Diseases of the SkinDiseases of the SkinDr G.O OgunDr G.O Ogun

Department of Pathology,Department of Pathology,College of Medicine,College of Medicine,University of IbadanUniversity of Ibadan

LEPROSYLEPROSYOROR

HANSENS DISEASEHANSENS DISEASE

Disease of Prehistoric timesDisease of Prehistoric times

A man with leprosyA man with leprosy…………………………..immediately he ..immediately he was cured of his leprosywas cured of his leprosy…………. .

Matthew 8:2Matthew 8:2--44Mark 1:40Mark 1:40--4242

IntroductionIntroduction►► Is a slowly progressive chronic infection caused Is a slowly progressive chronic infection caused

by by Mycobacterium Leprae. Mycobacterium Leprae. ►► It is an acidIt is an acid--fast obligate intracellular organism fast obligate intracellular organism

that does not grow in culture but can be grown that does not grow in culture but can be grown in the 9 band armadillo. in the 9 band armadillo.

►► It is grows slower than other mycobacterium at It is grows slower than other mycobacterium at 3232--343400CC

►► Affects cooler parts of the body, particularlyAffects cooler parts of the body, particularly1.1. SkinSkin2.2. Upper respiratory tractUpper respiratory tract3.3. Superficial peripheral nervesSuperficial peripheral nerves4.4. TestesTestes5.5. Anterior part of the eyeAnterior part of the eye

TransmissionTransmission►►Mostly contained within the skin.Mostly contained within the skin.►►Transmitted from person to person through Transmitted from person to person through

aerosol from lesions in the upper respiratory aerosol from lesions in the upper respiratory tract mucous membranes or direct contact tract mucous membranes or direct contact through the skinthrough the skin

►►Thru minor abrasions in Thru minor abrasions in LepromatousLepromatousleprosy and TT and BTL in reactionleprosy and TT and BTL in reaction

►►Incubation period is 3Incubation period is 3--5 years( shorter or 5 years( shorter or Longer)Longer)

►►Most people resist infectionMost people resist infection

PathogenesisPathogenesis

►►Inhaled Inhaled M. Leprae M. Leprae is taken up by the is taken up by the alveolar macrophages, disseminate in the alveolar macrophages, disseminate in the blood and only grow in the relatively cool blood and only grow in the relatively cool tissues of the skin and extremities.tissues of the skin and extremities.

►►M. M. lepraeleprae secrete no toxins but its virulence secrete no toxins but its virulence is based on the properties of its cell wall.is based on the properties of its cell wall.

Lipid-Rich Cell Wall of MycobacteriumMycolic acids

(Purified Protein Derivative)

GLOBAL LEPROSY CASEGLOBAL LEPROSY CASE--LOAD : LOAD : 1985 VS 2000 VS 20031985 VS 2000 VS 2003

19851985 19981998 20002000 20032003

12 Million12 Million < 1 Million< 1 Million 0.6 Million0.6 Million 0.5 Million0.5 Million

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

ParameterParameter 19851985 20002000 200320031. Number of Countries 1. Number of Countries

with Prevalence Rates of with Prevalence Rates of > 1/10,000 population> 1/10,000 population

122122 1414

1/10,0001/10,000100%100%11.2 million11.2 million

NILNIL-- MultiMulti--Drug Drug Resistance following Resistance following MDT is NOT reportedMDT is NOT reported

99

2. Global Prevalence2. Global Prevalence 10/10,00010/10,000 < 1/10,000< 1/10,0003. Patients on MDT3. Patients on MDT < 10%< 10% 100%100%4. Patients Cured4. Patients Cured Accurate Data Not Accurate Data Not

AvailableAvailable13.5 million13.5 million

5. Drug Resistance5. Drug Resistance HighHigh--since single drugsince single drug--dapsonedapsone was given for was given for long periods, in low long periods, in low dosesdoses

NIL NIL -- MultiMulti--Drug Drug Resistance following Resistance following MDT is NOT reportedMDT is NOT reported

HANSEN DISEASE (LEPROSY)Number of reported cases, by year

United States, 1973-2003

69%

1%

19% 9% 0%2%

Africa Americas East Mediterranean

South-East Asia Western Pacific Europe

GLOBAL LEPROSY SITUATION IN GLOBAL LEPROSY SITUATION IN JANUARY 2004JANUARY 2004

Prevalence as of 1 January 2004

GLOBAL LEPROSY SITUATION IN 2004GLOBAL LEPROSY SITUATION IN 2004

Annual new case detection 2003

10%1%

7%

1%

0%

81%

Africa

Americas

East Mediterranean

South-East Asia

Western Pacific

Europe

2.7%

2.4%

0.2%0.4%

0.0%

1.4%

0.1%1.9%

0.0%

91.0%

Bangladesh Bhutan

India Indonesia

Maldives Myanmar

Nepal Sri Lanka

Thailand Timor-Leste

Leprosy Situation in South-East Asia Region

Annual new case detection 2003

Classification and clinical featuresClassification and clinical features

►►LL BLLL BL BBBB BTBT TTTT

►►Ridley and Ridley and JoplingJopling classification is based on classification is based on clinical, bacteriologic and histopathology in clinical, bacteriologic and histopathology in correlation with correlation with leprominlepromin reactivityreactivity

Lepromatous vs. Tuberculoid Leprosy

LepromatousLepromatous LeprosyLeprosy

Lepromatous Leprosy Pre-and Post-Treatment

PathogenesisPathogenesis

►► The T helper response determine whether an The T helper response determine whether an individual has TT or LL via type IV hypersensitivityindividual has TT or LL via type IV hypersensitivity

►► APC IL12 TH1 APC IL12 TH1 IL2 & IFNIL2 & IFNγγ

►► TT there is high production of IL12 and TT there is high production of IL12 and infilteration of lesion by infilteration of lesion by γγ//δδ TT--cell receptor cell receptor lymphocytes leading to the production of lymphocytes leading to the production of IFNIFNγγ

►► LL there is low level of IL12 or unresponsiveness LL there is low level of IL12 or unresponsiveness of TH1 or a dominate TH2 with production of of TH1 or a dominate TH2 with production of IL4,5,10 which suppress macrophage activation in IL4,5,10 which suppress macrophage activation in response to M. Lepraeresponse to M. Leprae

PathogenesisPathogenesis

►►In some cases paradoxically in LL, In some cases paradoxically in LL, antibodies are produced which are usually antibodies are produced which are usually not protective.not protective.

►►The antibodies form immune complexes The antibodies form immune complexes with free antigen and lead to with free antigen and lead to

►►ErythemaErythema nodosumnodosum leprosumleprosum►►VasculitisVasculitis►►GlomerulonepritisGlomerulonepritis

DiagnosisDiagnosis

►►Microscopy is sensitive for the Microscopy is sensitive for the lepromatouslepromatousform but not for the form but not for the tuberculoustuberculous formform

►►Skin testing is required to confirm the Skin testing is required to confirm the tuberculoustuberculous formform

BURULI ULCER (BU)BURULI ULCER (BU)

IntroductionIntroduction►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.

IntroductionIntroduction-- 22

►Mycobacterium ulcerans is an acid fast is an acid fast bacillus that grows optimally at 32bacillus that grows optimally at 32oCC

►►It infects the skin and subcutaneous tissues It infects the skin and subcutaneous tissues of manof man

►►Survives exposure to UV light briefly so Survives exposure to UV light briefly so open reservoir such as vegetation is unlikelyopen reservoir such as vegetation is unlikely

►►No aquatic or land animal is know to be No aquatic or land animal is know to be naturally infectednaturally infected

►►The typical lesion is an indolent, necrotizing The typical lesion is an indolent, necrotizing ulcerulcer

EpidemiologyEpidemiology

►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 The organism enters the skin by percutaneouspercutaneous/penetrating injection/injuries/penetrating injection/injuries

PathogenesisPathogenesis

► 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. phospholipaseC

► 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)

PathogenesisPathogenesis-- Stage 1Stage 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 1Stage 1-- PreulcerativePreulcerative

PathogenesisPathogenesis-- Stage 2Stage 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 2Stage 2-- Necrotic slough and Necrotic slough and undermined edgesundermined edges

PathogenesisPathogenesis-- Stage 2 (Stage 2 (contdcontd))

►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.

StageStage-- 3 : A 3 : A granulomatousgranulomatous healing healing stage/ response sets instage/ response sets in

Stage 3Stage 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 4Stage 4

► Fibrosis, scarring, calcification and contractures may result.

Treatment Treatment

►►Surgical excision with skin graftingSurgical excision with skin grafting►►Heat therapy to temperatures of up to 40Heat therapy to temperatures of up to 400C C

may inhibit organismmay inhibit organism

ComplicationComplication

►►Broad depressed scars.Broad depressed scars.►►Contracture deformityContracture deformity►►LymphedemaLymphedema►►AmputationAmputation

DEEP MYCOSISDEEP 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.►► SporothrixSporothrix schenckiischenckii► Candida albicans and Penicillium marneffei.

DEEP MYCOSISDEEP MYCOSIS

►►Deep mycoses are caused by primary Deep mycoses are caused by primary pathogenic and opportunistic fungal pathogenic and opportunistic fungal pathogens. pathogens.

►►The primary pathogenic fungi are able to The primary pathogenic fungi are able to establish infection in a normal hostestablish infection in a normal host

►►Opportunistic pathogens require a Opportunistic pathogens require a compromised host in order to establish compromised host in order to establish infection (e.g., cancer, organ infection (e.g., cancer, organ transplantation, surgery, and AIDS transplantation, surgery, and AIDS

►►The primary deep pathogens usually gain The primary deep pathogens usually gain access to the host via the respiratory tract. access to the host via the respiratory tract.

►►Opportunistic fungi causing deep mycosis Opportunistic fungi causing deep mycosis invade via the respiratory tract, alimentary invade via the respiratory tract, alimentary tract, or intravascular devices. tract, or intravascular devices.

Primary systemic fungal pathogensPrimary systemic fungal pathogens

►►CoccidioidesCoccidioides immitisimmitis ((Coccidioidomycosis)►►HistoplasmaHistoplasma CapsulatumCapsulatum ( ( HistoplasmosisHistoplasmosis))►►BlastomycesBlastomyces dermatitidisdermatitidis ((Blastomycosis)►►ParacoccidioidesParacoccidioides brasiliensisbrasiliensis. .

((Paracoccidioidomycosis)►►Among the primary pathogens and Among the primary pathogens and S S schenckiischenckii, ,

the morphological transformation is from a the morphological transformation is from a hyphalhyphal form to a yeastform to a yeast--like form (or spherule in like form (or spherule in the case of the case of C C immitisimmitis) in tissue ) in tissue

►► Among the primary pathogens and Among the primary pathogens and S S schenckiischenckii, , the morphological transformation is from a the morphological transformation is from a hyphalhyphalform to a yeastform to a yeast--like form (or spherule in the case like form (or spherule in the case of of C C immitisimmitis) in tissue ) in tissue

►► However, the dimorphism of However, the dimorphism of Candida Candida albicansalbicans is is somewhat different in that the organism somewhat different in that the organism transforms from a budding yeasttransforms from a budding yeast--like structures like structures ((blastoconidiablastoconidia) to filamentous structures known ) to filamentous structures known as germ tubes as germ tubes

Opportunistic fungal pathogensOpportunistic fungal pathogens

►►Cryptococcus Cryptococcus neoformansneoformans►►CandidaCandida sppspp..►►AspergillusAspergillus sppspp..►►PenicilliumPenicillium marneffeimarneffei►►the the ZygomycetesZygomycetes►►TrichosporonTrichosporon beigeliibeigelii►►FusariumFusarium sppspp

African African histoplasmosishistoplasmosis due to due to H. H. capsulatumcapsulatum varvar. . duboisiiduboisii

►► African African histoplasmosishistoplasmosis is geographically confined is geographically confined to Central Africa. to Central Africa.

►► In the parasitic phase, In the parasitic phase, H. H. capsulatumcapsulatum var. var. duboisiiduboisiiexhibits large, round spores of 10exhibits large, round spores of 10--15 15 µµm. In the m. In the saprophytic phase, the two varieties are saprophytic phase, the two varieties are morphologically indistinguishable.morphologically indistinguishable.

►► Patients with this chronic mycosis always exhibit Patients with this chronic mycosis always exhibit polymorphous cutaneous lesions, bone and lymph polymorphous cutaneous lesions, bone and lymph node involvement and ultimately random deep node involvement and ultimately random deep localisations. localisations.

►► When the disease follows an acute course (e.g. in When the disease follows an acute course (e.g. in AIDSAIDS patients), the yeast cells remain small and patients), the yeast cells remain small and the infection is usually ascribed mistakenly to the the infection is usually ascribed mistakenly to the variety variety capsulatumcapsulatum..

HistoplasmosisHistoplasmosis

HistoplasmosisHistoplasmosis

AspergillosisAspergillosis

►► Invasive Invasive aspergillosisaspergillosis most frequently involves the lungs most frequently involves the lungs and and paranasalparanasal sinuses. sinuses.

►► may disseminate from the lungs to involve the brain, may disseminate from the lungs to involve the brain, kidneys, liver, heart, and bones. kidneys, liver, heart, and bones.

►► The main portal of entry for The main portal of entry for aspergillosisaspergillosis is the respiratory is the respiratory tract, however, injuries to the skin may also introduce the tract, however, injuries to the skin may also introduce the organism into susceptible hosts. organism into susceptible hosts.

►► Quantitative and functional defects in circulating Quantitative and functional defects in circulating neutrophilsneutrophils are key risk factors for development of invasive are key risk factors for development of invasive aspergillosisaspergillosis..

►► For example, For example, neutropenianeutropenia due to due to cytotoxiccytotoxic chemotherapy chemotherapy and systemic corticosteroids are common predisposing and systemic corticosteroids are common predisposing factors for invasive factors for invasive aspergillosisaspergillosis. .

AspergillosisAspergillosis

►► Pulmonary Pulmonary aspergillomaaspergillomaThis colonisation is characterised by the This colonisation is characterised by the development of a free and mobile fungal mass, development of a free and mobile fungal mass, the fungal ball, in a residual lung cavity (80% the fungal ball, in a residual lung cavity (80% postpost--tuberculosis). This mass consists of tuberculosis). This mass consists of interwoven interwoven hyphaehyphae. The most typical symptom is . The most typical symptom is haemoptysis, which can sometimes be profuse. haemoptysis, which can sometimes be profuse. SinusitisSinusitis

►► This chronic, unilateral, usually nonThis chronic, unilateral, usually non--invasive invasive infection is often localised in the maxillary sinus.infection is often localised in the maxillary sinus.

AspergillosisAspergillosis

CandidiasisCandidiasis

►► CandidiasisCandidiasis (due to (due to C C albicansalbicans and other and other CandidaCandidasppspp.) is the most common opportunistic fungal .) is the most common opportunistic fungal infection. infection.

►► Candida Candida albicansalbicans is the most common cause of is the most common cause of candidiasiscandidiasis. .

►► CandidiasisCandidiasis may be classified as superficial or may be classified as superficial or deep. deep.

►► Superficial Superficial candidiasiscandidiasis may involve the epidermal may involve the epidermal and mucosal surfaces, including those of the oral and mucosal surfaces, including those of the oral cavity, pharynx, cavity, pharynx, esophagusesophagus, intestines, urinary , intestines, urinary bladder, and vagina. bladder, and vagina.

CandidiasisCandidiasis

►► The alimentary tract and intravascular catheters The alimentary tract and intravascular catheters are the major portals of entry for deep (or are the major portals of entry for deep (or visceral) visceral) candidiasiscandidiasis. .

►► The kidneys, liver, spleen, brain, eyes, heart, and The kidneys, liver, spleen, brain, eyes, heart, and other tissues are the major organ sites involved in other tissues are the major organ sites involved in deep or visceral deep or visceral candidiasiscandidiasis. .

►► The principal risk factors predisposing to deeply The principal risk factors predisposing to deeply invasive invasive candidiasiscandidiasis are protracted courses of are protracted courses of broad spectrum antibiotics, broad spectrum antibiotics, cytotoxiccytotoxicchemotherapy, corticosteroids, and vascular chemotherapy, corticosteroids, and vascular catheterscatheters

CryptococcosisCryptococcosis

►► CryptococcosisCryptococcosis is most typically an opportunistic is most typically an opportunistic fungal infection that most frequently causes fungal infection that most frequently causes pneumonia and/or meningitis. pneumonia and/or meningitis.

►► Defective cellular immunity, especially that Defective cellular immunity, especially that associated with the acquired immune deficiency associated with the acquired immune deficiency syndrome, is the most common risk factor for syndrome, is the most common risk factor for developing developing cryptococcosiscryptococcosis. .

►► In patients with severe abnormalities of cellular In patients with severe abnormalities of cellular immunity such as immunity such as AIDS AIDS patients, there is often patients, there is often dissemination to multiple foci, including the dissemination to multiple foci, including the prostate prostate

►► PrimaryPrimary cutaneous cutaneous cryptococcosiscryptococcosis (the skin as the (the skin as the portal of entry) is extremely rare. In most cases, portal of entry) is extremely rare. In most cases, infection of the skin should be considered as infection of the skin should be considered as secondarysecondary

CryptococcosisCryptococcosis

►►Drop of Indian ink to CSF will show the Drop of Indian ink to CSF will show the capsule clearlycapsule clearly

►►For histological examination, For histological examination, mucicarminemucicarmine is is preferred, which stains the capsule, in preferred, which stains the capsule, in combination with silver impregnation combination with silver impregnation ((GomoriGomori--GrocottGrocott), which stains the yeast ), which stains the yeast wall. wall.

CryptococcosisCryptococcosis

ZygomycosisZygomycosis

►► Are usually due to Are usually due to RhizopusRhizopus, , RhizomucorRhizomucor, , AbsidiaAbsidia, , MucorMucorspecies, or other members of the class of species, or other members of the class of ZygomycetesZygomycetes, , also causes invasive also causes invasive sinopulmonarysinopulmonary infections. infections.

►► An especially lifeAn especially life--threatening form of threatening form of zygomycosiszygomycosis (also (also known as known as mucormycosismucormycosis), is known as the ), is known as the rhinocerebralrhinocerebralsyndrome, which occurs in diabetics with syndrome, which occurs in diabetics with ketoacidosisketoacidosis. .

►► NeutropeniaNeutropenia and corticosteroids are other major risk and corticosteroids are other major risk factors for factors for zygomycosiszygomycosis. .

►► AspergillusAspergillus sppspp and the and the ZygomycetesZygomycetes have a strong have a strong propensity for invading blood vessels. propensity for invading blood vessels.

►► The fungi appear in tissues as broad, The fungi appear in tissues as broad, nonseptatenonseptate hyphaehyphaeof uneven diameter (diameter ranging from 6 to 50 of uneven diameter (diameter ranging from 6 to 50 µµm) m)

ReferencesReferences

►►http://www.mgm.ufl.edu/~gulig/mmid/lectuhttp://www.mgm.ufl.edu/~gulig/mmid/lectures/Mycology%20Part%201.pdfres/Mycology%20Part%201.pdf-- MycologyMycology

►►http://http://www.ncbi.nlm.nih.gov/books/bv.fcgi?www.ncbi.nlm.nih.gov/books/bv.fcgi?ridrid=mmed.section.4006=mmed.section.4006-- for medical for medical microbiology for microbiology for texastexas medical branchmedical branch

►►www.life.umd.edu/classroom/bsci424/Lecturwww.life.umd.edu/classroom/bsci424/Lectures/LecturePP25Mycobacterium.pptes/LecturePP25Mycobacterium.ppt

►►http://www.itg.be/itg/DistanceLearning/Lecthttp://www.itg.be/itg/DistanceLearning/LectureNotesVandenEndenE/53_Medical_mycoloureNotesVandenEndenE/53_Medical_mycologyp4.htm#T36gyp4.htm#T36