#495 Fungal Infections -Histo/Blasto/Cocci with Dr. Andrej Spec

August 18, 2025 | By Beth “Garbs” Gasperlin

Audio

Video

Transcript available via YouTube

Why we need to stop calling them “endemic” mycoses & more fungi fun!

Feeling muddled about endemic mycoses? We tackle the clinical presentation of diseases like histoplasmosis, blastomycosis, and coccidioidomycosis, the importance of testing, and how to diagnose fungal infections  with our esteemed guest Dr. Andrej Spec, MD!

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Show Segments

• Introduction and icebreaker,  Fish Club?!  00:00
• Case 1 from Kashlak 07:27
• Diagnostic framework for dimorphic fungi 11:58
• Imaging presentations for fungal pneumonia, diagnostic schemas 18:23
• Testing options 27:48
• Treatment options 35:44
• Dimorphic Fungi Mnemonics 45:50
• Retail testing for mold 48:47
• Case 2 from Kashlak 56: 42
• Takeaways and Conclusions 1:05:19

Endemic Fungi Pearls

1. Endemic fungi or endemic mycoses are a subset of the thermally dimorphic fungi. In the domestic United States, histoplasmosis, blastomycosis, and coccidioidomycosis are commonly called endemic. However, these organisms are found globally (Ashraf 2020)  so the use of the word ‘endemic’ is somewhat misleading. 
2. Dimorphic fungi are not uncommon causes of respiratory disease, we just miss them.  For example, in one retrospective review of insurance claims data, over 80% of patients with histoplasmosis had at least 1 missed opportunity for diagnosis, but an average of up to 4 missed opportunities (Miller 2022). In the southwest United States, coccidioides is potentially implicated in up to ⅓ of community-acquired pneumonia cases (Valdivia 2006). 
3. If you have a patient who has failed one round of antibiotics for pneumonia, that should be a big red flag to evaluate for a fungal  diagnosis, per Dr. Spec. The CDC algorithm details a diagnostic pathway that may be considered (CDC 2023, CDC 2024). 
4. Also, it’s Dr. Spec’s expert opinion to let your lab team know when you have high clinical suspicion of these pathogens and are sending tissue for culture! The laboratory team needs to take care of them in a specific way so lab techs do not get infected. 
5. Reach out to ID if testing results are positive for the endemic mycoses! Generally, outpatients are treated with azoles and inpatients are treated with amphotericin B. 

What are ‘Endemic Fungi’? 

Endemic fungi or endemic mycoses are a subset of thermally dimorphic fungi. In the domestic United States, histoplasmosis, blastomycosis, and coccidioidomycosis are commonly called endemic. However, these organisms are found globally (Ashraf 2020)  so the use of the word ‘endemic’ is somewhat misleading. 

Dr. Spec says this geographic misunderstanding can lead to diagnostic errors due to delayed diagnosis, because providers may fail to consider these infections in their differential (“the diagnostic stewards in us are probably our biggest enemy– it is better to test early, test often and test broadly.”). These organisms are not uncommon causes of respiratory disease–we just miss them.  For example, in one retrospective review of insurance claims data, over 80% of patients with histoplasmosis had at least one missed opportunity for diagnosis, but an average of up to 4 missed opportunities (Miller 2022). In the southwest United States, coccidioides is potentially implicated in up to ⅓ of community-acquired pneumonia cases (Valdivia 2006). 

“The Maps are Changing”

Traditionally, histoplasmosis has been associated with the Ohio and Mississippi River Valleys. Blastomycosis has been associated with the Ohio and Mississippi River Valleys, Great Lakes region, and Southeastern United States. Coccidioidomycosis has been associated with the Southwestern United States.  Climate change seems to be broadening the map for these organisms. 

Coccidioidomycosis is projected to march northward (Gorris 2019). Histo and Blasto are moving eastward and north (Ashraf 2020, Benedict 2021, Borah 2024). As such, if you have a patient with subacute dyspnea and antibiotic failure, Dr. Spec recommends considering testing for all three pathogens. 

How Fungal Pneumonias Present

 It is worth noting that most patients who are exposed will have  self-limiting infections, per Dr. Spec. However, a subset goes on to develop more subacute disease that does not resolve. All of these patients will have pulmonary involvement. It usually starts as a subacute pneumonia for all three presentations. Dr. Spec notes that coccidioidomycosis might sometimes present more acutely.  In immunocompetent patients, the incubation period may be quite long.  If you have a patient who has failed one round of antibiotics for pneumonia that should be a big red flag for evaluating for a fungal infection, per Dr. Spec. The CDC algorithm details a diagnostic pathway that may be considered (CDC 2023, CDC 2024). 

While blastomycosis and coccidioidomycosis can be associated with consolidations, generally speaking, fungal pneumonias will cause an interstitial pneumonia that might not be impressive on a plain film x-ray, per Dr. Spec.  Because it’s a systemic infection, B-symptoms such as fever, chills, nightsweats, anorexia, and weight loss can also present with fungal pneumonia.  In particular, if you’re invoking etiologies such as malignancy or sarcoid, consider also testing for these dimorphic fungi (per Dr. Spec: “You can’t call it Sarcoid until you test for mycoses!”).  Blastomycosis may cause pseudoepitheliomatous hyperplasia on biopsy which Dr. Spec has seen mistaken for malignancy. Concomitant skin reactions (especially in coccidioidomycosis – Garcia 2015, DiCaudo 2006) are also quite common in these infections (Melton 2023, Ortega-Loayza 2013, Chang 2012). Remain skeptical of travel histories, per Dr. Spec, as some patients might be less than forthcoming or may simply forget recent relevant travel.  

Dr. Spec associates wooded areas/wetlands with blastomycosis and flood plains/caves with histoplasmosis. All three pathogens can have a spectrum of intensity for symptoms. Generally, immunocompromised or relatively immunosuppressed patients will have a more severe presentation than immunocompetent patients.  

Dr. Spec uses the analogy of driving on a highway– the immunocompetent patient might take 6 months for continued symptoms whereas an immunosuppressed patient might be barrelling down the highway to disseminate disease much more quickly.  One nuance is that with ARDS-associated blastomycosis there is strongly believed to be an to inoculum effect for severity of disease (Venkata 2020)

Testing Basics

For histoplasmosis and blastomycosis, you may order both urine antigen and serum antibodies (Thompson 2022). It is worth noting that blasto and histo have high cross-reactivity for the urine antigen testing. Testing for coccidioidomycosis requires testing serum antibodies (Thompson 2022).  Dr. Spec’s expert opinion is that if these are negative but you have a high clinical suspicion, you may repeat at intervals from 6 weeks up to 6 months after. Dr. Spec also generally checks cryptococcal antigen in patients where he suspects a dimorphic fungus.  IgM EIA tests have a high false positive, per Dr. Spec, however, because of the long time to develop symptoms, most patients will have developed their IgG response. Complement fixation testing exists as well, but this is beyond the scope of what would be tested in a primary care setting.

When you get positives for your patient’s antigen or antibody testing, it is completely reasonable to reach out to your local Infectious Disease team. 

Stay Cultured

Per Dr. Spec, these pathogens often don’t follow the textbook for how they present in culture. Coccidioides will appear large and a spherule (Homer 2024) with yeast inside of it. Blastomycosis is more extracellular and with broad based budding (McBride 2018) , although can be impacted by how the slide is sliced. Histoplasma will be intracellular (Valdez 2022) and in the Giemsa stain it has a pseudocapsule. Dr. Spec notes that pathologists will often be cautious in how they describe fungi.  Also, it’s his expert opinion to let your lab team know when you have high clinical suspicion of these pathogens and are sending tissue for culture! The laboratory team needs to take care of them in a specific way so lab techs do not get infected. 

Treatment Options

Dimorphic fungi such as blastomycosis or histoplasmosis are treated with azoles such as itraconazole or alternatively,  amphotericin B (Thompson 2022). Acuity is an important consideration for treatment. Itraconazole can take 5-7 days to work and is appropriate in a stable outpatient. Inpatients are generally treated with amphotericin B. The duration of treatment is generally 14 days but Dr. Spec reports that patients do not usually require this amount of amphotericin if they are clinically improving. If there is concern for blastomycosis causing brain abscess,  Dr. Spec reaches for voriconazole as itraconazole has less adequate CNS penetration. 

If you are caring for a pregnant person or someone with significant organ dysfunction (especially liver), please reach out to Infectious Disease physicians and pharmacists for further guidance. 

Dimorphic Fungi Mnemonics 

Dr. Spec likes to think about the systems that the specific fungi affect which can be useful in both diagnosis and treatment. Using this, Dr. Spec considers staging the infection (ie:  which organ systems are implicated as this impacts prognosis and treatment) which helps guide his treatment approach. 

Histoplasmosis – Reticuloendothelial system – lungs, spleen, liver, bones

Blastomycosis  – The 5 Bs – breath (lungs), body covering (skin), bone, brain (blasto likes to cause brain abscesses), ‘boy/girl’ parts (prostatitis and tuboovarian abscesses)

Coccidioidomycosis  – Lungs, lymph nodes, skin, bone, meninges 

Beware of Retail Fungi Testing 

Dr. Spec reports that retail fungal testing (ie: for mycotoxin) are not helpful in getting patients the right diagnosis for their symptoms as they are not standardized or validated (Kawamoto 2014). Dr. Spec reports that clinically significant mycotoxin exposure occurs from industrial, high-inoculum exposure or high-volume ingestion. Household exposures may cause worsening allergic symptoms, not subacute pneumonia.  He advises caution and emphasizes focusing on a holistic and patient-centered approach in getting to the bottom of the patient’s concerns. 

The Nuances of Valley Fever

A well-appearing and healthy patient with coccidioidomycosis may be observed without treatment. Dr. Spec reports that he generally advises a shared decision-making approach with his patients after telling them that most people improve on their own. There is a rare chance they may develop meningeal involvement, which requires lifelong treatment. Guidelines recommend initial valley fever treatment with fluconazole (Thompson 2022).  In Dr. Spec’s practice, because he finds the high dose fluconazole treatment to be challenging for patients, he uses itraconazole.

Links

1. Thompson et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-e374. doi: 10.1016/S1473-3099(21)00191-2. Epub 2021 Aug 6. Erratum in: Lancet Infect Dis. 2021 Nov;21(11):e341. doi: 10.1016/S1473-3099(21)00588-0. PMID: 34364529; PMCID: PMC9450022.
2. CDC 2024 – Fungal Pneumonias – https://www.cdc.gov/fungal/hcp/diagnosis-testing/index.html
3. CDC 2023 – Algorithms for Diagnosing the Endemic Mycoses Blastomycosis, Coccidioidomycosis, and Histoplasmosis (video presentation and slides)

Goal

Listeners will review presentation and treatment of infections caused by dimorphic ‘endemic’ mycoses.

Learning objectives

After listening to this episode listeners will…  

1. Define  dimorphic ‘endemic’ mycoses and which organisms fall under this classification.
2. Recognize common presentations of these types of infections.
3. Consider the initial basic treatments for infections caused by  dimorphic ‘endemic’ mycoses.

Citation

Gasperlin BG, Spec A, Williams PN, Watto MF. “#495 Fungal Infections -Histo/Blasto/Cocci”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast Final publishing date August 18, 2025.