Diseases of the Skin

Dr G.O Ogun
Department of Pathology,
College of Medicine,
University of Ibadan
 LEPROSY
OR
HANSENS DISEASE
 Disease of Prehistoric times
A man with leprosy……………..immediately he
was cured of his leprosy…….

Matthew 8:2-4
Mark 1:40-42
 Introduction
► Is a slowly progressive chronic infection caused
by Mycobacterium Leprae.
► It is an acid-fast obligate intracellular organism
that does not grow in culture but can be grown
in the 9 band armadillo.
► It is grows slower than other mycobacterium at
32-340C
► Affects cooler parts of the body, particularly
1. Skin
2. Upper respiratory tract
3. Superficial peripheral nerves
4. Testes
5. Anterior part of the eye
 Transmission
► Mostly contained within the skin.
► Transmitted from person to person through
aerosol from lesions in the upper respiratory
tract mucous membranes or direct contact
through the skin
► Thru minor abrasions in Lepromatous
leprosy and TT and BTL in reaction
► Incubation period is 3-5 years( shorter or
Longer)
► Most people resist infection
 Pathogenesis
► Inhaled M. Leprae is taken up by the
alveolar macrophages, disseminate in the
blood and only grow in the relatively cool
tissues of the skin and extremities.
► M. leprae secrete no toxins but its virulence
is based on the properties of its cell wall.
Lipid-Rich Cell Wall of Mycobacterium
Mycolic acids

(Purified Protein Derivative)

 GLOBAL LEPROSY CASE-LOAD :
1985 VS 2000 VS 2003
1985 1998 2000 2003

12 Million < 1 Million 0.6 Million 0.5 Million

The dramatic decline is attributed to the effective use of multi-drug therapy(MDT)

Parameter 1985 2000 2003

1. Number of Countries 122 14 9
with Prevalence Rates of
> 1/10,000 population

2. Global Prevalence 10/10,000 1/10,000 < 1/10,000

3. Patients on MDT
4. Patients Cured
5. Drug Resistance
< 10% 100% 100%
Accurate Data Not 11.2 million 13.5 million
Available
High-since single drug- NIL- Multi-Drug NIL - Multi-Drug
dapsone was given for Resistance following Resistance following
long periods, in low MDT is NOT reported MDT is NOT reported
doses
 HANSEN DISEASE (LEPROSY)
Number of reported cases, by year
United States, 1973-2003
GLOBAL LEPROSY SITUATION IN
JANUARY 2004
Prevalence as of 1 January 2004

69%

1% 2%
9% 0%
19%

Africa Americas East Mediterranean

South-East Asia Western Pacific Europe

GLOBAL LEPROSY SITUATION IN 2004

Annual new case detection 2003

1%
81%
0%

Africa
Americas
7%
East Mediterranean
1% 10%
South-East Asia
Western Pacific
Europe
 Leprosy Situation in South-East Asia Region

Annual new case detection 2003

91.0%

2.4%
0.0%
Bangladesh Bhutan
0.0% 2.7% 1.4%
India Indonesia
1.9%
Maldives Myanmar
0.1% 0.4%
Nepal Sri Lanka 0.2%
Thailand Timor-Leste
Classification and clinical features

► LL BL BB BT TT

► Ridley and Jopling classification is based on

clinical, bacteriologic and histopathology in
correlation with lepromin reactivity
Lepromatous vs. Tuberculoid Leprosy
Lepromatous Leprosy
Lepromatous Leprosy Pre-
and Post-Treatment
 Pathogenesis

► The T helper response determine whether an

individual has TT or LL via type IV hypersensitivity

► APC IL12 TH1 IL2 & IFNγ

► TT there is high production of IL12 and

infilteration of lesion by γ/δ T-cell receptor
lymphocytes leading to the production of IFNγ
► LL there is low level of IL12 or unresponsiveness
of TH1 or a dominate TH2 with production of
IL4,5,10 which suppress macrophage activation in
response to M. Leprae
 Pathogenesis
► In some cases paradoxically in LL,
antibodies are produced which are usually
not protective.
► The antibodies form immune complexes
with free antigen and lead to
► Erythema nodosum leprosum
► Vasculitis
► Glomerulonepritis
 Diagnosis
► Microscopy is sensitive for the lepromatous
form but not for the tuberculous form
► Skin testing is required to confirm the
tuberculous form
BURULI ULCER (BU)
 Introduction
► Is caused by Mycobacterium ulcerans
► Was identified as an emerging infectious
disease in West Africa

► At an international meeting in July 1998 in

Cote d'Ivoire ,the Yamoussoukro Declaration
on Buruli Ulcer was made
► The declaration expresses the concern that
little is known about this disease, and called
on the international community to support
control and research efforts.
 Introduction- 2
► Mycobacterium ulcerans is an acid fast
bacillus that grows optimally at 32oC
► It infects the skin and subcutaneous tissues
of man
► Survives exposure to UV light briefly so
open reservoir such as vegetation is unlikely
► No aquatic or land animal is know to be
naturally infected
► The typical lesion is an indolent, necrotizing
ulcer
 Epidemiology
► In the 1960s, many patients in refugee
camps in an area near the Nile River in
Uganda, called Buruli, had ulcers which
were caused by M. ulcerans.
► reported from mainly the tropics with the
highest numbers of patients reported from
Africa- Uganda, Zaire, Nigeria
► Those affected tend to live in swampy
lowlands and in river valleys
► The organism enters the skin by
percutaneous/penetrating injection/injuries
 Pathogenesis
► Subcutaneous inoculation may result in
amplification of bacteria in the subcutaneous fat
tissue.
► Secretion of toxins, one of which has been
identified as mycolactone, a polyketide toxin and
possibly other toxins as well ± e.g. phospholipase
C
► These are the major cause of extensive tissue
necrosis, resulting in the clinical hallmarks of BU.

► Inoculation is followed by a latent period

without clinical manifestations (stage 0)
 Pathogenesis- Stage 1
► Preulcerative subcutaneous nodule appears
► Lesions may consist of an intracutaneous
nodule.
► Occasionally, patients may develop
extensive indurated lesions, or oedema
► Nodule is not painful,nor tender or red.
► The overlying skin may be itchy
► A vesicle forms which is ruptured by
scratching that leads to ulcer formation
Stage 1- Preulcerative
 Pathogenesis- Stage 2
► Necrosis, the clinical hallmark of BU, sets in.
► The typically undermined necrotic ulcerative
lesions can be easily recognized
► As the ulcer enlarges the surrounding skin
becomes edematous
► The ulcer is covered by white necrotic
slough.
► Patient are well remain active, have no
fever, no regional lymphadenopathy, no
malaise and no leukocytosis
► Desquamation and hyperpigmentation of
skin around the advancing edge of the ulcer
may be prominent
Stage 2- Necrotic slough and
undermined edges
 Pathogenesis- Stage 2 (contd)
► Ulcers may be very large. Most ulcers are on
the limbs, frequently over major joints,
about 10% are on the trunk
► Palm and sole are spared, face and scalp
are rarely involved
► Occasionally, the infection may spread to
other tissues like bone.
Stage- 3 : A granulomatous healing
stage/ response sets in
 Stage 3
► Granuloma formation develops in BU during
the process of healing of necrotic ulcers
with resultant fibrosis.
► Disseminated BU and osteomyelitis might
conceivably be associated with inherited
defects in granuloma formation.
Stage 4
► Fibrosis,
scarring,
calcification
and
contractures
may result.
 Treatment
► Surgicalexcision with skin grafting
► Heat therapy to temperatures of up to 400C
may inhibit organism
 Complication
► Broad depressed scars.
► Contracture deformity
► Lymphedema
► Amputation
DEEP MYCOSIS
 FUNGUS

► Widely distributed in nature (air, water,

soil, decaying organic debris)
► ~400,000 types
► Eukaryotic, highly developed cellular
structure
► Facultatively anaerobic/strict aerobic
► Nonphotosynthetic
 DIMORPHIC FUNGI

► Capable of growing in mould or yeast form under

different environmental conditions (temperature,
CO2, nutrients)
► Coccidioides immitis
► Histoplasma capsulatum
► Blastomyces dermatitidis
► Paracoccidioides brasiliensis.
► Sporothrix schenckii
► Candida albicans and Penicillium marneffei.
 DEEP MYCOSIS
► Deep mycoses are caused by primary
pathogenic and opportunistic fungal
pathogens.
► The primary pathogenic fungi are able to
establish infection in a normal host
► Opportunistic pathogens require a
compromised host in order to establish
infection (e.g., cancer, organ
transplantation, surgery, and AIDS
► Theprimary deep pathogens usually gain
access to the host via the respiratory tract.

► Opportunistic fungi causing deep mycosis

invade via the respiratory tract, alimentary
tract, or intravascular devices.
 Primary systemic fungal pathogens

► Coccidioides immitis (Coccidioidomycosis)

► Histoplasma Capsulatum ( Histoplasmosis)
► Blastomyces dermatitidis (Blastomycosis)
► Paracoccidioides brasiliensis.
(Paracoccidioidomycosis)
► Among the primary pathogens and S schenckii,
the morphological transformation is from a
hyphal form to a yeast-like form (or spherule in
the case of C immitis) in tissue
► Among the primary pathogens and S schenckii,
the morphological transformation is from a hyphal
form to a yeast-like form (or spherule in the case
of C immitis) in tissue
► However, the dimorphism of Candida albicans is
somewhat different in that the organism
transforms from a budding yeast-like structures
(blastoconidia) to filamentous structures known
as germ tubes
 Opportunistic fungal pathogens
► Cryptococcus neoformans
► Candida spp.
► Aspergillus spp.
► Penicillium marneffei
► the Zygomycetes
► Trichosporon beigelii
► Fusarium spp
African histoplasmosis due to H.
capsulatum var. duboisii
► African histoplasmosis is geographically confined
to Central Africa.
► In the parasitic phase, H. capsulatum var. duboisii
exhibits large, round spores of 10-15 µm. In the
saprophytic phase, the two varieties are
morphologically indistinguishable.
► Patients with this chronic mycosis always exhibit
polymorphous cutaneous lesions, bone and lymph
node involvement and ultimately random deep
localisations.
► When the disease follows an acute course (e.g. in
AIDS patients), the yeast cells remain small and
the infection is usually ascribed mistakenly to the
variety capsulatum.
Histoplasmosis
Histoplasmosis
 Aspergillosis
► Invasive aspergillosis most frequently involves the lungs
and paranasal sinuses.
► may disseminate from the lungs to involve the brain,
kidneys, liver, heart, and bones.
► The main portal of entry for aspergillosis is the respiratory
tract, however, injuries to the skin may also introduce the
organism into susceptible hosts.
► Quantitative and functional defects in circulating
neutrophils are key risk factors for development of invasive
aspergillosis.
► For example, neutropenia due to cytotoxic chemotherapy
and systemic corticosteroids are common predisposing
factors for invasive aspergillosis.
 Aspergillosis
► Pulmonary aspergilloma
This colonisation is characterised by the
development of a free and mobile fungal mass,
the fungal ball, in a residual lung cavity (80%
post-tuberculosis). This mass consists of
interwoven hyphae. The most typical symptom is
haemoptysis, which can sometimes be profuse.
Sinusitis
► This chronic, unilateral, usually non-invasive
infection is often localised in the maxillary sinus.
Aspergillosis
 Candidiasis
► Candidiasis (due to C albicans and other Candida
spp.) is the most common opportunistic fungal
infection.
► Candida albicans is the most common cause of
candidiasis.
► Candidiasis may be classified as superficial or
deep.
► Superficial candidiasis may involve the epidermal
and mucosal surfaces, including those of the oral
cavity, pharynx, esophagus, intestines, urinary
bladder, and vagina.
 Candidiasis
► The alimentary tract and intravascular catheters
are the major portals of entry for deep (or
visceral) candidiasis.
► The kidneys, liver, spleen, brain, eyes, heart, and
other tissues are the major organ sites involved in
deep or visceral candidiasis.
► The principal risk factors predisposing to deeply
invasive candidiasis are protracted courses of
broad spectrum antibiotics, cytotoxic
chemotherapy, corticosteroids, and vascular
catheters
 Cryptococcosis
► Cryptococcosis is most typically an opportunistic
fungal infection that most frequently causes
pneumonia and/or meningitis.
► Defective cellular immunity, especially that
associated with the acquired immune deficiency
syndrome, is the most common risk factor for
developing cryptococcosis.
► In patients with severe abnormalities of cellular
immunity such as AIDS patients, there is often
dissemination to multiple foci, including the
prostate
► Primary cutaneous cryptococcosis (the skin as the
portal of entry) is extremely rare. In most cases,
infection of the skin should be considered as
secondary
 Cryptococcosis
► Drop of Indian ink to CSF will show the
capsule clearly
► For histological examination, mucicarmine is
preferred, which stains the capsule, in
combination with silver impregnation
(Gomori-Grocott), which stains the yeast
wall.
Cryptococcosis
 Zygomycosis
► Are usually due to Rhizopus, Rhizomucor, Absidia, Mucor
species, or other members of the class of Zygomycetes,
also causes invasive sinopulmonary infections.
► An especially life-threatening form of zygomycosis (also
known as mucormycosis), is known as the rhinocerebral
syndrome, which occurs in diabetics with ketoacidosis.
► Neutropenia and corticosteroids are other major risk
factors for zygomycosis.
► Aspergillus spp and the Zygomycetes have a strong
propensity for invading blood vessels.
► The fungi appear in tissues as broad, nonseptate hyphae
of uneven diameter (diameter ranging from 6 to 50 µm)
 References
► http://www.mgm.ufl.edu/~gulig/mmid/lectu
res/Mycology%20Part%201.pdf- Mycology
► http://www.ncbi.nlm.nih.gov/books/bv.fcgi?
rid=mmed.section.4006- for medical
microbiology for texas medical branch
► www.life.umd.edu/classroom/bsci424/Lectur
es/LecturePP25Mycobacterium.ppt
► http://www.itg.be/itg/DistanceLearning/Lect
ureNotesVandenEndenE/53_Medical_mycolo
gyp4.htm#T36