PANCE Blueprint Pulmonary (10%)

Fungal pneumonia

Patient will present with → a 21-year-old male presents with a cough and mild shortness of breath for three days. The cough is occasionally productive of yellowish mucus. He reports a low-grade fever with this episode but says that he has otherwise been healthy. He has spent the last month working in bat caves. He denies tobacco or alcohol use. (Histoplasmosis)

Common in immunocompromised patients – AIDS, steroid use, organ transplant

Coccidioides (valley fever): Look for this in a patient with non-remitting cough/bronchitis non-responsive to conventional treatments.

  • Caused by fungal inhalation in western states.
  • Serologic tests using enzyme-linked immunoassays (EIA) for IgM and IgG should be ordered first, if possible. If the EIA is positive, a confirmatory immunodiffusion test should be performed.
  • Treatment: fluconazole or itraconazole.

Pulmonary aspergillosis: The majority of cases occur in people with underlying illnesses such as tuberculosis or chronic obstructive pulmonary disease (COPD), but with otherwise healthy immune systems.

  • Treatment: fluconazole or itraconazole.

Cryptococcus: found in soil can disseminate and can cause meningitis 

  • Immunocompromised patients are usually symptomatic
  • Lumbar puncture for meningitis
  • Treatment: Amphotericin B

Histoplasma capsulatum: Chronic cavitary histoplasmosis is characterized by pulmonary lesions that are often apical and resemble cavitary TB. Manifestations are worsening cough and dyspnea, progressing eventually to disabling respiratory dysfunction. Dissemination does not occur.

  • Bird or bat droppings (caves, zoo, bird)
  • Mississippi or Ohio river valley
  • Mediastinal or hilar lymphadenopathy (looks like sarcoid)
  • Treatment: Amphotericin B

Pneumocystis Jiroveci: Formerly PCP Pneumonia now called (PJP) (there are other HIV-related pneumonias but this is the one you will need to know for the test)

  • Common in HIV-infected patients with a low CD4 count of less than 200
  • The radiograph shows diffuse interstitial or bilateral perihilar infiltrates
  • Diagnose with bronchoalveolar lavage (PCR), labs, and an HIV test
  • Treat with Trimethoprim-sulfamethoxazole (BACTRIM) and steroids
  • Prophylaxis for high-risk patients with a CD4 count of less than 200 or with a history of PJP infection. Daily Bactrim is the prophylaxis antibiotic of choice

Chest X-Ray Findings: 

  • Cryptococcus: Cryptococcal antigen can be detected in CSF and serum. India ink stain or serology with latex agglutination assay or cryptococcal antigen assay (CRAG) is helpful.
  • Histoplasma capsulatum causes mediastinal or hilar lymphadenopathy (looks like sarcoidosis)
  • Pneumocystis Jiroveci
    • Diagnose with bronchoalveolar lavage (PCR), labs, and an HIV test
    • causes diffuse interstitial or bilateral perihilar infiltrates

Cryptococcus and Histoplasma - Amphotericin B

Coccidioides - Azoles - fluconazole or itraconazole

Aspergillus - Triazoles - Triazole antifungal agents include voriconazole, posaconazole, itraconazole, and fluconazole

Histoplasmosis Infection with hilar lymphadenopathy

Histoplasmosis Infection with hilar lymphadenopathy



Coccidioidomycosis is a systemic fungal disease caused by Coccidioides immitis, a dimorphic fungus that exists as a mold in cool temperatures and spherules in warm temperatures like soft tissue. The fungus is found as a mold in the soil, and produces hyphae with arthrospores that are easily dispersed throughout the air and inhaled.  When the arthrospores are inhaled, they form spherules filled with endospores. These spherules measure 20-60 um and contain endospores that are slightly larger than red blood cells, which are around 6-8um. The spherules rupture and endospores spread throughout the body causing disease, most commonly in the lung, skin, bone, and brain. Most frequently, coccidiomycosis causes pneumonia, but it can also disseminate and cause meningitis or osteomyelitis. Common skin findings include erythema nodosum, which are painful red nodules found on the extensor surfaces like the anterior lower legs. Coccidioidomycosis typically causes granulomatous inflammation with caseous necrosis, which is a type of white cheesy appearing necrosis. C.immitis is commonly found in the Southwestern United States, particularly the San Joaquin valley region, in deserts and in construction zones where the spores can be carried by dust storms. Any disruption of the soil can increase spread of the organism; thus, coccidioidomycosis infections are also more frequent after earthquakes. No treatment is required for asymptomatic infections, but azoles can be used for systemic infections.

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Aspergillus is a genus of monomorphic fungi named after the shape of an aspergillum, which is an instrument used to sprinkle holy water. Aspergillus fumigatus is one of the most common Aspergillus species to cause disease. Its spores are ubiquitous in the atmosphere and estimated that everybody inhales several hundred spores daily.  The most common forms of disease are allergic bronchopulmonary aspergillosis, pulmonary aspergilloma, and invasive aspergillosis. On microscopy, Aspergillus can be identified by their septate hyphae that tend to have dichotomous branches at primarily acute angles of about 45 degrees. The organisms can also demonstrate fruiting bodies which are the conidial heads that produce spores. Allergic bronchopulmonary aspergillosis is associated with hypersensitivity to the spores of Aspergillus molds, commonly seen in asthmatics. It is characterized by numerous eosinophils and elevated IgE directed against aspergillus antigens. Thick mucus plugs can develop and overtime cause the bronchi to become dilated leading to bronchiectasis. Aspergilloma refers to growth of the fungus within a cavity of the lung, previously formed during an illness such as tuberculosis. The spores penetrate the cavity and germinate, causing the formation of a fungal ball within the cavity. Within the cavity, the fungus secretes toxic and allergic products. Hemoptysis is common, occurring in 50-80% of affected individuals. Invasive aspergillosis occurs in immunocompromised individuals including people with chronic granulomatous disease where the fungus transfers from the lungs to the bloodstream and can disseminate to the brain or other organs. Within the blood vessels, the organism can cause hemorrhagic infarctions and cause necrotizing bronchopneumonia in the lungs.

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Cryptococcus neoformans


Cryptococcus neoformans is an opportunistic fungal infection that causes cryptococcosis, a severe disease of the CNS. C. neoformans is monomorphic and only exists as yeast with narrow-based buds measuring 5-10 um. It is encapsulated with a polysaccharide capsule that helps evade phagocytosis. In addition, its virulence is increased by the ability to undergo phenotypic switching and change the structure of its capsule. It is commonly found in the soil or in pigeon droppings and can cause disease when inhaled. Healthy individuals can demonstrate a range of symptoms, from asymptomatic to pneumonia or meningoencephalitis. However, immunosuppressed patients, such as HIV/AIDS patients or patients on chronic corticosteroid therapy, are most commonly affected and more likely to have disseminated disease. Dissemination into the CSF can commonly cause meningitis that extends into the perivascular space with lesions that appear similar to soap bubbles.  Diagnosis of cryptococcosis can be made in many different ways. A Gram stain of the organism collected from CSF stained with India ink reveals the oval yeast with a halo surrounding it, signifying the capsule. A mucicarmine stain or periodic acid-Schiff stain can also be used, which stains the polysaccharide capsule a bright red. In addition, a latex agglutination test can also be used, which uses antibody-coated latex beads that binds to cryptococcal antigen present in the assay. Treatment includes amphotericin B and flucytosine for meningitis and disseminated disease. Fluconazole can also be used as long-term prophylaxis in immunosuppressed patients

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_DM_Histoplasmosis_v1.4_ (1)

Histoplasma is a genus of dimorphic fungi known to be the causative agent of histoplasmosis. This organism has a yeast form that is 2-5 um and found within macrophages within the body. It is commonly found in bat and Starling bird feces and contracted by inhalation of the spores. Therefore, it is commonly associated with entrance into caves and is most prevalent in the Ohio and Mississippi river valleys. Symptoms of this infection vary but the disease primarily affects the lungs, causing pneumonia. Occasionally, the organism can disseminate and affect other organs including the meninges, liver, or adrenals and widely disseminated disease can occur in the immunocompromised. Histoplasma infections produce granulomas, which usually undergo caseation necrosis and can form large areas of consolidation. Like most systemic mycoses, treatment includes an azole antifungal for local infection along with amphotericin B for systemic infection.

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Pneumocystis jiroveci


Pneumocystis jiroveci is a fungal infection which typically presents with hypoxia and fever in the lungs of immunocompromised patients. The infection is usually diagnosed using classic x-ray findings of diffuse interstitial infiltration bilaterally. Definitive diagnosis can be made using lavage or biopsy, were it can be identified by methenamine on silver stain. In order to prevent the disease in patients with HIV and CD4 counts below 200, TMP-SMX is used prophylactically. TMP-SMX is also used as treatment for diagnosed disease.

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Amphotericin B


Amphotericin B is a polyene medication, which works by binding to ergosterol in fungal cell membranes. It forms membrane pores, causing electrolytes to leak, killing the fungal cell. It is used for serious, systemic mycoses. It can lead to the side effects of fever and chills, nephrotoxicity, arrhythmias, anemia and IV phlebitis.

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Amphotericin B Side Effects & Toxicity

Amphotericin B is a polyene medication, which works by binding to ergosterol in fungal cell membranes. It forms membrane pores, causing electrolytes to leak, killing the fungal cell. It is used for serious, systemic mycoses. It can lead to the side effects of fever and chills, nephrotoxicity, hypotension, arrhythmias, anemia and IV phlebitis.<br />

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Question 1
Which of the following infectious agents is most likely to be found in a rural Kentucky farmer or in someone who is responsible for clearing bats out of the local caverns before the tourist season begins?
Cryptococcus is most likely in people exposed to pigeons and is also found in soil enriched by bird droppings or in cockroach-infested environments.
Parrots, parakeets, ducks, and turkeys are the usual hosts and most commonly infected species for psittacoccal infections as well. It is less common in humans.
Candidal species
Question 1 Explanation: 
Histoplasmosis is found throughout the continental United States with greater concentration in the Ohio and Mississippi river valleys. It is found in soil, particularly in areas with large quantities of decaying wood or bird droppings. Bats also carry histoplasma. Cryptococcus is most likely in people exposed to pigeons and is also found in soil enriched by bird droppings or in cockroach-infested environments. Parrots, parakeets, ducks, and turkeys are the usual hosts and most commonly infected species for psittacoccal infections as well. It is less common in humans.
Question 2
The drug of choice for treatment of severe coccidioidomycosis (“ valley fever”) is
Question 2 Explanation: 
Coccidioidomycosis (“ valley fever”) is an infection that is usually asymptomatic. In some cases, nonspecific respiratory symptoms resembling influenza or acute bronchitis occur. Less frequently, acute pneumonia or pleural effusion can develop. Symptoms include fever, cough, chest pain, chills, sputum production, sore throat, and hemoptysis. Physical signs may be absent or limited to scattered rales with or without areas of dullness to percussion over lung fields. Leukocytosis and, in some cases, eosinophilia is seen. Other symptoms include arthritis, conjunctivitis, erythema nodosum, or erythema multiforme. Primary pulmonary lesions sometimes resolve, leaving nodular coin lesions that may be confused with neoplasms and tuberculosis or other granulomatous infections. In some cases, cavitary lesions develop that may vary in size over time and often appear thin-walled. Although dissemination does not occur from these residual areas, a small percentage of these cavities fail to heal. Hemoptysis or the threat of rupture into the pleural space may occasionally require surgery. Treatment for mild primary coccidioidomycosis may be unnecessary in low-risk patients. Mild-to-moderate nonmeningeal extrapulmonary involvement should be treated with fluconazole or itraconazole. IV fluconazole is preferable for severely ill patients. Amphotericin B is an alternative treatment. As with histoplasmosis, patients with AIDS-associated coccidioidomycosis require maintenance therapy to prevent relapse. Treatment for meningeal coccidioidomycosis must be continued for many months, probably lifelong. Surgical removal of involved bone may be necessary to cure osteomyelitis.
Question 3
The treatment of choice for cryptococcal meningeal infection is
Amphotericin B and flucytosine
Penicillin G
Question 3 Explanation: 
Cryptococcus is an infection caused by the fungus Cryptococcus neoformans that usually involves the lungs with spread to the meninges and occasionally to other sites, including the kidneys, bones, and skin. The disease is found worldwide and tends to affect immunodeficient patients with lymphoma and AIDS or those chronically taking steroids. Symptoms include headaches (usually the first symptom), blurred vision, and mental status changes seen with meningeal involvement. In addition, the patient usually reports a persistent cough, which reflects pulmonary involvement. The disease is acquired by respiratory transmission. Skin lesions and the development of osteomyelitis are infrequent; however, as many as 33% of patients with meningeal involvement also have renal involvement. Laboratory tests show CSF with an increased protein, a white cell count that is mostly lymphocytes, and a decreased glucose level with meningeal involvement. Culture of sputum, blood, urine, or other areas of involvement is diagnostic. The diagnosis is also supported with the evidence of budding yeast seen with India ink preparation. The treatment of choice for cryptococcal meningitis is the administration of intravenous amphotericin B and oral flucytosine until lumbar cultures are clear, followed by lifelong prophylaxis with fluconazole; amphotericin and itraconazole are alternatives. Nonprogressive pulmonary cryptococcus may not require treatment in patients who are not immunocompromised.
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References: Merck Manual · UpToDate

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