December 15th - LBJ - Young Blebs

Of Blebs and Bullae

Today at LBJ a case was presented of a previously healthy 33 year old African American Male who presented to the ER with dyspnea.  He was found to have a large left-sided pleural effusion, was given IV azithromycin by the ED, and left Against Medical Advice.  He was readmitted to the medicine service with the same chief complaint - imaging revealed this large pleural effusion and multiple bullae located in various portions of the lung.  He did have a smoking history, but no history of chronic lung disease or prior pulmonary pathology.

These are some of the various causes of bullous disease in young patients:
1) "Normal" - The journal Chest published a review that 6% of healthy young adults can have bullous disease adjacent to the pleura - usually in those with low BMIs that have a positive smoking history.   This was postulated to be due to reduced pleural adipose tissue.

2) Connective Tissue Diseases - Marfan's Syndrome and Ehlers-Danos Syndrome are the most common in the literature.

3) Chronic Cocaine and Marijuana use - both have been linked to formation of bullae

4) Alpha-1-antitrypsin deficiency - Panacinar involvement and usually involves the lower lobes more than the upper lobes.  Emphysema usually develops in smokers around the age of 40, and in non-smokers in the mid 50s.  Depending on the genetic mutation, however, some patients can have emphysema by the age of 30.    

5) Sarcoidosis - Bullous disease can occur anytime during the course of the disease, and is sometimes a presenting finding or can precede the diagnosis by years. 

6) Pulmonary Langerhans Cell Histiocytosis - An Interstitial lung disease found almost exclusively in young male smokers.  Patients can have constitutional symptoms, or present with cough/dyspnea.  The bullae are usually upper-lobe predominant, and 25% of patients develop spontaneous pneumothorax.  Interestingly, 10-15% of patients are completely asymptomatic and the disease is found during "other reasons" to do lung imaging.  15% of patients have "extrapulmonary" involvement including bone pain from cysts, diabetes inspidus or rash.  Pulmonary cysts are usually visualized on CT Scans. Soking cessation usually leads to resolution of symptoms, although some patients are treated with corticosteroids. 

7) Lymphangioleiomyomatosis (LAM) affects pre-menopausal females.  Patients have multiple thin-walled cysts, lymphadenopathy,  diffuse interstitial infiltrates and eventual fibrosis.  They also have a tendancy to form recurrent chylous pleural effusions.  There is a disease association with  angiomyolipomas and tuberous sclerosis.  Patients with LAM are instructed to prevent pregnancy or not take estrogens, as there is evidence that hormones play a role in the pathogenesis of the disease.  Treatment involves general care and relieving symptoms of effusions. Some patients are put on bronchodilators.  Some have used medroxyprogesterone in the past - but the evidence supporting its use is lacking.  Experimental agents, such as chemotherapeutic drugs, are being investigated.  Some patients may need lung transplant.

Of note:  Centriacinar emphysema is the "classic" pattern seen in smokers, and predominantly affects the upper lobes. There is also a more rare variant called distal acinar emphysema/paraseptal emphysema which causes scattered bullous disease without airflow obstruction.  However, it would be RARE in a 33 year old - as it takes at least 20 cigarettes a day for 20 years to form the changes of chronic lung disease.

Some "board review" notes on pleural fluid (as the patient as a pleural effusion)

Light's Criteria (any of these present = exudate)
1. Pleural fluid protein/serum protein >0.5
2. Pleural fluid LDH/serum LDH > 0.6
3. Pleural fluid LDH > 2/3 upper limit of normal

Chest did an analysis of pleural fluid and found that any of the following characteristics are also consistent with "exudates":
1.Pleural fluid protein >2.9 g/dL
2.Pleural fluid cholesterol > 45 mg/dL
3.Pleural fluid LDH > 60 percent of upper limit for serum

Causes of Transudative Effusions:
Congestive Heart Failure (usually bilateral and small, but can be unilateral)
Cirrhosis
Nephrotic Syndrome
Pancreatitis (left sided)
Pulmonary Embolism

Causes of Exudative Effustions
Malignancy (Lung, Breast and Lymphoma)
Mesothelioma (usually bloody fluid)
Infectious (both bacterial and viral)
Esophageal perforation
Pulmonary Embolism
Rheumatic diseases (Rheumatoid arthritis, SLE)
Transudative causes that turn exudative secondary to diuresis
    (This occurs in less than 20% of these patients - to be sure/better classify - if the difference between serum protein and the pleural fluid protein is greater than 3.1 g/dL - the effusion is transudative.  Alternatively, a serum albumin-effusion albumin gradient greater than 1.2 g/dL is also suggestive that effusion is most likely a true transudate)

Other notes:
WBC >10,000 = parapneumonic
WBC >100,000 = empyema (this will be obvious as the fluid will be purulent)
High Eosinophil Count (10% of total) = Mesothelioma, parasites/fungal and drug reaction
High Lymphocye Count (>50% of total) = Malignancy or TB
High Amylase - Esophageal Rupture and sometimes malignancy
Glucose <60 = Malignancy or Infection. An even lower glucose can be see with rheum Dx
pH<7.2 (when collected quickly) - can see with infection and some malignant cases.  When
       seen in the face of infection, it is an indication for chest tube drainage
Pleural Fluid ADA>45 has a PPV of about 80%
High ANA Titers (>1:160) - SLE and drug-induced Lupus
TG>115 = chylous effusions (can be caused by cancer!)