SUBCUTANEOUS MYCOSES 1. SPOROTHRICOSIS 2. CHROMOBLASTOMYCOSIS 3. PHEOHYPOMYCOSIS 4.

MYCETOMA

Acquired through: TRAUMA & INHALATION

SPOROTHRIX SCHENKII
AKA: Rose Gardeners disease D/t trauma of the skin from picking roses Thermally DIMORPHIC FUNGUS 2 FORMS o MOLD @ room temperature/ ambient INFECTIVE STAGE o YEAST @ body temp (35-37 C)/ small budding PATHOGENIC STAGE CULTURE o Routine agar media using SABOURAUDs o Young colonies blackish & shiny o With age wrinkled & fuzzy MICROSCOPICALLY o Branching septate hyphae with distinct small conidia, delicately at the ends of tapering conidiophores Ubiquitous/ saprophytic lives in decaying wounds Occurs worldwide but most common in TROPICAL & SUBTROPICAL regions, endemic in Mexico, south Africa, & japan Isolated from: SOIL & PLANTS o Hay, straw, thorny plants esp. roses, sphagnum moss, decaying wood, pine, prairie grass vegetations) 75% of cases occur in MALE (coz mostly gardeners are males) o Maybe d/t increased exposure or X-linked)

OTHER FORMS PRIMARY PULMONARY SPOROTRICHOSIS o Inhalation of conidia o Mimics chronic cavitary TB among patients with impaired cell-mediated immunity DISSEMINATION in EYES, BONES & JOINTS, rarely in the MENINGES DIAGNOSTICS SPECIMEN Biopsy material or exudate from lesions MICROSCOPIC EXAMINATION KOH or CALCOFLOUR WHITE STAIN to digest the keratin GOMORIs methenamine silver see black cell wall Periodic Acid-Schiff (PAS) stain see red cell wall Flourescent antibody staining H&E stain: ASTEROID BODY* CULTURE SABORAUDs agar SEROLOGY only done in endemic area SPROROTRICHIN skin test o Antigen for skin test o Delayed hypersensitivity YEAST cell agglutination test o To indicate if + or has recovered already o 1:160 positive o 1:40 recovered patient TREATMENT Self-limited Solution of saturated potassium iodide (SSKI) o Oral o Topical DOC: AZOLES inhibit ergosterol synthesis of cell membrane Oral ITRACONAZOLE AMPHOTERICIN B o DOC for systemic disease o IV route o Wof renal toxicity

NICE TO KNOW Occurs mainly in tropics Saprophytic in nature Occurring on vegetation & soil

CHROMOBLASTOMYCOSIS
Caused by: DEMATIACEOUS FUNGI o An imperfect fungi that provide varying amount of melanin-like pigments o Imperfect lack of sexual spore

Rarely, elephantiasis develops farmers! LABORATORY DX SPECIMEN: scrapings or biopsies from lesion MICROSCOPIC EXAMINATION 10% KOH reveals dark spherical cells H&E stain o Sclerotic cells inside an abscess* o Round, thick-walled, cigarcolored structures CULTURE SABORAUDs agar o Black velvety colony o Unable to grow at 37 C TREATMENT Surgical excision FLUCYTOSINE or ITRACONAZOLE Local applied heat Relapse is common!

DSE: SPOROTRICHOSIS LYMPHOCUTANEOUS o 75% of cases o Introduced in the skin by trauma Chronic type Fixed type o Seen in endemic areas o Not common; self limited

OTHER SPP PHIALOPHORA VERRUCOSA o The conida are produced from flask-shaped phialides with cup shaped collaretes o Mature, spherical to oval conidia are extruded from the phialide & usually accumulate around it CLDOSPORUM CARIONII o Elongated conidiospores with long, branching chains of oval conidia FONSECA PEDROSOI o Polymorphic, mostly short braniching chains Phialides Chains of blastoconidia Sympoidal, rhinocladiella type RHINOCLADIELLA AQUASPERA o Produces lateral or terminal conidia from a lengthening conidiogenous cell o Conidia are elliptical to clavate (sausage-shaped) FONSECA COMPACTA o Blastoconidia are spherical, with a broad base connecting the conidia CLINICAL FINDINGS Acquired through trauma in the skin Verrucous & wart-like over months to years extending along draining lymphatics cauliflower-like nodules with crusting abscesses black-dots on warty surface*

PHAEOHYPOMYCOSIS
Common causative agents are: o Exiophiala jeanselmei o Phialophora richardsiae o Bipolaris specifera o Wangiella dermatitidis Presence of darkly pigmented septate hyphae in tissue

CLINICAL FINDINGS Vary from solitary encapsulated cysts in the subQ tissue To sinusitis To brain abscesses (Cladophialophora LABORATORY FINDINGS Brown, olivaceous black or black colony TREATMENT Itraconazole, subQ Flucytosine, subQ Amp B in case of brain abscess

Prepared by: EGBIIMD; 09-02-11

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MYCETOMA
DISEASE Chronic subcutaneous infections same w/ sporotrichosis Actinomycetoma caused by actinomycete (bacteria) Eumycetoma (fungi) o Maduramycosis, Madura foot o Caused by fungi o Prone to farmers ETIOLOGIC AGENT Pseudallescheria boydii white granules Exiophiala jenselmei black granules o Phaeohypomycosis Madurella grisea black granules Acromnium falciforme white granules CLINICAL FINDINGS Suppuration & abscess formation Granuloma Draining sinuses containing the granules LABORATORY DIAGNOSIS Histo: black grain mycetoma: due to Madurella mycetomatis using o Gridley stain Mycetoma with presence of geotrichum o A hair-like appendeges tissue form of fungi Blaack grain mycetoma: subQ nodule d/t Madurella mycetomatis TREATMENT Surgical debridement or excision & chemotherapy Topical Nystatin or Miconazole P. boydii Itraconazole, Ketoconazole, Amp B E.jeanselmei

GENERAL FEATURES Causative agents: are thermally dimorphic Exist in NATURE, SOIL Geographic distribution varies MOT: Inhalation Pulmonary infection Sissemination o Inhaled mold (conidia) NO evidence of transmission among humans or animals (not zoonotic) Otherwise healthy individuals are affected Infection requires a LARGE inoculum (except coccidiomycosis) & a SUSCEPTIBLE host Infection often occurs in ENDEMIC AREAS Most infections are: o Asymptomatic or o Self-limiting In immune-compromised hosts, infections are more often FATAL

IMMUNE COMPLEX FORMATION o Deposition leading to local inflammatory reactions o Immunosuppression resulting from the binding of complexes to cells bearing Fc receptors

Itraconazole can be for maintenance; less toxic; cant cross BBB Fluconazole particularly for meningitis; crosses BBB

COCCIDIOMYCOSIS
core in abarrel Etio: Coccidioides immitis Loc: Confined to southwestern US, northern Mexico, Central & South America Microbiology o 37 C (tissue): spherule filled with endospores o 25 C: hyphae, barrel-shaped arthroconidia

CLINICAL FINDINGS PRIMARY INFECTION o Asymptomatic (60%) o VALLEY fever (40%) San Joaquin valley f Influenza-like illness Fever, malaise Cough, arthralgia Headache o Nodular lesions in lungs o (+) skin test in 2 -4 weeks, remain for life SECONDARY (DISSEMINATED) INFN o 1%, rare o Chronic/ fulminant infection o Infection of lungs, meninges, bones & skin LABORATORY DIAGNOSIS HISTOPATHOLOGY Spherules or endospores seen in sputum, exudates or tissue affected CULTURE SDA: mould colonies at 25 C Spherule production in vitro by incubation in an enriched medium at 40 C + 20% CO2 SEROLOGY Compliment fixation assay (in CSF), particle agglutination assay SKIN TEST Utilizing COCCIDIOLIN & SPHERULINE antigen *specific test (-) result may rule out diagnosis *In infected tissues, C. immitis appears as a mixture of endospores & spherules TREATMENT Symptomatic tx for primary infection Antifungal agents for disseminated infn o Amp B max. for 1 mon; nephrotoxic

HISTOPLASMOSIS
Etio: Histoplasma capsulatum o Not capsulated! o All fungi are capsulated EXCEPT Cryptococcus Neoformans Reservoir: soil, bat & avian habitats Loc: may be prevalent all over the world, but the incidence varies widely (most endemic in Ohi, Mississipi, Kentucky) Microscopically: o @ 37 C yeast cell in tissue o @ 25 C hyphae, microconidia & macroconidia o (+) tuberculate chlamydospore

EPIDEMIOLOGY Inhalation of conidia from environment is source of infection More likely in endemic areas: o Atlantic ocean to N. Dakota (500 000 cases/ year in US), except New England & Florida o Most cases occur in Ohio Valley & Mississippi Valley PATHOGENESIS Inhalation of microconidia/ primary cutaneous inoculation Conversion to budding yeast cells Phagocytosis by alveolar macrophages Restriction of growth or dissemination to RES by bloodstream Suppression of cell-mediated immunity IMMUNE RESPONSE o Cell-mediated responses are primary importance o Phagocytic activity of macrophage considered an important component of resistance to drugs o Activated macrophage can kill yeast cells EVASION OF HOST DEFENSE: o Survival in macrophages elevated pH of phagosomes

SYSTEMIC MYCOSES 1. COCCIDIOIDOMYCOSIS 2. HISTOPLASMOSIS 3. BLASTOMYCOSIS 4. PARACOCCIDIOIDOMYCOSIS *ALL are dimorphic *Systemic fungal infections are UNCOMMON!

EPIDEMIOLOGY Endemic in hot, semi-arid regions (SW USA & Mexico) Reservoir: soil & indigenous rodents Highest during SUMMER & AUTUMN, when DUST is most prevalent Considered to be the MOST virulent of fungal pathogens INHALATION of a single spore can initiate infection PATHOGENESIS INHALATION of the infectious particle, arthroconidia & spherule formation in vivo ENGULFENT within phagosomes by alveolar macrophages ACTIVATION of macrophages phagosome-lysosome fusion killing

Prepared by: EGBIIMD; 09-02-11

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Yeast cells absorb IRON (siderophore) & Calcium from host Alteration of cell surface

BLASTOMYCOSIS
Etio: Blastomyces dermatitidis Loc: America, Africa, Asia Microbiology o Yeast @ 37C single bud is attached to parent cell by a broad base o Hyphae & conidia @ 25 C

CLINCAL FINDINGS PULMONARY INFECTION o Asymptomatic (95%) o Mild/ moderate/ severe/ chronic cavitary DISSEMINATED INFECTION (1/200) o RES (liver, spleen, LN, BM) o Mucocutaneous infection PRIMARY CUTANEOUS INFECTION LABORATORY DIAGNOSIS Histology CULTURE of blood or bone marrow SEROLOGY o Test for antibody & histoplasma antigen in blood & urine ANTIGEN o In HIV-infected patients with disseminated histoplasmosis, histoplasma antigen detection in serum & urine is at least 50% & 90% sensitive TREATMENT NOT required for several cases ANTIFUNGAL o AMP B o Itraconazole *Surgical resection of pulmonary lesions

BLASTOMYCOSIS o A granulomatous mycotic infections of: Lungs Skin Can spread to other

PARACOCCIDIOMYCOSIS
AKA: South American Blastomycosis Etio: Paracoccidiodes brasiliensis Thermally dimorphic fungi @ 36 C multiple budding yeast cells

EPIDEMIOLOGY Most cases are in southern, central, & southeastern USA Infection is by inhalation of spores Risk factors: o Occupation contact with soil (farmers) o Owning a DOG! o Living in ENDEMIC AREA PATHOGENESIS Inhalation of infectious particles PRIMARY cutaneous inoculation INFILTRATION of macrophages & neutrophils & granuloma formation Oxidative killing mechanisms of neutrophils & fungicidal activity of macrophages DEFENSE SYSTEM o Alveolar macrophage provide a modest 1st line of defense o T-cell stimulated PMNs kill Blastomyces cells by oxidative mechanisms CONIDIA are more sensitive to killing by PMNs coz yeast are too big o TH-1 response with primary importance EVASION OF DEFENSES o Escapes phagocytosis by neutrophils & monocytes by shedding its surface antigen after infection CLINICAL FINDINGS Asymptomatic infection Primary cutaneous infection Pulmonary infection Chronic cutaneous infection o SubQ nodule, ulceration Disseminated infection o Skin, bone, GUT, CNS, spleen

LABORATORY DIAGNOSIS Direct microscopic exam o KOH o H&E Culture Serology o Immunodiffusion test o ELISA to detect antibody to exoantigen A Skin test (BLASTOMYCIN Ag) o Limited/ NO dx.value TREATMENT Amp B for systemic Itraconazole Fluconazole in case of meningitis Corrective surgery

EPIDEMIOLOGY Mostly in RURAL areas of Latin America, particularly farmers MALES more than females NOT communicable! PATHOGENESIS & CLINICAL FINDINGS Inhaled, initial lesion occurs in the LUNGS Pulmonary granuloma chronic, progressive disease dissemination May spread into the skin, mucocutaneous tissues. LN, spleen, liver, adrenals & other sites LABORATORY DIAGNOSIS Microscopic examination: KOH Culture Serology o Complement fixation o Immunodiffusion TREATMENT Co-trimoxazole super infection Itraconazole Ketoconazole Amp B

Prepared by: EGBIIMD; 09-02-11

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Opportunistic Mycoses 1. Candidiasis 2. Cryptococcosis 3. Aspergillosis 4. Mucormycosis

CutaneousCandidiasis -Red -Moist -May develop vesicles Onychomycosis -Painful -Erythematous swelling of the nail fold (Drumstick appearance) -Destroy nails Risk Factors: -AIDS -Pregnancy -DM -Young and old -Pills -Trauma (Burns, maceration) -Treatment with Cortocosteroids/Antibiotics -Cellular immunodeficiency Systemic Candidiasis Candidemia Indwelling catheters, surgery, IV drug abuse, aspiration, damage to the skin or GIT Endocarditis Deposition and growth of yeast and pseudohyphae on prosthetic heart valves or vegetations UTI Foley catheters, Diabetes, Pregnancy, Antibacterial antibiotics Chronic Mucocutaneous Candidiasis Rare Onset: Early childhood III. TREATMENT: Superficial: Topical Nystatin / OralKetoconazole/ Fluconazole Systemic: Amp B + Oral flucytosisne/Fluconazole/ Caspofungin Eliminate contributing factors IV. PREVENTION: -Avoid disturbance of normal flora -NOT communicable

Cryptococcosis
Important sp: -Cryptococcus neoformans -Cryptococcus gattii Reservoir: -Bird droppings (Pigeon) Mode of transmission: -Inhalation of dessicated yeast/ smaller basidiospres I. DISEASES C. neoformans Morphology: -Spherical, budding yeast -Thick non-staining capsule -Produce whitish mucoid colonies 2-3days at 37 C -(+) Laccase Chronic meningitis -HA, Stiff neck, disorientation -Fatal if untreated -NOT contagious -Diff Dx: Brain tumor, Brain abscess, Degenerative CNS disease, Mycobacterialor other Fungalmenigitis Dx: Culture (w/o Cycloheximide); Serology (Latexagglutination) II. TREATMENT: -Amp B + Flucytosine(Standard) -Fluconazole III. PREVENTION: -Avoid exposure to reservoir

Aspergillosis
Important sp: -Aspergillus fumigatus(most common) -A. flavus -A. niger -A. terreus -A. lentulus MOT: Inhalation of conidia Morphology: -Long conidiospores with terminal vesicles on which phialides produce basipetal chains of conidia -Cottony colonies I. DISEASES Allergic Forms -Asthmatic reaction upon exposure Aspergilloma (fungus ball) -Inhaled conidia enter preexisting cavities -Previous Cavitary Disease (Tuberculosis, sarcoidosis, Emphysema) -Cough, dyspnea, weight loss, fatigue, hemoptysis Invasive Forms -Spread to GIT, kidney, liver, brain, other Organs II. TREATMENT -AmphotericinB -Itraconazole -Voriconazole -Posaconazole -Surgery III. PREVENTION -Monitor airborne contaminants in patients rooms -Reduce visiting -Isolate patient

Candidiasis
Normal Flora Most common systemic mycosis Important sp: -Candida albicans -Candida tropicalis -Candida parapsilosis -Candida glabrata -Candida guillermondii -Candida dubliniensis I. LABORATORY DIAGNOSIS Morphology: -Pseudohyphae -Clamydoconidia -Blastoconidia (Budding yeast) BAP -Moist, opaque colonies SDA -Soft, cream-colored colonies with yeast odor Germ Tube -Differentiating test -Serum; 37C X 90mins -True hyphae II. DISEASES Superficial Candidiasis Thrush -Tongue -Lips -Gums -Palate Patchy to confluent Whitish pseudomembrane (Epith. Cell, yeast, pseudohyphae) Vulvovaginitis -Irritating -Pruritic -Discharge

Prepared by: EGBIIMD; 09-02-11

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Mucormycosis
Important members: -Rhizopus sp. -Rhizomucor sp. -Absidia sp. -Cunninghamella sp. -Mucor sp. I. DISEASES Rhinocerebral mucormycosis -Germination of the sporangiospores in the nasal passages -Invasion of the hyphae into the blood vessels, causing thrombosis, infarction, and necrosis Thoracic mucormycosis -Inhalation of the sporangiospores with invasion of the lung parenchyma and vasculature II. TREATMENT -Aggressive surgical debridement -Amphotericin B -Control underlying disease

-Giemsa, Toluidine blue, Methamine silver, Calcoflour white

Treatment: -Trimethoprim-Sulfamethoxazole -Pentamidine isethionate

Penicilliosis
Important sp: Penicillium marneffei Reservoir: Soil; Soil associated with bamboo rats Morphology: -Septate, branching hyphae bearing phialides and basipetal chains of conidia -In tissue, unicellular yeast-like cells -Green-yellow colonies with diffusible reddish pigment Manifestation: -Cough, fever, fatigue, weight loss, lymphadenopathy -Cutaneous and subcutaneous papules, pustules or rashes Treatment: -Amphotericin B -Then Itraconazole -90% mortality if without treatment

Pneumocystis pneumonia
Pneumocystis jiroveci Pneumonia in immunosuppressed patients Previously a Protozoa (cysts and Trophozoite forms) Ascomycetes Reservoir: Maybe an obligate member of the normal flora Transmission: Aerosols Morphology: -Thick-walled cysts; spherical to elliptical 4-8 nuclei -Thin-walled trophozoite

Prepared by: EGBIIMD; 09-02-11

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