Leprosy

pathology inflammation

1. Presented by:
Dr. VAMSHIKRISHNA DUSSA

2. •Leprosy,alsoknownasHansen'sdisease(HD),is
achronicinfectiousdiseasecausedbythebacteria
MycobacteriumlepraeorMycobacterium
lepromatosis.

3. •TheMycobacteriumlepraebacteriawasfirst
discoveredbyDr.Hansenandhencethedisease
nameisalsoknownasHANSEN’SDISEASE.
•Howeverthediseasewasfirstdescribedin
ancientindiantextgoingbackto6
th
centuryB.C

4. MYCOBACTERIUM LEPRAE
•Itisanacidfast,rodshapedbacilliandanobligate
intracellularbacterium.
•Itmainlyaffectsnervesandskin.(onlybacillithatcanenter
thenerveschwanncell)
•Bacillihaveaffinityforthecoolertissues.
•Bacteriuminvadeseitherdermal(cutaneous)nervesor
mainperipheralnervetrunkssituatedsuperficially,in
regionsthatarerelativelycooler(face&limbs).

5. •Ithaslowpathogencity,onlyasmallproportionof
infectedpeopledevelopsignsofthedisease.
•Thoughinfected,majorityofthepopulationdonot
developthedisease.
•Afterenteringthebody,bacillimigratetowardsthe
neuraltissueandentertheSchwanncells.

6. Incidence
•EndemicinHOTANDMOISTCLIMATES,POORTROPICAL
COUNTRIES/POORDEVELOPINGNATIONS.
•MoreprevalentincountrieslikeIndia,China,Nepal,Brazil,
Indonesia,Myanmar(Burma),Madagascar,nigeria.
•Indiaaccountsforone-thirdofallregisteredleprosycases
globally.
•MorecommonlyinstatesofTamilNadu,Bihar,Puducherry,
AndhraPradesh,Odisha,WestBengalandAssam

7. Risk factors:
•Thegreatestriskfactorfordevelopingleprosyis
contactwithanotherpersoninfectedbyleprosy.
•Peoplewhoareexposed(incontact)witha
personwhohasleprosyare5-8timesmorelikely
todevelopleprosythanmembersofthegeneral
population.
•Leprosyalsooccursmorecommonlyamong
thoselivinginpoverty.

8. •NotallpeoplewhoareinfectedwithM.
lepraedevelopsymptoms.
•Conditionsthatreduceimmunefunction,suchas
malnutrition,otherillnesses,orgeneticmutations,
mayincreasetheriskofdevelopingleprosy.

9. Mode of Transmission:
•Leprosyisaslowcommunicabledisease.
•Theincubationperiodbetweenfirstexposureandappearance
ofsignsofdiseasevariesfrom2to20years(averageabout3
years).
•Thespreadofleprosyisbelievedtobevianasaldischarge
(dropletsinfection)
-Every1ccofnasalsecretioncontains1-2millionslepra
bacilli.

10. •Theinfectivitymaybefromthefollowingsources:
1.Directcontactwithuntreatedleprosypatientswho
shednumerousbacillifrom
-Damagedskin,
-Nasalsecretions,
-Mucousmembraneofmouth
-Hairfollicles.
2.Materno-foetaltransmissionacrosstheplacenta.
3.Transmissionfrommilkofleprosyaffectedmotherto
infant.

11. 4. From infected armadillo animals (carriers).

12. IMMUNOLOGY OF LEPROSY:
•TheimmuneresponseinleprosyisT-CellMediated(CMI)
DelayedHypersensitivity(typeIVreaction).
•Personwith“GOOD”CMIresponse(NORMALCD4-T
HELPERCELLS)developsmilder&localizedformofthe
disease(TuberculoidLeprosy)withlessbacterialload.
•Whereas,inpersonswithWEAKORABSENTCMI(LOW
CD4-THELPERCELLS),developdisseminatedwidespread
disease(LepromatousLeprosy)withhighbacterialload.

13. PATHOGENESIS:
•AfterenteringtheSchwanncells/macrophage,bacillistart
multiplyingslowly(about12-14daysforonebacteriumto
divideintotwo)withinthecells,getliberatedfromthe
destroyedcellsandenterotherunaffectedcells.
•Tillthisstagepersonremainsfreefromsignsandsymptoms
ofleprosy.
•Asthebacillimultiply,bacterialloadincreasesinthebody
andinfectionisrecognizedbytheimmunologicalsystem

14. •Asthebacillimultiply,bacterialloadincreasesinthebody
andinfectionisrecognizedbytheimmunologicalsystem.
•Lymphocytes(CD4-Thelpercells)andhistiocytes
(macrophages)invadetheinfectedtissue.
•Atthisstageclinicalmanifestationmayappearas
involvementofnerveswithimpairmentofsensation&/or
skinpatch.
•Ifitisnotdiagnosedandtreatedintheearlystages,further
progressofthediseasesisdeterminedbythestrengthof
thepatient’simmuneresponse

15. M.Lepraebacteria
Enter through respiratory tract
Schwann cells in cooler places (Cutaneous
nerves & peripheral nerve trunks of limbs and
face) Bacilli multiply in the Schwann cells
Good CMI Response Weak CMI Response
No Signs
and
Symptoms
Signs and
Symptoms:
SKIN/NERVE
LESIONS
(IL, TT, BT)
DISSEMINATED DISEASE
(BB, BL, LL)

16. Classification
RIDLEY AND JOPLING’S CLASSIFICATION
RidleyandJopling’sclassificationdividesleprosy
into5groupsbasedonhostimmunity:
•TT—TuberculoidPolar(Highresistance)
•BT—BorderlineTuberculoid
•BB—MidBorderline(dimorphic)
•BL—BorderlineLepromatous
•LL—LepromatousPolar(Lowresistance)

17. RIDLEY & JOPLING’S CLASSSIFICATION
BASED ON HOST’S IMMUNITY
LEPROSY
TUBERCULOID
(TT)
BORDERLINE
(BL)
BORDELINE
TUBERCULOID
(BT)
BORDERLINE
BORDERLINE
(BB)
BORDERLINE
LEPROMATOUS
(BL)
LEPROMATOUS
(LP)

18. Variants:
Inaddition,notincludedinRidley-Jopling’sClassificationare
followingtypes:
”1.Indeterminateleprosy(IL):Thisisaninitialnon-specificstageof
anytypeofleprosy.
2.Pureneuralleprosy:Inthesecases,skinlesionswhicharethe
cardinalfeatureofleprosyareabsentbutinsteadneurologic
involvementisthemainfeature.
”3.Histoidleprosy:ItisavariantofLLinwhichtheskinlesions
resemblenodulesofdermatofibromaandisthelesionsarehighly
positiveforleprabacilli

19. WHO CLASSIFICATION
BASED ON BACTERIAL LOAD
LEPROSY
NEGATIVE
PAUCIBACILLARY
(IL, TT, BT)
POSITIVE
MULTIBACILLARY
(BB, BL, LL)

20. •PaucibacillaryleprosytypeslikeIL,TT,BTarefoundin
peoplewithgoodCMI.
•Thediseaseremainslocalizedproducingasingleorfewskin
lesionswithorwithoutperipheralnervesinvolvement.
•Skinlesionsmaybemacule(flat)/papule(slightlyraised)
andplaque.
•Peoplewithstrongimmuneresponseareabletodestroy
largenumberoforganismsandroutineskinsmearsare
usuallynegativeinmostofthem.

21. •MultibacillaryleprosytypeslikeBB,BL,LLarefoundin
peoplewithpoorCMI.
•Bacillimultiplyandspreadmorewidelyresultingina
generalizeddisease.
•Itusuallypresentswithwidespreadlesionsintheskin,
nerve,andtolesserextentinotherorganslikeeyes,
respiratorymucosa,testesandreticulo-endothelialsystem.
•Itusuallysparesthecentralnervoussystemandupper
reproductivesysteminfemales

22. •Intheabsenceoftreatment,paucibacillaryformof
leprosymaydowngradetomultibacillary(from
tuberculoidtolepromatous)throughborderline
spectrum.

23. CLINICAL CYCLE OF LEPROSY
BORDERLINE
LEPROSY
BT->BB->BL
TUBERCULOID
LEPROSY
LEPROMATOUS
LEPROSY
INDETERMINATE
LEPROSY (IL)
PEOPLE INFECTED WITHM. LEPRAE
NO DISEASE
UNSTABLE IMMUNITY

24. The salient features of major types of leprosy:
1.INDETERMINATELEPROSY:(IL)
•Indeterminateleprosyreferstoaveryearlyform
ofleprosythatconsistsof
-Oneortwohypopigmentedmaculeswithslightly
diminishedsensationtotouch.(maculo-anesthetic
lesions)
•Itwillusuallyprogresstooneofthemajortypes
ofleprosyifuntreated.

26. Histopathology of Indeterminate Leprosy:
•Lymphocyticormononuclearcellinfiltrate,localised
particularlyaroundskinadnexalstructureslikehair
folliclesandsweatglandsoraroundbloodvessels.
•Nerveinvolvement,ifpresent,isstronglysupportive
ofdiagnosis.

27. 2. TUBERCULOID LEPROSY: (TT)
•SeeninpatientwithGoodCMI.
•Thepolartuberculoidformpresentsthefollowingfeatures:
•Lesionsare:
-SINGLEORFEWASYMMETRICALLESIONS(<5)
-RAISEDBORDERS,
-ATROPHICCENTRE,
-MACULARTYPE,
-HYPOANAESTHETIC/ANAESTHETIC
-HYPOPIGMENTED/ERTHYMATOUS
•Nervesneartothelesionsarethickened.

29. i)Thedermallesionsshowgranulomasresemblinghard
tuberclescomposedofepithelioidcells,Langhans’
giantcellsandperipheralmantleoflymphocytes.
ii)Lesionsoftuberculoidleprosyhavepredilectionfor
dermalnerveswhichmaybedestroyedandinfiltrated
byepithelioidcellsandlymphocytes.
iii)Thegranulomatousinfiltrateerodesthebasallayerof
epidermisi.e.thereisnoclearzone.
iv)Theleprabacilliarefewandseenindestroyednerves.
Histopathology of Tuberculoid Leprosy:

30. 3. BORDERLINE LEPROSY: (BL)
•Skinlesionsaresimilartotuberculoidleprosybutthenumber
is>5,<10andlargerinsizecomparedtoTT.
•Characteristicfeature:presenceofSATELLITELESIONSnear
themainlesion.
•SpectrumofBL:
I.BT
II.BB
III.BL

32. Histopathology of BORDERLINE LEPROSY:
1.Borderlinetuberculoid(BT)formshowsepithelioidcellsand
plentifullymphocytes.Thereisanarrowclearsubepidermalzone.
Leprabacilliarescantyandfoundinnerves.
2.Mid-borderline(BB)ordimorphicformshowssheetsof
epithelioidcellswithnogiantcells.Somelymphocytesareseenin
theperi-neurium.Leprabacilliarepresent,mostlyinnerves.
3.Borderlinelepromatous(BL)formshowspredominanceof
histiocytes,afewepithelioidcellsandsomeirregularlydispersed
lymphocytes.Numerousleprabacilliareseen.

33. 4. LEPROMATOUS LEPROSY: (LL)
•Seeninpatientwithweak/poorCMI.
•SevereformofLeprosy.
•Greaterbacterialloadisseeninthisstage,hencemore
chancesofinfectiontoothers.
•Lesionsare
•BILATERAL,SYMMETRICAL,
•HYPOPIGMENTED,
•SENSORYLOSSISLESSCOMPAREDTOTT.

34. •LesionsareMACULAR,PAPULAR,NODULARTYPES
•SMALLERTHANTUBERCULOIDLESIONSINSIZE.
NODULAR
MACULAR
PAPULAR

35. OTHER LESIONS: LEONINE FACE
•Extensive tissue destruction of NASAL CARTILAGE ->
NASAL COLLAPSE (Saddle nose deformity)
•Lost eye brows.
•Thickened ear lobes
•Lost upper incisor teeth
•Thickened Forehead skin.

36. LEONINE FACES

37. Otherclinicalfeatures:
-Rhinorrhoea(withnumerousbacteria)
-Gloveandstockinganaesthesia(duetodamagetonerveson
bothsideofthelimbs(symmetrical).
Lossoftemperaturesensation
Lossofsensationtotouch,pain,deeppain.
Thisresultintrophiculcersduetofrequent
traumatohandsandlegs.

38. •Resorptionofdistalphalanges(Acroosteolysis)due
todigitalnecrosis.

39. Contractures

40. •Renal damage
•Testicular damage
•Keratitis
•Ulceration of Hard palate.
•Nasal septum Ulceration.

41. Histopathology of LEPROMATOUS LEPROSY:
•Inthedermis,thereisproliferationofmacrophageswith
foamychange,particularlyaroundthebloodvessels,nerves
anddermalappendages.Thefoamymacrophagesarecalled
‘lepracells’orVirchowcells.

42. •Thelepracellsareheavilyladenwithacid-fastbacilli
demonstratedwithAFBstaining.TheAFBmaybe
seenascompactglobularmasses(globi)orarranged
inparallelfashionlike‘cigarettes-in-pack’.

43. LEPROMIN TEST
•ItisNOTADIAGNOSTICTESTbutisusedforclassifyingleprosyonthe
basisofimmuneresponse.
•Intradermalinjectionoflepromin,anantigenicextractofM.leprae,
revealsdelayedhypersensitivityreactioninpatientsoftuberculoid
leprosy:
1)Anearlypositivereactionappearingasaninduratedareain24-48
hoursiscalledFernandezreaction.
2)Adelayedgranulomatouslesionappearingafter3-4weeksiscalled
Mitsudareaction.

44. “PATIENTSOFLEPROMATOUSLEPROSYARENEGATIVEFOR
LEPROMINTEST”
•Thetestindicatesthatcell-mediatedimmunityisgreatly
suppressedinlepromatousleprosywhilepatientsoftuberculoid
leprosyshowgoodimmuneresponse.
•DelayedtypeofhypersensitivityisconferredbyThelpercells.The
granulomasoftuberculoidleprosyhavesufficientThelpercellsand
fewerTsuppressorcellsattheperipherywhilethecellular
infiltratesoflepromatousleprosylackThelpercellsandmoreT
suppressorcells.