Fungi

Tinea capitis, which instead presents as a circular area of scaling alopecia.

Trichophyton tonsurans is most often causal. Microsporum can also cause it.

Don’t confuse with seborrheic dermatitis, which is caused by Malassezia furfur (also causes tinea versicolor) and presents as an itchy, flaky scalp in someone with otherwise no observable cutaneous findings, or more severely as a scaly, erythematous hairline with weaping papules. Occasionally it affects the face itself.

Candida.

Diabetes causes dysglycemia, which is a major risk factor for candidal skin infections, as well as vulvovaginal candidiasis. This is because persistently elevated glucose can weaken the immune system (i.e., impair neutrophil and macrophage function). In addition, candida likes high-glucose environments, so persistent glycosuria supports growth. And high glucose also facilitates candidal biofilm production and growth on mucosal surfaces.

Yeast are a single-celled fungi and reproduce through budding. They tend to be round or oval in shape.

Latex agglutination testing of the CSF is most accurate, although India ink prep and mucicarmine staining are also often done.

The India ink prep is a spot-diagnosis for C. neoformans. There is a black background, where the only thing that doesn’t stain dark is the halo-like polysaccharide capsule of C. neoformans.

Mucicarmine staining is red. You don’t have to be a pathologist. The vignette might give you an IV drug user with fever, stiff neck, and photophobia (i.e., meningitis symptoms) + they show you this stain, and then the answer is just “C. neoformans,” or “amphotericin B” as the treatment.

Primary CNS lymphoma, not Toxo.

TMP/SMX is also the prophylaxis for Toxoplasmosis, although the treatment for Toxo is instead sulfadiazine and pyrimethamine. What USMLE loves to do is give you a patient with a low CD4 count (e.g., 47) who has ring-enhancing lesion of the brain who is taking HAART and TMP/SMX. The diagnosis is primary CNS lymphoma, not Toxo. And the way we know Toxo is wrong is because the patient is on TMP/SMX, which is the prophylaxis for both Pneumocystis and Toxo. So commencing TMP/SMX at a CD4 count of 200 for PJP is “two birds with one stone” by the time the patient gets to CD4 of 100, which is when Toxo comes in. It’s only patients who aren’t on TMP/SMX by the time they fall to CD4 of 100 who get Toxo.

Itraconazole.

Classic textbook descriptor of the histo is “spherules filled with endospores” (left image), although USMLE doesn’t really give a fuck about that. What they will do is show you the barrel-shaped hyphae (right image) in a patient who lives in California + ask you for the diagnosis –> answer = Coccidiodes. I point this out because, if you know the descriptor “spherules filled with endospores,” but then they show you the image on the right, you’re like what the fuck? So it’s to my observation based on the NBMEs that “barrel-shaped hyphae” is more important for Coccidiodomycosis.

Tinea pedis usually presents as itchy, scaling webs between the toes; the erythematous extension up to the ankle is likely a bacterial cellulitis that has superimposed on the cracked skin.

There is an NBME has a Q where they tell you a febrile patient has itchy, erythematous scaling on the foot that extends up the dorsum of the foot onto the ankle + they ask the cause of the fever in the patient. The wrong answer is Trichophyton. The correct answer is S. aureus. Students get confused by this, but there’s two points: 1) they ask for the cause of the fever; fungi rarely cause fever, whereas S. aureus is a more likely culprit; and 2) tinea pedis usually presents as itchy, scaling webs between the toes; the erythematous extension up to the ankle is likely a bacterial cellulitis that has superimposed on the cracked skin.

Mucorales (i.e., Mucor, Rhizopus, Absidia) have non-septate hyphae that branch at 90-degree (wide) angles. This is in contrast to Aspergillus, which produces branched, 45-degree (acute angle) septate hyphae.

Tinea corporis (ring worm).

The Q can say a patient has pet dogs or uses yoga mats at the gym. USMLE will show you this image and then the answer is just “clotrimazole” or “miconazole.”

We treat tinea corporis, tinea pedis, and tinea cruris with topical -azoles. You need to know clotrimazole and miconazole are specifically topical, whereas others like fluconazole and itraconazole are oral.

Tinea pedis can also be treated with topical terbinafine.

Uncomplicated fungal pneumonia is treated with fluconazole. I believe there’s a UWorld question floating around where they have “no treatment necessary” for simple pneumonia caused by Coccidioides, but this is garbage for USMLE. You give the patient fluconazole.

Treat severe/disseminated infections with IV amphotericin B.

Vulvovaginal (and penile, albeit more rare) candidiasis is treated with oral fluconazole or topical nystatin.

USMLE will give you an easy vignette where they describe thick white discharge per vaginum (buzzy for candida), or they’ll say there’s vulvovaginal erythema and itchiness, without saying there’s discharge, and then show you the image of the pseudohyphae, and then they’ll ask the MOA of the oral agent to be prescribed –> answer = “Inhibition of P-450-mediated demethylation,” which refers to fluconazole. -Azoles inhibit 14α-demethylase, which blocks the conversion of lanosterol to ergosterol (fungal equivalent of cholesterol in the cell membrane). Nystatin pokes holes in the ergosterol membrane.

Oropharyngeal candidiasis is not to be confused with candidal esophagitis, which always occurs in immunocompromised patients. Odynophagia (pain with swallowing) in an immunocompromised patient is candidal esophagitis till proven otherwise. Endoscopy will show white streaks. Treatment is oral fluconazole. In contrast, herpes esophagitis will show punched-out ulcers. CMV esophagitis will show linear/confluent ulcers.

Oropharyngeal candidiasis (oral thrush) can be seen in immunocompromised patients, but it is also seen in asthma patients who use inhaled corticosteroids (e.g., fluticasone). Patients must rinse their mouths out with water following inhaled corticosteroids, otherwise oropharyngeal mucosal immunity can be weakened. Oral thrush presents as white plaques on the palate or tongue that bleed when scraped off. Treatment for oral thrush is nystatin mouthwash. Nystatin pokes holes in the ergosterol cell membrane.

Oropharyngeal candidiasis is not to be confused with candidal esophagitis, which always occurs in immunocompromised patients. Odynophagia (pain with swallowing) in an immunocompromised patient is candidal esophagitis till proven otherwise. Endoscopy will show white streaks. Treatment is oral fluconazole.

Systemic candidal infections can occur in those receiving total parenteral nutrition (TPN; hyperalimentation), since a central venous line can become colonized and TPN contains glucose.

Systemic infections can also occur in those with neutropenia (agranulocytosis).

Serious fungal infection that loves to infect the sinuses, eyes, and brain, causing blindness and death. Infected tissue can appear black.

Immunocompromised patients and those with uncontrolled diabetes are at greatest risk.

USMLE can say a 9-year-old girl has a 4-year history of diabetes + has gangrene of the forehead and sinuses + light microscopy shows 90-degree hyphae –> answer = “mucormycosis” as the diagnosis, or “Rhizopus” as one of the causal fungi, or “amphotericin B” as the treatment.

Cryptococcal neoformans meningitis.

CSF analysis will show low glucose, high protein, and high lymphocytes.

High opening pressure can sometimes be seen with fungal meningitis and may be suggestive, although it is not specific, so do not use it as confirmatory when you are reading vignettes.

Causes fungal meningitis in immunocompromised patients (usually AIDS).

CSF analysis will show low glucose, high protein, and high lymphocytes.

High opening pressure can sometimes be seen with fungal meningitis and may be suggestive, although it is not specific, so do not use it as confirmatory when you are reading vignettes.

Found in the Ohio-Mississippi river valley (although not limited to).

Associated in particular with caves (i.e., spelunking) and bird droppings (i.e., person who feeds pigeons in park).

Aspergillus is also the most common cause of fungal otitis externa. NBME will give a vignette of black necrotic tissue of the ear + simply ask for the diagnosis (i.e., necrotizing otitis externa).

Coccidioides.

Classic textbook descriptor of the histo is “spherules filled with endospores” (left image), although USMLE doesn’t really give a fuck about that. What they will do is show you the barrel-shaped hyphae (right image) in a patient who lives in California + ask you for the diagnosis –> answer = Coccidiodes. I point this out because, if you know the descriptor “spherules filled with endospores,” but then they show you the image on the right, you’re like what the fuck? So it’s to my observation based on the NBMEs that “barrel-shaped hyphae” is more important for Coccidiodomycosis.

Yeast are a single-celled fungi and reproduce through budding. They tend to be round or oval in shape.

Paracoccidioides.

Found usually in South America; also in central America. Easy to remember, as the main species if Paracoccidioides brasiliensis (i.e., Brazil).

Causes pulmonary infections, ulcerative lesions of the pharynx, and skin infections.

Forms a distinctive “captain’s wheel” appearance, which is multiple buds in a radiating pattern from a singular parent cell.

Simple infections are treated with itraconazole. Treat severe/disseminated infections with IV amphotericin B.

The B’s go together – i.e., Broad-based budding for Blastomycosis. This is in contrast to C. neoformans, which is Narrow-based budding.

Yeast that demonstrates narrow-based budding. The N’s go together – i.e., Narrow-based budding for C. neoformans. This is in contrast to Blastomycosis, which is Broad-based budding.

Acute bronchopulmonary Aspergillosis (ABPA) presents as respiratory exacerbation in a patient with asthma or cystic fibrosis who has hypersensitivity to Aspergillus antigens. The diagnosis is easy, so the main point is just that you know ABPA “is a thing” / exists. The vignette will say 30-year-old + Hx of asthma + in respiratory distress and low-grade fever + skin test shows strong reactivity to Aspergillus antigens.

Blastomyces.

Found in the Ohio-Mississippi river valley (although not limited to). Associated in particular with decaying wood.

Likes to cause skin infections, resulting in ulcerative/necrotic lesions. Can sometimes present as pneumonia or osteomyelitis.

Treat simple infections with oral fluconazole. Treat severe/disseminated infections with IV amphotericin B.

Dermatophytes are fungi that cause skin infections.

Trichophyton, Microsporum, Epidermophyton.

Mold is fungus that is multicellular (hyphae) and reproduces via spores.

Sabouraud agar.

Mold is fungus that is multicellular (hyphae) and reproduces via spores.

Found in the Ohio-Mississippi river valley (although not limited to). Associated in particular with decaying wood.

Likes to cause skin infections, resulting in ulcerative/necrotic lesions. Can sometimes present as pneumonia or osteomyelitis.

Treat simple infections with oral fluconazole. Treat severe/disseminated infections with IV amphotericin B.

Malassezia furfur causing tinea versicolor, which is an extremely buzzy and pass-level spot-diagnosis on USMLE. This is a fungal infection of the shoulder blades, back, and upper torso that tends to occur in sub-tropical or tropical areas, where the patient presents with spotty hypopigmentation.

The hypopigmentation is due to fatty acid degradation within the skin, which releases an acidic product by the fungus that inhibits tyrosinase (enzyme necessary for melanin synthesis).

The vignette will give a 24-year-old male who frequently goes surfing in Florida + they show you the buzzy image:

Then the answer is just “topical selenium,” which is extremely HY as the treatment.

Found usually in South America; also in central America. Easy to remember, as the main species if Paracoccidioides brasiliensis (i.e., Brazil).

Causes pulmonary infections, ulcerative lesions of the pharynx, and skin infections.

Forms a distinctive “captain’s wheel” appearance, which is multiple buds in a radiating pattern from a singular parent cell.

Simple infections are treated with itraconazole. Treat severe/disseminated infections with IV amphotericin B.

PJP is diagnosed with bronchoalveolar lavage (after the CXR shows bilateral ground-glass pneumonia), which is when sterile saline is injected into the lungs via a bronchoscope and then aspirated/collected for examination.

Pneumocystis is classically visualized as oval yeast on silver stain.

Oropharyngeal candidiasis (oral thrush) can be seen in immunocompromised patients, but it is also seen in asthma patients who use inhaled corticosteroids (e.g., fluticasone). Patients must rinse their mouths out with water following inhaled corticosteroids, otherwise oropharyngeal mucosal immunity can be weakened. Oral thrush presents as white plaques on the palate or tongue that bleed when scraped off. Treatment for oral thrush is nystatin mouthwash. Nystatin pokes holes in the ergosterol cell membrane.

Oropharyngeal candidiasis is not to be confused with candidal esophagitis, which always occurs in immunocompromised patients. Odynophagia (pain with swallowing) in an immunocompromised patient is candidal esophagitis till proven otherwise. Endoscopy will show white streaks. Treatment is oral fluconazole.

Known for very small size (2-4 μm); smaller than RBCs.

Amphotericin B. It is hard-hitting and used for CNS and disseminated fungal infections.

For example, if a patient has a simple fungal pneumonia, he or she might receive oral fluconazole. But if a patient has fungemia with rigors, chills, and high fever (implying serious systemic infection), then amphotericin B is used.

Forms pseudohyphae. This detail for whatever reason is HY. Hyphae are multicellular structures formed by mold (a form of fungus). However, candida is a yeast, not a mold, so the structures it forms look like hyphae, but they’re not, hence pseudohyphae. The image is HY:

Yeast are a single-celled fungi and reproduce through budding. They tend to be round or oval in shape.

Comes in at a CD4 count of 200 in HIV/AIDS.

Causes bilateral pneumonia (Pneumocystis jiroveciii pneumonia; PJP) in immunocompromised patients (usually HIV/AIDS). Can sometimes be described as “ground-glass,” although this descriptor is only seen in a minority of Qs. A HY point about PJP is that it is specifically bilateral. If the vignette gives you an HIV patient with a lobar pneumonia, the answer is S. pneumo, not PJP. Students get this wrong all of the time, where they choose PJP in an AIDS patient with a lobar pneumonia, and then they’re somehow flummoxed that they got it wrong.

Prophylaxis and treatment is trimethoprim/sulfamethoxazole (TMP/SMX).

The India ink prep is a spot-diagnosis for C. neoformans. There is a black background, where the only thing that doesn’t stain dark is the halo-like polysaccharide capsule of C. neoformans.

Tinea capitis, usually caused by Trichophyton tonsurans or Microsporum.

USMLE will show you this image and then the answer is “oral griseofulvin for patient only”; “oral griseofulvin for patient and classmates” is wrong answer. Or they’ll show the above image and then the answer is just “Trichophyton tonsurans,” where it’s the only fungus listed.

If the USMLE asks how to prevent tinea capitis, the answer is “avoidance of sharing of hats.” Sounds easy, but it’s asked on an NBME and many students get it wrong. They select answers like “use of anti-fungal shampoo” or “avoidance of wooded areas,” which are wrong.

Malassezia furfur.

Fungal infection of the shoulder blades, back, and upper torso that tends to occur in sub-tropical or tropical areas, where the patient presents with spotty hypopigmentation.

The hypopigmentation is due to fatty acid degradation within the skin, which releases an acidic product by the fungus that inhibits tyrosinase (enzyme necessary for melanin synthesis).

The vignette will give a 24-year-old male who frequently goes surfing in Florida + they show you the buzzy image:

Then the answer is just “topical selenium,” which is extremely HY as the treatment.

If the vignette gives you an HIV patient with a lobar pneumonia, the answer is S. pneumo, not Pneumocystis jirovecii. Students get this wrong all of the time, where they choose Pneumocystis in an AIDS patient with a lobar pneumonia, and then they’re somehow flummoxed that they got it wrong.

Pneumocystis causes a bilateral pneumonia, not lobar, It can sometimes be described as “ground-glass,” although this descriptor is only seen in a minority of Qs.

Diaper rash caused by Candida.

Topical -azole such as clotrimazole or miconazole.

Malassezia furfur can also cause seborrheic dermatitis (aka dandruff), which is a fungal infection of the scalp, hairline, and sometimes face. It presents as an itchy, flaky scalp in someone with otherwise no observable cutaneous findings, or more severely as a scaly, erythematous hairline with weaping papules. Occasionally it affects the face itself. This is not to be confused with tinea capitis, which instead presents as a circular area of scaling alopecia.

Seborrheic dermatitis is treated with selenium or -azole shampoo.

Don’t confuse seborrheic dermatitis with seborrheic keratoses, which are dark, stuck-on, greasy lesions on the faces of elderly and smokers, where they appear as though they can be pealed off.

Can  cause pulmonary infections that resemble TB.

Disseminated histoplasmosis can cause adrenal insufficiency (you could be aware of it as a rare cause).

Treat simple infections with oral fluconazole. Treat severe/disseminated infections with IV amphotericin B.

1) Aspergilloma (“fungus ball”), which can present as a nodular density on chest x-ray, especially in those with history of TB. The latter can leave cavities within the lung that Aspergillus likes to occupy. NBME Q wants “biopsy and culture of the mass” as the answer for what is most likely to confirm the diagnosis (makes sense).

2) Acute bronchopulmonary Aspergillosis (ABPA) presents as respiratory exacerbation in a patient with asthma or cystic fibrosis who has hypersensitivity to Aspergillus antigens. The diagnosis is easy, so the main point is just that you know ABPA “is a thing” / exists. The vignette will say 30-year-old + Hx of asthma + in respiratory distress and low-grade fever + skin test shows strong reactivity to Aspergillus antigens.

3) Most common cause of fungal otitis externa. NBME will give a vignette of black necrotic tissue of the ear + simply ask for the diagnosis (i.e., necrotizing otitis externa).

Sporothrix schenckii.

Causes rosette- or daisy-like clusters of conidiophores (spores).

Demonstrates broad-based budding. The B’s go together – i.e., Broad-based budding for Blastomycosis. This is in contrast to C. neoformans, which is Narrow-based budding.

Cutaneous Candida.

Biggest risk factor is diabetes; obesity is wrong. When both answers are listed together, choose diabetes (or dysglycemia). Obesity is only an indirect risk factor in that it leads to insulin resistance and dysglycemia, so the latter is the direct risk factor.

Treatment for candidal skin infections is topical or oral -azole.

Skin infections with Candida tend to occur opportunistically – i.e., in 1) diabetics, 2) immunocompromised patients, or 3) those receiving ongoing broad-spectrum antibiotics (e.g., for endocarditis). In contrast, dermatophyte infections tend to occur sporadically in immunocompetent patients.

Persistent skin infections can occur in those with T cell dysfunction or deficiency – i.e., 4) chronic mucocutaneous candidiasis, which is a T cell dysfunction disorder. The USMLE will give a 17-year-old girl who’s had candidal skin infections since birth, and then the answer will just be “impaired cell-mediated immunity.” The answer can also just be “T cell” for which cell that’s fucked up.

Classic textbook descriptor of the histo is “spherules filled with endospores” (left image), although USMLE doesn’t really give a fuck about that. What they will do is show you the barrel-shaped hyphae (right image) in a patient who lives in California + ask you for the diagnosis –> answer = Coccidiodes. I point this out because, if you know the descriptor “spherules filled with endospores,” but then they show you the image on the right, you’re like what the fuck? So it’s to my observation based on the NBMEs that “barrel-shaped hyphae” is more important for Coccidiodomycosis.

Classically causes a papule at the finger in gardeners following a prick by a rose thorn. This is extremely buzzy and I’d say only mentioned in about 1/3 of vignettes.

The higher yield point about sporotrichosis is that it causes lymphangitis (i.e., lymphocutaneous sporotrichosis), where it ascends to the axilla as either an erythematous streak, or as erythematous ulcerative lesions on the forearm.

What the USMLE will do is show you the above image in guy who was doing house/yard work presents, and then they ask what is causing it (i.e., arteriitis, phlebitis, lymphangitis, etc.), and the answer is just lymphangitis.

You should also be aware tangentially that lymphangitis causing the pink streak can also be caused by general trauma and burns (i.e., it is not limited to sporotrichosis). USMLE can give you a guy who burned his hand + show you the image of the pink streak, and the answer is once again just lymphangitis.

Infections are treated with itraconazole.

Above image is onychomycosis. USMLE can show you this image and then the answer is just “oral terbinafine for 12 weeks.” You don’t have to memorize that 6 weeks is for fingernails and 12 weeks is for toenails. I’m just saying what the answer can show up as, where all the others are clearly wrong. Oral terbinafine is classic for onychomycosis because it has a unique ability to concentrate in keratinous tissues. Topical terbinafine, in contrast, is used for tinea pedis (or topical -azoles).

Mucormycosis.

Mucorales fungi (Mucor, Absidia, Rhizopus) are referred to as “bread mold” and are found ubiquitously in the environment.

Have non-septate hyphae that branch at 90-degree (wide) angles. This is in contrast to Aspergillus, which produces branched, 45-degree (acute angle) septate hyphae.

They cause mucormycosis, which is a serious fungal infection that loves to infect the sinuses, eyes, and brain, causing blindness and death. Infected tissue can appear black.

Immunocompromised patients and those with uncontrolled diabetes are at greatest risk.

USMLE can say a 9-year-old girl has a 4-year history of diabetes + has gangrene of the forehead and sinuses + light microscopy shows 90-degree hyphae –> answer = “mucormycosis” as the diagnosis, or “Rhizopus” as one of the causal fungi, or “amphotericin B” as the treatment.

Malassezia furfur not only causes tinea versicolor, but it also causes seborrheic dermatitis (aka dandruff), which is a fungal infection of the scalp, hairline, and sometimes face. It presents as an itchy, flaky scalp in someone with otherwise no observable cutaneous findings, or more severely as a scaly, erythematous hairline with weaping papules. Occasionally it affects the face itself. This is not to be confused with tinea capitis, which instead presents as a circular area of scaling alopecia.

Seborrheic dermatitis is treated with selenium or -azole shampoo.

Don’t confuse seborrheic dermatitis with seborrheic keratoses, which are dark, stuck-on, greasy lesions on the faces of elderly and smokers, where they appear as though they can be pealed off.

Lymphocutaneous sporotrichosis.

Sporotrichosis only presents in about a third of vignettes as the stereotypical papule on the finger following a prick by a rose thorn in a gardener. That presentation is too easy.

The higher yield point about sporotrichosis is that it causes lymphangitis (i.e., lymphocutaneous sporotrichosis), where it ascends to the axilla as either an erythematous streak, or as erythematous ulcerative lesions on the forearm.

What the USMLE will do is show you the above image in guy who was doing house/yard work presents, and then they ask what is causing it (i.e., arteriitis, phlebitis, lymphangitis, etc.), and the answer is just lymphangitis.

You should also be aware tangentially that lymphangitis causing the pink streak can also be caused by general trauma and burns (i.e., it is not limited to sporotrichosis). USMLE can give you a guy who burned his hand + show you the image of the pink streak, and the answer is once again just lymphangitis.

Cryptococcus neoformans meningitis.

Mucicarmine staining is red. You don’t have to be a pathologist. The vignette might give you an IV drug user with fever, stiff neck, and photophobia (i.e., meningitis symptoms) + they show you this stain, and then the answer is just “C. neoformans,” or “amphotericin B” as the treatment.

Presents usually as uncomplicated fungal pneumonia in patient living in western / south-western United States. Dust is the major risk factor, particularly in the setting of earthquakes (dumb, buzzy event USMLE likes).

Aspergilloma (“fungus ball”), which can present as a nodular density on chest x-ray, especially in those with history of TB. The latter can leave cavities within the lung that Aspergillus likes to occupy. NBME Q wants “biopsy and culture of the mass” as the answer for what is most likely to confirm the diagnosis (makes sense).

Tinea pedis.

Topical terbinafine or -azole (miconazole or clotrimazole).

Paracoccidioidomycosis.

Found usually in South America; also in central America. Easy to remember, as the main species if Paracoccidioides brasiliensis (i.e., Brazil).

Causes pulmonary infections, ulcerative lesions of the pharynx, and skin infections.

Forms a distinctive “captain’s wheel” appearance, which is multiple buds in a radiating pattern from a singular parent cell.

Simple infections are treated with itraconazole. Treat severe/disseminated infections with IV amphotericin B.

Yeast are a single-celled fungi and reproduce through budding. They tend to be round or oval in shape.