Today we learned about a patient who presented with hemoptysis in the setting of latent TB that was diagnosed as TB Bronchiectasis. We discussed the framework for hemoptysis:

We then reviewed the CT and determined it was bronchiectasis:

• Bronchioectasis is defined as “Irreversible dilation and destruction of larger bronchi caused by chronic infection and inflammation”
• Development of bronchiectasis always requires two factors
  • An infectious insult
  • Impaired drainage, airway obstruction or a defect in host defense
• Etiologies
  • Any pulmonary Infections
    • Childhood infections (bacterial, viral or mycoplasma PNA)
    • Mycobacterial infections
  • Cystic Fibrosis
    • up to 7 percent of patients with cystic fibrosis (CF) are diagnosed at age 18 years or older
    • Sinusitis and bronchiectasis are the major respiratory manifestations of CF in adults
  • Airway obstruction
    • FBA or any other intraluminar obstructing lesion (such as a carcinoid tumor) or extraluminal compression
  • Tracheobronchomalacia/tracheobronchomegaly
  • Defective host defenses
    • Local: Ciliary dyskinesia
    • Systemic: hypogammaglobulinemia/prolonged immunosuppression
  • Young Syndrome
    • Bronchiectasis, sinusitis and obstructive azoospermia who have no evidence of cystic fibrosis
  • Rheumatic/Systemic Disease
    • RA/Sjogrens
  • Primary Ciliary Dysfunction
  • Allergic bronchopulmonary aspergillosis
    • should be suspected in patients with a long history of asthma that is resistant to bronchodilator therapy and associated with a cough often productive of sputum that is mucopurulent or contains mucous plugs.
  • Alpha-1 antitrypsin deficiencies
• Signs and Symptoms
  • cough, mucopurulent sputum production, dyspnea, rhinosinusitis, hemoptysis (27%) and recurrent pleurisy
  • on exam crackles and wheezing are common
• Radiographic Findings
  • The internal diameter of the bronchus is larger than that of its accompanying vessel
  • the bronchus fails to taper in the periphery of the chest
• Treatment of Acute Exacerbation
  • Deciding when a patient has an acute exacerbation requires clinical judgement as there is no laboratory features specific for an exacerbation
  • Antibiotics decrease the existing bacterial burden and can decrease systemic inflammatory mediators
  • 10-14 day treatment course is appropriate (though the ERS 2017 guidelines suggest 14)

Credit goes to Dr. Scott Burns from Roper Hospital in Charleston for his case on the Human Diagnosis Project.

Today we discussed a case of a young man with otherwise no medical history presenting with subacute dry cough, malaise, and weight loss. On exam he was septic on presentation with notable oral thrush. CXR revealed bilateral interstitial infiltrates and a RUL cavity with air fluid level which was confirmed on CT. LDH was elevated. He was confirmed HIV positive with a low CD4 count in the single digits, and BAL confirmed the diagnosis of PCP/PJP pneumonia!

Oral Thrush: NEVER assume normal, extremely rare in immunocompetent patients, so if you see this, consider whether the patient could be immunocompromised.

Cavitary Lung Lesion DDX

• Mycobacteria
  • TB
  • M kansasii
• Bacterial
  • Pseudomonas
  • Enterobacteriaceae
  • Klebsiella
  • Streptococci
  • Nocardia
  • Anaerobes
  • Staph aureus
• Fungi
  • Crypto
  • Aspergillus
  • Histoplasma
• Rare
  • Bacterial: Legionella, rhodococcus
  • Mycobacteria: MAC
  • Fungi: PCP/PJP, mucormycosis, blasto
  • Others: Vasculitis

PCP

Epidemiology

• Immunocompromised patients
  • HIV with CD4 < 200
  • BMT, organ transplant patients
  • Leukemia/lymphomas
  • Rheumatology conditions
  • Primary immunodeficiencies
• Rarely occurs in immunocompetent patients

Presentation

• Typically subacute onset of pulmonary symptoms, non-productive cough, fever chills, malaise, SOB
• Might have other clues of immunocompromised status

Diagnosis

• CXR: Classic description is bilateral interstitial infiltrates
  • Rare instances: Lobar infiltration, nodules, cavitary lesions, pneumothorax
• CT: Higher sensitivity but might not be necessary for the dx
• LDH: Sensitive but not specific if elevated. An elevated LDH in an HIV patient without other medical co-morbidities that might inc LDH should raise suspicions for PCP
• Beta D glucan: For HIV patients, good sensitivity, not that specific. If elevated, raises suspicions for PCP.
• Gold standard: either visualize the organism via induced sputum (yield is variable, variable sensitivity but 100% specific), or via BAL.
• Can also use 18S PCR

Management

• First line: TMP-SMZ, 15-20 mg/kg. PO just as good as IV, duration 21 days
• Sulfa allergy:
  • Mild to moderate: Desensitization
  • Severe: alternative agents
    • Clinda + primaquine
    • Trimethoprim + dapsone
    • Atorvaquone
    • Pentamidine
    • For severe disease, Clinda + primaquine or IV pentamidine is preferred.
  • Adjunctive steroids
    • ABG: If PaO2 < 70, or Aa gradient > 35, or hypoxemia on pulse ox, adjunctive steroid is indicated and has been shown to improve mortality
    • Pred 40mg BID x 5 days, then 40mg daily x 5 days, then 20mg daily x 11 days, total 21 days

Remember your Aa gradient equation!

Aa-gradient = PAO2 (calculated from the alveolar gas equation) – PaO2 (measured PaO2 on ABG)

PAO2 = FiO2 (baromeric pressure – water pressure) – PaCO2/(respiratory quotient)

Assuming sea level and a standard respiratory quotient of 0.8, this equation can be simplified to:

PAO2 = 150 – PaCO2/0.8

Gray Medicine had an interesting case of a 80yo F with history of treated TB (60 years ago), thoracic artery aneurysm s/p recent TEVAR, presenting with 3-4 months history of throbbing chest and back pain. She was admitted one month prior to the same complaint, CXR and CT Cx did not reveal significant pathology other than mild distal TEVAR graft dilatation. She presents 1 month later with worsening chronic chest pain, anorexia, weight loss.

This is the chest X-ray during this current hospitalization…

Burn this image into your head! This is a classic miliary pattern on a chest radiograph! The term miliary stems from millet seed, a term used to describe a group of small-seeded species of cereal crops or grains

Subsequent chest CT revealed innumerable bilateral pulmonary nodules, which were not present a month prior.

Let’s go through possible causes for a miliary pattern on a chest radiograph. In general it can be divided into three categories. The DDx can be quite wide!

In our case, given that our patient is an elderly woman with a remote history of treated TB, this presentation is highly concerning for miliary TB leading to reactivation. In general, miliary and disseminated TB are often used interchangeably. Disseminated TB refers to TB that affects at least two organ systems.

The most commonly affects organs are:

• Lungs
• Liver/GI
• Spleen
• Adrenals
• CNS

Our patient was placed on airborne, and ultimately her sputum was MTB PCR positive! She has TB!

Presentation of Miliary TB

• Very common: B-symptoms, FFT, typically subacute to chronic. 80-95% will have a fever.
• Miliary, unlike typical TB, can present with acute sepsis or respiratory failure.
• Pain/organ dysfunction based on location of the spread. Basically can affect anywhere. Hepatic TB, 79% of cases are due to miliary TB. Other commonly affected organs are spleen, adrenals, BM, lymphatics, and CNS.
• Other manifestations: DIC, hyponatremia, pan-cytopenia, 50% cases will have normocytic anemia.

Risk Factors

• Immunocompromised status
  • HIV
  • Extremes of age (infants, elderly)
  • Immunosuppressives
  • Post transplant
  • Other medical co-morbidities (CKD, cirrhosis, EtOH, etc)

Diagnosis

• Chest radiograph: Classic faint reticulonodular infiltrate uniformly throughout lungs.
• CT is more sensitive for miliary TB and usually is recommended. Typical finding might reveal numerous 2-3mm nodules but this is not specific.
• Tissue, fluid, or lymph node biopsy
• Gastric aspirate
• Ultimately combination of clinical diagnosis with support labs/imaging.
• Gold standard: AFB and culture + MTB PCR
• All patient should have mycobacterial blood cultures
• Urine mycobacterial cell wall glycolipid lipoarabinomannan (urine LAM) is a highly specific test with high sensitivity in HIV patients for disseminated TB.

Management

• Intensive Phase: HREZ (aka RIPE) x 2 months
  • R: Rifampin
  • I: Isoniazid
  • P: Pyrazinamide
  • E: Ethambutol
• Continuation Phase
  • After, 2 months of HREZ (RIPE), the continuation phase consists of 4 months of isoniazid and Rifampin.
  • Choice of medication and duration will change depending on resistance of the organism and location affected
• Corticosteroids: Indicated if meninges or pericardium is involved.
• Make sure to fill out a GOTCH form (not the GOAT form, as someone answered on Kahoot this morning) for Santa Clara County if you have a patient with active TB since a safe dispo will involve multiple disciplines and careful planning!