L11 Fungal Infection. Introduction. Outline. Fungi. Site of infection

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1 Outline SCPA501: GENERAL PATHOLOGY L11 Fungal Infection Niwat Kangwanrangsan, Ph.D. Department of Pathobiology Faculty of Science, Mahidol University Introduction Pathogenesis of fungal infection Pathology of Fungal infection - superficial - cutaneous - subcutaneous - endemic (primary & systemic) - opportunistic <niwat.kan@mahidol.edu> Introduction Fungi Site of infection eukaryotes* non-motile cell membrane (ergosterol) cell wall (glucan & chitin) enzyme to degrade organic substrates toxin (but not potent to pathogenicity) skin respiratory tract GI tract Urogenital tract

2 Laboratory diagnosis culture - Sabouraud s dextrose agar (SDA) - Inhibitory mold agar (IMA) microscopic examination - Hematoxylin and Eosin (H&E) - Periodic acid-schiff (PAS) - Gomori-methenamine silver (GMS) genetic examination serology Morphologic types of fungi Yeast (unicellular, budding/pseudo-hyphae) Mold (hypha/mycelial, spore) Dimorphic fungi Pathogenesis highly accumulate of fungi related to host immunity (e.g. inflammation, hyperimmune, ) vary in their virulence Fungal infection term mycoses most are opportunists infect to people with impaired immune responses caused by - corticosteroid drugs - antineoplastic therapy - T-cell deficiency (congenital or acquired)

3 Category of major mycoses Pityriasis versicolor (1) Malasseziaspecies highly prevalent, chronic infection of stratum corneum usually on chest, upper back, arms, abdomen M. restricta - seborrheic dermatitis (ie, dandruff) discrete, serpentine hyper-, or hypopigmentedmaculae, may enlarge and coalesce, but scaling, inflammation, and irritation are minimal This common affliction is largely a cosmetic problems

4 Tinea nigra (1) Hortaea werneckii chronic and asymptomatic infection more prevalent in warm coastal regions and among young women lesions appear as dark discoloration (often on palm) skin scrapings will reveal septatehyphae and budding yeast with melanized cell walls White/Black piedra (1) Piedraia hortae Black piedra nodular infection of hair shaft Trichosporon species White piedra present as larger, softer, yellowish nodules on the hairs hair of axilla, genitalia, bread, scalp

5 Dermatophytosis (2) Microsporumspecies, Trichophyton species, Epidermophyton floccosum superficial infection of keratinized tissue, most prevalent in the world fungi proliferate in keratinized tissue and spread centrifugally, producing round, expanding lesions with sharp margins thickening of squamous epithelium, increase number of keratinized cells / hyaline, septate and branching hyphae severe infection shows a mild lymphocytic inflammation hyphae and spore are restricted to the nonviable portion of skin, hair, and nails asymptomatic / chronic / fiercely pruritic eruptions Cutaneous candidiasis (2) Candida albicans and other Candidaspecies skin (intertrigo), mucosa (oropharynx&esophagus; esophagitis), or nails (paronychia) superficial invasion, associated with acute inflammation deep infections are much less common abscesses (yeast, hyphae, necrotic debris, and neutrophils) rarely elicit granulomatous inflammation tender / erythrematouspapules

6 Sporotrichosis (3) Sporothrixschenckii mold form in soil / yeast form in body accidental inoculation from trauma (thorns or splinters) proliferate locally and elicit inflammation ulceronodular lesion / periphery of nodules is granulomatous and the center is suppurative/ pseudoepitheliomatous hyperplasia some yeasts may surrounded by eosinophilic speculated zone, asteroid bodies (Ag-Ab complexes) can be spread along lymphatic drainage extracutaneous disease (joint, bone; ankle, knee, elbow, wrist) Chromoblastomycosis (3) Phialophora verrucosa, Fonsecaea pedrosoi, slowly develop of granulomatous lesions that in time induce hyperplasia of epidermal tissue over months to years, primary lesions become verrucous and wart-like with extension along with lymphatics / clauliflower-like nodules with crusting abscesses eventually cover the area / black dot of hemopurulent dissemination, obstruction and fibrosis of lymphatic vessels are very rare

7 Mycetoma (3) Pheudallescheria boydii, Madurella mycetomatis, chronic subcutaneous infection local swelling of local infected tissue suppuration, abscesses, granulomata, and draining sinuses containing granules mycetomagranules (contain septatehyphae) may range up to 2 mm / the color of granule may provide information of agent lesion may persist for years and extend deeper causing organ deformation and loss of function actinomycetoma(more invasive) eumycetoma Phaeohyphomycosis (3) Histoplasmosis (4) Exophiala, Bipolaris, Exserohilum, hyphae are large and often distort and may and may be found with yeast form melanin in their cell walls can be used for differentiation to other fungi Histoplasma capsulatum primary infection in lung / resembles to TB /commonly found in people with impaired cell-mediated immunity yeast cell has central basophilic body surrounded by a clear zone or halo alveolar macrophage phagocytosemicroconidia/ fungi grow in macrophage before spread out to hilarand mediastinal lymph nodes and then throughout the body acute self-limited histoplasmosis / necrotizing granuloma (caseous material is surrounded by macrophages, Langhansgiant cells, lymphocytes, plasma cells) / granuloma later disappear, the caseous material calcifies and forming fibrocaseous nodule disseminated histoplasmosis progressive organ infiltration with macrophage carrying fungi

8 Blastomycosis (4) Blastomyces dermatitidis chronic granulomatous and suppurative pulmonary disease, often followed by dissemination to other body sites infection produce consolidation of fungi in mixed suppurative and granulomatous inflammation skin and bone are most common sites of extrapulmonary involvement flu-like illness/ fever, arthralgiasand myalgias, weight loss, cough / skin lesion resemble to squamous cell carcinoma / lung infection may appear to resolve but lesion at skin may appear at months to years later Coccidioidomycosis (4) Coccidioides posadasiiand C.immitis begin as local pneumonitis, where the spores are deposit mixed inflammatory cells (neutrophils and macrophages) / necrotizing caseous granuloma development disseminated coccidioidomycosisby involve almost any body site e.g. skin, bone, meninges, liver, spleen, genital tract

9 Paracoccidioidomycosis Paracoccidioides brasiliensis chronic granulomatous infection (mix with suppurative) may involve with lung alone or disseminate to other parts e.g. skin, oropharynx, adrenals, and macrophage of liver, spleen and lymph nodes overall lesions are similar to Blastomycosis (4) Systemic candidiasis (5) Candida albicans and other Candida species most common opportunistic pathogen produce polysaccharides, glycoproteins (agglutinin-like sequence; ALS) to facilitate attachment and invasion local invasion by yeasts and pseudohyphae pyogenic abscess to chronic granuloma containing budding yeast cells and pseudo hyphae administration of broad-spectrum antibiotics often promotes large increases in Candida growth in GI tract, oral, and vaginal mucosa systemic candidiasis yeast enters blood stream by crossing the intestinal mucosa / go to kidney, heart valves / later develops arthritis, meningitis, endophthalmitis Cryptococcosis Cryptococcus neoformans, C. gattii (pigeon droppings) proteoglycan capsule important in pathogenicity fungal meningoencephalitis (lung, skin, liver may also involved) the entire brain is swollen and soft, leptomeninges are thicken and gelatinous from infiltration by thickly encapsulated fungi poorly stain with H&E (appear as bubbles or holes) / PAS or GMS for demonstrate the yeast clearly (5)

10 Aspergillosis (5) Aspergillusfuminatus and other Aspergillusspecies pulmonary aspergillosis: 1)allergic bronchopulmonaryaspergillosis bronchi and bronchioles are infiltrated with lymphocytes, plasma cells, eosinophils 2)colonization of pre-existing pulmonary cavity dense, roundish mass of tangled hyphae with in fibrous cavity / the cavity wall is collagenousfiber with lymphocytes and plasma cells 3)invasive aspergillosis invasion of blood vessels and produces thrombosis / hyphae are arranged radially around blood vessels and extend to their walls

11 Mucormycosis (Zygomycosis) (5) Rhizopus, Lichthemia, Cunninghamella, produce severe, necrotizing, invasive opportunistic infection Fatal Gastrointestinal Mucormycosisin an Infant rhinocerebralmucormycosis proliferate in nasal sinuses, invade surrounding tissues and extend to facial and brain / nasal turbinatesare covered by black crust, underlying tissue is friable and hemorrhagic / hyphae grow into arteries, septic infarction, hemorrhagic encephalitis pulmonary mucormycosis resemble to aspergillosis subcutaneous mucormycosis produce an gradually enlarging, hard inflammatory mass (shoulder, trunk, buttock or thigh) Pneumocystis pneumonia (5) Pneumocystis jiroveci common in AIDS patients or those who treated with corticosteroids or cytotoxic therapy fungi reproduce in associated with alveolar type 1 lining cells, cause progressive consolidation, alveoli contain frothy eosinophilic material (alveolar macrophage, cysts, and trophozoites), in newborns alveolar septa are thickening by lymphoid cells and macrophages(plasma cell pneumonia) fever and progressive shortness of breath, exacerbated by exertion with nonreproductive cough, dyspnea, radiographs show diffuse pulmonary process Diag.:Bronchoscopy,sputuminduction

12 Penicilliosis Penicillium marneffei major risk for infection is HIV/AIDS, TB, corticosteroid treatment, or lymphoproloferation diseases fungemia, skin lesions, systemic involvement of multiple organs, especially reticuloendothelial system can observe papules, pustuls or rashes References Rubin s Pathology; Clinicopathologic Foundations of Medicine (2012). 7th Edition. Wolters Kruwer. Medical Microbiology (2013). 24th Edition. McGraw-Hill Education. (5)