Pneumonia in Immunosuppresion (Fungal) Flashcards
What are the 4 major types of fungal infections?
• what and who do these fungal infections affect?
Superfical and cutaneous mycoses:
• Limited to the skin, hair, and nails
Subcutaneous mycoses:
• involve skin, subcutaneous tissue, lymphatics
Endemic mycoses:
• caused by dimorphic fungi, can cause serious disease in both healthy and immunocompromised patients
Opportunistic mycosis:
• can cause life-threatening disease in immunosuppressed patients
What form do dimorphic fungi take in human tissue (37 degrees) vs. laboratory conditions (25 degrees)?
• which of the dimorphic fungi are capable of causing infection?
- Yeast at 37 in human tissues
- Mold at 25 at Room Temperature
**All dimorphic fungi are capable of causing infection**aka they can all form pneumonia and disseminate
What are the 4 Dimorphic fungi?
• what is the key to telling these appart?
Location is the key to telling these apart:
- Blastomyces dermatitidis - Mississippi and Ohio River Valley + Missouri and Arkansas River basins
- Histoplasma capsulatum - Mississippi and Ohio River valley
- Coccidiodes immitus - southwestern U.S. and Latin America
- Paracoccidiodes brasiliensis - Latin America, Especially Brazil
You have an AIDS patient in memphis who experiences severe symptoms as a result of Histoplasmosis infection.
• From what source did he likely contract this infection?
• What symptoms is he likely experiencing?
• Is there significant risk of him dying from this infection?
Source:
• Soil or Bird Droppings
Symptoms in AIDS:
• Pancytopenia (due to bone marrow infiltration)
• Mouth/GI ulcers
• Skin rash (pustules, nodules)
Risk:
• 10% of AIDS patients that contract Histoplasmosis Die
Contrast Histoplasmosis in an immunocompetent person from someone who is immunocompromised.
Immunocompetent:
• Asymptomatic pulmonary infection
• Respiratory infection characterized by fever, chills, cough, and chest pain (only follows intense exposure)
Immunocompromised (AIDS):
• Pancytopenia (bone marrow infiltration)
• Mouth/GI ulcers
• Skin Rash (nodules and pustules)
• Mortality up to 10%
What visual diagnostic methods can you use to diagnose histoplasmosis capsulatum?
• what are you looking for?
• Chemical methods of Dx?
Tissue Biopsy: Look for macrophages full of oval yeast cells
CXR: infiltrates, Mediastinal LAD, cavitary lesions
Serology and Urinary antigen are two chemical methods to diagnose
You have an AIDS patient in memphis who experiences severe symptoms as a result of Histoplasmosis infection.
• How should you treat him?
• Would you expect to see a skin rash in this patient?
• How would you treat if he was immunocompetent and his symptoms were mild?
Histoplasmosis Capsulatum Tx:
Amphotericin for severe disease or Itraconazole otherwise
Nodular Skin Rash is common in AIDS patients with disseminated infection
You have an AIDS patient in memphis who experiences severe symptoms as a result of Histoplasmosis infection. His CD4+ count is 200.
- Would you expect this patient to have erythema nodosum?
- What causes erythema nodosum/what are they?
Erythema Nodosum are red/tender nodules and are a good prognostic sign because its a delayed type IV hypersensitivity rxn, because its type IV this is an indicator of a adequate CD4+ T-cell count
WOULD NOT EXPECT THIS INDIVIDUAL TO HAVE THESE B/C HE HAS AIDS
How specific is an Erythema Nodosum rash to Histoplasmosis?
• Not that specific - can be seen in TB infections and coccidiomycosis infections too
When comparing the two fugal respiratory diseases that are endemic to the Ohio/Mississippi River Valley, which is most likely to cause disseminated infection?
Blastomyces dermatitidis causes infection in BOTH immunocompetent and immunocompromised people. Disseminated Histo. infections are pretty much limited to immunocompromised.
What are the 2 main clinical manifestations of Blastomyces dermatitidis?
- Asymptomatic Respiratory Illness
- Mild Disease: 50% of infected ppl. develop cough, chest pain, sputum production, fever/night sweats
- Disseminated Disease: seen in BOTH immunocompetent and immunocompromised
What are some of the manifestations of disseminated disease resulting from Blastomyces dermatitidus?
• who gets disseminated blasto infections?
• where does this stuff live?
Disseminated Disease:
• Ulcerated Granulomatous lesions of skin (70%)
• Bone (33%)
• GU tract (25%)
• CNS (10%)
BOTH immunocompetent and immunocompromised people get blasto infections
• Blasto lives in the soil
What do you look for in the CXR and Tissue biopsy of a patient with a suspected Blastomyces infection?
• which is more specific?
• Is serology useful in Dx?
CXR: Lobar consolidation, multilobar infiltrates, multiple nodules - very non-specific
Tissue Biopsy: thick-walled yeast cells with SINGLE BROAD-BASED BUD
• Serology is a method used in diagnosis
A patient from St. Louis presents with granulomatous lesions on his skin and remarks that he has recently broken his wrist. Empirical abx are used to treat the patient but the infection only progresses. CXR shows lobar consolidation and multiple nodules.
• What are some factors to knowing this is fungal and not viral?
• How would you treat this patient?
Key:
• CXR shows lobar consolidation - this is not typical of antiviral pneumonia so that leaves bacterial and fungal, but pt. did not improve on empirical abx so its fungal.
Tx:
• Itraconazole or Amphotericin if sever
Compare treatment methods for Histoplasmosis and Blastomyces.
they are identical: Itraconazole for a non-severe infection, Amphotericin for a severe infection
What is the pathogenesis of Coccidiodes immitus?
Large spherules form and are filled with endospores when the spherule wall ruptures, endospores are released and differentiate to form new spherules
What are the most common clinical manifestations of someone who gets infected with the dimorphic bacteria from the southwest U.S?
• what normal healthy people are most likely to experience a disseminated infection by this pathogen?
Coccidiodes immitus
• ~90% - ASYMPTOMATIC
• ~10% - mild FLU-LIKE illness - valley fever - Erythema Noduosum
Higher Risk of Dissemination:
• 1% disseminated - African Americans, FIlipinos, and women in the 3rd trimester of pregnancy
T or F: TB, Histo, and Coccidiodes immitis can all causes Erythema Nodusum (tender nodular type IV hypersensitivy rxn localized to arms and legs typically).
True
A patient comes in after a visit to california and is experiencing dyspnea, myalgia, fever, and has noticed tender red nodules have started to manifest on his arms and legs.
• Suspected fungal pathogen?
• What are the key microscopic features of this bug?
• How will you treat this patient?
• How would youre treatment change if he started experiencing intense headache with neck stiffness?
Coccidiodes immitis shows up as spherules that are filled with yeast EOSINOPHILIA is common (LOOK at CBC and histo)
Tx:
• Amphotericin for persistent lung lesions or disseminated disease
• Fluconazole for Meningitis - LONG TERM
Paracoccidiodes brasiliensis
• where is this typically seen?
• Clinical manifestation?
• How to Dx?
• Tx?
Rural Latin America, especially Brazil = Paracoccidiodes brasilienes
Manifests as mild URI that can progress to dissemination and ulcerated lesion on the face as well as intense LAD (submandibular)
Dx:
• Serology and Tissue biopsy to look for yeast will multiple buds
Tx:
• Itraconazole for SEVERAL mo.
• Amphotericin if severe
Compare the ulcerated facial lesions seen in Paracoccidioides to Blasto.
• What are you looking for in the histology of either of these bugs?
Paracoccidiodes has much more severe facial lesions
Paracoccidiodes:
• Yeast with many buds - Pilot wheel
Blastomyces:
• Broad Based Bud (single bud)
Where is Aspergillus fumigatus found?
• what is its morphology?
Aspergillus is found worldwide growing on decaying vegetation it has septate, Acute-Angle branching hyphae and radiating chains of conidia
What patients are at the greatest risk of getting an invasive infection from Aspergillus?
• what symptoms would you see?
• Compare these symptoms to someone experiencing an Allergic Aspergillus infection.
Hematologic Malignancies with neutropenia - in these people we see invasive pneumonia with HEMORRHAGE, INFARCTION and NECROSIS
Allergic infection produces asthmatic symptoms - these people will cough up brown plugs made of hyphae
What antibody will be elevated in allergic reactions to Aspergillus?
pts. have high IgE titer - they’ll be coughing up brown hyphae
T or F: Aspergillus can form a fungus ball in the cavities of the lung producing hemoptysis.
True
A patient with agranulocytosis gets infected with a bug that causes a severe pneumonia accompanied by hemoptysis. CXR shows the presence of a mass in a lung cavity.
• what is the bug?
• How should you treat it?
Aspegillus is known to form masses in lung cavities
Tx: VORICONAZOLE - if patients can’t handle this amphotericin or echinocandins are good alternates
How are all of the dimorphic fungal infections treated?
• what is the only exception?
Dimorphics - (Histo, Blasto, Coccidio, P. Immitus)
Amphotericin for severe infection and Itraconazole for less severe infection
Only exceception is Coccidio where you use Amphotericin or Fluconazole if the infection turns into meningitis (b/c it crosses the BBB)
Who is at high risk of infection by mucormycosis?
• how is it transmitted?
High Risk:
• Diabetics - in DKA
• Neutropenia
• Iron Overload (hemochromatosis)
• Burns/surgical wounds
• Corticosteroid use
Transmission:
• Airborne Spores
What are the clinical manifestation of a Mucormycosis infection?
Really Shitty:
• Paranasal sinuses => Orbit => hard Palate and Brain
• Frontal lobe abscesses
Kinda Shitty:
• Pneumonia
Not that Shitty:
• cutaneous infections
A patient presents with an anion gap acidosis and has forgotten to take their insulin for several days. After blood sugar is stabilized this patient continues to experience Headache and facial pain.
• What bug could be responsible for this pain?
• Where does it grow?
• What would you look for on histo to make a Dx?
Mucormycosis => this diabetic patient is at a high risk for infection.
Mucor grows on bread
Histology should show NON-SEPTATE BROAD HYPHAE WITH FREQUENT RIGHT ANGLE BRANCHING
What two bugs show hyphae on histology?
• differentiate these.
• are these dimorphic?
Aspergillus and Mucormycoses have Hyphae
Asperguillus = Acute angled and Septate
Mucor = Right angled, broad, and NON-septate
NO - these are not dimophic (hence the hyphae)
A patient presents with an anion gap acidosis and has forgotten to take their insulin for several days. After blood sugar is stabilized this patient continues to experience Headache and facial pain.
• How do you treat this patient?
#1 treat the underlying illness - get their diabetes under control
Use Amphotericin or Posaconazole and Surgically remove necrotic tissue
What fungal bug that is common to AIDS patients causes alveoli to produce an inflammatory response that results in the production of a frothy exudate?
• what cells are important in clearance of this organism?
Pneumocystis Jiroveci - known to cause alveoli to produce a frothy exudate that BLOCKS O2 exchange alveolar gas exchange
• CD4+ T cell are recruit MACROPHAGES that are important for clearance - lack of CD4+ cells is what puts AIDS patients at high risk
When should you start worrying about you AIDS patient getting pneumocystis?
When CD4 count drops below 200.
T or F: Pneumocystis jiroveci does not invade lung tissue.
True - there is no invasion of tissue - the problem is the inflammation that blocks alveolar gas exchange
What happens to most people that get infected by Pneumocystis?
• how many people are infected by this bug?
Most people = Asymptomatic, 70% of the world is infected
Your AIDS patient presents with progressive dyspnea and fever accompanied by dry cough. Lung biopsy indicates the presence of a non-invasive organism that is present in the yeast form.
• what is the infectious agent?
• what are some keys to knowning this?
• Guess the patients Tcell count?
Pneumocystis has caused the infection.
Keys:
• Dyspnea - patients with pneumocytsis may have O2 sats in the 80s
• dry cough
• NON-invase
• AIDS patient
T cell count is LESS THAN 200
You suspect that a patient has PCP after visualizing ________ (a) cysts by ___________(b) stain or ________(c) stain.
• could PCP also be detected by doing PCR on respiratory tract secretions?
(a) Crushed ping pong ball
(b) Methanamine silver
(c) Giemsa Stain
What is the most common cause of life threatening disease in AIDS patients?
• what are the two major manifestations of this disease in AIDS patients?
Most common cause of life-threatening disease in AIDS patients = Cryptococcus neoformans
2 major diseases:
• Meningitis - remember its encapsulated - immunocompromised only
• Pneumonia - in in both immunocompetent and immunocompromised
Describe the symptoms of cryptococcal respiratory infections as they occur in the immunocompetent and the immunocompromised.
Immunocompetent:
• Mild respiratory symptoms but most will be asymptomatic
Immunocompromised:
• Fever, Chest pain, Dyspnea, cough, hemoptysis
What is the structure of crytpococcus?
Narrow Based Bud
Compare the manifestation of CMV (cytomegalovirus) in the normal population, immunosuppressed, and those with AIDS?
CMV:
Normal Population:
• Asymptomatic - 80% of the population has antibodies against this virus
Immunosuppressed:
•Pneumonitis commonly developes (in this population are renal and stem cell transplant ppl)
AIDS:
•Colitis and Retinitis are most typical (NOT pneumonitis, in fact its rare)
What type of virus is CMV?
Enveloped DNA virus similar in morphology to other Herpes viruses
What are the symptoms and manifestations of infections by the gram-positive acid fast bacteria that grows in thin branching filaments?
• Who gets infected?
• What tissues does this bug like to affect?
• What does it do once it gets there?
Norcardia Asteroides - gram positive acid fast bacteria
Immunocompromised get infected and get a lung infection that may disseminate and have a predilication for brain tissue and lung tissue - here it may cavitate and cause nodules or cause empyema in the lungs
A patient recently recieving a bone marrow transplant missed several days of antibiotics and has developed several neurological symptoms. Cultures show a gram positive acid fast bacteria is responsible.
• What bacteria is this?
• How do you treat?
• Do you need to perform sensitivities?
Bacteria:
• Norcardia asteroides
Treatment:
• TMX-SMX - may need combo therapy if resistant
Sensitivities:
• YES, you need these because resistance in norcardia can develope
