PANCE Blueprint Pulmonary (10%)

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.

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 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

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.

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.

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.

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 />