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Cutaneous mycosis

I. Superficial (attacks only stratum corneum, and no host response, and therefore noinflammation): tinea versicolor (hyper or hypopigmented patchesaround neck like a

turtleneck)in the yeast form everyone has it normally, but the hyphae form cauases the

tinea versicolor: main culprit: yeast Malassezia fur furand treated with selsenium sulfide(was entire body), topical azoles (ketoconazole) and in refractory cases systemics (terbinafine

and itraconazole, just like onychomychosis--WHY????); common in humid, hot places

some people get it, some dont, bc some people are more susceptible

II. Cutaneous (infections of the dermis and epidermis with inflammation unlike superficial, butfungi do not invade viable tissue): mucocutaneous candidiasis and DERMATOPHYTOSIS:

a. Microsporum genus cause tiniea capitis, corporis, and pedis, but NOT tinea unguium;most common world wide. Most common species: M. canis

b. Epidermapyhton fluccosum is the only medically important species of the genus andcauses tinea cruris and tinea pedis

c. Tricophyton spp: MOST COMMON IN THE USmost common species is T.tonsuranscan cause infections in all locations:

Dermatophytosis use keratin as their primary source and are characterized by location of

the infection: tinea pedis, tinea corporis, tinea capitis, tinea barbae, tinea cruris (groin),

tinea manuum (hand), tinea unguium (nails); tinea comes from the raised erythema of

tinea corporis,. Cellular immunity is a key factor in control of them so

immunocompromised and HIV patients will have more dermatophytosis.

Dermatophytoses can also be characterized according to their environmental reservoir: 1)

Anthropophilic: in humans (T. Tonsurans), 2) zoophilic: in animals (microsporum

canis), and 3) geophilic: in soil (Microsporum gypseum)

Tinea corporis: ringworm which forms an erythematous, round, raised patch; it can betreated only with topicals such as clotrimazole and miconozole; there is also topical

terbinafine, but it costs more so not preferred

Tinea capitis: occurs in two ways: 1) ectothrix invasion: arthroconidia form on outsideof hair shaft, but cuticle is destroyedbecause it is outside the hair bulb, the hair can

grow back; 2) endothrix invasion: arthroconidia form within hair shaft, leaving cuticle

intactbc it is inside the hair, the bulb is permanently damaged. Breakage of hairs leads

to black dot alopecia, and a kerion forms as a result of increased T cell immune

response which causes even more inflammation and damage to the hair bulbs and can

even cause cervical lymphadenopathy

Tinea capitis mainly happens in children, infants, usually urban people like AfricanAmericans or Hispanics, and transmitted from child to child or from animals (if see

alopecia, ask about petsalso presents with erythema, papules, scaling, exudate); main

species responsible is Tr icophytan tonsuransin the US (causes endothrix invasion and is

more subtle) and it does not fluoresce with Woods lamp; most common tinea capitis in

the world is caused by Microsporum canis(causes the ectothrix invastioncuts straight

through hair); TREATMENT of children with tinea capitis: systemic with fluconazole

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(griseofulvin old school but fluc is better) and terbinafine and topical with ketoconazole

shampoo and selenium sulfide shampoo (Selsen). Do hail pull and culture them, but KOH

is not as good

Tinea pedis is most common dermatophytosis. May be common portal for cellulitisinjury, esp in diabetics. Tri cophyton rubrumis most common cause of tinea pedis;

THREE CLINICAL FORMS: interdigial, moccasin (sole of foot and side), andvesiculobullous; sometime hand can be involved with feet (touching feet causes auto-

inoculation); onychomycosis also can come with tinea pedis; interdigital is easily treated

with topicals such as miconazole and clotrimazole. In the case of onychomycosis, then:

ONYCHOMYCOSIS: source of infection for Staph and strepproblematic for peoplewith vascular disease. The fungus is eating away at the nail bed, and has gotten inside, so

needs to be treated with systemics: itraconazole and terbinafine. Caused by T. rubrum

and T. mentagophytes. Three clinical subtypes:proximal subungual, distal subungual

(DSO), and white superficial (WSO); DSO are most commonhyphae enter distally

under nail plate and spread proximally, digesting stratum corneum of nail bed as well as

nail plate. PSO most common by T. rubrum, almost exclusively presented by

immunocompromisedearly indication of HIV. WSO caused by T. mentagrophytes

minimal inflammation, since dorsal surface of nail is attacked, and no viable tissue is

involvedmore common in water sports

Tinea cruris (groin) is invasion of the hair follicles that can easily be confused withcutaneous candida infection. Concomitant tinea pedis oronychomycosis can predispose

to recurrence suggesting possible transfer of organisms.

Sporotrichosis: gardening, and spreads along nerves, and gets pricked and cant feelON BOARDS sometimes

-If the fungus are resistant, the fungi in the environment need to be destroyed, so get all the clothes and

hair pieces and boil them in the laundry-MOST mycoses are not transmissible but two are: 1) dermatophytosis and 2) vulvovaginal candidiasis(general Candida?)-LAB DIAGNOSIS: KOH orcalcofluorprep of scale scraped from edge of lesion; KOH testdistinguishes between detmatophytes and Candida albicans versus psoriasis. Tinea capitis diagnosed onKOH exam of hair if causesd by Tricophytan spp as spores can attach to or reside on the hair shaft;

culture it on Sabouraud dextrose agar with cycloheximide for four weeks; any growth of dermatophytesis significant, since most dermatophytes are zoophilic or anthropophilic and cannot be contaminants.Tinea capitis baused by Microsporum. Audounii or M. canis fluoresces blue-green under Woods lightexamination

Opportunistic Mycoses

I. Altered T cell function (AIDS, chemotherapy, radiation therapy patients)a. Mucocutaneous candidiasis: (comes from HIV, pregnangy, age, antibiotics): give topicals

(clotrimazole or nystatin), or oral fluconazole but for esophageal where orals cannot begiven, give IV fluconazole, or IV echinocandins

i. oropharyngeal candidiasis (thrush)laryngeal strideor (loud breathing)

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ii. esophageal candidiasis: dysphagia presents, weight loss bc of no eating; only inesophagus with squamous non-keratinized esophagus, and not in gastric mucosa,

since Candida does not do well theregive fluconazoleiii. cutaneous candidiasis: most common in diaper dermatitis of babieskeep dry,

seen only early postpartum; also under breasts, under armpitsfor fat peopleskin surfaces rubbing against each other will be moistred and inflamedbut it

has to have satellites (if only red, then just dermatitis and give steroids); commonin diabetics. Topicals and orals depending

iv. keratitis:v. chronic mucocutaneous candidiasis: inherited disorder of cell immunity to

Candida with concomitant polyendocrinpothies (disease where autoimmunity isagainst several different endocrine organsin this case kidney, thyroid, adrenals,

etc.) Autosomal recessive. Give fluconazoleb. Cryptococcus: yeast that is CAPSULATED; causes meningoencephalitis; main species:

Cryptococcus neoformans. Causes pulmonary disease in some patients as well (atopicpatients), but mainly CNS with meningoencephalitis. Only T lymphopenia not

neutropenia causes it: HIV patients, and immunosuppressed transplant recipients are atincreased risk. CD4 less than 100/microliter. It is also inhaled just like Aspergillus and

Zgomycoses (???????), and replicates in the lung and hematogenously disseminates andactually gets across the BBB, which is why it causes meningoencephalitis. Do LP forCNS diseasethese are humongous bc of the capsule, and the capsule is toxic too, so

tough to eradicate. It is heteropolysaccharide capsule which produces a lot of antigen (soeasily diagnosed by LP) and inhibits phagocytosis, but the antigen is not chemotactic. KOmutants are less virulent. Cryptococcus neoformans also produce phenoloxidase which

produces melanin which inhibits oxygen-dependent killing mechanisms. It is visualizedwith the FONTANA-MASSON stain. Treated by Ampo + 5FC, a lot of relapse, so add

some oral fluconazole a few months later, to prevent it. Fluconazole is a tiny molecule, soit gets across the BBB. Also check intracranial pressure when diagnosing it, bc it cancause elevated pressure and it will get into the calcarian fissure and cause blindness (so

blindness can be caused by Candida endopthamitis and cryptoccus neoformans). If too

much pressure, call neurosurgeon to drain it.c. Pneumocytosis: Pneumocystis car in ii /ji roveciis most common species. Opportunistic

and causes pneumonia, not much else. T cell decrease by HIV, immunosuppression, andcorticosteroids for lupus or something else can increase risk for it. There is infiltrate in

alveolus, so there is shunt with perfusion, but not ventilation, and they are tachypnicandhypoxic, but not chest pain, because it is not ANGIOINVASIVEonly Aspergillusand zygomycoses. Also, Aspergillus does not cause hypoxia to that degree, since itcauses dead space. Treatment: TRIMEOPRIM-SULFAMETHOXAZOLEshuts downfolate synthesis.

II. Altered phagocytic activity (neutropenia)a. Invasive candidiasis (all Candida covered here except mucocutaneous): people at risk are

those with surgery, corticosteroids, neutropenia, bone marrow transplantation that

destroys barriers. Albicans most virulaent and common; it is always present but othercommensals prevent it from taking over, and antibiotics will allow it space. DEEPLYINVASIVE includes candidemia, endocarditis, actue disseminated candidiasis, renalcandidiasis (anything Staph can do, Candida can do it); for this, there needs to be major

destruction-needs help since it cannot get in directly itselfneutropenia, transplantation,surgery, antibiotics. GIVE IV fluconazole, or echinocandins, add AmB as backup forAlbicans. For non-albicans, give echinocandins right away bc it might be resistant.

i. Invasive candidiasis is so virulent because it has powerful adherence andcolonization and can penetrate through mucosal barriers, and is angioinvasive, so

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it has hematognous dissemination; it can get into the eyes, so you need to do adilated retinal exam, so if patient cannot see well, it might be invasive Candidasis

(Candida Endopthalmi tisif it gets into the eye). It generally adheres to thechoriocappilaris (capillary lamina of choroid); they might have broken into thevitreous and grow, and there is then an inflammatory response in the eye, whichis not good; at this point you aspirate out the vitreous and inject AmB in the eye.

If not done, it will destroy the eye, esp the macula. Systemic infections due toinvasive Candida can result in inflammation, but if the person is neutropenic,then the hyphae will grow unhindered. The host response can be seen on an H&Estain, but it is not sensitive for fungal detetion. PAS stains the acid

polysaccharide cell wall of the fungi, and Gamorris Methanamine silver(GMS) deposits silver on the cell wal of the fungus, increasing sensitivity of

detection.ii. In particular, Candida albicans is virulent: it has surface receptorsepithelial

and endothelial cells, and the cell wall can serve to preven immunodetection; italso has hydrolytic enzyme activityacid protease and phospholipases; it has

host mimicry, since it produces a surface complement C3d receptor; it isdimorphic (converts from yeast to hyphal form in hostreverse of classical

dimorphism); germ tube is used for ID; it also activates metalloenzymes (whichour own damaged tissue secretes to destroy tissue, but this time it is not damagedtissue, but the fungus is secreting it to destroy perfectly good tissue). SYSTEMIC

CANDIDIASIS causes disseminated disease and SEPSISb. Aspergillosis: filamentous fungi known as moldsunlike Candida, it is not normally part

of our flora as Candida is. It IS ALWAYS OPPORTUNISTICchronic granulomatous

disease or bone versus host disease from bone marrow transplant for instance. Alwaysask why a person has it, bc there is some immune problem. Normally, in culture, it looks

like a tree with a round bush with the conidia flying off from the top, but in our bodies,they become ANGULAR DICHOTOMOUSLY BRANCHING SEPTATE HYPHAE.Main species fumigatus, which has many of the same virulence factors as Candida

Albicanssuch as adherence receptors, hydrolytic enzymes, complement inhibitor, and

toxins. Treatment: first line therapy is voriconazole, and liposomal AmB (V onvorizonazole like branching septate hyphae).

i. Produces aflatoxins which cause hepatocellular carcinoma from peanuts andgrains in warm temp, and can cause endemic cancer

ii. Can cause allergies in atopic individuals (tendency to develop allergies)iii. Respiratory problems in people who have TB or sarcoidosisAspergilloma in

lungs that cause bleeding and hemoptysis. It ONLY HAPPENS with 1)neutropenic, or 2) corticosteroid patients. Neutropenia is usually a result ofleukemia therapy, corticosteroids for transplant patients, autoimmune disease.

Can also happen with CGD (chronic granulomatous disease). What happens: youinhale the conidia (sporescolloquial); normally, the alverolar macrophages and

defensins/cathepsins will destroy them (through non-oxidative killing), but in the

case of a compromised host, there is no killing either because of lack ofphagocytosis ore lack of fusion of lysosome and phagosome, and there isgermination where the conidia form hyphae and get into the pleural space andeventually blood vessels causing ischemia, thrombosis, and infarction, and

potentially hematogenous dissemination (pleuritis causes pain when inhaling).ASPERGILLUS WILL ALWAYS HAVE DICHOTOMOUSLY BRANCHINGseptate hyphae that is Y shaped. They usually invade blood vessels with necrosisof tissue. Can cause death by infarction of different organs. HALO SIGN: nodulewith dense infarction with light part that is fluid from ischemic alveola that is

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leakingcalssic for angioinvasive organismssuch as Aspergillus. When thepatitent covers from the neutropenia, there is a crescent sign with the neutrophils

coming in, showing intact tissue, and invading, with wedge shape ischemicpotion still present.

iv. Infections: keratitis following corneal traumac. Zygomycosis (Mucormycosis): opportunistic fungi that are ubiquitous; Rhizopusspecies

most common. Diabetics are at high risk forrhinocerebral zygomycosis with infectionin the peri-orbital, ethmoidal sinus area because the zygomyces can eat all the highglucose, and also patients with pulmonary problems who are neutropenic, for the samereasons as Aspergillus. Just like Aspergillus, they are angioinvasive organisms, that causeinfarction. They invade the orbit and eye, and sometimes brain, and can even causecranial nerve palsies. They can directly invade or thrombose the vessels surrounding the

eye or the optic nerve. Much larger than Aspergillus though, (15 vs 5 microns), and theyare NONSEPTATE HYPHAE at right angles, not V shaped like Aspergillus. They grow

so fast, that you need a lid on the culture, and they will push the lid off. They havesporangiosphores which beares a large sac-like structures called sporangia, and that is

filled with sporangiospores which break off like conidia of dermatophytes. HALOimage is for all angioinvasive organisms including zygo. Causes coagulative necrosis of

tissue. TREATMENT ONLY AmB (A for Zbeginning to end), also adjunctive therapyby surgery, and get back innate host defense by stopping the corticosteroids, for example.So three-pronged approach: AmB, with surgery and immune system revitalization. If

disagnose this, start AmB right away, but call ENT surgeon right away

CANDIDA is OPPORTUNISTIC: should not be seen; it is NORMALLY present in the skin, GItract, GU tract, oral mucosa; if white plaques are seen withpseudohypae, hyphae, and budding

yeast cells it is Candida; presents in infants often, since their immune systems are not asadvanced; GIVE Nyastatin to children with it

DO NOT USE ITRACONAZOLE for Candida, and do NOT USE FLUCONAZOLE forAspergillus; do NOT use Voriconazole for Zygo but otherwise Voriconazole is broad spectrumlike AmB (yeasts and molds)

Angioinvasive organisms: Aspergillus and zygomycoses, and Candida Candida can get into eye, but also Cryptococcus neoformans Conidia inhaled for Aspergillus and Blastomyces dermatidis; arthroconydia of Cocci inhaled.

Sporangiospores for zygo; microconidia for Histo.

Aspergillus spores 5 microns. Zygo 15 microns; Blastomyces 15 microns. Cocci spherules 80microns

Ergosterol is also in protozoa such as Leishmania, so AmB can also function against them Clotrimazole/miconazole are topicals for 1) diaper rash, 2) oroesophageal candidiasis, and 3)

vulvo-vaginal candidiasis

Posaconazole is more potent than intra and has a lower MIC All azoles are heptatotoxic; all of them, except for fluconazole are anti-yeast and mold, but

fluconazole is only anti-yeast, so it does not work against Aspergillus; all azoles are eliminated bythe liver, except for fluconazole which goes out by kidney. (AmB goes out by both liver andkidney)

Cultures of fungus are insensitive, and people can go completely undiagnosed, and even die, so abetter way is to use either 1-3 B-D-glucan (for Candida and Aspergillus) and galactomannan (forAspergillus) as a biomarker, and these are part of the cell wall of the fungus and are released in

the bloodstream. These two can also be targeted for cell degradation by echinocandins

Echinocandins are circular to resist proteolytic degradationattacks ONLY Candida andAspergillus

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All routes of elimination are hepatic, and the only ones that are eliminated by the kidney are AmB(liver also), fluconazole (mainly kidney, some liver), and 5FC.

Nystatin for oropharyngeal candidiasis, vulvo-vaginal candidiasis, diaper rash Spores of histo are small in us (2-3 microns) and at 25 C they become humongous macroconidia

with hyphae

Pathogenic Infection

These fungi cause infections in normal, non-immunocompromised hosts; portal of entry: inhalation of

asexual spores from environment; they HAVE SYMPTOMS LIKE TB, but they are not transmitted, bcthey are DIMORPHIC, and in tissue, they are yeasts, and it is in the hyphae form that they reproduce. Sowhen the person has contracted it, they cannot transmit it, bc in them it is in the yeast form. Diseases areasymptomatic or mild in most hosts, but atopic people have DISSEMINATED, PROGRESSIVEINFECTION, but more common in T-cell compromised hosts, or corticosteroids, TNF alpha inhibitors,

etcso happens in normal people, but still increased risk of immune-compromised patientsand that Tcell leukopenic, not neutropenic. Pathology is usually chronic inflammation and granuloma formation.

VERY TOXIC, and can kill people, so if suspected, write it down, so people in micro can put it under

hood. TREATMENT for all of them: itraconazole for stable patients; treat for six months, bc it isintracellular so hard to kill; if person is going into septic shock bc of Histo, unstable, give lipo

formulation AmB, which get into cell

I. H istoplasma capsulatuma. Present in Maryland but mainly in soil and caves enriched with bird or bat fecal material

(Ohio Mississippi River valley regionspretty much all of east US, except for coastlineof Atlantic); fecal matter of birds, especially Starlings, with hyperosmotic is used by

histoplasma since it is too toxic for most bacteria. MICROCONIDIUM are the infectiveinoculum

b. TNF alpha inhibitors such as infliximab, entanercept, adalimumab cause TB infectionand Histothese are both granulomatous diseases, so a histological slide will showcaseating granulomas; distinguish by GMS and PAS test for fungi and acid test for

bacteria. In the early part of the infection, there will be small budding yeast cells in thecytoplasm of macrophages/monocytes (intracellular); then you will see granulomas just

like TB granulomas. Immunosuppressed hosts (such as HIV patients) dont have theability to make good granulomas (like the leprematous leprosy). The neutrophils will nottake part of the inflammatory response. The intracellular histo will not be hyphenated but

only as yeast, because Histo is dimorphic and at 37 turns into yeast. These characteristicfeatures will not be apparent in a culture right away, so DNA probes are used for ID,

otherwise wait two weeksc. Only intracellular, not extracellular; it stays inside to evade killing by phagocytic cells; it

replicates in the phagolysosome by neutralizing acid environment

d. Pulmonary portal of entry; most hosts following low inoculum exposure will beasymptomatic or with mild respiratory symptoms; 5% will have mild to severe

respiratory disease (atopic and also inoculum size dependent); VERY FEW will have theworstDISSEMINATED infections, which occurs in normal hosts, but more in T-cellcompromised.

e. Causes a disease of the reticuloendothelial system (RES)liver, spleen, lymph nodes,bone marrow, with all these other types of macrophages (Kuppfer cells, osteoclasts, etc.)

so the circulating monocytes that connect these various compartments will haveintracellular Histo.

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f. Very similar to Penicil li um marneffeiwhich is indigenous to Southeast AsiaII. Coccidiones immi tis

a. Present in desert soil in southwest USA (south Califronia, New Mexico, west Texas,Arizona)they live in dry areas where the arthroconydia start to fly everywhere where

people can inhale them. If it rains, they form hyphae and feed on surrounding organicmaterial; once it becomes dry, they disseminate once again until it rains and they start to

fly everywhere where people can inhale them. If it rains, they form hyphae and feed onsurrounding organic material; once it becomes dry, they disseminate once again until itrains again; colloquially causes Valley Fever

b. Presents as erythema nodosum which is a red bump on skin due to fat cell accumulationor macrophage accumulation under skin.

c. Atopic people can develop more subtle disease; symptoms are vague and not specific,and diagnosis is not done by symptoms, which can be confused for lung cancer.

d. Exposure by inhalation that disseminates; starts as pulmonary problem, with perhaps abony problem (like Blasto); forms arthroconidia at room temp which is the hyphal form,and then becomes spherules in tissue. Virulent, since only one arthroconidia can kill a

mouse. Spherules are humongous 60-80 microns, and are not yeast, and they release a lotof endospores which can go on and infect the rest of the body; the endospores can be

destroyed by the immune system (the spherules are hard to destroy since they are solarge)

e. Africans and Filipinos are at higher riskIII. Blastomyces dermatidis

a. In Virginia but mainly in water in North Central (Wisconsin, Michigan, Minnesota,Illinois) and south east USA (Alabama, Mississippi)

b. We inhale conidia on the terminal portion of hyphae and it transforms into large 12-15micron (dwarf Histo) yeasts in us; neutrophils attack and then onslaught of macrophages;

it does not involve RES as does Histo, but hits lung, skin, bone, urinary-tract. Presents asbony manifestation. Can simulate lung cancer or other diseases.

IV. Paracoccioides brasil iensisa. Present in South America (Columbia, Brazil)

b. Estrogen protects women from infection, so mainly in malesc. If itraconazole is not present, give trimethoprim sulfamethoxazole (just like pneumocystisinfections)

Big three for respiratory infections: Strep. Pneumonia, H. influenza,