Diseases Of The Skin 2 Pdf

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 ► ►

► ► 1. 2. 3. 4. 5.

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 Skin Upper respiratory tract Superficial peripheral nerves Testes 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 12 Million

1998

2000

2003

< 1 Million

0.6 Million

0.5 Million

The dramatic decline is attributed to the effective use of multi-drug therapy(MDT) Parameter 1. Number of Countries with Prevalence Rates of > 1/10,000 population

1985

2000

122

14

2003 9

2. Global Prevalence

10/10,000

1/10,000

< 1/10,000

3. Patients on MDT

< 10%

100%

100%

4. Patients Cured

Accurate Data Not Available

11.2 million

13.5 million

5. Drug Resistance

High-since single drugdapsone was given for long periods, in low doses

NIL- Multi-Drug Resistance following MDT is NOT reported

NIL - Multi-Drug Resistance following MDT is NOT reported

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%

19%

0%

Africa

Americas

East Mediterranean

South-East Asia

Western Pacific

Europe

GLOBAL LEPROSY SITUATION IN 2004 Annual new case detection 2003

1% 81% 0%

Africa

7%

Americas East Mediterranean South-East Asia Western Pacific Europe

1%

10%

Leprosy Situation in South-East Asia Region Annual new case detection 2003

91.0%

2.4% 0.0% Bangladesh

Bhutan

India

Indonesia

Maldives

Myanmar

Nepal

Sri Lanka

Thailand

Timor-Leste

0.0% 1.9%

2.7% 0.4%

0.1% 0.2%

1.4%

Classification and clinical features

► LL

► Ridley

BL

BB

BT

TT

and Jopling classification is based on clinical, bacteriologic and histopathology in correlation with lepromin reactivity

Lepromatous vs. Tuberculoid Leprosy

Lepromatous Leprosy

Lepromatous Leprosy Preand Post-Treatment

Pathogenesis ► The

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

► APC ► TT

IL12

TH1

IL2 & IFNγ

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 ► Surgical

excision 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

► The

primary 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

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 ► Among

Opportunistic fungal pathogens ► Cryptococcus

neoformans

► Candida

spp. ► Aspergillus spp. ► Penicillium ► the

marneffei

Zygomycetes

► Trichosporon ► Fusarium

spp

beigelii

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 (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

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