1. DR. SHILPA SONI

2.  CAUSATIVE ORGANISM???????
 HISTORY OF MYCOBACTERIUM TUBERCULOSIS
 MORPHOLOGY OF M.TUBERCULOSIS??????
 CLASSIFICATION OF CUTANEOUS
TUBERCULOSIS????

3.  Mycobacterium tuberculosis
 Mycobacterium bovis
 BCG (Bacille calmette guerin)

4.  Signs of skeletal TB (Pott disease) were evident
in Europe from Neolithic times (8000 BCE), in
ancient Egypt (1000 BCE), and in the pre-
Columbian New World.
 TB was recognized as a contagious disease by the
time of Hippocrates (400 BCE), when it was
termed "phthisis" (Greek from phthinein, to
waste away).
 In 1720, physician Benjamin Marten described in
his A Theory of Consumption, tuberculosis may
be caused by small living creatures that are
transmitted through the air to other patients.

5.  M. tuberculosis, then known as the "tubercle
bacillus", was first described on 24 March
1882 by Robert Koch
 Term ‘mycobacterium’ was given in 1896 to a
large group of bacteria producing mould-like
pellicles when grown on liquid media.

6.  Weakly gram-positive, strongly
acid fast, aerobic, nonspore
forming, nonmotile, facultative,
intracellular, curved rods
measuring 0.2-0.5 X 2-4 um.
 Cell wall, rich in lipids (e.g.,
mycolic acid).
 M. tuberculosis divides every 15–
20 hours.
 Organisms are identified by their
red color on acid-fast staining.

7. Route of infection Clinical type histology course
Inoculation tuberculosis
(exogenous source)
Tuberculosis chancre
Tuberculosis verrucoasa cutis
Lupus vulgaris (occasionally)
Non specific
TB specific
TB specific
Localized
Localized
Localized
Secondary tuberculosis
( endogenous source)
Contiguous spread
Auto-inoculation
Scrofuloderma
Orificial tuberculosis
TB specific
TB specific
Localized
Progressive
Haematogenous
tuberculosis
Acute military tuberculosis
Lupus vulgaris
Tuberculous gumma
TB specific
TB specific
TB specific
Generalized
Localized
Localized
Eruptive tuberculosis
(Tuberculids)
Micropapular
Papular
Nodular
Lichen scrofulosorum
Papular or papulonecrotic
tuberculid
Erythma induratum of Bazin
Variable
variable
variable
Localized
Scattered
Crops
Generalized

8.  Not previously exposed
 Tuberculosis chancre
 Milliary tuberculosis of the skin
 Previously sensitized hosts
 Lupus vulgaris
 Scrofuloderma
 Tuberculosis verrucosa cutis
• Multibacillary
 Primary inoculation TB,
scrofuloderma, tuberculosis
periorificialis, acute military
tuberculosis, gumma
• Paucibacillary
Tuberculosis verrucosa cutis,
lupus vulgaris

9.  EPIDEMIOLOGY OF CUT. TUBERCULOSIS?????
 PATHOGENESIS???????

10.  1/3rd world’s population infected with
Mycobacterium tuberculosis bacteria
 In India cutaneous manifestations of TB
(including tuberculids) are found in < 0.1% of
individuals seen in dermatology clinics.
 Cutaneous TB- 1.5% of extrapulmonary TB.
 70% developed disease in spite of being
vaccinated with BCG
 Male:female = 1.3:1.

11.  Most patients show clinical infection within first
3 decades of life.
 Female preponderance in scrofuloderma & lupus
vulgaris.
 M. bovis found in 1–1.5%
 Childhood TB
 5-15% of all cases of TB
 most commonly in 10-14 years of age
 Commonest form
 In adults: Lupus Vulgaris
 In childhood: Scrofuloderma and Lichen
scrofulosorum

12.  Its cell wall prevents the fusion of the
phagosome with a lysosome
 M. tuberculosis blocks the bridging molecule,
early endosomal autoantigen 1
 bacteria also carry the UreC gene, which
prevents acidification of the phagosome.[5]
 production of the diterpene Isotuberculosinol
prevents maturation of the phagosome
 The bacteria also evade macrophage-killing
by neutralizing reactive nitrogen
intermediates.[7]

13.  Key cell is activated CD4+ helper T cellTh-1
or Th-2 cell , releasing cytokines such as
interferon gamma, interleukins 1 & 2, TNF
alpha activate macrophages resulting in
protective immunity & containment of
infection or induce delayed type
hypersensitivity, tissue destruction and
progressive disease

14.  Tubercle an avascular
granuloma composed of
a central zone
containing giant cells,
with or without
caseation, and a
peripheral zone of
lymphocyte and
fibroblast

15.  LUPUS VULGARIS????????
 SCROFULODERMA????????
 TUBERCULOSIS VERRUCOSA CUTIS????????

16. 1808, Robert willan
Founder of british
derma.
Gave term LUPUS
To nodular eruption
on face
1887, William
Tilburg Fox
used term LUPUS
VLGARIS
for skin TB
LUPUS word Origin
? Latin word of wolf
? Greek word lepros

17.  > 90% involve head and neck in western
countries.
 In India, Mostly lower half of the body
 It begins as painless reddish-brown soft
nodules which slowly enlarge to form
irregularly shaped plaque.
 Central healing with scarring while periphery
continues to spread

18.  Diascopy test:
 If lesion is pressed
by a glass slide to
diminish vascular
component of
inflammation,
individual nodules
appear as yellow
brown spots (apple
jelly color), so
nodules are named
“apple jelly nodules”.

19.  Mucosa- small, soft
pink papule/ ulcer
 Nasal & auricular
cartilage
extensive
destruction &
disfigurement

20.  Morphological variants
 classic plaque or keratotic type (most common)
 hypertrophic
 ulcerative
 atrophic
 Unusual presentations
 sporotrichoid pattern
 site of BCG vaccination
 vicinity of Scrofuloderma

21.  Epidermal atrophy, ulceration, or
hyperplasia showing Acanthosis,
Hyperkeratosis, Papillomatosis
 Epitheloid cells tuberculoid
granulomas
 Giant cells (usually of langhans
type) with slight or absent
caseation necrosis within the
tubercle
 Infiltrate of lymphocytes may be
so prominent that the
granulomatous component
obscured

22.  Basal cell carcinoma
 Sarcoidosis
 Discoid lupus erythomatosus
 Leprosy
 Deep fungal infection

23. 1883, Ernest Besnier wrote about scrofulous gumma
Latin word scrofa means a breeding sow, b/c swine
were supposed to be subject to the complaint

24.  Involvement of skin
overlying contiguous
tuberculosis focus usually in
lymph gland, bone, joint,
lacrymal gland or duct
 Asymptomatic, well defined
,firm, freely movable,
bluish-red nodule breaks
down to form undermined
ulceration with granulating
tissue at base

25.  Scarring and fibrosis of lymph
nodes may lead to
lymphoedema and
elephantiasis
 Numerous fistulae may
intercommunicate beneath
ridges of a bluish skin
 Skin of the lymphoedematous
area may show lesions of
cutaneous TB, usually lupus
vulgaris
 Spontaneous healing with
cribriform scarring possible

26. • Center of lesion abscess
formation or ulceration
• Deeper portions and at
periphery
– Diffuse dense mixed cell
infiltrate of neutrophils,
some eosinophils, plasma
cells, lymphocytes and
histiocytes
 Tuberculoid granulomas with
caseation necrosis seen in
most cases.

27.  Sporotrichosis
 Actinomycosis
 chronic bacterial osteomyelitis
 hidradenitis suppurativa
 severe acne conglobata

28. Synonyms:
Tuberculosis verrucosa cutis
Anatomist’s warts
Prosector’s warts
Verruca necrogenica

29.  Accidental exogenous innoculation
 Physicians, pathologists and post-mortem
attendants
 Autoinoculation with sputum
 Lower limbs most common site for warty TB in
children
 Lymphadenopathy not seen in contrast to
Scrofuloderma and Lupus vulgaris

30.  Small, asymptomatic, firm ,
red or brown warty papule
with slight inflammatory
areola
 Extends to form verrucous
plaque
 Irregular extension at edges
leads to serpiginous outline
 Fissure discharging pus can
be seen
 Spontaneous involution
forming white atrophic scar

31.  Hyperkeratosis and
Acanthosis
 Acute inflammatory
infiltrate
 Abscess formation in
upper dermis or within
downward extensions
of epidermis
 Mid-dermis tuberculoid
granulomas with
necrosis

32.  wart
 blastomycosis
 chromoblastomycosis
 sporotrichosis
 hypertrophic lupus vulgaris
 hypertrophic lichen planus
 squamous cell carcinoma

33.  PRIMARY INNOCULATION TUBERCULOSIS??????
 MILIARY TUBERCULOSIS???????
 ORIFICIAL TUBERCULOSIS???????
 TUBERCULOUS GUMMA????????

34.  Earliest lesions
– 2–4 weeks after inoculation
– brownish papule, nodule, or ulcer with an undermined
edge and granular haemorrhagic base
 Induration with adherent crust
 Painless, non-healing ulcer with unilateral regional
lymphadenopathy, especially in child, should arouse
suspicion

35.  Usually affects
– Young children
– Immunosuppressed patients
– Concurrent HIV infection
 Crops of minute bluish papules, vesicles,
pustules , nodules or haemorrhagic lesions
 Enlarged liver (40% of cases), enlarged spleen
(15%), inflammation of the pancreas (<5%), and
multiple organ dysfunction with adrenal
insufficiency(adrenal glands do not produce
enough steroid hormones to regulate organ
function)

36.  More common in males with impaired cell mediated
immunity
 Site oral mucosa, anal mucosa & vulva
 Small oedematous red nodules rapidly break down to
form painful, shallow ulcers with undermined bluish
edges and hemorrhagic base.

37.  Associated with granulomatous
swelling of lips & tongue
 Fatal outcome due to advanced
internal disease.
 Histopathology
inflammatory infiltrate,
tuberculoid granulomas with
pronounced necrosis deep in
dermis

38.  Malnourished children, immunosuppressed patients,
and in association with underlying lymphoma
 Firm subcutaneous nodule or fluctuant abscess most
commonly on extremities
 May break down to form an undermined ulcer often
with sinuses
 Histopathology caseation necrosis with rim of
eosinophils and giant cells

39.  TUBERCULIDS???????

40.  Darier in 1896
 Hypersensitivity reaction to M. tuberculosis or its
products in patient with significant immunity
 Following criteria must be fulfilled to designate a
condition as tuberculid:
– Skin lesion must show tuberculoid histopathology
– Mycobacterium tuberculosis must not be
demonstrated in the lesion
– Tuberculin test must be strongly positive
– Treatment of underlying TB focus must lead to
resolution of skin lesion

41.  Hebra in 1868
 Second most common pattern
of cutaneous TB in children
 Systemic focus of TB
detected in majority cases
 Most commonly involve
cervical, mediastinal or hilar
lymph nodes
 Mainly found on the trunk

42.  Asymptomatic, 0.5– 3.0 mm,
closely grouped lichenoid ,
firm, follicular or perifollicular
papules with fine scales 
discoid plaque .
 Antituberculous therapy, the
lesions usually clear within 4–8
weeks without scarring.
 Spontaneous involution seen
 HistologySuperficial dermal
granulomas, usually in vicinity
of hair follicles or sweat ducts

43.  Necrotizing papulonodular lesions
of size 2 to 8 mm in widespread &
symmetrical crops
 Preceded by fever and
constitutional symptoms
 Heal with varioliform scarring in
4-6 weeks
 Sites of predilection extensor
aspect of extrimities, lower trunk
& buttocks

44.  Child & young adults
predominantly
affected
 Spontaneous
involution with pitted
scar
 Histology wedge
shaped necrosis in
dermis, tuberculoid
infiltrates &
obliterative vasculitis

45.  Main pathology in subcutaneous fat
 Four times more common in women
 Indolent, mildly tender, dull red
nodules ranging in size from 5 to 7.5
cm develop on calves
 Lesions may ulcerate
 Ragged, irregular and shallow ulcers
with bluish edge.

46.  Erytematous, tender, 2.5 to 5 cm nodules that
usually develop on shins
 May also involve the thighs, buttoks and
forearm in severe cases
 Low grade fever and swelling of ankle joints
accompany the skin lesions in some patients
 The lesions regress spontaneously
 Ulceration and scarring not the features
 Skin biopsy reveals a septal panniculitis with no
evidence of vasculitis

47.  INVESTIGATIONS?????
 TREATMENT???????

48. Nucleic acid probes
Nucleic acid sequencing

49.  Tuberculin is made from
proteins derived from
inactive tubercle bacilli
 Most people who have TB
infection will have a
reaction at injection site
 0.1 ml of 5 tuberculin
units of liquid tuberculin
are injected between the
layers of skin on forearm

50.  Forearm should be
examined within 48 - 72
hours
 Reaction is an area of
induration (swelling)
around injection site
 Induration is measured in
millimeters
 Erythema (redness) is not
measured
Only the induration is measured

51.  Positive test  >10 mm
– Clinical or latent tuberculosis infection
– Contact with environmental mycobacteria
 Low sensitivity (false negative reactions)
– Immunosuppressed patients
– Patients with severe illness
– Active tuberculosis
– HIV infection
– Immunosuppressant drugs
 sensitivity 58.97%
 specificity 62.50%

52.  Ziehl-Neelsen stain is
used most commonly to
demonstrate the
presence of the bacilli in
a smear. The technique
is simple and
inexpensive
 Fluorescent dye
(Auramine O and
Rhodamine B)

53. 53
 Solid media - colonies in
three to six weeks.
 These colonies are usually a
buff or beige color and have
a rough, dry, granular
appearance
 Liquid media – surface
pellicle
 Solid media: 3 - 6 weeks
 Liquid media: 4 - 14 days

54.  Contains-
7 mL of modified Middlebrook 7H9 Broth base
PANTA antibiotic mixture
 A fluorescent compound is embedded in
silicone on the bottom of 16 x 100 mm
round-bottom tubes
 The fluorescent compound is sensitive to the
presence of oxygen
 Consumption of oxygen and fluorescence can
be detected

55. • Epithelioid cell granuloma 60 to 100 %
 Recent series histopathology suggestive of
tuberculosis
– Total 175(86%) out of 202
– lupus vulgaris 82%
– tuberculosis verrucosa cutis 90%
– Scrofuloderma 95%
 Caseation necrosis
 Scrofuloderma all cases
 Lupus vulgaris 3 of 108
 Tuberculosis verrucosa cutis none

56.  Victor et al first described use of PCR in
cutaneous TB
 confirmation of M. tuberculosis
 – PCR 1-3 days
 – culture 2-6 weeks
 mycobacterial DNA demonstrated in
– all different histopathological variants of
cutaneous tuberculosis
– two of tuberculids (papulonecrotic tuberculid
and erythema induratum)

57.  QFT-Ginvitro diagnostic aid
 Based on quantification of interferon gamma release
from sensitized lymphocyte
 Approved in 2005 by US FDA for diagnosis of both latent
& active tuberculous infection.
 Enzyme-linked immunospot (ELISpot) enumerates IFN-γ
secreting T cells, FDA approved in july 2008,expected to
replace TST, Sensitivity-87.5%,specificity-86.7%
 Whole-blood ELISA, QuantiFERON-TB Gold measures IFN-γ
concentration in supernatant by enzyme linked
immunosorbent assay (ELISA), Uses antigens ESAT-6,CFP-10
and TB7.7, Sensitivity-81%,specificity-99.2%

58.  Rifampicin(R) – Bactericidal, all bacilli
 Pyrazinamide(Z) – Bactericidal, all bacilli
 Isoniazid(H) – Bactericidal, replicating
bacilli
 Streptomycin(S) – Bactericidal, Extracellular
bacilli
 Ethambutol(E) - Bacteristatic

60. • WHO(2009) recommendations for cutaneous TB
• HIV-negative individuals (adults as well as children)
DOTS
– intensive phase 4 drugs H, R, Z, E x 2 mths
– continuation phase H and R x 4 mths
 Daily dosing (2HRZE/4HR) recommended for all newly
diagnosed
 Alternatively
– [2HRZE/4(HR)3]: daily intensive phase followed by
3/wkly continuation phase
– [2(HRZE)3/4(HR)3]: 3/weekly dosing throughout
therapy, provided every dose directly observed

61. 61
Mono-resistant Resistant to any one TB treatment drug
Poly-resistant Resistant to at least any two TB drugs
(but not both isoniazid and rifampin)
Multidrug-
resistant
(MDR TB)
Resistant to at least isoniazid and
rifampin, the two best first-line TB
treatment drugs
Extensively
drug-resistant
(XDR TB)
Resistant to isoniazid and rifampin,
PLUS resistant to any fluoroquinolone
AND at least 1 of the 3 injectable
second-line drugs (e.g., amikacin,
kanamycin, or capreomycin)

62. THANKS