” in cross section.
 Midborderline (BB) leprosy
 The lesions are irregularly dispersed and shaped
erythematous plaques with punched-out centers.
 Dermal edema is prominent in the lesions.
 Macrophages are activated to epitheloid cells

18.  Clinical Pathology of Leprosy
 Borderline tuberculoid (BT) leprosy
 The lesions are asymmetrical and may be scanty.
 Dry, hairless plaques with central hypopigmentation.
 Nerve enlargement is usually found and the lesions
are usually anesthetic.
 Granulomas with peripheral lymphocytes follow the
neurovascular bundles and infiltrate sweat glands and
erector pili muscles.
 Langhans’ giant cell are variable in number and are
not large in size.
 Typical nerve erosion and obliteration.
 Granulomas along superficial vascular plexus frequently
 S-100 stain showed perineural & intraneural granuloma.

19.  Clinical Pathology of Leprosy
 Tuberculoid (TT) leprosy
 The lesions are scanty, dry, erythematous, hypo-
pigmented papules or plaques with sharply defined
edges.
 Anesthesia is prominent (except on the face).
 The number of lesions ranges from 1 to 5, and the
lesions heal rapidly on chemotherapy.
 Primary TT leprosy has large epitheloid cells arranged
in compact granulomas along with neurovascular
bundles with dense peripheral lymphocyte accumulation
 Langhans’ giant cells are typically absent.
 Dermal nerve may be absent or surrounded and eroded
by dense lymphocyte cuffs. Bacilli are rarely found.

20.  Histopathologic Differential Diagnosis
 Tuberculoid leprosy should be D.D. with:
 Sarcoidosis, tuberculosis, granuloma annulare
granulomatous leishmaniasis.
 Lepromatous leprosy should be D.D. with:
 Xanthoma
 Other mycobacterioses: M. avium-intracellulare
-- histoid-like multibacillary lesions.

21. (Jopling’s type 1 reaction)
 Leprosy Reaction
 The reactional status of leprosy are distinctive, tissue
destructive, inflammatory processes, putatively immuno-
logically driven greatly increasing the morbidity of the
disease.
 Delay-Type Hypersensitivity Reaction
(Jopling’s type 1 reaction)
 Type 1 reactions are common in BL patients, but are
not rare in LL or BT patients.
 Reaction induces increased intraneural inflammation
and edema, which is damaging.
 At worst, there is a caseous necrosis of large peripheral
nerves resulting from upgrading reactions. .

22.  Leprosy Reaction
 Delay-Type Hypersensitivity Reaction
 Edema within and about the granulomas and prolifer-
ation of fibrocytes in the dermis.
 In upgrading reactions, the granuloma becomes more
epitheloid and Langhans’ giant cells are larger.
 There may be erosion of granulomas into the lower
epidermis and fibrinoid necrosis with granulomas and
even within dermal nerves.
 In downgrading reactions, necrosis is much less
common and the density of bacilli increases.

23.  Leprosy Reaction  ENL occurs most commonly in LL, less in BL.
 Type 2 reaction (Erythema nodosum leprosum, ENL)
 ENL occurs most commonly in LL, less in BL.
 Tender, red plaques and nodules together with areas of
erythema and occasionally also purpura and vesicles.
 It is accompanied by fever, malaise, arthralgia and
leukocytosis.
 This is the only type of reactional leprosy that responds
to treatment with thalidomide.
 Polymorph neutrophils may be scanty or so abundant as
to form a dermal abscess with ulceration
 Foamy macrophage containing fragmented bacilli or
mycobacterial debris.
 A necrotising vasculitis in some cases of ENL.

24.  Leprosy Reaction  Occur exclusively in diffuse lepromatous leprosy.
 Lucio Reaction
 Occur exclusively in diffuse lepromatous leprosy.
 It usually occurs in patients who have received either
no treatment or inadequate treatment.
 The lesions consist of barely palpable, hemorrhagic,
sharply marginated, irregular plaques.
 There may be repeated attacks or continuous
appearance of new lesions for years.
 Endothelial proliferation leading to luminal obliteration
with thrombosis in the medium-sized vessels of the
dermis and subcutis.
 Dense aggregates of bacilli are found in the walls and
the endothelium of vessels.

25.  Treatment  WHO: the combination of dapsone (bacteriostatic)
 Paucibacillary disease (TT or BT)
 WHO: the combination of dapsone (bacteriostatic)
100mg QD and rifampin (bactericidal) 600mg monthly
for a duration of 6 months.
 Fitzpatrick: dapsone 100mg QD for 3-5 years, with or
without rifampin 600mg monthly, and follow-up exam
at 1-2 years after discontinuing treatment
.  Multibacillary disease (BB, BL, and LL)
 WHO: dapsone 100mg QD, rifampin 600 mg monthly
and clofazimine (bacteriostatic) 50mg QD and 300mg
monthly for a routine duration of 2 years.
 20% relapse rate within 8 years after completion of
this regimen.

26.  Treatment  Fitzpatrick: rifampin 600mg QD, dapsone 100mg QD
 Other regimens for multibacillary diseases
 Fitzpatrick: rifampin 600mg QD, dapsone 100mg QD
for 3 years, followed by dapsone 100mg QD
indefinitely.
 minocycline (bactericidal) 100mg QD and rifampin
600mg QD for 2-3 years followed by monotherapy.
 Others: clarithromycin and fluoroquinolone
(bactericidal)
 In reversal reaction:
 Prednisolone therapy ( mg/kg per day), tapered
slowly and continued for a minimum of 6 months.

27.  Treatment  Thalidomide is dramatically effective in a majority of
 In ENL:
 Thalidomide is dramatically effective in a majority of
patients.
 Thalidomide mg QN, may add prednisolone
( mg/kg), tapering later over 6-8 weeks.
 Glucocorticoid in conjunction with clofazimine at 200
mg/day may be effective.
 Thalidomide is slowly tapered to 100mg and then
50mg QD.
 Adverse reactions of dapsone treatment:
 Dapsone syndrome, hemolytic anemia, peripheral
neuropathy, bone marrow suppression

28. Thank You